UHSP Collections (University of Health Sciences and Pharmacy)
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Computational Modeling of the Disulfide Cross-Linking Reaction
No full textDisulfide cross-linking is one of the fundamental covalent bonds that exist prevalently in many biological molecules that is involved in versatile functional activities such as antibody stability, viral assembly, and protein folding. Additionally, it is a crucial factor in various industrial applications. Therefore, a fundamental understanding of its reaction mechanism would help gain insight into its different functional activities. Computational simulation of the disulfide cross-linking reaction with hydrogen peroxide (H2O2) was performed at the integrated quantum mechanical/molecular mechanical (QM/MM) level of theory in a water box under periodic boundary conditions. A benchmarking study for the barrier height of the disulfide formation step was performed on a model system between methanethiol and methane sulfenic acid to determine, for the QM system, the best-fit density functional theory (DFT) functional/basis set combination that produces comparable results to a higher-level theory of the coupled-cluster method. Computational results show that the disulfide cross-linking reaction with H2O2 reagent can proceed through a one-step or a two-step pathway for the high pKa cysteines or two different pathways for the low pKa cysteines to ultimately produce the sulfenic acid/sulfenate intermediate complex. Subsequently, those intermediates react with another neutral/anionic cysteine residue to form the cysteine product. In addition, the solvent-assisted proton-exchange/proton-transfer effects were examined on the energetic barriers for the different transition states, and the molecular contributions of the chemically involved water molecules were studied in detail
Advisor Interaction Goals and Verbal Messages: Merging a Multiple Goals Approach and the Integrated Model of Advice Giving
No full textBased on the integrated model of advice giving and theorizing about interaction goals, we examined how advisors’ goal intensity and complexity predicted perceptions of advisor harmfulness and helpfulness. We also examined predictors of goal intensity and complexity, such as advisors’ relational satisfaction with recipients, which generally increased goal intensity and complexity. Recipients and advisors rated advisors’ behaviors as more helpful when advisors reported greater intensity of the problem-solving goal but not the other three goals (emotional support, eliciting disclosure, and facilitating reappraisal). However, recipients and advisors rated advisors’ behaviors as more harmful when advisors had low versus moderate or high goal complexity. Qualitative analyses of conversation transcripts revealed patterns of interaction behavior associated with goal intensity and complexity. We discuss how goal intensity and complexity may relate to advisors’ messages and interaction patterns during the conversation, and therefore recipient and advisor perceptions of advisors’ helpfulness and harmfulness
Randomised controlled trial of a theory-based intervention to prompt front-line staff to take up the seasonal influenza vaccine
No full textObjective To evaluate the effectiveness of reminder letters informed by social normative theory (a type of \u27nudge theory\u27) on uptake of seasonal influenza vaccination by front-line hospital staff. Design Individually randomised controlled trial. Setting A large acute care hospital in England. Participants Front-line staff employed by the hospital (n=7540) were randomly allocated to one of four reminder types in a factorial design. Interventions The standard letter included only general information directing the staff to take up the vaccine. A second letter highlighted a type of social norm based on peer comparisons. A third letter highlighted a type of social norm based on an appeal to authority. A fourth letter included a combination of the social norms. Main outcome measure The proportion of hospital staff vaccinated on-site. Results Vaccine coverage was 43% (812/1885) in the standard letter group, 43% (818/1885) in the descriptive norms group, 43% (814/1885) in the injunctive norms group and 43% (812/1885) in the combination group. There were no statistically significant effects of either norm or the interaction. The OR for the descriptive norms factor is 1.01 (0.89-1.15) in the absence of the injunctive norms factor and 1.00 (0.88-1.13) in its presence. The OR for the injunctive norms factor is 1.00 (0.88-1.14) in the absence of the descriptive norms factor and 0.99 (0.87-1.12) in its presence. Conclusions We find no evidence that the uptake of the seasonal influenza vaccination is affected by reminders using social norms to motivate uptake
Female victims and female perpetrators: medical students’ narratives of gender dynamics and professionalism dilemmas
No full textMedicine is a gendered discipline, in which women, both as patients and practitioners, have often held subordinate positions. The reproduction of dominant gender biases in the medical setting can negatively impact the professional development of medical students and the wellbeing of patients. In this analysis of medical students’ narratives of professionalism dilemmas, we explore students’ experiences of gender bias in hospital settings. Seventy-one students participated in 12 group interviews, where they discussed witnessing or participating in various activities that they thought were professionalism lapses. Within the dataset, 21 narratives had a distinctly gendered component broadly pertaining to patient dignity and safety dilemmas, informed consent issues, and female student abuse. Interestingly, perpetrators of such acts were commonly female healthcare professionals and educators. Although students recognized such acts as professionalism lapses and often expressed concern for patient wellbeing, students did not intervene or report such acts due to hierarchical cultural contexts, and at times even reproduced the discriminatory behavior they were criticizing. This raises concerns about medical students’ professionalism development and the extent to which gender bias is ingrained within particular medical systems. The normalization of disrespectful and abusive treatment of female patients poses immediate and future consequences to the wellbeing and safety of women. Furthermore, the same socio-cultural values that sustain these acts may account for perpetrators often being women themselves as they strive to overcome their subordinate position within medicine
A Selective ERRα/γInverse Agonist, SLU-PP-1072, Inhibits the Warburg Effect and Induces Apoptosis in Prostate Cancer Cells
No full textThe estrogen related receptors (ERRs) are a subgroup of nuclear receptors that play a role in regulation of cellular metabolism. Prostate cancer (PCa) cells display altered metabolic signatures, such as the Warburg effect, and the ERRs have been implicated in driving this phenotype. Despite the lack of a known endogenous ligand, synthetic ligands that target the ERRs have been discovered. For example, the ERRα inverse agonist XCT790 modulates metabolic pathways in PCa cells, but it also functions as a mitochondrial uncoupler independent of targeting ERRα. Here, we describe a novel dual ERRα/γinverse agonist, SLU-PP-1072, derived from the GSK4716 ERRγagonist scaffold that is distinct from the XCT790 scaffold. SLU-PP-1072 alters PCa cell metabolism and gene expression, resulting in cell cycle dysregulation and increased apoptosis without acute mitochondrial uncoupling activity. Our data suggest that inhibition of ERRα/γmay be beneficial in treatment of PCa, and SLU-PP-1072 provides a unique chemical tool to evaluate the pharmacology of ERRα and ERRγ
Use of Nonselective β-Blockers in Patients With End-Stage Liver Disease and Select Complications
No full textObjective: To review the literature and recommendations for nonselective β-blockers (NSBBs) in the setting of variceal bleeding prophylaxis and decompensated liver disease. Data Sources: Literature search of MEDLINE was performed (1988 to October 2019) using the following search terms: cirrhosis, advanced cirrhosis, β-blocker, decompensation, prophylaxis. Abstracts, peer-reviewed publications, clinical practice guidelines, and product monographs were reviewed. Study Selection and Data Extraction: Relevant English language studies and those conducted in humans were considered for analysis and inclusion. Data Synthesis: Evidence that suggests that NSBBs are harmful in advanced cirrhosis is overshadowed by confounding variables and small patient populations. The majority of the available evidence suggests neutral or beneficial effects on mortality with continuation of NSBBs despite liver disease progression. Based on the available literature, guidelines, and expert consensuses, NSBBs can be considered within this patient population and may have a positive impact on the majority of these patients. Relevance to Patient Care and Clinical Practice: This review summarizes current place in therapy for NSBBs in the setting of cirrhosis and variceal bleeding prophylaxis. It also includes a discussion of the literature for use of NSBBs within the setting of different acute decompensations in which the data and recommendations for use are less clear. Conclusions: Recent evidence shows neutral or positive results for NSBB use in particular decompensation subgroups, which suggests that NSBBs can be used cautiously with close monitoring in patients with advanced cirrhosis. Questions still remain regarding optimal agent and dose and whether agents can be safely restarted after an acute decompensation episode
A Research Partnership to Enhance Postgraduate Pharmacy Residency Training Outcomes
No full textPharmacy residents must complete research as part of their program; however, challenges exist in providing experiences that result in successful research dissemination outcomes. A university-based research team, integrated into an ambulatory care pharmacy residency program aimed to improve presentation and publication rates of pharmacy resident research projects. Data on the number of postgraduate year-2 (PGY2) residents and their productivity were collected and summarized to assess progress. A total of 13 residents completed their residency over seven years. Each resident produced one regional presentation, and one national presentation beginning in year four. To date, three peer-reviewed papers have been published, with another one in-press. Responses from residents found lack of guidance, lack of data availability for projects and feedback fatigue were barriers to a positive research experience. To address these problems, a university-based research team was integrated to provide research mentor guided support, ensure study feasibility, and provide structured feedback. This program evaluation highlighted the integration of a PGY2 ambulatory care pharmacy residency with a designated, interprofessional university-based research team. Future work is warranted to reduce research-related barriers and formally evaluate resident post-program knowledge, skills, and subsequent dissemination rates
Predictors of student failure or poor performance on advanced pharmacy practice experiences
No full textObjective. To determine factors predictive of student failure or poor performance on advanced pharmacy practice experiences (APPEs) at a single pharmacy program. Methods. This retrospective cohort evaluated students entering the Doctor of Pharmacy (PharmD) program from 2012-2014 at St. Louis College of Pharmacy. Students who received a grade of F for one or more APPEs (failure group) were compared to all other students (non-failure group). A secondary evaluation compared students with a C or F on one or more APPEs (poor performers) to all other students (non-poor performers). Data were collected on didactic and experiential performance, identifiable professionalism issues from introductory pharmacy practice experiences (IPPEs), and academic honor code violations. Univariable and multivariable logistic regressions were performed to determine factors associated with APPE failure and poor performance. Results. A total of 669 students were analyzed. Twenty-eight students (4.2%) failed one or more APPEs and 81 students (12.1%) were identified as poor performers (grade of C or F). For the primary outcome, professional grade point average (GPA) of less than 2.7, practicum failure, IPPE professionalism issue(s), and pharmacotherapy course failure were identified for inclusion in the multivariable analysis. The IPPE professionalism issue(s) (HR 4.8 [95% CI 1.9-12.4]) and pharmacotherapy course failure (HR 4.2 [95% CI, 1.6-11.1]) were associated with APPE failure on multivariable regression. On the secondary analysis, the same variables were identified for multivariable regression, with professional GPA of less than 2.7 (HR 2.7 [95% CI 1.5-5]), IPPE professionalism issue(s) (HR 3.9 [95% CI 2.2-6.9]), and pharmacotherapy course failure (HR 2.0 [95% CI 1.1-3.7]) associated with poor performance. Conclusion. Poor academic performance and/or identified unprofessional behavior while completing IPPEs are associated with APPE failure and poor performance. Interventions should be aimed at identifying at-risk students and addressing risk factors prior to APPEs
Direct to Consumer Telemedicine: Is Healthcare From Home Best?
No full textDirect-to-consumer (DTC) telemedicine is increasingly popular and enables patients to obtain medical advice and treatment via electronic media (e.g., computer, telephone, or smartphone) without a prior doctor-patient relationship. Convenience, accessibility, and home delivery make DTC telemedicine attractive to patients. Concerns about DTC telemedicine include: a lack of regulation, transparency, and an established patient-provider relationship (physician and pharmacist). In future, researchers, providers, and insurers need to better understand the concerns and challenges that this new form of healthcare poses