Evaluating the effectiveness of physical exercise in improving standardized testing performances through attention indices.

INTRODUCTION: In the United States, standardized tests have risen in prevalence, extending their importance from education placement to employment. Attention is crucial to improving testing performance. Past studies have established that acute, coordinative, aerobic exercise improves attention, which is measured by the D2 Attention Test, emotional analysis, reading time, and eye movement tracking. No studies have drawn connections between physical exercise's quantifiable improvement in attention to improvements in standardized tests; therefore, this study would attempt to do so. METHODS: This study defines attention to be positively related to reading speed and negatively related to the number of eye drifts. High school students were selected to read and answer two reading passages from an SAT (Scholastic Assessment Test) exam, before and after a short 80% intensity run. Their reading times, facial video, and test scores were recorded. Dlib plots the facial landmark and OpenCV tracks movement of the pupil. RESULTS: Through paired-samples t-tests, this study found out that after exercise, subjects displayed increased reading speed and fewer eye drifts, coupled with increased mean scores. CONCLUSION: Thus, this study demonstrated that running, as an acute, coordinative, aerobic exercise, helps increase the testing performance of the SAT reading section by measuring attention. Future research could focus on including head movement as an attention index, replicate the experiment on different standardized tests or exercises, and conduct natural experiments to better simulate real-life conditions to increase applicability.

Exploring the target scope of KEAP1 E3 ligase-based PROTACs.

Targeted protein degradation (TPD) uses small molecules to recruit E3 ubiquitin ligases into the proximity of proteins of interest, inducing ubiquitination-dependent degradation. A major bottleneck in the TPD field is the lack of accessible E3 ligase ligands for developing degraders. To expand the E3 ligase toolbox, we sought to convert the Kelch-like ECH-associated protein 1 (KEAP1) inhibitor KI696 into a recruitment handle for several targets. While we were able to generate KEAP1-recruiting degraders of BET family and murine focal adhesion kinase (FAK), we discovered that the target scope of KEAP1 was narrow, as targets easily degraded using a cereblon (CRBN)-recruiting degrader were refractory to KEAP1-mediated degradation. Linking the KEAP1-binding ligand to a CRBN-binding ligand resulted in a molecule that induced degradation of KEAP1 but not CRBN. In sum, we characterize tool compounds to explore KEAP1-mediated ubiquitination and delineate the challenges of exploiting new E3 ligases for generating bivalent degraders.

Surgery associated with increased survival compared to radiation in clinically localized Gleason 9-10 prostate cancer: a SEER analysis.

PURPOSE: Men with Gleason score 9-10 prostate cancer have worse outcomes compared to those with Gleason 8 disease. Upfront treatments remain controversial for these patients. Using the Surveillance, Epidemiology, and End Results (SEER) database, we evaluated the impact of initial treatment with external beam radiation therapy (EBRT), external beam radiation therapy with brachytherapy (EBRT + BT), or surgery on prostate cancer-specific mortality (PCSM) and overall mortality (OM) in Gleason 9-10 disease. METHODS: The SEER database was queried for men diagnosed with biopsy Gleason 9-10 prostate cancer from 2005 to 2014. Gathered data included demographic, pathologic, therapy received, and survival outcomes. Kaplan-Meier survival curves and crude and multivariate analyses were generated for initial therapy with EBRT, EBRT + BT, or surgery. RESULTS: A total of 7877 men were included, 4465 (56.7%) who underwent upfront treatment with EBRT alone, 623 (7.9%) with EBRT + BT, and 2789 (35.4%) with surgery. The 7 year PCSM rates were 29.2, 15.0, and 14.6% for EBRT, EBRT + BT, and surgery respectively (p < 0.001). The 7 year OM rates were 43.8, 27.2, and 20.0% for EBRT, EBRT + BT, and surgery, respectively (p < 0.001).When controlling for age, year of diagnosis, Gleason score, clinical T stage, and PSA level on multivariate analysis, EBRT had greater PCSM and OM than surgery (HR 0.41, 95% CI 0.28-0.61, p < 0.001 and HR 0.44, 95% CI 0.34-0.57, p < 0.001 respectively), but the mortality differences was not statistically significant between EBRT and EBRT + BT. CONCLUSION: Among men with localized Gleason 9-10 disease, surgery was associated with statistically significant improved survival outcomes compared to EBRT alone.

Evaluation of Cancer Specific Mortality with Surgery versus Radiation as Primary Therapy for Localized High Grade Prostate Cancer in Men Younger Than 60 Years.

PURPOSE: The optimal primary treatment of localized high grade prostate cancer in younger men remains controversial. The objective of this project was to compare the impact of initial radical prostatectomy vs radiation therapy on survival outcomes in young men less than 60 years old with high grade prostate cancer. MATERIALS AND METHODS: We retrospectively analyzed the records of men younger than 60 years in the SEER (Surveillance, Epidemiology and End Results) database who underwent initial surgery or radiation therapy of high grade (Gleason score 8 or greater) localized (N0M0 TNM stage) prostate cancer from 2004 to 2012. Univariate and multivariate Cox proportional hazards regression models were used to examine prostate cancer specific and overall mortality. RESULTS: A total of 2,228 men were identified, of whom 1,459 (65.5%) underwent initial surgery and had a median followup of 43 months and 769 (34.5%) underwent initial external beam radiation therapy with or without brachytherapy and had a median followup of 44 months. On multivariate analysis initial treatment with surgery was associated with improved prostate cancer specific and overall mortality compared with initial radiation treatment (HR 0.37, 95% CI 0.19-0.74, p = 0.005 vs HR 0.41, 95% CI 0.24-0.70, p = 0.001) when controlling for age, biopsy Gleason score, T stage and prostate specific antigen. CONCLUSIONS: Our data showed significant survival differences in young men treated initially with surgery vs external beam radiation therapy of high grade prostate cancer. Future prospective randomized trials are needed to confirm the long-term outcomes of these treatment approaches.

Simulation for Assessment of Milestones in Emergency Medicine Residents.

OBJECTIVES: All residency programs in the United States are required to report their residents' progress on the milestones to the Accreditation Council for Graduate Medical Education (ACGME) biannually. Since the development and institution of this competency-based assessment framework, residency programs have been attempting to ascertain the best ways to assess resident performance on these metrics. Simulation was recommended by the ACGME as one method of assessment for many of the milestone subcompetencies. We developed three simulation scenarios with scenario-specific milestone-based assessment tools. We aimed to gather validity evidence for this tool. METHODS: We conducted a prospective observational study to investigate the validity evidence for three mannequin-based simulation scenarios for assessing individual residents on emergency medicine (EM) milestones. The subcompetencies (i.e., patient care [PC]1, PC2, PC3) included were identified via a modified Delphi technique using a group of experienced EM simulationists. The scenario-specific checklist (CL) items were designed based on the individual milestone items within each EM subcompetency chosen for assessment and reviewed by experienced EM simulationists. Two independent live raters who were EM faculty at the respective study sites scored each scenario following brief rater training. The inter-rater reliability (IRR) of the assessment tool was determined by measuring intraclass correlation coefficient (ICC) for the sum of the CL items as well as the global rating scales (GRSs) for each scenario. Comparing GRS and CL scores between various postgraduate year (PGY) levels was performed with analysis of variance. RESULTS: Eight subcompetencies were chosen to assess with three simulation cases, using 118 subjects. Evidence of test content, internal structure, response process, and relations with other variables were found. The ICCs for the sum of the CL items and the GRSs were >0.8 for all cases, with one exception (clinical management GRS = 0.74 in sepsis case). The sum of CL items and GRSs (p < 0.05) discriminated between PGY levels on all cases. However, when the specific CL items were mapped back to milestones in various proficiency levels, the milestones in the higher proficiency levels (level 3 [L3] and 4 [L4]) did not often discriminate between various PGY levels. L3 milestone items discriminated between PGY levels on five of 12 occasions they were assessed, and L4 items discriminated only two of 12 times they were assessed. CONCLUSION: Three simulation cases with scenario-specific assessment tools allowed evaluation of EM residents on proficiency L1 to L4 within eight of the EM milestone subcompetencies. Evidence of test content, internal structure, response process, and relations with other variables were found. Good to excellent IRR and the ability to discriminate between various PGY levels was found for both the sum of CL items and the GRSs. However, there was a lack of a positive relationship between advancing PGY level and the completion of higher-level milestone items (L3 and L4).

Clustering of Cyclodextrin-Functionalized Microbeads by an Amphiphilic Biopolymer: Real-Time Observation of Structures Resembling Blood Clots.

Colloidal particles can be induced to cluster by adding polymers in a process called bridging flocculation. For bridging to occur, the polymer must bind strongly to the surfaces of adjacent particles, such as via electrostatic interactions. Here, we introduce a new system where bridging occurs due to specific interactions between the side chains of an amphiphilic polymer and supramolecules on the particle surface. The polymer is a hydrophobically modified chitosan (hmC) while the particles are uniform polymeric microbeads (∼160 µm in diameter) made by a microfluidic technique and functionalized on their surface by α-cyclodextrins (CDs). The CDs have hydrophobic binding pockets that can capture the n-alkyl hydrophobes present along the hmC chains. Clustering of CD-coated microbeads in water by hmC is visualized in real time using optical microscopy. Interestingly, the clustering follows two distinct stages: first, the microbeads are bridged into clusters by hmC chains, which occurs by the interaction of individual chains with the CDs on adjacent particles. Thereafter, additional hmC from the solution adsorbs onto the surfaces of the microbeads and an hmC "mesh" grows around the clusters. This growing nanostructured mesh can trap surrounding microsized objects and sequester them within the overall cluster. Such clustering is reminiscent of blood clotting where blood platelets initially cluster at a wound site, whereupon they induce growth of a protein (fibrin) mesh around the clusters, which entraps other passive cells. Clustering does not occur with the native chitosan (lacking hydrophobes) or with the bare particles (lacking CDs); these results confirm that the clustering is indeed due to hydrophobic interactions between the hmC and the CDs. Microbead clustering via amphiphilic biopolymers could be applicable in embolization, which is a surgical technique used to block blood flow to a particular area of the body, or in agglutination assays.

Host factors do not influence the colonization or infection by fluconazole resistant Candida species in hospitalized patients.

Nosocomial yeast infections have significantly increased during the past two decades in industrialized countries, including Taiwan. This has been associated with the emergence of resistance to fluconazole and other antifungal drugs. The medical records of 88 patients, colonized or infected with Candida species, from nine of the 22 hospitals that provided clinical isolates to the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) program in 1999 were reviewed. A total of 35 patients contributed fluconazole resistant strains [minimum inhibitory concentrations (MICs) > or = 64 mg/l], while the remaining 53 patients contributed susceptible ones (MICs < or = 8 mg/l). Fluconazole resistance was more frequent among isolates of Candida tropicalis (46.5%) than either C. albicans (36.8%) or C. glabrata (30.8%). There was no significant difference in demographic characteristics or underlying diseases among patients contributing strains different in drug susceptibility.