The ACPHS Research Commons collects in one space the digitised research and scholarship generated by the college’s faculty, students, and staff.

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Recent Submissions

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    RNA Polymerase III Regulates HIV Replication and Latency.
    (Viruses., 2025-09-20) Thompson, Landon*; Jamal, Imran*; Das, Juthika*; Dang, Casey*; Hong, Zhenzi*; Katz, Doran*; Bosque, Alberto; Singh, Vir B
    The elimination of HIV latent reservoirs is an extremely challenging task due to the interplay of multiple mechanisms regulating latency. Thus, we need to identify novel strategies to target heterogeneous reservoirs uniformly. Recent reports have provided intriguing evidence for the novel antiviral function of RNA Polymerase III (RNAP III), which remains to be further explored. In this study, we evaluated the role of RNA Pol III in regulating HIV latency and replication. We first demonstrated that the pharmacological inhibition of RNAP III can lead to a strong reactivation of latency in cell lines representing both T and monocytic cellular reservoirs. Next, we investigated the involvement of RNA Pol III in regulating HIV-1 replication using HIV-1 pseudotyped (DuoFluo) virus and HIV-1-Bal in THP-1 and Sup-T1 cells. We show that the pharmacological inhibition of RNAP III significantly induced HIV transcription. These findings were further confirmed in physiologically relevant primary CD4 T cells, and a consistent increase in HIV transcription was observed up to 72 h. Collectively, our study suggests that inhibition of RNAP III can increase the rate of HIV transcription, while the total HIV DNA remains unchanged. Overall, our study identifies a previously unknown role of RNA Pol III in restricting HIV transcription and advocates that targeting RNAP III-driven mechanisms could be a novel strategy to reactivate HIV latent reservoirs.
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    Comparison of early treatment with ceftolozane/tazobactam versus polymyxin-based therapy of pneumonia due to MDR (PUMA).
    (Antimicrobial Agents and Chemotherapy., 2025-09-18) Lodise, Thomas P; Min, Jae; Nathanson, Brian H; Yücel, Emre
    Ceftolozane/tazobactam and polymyxin-based regimens are frequently used to treat pneumonia caused by multi-drug-resistant (MDR-PSA). However, comparative data on global clinical outcomes between these therapies are limited. A multi-centered observational study was performed using the PINC AI Healthcare Database (2016-2022). The study population included hospitalized patients ≥ 18 years who were diagnosed with pneumonia and had MDR-PSA (defined as non-susceptible to ≥1 agent in ≥3 antimicrobial categories) on a respiratory or blood culture, receipt of ceftolozane/tazobactam or a polymyxin-based regimen within 3 days of index MDR-PSA culture, receipt of ≥2 days of ceftolozane/tazobactam or a polymyxin-based regimen, and without a COVID-19 diagnosis. A Desirability of Outcome Ranking (DOOR) analysis was performed. Components of the DOOR included in-hospital mortality, discharge destination (home vs other), recurrent MDR-PSA pneumonia, receipt of any renal replacement therapy (RRT) post-index culture in RRT-naive patients, and 30-day pneumonia-related readmissions. In total, 186 patients met the study criteria (104 ceftolozane/tazobactam and 82 polymyxin). In the IPW-adjusted DOOR analysis, a ceftolozane/tazobactam-treated patient had a higher probability of a more favorable outcome (DOOR probability: 61.3%; 95% CI: 56.8%, 65.7%). In the DOOR partial credit analyses, a ceftolozane/tazobactam-treated patient had a higher probability of being discharged home alive with no undesirable outcomes than a polymyxin-treated patient (20.2% vs 9.8%, = 0.04). This real-world evidence study of non-COVID-19 patients with MDR-PSA pneumonia suggests that patients treated with ceftolozane/tazobactam have a higher probability of a more favorable outcome compared with patients treated with a polymyxin-based regimen. Further large-scale studies with detailed dosing are needed to validate the findings.
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    Association between Duration of Candidemia and Clinical and Healthcare Resource Utilization Outcomes among Hospitalized Adult Patients with Candidemia Who Received Empiric Treatment with an Echinocandin Across United States Hospitals.
    (Clinical Infectious Diseases, 2025-09-01) Lodise, Thomas P; Garey, Kevin W; Aram, Jalal A; Nathanson, Brian H
    Background: Time to bloodstream clearance is a critical prognostic indicator in various infections, yet limited data exist on the relationship between time to mycological clearance and outcomes in candidemia. This study aimed to assess the association between the duration of candidemia and outcomes in adult, hospitalized patients receiving empiric echinocandin treatment across U.S. hospitals.
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    Tamsulosin for Urinary Retention in Older Women: Maximizing the Flow.
    (Journal of Gerontological Nursing, 2025-09-01) Becerra, Kalayaan; Saño, Ugene
    Purpose: Urinary retention (UR) is a lower urinary tract symptom (LUTS) that can present in men and women aged ≥65 years. However, unlike the medications available for men to treat this condition, the current approach to management of chronic UR in women is limited to conservative methods and urinary catheterization, which have various risks. The current article reviews the use of tamsulosin as a potential pharmacological alternative for the management of chronic UR in older women.
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    Dalbavancin for Treatment of Staphylococcus aureus Bacteremia: The DOTS Randomized Clinical Trial.
    (JAMA, 2025-08-13) Turner, Nicholas A; Hamasaki, Toshimitsu; Doernberg, Sarah B; Lodise, Thomas P; King, Heather A; Ghazaryan, Varduhi; Cosgrove, Sara E; Jenkins, Timothy C; Liu, Catherine; Sharma, Shrabani; Zaharoff, Smitha; Wahid, Lana; Renard, Valerie J; Cook, Paul; Raad, Issam; Hachem, Ray; Chaftari, Anne-Marie; Sims, Matthew; DeMarco, Carmen; Miller, Loren G; McCarthy, Matthew W; Morse, Caryn G; Lucasti, Chris; Forrest, Graeme N; Cherabuddi, Kartikeya; Polk, Christopher; Fazili, Tasaduq; Rupp, Mark E; Thompson, George R; Kim, Kami; Strnad, Luke; Schnee, Amanda E; McKinnell, James A; Ramesh, Mayur; Silveira, Fernanda P; McCarty, Todd P; Lee, Todd C; McDonald, Emily G; Paolino, Kristopher; Wiegand, Katie; Wall, Alison; Riccobene, Todd; Patel, Rinal; Rappo, Urania; Evans, Scott; Chambers, Henry F; Fowler, Vance G; Holland, Thomas L
    Importance: Dalbavancin is a long-acting intravenous lipoglycopeptide that may be effective for treatment of complicated Staphylococcus aureus bacteremia without requiring long-term intravenous access.