Comparison of electronic versus conventional assessment methods in ophthalmology residents; a learner assessment scholarship study

Background: Assessment is a necessary part of training postgraduate medical residents. The implementation of methods located at the �shows how� level of Miller�s pyramid is believed to be more effective than previous conventional tools. In this study, we quantitatively compared electronic and conventional methods in assessing ophthalmology residents. Methods: In this retrospective study, eight different conventional methods of assessment including residents� attendance, logbook, scholarship and research skills, journal club, outpatient department participation, Multiple Choice Question (MCQ), Objective Structured Clinical Examination (OSCE), and professionalism/360-degree (as one complex) were used to assess 24 ophthalmology residents of all grades. Electronic media consisting of an online Patient Management Problem (e-PMP), and modified electronic OSCE (me-OSCE) tests performed 3 weeks later were also evaluated for each of the 24 residents. Quantitative analysis was then performed comparing the conventional and electronic assessment tools, statistically assessing the correlation between the two approaches. Results: Twenty-four ophthalmology residents of different grades were included in this study. In the electronic assessment, average e-PMP scores (48.01 ± 12.40) were much lower than me-OSCE (65.34 ± 17.11). The total average electronic score was 56.67 ± 11.28, while the total average conventional score was 80.74 ± 5.99. Female and male residents� average scores in the electronic and conventional method were (59.15 ± 12.32 versus 83.01 ± 4.95) and (55.19 ± 10.77 versus 79.38 ± 6.29), respectively. The correlation between modified electronic OSCE and all conventional methods was not statistically significant (P-value >0.05). Correlation between e-PMP and six conventional methods, consisting of professionalism/360-degree assessment tool, logbook, research skills, Multiple Choice Questions, Outpatient department participation, and Journal club active participation was statistically significant (P-value < 0.05). The overall correlation between conventional and electronic methods was significant (P-value = 0.017). Conclusion: In this study, we conclude that electronic PMP can be used alongside all conventional tools, and overall, e-assessment methods could replace currently used conventional methods. Combined electronic PMP and me-OSCE can be used as a replacement for currently used gold-standard assessment methods, including 360-degree assessment. © 2021, The Author(s)

Autoinhibition of TBCB regulates EB1-mediated microtubule dynamics

Tubulin cofactors (TBCs) participate in the folding, dimerization, and dissociation pathways of the tubulin dimer. Among them, TBCB and TBCE are two CAP-Gly domain-containing proteins that interact and dissociate the tubulin dimer. Here we show how TBCB localizes at spindle and midzone microtubules during mitosis. Furthermore, the motif DEI/M-COO– present in TBCB, which is similar to the EEY/F-COO– element characteristic of EB proteins, CLIP-170, and α-tubulin, is required for TBCE–TBCB heterodimer formation and thus for tubulin dimer dissociation. This motif is responsible for TBCB autoinhibition, and our analysis suggests that TBCB is a monomer in solution. Mutants of TBCB lacking this motif are derepressed and induce microtubule depolymerization through an interaction with EB1 associated to microtubule tips. TBCB is also able to bind to the chaperonin complex CCT containing α-tubulin, suggesting that it could escort tubulin to facilitate its folding and dimerization, recycling or degradation

Faithful chaperones

This review describes the properties of some rare eukaryotic chaperones that each assist in the folding of only one target protein. In particular, we describe (1) the tubulin cofactors, (2) p47, which assists in the folding of collagen, (3) α-hemoglobin stabilizing protein (AHSP), (4) the adenovirus L4-100 K protein, which is a chaperone of the major structural viral protein, hexon, and (5) HYPK, the huntingtin-interacting protein. These various-sized proteins (102–1,190 amino acids long) are all involved in the folding of oligomeric polypeptides but are otherwise functionally unique, as they each assist only one particular client. This raises a question regarding the biosynthetic cost of the high-level production of such chaperones. As the clients of faithful chaperones are all abundant proteins that are essential cellular or viral components, it is conceivable that this necessary metabolic expenditure withstood evolutionary pressure to minimize biosynthetic costs. Nevertheless, the complexity of the folding pathways in which these chaperones are involved results in error-prone processes. Several human disorders associated with these chaperones are discussed

A Genome-Wide Homozygosity Association Study Identifies Runs of Homozygosity Associated with Rheumatoid Arthritis in the Human Major Histocompatibility Complex

Rheumatoid arthritis (RA) is a chronic inflammatory disorder with a polygenic mode of inheritance. This study examined the hypothesis that runs of homozygosity (ROHs) play a recessive-acting role in the underlying RA genetic mechanism and identified RA-associated ROHs. Ours is the first genome-wide homozygosity association study for RA and characterized the ROH patterns associated with RA in the genomes of 2,000 RA patients and 3,000 normal controls of the Wellcome Trust Case Control Consortium. Genome scans consistently pinpointed two regions within the human major histocompatibility complex region containing RA-associated ROHs. The first region is from 32,451,664 bp to 32,846,093 bp (−log10(p)>22.6591). RA-susceptibility genes, such as HLA-DRB1, are contained in this region. The second region ranges from 32,933,485 bp to 33,585,118 bp (−log10(p)>8.3644) and contains other HLA-DPA1 and HLA-DPB1 genes. These two regions are physically close but are located in different blocks of linkage disequilibrium, and ∼40% of the RA patients' genomes carry these ROHs in the two regions. By analyzing homozygote intensities, an ROH that is anchored by the single nucleotide polymorphism rs2027852 and flanked by HLA-DRB6 and HLA-DRB1 was found associated with increased risk for RA. The presence of this risky ROH provides a 62% accuracy to predict RA disease status. An independent genomic dataset from 868 RA patients and 1,194 control subjects of the North American Rheumatoid Arthritis Consortium successfully validated the results obtained using the Wellcome Trust Case Control Consortium data. In conclusion, this genome-wide homozygosity association study provides an alternative to allelic association mapping for the identification of recessive variants responsible for RA. The identified RA-associated ROHs uncover recessive components and missing heritability associated with RA and other autoimmune diseases

Dilated cardiomyopathy myosin mutants have reduced force-generating capacity

Dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) can cause arrhythmias, heart failure, and cardiac death. Here, we functionally characterized the motor domains of five DCM-causing mutations in human ?-cardiac myosin. Kinetic analyses of the individual events in the ATPase cycle revealed that each mutation alters different steps in this cycle. For example, different mutations gave enhanced or reduced rate constants of ATP binding, ATP hydrolysis, or ADP release or exhibited altered ATP, ADP, or actin affinity. Local effects dominated, no common pattern accounted for the similar mutant phenotype, and there was no distinct set of changes that distinguished DCM mutations from previously analyzed HCM myosin mutations. That said, using our data to model the complete ATPase contraction cycle revealed additional critical insights. Four of the DCM mutations lowered the duty ratio (the ATPase cycle portion when myosin strongly binds actin) because of reduced occupancy of the force-holding A·M.D complex in the steady-state. Under load, the A·M·D state is predicted to increase owing to a reduced rate constant for ADP release, and this effect was blunted for all five DCM mutations. We observed the opposite effects for two HCM mutations, namely R403Q and R453C. Moreover, the analysis predicted more economical use of ATP by the DCM mutants than by WT and the HCM mutants. Our findings indicate that DCM mutants have a deficit in force generation and force holding capacity due to the reduced occupancy of the force-holding state

Doubly heterozygous LMNA and TTN mutations revealed by exome sequencing in a severe form of dilated cardiomyopathy

Familial dilated cardiomyopathy (DCM) is a heterogeneous disease; although 30 disease genes have been discovered, they explain only no more than half of all cases; in addition, the causes of intra-familial variability in DCM have remained largely unknown. In this study, we exploited the use of whole-exome sequencing (WES) to investigate the causes of clinical variability in an extended family with 14 affected subjects, four of whom showed particular severe manifestations of cardiomyopathy requiring heart transplantation in early adulthood. This analysis, followed by confirmative conventional sequencing, identified the mutation p.K219T in the lamin A/C gene in all 14 affected patients. An additional variant in the gene for titin, p.L4855F, was identified in the severely affected patients. The age for heart transplantation was substantially less for LMNA:p.K219T/TTN:p.L4855F double heterozygotes than that for LMNA:p.K219T single heterozygotes. Myocardial specimens of doubly heterozygote individuals showed increased nuclear length, sarcomeric disorganization, and myonuclear clustering compared with samples from single heterozygotes. In conclusion, our results show that WES can be used for the identification of causal and modifier variants in families with variable manifestations of DCM. In addition, they not only indicate that LMNA and TTN mutational status may be useful in this family for risk stratification in individuals at risk for DCM but also suggest titin as a modifier for DCM

Ethylene Dimerization by a Homogeneous Ti-Based Three-Component Catalyst System: Process Evaluation and Optimization of Parametric Performance

AbstractThis research utilizes the design of experimental (DOE) methodology by Taguchi orthogonal array (OA) to optimize various operating parameters of a Ti-based homogeneous catalyst in presence of the mixture of two modifiers and triethylaluminum (TEA) as activator for production of 1-butene in the ethylene dimerization reaction. 2,5–dimethoxytetrahydrofuran (2,5-DMTHF) and tetrahydropyran (THP) were used as modifiers. L9 OA of the Taguchi technique was implemented to evaluate the influence of four factors (i.e. reaction temperature, ethylene pressure, Al/Ti molar ratio, and mixed modifiers/Ti molar ratio) at three levels on the overall selectivity to 1-butene (wt. %). The process parameters were optimized and ranked using data obtained from mean S/N ratios for overall selectivity to 1-butene. Also, confirmation experiment was performed to prove effectiveness of the Taguchi technique and validity of the predicted results