Physician’s Ability to Manually Detect Isolated Elevation in Leg Intracompartmental Pressure.

Background: Serial physical examination is recommended for patients for whom there is a high index of suspicion for compartment syndrome. This examination is more difficult when performed on an obtunded patient and relies on the sensitivity of manual palpation to detect compartment firmness—a direct manifestation of increased intracompartmental pressure. This study was performed to establish the sensitivity of manual palpation for detecting critical pressure elevations in the leg compartments most frequently involved in clinical compartment syndrome. Methods: Reproducible, sustained elevation of intracompartmental pressure was established in fresh cadaver leg specimens. Pressures tested included 20 and 40 mm Hg (negative controls) and 60 and 80 mm Hg (considered to be consistent with a compartment syndrome). Each leg served as an internal control, with three compartments having a noncritical pressure elevation. Orthopaedic residents and faculty were individually invited to manually palpate the leg with a known compartment pressure and to answer the following questions: (1) Is there a compartment syndrome? (2) In which compartment or compartments do you believe the pressure is elevated, if at all? (3) Describe your examination findings as soft, compressible, or firm. Results: When a true-positive result was considered to be the correct detection of an elevation of intracompartmental pressures and correct identification of the compartment with the elevated pressure, the sensitivity of manual palpation was 24%, the specificity was 55%, the positive predictive value was 19%, and the negative predictive value was 63%. With increasing intracompartmental pressure, fasciotomy was recommended with a higher frequency (19% when the pressure was 20 mm Hg, 28% when it was 40 mm Hg, 50% when it was 60 mm Hg, and 60% when it was 80 mm Hg). When a true-positive result of manual palpation was considered to be an appropriate recommendation of fasciotomy, regardless of the ability of the examiner to correctly localize the compartment with the critical pressure elevation, the sensitivity was 54%,the specificity was 76%, the positive predictive value was 70%, and the negative predictive value was 63%. Conclusions: Manual detection of compartment firmness associated with critical elevations in intracompartmentalpressure is poor

Impact of Study Skills and Parent Education on First-Year GPA Among College Students With and Without ADHD: A Moderated Mediation Model

Objective: To test if the relationship between ADHD and academic achievement is mediated by service utilization and/or study skills, and if these mediation effects are moderated by parental education level. Method: A bootstrapping method within structural equation modeling was used with data from 355 first year college students meeting strict criteria for ADHD or clearly without ADHD to test the mediation and moderation effects. Results: Study skills, but not service utilization, significantly mediated the relationship between ADHD status and GPA; however, this relationship was not significant among students with at least one parent holding a master’s degree or higher. Conclusion: Among first year college students study skills may be a more salient predictor of educational outcomes relative to ADHD status. Additional research into support services for college students with ADHD is needed, however, results suggest interventions targeting study skills may hold particular promise for these students

Quantifying the Relationship between Capability and Health in Older People: Can't Map, Won't Map

BACKGROUND: Intuitively, health and capability are distinct but linked concepts. This study aimed to quantify the link between a measure of health status (EQ-5D-3L) and capability (ICECAP-O) using regression-based methods. METHODS: EQ-5D-3L and ICECAP-O data were collected from a sample of older people ( n = 584), aged over 65 years, requiring a hospital visit and/or care home resident, and recruited to one of 3 studies forming the Medical Crisis in Older People (MCOP) program in England. The link of EQ-5D-3L with 1) ICECAP-O tariff scores were estimated using ordinary least squares (OLS) or censored least absolute deviation (CLAD) regression models; and 2) ICECAP-O domain scores was estimated using multinomial logistic (MNL) regression. Mean absolute error (MAE), root mean squared error (RMSE), absolute difference (AD) between mean observed and estimated values, and the R(2) statistic were used to judge model performance. RESULTS: In this sample of older people ( n = 584), higher scores on the EQ-5D-3L were shown to be linked with higher ICECAP-O scores when using linear regression. An OLS-regression model was identified to be the best performing model with the lowest error statistics (AD = 0.0000; MAE = 0.1208; MSE = 0.1626) and highest goodness of fit ( R(2) = 0.3532); model performance was poor when predicting the lower ICECAP-O tariff scores. The three domains of the EQ-5D-3L showing a statistically significant quantifiable link with the ICECAP-O tariff score were self-care, usual activities, and anxiety/depression. CONCLUSION: A quantifiable, but weak, link between health (EQ-5D-3L) and capability (ICECAP-O) was identified. The findings from this study add further support that the ICECAP-O is providing complimentary information to the EQ-5D-3L. Mapping between the 2 measures is not advisable and the measures should not be used as direct substitutes to capture the impact of interventions in economic evaluations

Androgen Receptor Modulation Optimized for Response (ARMOR) Phase I and II Studies: Galeterone for the Treatment of Castration-Resistant Prostate Cancer

Purpose: Galeterone is a selective, multitargeted agent that inhibits CYP17, antagonizes the androgen receptor (AR), and reduces AR expression in prostate cancer cells by causing an increase in AR protein degradation. These open-label phase I and II studies [Androgen Receptor Modulation Optimized for Response-1 (ARMOR1) and ARMOR2 part 1] evaluated the efficacy and safety of galeterone in patients with treatment-naive nonmetastatic or metastatic castration-resistant prostate cancer (CRPC) and established a dose for further study. Experimental Design: In ARMOR1, 49 patients received increasing doses (650–2,600 mg) of galeterone in capsule formulation; 28 patients in ARMOR2 part 1 received increasing doses (1,700–3,400 mg) of galeterone in tablet formulation for 12 weeks. Patients were evaluated biweekly for safety and efficacy, and pharmacokinetic parameters were assessed. Results: In ARMOR1, across all doses, 49.0% (24/49) achieved a ≥30% decline in prostate-specific antigen (PSA; PSA30) and 22.4% (11/49) demonstrated a ≥50% PSA decline (PSA50). In ARMOR2 part 1, across all doses, PSA30 was 64.0% (16/25) and PSA50 was 48.0% (12/25). In the 2,550-mg dose cohort, PSA30 was 72.7% (8/11) and PSA50 was 54.5% (6/11). Galeterone was well tolerated; the most common adverse events were fatigue, increased liver enzymes, gastrointestinal events, and pruritus. Most were mild or moderate in severity and required no action and there were no apparent mineralocorticoid excess (AME) events. Conclusions: The efficacy and safety from ARMOR1 and ARMOR2 part 1 and the pharmacokinetic results support the galeterone tablet dose of 2,550 mg/d for further study. Galeterone was well tolerated and demonstrated pharmacodynamic changes consistent with its selective, multifunctional AR signaling inhibition

Cortical tau is associated with microstructural imaging biomarkers of neurite density and dendritic complexity in Alzheimer's disease

INTRODUCTION: In Alzheimer's disease (AD), hyperphosphorylated tau is closely associated with focal neurodegeneration, but the mechanism remains uncertain. METHODS: We quantified cortical microstructure using neurite orientation dispersion and density imaging in 14 individuals with young onset AD. Diffusion tensor imaging measured mean diffusivity (MD). Amyloid beta and tau positron emission tomography were acquired and associations with microstructural measures were assessed. RESULTS: When regional volume was adjusted for, in the medial temporal lobe there was a significant negative association between neurite density and tau (partial R2  = 0.56, p = 0.008) and between orientation dispersion and tau (partial R2  = 0.66, p = 0.002), but not between MD and tau. In a wider cortical composite, there was an association between orientation dispersion and tau (partial R2  = 0.43, p = 0.030), but not between other measures and tau. DISCUSSION: Our findings are consistent with tau causing first dendritic pruning (reducing dispersion/complexity) followed by neuronal loss. Advanced magnetic resonance imaging (MRI) microstructural measures have the potential to provide information relating to underlying tau deposition

Ginsenosides act as positive modulators of P2X4 receptors

We investigated the selectivity of protopanaxadiol ginsenosides from Panax ginseng acting as positive allosteric modulators on P2X receptors. ATP-induced responses were measured in stable cell lines overexpressing human P2X4 using a YOPRO-1 dye uptake assay, intracellular calcium measurements, and whole-cell patch-clamp recordings. Ginsenosides CK and Rd were demonstrated to enhance ATP responses at P2X4 by ∼twofold, similar to potentiation by the known positive modulator ivermectin. Investigations into the role of P2X4 in mediating a cytotoxic effect showed that only P2X7 expression in HEK-293 cells induces cell death in response to high concentrations of ATP, and that ginsenosides can enhance this process. Generation of a P2X7-deficient clone of BV-2 microglial cells using CRISPR/ Cas9 gene editing enabled an investigation of endogenous P2X4 in a microglial cell line. Compared with parental BV-2 cells, P2X7-deficient BV-2 cells showed minor potentiation of ATP responses by ginsenosides, and insensitivity to ATP 2 or ATP 1 ginsenoside-induced cell death, indicating a primary role for P2X7 receptors in both of these effects. Computational docking to a homology model of human P2X4, based on the open state of zfP2X4, yielded evidence of a putative ginsenoside binding site in P2X4 in the central vestibule region of the large ectodomain

Superconductivity in potassium-doped 2,2′'-bipyridine

Organic compounds are always promising candidates of superconductors with high transition temperatures. We examine this proposal by choosing 2,2$'$-bipyridine solely composed by C, H, and N atoms. The presence of Meissner effect with a transition temperature of 7.2 K in this material upon potassium doping is demonstrated by the $dc$ magnetic susceptibility measurements. The real part of the $ac$ susceptibility exhibits the same transition temperature as that in $dc$ magnetization, and a sharp peak appeared in the imaginary part indicates the formation of the weakly linked superconducting vortex current. The occurence of superconductivity is further supported by the resistance drop at the transition together with its suppression by the applied magnetic fields. The superconducting phase is identified to be K$_3$-2,2$'$-bipyridine from the analysis of Raman scattering spectra. This work not only opens an encouraging window for finding superconductivity after optoelectronics in 2,2$'$-bipyridine-based materials but also offers an example to realize superconductivity from conducting polymers and their derivatives.Comment: 6 pages, 3 figure