GPR97 triggers inflammatory processes in human neutrophils via a macromolecular complex upstream of PAR2 activation.

Neutrophils play essential anti-microbial and inflammatory roles in host defense, however, their activities require tight regulation as dysfunction often leads to detrimental inflammatory and autoimmune diseases. Here we show that the adhesion molecule GPR97 allosterically activates CD177-associated membrane proteinase 3 (mPR3), and in conjugation with several protein interaction partners leads to neutrophil activation in humans. Crystallographic and deletion analysis of the GPR97 extracellular region identified two independent mPR3-binding domains. Mechanistically, the efficient binding and activation of mPR3 by GPR97 requires the macromolecular CD177/GPR97/PAR2/CD16b complex and induces the activation of PAR2, a G protein-coupled receptor known for its function in inflammation. Triggering PAR2 by the upstream complex leads to strong inflammatory activation, prompting anti-microbial activities and endothelial dysfunction. The role of the complex in pathologic inflammation is underscored by the finding that both GPR97 and mPR3 are upregulated on the surface of disease-associated neutrophils. In summary, we identify a PAR2 activation mechanism that directs neutrophil activation, and thus inflammation. The PR3/CD177/GPR97/PAR2/CD16b protein complex, therefore, represents a potential therapeutic target for neutrophil-mediated inflammatory diseases.

Overexpression of FAM46A, a Non-canonical Poly(A) Polymerase, Promotes Hemin-Induced Hemoglobinization in K562 Cells.

FAM46A belongs to the FAM46 subfamily of the nucleotidyltransferase-fold superfamily and is predicted to be a non-canonical poly(A) polymerase. FAM46A has been linked to several human disorders including retinitis pigmentosa, bone abnormality, cancer, and obesity. However, its molecular and functional characteristics are largely unknown. We herein report that FAM46A is expressed in cells of the hematopoietic system and plays a role in hemin-induced hemoglobinization. FAM46A is a nucleocytoplasmic shuttle protein modified by Tyr-phosphorylation only in the cytosol, where it is closely associated with ER. On the other hand, it is located proximal to the chromatin regions of active transcription in the nucleus. FAM46A is a cell cycle-dependent poly-ubiquitinated short-lived protein degraded mostly by proteasome and its overexpression inhibits cell growth and promotes hemin-induced hemoglobinization in K562 cell. Site-directed mutagenesis experiments confirm the non-canonical poly(A) polymerase activity of FAM46A is essential for enhanced hemin-induced hemoglobinization. In summary, FAM46A is a novel poly(A) polymerase that functions as a critical intracellular modulator of hemoglobinization.

Development and Psychometric Evaluation of the Cancer Health Literacy Scale in Newly Diagnosed Cancer Patients.

BACKGROUND: Health literacy (HL) influences a patient's comprehension and judgment of health-related information. A rigorous assessment tool is needed to screen for low HL in order to improve it. OBJECTIVE: The aim of this study was to develop and validate the Cancer Health Literacy Scale (C-HLS). METHODS: The framework of the C-HLS is based on the Levels of Prevention model. The scale items were developed according to Nutbeam's 3 constructs of HL. We employed several procedures to develop the C-HLS, including focus group interviews, item generation, the expert Delphi process, and face validity. Various types of analysis, including reliability and split-half reliability testing, confirmatory factor analysis, and criterion-related validity testing, were performed; receiver operating characteristic curve analysis was also performed to confirm sensitivity and specificity. RESULTS: There were 33 items included in the C-HLS for validation; 360 newly diagnosed cancer patients completed the survey. The administration time is only 10 to 15 minutes. Results showed that C-HLS had good reliability, split-half reliability, and validity. All confirmatory factor analysis model fit indices reached acceptable thresholds. The receiver operating characteristic curve analyses suggested that the C-HLS had an adequate combination of sensitivity and specificity to distinguish between high and low HL. CONCLUSIONS: The C-HLS is a reliable, valid tool capable of discriminating levels of HL in the assessment of cancer patients and does not have an excessive administration time. IMPLICATIONS FOR PRACTICE: This scale can aid our understanding of HL in newly diagnosed cancer patients and can serve as a basis for providing individual care interventions.

Perineal Assessment Tool (PAT-C): Validation of a Chinese Language Version and Identification of a Clinically Validated Cut Point Using ROC Curve Analysis.

PURPOSE: The purpose of this study was to evaluate content validity and feasibility of the Chinese language perineal assessment tool (PAT-C), to assess its use in the clinical setting, and establish an optimal cut point for identifying patients at high risk for incontinence-associated dermatitis (IAD). DESIGN: Psychometric evaluation of existing instrument. SUBJECTS AND SETTING: The sample comprised 440 patients managed in intensive care units of 3 hospitals across the island of Taiwan and an affiliated home care service. One hundred three nurses practicing throughout Taiwan participated in the workshops in the third phase of the experiment. METHODS: The content validity of the PAT-C was evaluated by 3 experienced nurses using the content validity index statistic. We calculated a receiver operating characteristics (ROC) curve to determine a cut point of high-risk IAD. The curve was based on assessment of patients from receiving care from the intensive care unit and home care service of Cathay General Hospital (located in Taipei, New Paipei and Hsinchu). Nurse perceptions on the feasibility of PAT-C were assessed using an investigator-developed survey. RESULTS: Three experienced nurses rated the PAT-C and gave a robust overall content validity index score of 97.22%. The cut point for identifying patients at high risk for developing IAD via ROC curve analysis of 440 patients was 7.5 (sensitivity: 0.85; specificity: 0.79, area under curve: 0.82, P value < .001). One hundred three enrolled nurses attended the workshops and evaluated the feasibility using the PAT-C. Most of the participants considered the PAT-C as necessary (97.90%), 49.7% of participants suggested IAD risk assessment should be implemented by first-line (generalist) nurses, and 40% of participants recommended assessment on a daily basis. CONCLUSIONS: Study findings indicate robust content validity, and results of the investigator survey of nurse perceptions of the PAT-C indicate the potential for its widespread use in the clinical setting. We found that a cut point score 8 or more indicates a high risk for developing IAD.

A Synthesis of Research on Informational Text Reading Interventions for Elementary Students With Learning Disabilities.

This research synthesis was conducted to understand the effectiveness of interventions designed to improve learning from informational text for students with learning disabilities in elementary school (K-5). The authors identified 18 studies through a comprehensive search. The interventions were evaluated to determine treatment effects and to understand implementation and methodological variables that influenced outcomes. Moderate to large effect sizes on researcher-developed measures for cognitive strategy interventions were reported. Interventions that utilized graphic organizers as study guides to support social studies learning were also associated with improved outcomes. The findings are considered within the context of limited implementation of standardized measures. The authors extend findings from previous research by reporting a paucity of interventions to enhance higher-level cognitive and comprehension skills. The majority of reviewed studies targeted fact acquisition and main idea identification, and overall encouraging findings were noted for these skills. Implications for future research are discussed.