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Purpose: Assessing expertise using psychometric models usually yields a measure of ability that is difficult to generalize to the complexity of diagnoses in clinical practice. However, using an item response modeling framework, it is possible to create a decision-aligned response model that captures a clinician's decision-making behavior on a continuous scale that fully represents competing diagnostic possibilities. In this proof-of-concept study, the authors demonstrate the necessary statistical conceptualization of this model using a specific electrocardiogram (ECG) example., Method: The authors collected a range of ECGs with elevated ST segments due to either ST-elevation myocardial infarction (STEMI) or pericarditis. Based on pilot data, 20 ECGs were chosen to represent a continuum from "definitely STEMI" to "definitely pericarditis," including intermediate cases in which the diagnosis was intentionally unclear. Emergency medicine and cardiology physicians rated these ECGs on a 5-point scale ("definitely STEMI" to "definitely pericarditis"). The authors analyzed these ratings using a graded response model showing the degree to which each participant could separate the ECGs along the diagnostic continuum. The authors compared these metrics with the discharge diagnoses noted on chart review., Results: Thirty-seven participants rated the ECGs. As desired, the ECGs represented a range of phenotypes, including cases where participants were uncertain in their diagnosis. The response model showed that participants varied both in their propensity to diagnose one condition over another and in where they placed the thresholds between the 5 diagnostic categories. The most capable participants were able to meaningfully use all categories, with precise thresholds between categories., Conclusions: The authors present a decision-aligned response model that demonstrates the confusability of a particular ECG and the skill with which a clinician can distinguish 2 diagnoses along a continuum of confusability. These results have broad implications for testing and for learning to manage uncertainty in diagnosis., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Association of American Medical Colleges.)

Knee dislocations (KDs) are devastating injuries for patients and present complex challenges for orthopaedic surgeons. Although short-term outcomes have been studied, there are few long-term outcomes of these injuries available in the literature. The purpose of this study is to determine factors that influence mid- to long-term clinical outcomes following surgical treatment of KD. A review of the current literature was performed by searching PubMed, the Cochrane Library, and Embase to identify clinical studies published from 2010 to 2019 with a minimum 2-year follow-up that reported outcomes following surgical treatment of KDs. Ten studies (6 level III, 4 level IV) were included. At mid- (2-10 y) to long-term (>10 y) follow-up, concomitant arterial, cartilage, and combined meniscus damage were predictive factors for inferior Lysholm and International Knee Documentation Committee (IKDC) scores when compared with patients without these associated injuries. Although concomitant neurological damage may influence short-term outcomes due to decreased mobility, at longer follow-up periods it does not appear to predict worse clinical outcomes when compared with patients without concomitant neurological injury. Frank and polytrauma KDs have been associated with worse mid- to long-term outcomes when compared with transient and isolated KDs. Patients who underwent surgery within 6 weeks of trauma experienced better long-term outcomes than those who underwent surgery longer than 6 weeks after the initial injury. However, the small sample size of this study makes it difficult to make valid recommendations. Lastly, female sex, patients older than 30 years at the time of injury and a body mass index (BMI) greater than 35 kg/m 2 are factors that have been associated with worse mid- to long-term Lysholm and IKDC scores. The results of this review suggest that female sex, age >30 years, BMI >35 kg/m 2 , concomitant cartilage damage, combined medial and lateral meniscal damage, KDs that do not spontaneously relocate, and KDs associated with polytrauma may predict worse results at mid- to long-term follow-up., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Despite the evolution of acromioclavicular joint surgery to a more anatomic coracoclavicular (CC) ligament reconstruction, no definitive guidance regarding the number and position of bone tunnels in the clavicle, as well as the ideal graft choice, is established., Purpose/hypothesis: The purpose of this study was to biomechanically compare the reconstruction of the CC ligament complex between gracilis- and semitendinosus-tendon grafts in 1- and 2-tunnel techniques. It was hypothesized that the gracilis tendon graft will provide comparable primary stability in both tunnel techniques while utilizing a smaller tunnel diameter., Study Design: Controlled laboratory study., Methods: A total of 24 cadaveric shoulders (13 men, 11 women; 66 ± 7.5 years) were randomly allocated to 4 repair groups: gracilis with 1 tunnel (GT-1), gracilis with 2 tunnels (GT-2), semitendinosus with 1 tunnel (ST-1), and semitendinosus with 2 tunnels (ST-2). First, specimens were tested for native anterior, posterior, and superior translations. Then, specimens were randomly assigned to 1 of the 4 CC reconstruction groups before undergoing the same testing, followed by cyclic loading and load to failure (LTF)., Results: The GT-2 reconstruction demonstrated significantly less translation when compared with ST-2 in anterior ( P = .024) and posterior ( P = .048) directions. GT-1 and ST-2 both showed significantly less translation than ST-1 in anterior and superior directions ( P < .001). All reconstructions demonstrated less superior translation compared with native testing, with GT-1 and ST-2 significantly less than ST-1 ( P < .001). There were no significant differences for peak displacement and LTF between groups., Conclusion: Gracilis tendon grafts using a 1- or 2-tunnel technique for CC ligament reconstruction provided comparable translation, displacement, and LTF as corresponding semitendinosus grafts. Therefore, the gracilis tendon should be considered as a biomechanical equivalent graft choice for the reconstruction of the CC ligament complex., Clinical Relevance: In a cadaveric model, the gracilis tendon demonstrated adequate fixation with minimal translation in CC ligament reconstruction while utilizing smaller diameter bone tunnels, which may help minimize the risk of complications such as loss of reduction and fracture.

Introduction: Electrocardiogram interpretation is an essential skill for emergency and critical care nurses and physicians. There remains a gap in standardized curricula and evaluation strategies used to achieve and assess competence in electrocardiogram interpretation. The purpose of this study was to develop an importance ranking of the 120 American Heart Association electrocardiogram diagnostic labels with interdisciplinary perspectives to inform curriculum development., Methods: Data for this mixed methods study were collected through focus groups and individual semi-structured interviews. A card sort was used to assign relative importance scores to all 120 American Heart Association electrocardiogram diagnostic labels. Thematic analysis was used for qualitative data on participants' rationale for the rankings., Results: The 18 participants included 6 emergency and critical care registered nurses, 5 cardiologists, and 7 emergency medicine physicians. The 5 diagnoses chosen as the most important by all disciplines were ventricular tachycardia, ventricular fibrillation, atrial fibrillation, complete heart block, and normal electrocardiogram. The "top 20" diagnoses by each discipline were also reported. Qualitative thematic content analysis revealed that participants from all 3 disciplines identified skill in electrocardiogram interpretation as clinically imperative and acknowledged the importance of recognizing normal, life threatening, and time-sensitive electrocardiogram rhythms. Additional qualitative themes, identified by individual disciplines, were reported., Discussion: This mixed-methods approach provided valuable interdisciplinary perspectives concerning electrocardiogram curriculum case selection and prioritization. Study findings can provide a foundation for emergency and critical care educators to create local ECG educational programs. Further work is recommended to validate the list amongst a larger population of emergency and critical care frontline nurses and physicians., (Copyright © 2020 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

Background: Guidelines for return to driving after anterior cruciate ligament reconstruction (ACLR) have not been established., Purpose: To review the literature pertaining to driving after ACLR and provide evidence-based guidelines to aid clinicians in counseling patients about driving after ACLR., Study Design: Systematic review; Level of evidence, 4., Methods: A systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Two independent reviewers searched PubMed, EMBASE, and the Cochrane Library using the terms anterior cruciate ligament , ACL , drive , and driving . Studies reporting on functional recovery after ACLR were included when data regarding return to driving were reported., Results: Five studies were included. Two studies included patients who underwent right-sided ACLR. Of these, 1 study evaluated bone-patellar tendon-bone autograft and reported that brake response time (BRT) returned to normal approximately 4 to 6 weeks postoperatively. The other study found that BRT returned to normal 3 weeks after allograft ACLR, but 6 weeks elapsed after autograft ACLR before values were not significantly different than controls. One study reported that patients who underwent left-sided hamstring tendon autograft ACLR demonstrated BRTs similar to controls within 2 weeks, while those with right-sided ACLR had significantly slower BRTs until 6 weeks postoperatively. Another study including patients who underwent either right- or left-sided ACLR and employed a manual transmission simulator found that 4 to 6 weeks should elapse after ACLR with hamstring tendon autograft. Survey data from 1 study demonstrated that the mean time for patients to resume driving was 13 and 10 days after right- and left-sided ACLR, respectively., Conclusion: BRT returned to normal values approximately 4 to 6 weeks after right-sided ACLR and approximately 2 to 3 weeks after left-sided ACLR. According to 1 study in this review, ACLR laterality should be disregarded for patients who drive manual transmission automobiles, as a 4- to 6-week time period was required for driving ability to reach the level of healthy controls. Future studies should aim to elucidate the influence of graft choice and transmission type on return to driving after ACLR., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: J.T.B. has received consulting fees from DJO, Encore Medical, and Smith & Nephew; nonconsulting fees from Mitek, Smith & Nephew, and Stryker; and royalties from Shukla Medical. E.C.M. has received educational support from Mitek, Smith & Nephew, Stryker, and Zimmer Biomet; consulting fees from Zimmer Biomet; speaking fees from Arthrex and Stryker; and royalties from Zimmer Biomet. R.M.F. has received grant support from Arthrex, educational support from Arthrex/Medwest and Smith & Nephew, speaking fees from Arthrex, and royalties from Elsevier. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2021.)

Introduction: Primary care clinics increasingly hire medical assistants (MAs) to perform a variety of clinical and administrative tasks. Anecdotal reports suggest that MA turnover is high, but no studies to date have calculated the rate or cost of MA turnover. The purpose of this study was to calculate the rate of MA turnover and associated costs in a single, large academic Family Medicine clinic., Methods: Retrospective data were collected from clinic administrators regarding MA turnover, overtime worked, salaries and benefits as well as administrator salaries and benefits and the amount of administrator time spent in MA hiring, training, and termination in 2017., Results: During 2017, MA turnover rate was 59%. The total estimated cost of MA turnover was $213,000. The per-MA cost of turnover was $14,200, or approximately 40% of the average annual salary of MAs., Conclusion: Turnover rate in this practice was similar to other estimates of primary care clinic staff and allied health professionals. The estimated cost of MA turnover relative to annual salary was significantly greater than that in other fields, likely reflecting the costs of training MAs. Establishing a method for calculating the turnover rate and costs can allow other healthcare systems to better describe turnover and evaluate retention strategies., Competing Interests: Conflicting and Competing Interests: All authors have indicated that they have no potential conflicts of interest or financial relationships to disclose., (© Copyright 2020 by the American Board of Family Medicine.)

Objective: Tuberous sclerosis complex (TSC) is one of the most common genetic causes of epilepsy. Seizures in TSC typically first present in infancy or early childhood, including focal seizures and infantile spasms. Infantile spasms in TSC are particularly characteristic in its strong responsiveness to vigabatrin. Although a number of mouse models of epilepsy in TSC have been described, there are very limited electroencephalographic (EEG) or seizure data during the preweanling neonatal and infantile-equivalent mouse periods. Tsc1 GFAP CKO mice are a well-characterized mouse model of epilepsy in TSC, but whether these mice have seizures during early development has not been documented. The objective of this study was to determine whether preweanling Tsc1 GFAP CKO mice have developmental EEG abnormalities or seizures, including spasms., Methods: Longitudinal video-EEG and electromyographic recordings were performed serially on Tsc1 GFAP CKO and control mice from postnatal days 9-21 and analyzed for EEG background abnormalities, sleep-wake vigilance states, and spontaneous seizures. Spasms were also induced with varying doses of N-methyl-D-aspartate (NMDA)., Results: The interictal EEG of Tsc1 GFAP CKO mice had excessive discontinuity and slowing, suggesting a delayed developmental progression compared with control mice. Tsc1 GFAP CKO mice also had increased vigilance state transitions and fragmentation. Tsc1 GFAP CKO mice had spontaneous focal seizures in the early neonatal period and a reduced threshold for NMDA-induced spasms, but no spontaneous spasms were observed., Significance: Neonatal Tsc1 GFAP CKO mice recapitulate early developmental aspects of EEG abnormalities, focal seizures, and an increased propensity for spasms. This mouse model may be useful for early mechanistic and therapeutic studies of epileptogenesis in TSC., (© 2020 International League Against Epilepsy.)

Objective: Over one-third of all patients with epilepsy are refractory to treatment and there is an urgent need to develop new drugs that can prevent the development and progression of epilepsy. Epileptogenesis is characterized by distinct histopathologic and biochemical changes, which include astrogliosis and increased expression of the adenosine-metabolizing enzyme adenosine kinase (ADK; EC 2.7.1.20). Increased expression of ADK contributes to epileptogenesis and is therefore a target for therapeutic intervention. We tested the prediction that the transient use of an ADK inhibitor administered during the latent phase of epileptogenesis can mitigate the development of epilepsy., Methods: We used the intrahippocampal kainic acid (KA) mouse model of temporal lobe epilepsy, which is characterized by ipsilateral hippocampal sclerosis with granule cell dispersion and the development of recurrent hippocampal paroxysmal discharges (HPDs). KA-injected mice were treated with the ADK inhibitor 5-iodotubercidin (5-ITU, 1.6 mg/kg, b.i.d., i.p.) during the latent phase of epileptogenesis from day 3-8 after injury; the period when gradual increases in hippocampal ADK expression begin to manifest. HPDs were assessed at 6 and 9 weeks after KA administration followed by epilepsy histopathology including assessment of granule cell dispersion, astrogliosis, and ADK expression., Results: 5-ITU significantly reduced the percent time in seizures by at least 80% in 56% of mice at 6 weeks post-KA. This reduction in seizure activity was maintained in 40% of 5-ITU-treated mice at 9 weeks. 5-ITU also suppressed granule cell dispersion and prevented maladaptive ADK increases in these protected mice., Significance: Our results show that the transient use of a small-molecule ADK inhibitor, given during the early stages of epileptogenesis, has antiepileptogenic disease-modifying properties, which provides the rationale for further investigation into the development of a novel class of antiepileptogenic ADK inhibitors with increased efficacy for epilepsy prevention., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

The neonatal brain undergoes rapid maturational changes that facilitate the normal development of the nervous system and also affect the pathological response to brain injury. Electroencephalography (EEG) and analysis of sleep-wake vigilance states provide important insights into the function of the normal and diseased immature brain. While developmental changes in EEG and vigilance states are well-described in people, less is known about the normal maturational properties of rodent EEG, including the emergence and evolution of sleep-awake vigilance states. In particular, a number of developmental EEG studies have been performed in rats, but there is limited comparable research in neonatal mice, especially as it pertains to longitudinal EEG studies performed within the same mouse. In this study, we have attempted to provide a relatively comprehensive assessment of developmental changes in EEG background activity and vigilance states in wild-type mice from postnatal days 9-21. A novel EEG and EMG method allowed serial recording from the same mouse pups. EEG continuity and power and vigilance states were analyzed by quantitative assessment and fast Fourier transforms. During this developmental period, we demonstrate the timing of maturational changes in EEG background continuity, frequencies, and power and the emergence of identifiable wake, NREM, and REM sleep states. These results should serve as important control data for physiological studies of mouse models of normal brain development and neurological disease., Competing Interests: The authors have declared that no competing interests exist.

Objective: Microglial abnormalities have been reported in pathologic specimens from patients with tuberous sclerosis complex (TSC), a genetic disorder characterized by epilepsy, intellectual disability, and autism. However, the pathogenic role of microglia in epilepsy in TSC is poorly understood, particularly whether microglia defects may be a primary contributor to epileptogenesis or are secondary to seizures or simply epiphenomena. In this study, we tested the hypothesis that Tsc1 gene inactivation in microglia is sufficient to cause epilepsy in mouse models of TSC., Methods: Using a chemokine receptor, Cx3cr1, to target microglia, conventional Tsc1 Cx3cr1-Cre CKO (conditional knockout) mice and postnatal-inducible Tsc1 Cx3cr1-Cre ER CKO mice were generated and assessed for molecular and histopathologic evidence of microglial abnormalities, mechanistic target of rapamycin 1 (mTORC1) pathway activation, and epilepsy., Results: Tsc1 Cx3cr1-Cre CKO mice exhibited a high efficiency of microglia Tsc1 inactivation, mTORC1 activation, increased microglial size and number, and robust epilepsy, which were rapamycin-dependent. However, Cre reporter studies demonstrated that constitutive Cx3cr1 expression affected not only microglia, but also a large percentage of cortical neurons, confounding the role of microglia in epileptogenesis in Tsc1 Cx3cr1-Cre CKO mice. In contrast, postnatal inactivation of Tsc1 utilizing a tamoxifen-inducible Cx3cr1-CreER resulted in a more-selective microglia Tsc1 inactivation with high efficiency, mTORC1 activation, and increased microglial size and number, but no documented epilepsy., Significance: Microglia abnormalities may contribute to epileptogenesis in the context of neuronal involvement in TSC mouse models, but selective Tsc1 gene inactivation in microglia alone may not be sufficient to cause epilepsy, suggesting that microglia have more supportive roles in the pathogenesis of seizures in TSC., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Background: Little is known about baseline diastolic dysfunction and changes in diastolic dysfunction grade after transcatheter aortic valve replacement (TAVR) for aortic stenosis (AS) and its impact on overall outcomes. The aim of this study was to describe baseline diastolic dysfunction and changes in diastolic dysfunction grade that occur with TAVR and their relationship to mortality and rehospitalization., Methods: This was a single-center study evaluating all TAVRs from January 2012 to June 2014. We compared parameters of diastolic dysfunction grade on pre-TAVR and 1 month post-TAVR echocardiograms for all patients undergoing the procedure. Descriptive statistics, Kaplan-Meier time-to-event analysis, and multivariate logistic regression were used., Results: Of a sample size of 120 patients undergoing TAVR for symptomatic severe AS, 90 were included in the final analysis after excluding significant mitral valve disease. There were improvements in individual parameters of diastolic dysfunction grade such as lateral e' velocity, E/lateral e', and left atrial volume index (nonsignificant trend) in the setting of improvement in aortic valve area and gradients and functional class pre- and post-TAVR. Multivariate analysis revealed that baseline diastolic dysfunction grade, but not post-TAVR or changes in diastolic dysfunction grade, was associated with 1-year death (hazard ratio, 1.163; 95% CI, 1.049-1.277, P = .005) and combined death/cardiovascular hospitalization (hazard ratio, 1.174; 95% CI, 1.032-1.318; P = .018)., Conclusions: In this single-center retrospective study of patients with symptomatic severe AS who underwent TAVR, several diastolic function parameters improved on echocardiography, but baseline diastolic dysfunction grade remained the most important echocardiographic factor associated with adverse 1-year outcomes., (Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Clinical guidelines recommend addressing adolescent alcohol use in primary care; the 5 As (Ask, Advise, Assess, Assist, Arrange) may be a useful model for intervention. We audio-recorded 540 visits with 49 physicians and adolescents, compared alcohol disclosure rates in the encounter with those in a survey, and analyzed conversations for use of the 5 As and their relation to adolescent reports of drinking 3 months after the encounter. When physicians asked clear, nonleading questions, drinkers were more likely to disclose alcohol use ( P = .004). In 64% of visits in which alcohol was discussed, physicians used one or more of the 5 As, most frequently "Ask." No physician used all 5 As. Among drinkers, there was no association between physicians' partial use of the 5 As and adolescent alcohol consumption at 3 months. Physicians can learn more effective ways to "Ask" about alcohol use to increase disclosure of drinking and to be more comprehensive in their counseling.

Frailty is a syndrome of older adults associated with increased morbidity and mortality. We aimed to assess the impact of frailty status on outcomes after transcatheter aortic valve implantation (TAVI). We reviewed all 191 patients who underwent a modified Fried frailty assessment before TAVI between February 2012 and September 2015 at a single academic medical center, and we assessed the impact of preoperative frailty status on morbidity, mortality, and health care utilization after TAVI. Frailty, pre-frailty, and nonfrailty were present in 33% (n = 64), 37% (n = 70), and 30% (n = 57) of patients, respectively. Slowness (75% vs 54%, p = 0.003) and low physical activity (55% vs 31%, p = 0.001) were more common in women than men. With increasing frailty status, the proportion of women increased (35% nonfrail, 44% pre-frail, and 66% frail, p = 0.002) and stature decreased (1.68 ± 0.11 m nonfrail, 1.66 ± 0.11 m pre-frail, 1.62 ± 0.12 m frail, p = 0.028). There was no difference in post-TAVI 30-day mortality, stroke, major vascular injury, major or life-threatening bleeding, respiratory failure, mean hospital length of stay, 30-day hospital re-admission, or overall survival between groups. The rate of discharge to a rehabilitation facility increased with increasing frailty status (14% nonfrail, 22% pre-frail, and 39% frail, p = 0.005). Frailty was independently associated with discharge to a rehabilitation facility (odds ratio 4.80, 95% confidence interval 1.66 to 13.85, p = 0.004). In conclusion, the safety of TAVI is not affected by frailty status, but patients with frailty are less likely to be discharged directly home after TAVI., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cytochrome P450 monooxygenases typically catalyze the insertion of one atom of oxygen from O2 into unactivated carbon-hydrogen and carbon-carbon bonds, with concomitant reduction of the other oxygen atom to H2O by NAD(P)H. Comparison of the average structures of the camphor hydroxylase cytochrome P450(cam) (CYP101) obtained from residual dipolar coupling (RDC)-restrained molecular dynamics (MD) in the presence and absence of substrate camphor shows structural displacements resulting from the essential collapse of the active site upon substrate removal. This collapse has conformational consequences that extend across the protein structure, none of which were observed in analogous crystallographic structures. Mutations were made to test the involvement of the observed conformational changes in substrate binding and recognition. All of the mutations performed based upon the NMR-detected perturbations, even those remote from the active site, resulted in modified substrate selectivity, enzyme efficiency and/or haem iron spin state. The results demonstrate that solution NMR can provide insights into enzyme structure-function relationships that are difficult to obtain by other methods.

The aim of this study was to determine the influence of inhospital and post-discharge worsening renal function (WRF) on prognosis after transcatheter aortic valve replacement (TAVR). Severe chronic kidney disease and inhospital WRF are both associated with poor outcomes after TAVR. There are no data available on post-discharge WRF and outcomes. This was a single-center study evaluating all TAVR from June 1, 2008, to June 31, 2014. WRF was defined as an increase in serum creatinine of ≥0.3 mg/dl. Inhospital WRF was measured from day 0 until discharge or day 7 if the hospitalization was >7 days. Post-discharge WRF was measured at 30 days after discharge. Descriptive statistics, Kaplan-Meier time-to-event analysis, and multivariate logistic regression were used. In a series of 208 patients who underwent TAVR, 204 with complete renal function data were used in the inhospital analysis and 168 who returned for the 30-day follow-up were used in the post-discharge analysis. Inhospital WRF was seen in 28%, whereas post-discharge WRF in 12%. Inhospital and post-discharge WRF were associated with lower rates of survival; however, after multivariate analysis, only post-discharge WRF remained a predictor of 1-year mortality (hazard ratio 1.18, p = 0.030 for every 1 mg/dl increase in serum creatinine). In conclusion, the rate of inhospital WRF is higher than the rate of post-discharge WRF after TAVR, and post-discharge WRF is more predictive of mortality than inhospital WRF., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: Chronic kidney disease (CKD) is associated with worse outcomes in heart failure with preserved ejection fraction (HFpEF). Whether this association is due the effect of CKD on intrinsic abnormalities in cardiac function is unknown. We hypothesized that CKD is independently associated with worse cardiac mechanics in HFpEF., Methods and Results: We prospectively studied 299 patients enrolled in the Northwestern University HFpEF Program. Using the creatinine-based CKD-Epi equation to calculate estimated glomerular filtration rate (eGFR), study participants were analysed by CKD status (using eGFR <60 mL/min/1.73 m(2) to denote CKD). Indices of cardiac mechanics (longitudinal strain parameters) were measured using speckle-tracking echocardiography. Using multivariable-adjusted linear and Cox regression analyses, we determined the association between CKD and echocardiographic parameters and clinical outcomes (cardiovascular hospitalization or death). Of 299 study participants, 48% had CKD. CKD (dichotomous variable) and reduced eGFR (continuous variable) were both associated with worse cardiac mechanics indices including left atrial (LA) reservoir strain, LV longitudinal strain, and right ventricular free wall strain even after adjusting for potential confounders, including co-morbidities, EF, and volume status. For example, for each 1-SD decrease in eGFR, LA reservoir strain was 3.52% units lower (P < 0.0001) after multivariable adjustment. Reduced eGFR was also associated with worse outcomes [adjusted hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01-1.61 per 1-SD decrease in eGFR; P = 0.039]. The association was attenuated after adjustment for indices of cardiac mechanics (P = 0.064)., Conclusion: In HFpEF, CKD is independently associated with worse cardiac mechanics, which may explain why HFpEF patients with CKD have worse outcomes., Trial Registration: NCT01030991., (© 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.)

Background: Proximal biceps pathology is a significant factor in shoulder pain. Surgical treatment options include biceps tenotomy and subpectoral biceps tenodesis. Tenotomy is a simple procedure, but it may produce visible deformity, subjective cramping, or loss of supination strength. Tenodesis is a comparatively technical procedure involving a longer recovery, but it has been hypothesized to achieve better outcomes in younger active patients (<55 years)., Hypothesis: This study investigated the outcomes of younger patients who underwent either a biceps tenotomy or tenodesis as part of treatment for shoulder pain. The hypothesis was that, apart from cosmetic deformity, there will be no difference in outcome between the 2 treatment options., Study Design: Cohort study; Level of evidence, 3., Methods: Isometric strength and endurance testing of operative and nonoperative shoulders for forearm supination (FS) and elbow flexion (EF) were tested utilizing an isometric dynamometer. Objective physical assessment was also performed. Subjective outcomes using the modified American Shoulder and Elbow Surgeons score (ASES); Disability of the Arm, Shoulder, and Hand (DASH); visual analog scale (VAS); and perceived biceps symptoms were collected., Results: A total of 42 patients (22 tenotomy, 20 tenodesis) with an average follow-up of 3.3 years were studied. The average age at follow-up was 49.9 years. Thirty-five percent (7/20) of tenotomy patients exhibited a "Popeye" deformity, compared with 18.2% (4/22) of tenodesis patients. Strength prior to fatiguing exercise was similar between tenodesis and tenotomy for FS (6.9 vs 7.3 lbs; P < .05), EF in neutral (35.4 vs 35.4 lbs), and EF in supination (33.8 vs 34.2 lbs). Strength was not significantly different between groups for isometric strength and endurance measures. Subjective functional outcome measured by the DASH, ASES, and VAS scores were similar between groups. Frequency of complaints of cramping was higher in the tenotomy group (4/20 vs 1/22), and complaints of pain were higher in the tenodesis group (11/22 vs 5/20)., Conclusion: Despite increased demands and activity placed on biceps function in a younger population, this study showed no differences in functional and subjective outcome measurements. The choice between biceps tenotomy and tenodesis for pathology of the proximal biceps tendon can continue to be based on surgeon and patient preference.

Granular cell tumor (GCT) is exceedingly rare in the genitourinary tract. We report a case of GCT arising in the tunica albuginea of the testis. A 42-year-old male presented with a painless left testicular mass. Scrotal ultrasound studies showed an intratesticular mass that was suspicious for a testicular malignancy; a left orchiectomy was subsequently performed. Grossly, there was a well-circumscribed tumor mass in the periphery of the testis abutting the tunica albuginea. Microscopically, the tumor was poorly delimited and located in the tunica albuginea with minimal infiltration to the underlying testicular parenchyma. The lesion consisted of clusters and sheets of large polygonal cells dissected by fibrous septa. The tumor cells had indistinct cellular borders, abundant granular eosinophilic cytoplasm, and small nuclei with indistinct nucleoli. No cytologic atypia or increased mitotic activity was seen. Immunohistochemically, the tumor cells were positive for S-100, inhibin-α, and CD68 and negative for calretinin, Melan-A, and WT-1. Ki-67 showed a low proliferation index (<1%). The morphology, in conjunction with immunohistochemical profile, led to a diagnosis of GCT of the tunica albuginea. Although GCT can occur in almost any location of the body, it has not been described to involve the human testis.

The receptor for advanced glycation end products (RAGE) is a multiligand pattern recognition receptor implicated in multiple disease states. Although RAGE is expressed on systemic vascular endothelium, the expression and function of RAGE on lung endothelium has not been studied. Utilizing in vitro (human) and in vivo (mouse) models, we established the presence of RAGE on lung endothelium. Because RAGE ligands can induce the expression of RAGE and stored red blood cells express the RAGE ligand N(ε)-carboxymethyl lysine, we investigated whether red blood cell (RBC) transfusion would augment RAGE expression on endothelium utilizing a syngeneic model of RBC transfusion. RBC transfusion not only increased lung endothelial RAGE expression but enhanced lung inflammation and endothelial activation, since lung high mobility group box 1 and vascular cell adhesion molecule 1 expression was elevated following transfusion. These effects were mediated by RAGE, since endothelial activation was absent in RBC-transfused RAGE knockout mice. Thus, RAGE is inducibly expressed on lung endothelium, and one functional consequence of RBC transfusion is increased RAGE expression and endothelial activation.

Background: Patients being transferred to a nursing home (NH) after an acute hospitalization are subject to adverse effects, including medication errors, related to poor coordination of care across settings., Objective: The goal of this study was to develop, implement, and evaluate the impact of a pilot intervention to improve patient safety by reducing delays in administration and omission of medications among patients discharged from the hospital to the NH., Methods: An expedited discharge protocol was developed in collaboration with hospital physician residents, hospital discharge planners, and NH staff (administrators, directors of nursing services, and licensed nurses). The intervention included education of the involved health care professionals and implementation of the expedited protocol to ensure that medication orders were transmitted to the NH-contracted pharmacy before patients' arrival at the NH. The intervention protocol was compared with a standard discharge protocol among patients aged > or =65 years being discharged from 2 university-affiliated hospitals to a single proprietary NH. The primary outcomes were the time between arrival at the NH and administration of first dose of an ordered medication; the number of omitted medications; the proportion of patients experiencing medication omissions; and the proportion of patients with omitted medications that had a low, medium, and high potential for negative consequences., Results: The study involved 10 patients discharged from each of the 2 hospitals and transferred to the NH. Although several components of the intervention were successfully implemented, none of the medication orders were transmitted to the NH-ccontracted pharmacy before patients' arrival at the NH. All 17 patients with medications ordered to be administered in the evening had > or =1 dose of a medication omitted after their arrival at the NH. The mean (SD) delay from arrival at the NH to administration of the first dose of an ordered medication was 12.55 (7.45) hours. The mean number of doses of different medications omitted per patient was 3.4 (2.60). Sixty-seven doses of medications were omitted; 53 of these omissions involved only 1 dose of a medication. Thirty-three percent of omitted doses involved medications with the highest potential for resulting in a negative consequence., Conclusions: The intervention to improve patient safety by reducing medication delays for patients making the transition from the hospital to the NH was not successfully implemented, as medication orders were not transmitted to the NH-contracted pharmacies before patients' arrival at the NH. All patients making the transition from hospital to NH experienced a >12-hour delay in medication administration, and the mean number of missed doses of medications was >3. There is a need for further exploration of the reasons for and possible solutions to delays in medication administration during the transition to the NH, as well as of the impact of such delays on patient outcomes, including adverse drug events, emergency department visits, and rehospitalizations.

The ubiquitin-proteasome system (UPS) plays a critical role in protein degradation. The 19S regulatory particle (RP) of the 26S proteasome mediates the recognition, deubiquitylation, unfolding, and channeling of ubiquitylated substrates to the 20S proteasome. Several subunits of the 19S RP interact with a growing number of factors. The cyclophilin-like domain (CLD) of Ran-binding protein-2 (RanBP2/Nup358) associates specifically with at least one subunit, S1, of the base subcomplex of the 19S RP, but the functional implications of this interaction on the UPS activity are elusive. This study shows the CLD of RanBP2 promotes selectively the accumulation of a subset of reporter substrates of the UPS, such as the ubiquitin (Ub)-fusion yellow fluorescent protein (YFP) degradation substrate, Ub(G76V)-YFP, and the N-end rule substrate, Ub-R-YFP. Conversely, the degradation of endoplasmic reticulum and misfolded proteins, and of those linked to UPS-independent degradation, is not affected by CLD. The selective effect of CLD on the UPS in vivo is independent of, and synergistic with, proteasome inhibitors, and CLD does not affect the intrinsic proteolytic activity of the 20S proteasome. The inhibitory activity of CLD on the UPS resides in a purported SUMO binding motif. We also found two RanBP2 substrates, RanGTPase-activating protein and retinitis pigmentosa GTPase regulator interacting protein-1alpha1, whose steady-state levels are selectively modulated by CLD. Hence, the CLD of RanBP2 acts as a novel auxiliary modulator of the UPS activity; it may contribute to the molecular and subcellular compartmentation of the turnover of properly folded proteins and modulation of the expressivity of several neurological diseases.

Equilibria of binary neutron stars in close circular orbits are computed numerically in a waveless formulation: the full Einstein-relativistic-Euler system is solved on an initial hypersurface to obtain an asymptotically flat form of the 4-metric and an extrinsic curvature whose time derivative vanishes in a comoving frame. Two independent numerical codes are developed, and solution sequences that model inspiraling binary neutron stars during the final several orbits are successfully computed. The binding energy of the system near its final orbit deviates from earlier results of third post-Newtonian and of spatially conformally flat calculations. The new solutions may serve as initial data for merger simulations and as members of quasiequilibrium sequences to generate gravitational-wave templates, and may improve estimates of the gravitational-wave cutoff frequency set by the last inspiral orbit.

This study examined the relation between parental coping styles, discipline, and child behavior before and after participating in a parent training program for parents of children with Attention-Deficit/Hyperactivity Disorder (ADHD) and oppositional behavior. For mothers, use of more maladaptive and less adaptive coping styles was related to more self-reported lax and overreactive discipline, more observed coercive parenting, and more observed child misbehavior prior to parent training. No significant relations were found for mothers following parent training after controlling for pretreatment variables. For fathers, use of more maladaptive and less adaptive coping styles was related to self-reported lax discipline before and after parent training. Contrary to prediction, fathers who reported less seeking support and adaptive-focused coping showed the most improvement in their children's behavior. Most results remained significant after controlling for self-reported depression. Implications for improving parent training research and programs were discussed.

Objective: The present study examined the relation between parental ADHD symptomatology and parent-child behavior among 46 mothers and 26 fathers of ADHD children., Results: Fathers' self-reports of inattention and impulsivity were strongly associated with self-reports of lax parenting both before and after parent training, and with self-reports of overreactivity after parent training. Fathers' impulsivity was also associated with more arguing during audiotaped observations of parent-child interactions prior to parent training. Mothers' self-reports of inattention were modestly associated with self-reports of laxness before and after parent training. Prior to parent training, there were non-linear relations between mothers' inattention and observations of mother-child behavior, with mothers who reported moderate levels of inattention engaging in the most negative parent-child interactions. After parent training, these relations were linear, with the mothers who reported the most inattention engaging in the most negative parent-child interactions. These results were weakened but were generally still significant when parental depression and alcohol use were controlled.

Utilized a pattern-based approach to discover the different constellations of perceived social transactions separately for family and peer systems and explored the risk and protective functions of these microsystem profiles for both depression and antisocial behavior among a sample of ethnically and racially diverse urban adolescents living in poverty. Measures of perceived social support, involvement and hassles with family and peers, as well as perceived social acceptance and peers' values were entered into two sets of iterative cluster analyses to identify distinct profiles of family and peer transactions. From each of the perceived family and peer transactional analyses, six replicated profiles emerged. Several of the profiles were consistent with expectations from prior literature such as Enmeshing families and Rejecting peer networks, while others were novel and intriguing such as Entangling peers. Family profiles were consistent in their risk and protective associations for both depression and antisocial behavior, while the peer profiles varied in their effects for each developmental outcome. For example, the Rejecting peer profile placed adolescents at increased risk for depression but protected them from antisocial behavior. Implications for future research and preventive intervention are discussed.

This study explored the effects of structural and experiential neighborhood factors and developmental stage on antisocial behavior, among a sample of poor urban adolescents in New York City. Conceptually and empirically distinct profiles of neighborhood experience were derived from the data, based on measures of perceived neighborhood cohesion, poverty-related hassles, and involvement in neighborhood organizations and activities. Both the profiles of neighborhood experience and a measure of census-tract-level neighborhood hazard (poverty and violence) showed relationships to antisocial behavior. Contrary to expectation, higher levels of antisocial behavior were reported among adolescents residing in moderate-structural-risk neighborhoods than those in high-structural-risk neighborhoods. This effect held only for teens in middle (not early) adolescence and was stronger for teens perceiving their neighborhoods as hassling than for those who did not. Implications for future research and preventive intervention are discussed.

Liposarcoma of the head and neck is rare. Because of its rarity, we report this case of pleomorphic liposarcoma of the left pterygomandibular space, involving the maxilla, maxillary sinus, left lateral maxillary wall, left maxillary gingiva with extension into the buccal space, retro-orbital region, left mandibular ramus, and left zygomatic process. To our knowledge, there are only two other reported cases of liposarcoma involving the maxilla, one of which was a pleomorphic liposarcoma. The pertinent literature is reviewed with an emphasis on the importance of histopathologic classification.

Pyxis--an automated dispensing and inventory control system that provides supply management at point-of-use--helped us reduce supply expenses and improve productivity.