Search

Michael Stanley Ellis,1 Joseph T Nelson,2 Jeffrey Zane Kartchner,1 Karl Andrew Yousef,1 William J Adamas-Rappaport,3 Richard Amini4 1College of Medicine, The University of Arizona, Tucson, AZ, USA; 2Department of Orthopedic Surgery, The University of Michigan, Ann Arbor, MI, USA; 3Department of Surgery, 4Department of Emergency Medicine, The University of Arizona, Tucson, AZ, USA Abstract: Ultrasound imaging is a rapid and noninvasive tool ideal for the imaging of soft tissue infections and is associated with a change of clinician management plans in 50% of cases. We developed a realistic skin abscess diagnostic and therapeutic training model using fresh frozen cadavers and common, affordable materials. Details for construction of the model and suggested variations are presented. This cadaver-based abscess model produces high-quality sonographic images with internal echogenicity similar to a true clinical abscess, and is ideal for teaching sonographic diagnostic skills in addition to the technical skills of incision and drainage or needle aspiration. Keywords: undergraduate medical education, abscess model, ultrasound, ultrasound education, ultrasound-guided needle aspiration

Background: Diabetes mellitus often exists for many years prior to diagnosis, and very little is known about the role of the prediagnosis stage of metabolic impairment in contributing to hand and upper-extremity pathology. The goal of this study is to determine the prevalence of undiagnosed glucose dysregulation in patients presenting with the 2 most commonly treated conditions of the hand and wrist., Methods: A retrospective study was performed of hand surgery patients with no established diagnosis of prediabetes or diabetes referred for a 2-hour glucose tolerance test according to American Diabetes Association criteria. Patients were divided into 3 groups: peripheral neuropathies, trigger finger, and controls with various upper-extremity diagnoses. Rates of undiagnosed prediabetes and diabetes were compared between groups, including subgroup analysis of patients based on unilateral or bilateral presentation. Binary logistic regression analysis was also used to calculate odds ratios for multiple variables., Results: Patients with neuropathy had a significantly higher incidence of undiagnosed dysglycemia compared with the control group. Of those patients, 51.3% were prediabetic and 12.8% were diabetic. The control group had significantly lower rates. Within the bilateral neuropathy patients, 59.6% had prediabetes and 15.4% had diabetes, versus 34.6% with prediabetes and 7.7% with diabetes in the unilateral group., Conclusions: Hand surgeons encounter a patient population with high rates of undiagnosed prediabetes and diabetes, with some presentations as much as 6 times higher than the general population. Certain patient presentations should prompt appropriate diagnostic testing and referral, especially those presenting with bilateral compression neuropathy and elevated body mass index., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Tick-borne flaviviruses (TBFV) can cause severe neuroinvasive disease which may result in death or long-term neurological deficit in over 50% of survivors. Multiple mechanisms for invasion of the central nervous system (CNS) by flaviviruses have been proposed including axonal transport, transcytosis, endothelial infection, and Trojan horse routes. Flaviviruses may utilize different or multiple mechanisms of neuroinvasion depending on the specific virus, infection site, and host variability. In this work we have shown that the infection of BALB/cJ mice with either Powassan virus lineage I (Powassan virus) or lineage II (deer tick virus) results in distinct spatial tropism of infection in the CNS which correlates with unique clinical presentations for each lineage. Comparative transcriptomics of infected brains demonstrates the activation of different immune pathways and downstream host responses. Ultimately, the comparative pathology and transcriptomics are congruent with different clinical signs in a murine model. These results suggest that the different disease presentations occur in clinical cases due to the inherent differences in the two lineages of Powassan virus.

Purpose: The purpose of this study was to determine the safety and effectiveness of office-based carpal tunnel release with ultrasound guidance (CTR-US)., Methods: In this prospective multicenter observational study, patients were treated with CTR-US in an office setting. Outcomes were time to resume normal daily activities, time to return to work, Boston Carpal Tunnel Questionnaire Symptom Severity Scale and Functional Status Scale scores, Michigan Hand Questionnaire, Numeric Pain Scale, EuroQoL-5 Dimension 5-Level score, procedure satisfaction, and adverse events over 6 months., Results: A total of 149 participants (226 hands) from seven centers underwent office-based CTR-US. The mean age was 58 years, 52% were women, and 68% were employed. The mean incision length was 5 mm, 52% had simultaneous bilateral procedures, and wide-awake local anesthesia no tourniquet was used in all cases. All procedures were completed as planned, with no conversions to open repair and mean intraoperative pain severity of 1.6 ± 1.5. The median time to resume normal activities was 2 days (interquartile range: 1-4 days) and return to work was 4 days (interquartile range: 1-5 days). Over 6 months, Boston Carpal Tunnel Questionnaire Symptom Severity Scale decreased by a mean of 1.7 points, Boston Carpal Tunnel Questionnaire Functional Status Scale decreased by 1.1 points, Michigan Hand Questionnaire Global score increased by 35 points, Numeric Pain Scale decreased by 3.7 points, and EuroQoL-5 Dimension 5-Level score increased by 0.11 points. At 6 months, 94% reported procedure satisfaction. Unilateral and simultaneous bilateral procedures were similarly effective. There was one (0.4%) adverse event, a nerve contusion treated with neurolysis and nerve wrap where the patient fully regained normal function within 7 weeks. There were no revisions for persistent or recurrent carpal tunnel syndrome symptoms., Conclusions: Office-based CTR-US, performed either unilaterally or as simultaneous bilateral procedures, is well tolerated with a low complication rate and associated with rapid recovery, sustained improvement in symptoms and function, and high procedure satisfaction., Type of Study/level of Evidence: Therapeutic III., (© 2024 The Authors.)

Introduction: Hearing protection devices (HPDs) are standard personal protective equipment in military settings, but many service members may choose to not use HPDs because they impair spatial hearing and situation awareness. In an effort to reduce barriers to compliance by improving situation awareness while wearing HPDs, this study investigated whether brief training could counteract spatial hearing deficits when wearing HPDs. Participant's ability to correctly apply the HPDs across days was also examined., Materials and Methods: Young adults were randomly assigned to one of two groups: training or control (n = 25/group). Participants in each group performed a spatial hearing task while wearing HPDs and in an open ear condition without HPDs. Individual targets were battlefield sounds or white noise presented from a speaker array that surrounded the participant in the horizontal plane. After presentation of each target sound, the participant then controlled a white noise "auditory pointer," which they moved to the perceived location of the target. The two primary measures were the percent of trials with very large errors (> 45°), which were usually due to confusing front and back locations, and absolute localization, which is the difference between the pointer location and the true sound location. Both groups were tested on Days 1 (baseline) and 5 (post-test). On Days 2 to 4, the training group wore HPDs while receiving auditory and visual feedback after each trial., Results: Across all participants on Day 1, wearing HPDs increased the frequency of very large errors by about 3× and impaired localization by about 40%, relative to the open ear condition. When comparing performance at baseline (Day 1) and post-training Day 5, the training group with HPDs had significant reductions in very large errors and improved absolute localization (P values < .001). The training group also had significant improvements from Days 1 to 5 in the open ear condition. When the control group wore HPDs, there were also significant improvements from Days 1 to 5 (fewer very large errors and better localization), with smaller effect sizes vs. the training group. Controls did not have significant improvement in the open ear condition, but had similar trends. Most participants consistently applied the HPDs, but a subset of ∼20% frequently failed to achieve the criterion attenuation of 15 dB (over 0.25-4.0 kHz) in both ears., Conclusions: These findings show that simple, relatively brief practice and training can substantially reduce HPD impairments on spatial hearing and situation awareness. The gains from training and practice can inform the development of relatively simple, brief methods to reduce HPD spatial hearing impairments, potentially leading to increased HPD compliance. Longitudinal data show that a subset of participants would not have received the full benefit of hearing protection because of improper application of the HPDs., (© The Association of Military Surgeons of the United States 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: This study aimed to determine if "short" femoral stems were noninferior to (at least as good as) standard-length stems in regards to 90-day periprosthetic fracture and 1-year revision rates., Methods: Using the MARCQI implant registry, a retrospective study of statewide data was carried out on 64,084 total hip arthroplasties (THAs) between 2012 and 2017. We noticed an increase in the use of "short" uncemented femoral hip stems during THA. Chi-square tests were used to test homogeneity of categorical variables. The covariates included in the analyses were identified using modern epidemiological methods. A Type I probability of 0.05 was used as the level of statistical significance. Inverse probability of treatment weighting (IPTW) was used to mitigate confounding variables., Results: One hundred and seven stems were implanted by surgeons in the state of Michigan. They were classified according to the Khanuja Classification System as Type 2A (trapezoidal, double-tapered calcar loading, n = 3,281), Type 3 (calcar loading with lateral flare, n = 1,898), and Type 4 (shortened, tapered, conventional, n = 19,580), and were compared to standard-length, type 5, stems (n = 33,322) in regards to the 2 outcomes (periprosthetic fractures and 1-year revision rates). Overall, 1-year revision and the 90-day fracture rates were 1.3% (791/57,853) and 1.1% (631/57,968), respectively. Noninferiority was established for all short stems at the clinical threshold of an odds ratio (OR) of 1.5 with P-values <0.05 for 90-day fractures. In regards to 1-year revision rates, noninferiority was also established for Type 3 and 4 stems (P < .05)., Conclusion: The increased use of "short stems" in Michigan did not lead to increased 1-year revision or 90-day fracture rates., (Copyright © 2023. Published by Elsevier Inc.)

Background: A limited number of studies have been conducted to test the magnitudes of the association between apparent treatment resistant hypertension (aTRH) and risk of cardiovascular disease (CVD)., Aim: To investigate the association between aTRH and risk of CVD and examine whether sex and age modify this association., Methods: We applied an observational analysis study design using data from the United States Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT recruited participants ( n = 25516) from 625 primary care settings throughout the United States, Canada, Puerto Rico, and United States Virgin Islands, aged 55 and older with hypertension and at least one additional risk factor for heart disease. aTRH was assessed from the year 2 visit. CVD event was defined as one of the following from the year 2 follow-up visit: Fatal or non-fatal myocardial infarction, coronary revascularization, angina, stroke, heart failure, or peripheral artery disease. Cox proportional hazards regression was used to examine the effect of aTRH on CVD risk. Potential modifications of sex and age on this association were examined on the multiplicative scale by interaction term and additive scale by joint effects and relative excess risk for interaction., Results: Of the total study participants ( n = 25516), 5030 experienced a CVD event during a mean of 4.7 years follow-up. aTRH was associated with a 30% increase in risk of CVD compared to non-aTRH [hazards ratio (HR) = 1.3, 95%CI: 1.19-1.42]. Sex and age modified this relationship on both multiplicative and additive scales independently. Stratified by sex, aTRH was associated with a 64% increase in risk of CVD (HR = 1.64, 95%CI: 1.43-1.88) in women, and a 13% increase in risk of CVD (HR = 1.13, 95%CI: 1.01-1.27) in men. Stratified by age, aTRH had a stronger impact on the risk of CVD in participants aged < 65 (HR = 1.53, 95%CI: 1.32-1.77) than it did in those aged ≥ 65 (HR = 1.18, 95%CI: 1.05-1.32). Significant two-way interactions of sex and aTRH, and age and aTRH on risk of CVD were observed ( P < 0.05). The observed joint effect of aTRH and ages ≥ 65 years (HR = 1.85, 95%CI: 1.22-2.48) in males was less than what was expected for both additive and multiplicative models (HR = 4.10, 95%CI: 3.63-4.57 and 4.88, 95%CI: 3.66-6.31), although three-way interaction of sex, age, and aTRH on the risk of CVD and coronary heart disease did not reach a statistical significance ( P > 0.05)., Conclusion: aTRH was significantly associated with an increased risk of CVD and this association was modified by both sex and age. Further studies are warranted to test these mechanisms., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

A 5-month-old castrated male Smooth Fox Terrier presented for a 1-month history of right thoracic limb lameness. Physical examination revealed right elbow pain on extension and mild soft tissue swelling of the distal antebrachium. Radiographs and computed tomography showed elongated focal radiolucent regions in the distal radial metaphysis. There was incongruity of the right elbow with a short radius. Bone biopsy and histopathology of the regions confirmed a retained cartilaginous core characterised by bony trabeculae with frequently retained central cartilaginous cores. A dynamic proximal ulnar ostectomy was performed to improve elbow congruity. The owner was instructed to restrict activity to short leash walks for 8 weeks followed by a gradual activity increase. On follow-up examination 16 weeks after operatively, the lameness and elbow pain were resolved. Radiographs at that time showed a healed ulnar ostectomy, proper elbow congruity, and resolved retained cartilaginous core., (© 2023 British Small Animal Veterinary Association.)

The present study evaluated whether Grooved Pegboard (GPB), when used as a performance validity test (PVT), can incrementally predict psychiatric symptom report elevations beyond memory-apparent PVTs. Participants ( N  = 111) were military personnel and were predominantly White (84%), male (76%), with a mean age of 43 ( SD =  12) and having on average 16 years of education ( SD  = 2). Individuals with disorders potentially compromising motor dexterity were excluded. Participants were administered GPB, three memory-apparent PVTs (Medical Symptom Validity Test, Non-Verbal Medical Symptom Validity Test, Reliable Digit Span), and a symptom validity test (Personality Assessment Inventory Negative Impression Management [NIM]). Results from the three memory-apparent PVTs were entered into a model for predicting NIM, where failure of two or more PVTs was categorized as evidence of non-credible responding. Hierarchical regression revealed that non-dominant hand GPB T-score incrementally predicted NIM beyond memory-apparent PVTs ( F (2,108) = 16.30, p < .001; R 2 change = .05, β = -0.24, p < .01). In a second hierarchical regression, GPB performance was dichotomized into pass or fail, using T -score cutoffs (≤29 for either hand, ≤31 for both). Non-dominant hand GPB again predicted NIM beyond memory-apparent PVTs ( F (2,108) = 18.75, p <.001; R 2 change = .08, β = -0.28, p < .001). Results indicated that noncredible/failing GPB performance adds incremental value over memory-apparent PVTs in predicting psychiatric symptom report.

Objectives: To examine and categorize symptoms occurring within 60 s of vertebrobasilar-insufficiency (VBI) testing (left- and right-neck rotation) in individuals with persistent post-traumatic headache., Background: As part of routine clinical cervical screening in our patients, we found extended VBI testing often triggered additional symptoms. Therefore, we aimed to document the prevalence and precise symptoms occurring during each movement direction of this test and determine any demographic or baseline signs or symptoms associated with a positive test., Methods: A retrospective medical record review on military personnel receiving treatment for persistent post-traumatic headache was performed. Participants were grouped according to presence of non-headache related symptoms triggered during the tests. Frequency, onset, and symptom characteristics reported were categorized as potentially vascular and/or possible autonomic or cranial nerve in nature., Results: At least one symptom was reported by 81.3% of 123 patients. Of these, 54% reported symptoms in one and 46% in both directions of rotation, yielding 146 abnormal tests. Most reported symptoms were tear disruption (41%), altered ocular-motor-control (25%), and blepharospasm (16%). Enlisted individuals and those with altered baseline facial sensation were more likely to have a positive test., Conclusions: The majority reported symptoms not typical of VBI within 60 seconds of sustained neck rotation. Further study is needed to better understand the mechanisms and clinical relevance.

Rapid detection of volatile organic compounds (VOCs) is growing in importance in many sectors. Noninvasive medical diagnoses may be based upon particular combinations of VOCs in human breath; detecting VOCs emitted from environmental hazards such as fungal growth could prevent illness; and waste could be reduced through monitoring of gases produced during food storage. Electronic noses have been applied to such problems, however, a common limitation is in improving selectivity. Graphene is an adaptable material that can be functionalized with many chemical receptors. Here, we use this versatility to demonstrate selective and rapid detection of multiple VOCs at varying concentrations with graphene-based variable capacitor (varactor) arrays. Each array contains 108 sensors functionalized with 36 chemical receptors for cross-selectivity. Multiplexer data acquisition from 108 sensors is accomplished in tens of seconds. While this rapid measurement reduces the signal magnitude, classification using supervised machine learning (Bootstrap Aggregated Random Forest) shows excellent results of 98% accuracy between 5 analytes (ethanol, hexanal, methyl ethyl ketone, toluene, and octane) at 4 concentrations each. With the addition of 1-octene, an analyte highly similar in structure to octane, an accuracy of 89% is achieved. These results demonstrate the important role of the choice of analysis method, particularly in the presence of noisy data. This is an important step toward fully utilizing graphene-based sensor arrays for rapid gas sensing applications from environmental monitoring to disease detection in human breath.

Selection and effort are central to attention, yet it is unclear whether they draw on a common pool of cognitive resources, and if so, whether there are differences for early versus later stages of cognitive processing. This study assessed effort by quantifying the vigilance decrement, and spatial processing at early and later stages as a function of time-on-task. Participants performed an auditory spatial attention task, with occasional "catch" trials requiring no response. Psychophysiological measures included bilateral cerebral blood flow (transcranial Doppler), pupil dilation, and blink rate. The shape of attention gradients using reaction time indexed early processing, and did not significantly vary over time. Later stimulus-response conflict was comparable over time, except for a reduction to left hemispace stimuli. Target and catch trial accuracy decreased with time, with a more abrupt decrease for catch versus target trials. Diffusion decision modeling found progressive decreases in information accumulation rate and non-decision time, and the adoption of more liberal response criteria. Cerebral blood flow increased from baseline and then decreased over time, particularly in the left hemisphere. Blink rate steadily increased over time, while pupil dilation increased only at the beginning and then returned towards baseline. The findings suggest dissociations between resources for selectivity and effort. Measures of high subjective effort and temporal declines in catch trial accuracy and cerebral blood flow velocity suggest a standard vigilance decrement was evident in parallel with preserved selection. Different attentional systems and classes of computations that may account for dissociations between selectivity versus effort are discussed., (© 2021 Society for Psychophysiological Research.)

Predicting the potential fate of a species in the face of climate change requires knowing the distribution of molecular adaptations across the geographic range of the species. In this work, we analysed 79 genomes of Theobroma cacao, an Amazonian tree known for the fruit from which chocolate is produced, to evaluate how local and regional molecular signatures of adaptation are distributed across the natural range of the species. We implemented novel techniques that incorporate summary statistics from multiple selection scans to infer selective sweeps. The majority of the molecular adaptations in the genome are not shared among populations. We show that ~71.5% of genes under selection also show significant associations with changes in environmental variables. Our results support the interpretation that these genes contribute to local adaptation of the populations in response to abiotic factors. We also found strong patterns of molecular adaptation in a diverse array of disease resistance genes (6.5% of selective sweeps), suggesting that differential adaptation to pathogens also contributes significantly to local adaptations. Our results are consistent with the interpretation that local selective pressures are more important than regional selective pressures in explaining adaptation across the range of a species., (© 2020 John Wiley & Sons Ltd.)

Inclusion and subsequent reporting of minority participants in clinical trials are critical for ensuring external validity and detecting differences among subgroups, however reports suggest that ongoing gaps persist. ClinicalTrials.gov began requiring the reporting of race/ethnicity information (if collected) during results submission for trials in April 2017. For this study, we downloaded and compared trial race/ethnicity information from ClinicalTrials.gov submitted before (N = 3540) and after (N = 3542) the requirement date. We found that 42.0% of pre-requirement trials compared to 91.4% of post-requirement trials reported race/ethnicity information in ClinicalTrials.gov; 8.6% of post-requirement trials indicated race/ethnicity information was not collected. Use of NIH/U.S. Office of Management and Budget (OMB) classification categories was slightly higher in the post-requirement (77.1%) compared to pre-requirement (72.8%) samples. Additionally, we examined two 10% random samples of post-requirement trials - one with customized race/ethnicity reporting in ClinicalTrials.gov and the other with corresponding results publications available in PubMed. In the first random sample, 95.9% of customized categories included race information and 52.7% included ethnicity information. In the other random sample, 33.1% had a corresponding results publication, of which 62.4% reported race/ethnicity information in the publication. Among trials without published race/ethnicity information, 90.0% reported race/ethnicity information on ClinicalTrials.gov. This analysis demonstrates that the requirement has advanced public availability of information on the inclusion of minorities in research, but that further work remains to systematically ensure collection and complete reporting of race/ethnicity information., (Published by Elsevier Inc.)

To maintain energy homeostasis during cold exposure, the increased energy demands of thermogenesis must be counterbalanced by increased energy intake. To investigate the neurobiological mechanisms underlying this cold-induced hyperphagia, we asked whether agouti-related peptide (AgRP) neurons are activated when animals are placed in a cold environment and, if so, whether this response is required for the associated hyperphagia. We report that AgRP neuron activation occurs rapidly upon acute cold exposure, as do increases of both energy expenditure and energy intake, suggesting the mere perception of cold is sufficient to engage each of these responses. We further report that silencing of AgRP neurons selectively blocks the effect of cold exposure to increase food intake but has no effect on energy expenditure. Together, these findings establish a physiologically important role for AgRP neurons in the hyperphagic response to cold exposure., Competing Interests: JD, CF, CP, BP, SL, KO, JN, VD, MT, RP, KK, JS, MB, MS, GM No competing interests declared, (© 2020, Deem et al.)

Background: Young-Burgess classification (YB) is a mechanistic system which classifies pelvic ring injuries into anterior-posterior compression (APC), lateral compression (LC), vertical shear (VS) injuries, and combined mechanism (CM). The objective of this study was to identify associated injuries which require urgent operative intervention by YB classification. We hypothesize that YB classification is associated with 1) need for urgent intervention for pelvic fracture-related hemorrhage and 2) patterns of injury complexes requiring surgery., Methods: This is a retrospective study of severely injured trauma patients with pelvic ring injuries who presented to an urban Level-1 trauma center from 2007 to 2017. Associated injuries and procedures were determined by Abbreviated Injury Scale (AIS) and ICD-9/10 codes. YB classes were compared, followed by a cluster analysis to identify injury patterns and association with YB classifications., Results: Overall, 135 patients were included. 98 (72%) of patients presented with LC, 16 (12%) with APC, 8 (6%) with VS, and 13 (10%) with CM. VS and APC groups had higher rates of REBOA use compared to LC and CM groups (38% and 31% versus 11% and 0%, respectively, p = 0.01). The CM group, compared to LC, APC, and VS, had higher rates of urgent operative intervention for bleeding control (69% versus 32%, 50% and 43%, respectively, p = 0.01). 39 (29%) patients had a concomitant injury which was identified by CT scan in initial trauma work up and altered management, 46% which merited urgent intervention. On cluster analysis, there were no distinct injury complexes which required urgent operative intervention by YB class., Conclusions: These data failed to identify unique injury complexes which merit urgent operative intervention by YB class. Nearly one in four patients had injuries identified by initial CT imaging which altered initial management, demonstrating the importance of early, full body CT imaging in severely injured patients with pelvic ring injuries., (© 2020 Delhi Orthopedic Association. All rights reserved.)

Objective: To describe the prevalence and impact of vestibular dysfunction and nonspecific dizziness diagnoses and explore their associations with traumatic brain injury (TBI) severity, mechanism, and postconcussive comorbidities among post-9/11 veterans., Setting: Administrative medical record data from the US Departments of Defense and Veterans Affairs (VA)., Participants: Post-9/11 veterans with at least 3 years of VA care., Design: Cross-sectional, retrospective, observational study., Main Measures: International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for TBI, vestibular dysfunction, dizziness, and other commonly associated postconcussive conditions; Neurobehavioral Symptom Inventory., Results: Of the 570 248 post-9/11 veterans in this sample, 0.45% had a diagnosis of vestibular dysfunction and 2.57% had nonspecific dizziness. Those with either condition were more likely to have evidence of TBI (57.11% vs 28.51%) and reported more disruption from neurobehavioral symptoms. Blast and nonblast injuries were associated with greater symptom disruption, particularly in combination., Conclusions: There was a consistent, significant association between TBI and vestibular dysfunction or nonspecific dizziness, after controlling for sociodemographic factors, injury mechanism, and comorbid conditions. Given that most deployed post-9/11 veterans report blast and/or nonblast injuries, the need for prompt identification and management of these conditions and symptoms is clear.

Background: Trauma patients with pelvic fractures have a high rate of venous thromboembolism (VTEs). The reason for this high rate is unknown. We hypothesize that fibrinolysis shutdown (SD) predicts VTE in patients with severe pelvic fracture., Methods: Retrospective chart review of trauma patients who presented with pelvic fracture from 2007 to 2017 was performed. Inclusion criteria were injury severity score > 15, abdomen/pelvis abbreviated injury scale >/= 3, blunt mechanism, admission citrated rapid thrombelastography (TEG). Fibrinolytic phenotypes were defined by fibrinolysis on citrated rapid TEG as hyperfibrinolysis, physiologic lysis, and SD. Univariate analysis of TEG measurements and clinical outcomes, followed by multivariable logistic regression (MV) with stepwise selection, was performed., Results: Overall, 210 patients were included. Most patients (59%) presented in fibrinolytic shutdown. VTE incidence was 11%. There were no significant differences in fibrinolytic phenotypes or other TEG measurements between those who developed VTE and those who did not. There was a higher rate of VTE in patients who underwent pelvic external fixation or resuscitative thoracotomy. On MV, pelvic fixation and resuscitative thoracotomy were independent predictors of VTE., Conclusions: In severely injured patients with pelvic fractures, there was a high rate of VTE and the majority presented in SD. However, we were unable to correlate initial SD with VTE. Ultimately, the high rate of VTE in this patient population supports the concept of implementing VTE chemoprophylaxis measures as soon as hemostasis is achieved., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Plasma thrombin generation has been used to characterize trauma-induced coagulopathy, but description of whole blood thrombin generation is lacking. This study aimed to evaluate plasma and whole blood thrombin generation in healthy volunteers and trauma patients. We hypothesized that (1) plasma and whole blood thrombin generation are distinct, (2) whole blood thrombin generation is more pronounced in trauma patients than in healthy volunteers, and (3) thrombin generation correlates with clinical coagulation assays., Methods: Blood was collected from healthy volunteers and trauma patients at a single, level-1 trauma center. Whole blood thrombin generation was assessed with a prototype point-of-care whole blood thrombin generation device, and plasma thrombin generation was measured with a calibrated automated thrombogram analogue. Plasma and whole blood thrombin generation were compared and correlated with international normalized ratio and thrombelastography., Results: Overall, 10 healthy volunteers (average age 30, 50% men) were included and 58 trauma patients (average age 34, 76% men, 55% blunt mechanism, and with a median new injury severity score of 17) were included. Plasma and whole blood thrombin generation differed with more robust thrombin generation in plasma. Trauma patients had a significantly increased whole blood thrombin generation compared with healthy volunteers]. Plasma thrombin generation correlated with international normalized ratio, whereas whole blood thrombin generation did not correlate with thrombelastography., Conclusion: Plasma and whole blood thrombin generation are distinct, highlighting the need to perform standardized assays to better understand their correlation and to assess how whole blood thrombin generation confers differential outcomes in trauma., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We propose a statistical multiscale mapping approach to identify microscopic and molecular heterogeneity across a tumor microenvironment using multiparametric MR (mp-MR). Twenty-nine patients underwent pre-surgical mp-MR followed by MR-guided stereotactic core biopsy. The locations of the biopsy cores were identified in the pre-surgical images using stereotactic bitmaps acquired during surgery. Feature matrices mapped the multiparametric voxel values in the vicinity of the biopsy cores to the pathologic outcome variables for each patient and logistic regression tested the individual and collective predictive power of the MR contrasts. A non-parametric weighted k-nearest neighbor classifier evaluated the feature matrices in a leave-one-out cross validation design across patients. Resulting class membership probabilities were converted to chi-square statistics to develop full-brain parametric maps, implementing Gaussian random field theory to estimate inter-voxel dependencies. Corrections for family-wise error rates were performed using Benjamini-Hochberg and random field theory, and the resulting accuracies were compared. The combination of all five image contrasts correlated with outcome (P < 10 -4 ) for all four microscopic variables. The probabilistic mapping method using Benjamini-Hochberg generated statistically significant results (α ≤ 0.05) for three of the four dependent variables: (1) IDH1, (2) MGMT, and (3) microvascular proliferation, with an average classification accuracy of 0.984 ± 0.02 and an average classification sensitivity of 1.567% ± 0.967. The images corrected by random field theory demonstrated improved classification accuracy (0.989 ± 0.008) and classification sensitivity (5.967% ± 2.857) compared with Benjamini-Hochberg. Microscopic and molecular tumor properties can be assessed with statistical confidence across the brain from minimally-invasive, mp-MR.

In this work, we investigated the use of real-time functional magnetic resonance imaging (fMRI) with neurofeedback training (NFT) to teach volitional down-regulation of the auditory cortex (AC) using directed attention strategies as there is a growing interest in the application of fMRI-NFT to treat neurologic disorders. Healthy participants were separated into two groups: the experimental group received real feedback regarding activity in the AC; the control group was supplied sham feedback yoked from a random participant in the experimental group and matched for fMRI-NFT experience. Each participant underwent five fMRI-NFT sessions. Each session contained 2 neurofeedback runs where participants completed alternating blocks of "rest" and "lower" conditions while viewing a continuously-updated bar representing AC activation and listening to continuous noise. Average AC deactivation was extracted from each closed-loop neuromodulation run and used to quantify the control over AC (AC control), which was found to significantly increase across training in the experimental group. Additionally, behavioral testing was completed outside of the MRI on sessions 1 and 5 consisting of a subjective questionnaire to assess attentional control and two quantitative tests of attention. No significant changes in behavior were observed; however, there was a significant correlation between changes in AC control and attentional control. Also, in a neural assessment before and after fMRI-NFT, AC activity in response to continuous noise stimulation was found to significantly decrease across training while changes in AC resting perfusion were found to be significantly greater in the experimental group. These results may be useful in formulating effective therapies outside of the MRI, specifically for chronic tinnitus which is often characterized by hyperactivity of the primary auditory cortex and altered attentional processes. Furthermore, the modulation of attention may be useful in developing therapies for other disorders such as chronic pain., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to assess the outcomes of 2 treatments for patients with dizziness after mild traumatic brain injury (mTBI) who demonstrate abnormal cervical spine proprioception (CSP)., Methods: A retrospective records review was conducted on the medical charts of patients treated for dizziness after mTBI who received either standard care (vestibular rehabilitation therapy [VRT]) or cervical spine proprioceptive retraining (CSPR) from 2009 to 2013. All patients included in the analysis were active-duty military with recurring dizziness after mTBI who had at least 1 abnormal CSP test. Patients were excluded for dizziness with a clear peripheral vestibular or central symptom origin, incomplete data, or no CSP assessment, or if both treatments were administered. Forty-eight total patients were included in the final dataset (22 VRT; 26 CSPR). Traditional VRT was compared with CSPR when abnormal CSP tests were present, regardless of the presence or absence of neck pain. A clinician review of records was used to determine improvement of dizziness based on patient reports of symptoms at discharge evaluation (ie, no symptoms for at least 2 weeks)., Results: Patients who received CSPR were 30 times more likely to report improvement in dizziness symptoms compared with those who received VRT (adjusted odds ratio: 30.12; 95% confidence interval 4.44-204.26, P < .001) when abnormal CSP tests were present. Patients with dizziness over 1 year were significantly less likely to improve., Conclusion: These results suggest that patients with dizziness after mTBI and who had abnormal CSP assessments responded better to CSPR compared with those who received VRT., (Copyright © 2019. Published by Elsevier Inc.)

Research has demonstrated that hyperbaric oxygen (HBO 2 ) treatment produced relief of both acute and chronic pain in patients and animal models. However, the mechanism of HBO 2 antinociceptive effect is still elusive. Based on our earlier findings that implicate NO in the acute antinociceptive effect of HBO 2 , the purpose of this study was to ascertain whether HBO 2 -induced antinociception in a chronic neuropathic pain model is likewise dependent on NO. Neuropathic pain was induced in male Sprague Dawley rats by four injections of paclitaxel (1.0 mg/kg, i.p.). Twenty-four hours after the last paclitaxel injection, rats were treated for one day or four consecutive days with 60-min HBO 2 at 3.5 atmospheres absolute (ATA). Two days before HBO 2 treatment, some groups of rats were implanted with Alzet® osmotic minipumps that continuously infused a selective inhibitor of neuronal NO synthase (nNOS) into the lateral cerebral ventricle for 7 days. Mechanical and cold allodynia were assessed every other day, using electronic von Frey and acetone assays, respectively. Rats in the paclitaxel control group exhibited a mechanical or cold allodynia that was significantly reversed by one HBO 2 treatment for mechanical allodynia and four HBO 2 treatments for cold allodynic. In rats treated with the nNOS inhibitor, the effects of HBO 2 were nullified in the mechanical allodynia test but unaffected in the cold allodynia test. In summary, these results demonstrate that the antiallodynic effect of HBO 2 in two different pain tests is dependent on NO in the CNS., (Copyright © 2019. Published by Elsevier B.V.)

Introduction: To date, no method has been described or utilized to study the distribution of symptoms in carpal tunnel syndrome. We describe a technique of symptom-mapping that yields a population-based "anatomic profile" of carpal tunnel syndrome., Methods: Symptoms were mapped on visual questionnaires depicting the volar hand, wrist, and forearm. Thirty-four hands in 26 patients with isolated carpal tunnel syndrome were included in the study., Results: Painful symptoms were clearly centered over the carpal tunnel and were reported much less frequently in the digits. Nonpainful sensory disturbances (e.g., numbness, paresthesias) were found to have a much more peripheral and lateral distribution., Discussion: Our technique serves to establish a population-based "anatomic profile" of carpal tunnel syndrome, assisting with clinical diagnosis and serving as a reference point for the comparison of pretreatment and posttreatment clinical data. Muscle Nerve 59:321-325, 2019., (© 2018 Wiley Periodicals, Inc.)

Background: La Crosse virus (LACV) causes pediatric encephalitis in the USA. LACV induces severe inflammation in the central nervous system, but the recruitment of inflammatory cells is poorly understood. A deeper understanding of LACV-induced neural pathology is needed in order to develop treatment options. However, there is a severe limitation of relevant human neuronal cell models of LACV infection., Methods: We utilized human neural stem cell (hNSC)-derived neuron/astrocyte co-cultures to study LACV infection in disease-relevant primary cells. hNSCs were differentiated into neurons and astrocytes and infected with LACV. To characterize susceptibility and responses to infection, we measured viral titers and levels of viral RNA, performed immunofluorescence analysis to determine the cell types infected, performed apoptosis and cytotoxicity assays, and evaluated cellular responses to infection using qRT-PCR and Bioplex assays., Results: hNSC-derived neuron/astrocyte co-cultures were susceptible to LACV infection and displayed apoptotic responses as reported in previous in vitro and in vivo studies. Neurons and astrocytes are both targets of LACV infection, with neurons becoming the predominant target later in infection possibly due to astrocytic responses to IFN. Additionally, neuron/astrocyte co-cultures responded to LACV infection with strong proinflammatory cytokine, chemokine, as well as MMP-2, MMP-7, and TIMP-1 responses., Conclusions: hNSC-derived neuron/astrocyte co-cultures reproduce key aspects of LACV infection in humans and mice and are useful models to study encephalitic viruses. Specifically, we show astrocytes to be susceptible to LACV infection and that neurons and astrocytes are important drivers of the inflammatory responses seen in LACV infection through the production of proinflammatory cytokines and chemokines.

The ability to maintain core temperature within a narrow range despite rapid and dramatic changes in environmental temperature is essential for the survival of free-living mammals, and growing evidence implicates an important role for the hormone leptin. Given that thyroid hormone plays a major role in thermogenesis and that circulating thyroid hormone levels are reduced in leptin-deficient states (an effect partially restored by leptin replacement), we sought to determine the extent to which leptin's role in thermogenesis is mediated by raising thyroid hormone levels. To this end, we 1) quantified the effect of physiological leptin replacement on circulating levels of thyroid hormone in leptin-deficient ob/ob mice, and 2) determined if the effect of leptin to prevent the fall in core temperature in these animals during cold exposure is mimicked by administration of a physiological replacement dose of triiodothyronine (T 3 ). We report that, as with leptin, normalization of circulating T 3 levels is sufficient both to increase energy expenditure, respiratory quotient, and ambulatory activity and to reduce torpor in ob/ob mice. Yet, unlike leptin, infusing T 3 at a dose that normalizes plasma T 3 levels fails to prevent the fall of core temperature during mild cold exposure. Because thermal conductance (e.g., heat loss to the environment) was reduced by administration of leptin but not T 3 , leptin regulation of heat dissipation is implicated as playing a uniquely important role in thermoregulation. Together, these findings identify a key role in thermoregulation for leptin-mediated suppression of thermal conduction via a mechanism that is independent of the thyroid axis.

The present work assessed the efficacy of training volitional down-regulation of the primary auditory cortex (A1) based on real-time functional magnetic resonance imaging neurofeedback (fMRI-NFT). A1 has been shown to be hyperactive in chronic tinnitus patients, and has been implicated as a potential source for the tinnitus percept. 27 healthy volunteers with normal hearing underwent 5 fMRI-NFT sessions: 18 received real neurofeedback and 9 sham neurofeedback. Each session was composed of a simple auditory fMRI followed by 2 runs of A1 fMRI-NFT. The auditory fMRI alternated periods of no auditory with periods of white noise stimulation at 90 dB. A1 activity, defined from a region using the activity during the preceding auditory run, was continuously updated during fMRI-NFT using a simple bar plot, and was accompanied by white noise (90 dB) stimulation for the duration of the scan. Each fMRI-NFT run alternated "relax" periods with "lower" periods. Subjects were instructed to watch the bar during the relax condition and actively reduce the bar by decreasing A1 activation during the lower condition. Average A1 de-activation, representative of the ability to volitionally down-regulate A1, was extracted from each fMRI-NFT run. A1 de-activation was found to increase significantly across training and to be higher in those receiving real neurofeedback. A1 de-activation in sessions 2 and 5 were found to be significantly greater than session 1 in only the group receiving real neurofeedback. The most successful subjects reportedly adopted mindfulness tasks associated with directed attention. For the first time, fMRI-NFT has been applied to teach volitional control of A1 de-activation magnitude over more than 1 session. These are important findings for therapeutic development as the magnitude of A1 activity is altered in tinnitus populations and it is unlikely a single fMRI-NFT session will reverse the effects of tinnitus., Competing Interests: Conflict of interest: The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2018 the Author(s), licensee AIMS Press.)

Influenza virus infections can be complicated by bacterial superinfections, which are medically relevant because of a complex interaction between the host, the virus, and the bacteria. Studies to date have implicated several influenza virus genes, varied host immune responses, and bacterial virulence factors, however, the host-pathogen interactions that predict survival versus lethal outcomes remain undefined. Previous work by our group showed that certain influenza viruses could yield a survival phenotype (A/swine/Texas/4199-2/98-H3N2, TX98), whereas others were associated with a lethal phenotype (A/Puerto Rico/8/34-H1N1, PR8). Based on this observation, we developed the hypothesis that individual influenza virus genes could contribute to a superinfection, and that the host response after influenza virus infection could influence superinfection severity. The present study analyzes individual influenza virus gene contributions to superinfection severity using reassortant viruses created using TX98 and PR8 viral genes. Host and pathogen interactions, relevant to survival and lethal phenotypes, were studied with a focus on pathogen clearance, host cellular infiltrates, and cytokine levels after infection. Specifically, we found that the hemagglutinin gene expressed by an influenza virus can contribute to the severity of a secondary bacterial infection, likely through modulation of host proinflammatory responses. Altogether, these results advance our understanding of molecular mechanisms underlying influenza virus-bacteria superinfections and identify viral and corresponding host factors that may contribute to morbidity and mortality.

Background : Dorsolateral prefrontal cortex (DLPFC) low frequency repetitive transcranial magnetic stimulation (LF-rTMS) has shown promise as a treatment and investigative tool in the medical and research communities. Researchers have made significant progress elucidating DLPFC LF-rTMS effects-primarily in individuals with psychiatric disorders. However, more efforts investigating underlying molecular changes and establishing links to functional and behavioral outcomes in healthy humans are needed. Objective : We aimed to quantify neuromolecular changes and relate these to functional changes following a single session of DLPFC LF-rTMS in healthy participants. Methods : Eleven participants received sham-controlled neuronavigated 1 Hz rTMS to the region most activated by a 7-letter Sternberg working memory task (SWMT) within the left DLPFC. We quantified SWMT performance, functional magnetic resonance activation and proton Magnetic resonance spectroscopy (MRS) neurometabolite measure changes before and after stimulation. Results : A single LF-rTMS session was not sufficient to change DLPFC neurometabolite levels and these changes did not correlate with DLPFC activation changes. Real rTMS, however, significantly altered neurometabolite correlations (compared to sham rTMS), both with baseline levels and between the metabolites themselves. Additionally, real rTMS was associated with diminished reaction time (RT) performance improvements and increased activation within the motor, somatosensory and lateral occipital cortices. Conclusion : These results show that a single session of LF-rTMS is sufficient to influence metabolite relationships and causes widespread activation in healthy humans. Investigating correlational relationships may provide insight into mechanisms underlying LF-rTMS.

Objectives: To describe the prevalence of sensory dysfunction (i.e. auditory, visual, vestibular, chemosensory and multiple sensory problems) and explore associations with traumatic brain injury (TBI) severity and injury mechanism among deployed Post-9/11 Veterans., Methods: This retrospective cohort analysis used Departments of Defense and Veterans Affairs diagnostic codes and administrative data., Results: Among the 570,248 Veterans in this cohort, almost 23% had at least one diagnosis of sensory dysfunction. In the multinomial regression analysis, the odds of all types of sensory dysfunction were greater among those with any TBI relative to those with no TBI. The odds for auditory or multisensory problems were higher among those that indicated exposure to blast. In particular, exposure to quaternary blast injury (e.g. crush, respiratory and burn injuries) was associated with increased odds for auditory, visual, vestibular and multisensory problems., Conclusions: Sensory problems affect a substantial number of deployed Post-9/11 Veterans and are more common among those with TBI or with exposure to deployment-related blast exposure. Because sensory problems profoundly impact quality of life, their identification and enhanced education and therapy are vital tools to improve prognosis for these relatively young Veterans.

Neurologic disorders are characterized by abnormal cellular-, molecular-, and circuit-level functions in the brain. New methods to induce and control neuroplastic processes and correct abnormal function, or even shift functions from damaged tissue to physiologically healthy brain regions, hold the potential to dramatically improve overall health. Of the current neuroplastic interventions in development, neurofeedback training (NFT) from functional Magnetic Resonance Imaging (fMRI) has the advantages of being completely non-invasive, non-pharmacologic, and spatially localized to target brain regions, as well as having no known side effects. Furthermore, NFT techniques, initially developed using fMRI, can often be translated to exercises that can be performed outside of the scanner without the aid of medical professionals or sophisticated medical equipment. In fMRI NFT, the fMRI signal is measured from specific regions of the brain, processed, and presented to the participant in real-time. Through training, self-directed mental processing techniques, that regulate this signal and its underlying neurophysiologic correlates, are developed. FMRI NFT has been used to train volitional control over a wide range of brain regions with implications for several different cognitive, behavioral, and motor systems. Additionally, fMRI NFT has shown promise in a broad range of applications such as the treatment of neurologic disorders and the augmentation of baseline human performance. In this article, we present an fMRI NFT protocol developed at our institution for modulation of both healthy and abnormal brain function, as well as examples of using the method to target both cognitive and auditory regions of the brain.

Background: Bovine tuberculosis (TB) control programs generally rely on the tuberculin skin test (TST) for ante-mortem detection of Mycobacterium bovis-infected cattle., Results: Present findings demonstrate that a rapid antibody test based on Dual-Path Platform (DPP ® ) technology, when applied 1-3 weeks after TST, detected 9 of 11 and 34 of 52 TST non-reactive yet M. bovis-infected cattle from the US and GB, respectively. The specificity of the assay ranged from 98.9% (n = 92, US) to 96.0% (n = 50, GB) with samples from TB-free herds. Multi-antigen print immunoassay (MAPIA) revealed the presence of antibodies to multiple antigens of M. bovis in sera from TST non-reactors diagnosed with TB., Conclusions: Thus, use of serologic assays in series with TST can identify a significant number of TST non-reactive tuberculous cattle for more efficient removal from TB-affected herds.

Hearing loss is the second most common disability awarded by the U.S. Department of Veterans Affairs (VA) to former members of the U.S. uniformed services. Hearing readiness and conservation practices differ among the four largest uniformed military services (Air Force, Army, Marine Corps, and Navy). Utilizing a data set consisting of all hearing loss claims submitted to the VA from fiscal years 2003-2013, we examined characteristics of veterans submitting claims within one year of separation from military service. Our results indicate that having a hearing loss disability claim granted was significantly more likely for men, individuals over the age of 26 years at the time of the claim, individuals most recently serving in the U.S. Army, and those with at least one hearing loss diagnosis. Importantly, individuals with at least one test record in the Defense Occupational and Environmental Health Readiness System-Hearing Conservation (DOEHRS-HC) system were significantly less likely to have a hearing loss disability claim granted by the VA. Within the DOEHRS-HC cohort, those with at least one threshold shift or clinical hearing loss diagnosis while on active duty were more than two and three times more likely to have a hearing loss disability claim granted, respectively. These findings indicate that an established history of reduced hearing ability while on active duty was associated with a significantly increased likelihood of an approved hearing loss disability claim relative to VA claims without such a history. Further, our results show a persistent decreased rate of hearing loss disability awards overall. These findings support increased inclusion of personnel in DoD hearing readiness and conservation programs to reduce VA hearing loss disability awards., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Hearing is an extremely complex phenomenon, involving a large number of interrelated variables that are difficult to measure in vivo. In order to investigate such process under simplified and well-controlled conditions, models of sound transmission have been developed through many decades of research. The value of modeling the hearing system is not only to explain the normal function of the hearing system and account for experimental and clinical observations, but to simulate a variety of pathological conditions that lead to hearing damage and hearing loss, as well as for development of auditory implants, effective ear protections and auditory hazard countermeasures. In this paper, we provide a review of the strategies used to model the auditory function of the external, middle, inner ear, and the micromechanics of the organ of Corti, along with some of the key results obtained from such modeling efforts. Recent analytical and numerical approaches have incorporated the nonlinear behavior of some parameters and structures into their models. Few models of the integrated hearing system exist; in particular, we describe the evolution of the Auditory Hazard Assessment Algorithm for Human (AHAAH) model, used for prediction of hearing damage due to high intensity sound pressure. Unlike the AHAAH model, 3D finite element models of the entire hearing system are not able yet to predict auditory risk and threshold shifts. It is expected that both AHAAH and FE models will evolve towards a more accurate assessment of threshold shifts and hearing loss under a variety of stimuli conditions and pathologies., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

The purpose of this study was to describe the prevalence of hearing loss and tinnitus in a cohort of Iraq and Afghanistan Veterans (IAV) with common post-deployment conditions, including traumatic brain injury (TBI), post-traumatic stress disorder (PTSD), and other typical post-concussive conditions such as headaches and vertigo/dizziness. This retrospective observational study used data from the national Veterans Health Administration (VA) data repository from fiscal years 2001-2014. Veteran data was included if there were at least three years of VA care, with one or more years of care in 2007 or after. We identified comorbidities that may be associated with post-deployment hearing loss or tinnitus including TBI, PTSD, depression, and common post-concussive symptoms using International Classification of Diseases, 9th Revision, Clinical Modification codes. A multinomial logistic regression analysis was used to examine conditions associated with hearing loss or tinnitus. Among IAV, 570,332 were included in the final analysis. Of these, 7.78% of these were diagnosed with hearing loss alone, 6.54% with tinnitus alone, and 6.24% with both hearing loss and tinnitus. Comorbid TBI, PTSD, and depression were significantly associated with increased rates of hearing loss, tinnitus, or both conditions together. Older individuals, males, and those with TBI, PTSD, or vertigo/dizziness were significantly more likely to have hearing loss, tinnitus, or both. In order to provide more holistic post-deployment support, this myriad of conditions should be carefully considered in the planning of clinical care and beyond., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Dynamic adjustment of insulin secretion to compensate for changes of insulin sensitivity that result from alteration of nutritional or metabolic status is a fundamental aspect of glucose homeostasis. To investigate the role of the brain in this coupling process, we used cold exposure as an experimental paradigm because the sympathetic nervous system (SNS) helps to coordinate the major shifts of tissue glucose utilization needed to ensure that increased thermogenic needs are met. We found that glucose-induced insulin secretion declined by 50% in rats housed at 5°C for 28 h, and yet, glucose tolerance did not change, owing to a doubling of insulin sensitivity. These potent effects on insulin secretion and sensitivity were fully reversed by returning animals to room temperature (22°C) for 4 h or by intravenous infusion of the α-adrenergic receptor antagonist phentolamine for only 30 min. By comparison, insulin clearance was not affected by cold exposure or phentolamine infusion. These findings offer direct evidence of a key role for the brain, acting via the SNS, in the rapid, highly coordinated, and reciprocal changes of insulin secretion and insulin sensitivity that preserve glucose homeostasis in the setting of cold exposure., (© 2017 by the American Diabetes Association.)

Measurements of perilymph hydrodynamics in the human cochlea are scarce, being mostly limited to the fluid pressure at the basal or apical turn of the scalae vestibuli and tympani. Indeed, measurements of fluid pressure or volumetric flow rate have only been reported in animal models. In this study we imaged the human ear at 6.7 and 3-µm resolution using µCT scanning to produce highly accurate 3D models of the entire ear and particularly the cochlea scalae. We used a contrast agent to better distinguish soft from hard tissues, including the auditory canal, tympanic membrane, malleus, incus, stapes, ligaments, oval and round window, scalae vestibule and tympani. Using a Computational Fluid Dynamics (CFD) approach and this anatomically correct 3D model of the human cochlea, we examined the pressure and perilymph flow velocity as a function of location, time and frequency within the auditory range. Perimeter, surface, hydraulic diameter, Womersley and Reynolds numbers were computed every 45° of rotation around the central axis of the cochlear spiral. CFD results showed both spatial and temporal pressure gradients along the cochlea. Small Reynolds number and large Womersley values indicate that the perilymph fluid flow at auditory frequencies is laminar and its velocity profile is plug-like. The pressure was found 102-106° out of phase with the fluid flow velocity at the scalae vestibule and tympani, respectively. The average flow velocity was found in the sub-µm/s to nm/s range at 20-100Hz, and below the nm/s range at 1-20kHz., Competing Interests: The authors have no conflict of interest., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Hyperbaric oxygen (HBO2) therapy reportedly reduces opiate withdrawal in human subjects. The purpose of this research was to determine whether HBO2 treatment could suppress physical signs of withdrawal in opiate-dependent mice. Male NIH Swiss mice were injected s.c. with morphine sulfate twice a day for 4 days, the daily dose gradually increasing from 50mg/kg on day 1 to 125mg/kg on day 4. On day 5, withdrawal was precipitated by i.p. injection of 5.0mg/kg naloxone. Mice were observed for physical withdrawal signs, including jumping, forepaw tremor, wet-dog shakes, rearing and defecation for 30min. Sixty min prior to the naloxone injection, different groups of mice received either a 30-min or 60-min HBO2 treatment at 3.5atm absolute. HBO2 treatment significantly reduced naloxone-precipitated jumping, forepaw tremor, wet-dog shakes, rearing and defecation. Based on these experimental findings, we concluded that treatment with HBO2 can suppress physical signs of withdrawal syndrome in morphine-dependent mice., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The concept of a neutral hole-transporting polymer is realized for the first time, by integrating patterned Cl(-) -doped poly(3,4-dimethoxythiophene) thin films into organic solar cells through a vacuum-based polymer vapor printing technique. Due to this novel polymer's neutrality, high transparency, good conductivity, and appropriate energy levels, the solar-cell efficiency and lifetime are significantly enhanced., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To investigate the role played by leptin in thermoregulation, we studied the effects of physiological leptin replacement in leptin-deficient ob/ob mice on determinants of energy balance, thermogenesis and heat retention under 3 different ambient temperatures., Methods: The effects of housing at 14 °C, 22 °C or 30 °C on core temperature (telemetry), energy expenditure (respirometry), thermal conductance, body composition, energy intake, and locomotor activity (beam breaks) were measured in ob/ob mice implanted subcutaneously with osmotic minipumps at a dose designed to deliver a physiological replacement dose of leptin or its vehicle-control., Results: As expected, the hypothermic phenotype of ob/ob mice was partially rescued by administration of leptin at a dose that restores plasma levels into the physiological range. This effect of leptin was not due to increased energy expenditure, as cold exposure markedly and equivalently stimulated energy expenditure and induced activation of brown adipose tissue irrespective of leptin treatment. Instead, the effect of physiological leptin replacement to raise core body temperature of cold-exposed ob/ob mice was associated with reduced thermal conductance, implying a physiological role for leptin in heat conservation. Finally, both leptin- and vehicle-treated ob/ob mice failed to match energy intake to expenditure during cold exposure, resulting in weight loss., Conclusions: The physiological effect of leptin to reduce thermal conductance contributes to maintenance of core body temperature under sub-thermoneutral conditions.