105 research outputs found

    Can a reflective rubric be applied consistently with raters globally? A study across three countries

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    Introduction Reflection is a powerful tool for assisting students to develop the skills to make better informed decisions. As a pharmacy competency standard, reliable and fair assessment strategies are required to measure reflective skills and support students in developing their reflective capacity. The aim of this research was to explore whether we can extend the applicability of a previously tested rubric to a range of educational settings, to account for diversity of pharmacy educators and curricula internationally. Methods Four raters from three countries applied a reflective rubric to assess a sample (n = 43) of reflective accounts, representing 41% of a cohort of 105 second-year undergraduate pharmacy students. The interrater reliability (IRR) was measured utilizing the intra-class correlation coefficient (ICC), using a two-way random effects model with absolute agreement, to determine the level of agreement between the raters' absolute scores. Generalizability Theory analysis was used to estimate generalizability of raters and stages. Results Results indicated agreement of raters for (i) each of the seven stages of reflection and (ii) overall score for the reflective account, with moderate to substantial agreement (ICC = 0.55–0.69, p < 0.001); and high agreement for all raters for the overall score (ICC = 0.96, p < 0.001), respectively. The G-Study estimated a relative error coefficient of 0.78. Conclusion This additional analysis further confirms the reliability and applicability of the rubric to a range of rater academic backgrounds

    Exploring the binding sites of Staphylococcus aureus phenylalanine tRNA synthetase: A homology model approach

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    Increased resistance of MRSA (multidrug resistance Staphylococcus aureus) to anti-infective drugs is a threat to global health necessitating the development of anti-infectives with novel mechanisms of action. Phenylalanine tRNA synthetase (PheRS) is a unique enzyme of the aminoacyl-tRNA synthetases (aaRSs), which are essential enzymes for protein biosynthesis. PheRS is an (αb)2 tetrameric enzyme composed of two alpha subunits (PheS) and two larger beta subunits (PheT). Our potential target in the drug development for the treatment of MRSA infections is the phenylalanine tRNA synthetase alpha subunit that contains the binding site for the natural substrate. There is no crystal structure available for S. aureus PheRS, therefore comparative structure modeling is required to establish a putative 3D structure for the required enzyme enabling development of new inhibitors with greater selectivity. The S. aureus PheRS alpha subunit homology model was constructed using Molecular Operating Environment (MOE) software. Staphylococcus haemolyticus PheRS was the main template while Thermus thermophilus PheRS was utilised to predict the enzyme binding with tRNAphe. The model has been evaluated and compared with the main template through Ramachandran plots, Verify 3D and Protein Statistical Analysis (ProSA). The query protein active site was predicted from its sequence using a conservation analysis tool. Docking suitable ligands using MOE into the constructed model were used to assess the predicted active sites. The docked ligands involved the PheRS natural substrate (phenylalanine), phenylalanyl-adenylate and several described S. aureus PheRS inhibitors

    A Comparative Approach Linking Molecular Dynamics of Altered Peptide Ligands and MHC with In Vivo Immune Responses

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    The recognition of peptide in the context of MHC by T lymphocytes is a critical step in the initiation of an adaptive immune response. However, the molecular nature of the interaction between peptide and MHC and how it influences T cell responsiveness is not fully understood.We analyzed the immunological consequences of the interaction of MHC class II (I-Au) restricted 11-mer peptides of myelin basic protein with amino acid substitutions at position 4. These mutant peptides differ in MHC binding affinity, CD4+ T cell priming, and alter the severity of peptide-induced experimental allergic encephalomyelitis. Using molecular dynamics, a computational method of quantifying intrinsic movements of proteins at high resolution, we investigated conformational changes in MHC upon peptide binding. We found that irrespective of peptide binding affinity, MHC deformation appears to influence costimulation, which then leads to effective T cell priming and disease induction. Although this study compares in vivo and molecular dynamics results for three altered peptide ligands, further investigation with similar complexes is essential to determine whether spatial rearrangement of peptide-MHC and costimulatory complexes is an additional level of T cell regulation

    Development, implementation and evaluation of the digital transformation of renal services in Wales: the journey from local to national

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    Background Treatment for people with kidney disease is often associated with complicated combinations of medicines. Logistical challenges with traditiona paper-based prescribing means that these patients are particularly susceptible to medication-relation errors and harm. Aim To improve the quality of care that people with kidney disease receive across Wales through a Value-Based digital transformation programme. Setting Renal units within the National Welsh Renal Clinical Network (WRCN). Development A novel Electronic Prescribing & Medicines Administration (EPMA) system, integrated into a patient care record and linked to a patient portal was developed in South West Wales (SWW) region of the WRCN, enabled by the Welsh Government (WG) Efficiency Through Technology Fund. National upscale was enabled through the WG Transformation Fund. Implementation EPMA was designed and rolled out initially in SWW region of the WRCN (2018). A dedicated delivery team used the blueprint to finalise and implement a strategy for successful national roll-out eventually across all Wales (completed 2021). Evaluation A multi-factorial approach was employed, as both the technology itself and the healthcare system within which it would be introduced, were complex. Continuous cycles of action research involving informal and formal qualitative interviews with service-users ensured that EPMA was accessible and optimally engaging to all target stakeholders (patients and staff). Results confirmed that EPMA was successful in improving the quality of care that people with kidney disease receive across Wales, contributed to Value-Based outcomes, and put people who deliver and access care at the heart of transformation. Conclusion Key findings of this study align directly with the national design principles to drive change and transformation, put forward by the WG in their plan for Health and Social Care: prevention and early intervention; safety; independence; voice; seamless care

    The Bifidobacterium dentium Bd1 Genome Sequence Reflects Its Genetic Adaptation to the Human Oral Cavity

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    Bifidobacteria, one of the relatively dominant components of the human intestinal microbiota, are considered one of the key groups of beneficial intestinal bacteria (probiotic bacteria). However, in addition to health-promoting taxa, the genus Bifidobacterium also includes Bifidobacterium dentium, an opportunistic cariogenic pathogen. The genetic basis for the ability of B. dentium to survive in the oral cavity and contribute to caries development is not understood. The genome of B. dentium Bd1, a strain isolated from dental caries, was sequenced to completion to uncover a single circular 2,636,368 base pair chromosome with 2,143 predicted open reading frames. Annotation of the genome sequence revealed multiple ways in which B. dentium has adapted to the oral environment through specialized nutrient acquisition, defences against antimicrobials, and gene products that increase fitness and competitiveness within the oral niche. B. dentium Bd1 was shown to metabolize a wide variety of carbohydrates, consistent with genome-based predictions, while colonization and persistence factors implicated in tissue adhesion, acid tolerance, and the metabolism of human saliva-derived compounds were also identified. Global transcriptome analysis demonstrated that many of the genes encoding these predicted traits are highly expressed under relevant physiological conditions. This is the first report to identify, through various genomic approaches, specific genetic adaptations of a Bifidobacterium taxon, Bifidobacterium dentium Bd1, to a lifestyle as a cariogenic microorganism in the oral cavity. In silico analysis and comparative genomic hybridization experiments clearly reveal a high level of genome conservation among various B. dentium strains. The data indicate that the genome of this opportunistic cariogen has evolved through a very limited number of horizontal gene acquisition events, highlighting the narrow boundaries that separate commensals from opportunistic pathogens

    Gene expression of bacterial collagenolytic proteases in root caries

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    Objective: It is unknown whether bacteria play a role in the collagen matrix degradation that occurs during caries progression. Our aim was to characterize the expression level of genes involved in bacterial collagenolytic proteases in root biofilms with and without caries. Method: we collected samples from active cavitated root caries lesions (RC, n = 30) and from sound root surfaces (SRS, n = 10). Total microbial RNA was isolated and cDNA sequenced on the Illumina Hi-Seq2500. Reads were mapped to 162 oral bacterial reference genomes. Genes encoding putative bacterial collagenolytic proteases were identified. Normalization and differential expression analysis was performed on all metatranscriptomes (FDR8) but none in SRS were Pseudoramibacter alactolyticus [HMPREF0721_RS02020; HMPREF0721_RS04640], Scardovia inopinata [SCIP_RS02440] and Olsenella uli DSM7084 [OLSU_RS02990]. Conclusion: Our findings suggest that the U32 proteases may be related to carious dentine. The contribution of a small number of species to dentine degradation should be further investigated. These proteases may have potential in future biotechnological and medical applications, serving as targets for the development of therapeutic agents
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