Colloidal Synthesis of Monodisperse High-Entropy Spinel Oxide Nanocrystals.

Synthesis of high-entropy oxide (HEO) nanocrystals has focused on increasing the temperature in the entropy term (T(ΔS)) to overcome the enthalpy term. However, these high temperatures lead to large, polydisperse nanocrystals. In this work, we leverage the low solubility product (Ksp) of metal oxides and optimize the Lewis-acid-catalyzed esterification reaction for equal rate production of the cation monomers to synthesize HEO nanocrystals at low temperatures, producing the smallest (<4 nm) and most monodisperse (<15% size dispersity) HEOs to date. We apply these HEO nanocrystals as electrocatalysts, exhibiting promising activity toward the oxygen evolution reaction in alkaline media, with an overpotential of 345 mV at 10 mA/cm2.

Willingness to use PrEP among PrEP naïve men who have sex with men: a meta-analysis.

This study aimed to measure the pooled estimate of willingness to use HIV pre-exposure prophylaxis (PrEP) (WTUP) among PrEP-naïve United States (U.S.)-based men who have sex with men (MSM). PubMed, Embase, Web of Science, CINAHL, and PsycINFO were searched. The search strategy contained the keyword willingness and interest and the MeSH terms for HIV and PrEP. Articles were included if they were published between January 2005 and May 2022, reported quantitative data on WTUP among PrEP-naïve US-based MSM, and were available as full text in English. Meta-analysis was conducted to assess the pooled effect size of WTUP prevalence using a random-effects model, heterogeneity in the pooled estimate was assessed, and subgroup analyzes were conducted. Fifteen studies were included based on the inclusion and exclusion criteria. Meta-analysis revealed a pooled prevalence proportion for WTUP of 0.58 (95% CI 0.54-0.61) (or 58 out of 100) among PrEP-naïve MSM. High inter-study heterogeneity (Q = 548.10, df = 19, p < 0.01, I2 = 96.53, τ2 = 0.09) was observed. Age of the study sample and region where the data were collected significantly moderated the pooled WTUP estimate. Age-appropriate PrEP related messaging and a focus on HIV priority areas of the U.S. would be important strategies to improve WTUP among MSM in the U.S. moving forward.

Preferences for a community pharmacy-based pre-exposure prophylaxis (PrEP) delivery program: A discrete choice experiment.

BACKGROUND: Community pharmacies are ideal venues for pre-exposure prophylaxis (PrEP) delivery. Pharmacists and pharmacy-based PrEP delivery programs have the potential to improve access. OBJECTIVES: This study elicited preferences for attributes of a hypothetical community pharmacy-based PrEP delivery program among US men who have sex with men (MSM) and assessed predictors of their preferences. METHODS: Data were collected via a cross-sectional anonymous survey of US MSM, who were aged 18-65 years, not transgender, reported HIV status negative/unknown, and PrEP eligible. A discrete choice experiment was conducted with seven attributes of a pharmacy-based PrEP program: initial PrEP eligibility screening mode, location for human immunodeficiency virus (HIV) tests, timing for HIV test results, PrEP decision-making style, location of PrEP consultations, PrEP medication fill method, and mode for ongoing monitoring. Latent class analysis was performed to analyze preference heterogeneity. Multinomial logistic regression assessed predictors of latent class membership. RESULTS: This study included 390 MSM. Time to receive HIV test results was the most important attribute; receiving results on the same day had the highest preference. The next most important attribute was PrEP screening mode; online questionnaires were the most preferred. Respondents' preferences clustered into four classes: 1) "Same day results and online monitoring" (SDROM) group (63.1%), 2) "Consumerist decision-making" (CDM) group (16.2%), 3) "Self-screening (online questionnaire)" (SOQ) group (11.3%), and 4) "Same day results preferring" (SDRP) group (9.5%). Hispanic MSM (adjusted odds ratio [aOR] =0.31, 95% confidence interval [CI] [0.12-0.84], P = 0.020), MSM of other races (aOR=0.38, 95% CI [0.15-0.97], P = 0.044) vs. White MSM; and those having a sexually transmitted disease recently (aOR=0.37, 95% CI [0.16-0.85], P = 0.018), had lower odds of being in the CDM group vs. the SDROM group. CONCLUSIONS: MSM's preferences for a pharmacy-based PrEP program are heterogeneous. Same day results for HIV tests and online PrEP screening are key components when designing a community pharmacy-based PrEP program.

General Route to Colloidally Stable, Low-Dispersity Manganese-Based Ternary Spinel Oxide Nanocrystals.

While certain ternary spinel oxides have been well-explored with colloidal nanochemistry, notably the ferrite spinel family, ternary manganese (Mn)-based spinel oxides have not been tamed. A key composition is cobalt (Co)-Mn oxide (CMO) spinel, CoxMn3-xO4, that, despite exemplary performance in multiple electrochemical applications, has few reports in the colloidal literature. Of these reports, most show aggregated and polydisperse products. Here, we describe a synthetic method for small, colloidally stable CMO spinel nanocrystals with tunable composition and low dispersity. By reacting 2+ metal-acetylacetonate (M(acac)2) precursors in an amine solvent under an oxidizing environment, we developed a pathway that avoids the highly reducing conditions of typical colloidal synthesis reactions; these reducing conditions typically push the system toward a monoxide impurity phase. Through surface chemistry studies, we identify organic byproducts and their formation mechanism, enabling us to engineer the surface and obtain colloidally stable nanocrystals with low organic loading. We report a CMO/carbon composite with low organic contents that performs the oxygen reduction reaction (ORR) with a half-wave potential (E1/2) of 0.87 V vs RHE in 1.0 M potassium hydroxide at 1600 rpm, rivaling previous reports for the highest activity of this material in ORR electrocatalysis. We extend the general applicability of this procedure to other Mn-based spinel nanocrystals such as Zn-Mn-O, Fe-Mn-O, Ni-Mn-O, and Cu-Mn-O. Finally, we show the scalability of this method by producing inorganic nanocrystals at the gram scale.

Small leucine zipper protein functions as a modulator for metabolic reprogramming of colorectal cancer cells by inducing nutrient stress-mediated autophagy.

In multiple cancers, autophagy promotes tumor development by recycling intracellular components into metabolic pathways. Autophagy-induced metabolic reprogramming and plasticity lead to cancer cell survival and resistance to anticancer therapy. We investigated the role of small leucine zipper protein (sLZIP) in autophagy and cell survival under nutrient-deficient conditions in colorectal cancer (CRC). sLZIP was induced by nutrient stress and increased the transcription of microtubule-associated protein 1A/1B-light chain 3 (LC3), by directly binding to its promoter. Under nutrient stress conditions, sLZIP activated autophagy and promoted the survival of CRC cells. sLZIP induced metabolic reprogramming of CRC cells, to activate glutaminolysis and the tricarboxylic acid cycle. sLZIP also enhanced the autophagic degradation of Keap1 and the nuclear accumulation of Nrf2, leading to NQO1 expression, for maintenance of redox homeostasis. sLZIP-knockout CRC cells exhibited impaired autophagy induction in the glycolytic inhibition state. Xenograft mice lacking sLZIP showed decreased tumor growth, by rendering CRC cells sensitive to glycolysis inhibition. The expression of sLZIP and LC3B was highly elevated in tumors of CRC patients compared to that in normal tissues, and correlated with the progression of CRC. These findings suggest that sLZIP drives autophagy and metabolic reprogramming to promote colorectal tumorigenesis.

Age-varying association between depression and cognitive function among a national sample of older U.S. immigrant adults: the potential moderating role of physical activity.

OBJECTIVES: This study aimed to (1) investigate age-associated trends in depression and cognition, (2) determine whether the association between depression and cognition varies across age, and (3) test whether this association is moderated by different levels of physical activity among older U.S. immigrant adults aged 60 to 80 years. METHODS: Using national data on elderly U.S. immigrants (N = 375) from the 2011-2014 NHANES, we employed weighted intercept-only linear time-varying effect modeling (TVEM) and weighted linear TVEM to address our research questions. RESULTS: Weighted intercept-only linear TVEM indicated no trend in depression, but its mean peaked at age 67. Cognition consistently decreased with age, reaching its lowest point at age 78. Weighted linear TVEM revealed a significant inverse association between depression and cognition at some age ranges, with the strongest association at around age 66. Yet, we did not find the moderational relation of physical activity to this age-varying association. CONCLUSIONS: Although we observed a significant inverse relationship between depression and cognition at a certain age point, physical activity did not moderate the age-varying association. Understanding of age-varying effects on the depression-cognition interaction will promote prevention efforts targeting aging immigrant populations at highest risk for these health outcomes. Further work is needed to test moderating effects of other health behaviors on this association across age.Supplemental data for this article is available online at https://doi.org/10.1080/13607863.2022.2056139 .

Contralateral protective effect against repeated bout of damaging exercise: A meta-analysis.

The purpose was to summarize the studies examining the contralateral protective effect on the maximal strength in the subsequent bout of muscle-damaging exercise. The literature search was conducted through CINAHL plus, SportDiscus, and PubMed. Hedge's g effect size (ES) and 95% confidence intervals (CIs) were computed using a random effects model. From 14 papers and 25 ESs, the mean ES for contralateral repeated bout effect (CL-RBE) on 1-, 2-, and 3-day post maximal strength were -0.61 (95% CI = -0.80, -0.41), -0.50 (95% CI = -0.67, -0.33), and -0.74 (95% CI = -1.01, -0.48), respectively. For moderator analyses, the mean ESs were not influenced by type (isometric vs. isokinetic) of strength, but CL-RBE on maximal strength was influenced by duration (≤6 weeks) between bouts. Therefore, the meta-analysis demonstrated that an initial bout of exercise induces the protective effect on contralateral limb muscles regardless of the different type of strength, but can be affected by different duration (≤6 weeks) between exercise bouts.

Gas-Phase Alkali Metal-Assisted MOCVD Growth of 2D Transition Metal Dichalcogenides for Large-Scale Precise Nucleation Control.

Advances in large-area and high-quality 2D transition metal dichalcogenides (TMDCs) growth are essential for semiconductor applications. Here, the gas-phase alkali metal-assisted metal-organic chemical vapor deposition (GAA-MOCVD) of 2D TMDCs is reported. It is determined that sodium propionate (SP) is an ideal gas-phase alkali-metal additive for nucleation control in the MOCVD of 2D TMDCs. The grain size of MoS2 in the GAA-MOCVD process is larger than that in the conventional MOCVD process. This method can be applied to the growth of various TMDCs (MoS2 , MoSe2 , WSe2 , and WSe2 ) and the generation of large-scale continuous films. Furthermore, the growth behaviors of MoS2 under different SP and oxygen injection time conditions are systematically investigated to determine the effects of SP and oxygen on nucleation control in the GAA-MOCVD process. It is found that the combination of SP and oxygen increases the grain size and nucleation suppression of MoS2 . Thus, the GAA-MOCVD with a precise and controllable supply of a gas-phase alkali metal and oxygen allows achievement of optimum growth conditions that maximizes the grain size of MoS2 . It is expected that GAA-MOCVD can provide a way for batch fabrication of large-scale atomically thin electronic devices based on 2D semiconductors.

Association among length of residence, physical activity, and obesity in the US immigrants: A regression-based mediation analysis.

OBJECTIVES: To examine the mediated relationship between objectively measured obesity, accelerometer-based moderate-to-vigorous physical activity (MVPA), and length of residence among US immigrants. METHODS: A total of 885 adults (≥18 years) who were born outside the United States from the 2003 to 2006 National Health and Nutrition Examination Survey were included in the analysis. The participants were categorized into two groups (i.e., living in the United States ≥15 years vs. <15 years). MVPA time (minutes/day) was measured by ActiGraph accelerometry. Obesity was defined as body fat percentage measured by dual-energy X-ray absorptiometry. Regression-based mediation analysis was conducted using SURVEY procedures in SAS version 9.4. RESULTS: When controlling for covariates, immigrants living in the United States for ≥15 years were significantly less likely to spend time participating in MVPA (c; ß = -4.50, p = .04), and more likely to be at high risk of obesity (a; ß = 1.70, p = .01) compared to those living in the United States for <15 years. Also, the relationship between obesity and MVPA was statistically significant (b; ß = -0.80, p = .003). Length of residence was indirectly associated with MVPA (ab; ß = -1.37, p = .03), suggesting that obesity mediated the association of length of residence on MVPA (c'; ß = -3.13, p = .20). CONCLUSIONS: Obesity mediated the association between length of residence and MVPA in the US immigrants. These findings may encourage long-term US immigrants to prevent and treat obesity for increasing the amount of MVPA time.

Vigorous-intensity acute exercise during encoding can reduce levels of episodic and false memory.

The potential benefits (veridical memory) and, importantly, costs (false memory) of acute exercise on memory in conjunction with the timing and type of exercise have not been fully studied. In Experiment 1, we employed a three-condition (15-minute vigorous-intensity acute exercise Before or During memory encoding, or a Control condition of watching a video), within-subjects, counterbalanced design. The procedures included an immediate and delayed (20-minute post encoding) free recall assessment. Veridical memory was determined by the number of studied words that were recalled, whereas false memory was determined by retrieving a non-presented, critical item. For veridical memory, Before was not different than Control (p = .42), however, During was worse than Before and Control (p's < .001). No differences occurred for false memory. Experiment 2 was conducted that included several additional exercise conditions (e.g., light-intensity exercise) during memory encoding, used a recognition task instead of a free recall task, and extended the long-term memory assessment out to 24-hours. Experiment 2 demonstrated that vigorous-intensity acute exercise during encoding reduced both veridical and false memory for related new items (p < .05). These findings demonstrate that the timing and intensity of exercise play an important role in influencing memory performance.

A simple method for extracting phycocyanin from Arthrospira (Spirulina) platensis by autolysis.

Phycocyanin (PC) is a natural blue pigment that has great commercial value in food and pharmaceutical industry. Arthrospira (Spirulina) platensis is a photosynthetic spiral-shaped cyanobacterium containing a rich PC pigment. Autolysis is the enzymatic digestion of cells by the action of its own enzymes. To develop an effective and economical extraction process, an autolysis process was incorporated into the conventional freezing-thawing method. In the present study, 91% of maximal extraction yield of PC with 1.194 purity (A620/A280) was obtained via autolysis after 3 h of incubation at 37 °C without using an extraction salt solution or a successive freezing-thawing process. In addition to temperature, the initial concentration of bicarbonate in growth medium and the concentration of wet biomass are important parameters that influence the extraction yield of PC by autolysis.

Alloferon and Zanamivir Show Effective Antiviral Activity against Influenza A Virus (H1N1) Infection In Vitro and In Vivo.

The use of vaccines is the most effective and reliable method for the prevention of viral infections. However, research on evaluation of effective therapeutic agents for use in treatment after infection is necessary. Zanamivir was administered through inhalation for treatment of pandemic influenza A/H1N1 in 2009. However, the emergence of drug-resistant strains can occur rapidly. Alloferon, an immunomodulatory drug developed as an NK cell activator, exerts antiviral effects against various viruses, particularly influenza viruses. Therefore, alloferon and zanamivir were administered in combination in an effort to improve the antiviral effect of zanamivir by reducing H1N1 resistance. First, we confirmed that administration of combined treatment would result in effective inhibition of viral proliferation in MDCK and A549 cells infected with H1N1. Production of IL-6 and MIP-1α in these cells and the activity of p38 MAPK and c-Jun that are increased by H1N1 were inhibited by combined treatment. Mice were then infected intranasally with H1N1, and examination of the antiviral efficacy of the alloferon/zanamivir combination was performed. The results showed that combined treatment after infection with H1N1 prevented weight loss, increased the survival rate, and improved lung fibrosis. Combined treatment also resulted in reduced infiltration of neutrophils and macrophages into the lungs. Combined treatment effectively inhibited the activity of p38 MAPK and c-Jun in lung tissue, which was increased by infection with H1N1. Therefore, the combination of alloferon/zanamivir effectively prevents the development of H1N1-mediated inflammation in the lungs by inhibiting the production of inflammatory mediators and migration of inflammatory cells into lung tissue.

Prediction of Elastic Properties Using Micromechanics of Polypropylene Composites Mixed with Ultrahigh-Molecular-Weight Polyethylene Fibers.

In this study, we calculated the elastic properties of polypropylene composites mixed with ultrahigh-molecular-weight polyethylene (UHMWPE) fibers. We applied micromechanics models that use numerical analysis, conducted finite element analysis using the homogenization method, and comparatively analyzed the characteristics of polypropylene (PP) containing UHMWPE fibers as reinforcement. The results demonstrate that elastic properties improved as the volume fraction of UHMWPE fiber increased. It was confirmed that the fibers had anisotropic elastic properties due to the shape of the fibers. In addition, it is necessary to compare these findings with future experimental results to obtain data for developing UHMWPE-PP composites.

Evaluation of Caspase-3 and Ki-67 expression in squamous cell hyperplasia of the stomach induced by Platycodi radix water extract in Sprague-Dawley rats.

Platycodi radix is widely used in traditional herbal medicine for the treatment of bronchitis, asthma, pulmonary tuberculosis, hypertension, hyperlipidemia, and diabetes. This study aimed to investigate cell proliferation (Ki-67) and apoptosis (Caspase-3) potential in squamous cell hyperplasia of the stomach induced by a Platycodi radix water extract in a subchronic toxicity study. One hundred formalin-fixed, paraffin-embedded stomach tissues of rats treated with Platycodi radix at doses of 0, 500, 1,000, and 3,000 mg/kg body weight/day were used for the analysis. They were conventionally stained using hematoxylin and eosin (H&E) and immunohistochemically (IHC) stained using caspase-3 and Ki-67 antibodies. The incidence of squamous cell hyperplasia was significantly increased in the 3,000 mg/kg b.w./day treatment group in both sexes (p<0.01). However, the hyperplastic change was completely repaired after 4 weeks of recovery period. Ki-67 expression was similar in all groups, with no statistically significant differences among the groups. Caspase-3 expression was significantly increased in both sexes in the 3,000 mg/kg b.w./day treatment group (p<0.01), compared with the vehicle control groups, and then reduced to normal levels in the recovery groups in both sexes. In conclusion, this study showed that squamous cell hyperplasia induced by the Platycodi radix water extract in the limiting ridge of the stomach is not considered to be abnormal proliferative change; as a result, squamous cell hyperplasia is considered to be a non-adverse effect when induced by the oral administration of the Platycodi radix water extract once daily for 13 weeks in rats.

Small leucine zipper protein promotes the metastasis of castration-resistant prostate cancer through transcriptional regulation of matrix metalloproteinase-13.

Matrix metalloproteinases (MMPs) function as central modulators of tissue remodeling. Abnormal expression and altered activity of MMPs result in excessive extracellular matrix degradation and increased tumor metastasis in various cancers. Small leucine zipper protein (sLZIP), belonging to the leucine zipper transcription factor family, functions as a transcriptional regulator of genes involved in various cellular processes. However, its role in MMP expression and castration-resistant prostate cancer (CRPC) metastasis remains unclear. In this study, we investigated the role of sLZIP in MMP-13 expression and its involvement in CRPC metastasis. sLZIP increased MMP-13 transcription by directly binding to its promoter in CRPC cells. We found that the expression levels of glucocorticoid receptor (GR), which represses MMP transcription, were elevated in CRPC cells. However, sLZIP suppressed the inhibitory effect of GR and enhanced the secretion of MMP-13 in CRPC cells. sLZIP promoted cell migration and invasion; however, a specific MMP-13 inhibitor blocked sLZIP-induced cell motility. Depletion of sLZIP using the CRISPR/Cas9 system downregulated MMP-13 messenger RNA expression in PC3 cells. Mice injected with sLZIP-depleted PC3 cells showed significantly reduced metastatic tumor volume in the lung compared with mice injected with control PC3 cells. Our findings suggest that sLZIP plays an important role in MMP-13 induction and CRPC metastasis. Therefore, sLZIP inhibition could be a novel therapeutic strategy for metastatic GR-enriched CRPC.

Focal vasculitic myositis as a primary manifestation of Behçet's disease: a case series of 10 Korean patients in a locomotive medicine clinic.

OBJECTIVES: Muscle involvement in Behçet's disease (BD) is rare, and several cases have been reported in the literature. Therefore, this study aimed to describe the clinical, laboratory and imaging findings in adult patients presenting with BD-associated myositis before the diagnosis of BD. METHODS: We retrospectively screened patients who visited a locomotive medicine clinic presenting with myalgia, local swelling, or tenderness of extremities without an established diagnosis of BD. We enrolled patients whose pain in the extremities was proven to be suggestive of focal vasculitic myositis and who were eventually diagnosed as having BD at the initial visit or during follow-up. We thoroughly reviewed the clinical, histological and imaging findings and treatment outcomes in patients who presented with focal vasculitic myositis as the primary manifestation of BD. RESULTS: Ten adult patients with focal vasculitic myositis as the primary manifestation of BD were enrolled. The lower and upper extremities were affected in eight and two patients, respectively. The affected lower extremities were the calf (n = 6) and thigh muscles (n = 2). The common findings of MRI included high signal intensity of the affected muscles and intermuscular fascia on fat-suppressed images, suggestive of myofascitis and oedematous changes in the subcutaneous layer. The results of skin or muscle biopsy were suggestive of vasculitis. All the patients were pain-free at the short-term follow-up (1-3 weeks) after oral steroid therapy. CONCLUSION: Focal vasculitic myositis can be a primary manifestation of BD warranting medical attention. BD-associated myositis responds well to oral steroid therapy.

The impact of medication synchronization programs on medication adherence: A meta-analysis.

BACKGROUND: Medication nonadherence is associated with more than $100 billion in preventable medical costs each year in the United States. Medication synchronization (med sync) programs have emerged as a potential solution to addressing nonadherence. OBJECTIVES: To assess the impact of med sync programs on adherence in adults on chronic medications through a meta-analysis. METHODS: A comprehensive literature search was conducted for studies of med sync and adherence in adults published in English from database inception to May 2020. Studies were included if they provided a description of the med sync program, reported a quantitative measure of medication adherence using the proportion of days covered metric, and were conducted in the United States. The search terms included "medication synchronization," "med sync," "adherence," and "PDC." Pooled odds ratios (ORs) and 95% CIs using random-effects models were calculated to assess overall impact and subgroup analyses. The risk of bias of individual studies was assessed using the Downs and Black checklist. RESULTS: Nine studies reporting 30 effect sizes were included in the meta-analysis. On the basis of the Downs and Black checklist, the methodological quality of the studies was fair (mean [SD] 17.6 [1.7]). Med sync was associated with greater odds of adherence (pooled OR 2.29 [95% CI 1.99-2.64], I2 = 93.3%, τ2 = 1.11). In addition, the type of med sync program influenced the variation in effect sizes (Cochran Q statistic [Qbetween] = 45.4, P < 0.001), with appointment-based med sync programs having the largest impact on adherence (3.14 [95% CI 2.72-3.63]). CONCLUSION: In this meta-analysis of the impact of med sync on adherence, med sync was associated with statistically significant improvement in adherence. Policy makers and payers should consider reimbursement to pharmacies to support med sync programs in efforts to combat medication nonadherence and improve health outcomes.

Does Performance-Related Information Augment the Maximal Isometric Force in the Elbow Flexors?

The effects of different feedback conditions on the elbow flexors maximal voluntary isometric (MVIC) force were examined. In a single visit, twenty participants (10 males) were exposed to four conditions including, Visual only; (i.e., knowledge of results [VI]); Verbal encouragement (i.e., verbally stating pull, pull [VE]); VI and VE (VIVE); and no VI or VE (NOVIVE). Three, 5-s MVIC trials were completed for each condition. Separate 2 × 4 (sex × condition) repeated measures analyses of variance (ANOVA) were used to examine MVIC force, rate of force development (RFD200), and rate of electromyography (EMG) rise (RER200) for the 0-200-ms window. There was a significant main condition effect for MVIC force (p < 0.001). Significantly greater MVIC force was shown for VIVE compared to VE (p < 0.001) and NOVIVE (p = 0.002) conditions, and VI compared to VE (p = 0.011) and NOVIVE (p = 0.009) conditions. A significant sex × condition interaction (p = 0.036) was observed for RFD200, with significantly (p = 0.003) greater RFD200 in males compared to females, in the VI condition only. There were no significant differences in RFD200 among condition for males (p = 0.033) or females (p = 0.194). There was a significant main effect for sex (p = 0.006) for RER200, with significantly greater (p = 0.003) RER200 (conditions merged) in males (mean ± standard deviation (SD): 422.99 ± 124.67%), compared to females (220.68 ± 134.01%). Here we suggest the importance of providing VI feedback alone, or in conjunction with VE, for the measurement of elbow flexion MVIC. Additionally, these results provide a foundational framework for future studies aiming to improve feedback modalities during training or rehabilitation.

Roles of CD133 in microvesicle formation and oncoprotein trafficking in colon cancer.

Extracellular vesicles contain various cellular components that are involved in tumor growth, metastasis, and immune escape. Extracellular vesicles are classified into 2 groups, namely, exosomes and microvesicles (MV). Although the formation and roles of exosomes have been studied, the exact functions of MVs and mechanisms underlying MV release are not fully understood. We found that epidermal growth factor accelerates the release of MVs from the plasma membrane by inducing NF-κB activation and CD133 expression. The amount and sizes of budding MVs were found to be dependent on the expression level of CD133, which regulates the activities of the small guanosine 5'-triphosphatases RhoA and Rac1. CD133-containing MVs released from KRAS mutant colon cancer cells delivered KRAS mutant to adjacent nontumorigenic cells and activated KRAS downstream signaling. CD133-containing MVs were found to promote the migration and invasion of adjacent cells. CD133-containing MVs induced the development of chemoresistance by abolishing the inhibitory effects of anti-epidermal growth factor receptor (EGFR) drugs on cell proliferation and motility in colon cancer. These results suggest that CD133 acts as a novel modulator in MV release and in oncoprotein trafficking. CD133 can serve as a therapeutic target for treatment of anti-EGFR drug-resistant colon cancer.-Kang, M., Kim, S., Ko, J. Roles of CD133 in microvesicle formation and oncoprotein trafficking in colon cancer.

Evaluation of Knee-Specific Patient-Reported Outcome Measures Using Rasch Analysis.

CONTEXT: Documentation of patient outcomes following injury is critical to ensure that patients are receiving the best care. Several patient-reported outcome measures (PROMs) have been developed to assess knee-related function following injury; however, there is limited data investigating the measurement properties of these instruments using Rasch model analyses. OBJECTIVE: To evaluate the measurement properties of several PROMs through application of the Rasch measurement model. DESIGN: Cross-sectional study. SETTING: Clinical setting. PATIENTS OR OTHER PARTICIPANTS: A convenience sample of 160 adults (mean age = 28.08 [10.95] y; male = 38.10%) were recruited for this study. Data collected were combined with existing pilot data from an earlier study containing de-identified Knee Injury and Osteoarthritis Outcome Score (KOOS) data from 79 adults with knee injuries resulting in a total sample size of 239 adults. INTERVENTION(S): Psychometric evaluation of the KOOS, International Knee Documentation Committee subjective knee form, and the Marx Activity Rating Scale using the Rasch partial credit model. MAIN OUTCOME MEASURES: Infit and outfit statistics, item step difficulties, person ability parameters, category function, and item and test information functions. RESULTS: Large ceiling effects were present in the KOOS and International Knee Documentation Committee subjective knee form. Of the 65 items examined in this study, 35 items showed poor measurement properties. Item step difficulty for the remaining 30 items ranged from -5.45 (least difficult) to 0.57 logits (most difficult). The 5-category response options did not function well. Measurement precision decreased significantly as ability score increased beyond 0.30 logits. CONCLUSIONS: Despite their use in clinical practice, several items showed poor measurement properties. Future studies are needed to develop and evaluate novel items that are suitable for measuring knee-related function in high-functioning populations to ensure continuity of PROMs as individuals recover from injuries.