UHSP Collections (University of Health Sciences and Pharmacy)
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Absences Due to Illness-Sick Time Policy
No full textFrom time-to-time employees will miss work due to illness or injury. The University provides an accrued sick time benefit intended to offer employees paid time off to deal with minor, short-term illnesses or injuries as well as allow longer-term employees enough banked leave to cover a short-term disability. Employees are expected to accurately report sick time and avoid excessive or unexcused absences. Employees may use up to half of a year’s earned sick time, six (6) sick days per benefit year to care for qualifying immediate family members for qualifying reasons. The University does not interfere with, restrain or deny, or discriminate or retaliate against employees for taking protected leave such as Family and Medical Leave, Illinois Employee Sick Leave Act, or having a protected disability requiring use of accrued sick time
Respiratory Complex III: A Bioengine with a Ligand-Triggered Electron-Tunneling Gating Mechanism
No full textRespiratory complex III (a.k.a., the bc1 complex) plays a key role in the electron transport chain in aerobic cells. The bc1 complex exhibits multiple unique electron tunneling (ET) processes, such as ET-bifurcation at the Qo site and movement of the Rieske domain. Moreover, we previously discovered that electron tunneling in the low potential arm of the bc1 complex is regulated by a key phenylalanine residue (Phe90). The main goal of the current work is to study the dynamics of the key Phe90 residue in the electron tunneling reaction between heme bL and heme bH as a function of the occupancy of the Qo and Qi binding sites in the bc1 complex. We simulated the molecular dynamics of four model systems of respiratory complex III with different ligands bound at the Qo and Qi binding sites. In addition, we calculated the electron tunneling rate constants between heme bL and heme bH along the simulated molecular dynamics trajectories. The binding of aromatic ligands at the Qo site induces a conformational cascade that properly positions the Phe90 residue, reducing the through-space ET distance from ∼7 to ∼5.5 Å and thus enhancing the electron transfer rate between the heme bL and the heme bH redox pair. Also, the binding of aromatic ligands at the Qi site induces conformational changes that stabilize the Phe90 conformational variation from ∼1.5 to ∼0.5 Å. Hence, our molecular dynamics simulation results show an on-demand two-step conformational connection between the occupancy of the Qo and Qi binding sites and the conformational dynamics of the Phe90 residue. Additionally, our dynamic electron tunneling results confirm our previously reported findings that the Phe90 residue acts as an electron-tunneling gate or switch, controlling the electron transfer rate between the heme bL and heme bH redox systems
Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function
No full textBACKGROUND: Cardiac metabolic dysfunction is a hallmark of heart failure. Estrogen-related receptors ERRα and ERRγ are essential regulators of cardiac metabolism. Therefore, activation of ERR could be a potential therapeutic intervention for HF. However, in vivo studies demonstrating the potential usefulness of ERR agonist for HF treatment are lacking, because compounds with pharmacokinetics appropriate for in vivo use have not been available. METHODS: Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915. We investigated the effect of ERR agonist on cardiac function in a pressure overload-induced HF model in vivo. We conducted comprehensive functional, multi-omics (RNA sequencing and metabolomics studies), and genetic dependency studies both in vivo and in vitro to dissect the molecular mechanism, ERR isoform dependency, and target specificity. RESULTS: Both SLU-PP-332 and SLU-PP-915 significantly improved ejection fraction, ameliorated fibrosis, and increased survival associated with pressure overload-induced HF without affecting cardiac hypertrophy. A broad spectrum of metabolic genes was transcriptionally activated by ERR agonists, particularly genes involved in fatty acid metabolism and mitochondrial function. Metabolomics analysis showed substantial normalization of metabolic profiles in fatty acid/lipid and tricarboxylic acid/oxidative phosphorylation metabolites in the mouse heart with 6-week pressure overload. ERR agonists increase mitochondria oxidative capacity and fatty acid use in vitro and in vivo. Using both in vitro and in vivo genetic dependency experiments, we show that ERRγ is the main mediator of ERR agonism-induced transcriptional regulation and cardioprotection and definitively demonstrated target specificity. ERR agonism also led to downregulation of cell cycle and development pathways, which was partially mediated by E2F1 in cardiomyocytes. CONCLUSIONS: ERR agonists maintain oxidative metabolism, which confers cardiac protection against pressure overload-induced HF in vivo. Our results provide direct pharmacologic evidence supporting the further development of ERR agonists as novel HF therapeutics
A Synthetic ERR Agonist Alleviates Metabolic Syndrome
No full textPhysical exercise induces physiologic adaptations and is effective at reducing the risk of premature death from all causes. Pharmacological exercise mimetics may be effective in the treatment of a range of diseases including obesity and metabolic syndrome. Previously, we described the development of SLU-PP-332, an agonist for the estrogen-related receptor (ERR)α, β, and γ nuclear receptors that activates an acute aerobic exercise program. Here we examine the effects of this exercise mimetic in mouse models of obesity and metabolic syndrome. Diet-induced obese or ob/ob mice were administered SLU-PP-332, and the effects on a range of metabolic parameters were assessed. SLU-PP-332 administration mimics exercise-induced benefits on whole-body metabolism in mice including increased energy expenditure and fatty acid oxidation. These effects were accompanied by decreased fat mass accumulation. Additionally, the ERR agonist effectively reduced obesity and improved insulin sensitivity in models of metabolic syndrome. Pharmacological activation of ERR may be an effective method to treat metabolic syndrome and obesity. SIGNIFICANCE STATEMENT: An estrogen receptor-related orphan receptor agonist, SLU-PP-332, with exercise mimetic activity, holds promise as a therapeutic to treat metabolic diseases by decreasing fat mass in mouse models of obesity
Fire Pit Policies and Procedures
No full textThe purpose of this policy is to establish the methods and accountability for fire protection and safety with regards to use of the fire pit at student events at University of Health Sciences and Pharmacy in St. Louis. This policy aligns with Missouri DNR Air Pollution Control Program (PUB2047) and City of St. Louis Ordinance 70932. The UHSP fire pit may only be used for recreational burning of untreated wood. Burning of any waste or material that emits smoke, odor, or toxic fumes is strictly prohibited
Oritavancin vs Standard of Care for Treatment of Nonendovascular Gram-Positive Bloodstream Infections
No full textBackground: Data is limited comparing oritavancin (ORT) to the standard-of-care (SOC) for the treatment gram-positive blood stream infections (BSI). Methods: This was a retrospective study of all patients in the Veteran\u27s Affairs Health Care System treated with at least 1 dose of oritavancin or at least 5 days of vancomycin, daptomycin, ceftaroline, ampicillin, ampicillin-sulbactam, nafcillin, oxacillin, or cefazolin for a documented gram-positive BSI from 1 January 2015 to 30 June 2021. Patients with polymicrobial blood cultures or positive cultures from other sites were included if the organisms were sensitive to the incident antimicrobial; no concomitant antimicrobials could be used once the incident agent was started. Individuals were also excluded if they were diagnosed with endocarditis, had a neutrophil count 96-hours of treatment before the incident antimicrobial was started. The primary composite outcome was clinical failure, defined as all-cause mortality within 30-days from the end of therapy, or blood cultures positive for the incident organisms ≥72 hours after administration of the first dose and ≤30 days after the administration of the final dose of the study antimicrobial, or any drug or line-related readmissions within 30-days of hospital discharge. Results: Two hundred-forty patients were identified for screening with 96 meeting criteria (27 in ORT and 69 in SOC groups). Baseline characteristics were generally balanced between groups except more patients in the ORT group received \u3e96-hours of treatment before the incident antimicrobial was started (70.3% (19/27) vs 13.04% 9/69); P \u3c. 001). The pathogen most prevalent was methicillin susceptible Staphylococcus aureus (MSSA) (ORT 33.3% (9/27) vs SOC 46.4% (32/69)). Clinical failure occurred in 7.4% (2/27) in the ORT group and 17.4% (12/69) in SOC (P =. 34). No components of the primary outcome were significantly different between groups, but AKI did occur more commonly in the SOC group (27.5% (19/69) vs 3.7% (1/27); P =. 01). Conclusions: ORT appears to be a safe and effective option when directly compared to the SOC for non-endocarditis BSIs
A checklist for a consistent, comprehensive medication review
No full textIntroduction: Medicare Advantage Part D plans and stand-alone Part D prescription drug plans are required by the Centers for Medicare and Medicaid Services to have qualified providers, including pharmacists, and offer annual comprehensive medication reviews (CMRs) for eligible Medicare beneficiaries. Although guidance on the components of a CMR is available, providers have flexibility in how to deliver the CMR to patients and which content to cover. With the variety of patient needs, CMR content is not always consistently delivered in practice. Our research group performed an extensive evaluation to create and test an ideal CMR content coverage checklist for CMR provision. CMR Content Checklist: The CMR Content Checklist can be used for quality improvement purposes to evaluate the comprehensiveness of pharmacist services—to assess either within pharmacist variation across patients or within organization variations between pharmacists or sites. Incorporating the CMR Content Checklist into practice: Testing in a real-world setting demonstrated where gaps in service coverage existed. The CMR Content Checklist could be used as the first step for quality improvement given that it provides details on the key aspects of the service that can inform quality measure development
Using Normative Rhetorical Theory to Identify Dilemmas and Responses in Internal Medicine Patient-Provider Communication
No full textDrawing on normative rhetorical theory (NRT), we examined communication dilemmas that internal medicine residents (IMRs) experience when interacting with patients and responses they adopt to manage these dilemmas. We conducted semi-structured, intensive interviews with 15 IMRs and analyzed the data using the phronetic iterative approach. Findings suggested that IMRs experienced two interpersonal dilemmas: (a) asserting expertise while respecting patients and (b) discussing patient behaviors without indicating deviance. The two dilemmas were more salient for international IMRs who were less familiar with the local culture and embraced a different perspective of the IMR-patient relationship. The two interpersonal dilemmas were connected to a supra-level dilemma of practicing tasks required by evidence-based medicine while being patient-centered. IMRs reported engaging in an interpretive lens to view patients as “people” and communicative responses to manage the dilemmas. By applying NRT to a novel context, our findings demonstrate the impact of macro-level paradigms on IMRs’ conflicting purposes in medical encounters and offer practical implications for communication interventions for IMRs
Corrigendum to: Efficacy and acceptability of \u27nudges\u27 aimed at promoting pre-exposure prophylaxis (PrEP) use: a survey of overseas born men who have sex with men
No full textBACKGROUND: This study explores the potential for behavioural economics techniques called \u27nudges\u27 to encourage the use of HIV pre-exposure prophylaxis (PrEP) by overseas-born men who have sex with men (MSM) in Australia. We investigated the preferences of overseas-born MSM for different nudges and the effect of nudges on reported likelihood of seeking information about PrEP. METHODS: We conducted an online survey of overseas-born MSM, in which they were asked: (1) how likely they and a relevant friend would be to click on PrEP advertisements that used behavioural economics strategies; and (2) what they most and least liked about each ad. We conducted ordered logistic regression of reported likelihood scores against participant age and sexual orientation, use of a model in an advertisement, use of statistics about PrEP, reference to the World Health Organization (WHO), rewards for seeking further information, and use of a call-to-action. RESULTS: Participants (n =324) reported higher likelihoods of clicking on advertisements with images of people, statistics about PrEP, rewards for seeking further information, and calls-to-action. They reported lower likelihoods of clicking on advertisements referencing the WHO. They had negative emotional responses to sexualised humour, gambling metaphors, and the slogan \u27Live Fearlessly\u27. CONCLUSIONS: Overseas-born MSM prefer public health messages that feature representative messengers and statistics about PrEP. These preferences are consistent with previous data on descriptive norms (i.e. statistics about the number of peers doing the desired behaviour) and gain-framed information (i.e. focusing on what can be gained from an intervention)