Modeling Sepsis-Associated ARDS Using a Lung Endothelial Microphysiological System.

Acute respiratory distress syndrome due to non-pulmonary causes exhibits prominent endothelial activation which is challenging to assess in critically ill patients. Preclinical in vivo models of sepsis and ARDS have failed to yield useful therapies in humans, perhaps due to interspecies differences in inflammatory responses. Use of microphysiological systems (MPS) offer improved fidelity to human biological responses and better predict pharmacological responses than traditional culture. We adapted a lung endothelial MPS based on the LumeNEXT platform to evaluate the effect of plasma from critically ill sepsis patients on endothelial permeability, adhesion molecule expression and inflammatory cytokine production. Lumens incubated with sepsis plasma exhibited areas of contraction, loss of cellular coverage, and luminal defects. Sepsis plasma-incubated lumens had significantly increased permeability compared to lumens incubated with healthy donor plasma. ICAM-1 expression increased significantly in lumens incubated with sepsis plasma compared with those incubated with healthy control plasma, while concentrations of IL-6, IL-18, and soluble VEGF-R1 increased in sepsis plasma before and after incubation in the MPS compared with healthy control plasma. Use of the lung endothelial MPS may enable interrogation of specific mechanisms of endothelial dysfunction that promote ARDS in sepsis patients.

The timing and value of early postoperative computed tomography after head surgery in traumatic brain injury patients.

OBJECTIVE: To analyze the timing of the early postoperative computed tomography (CT) in traumatic brain injury (TBI) patients, and compare CT and neurological examination (NE) findings. METHODS: Retrospective analysis included 353 TBI patients admitted to two level 1 trauma centers (2016-2020) who underwent head surgery and postoperative CT within 24 h. Analyzed variables: age, Injury Severity Score (ISS), Glasgow Coma Score (GCS), Abbreviated Injury Scale head (AISh), comorbidities, CT and NE findings and timing, head surgery type, and mortality. RESULTS: Patients mean age was 61.9 years, ISS 25.1, GCS 11.0, AISh 4.7. Postoperatively, mean time to first positive CT was 6.1 h and to first positive NE was 13.2 h. Positive CT alone was more accurate in identifying need for 2nd head surgery than positive NE alone (21.8 % vs 6.0 %, p = 0.04). There was no difference between patients with CT done earlier than 6 h compared to patients with CT done after 6 h in mortality (26.1 % vs 22.0 %, p = 0.4) or 2nd surgery rate (12.2 % vs 12.2 %, p = 1.0). Reversal of postoperative CT findings occurred in 1/6 of patients and was more common when CT was done earlier than 6 h compared to CT done later (25.7 % vs 0.8 %, p < 0.001). Early CT within 1 h rarely leads to the change of management but often is followed by another CT within 12 h. CONCLUSION: In TBI patients postoperative CT was more effective than NE in predicting a need for 2nd head surgery. Postoperative head CT at 6 h is recommended to allow timely detection of intracranial deterioration, reduce the number of CTs and reversal findings as it does not increase 2nd surgery rates and mortality.

Psychometric Evaluation of the Affect Regulation Checklist: Clinical and Community Samples, Parent-Reports and Youth Self-Reports.

The Affect Regulation Checklist (ARC) was designed to capture affect dysregulation, suppression, and reflection. Importantly, affect dysregulation has been established as a transdiagnostic mechanism underpinning many forms of psychopathology. We tested the ARC psychometric properties across clinical and community samples and through both parent-report and youth self-report information. Clinical sample: Participants included parents (n = 814; Mage = 43.86) and their child (n = 608; Mage = 13.98). Community sample: Participants included independent samples of parents (n = 578; Mage = 45.12) and youth (n = 809; Mage = 15.67). Exploratory structural equation modeling supported a three-factor structure across samples and informants. Dysregulation was positively associated with all forms of psychopathology. In general, suppression was positively associated with many forms of psychopathology, and reflection was negatively associated with externalizing problems and positively associated with internalizing problems.

Acute cardiac tamponade secondary to nonpenetrating injury from gunshot with beanbag round: A case report and literature review.

Over the past twenty years, "less-lethal" munitions have caused a variety of significant, life-threatening injuries. However, evidence of blunt cardiac injury due to these weapons is sparse. A healthy 44-year old man presented with hemodynamic instability due to cardiac tamponade after he was shot with a beanbag, ultimately requiring operative intervention. This case report describes a unique clinical presentation of blunt cardiac injury and the diagnostic and therapeutic steps that the trauma surgery team took to appropriately manage this rare injury.

Exploring the Semantic Structure of WMS-IV Verbal Paired Associates using the Hub-and-Spoke Model.

OBJECTIVES: This study aimed to identify a well-fitting and theoretically justified item-level latent factor structure for the Wechsler Memory Scales (WMS)-IV verbal paired associates (VerbalPA) subtest to facilitate the ease and accuracy of score interpretations for patients with lateralized temporal lobe epilepsy (TLE). METHODS: Archival data were used from 250 heterogeneous neurosciences patients who were administered the WMS-IV as part of a standard neuropsychological assessment. Three theoretically motivated models for the latent structure of VerbalPA were tested using confirmatory factor analysis. The first model, based on cognitive principles of semantic processing from hub-and-spoke theory, tested whether performance is related to specific semantic features of target words. The second, motivated by the Cattell-Horn-Carroll (CHC) model of cognitive abilities, investigated whether the associative properties of items influence performance. A third, Hybrid model tested whether performance is related to both semantic and associative properties of items. The best-fitting model was tested for diagnostic group effects contrasting the heterogeneous neuroscience patients with subsets of left and right TLE (n = 51, n = 26, respectively) patients. RESULTS: The Hybrid model was found to have the best fit. Patients with left TLE scored significantly less well than the heterogeneous neurosciences sample on selected semantic factor scores, although the effect size was small. CONCLUSIONS: Future editions of the WMS may consider implementing a semantic scoring structure for the VerbalPA to facilitate test score interpretation. Additionally, these results suggest that principles of hub-and-spoke theory may be integrated into CHC cognitive ability taxonomy.

Latent Semantic Structure of the WMS-III Verbal Paired-Associates.

OBJECTIVE: To investigate the factor structure of the verbal paired-associates (VPA) subtest in the WMS-III using a theoretically driven model of semantic processing previously found to be well-fitting for the WMS-IV version of the test. METHOD: Archival data were used from 267 heterogeneous neurosciences patients and 223 seizure disorder patients who completed the WMS-III as part of a standard neuropsychological evaluation. Confirmatory factor analysis was used to test theoretically driven models for VPA based on principles of semantic processing. Four nested models of different complexities were examined and compared for goodness-of-fit using chi-squared difference testing. Measurement invariance testing was conducted across heterogeneous neuroscience and seizure disorder samples to test generality of the factor model. RESULTS: After removing items with limited variability (very easy or very hard; 12 of 40 items), a four-factor model was found to be best-fitting in the present patient samples. The four factors were "recreational", "functional", "material", and "symbolic", each representing semantic knowledge associated with the function of the target word referent. This model subsequently met the criteria for the strict measurement invariance, showing good overall fit when factor loadings, thresholds, and residuals were held to equality across samples. CONCLUSIONS: The results of this study provide further evidence that "arbitrary" associations between word pairs in VPA items have an underlying semantic structure, challenging the idea that unrelated hard-pairs are semantic-free. These results suggest that a semantic-structure model may be implemented as an alternative scoring in future editions of the WMS to facilitate interpretation.

Delivery of a Vitamin D Intervention in Homebound Older Adults Using a Meals-on-Wheels Program: A Pilot Study.

OBJECTIVES: To assess the feasibility of a vitamin D intervention delivered through a Meals-on-Wheels (MOW) program to improve 25-hydroxyvitamin D (25(OH)D) concentrations and reduce falls in homebound older adults. DESIGN: Single-blind, cluster randomized trial. SETTING: MOW, Forsyth County, North Carolina. PARTICIPANTS: Community-dwelling homebound adults aged 65 to 102 (N = 68). INTERVENTION: MOW clients were randomized to vitamin D3 (100,000 IU/month; n = 38) or active placebo (400 IU vitamin E/month; n = 30) according to MOW delivery route. MEASUREMENTS: Serum 25(OH)D was assessed at baseline and 5-month follow-up; proportions of participants in 25(OH)D categories were compared using Fisher exact test. Falls were assessed using monthly fall calendars, and rate of falls was estimated using negative binomial generalized estimating equation models. RESULTS: Mean ± standard deviation 25(OH)D concentrations were 20.9 ± 11.5 ng/mL at baseline, with 57% having 25(OH)D concentrations less than 20 ng/mL. Retention and adherence were high (>90%). After the 5-month intervention, only one of 34 participants randomized to vitamin D3 had 25(OH)D concentrations less than 20 ng/mL, compared with 18 of 25 participants randomized to placebo (P < .001). In unadjusted analyses, the rate of falls over 5 months was not significantly different according to intervention group (risk ratio (RR) = 0.48, 95% confidence interval (CI) = 0.19-1.19), but after adjustment for sex, race, season of year, baseline 25(OH)D status, and history of falls, participants randomized to vitamin D3 had a lower rate of falling than those randomized to placebo (RR = 0.42, 95% CI = 0.21-0.87). CONCLUSION: A vitamin D intervention delivered through MOW was feasible, resulting in improvements in 25(OH)D concentrations and a lower rate of falls in adjusted analyses. Further research is needed to validate the reduction in falls from this type of intervention.

Comorbid psychosocial issues seen in pediatric otolaryngology clinics.

Common disorders seen in frequently have related comorbid psychosocial issues and conditions. This article reviews the literature on these comorbidities in commonly seen otolaryngology conditions and heightens awareness of the cognitive, developmental, behavioral, emotional, and social correlates of these commonly treated conditions. Evidence-based practice would suggest identification and appropriate referrals would be helpful; therefore, a time-efficient and accurate screening mechanism is needed within the context of a busy clinical practice. A screening algorithm for identifying these issues and providing appropriate referrals is provided.

Utilizing a Meals on Wheels program to teach falls risk assessment to medical students.

Falls are a critical public health issue for older adults, and falls risk assessment is an expected competency for medical students. The aim of this study was to design an innovative method to teach falls risk assessment using community-based resources and limited geriatrics faculty. The authors developed a Fall Prevention Program through a partnership with Meals-on-Wheels (MOW). A 3rd-year medical student accompanies a MOW client services associate to a client's home and performs a falls risk assessment including history of falls, fear of falling, medication review, visual acuity, a Get Up and Go test, a Mini-Cog, and a home safety evaluation, reviewed in a small group session with a faculty member. During the 2010 academic year, 110 students completed the in-home falls risk assessment, rating it highly. One year later, 63 students voluntarily completed a retrospective pre/postsurvey, and the proportion of students reporting moderate to very high confidence in performing falls risk assessments increased from 30.6% to 87.3% (p < .001). Students also reported using most of the skills learned in subsequent clerkships. A single educational intervention in the MOW program effectively addressed geriatrics competencies with minimal faculty effort and could be adopted by many medical schools.

Teaching medical student geriatrics competencies in 1 week: an efficient model to teach and document selected competencies using clinical and community resources.

The Association of American Medical Colleges (AAMC) and the John A. Hartford Foundation published geriatrics competencies for medical students in 2008 defining specific knowledge and skills that medical students should be able to demonstrate before graduation. Medical schools, often with limited geriatrics faculty resources, face challenges in teaching and assessing these competencies. As an initial step to facilitate more-efficient implementation of the competencies, a 1-week geriatrics rotation was developed for the third year using clinical, community, and self-directed learning resources. The Wake Forest University School of Medicine Acute Care for the Elderly Unit serves as home base, and each student selects a half-day outpatient or long-term care experience. Students also perform a home-based falls-risk assessment with a Meals-on-Wheels client. The objectives for the rotation include 20 of the 26 individual AAMC competencies and specific measurable tracking tasks for seven individual competencies. In the evaluation phase, 118 students completed the rotation. Feedback was positive, with an average rating of 7.1 (1 = worst, 10 = best). Students completed a 23-item pre- and post-knowledge test, and average percentage correct improved by 15% (P < .001); this improvement persisted at graduation (2 years after the pretest). On a 12-item survey of attitudes toward older adults, improvement was observed immediately after the rotation that did not persist at graduation. Ninety-seven percent of students documented completion of the competency-based tasks. This article provides details of development, structure, evaluation, and lessons learned that will be useful for other institutions considering a brief, concentrated geriatrics experience in the third year of medical school.

Effectiveness of Spirometry Fundamentals™ for increasing the proper use of spirometry in patients with asthma and COPD.

AIM: To examine whether exposure to the Spirometry Fundamentals™ CD-ROM results in improved quality of spirometry testing in primary care. METHODS: Spirometry tests performed in 20 intervention and 19 control practices were analysed using American Thoracic Society grades A and B for 'passing' and grades C, D and F for 'failing'. Intervention effects on spirometry quality were assessed using random effects multivariate logistic regression. RESULTS: Adjusted analyses revealed no intervention effect. The likelihood of passing tests was higher in paediatrics-only practices (adjusted odds ratio (AOR) 2.60, 95% confidence interval (CI) 1.32 to 5.12; p=0.01). Hospital or university-based clinics had a lower performance than private or community-based practices in unadjusted analysis (7% vs. 22% passing tests; p=0.05). However, this relationship was not significant in adjusted analyses. CONCLUSIONS: Spirometry Fundamentals™ is insufficient to improve the quality of spirometry in primary care, suggesting the need for more comprehensive multifaceted training resources.

Inter-examiner reliability of salivary diagnostic tests in a practice-based research network.

PURPOSE: Patient salivary characteristics are being measured as part of the Northwest PRECEDENT (Practice-based REsearch Collaborative in Evidence-based DENTistry) study on caries risk assessment. Prior to the implementation of these salivary diagnostic tests in a practice-based cohort study, inter-examiner reliability was assessed for resting salivary pH, stimulated salivary flow rate, pH and buffering capacity. METHODS: An initial evaluation of inter-examiner reliability of the 4 salivary tests was conducted among 6 dental auxiliary examiners using a convenience sample of 40 dental students. An in complete block design was used to assign samples to examiners (3 examiners per sample and 20 samples per examiner). Inter-examiner reliability testing was conducted on a patient population representative of the practice-based network in 4 member practices. Two dental assistants per practice independently conducted the salivary tests on samples provided by a random selection of 20 to 25 patients. A separate analysis was performed for each study. For each test, an inter-examiner reliability index was computed. RESULTS: Results from two studies are reported. In the first, stimulated salivary flow rate demonstrated excellent inter-examiner reliability, and resting salivary pH showed high inter-examiner reliability, while buffering capacity and stimulated salivary pH had moderate and very low inter-examiner reliability, respectively. In the second, inter-examiner reliability was excellent for the stimulated salivary flow rate and the resting salivary pH. The inter-examiner reliability for the stimulated salivary pH was also high and the stimulated salivary buffering capacity test had moderate reliability. CONCLUSION: The small variance in stimulated salivary pH and buffering capacity in dental students may have artificially made the reliability appear low in the first attempt at inter-examiner reliability testing. In the second study, all 4 tests had an accept able performance.

The effects of novelty-seeking phenotypes and sex differences on acquisition of cocaine self-administration in selectively bred High-Responder and Low-Responder rats.

Individual differences in exploratory behavior can predictably influence psychostimulant self-administration behavior. Male rats that exhibit a high degree of locomotor activity in a novel environment (High Responders, HR) will self-administer cocaine more readily than males exhibiting low levels of novelty-induced locomotion (Low Responders, LR). The present experiment investigates the combined influences of the sex of an individual and individual phenotypes in novelty-induced locomotion to predispose animals to acquire cocaine self-administration behavior, in male and female rats selectively bred for the HR-LR phenotypes. We first established that HR females, like their male counterparts, exhibit a dramatically greater locomotor response to novelty and less anxiety-like behavior than do LR females. While locomotor behavior was subtly influenced by estrous stage, with both HR and LR females showing increased activity during metestrus and diestrus compared to proestrus and estrus, the effect did not obscure HR-LR differences. When male and female HR-LR animals were trained to self-administer cocaine (2 h/day, 5 days/wk x 3 wk, 0.2 mg cocaine/kg/infusion), HR males and females acquired cocaine self-administration significantly faster than their LR counterparts. Furthermore, HR females self-administered significantly more cocaine than all other groups. In conclusion, female rats, like males, exhibit HR-LR phenotypes that predict rapidity of acquiring cocaine self-administration. Moreover, HR females self-administer more cocaine than HR males and both LR groups.

Activation of POMC neurons during general arousal but not sexual behavior in male rats.

Exogenous opioids influence male rat sexual behavior, suggesting that endogenous opioid peptides are released during mating. Supporting this hypothesis, the authors recently showed that mating induced activation of mu opioid receptors. However, it is unknown which ligand(s) is acting on these receptors during mating. The current set of experiments tested the hypothesis that beta-endorphin-producing neurons, that is, proopiomelanocortin (POMC) neurons, are activated during sexual behavior. Mating-induced activation of POMC neurons was investigated during either the dark phase or the light phase, following different components of male rat sexual behavior or following control manipulations that resulted in general arousal. Results show activation of POMC neurons in the mediobasal hypothalamus following general arousal but not specifically related to sexual behavior per se. In addition, mating did not activate the subpopulation of POMC neurons that project to the medial preoptic nucleus. These results suggest that it is unlikely that POMC neurons contribute to the action of endogenous opioids in the brain area during sexual behavior but instead may contribute to the change in arousal state essential for the expression of sexual behavior.

Mating activates NMDA receptors in the medial preoptic area of male rats.

Studies have emphasized the role of the medial preoptic area (MPOA) as an important site for the regulation of male sexual behavior. Indeed, ablations of the MPOA impair sexual behavior, whereas stimulation of the MPOA enhances behavior. Furthermore, neural activity in the MPOA increases with mating. The current study tested the hypothesis that activation of N-methyl-D-aspartate (NMDA) receptors occurs in MPOA neurons and is essential for the expression of male sexual behavior in rats. Results indicate that nearly all MPOA neurons that expressed Fos following mating also contained the NR1 subunit of NMDA receptors. Furthermore, mating increased phosphorylation, thus activation, of NR1 in the MPOA. Additionally, blocking NMDA receptors significantly decreased mating-induced Fos expression and mating-induced phosphorylation of NMDA receptors and impaired male sexual behavior. These results provide evidence that mating activates NMDA receptors in the MPOA and that this activation is important for the expression of male sexual behavior.

Resection of a benign brachial plexus nerve sheath tumor using intraoperative electrophysiological monitoring.

OBJECTIVE: Benign peripheral nerve sheath tumors arising from the brachial plexus are rare. Neurosurgeons often lack the clinical and surgical experience to optimize the management of these uncommon tumors. We filmed a video depicting the surgical resection of a benign peripheral nerve sheath tumor involving the brachial plexus. METHODS: An illustrative case was used to demonstrate the proper management of a brachial plexus nerve sheath tumor including the important role of intraoperative electrophysiological neuromonitoring during tumor resection. RESULTS: Using an illustrative case, we describe a systematic approach in the evaluation and surgical management of patients with a brachial plexus nerve sheath tumor. The importance of taking a thorough clinical history, performing a thorough physical examination, applying high-resolution magnetic resonance imaging techniques to visualize the pathology, and using intraoperative electrophysiological neuromonitoring during surgical exposure and resection of the tumor are stressed. Combined with appropriate postoperative treatment, these techniques minimize the risks and increase the likelihood of achieving a good clinical outcome. CONCLUSION: Brachial plexus nerve sheath tumors are challenging mass lesions that should be evaluated and surgically resected by an experienced team of physicians to optimize clinical outcome.