Analysis of item writing flaws (IWFs) evident in objective formats examination questions in federal college of education (technical) Asaba, Nigeria

Purpose: The purpose of this study was to ascertain IWFs contained in objective formats examination questions for assessment of students in the Nigeria Certificate in Education (NCE) programme in 2016/2017, 2017/2018 and first semester 2018/2019 academic sessions. Methodology: Descriptive cross-sectional design was adopted which enabled the researchers to estimate prevalence (number of cases) of IWFs associated with objective questions constructed for end-of-semester examinations. The researchers retrieved 57 objective question papers administered in end-of-semester examinations centrally conducted in the College within the period of three academic sessions (2016/2017, 2017/2018 and first semester 2018/2019). 19 common violations of item writing principles were selected from literature and used in assessing the quality of 57 objective questions. The study classified test items in each of the 57 objective question papers into standard and flawed categories such that if an item is flawed, the exact type of flaw(s) (including options) was recorded. Results: The results showed that short answer, multiple choice and alternate response questions are the types of objective test formats constructed by lecturers; there was a high rate of violation of standard item writing rules in most objective semester examination questions constructed by lecturers; and the nature of the four most frequently violated IWFs were related to irrelevant difficulty which tended to make questions or tasks more difficult than intended. Recommendations/Classroom Implications: College management should organize seminar or workshop at regular interval to train or update lecturers’ knowledge on test construction skills and tips

A novel high mobility group box 1 neutralizing chimeric antibody attenuates drug-induced liver injury and postinjury inflammation in mice

Acetaminophen (APAP) overdoses are of major clinical concern. Growing evidence underlines a pathogenic contribution of sterile postinjury inflammation in APAP‐induced acute liver injury (APAP‐ALI) and justifies development of anti‐inflammatory therapies with therapeutic efficacy beyond the therapeutic window of the only current treatment option, N‐acetylcysteine (NAC). The inflammatory mediator, high mobility group box 1 (HMGB1), is a key regulator of a range of liver injury conditions and is elevated in clinical and preclinical APAP‐ALI. The anti‐HMGB1 antibody (m2G7) is therapeutically beneficial in multiple inflammatory conditions, and anti‐HMGB1 polyclonal antibody treatment improves survival in a model of APAP‐ALI. Herein, we developed and investigated the therapeutic efficacy of a partly humanized anti‐HMGB1 monoclonal antibody (mAb; h2G7) and identified its mechanism of action in preclinical APAP‐ALI. The mouse anti‐HMGB1 mAb (m2G7) was partly humanized (h2G7) by merging variable domains of m2G7 with human antibody‐Fc backbones. Effector function‐deficient variants of h2G7 were assessed in comparison with h2G7 in vitro and in preclinical APAP‐ALI. h2G7 retained identical antigen specificity and comparable affinity as m2G7. 2G7 treatments significantly attenuated APAP‐induced serum elevations of alanine aminotransferase and microRNA‐122 and completely abrogated markers of APAP‐induced inflammation (tumor necrosis factor, monocyte chemoattractant protein 1, and chemokine [C‐X‐C motif] ligand 1) with prolonged therapeutic efficacy as compared to NAC. Removal of complement and/or Fc receptor binding did not affect h2G7 efficacy. Conclusion: This is the first report describing the generation of a partly humanized HMGB1‐neutralizing antibody with validated therapeutic efficacy and with a prolonged therapeutic window, as compared to NAC, in APAP‐ALI. The therapeutic effect was mediated by HMGB1 neutralization and attenuation of postinjury inflammation. These results represent important progress toward clinical implementation of HMGB1‐specific therapy as a means to treat APAP‐ALI and other inflammatory conditions. (Hepatology 2016;64:1699‐1710)

Crystal Structure of the HSV-1 Fc Receptor Bound to Fc Reveals a Mechanism for Antibody Bipolar Bridging

Herpes simplex virus type-1 expresses a heterodimeric Fc receptor, gE-gI, on the surfaces of virions and infected cells that binds the Fc region of host immunoglobulin G and is implicated in the cell-to-cell spread of virus. gE-gI binds immunoglobulin G at the basic pH of the cell surface and releases it at the acidic pH of lysosomes, consistent with a role in facilitating the degradation of antiviral antibodies. Here we identify the C-terminal domain of the gE ectodomain (CgE) as the minimal Fc-binding domain and present a 1.78-Å CgE structure. A 5-Å gE-gI/Fc crystal structure, which was independently verified by a theoretical prediction method, reveals that CgE binds Fc at the C (H)2-C (H)3 interface, the binding site for several mammalian and bacterial Fc-binding proteins. The structure identifies interface histidines that may confer pH-dependent binding and regions of CgE implicated in cell-to-cell spread of virus. The ternary organization of the gE-gI/Fc complex is compatible with antibody bipolar bridging, which can interfere with the antiviral immune response

Natural Form of Noncytolytic Flexible Human Fc as a Long-Acting Carrier of Agonistic Ligand, Erythropoietin

Human IgG1 Fc has been widely used as a bioconjugate, but exhibits shortcomings, such as antibody- and complement-mediated cytotoxicity as well as decreased bioactivity, when applied to agonistic proteins. Here, we constructed a nonimmunogenic, noncytolytic and flexible hybrid Fc (hyFc) consisting of IgD and IgG4, and tested its function using erythropoietin (EPO) conjugate, EPO-hyFc. Despite low amino acid homology (20.5%) between IgD Fc and IgG4 Fc, EPO-hyFc retained “Y-shaped” structure and repeated intravenous administrations of EPO-hyFc into monkeys did not generate EPO-hyFc-specific antibody responses. Furthermore, EPO-hyFc could not bind to FcγR I and C1q in contrast to EPO-IgG1 Fc. In addition, EPO-hyFc exhibited better in vitro bioactivity and in vivo bioactivity in rats than EPO-IgG1 Fc, presumably due to the high flexibility of IgD. Moreover, the mean serum half-life of EPO-hyFc(H), a high sialic acid content form of EPO-hyFc, was approximately 2-fold longer than that of the heavily glycosylated EPO, darbepoetin alfa, in rats. More importantly, subcutaneous injection of EPO-hyFc(H) not only induced a significantly greater elevation of serum hemoglobin levels than darbepoetin alfa in both normal rats and cisplatin-induced anemic rats, but also displayed a delayed time to maximal serum level and twice final area-under-the-curve (AUClast). Taken together, hyFc might be a more attractive Fc conjugate for agonistic proteins/peptides than IgG1 Fc due to its capability to elongate their half-lives without inducing host effector functions and hindering bioactivity of fused molecules. Additionally, a head-to-head comparison demonstrated that hyFc-fusion strategy more effectively improved the in vivo bioactivity of EPO than the hyperglycosylation approach

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis

One of the important ‘hallmarks’ of cancer is angiogenesis, which is the process of formation of new blood vessels that are necessary for tumor expansion, invasion and metastasis. Under normal physiological conditions, angiogenesis is well balanced and controlled by endogenous proangiogenic factors and antiangiogenic factors. However, factors produced by cancer cells, cancer stem cells and other cell types in the tumor stroma can disrupt the balance so that the tumor microenvironment favors tumor angiogenesis. These factors include vascular endothelial growth factor, endothelial tissue factor and other membrane bound receptors that mediate multiple intracellular signaling pathways that contribute to tumor angiogenesis. Though environmental exposures to certain chemicals have been found to initiate and promote tumor development, the role of these exposures (particularly to low doses of multiple substances), is largely unknown in relation to tumor angiogenesis. This review summarizes the evidence of the role of environmental chemical bioactivity and exposure in tumor angiogenesis and carcinogenesis. We identify a number of ubiquitous (prototypical) chemicals with disruptive potential that may warrant further investigation given their selectivity for high-throughput screening assay targets associated with proangiogenic pathways. We also consider the cross-hallmark relationships of a number of important angiogenic pathway targets with other cancer hallmarks and we make recommendations for future research. Understanding of the role of low-dose exposure of chemicals with disruptive potential could help us refine our approach to cancer risk assessment, and may ultimately aid in preventing cancer by reducing or eliminating exposures to synergistic mixtures of chemicals with carcinogenic potential

SCHOOL CULTURE, PRACTICES AND STRUCTURE AS PREDICTORS OF PERFORMANCE OF SECONDARY SCHOOL STUDENTS IN EDO STATE, NIGERIA

Quality in education can be seen as fitness for purpose and one indicator of this is the quality of the learning environment within the school system. At play in this environment are factors of school culture, practice and structure and one measure of the quality of schools is students’ performance. The relationship between each of these factors and performance has been variously investigated but their combined predictive ability of performance does not seem to have been examined in the literature. This is the focus of the study. The survey design was utilized in the study. The population consists of all the 1700 teachers in Edo State, Nigeria who teach in the three hundred and nine public senior secondary schools. Out of the schools, 62 schools representing 20% of the schools were selected. From the schools selected, five teachers each of whom teach English Language, Mathematics, Economics, Biology and Christian Religious Studies were selected to provide the information. On the whole, 285 teachers returned usable questionnaires. The draft questionnaire adapted from those constructed earlier by Gruenert and Valentine (1998) was composed of four sections, namely personal information of the teachers, School structure, school practices and school culture. The questionnaire was given to five experts knowledgeable in assessment, educational management and experienced senior secondary school principals. These experts were expected to examine the items on the questionnaire to ensure that they were adequate in content, comprehension and readability. Based on their comments, the items were modified and the resulting instrument was administered to 30 teachers outside the sample used in the study for purposes of determining the reliability using Cronbach alpha. The reliability coefficients that emerged were .78, .83 and .75 for school culture, school structure and school practice respectively. Cooperation of Principals of the schools selected for the study was solicited for the administration of the questionnaire and making available records of WASSCE results for their schools for the year 2018. The performance of the school was calculated by finding a weighted mean for the grades obtained by the students who sat for the WASSCE in each of the subjects and cumulated across the school subjects for each school. Multiple regression was used in the analysis at 5% level of significance. School culture was related to performance while school practice and structure were not. In addition, the three factors were useful in jointly predicting performance in schools. It was therefore recommended that schools should examine these factors properly if they intend to shore up their performance.  Article visualizations