Albany College of Pharmacy and Health Sciences

Few treatment options exist for serious infections caused by metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa. This study evaluated imipenem/relebactam (I/R) plus aztreonam (ATM) against Pseudomonas-derived cephalosporinase (PDC)- and MBL-producing P. aeruginosa in a hollow fiber infection model, with ceftazidime/avibactam (CZA) plus ATM as a comparator. Two isogenic PDC- and MBL-producing P. aeruginosa isolates (MB10480: IMP-1; MB10620: VIM-1) were studied at a starting inoculum of ∼8 log10 CFU/mL over 96 hours. Humanized I/R exposures were evaluated alone and with extended-infusion ATM (1.5 g every 6 hours [q6h], 2 g q8h, and 2 g q6h), with CZA plus ATM (2 g q6h) as a comparator. Combinations were tested in triplicate, and ATM/relebactam or ATM/avibactam minimum inhibitory concentrations (MICs) were assessed at 96 hours. For both MB10480 (ATM/relebactam MIC: 8/4 mg/L) and MB10620 (4/4 mg/L), monotherapy arms mirrored the growth control. Both I/R plus ATM and CZA plus ATM produced early synergy (≥2 log10 CFU/mL reduction relative to the most active monotherapy) with >1 log10 CFU/mL killing relative to the starting inoculum at 24 hours, followed by regrowth, with bacteriostasis observed at 96 hours across regimens. However, bacterial counts at 96 hours were lowest with I/R plus ATM 2 g q6h. Two colony morphologies were recovered, and retested MICs were occasionally, but not consistently, elevated. Both I/R plus ATM and CZA plus ATM showed early synergy against PDC- and MBL-producing P. aeruginosa, but regrowth occurred with all regimens. Higher-dose ATM with I/R provided more durable suppression, though persistence remained common, underscoring the need to better define dosing and mechanisms of regrowth.

Long-term reactivated memories undergo a time-dependent reconsolidation process during which they are susceptible to modulation. We report the results of an experiment examining the effect of multiple reminder treatments on reconsolidation of a long-term memory. Participants were trained on a procedural finger tapping task and were either reminded of that training 5 days later or not, immediately prior to learning a new tapping sequence. An additional group was given a reminder treatment of original learning on each of the interim days. Contrary to our hypothesis, results indicate that multiple reminder treatments rendered the training memory significantly more susceptible to disruption in comparison to controls that did not receive any reminders of original learning prior to learning the new motor sequence.

Pregnancy is a critical window for tobacco cessation; socio-demographic correlates and prenatal care (PNC) utilization behaviors associated with quitting e-cigarette and dual use with conventional cigarettes remain understudied. To examine the influence of socio-demographic characteristics and PNC utilization in the cessation of cigarette, e-cigarette, and dual-use during pregnancy, using Pregnancy Risk Assessment Monitoring System (2016-2022) data. We analyzed data from 223,793 respondents (weighted count = 11,475,844) with singleton births who reported cigarette and/or e-cigarette use during the three months before and the last three months of pregnancy. Socio-demographic and PNC cessation correlates for cigarette, e-cigarette, and dual-use were examined versus continuation using logistic regression analysis. The Adequacy of Prenatal Care Utilization (APNCU) Index assessed PNC. Associations were expressed as adjusted odds ratios with 95% confidence intervals [AOR (95%CIs)]. Tobacco product use declined from 16.9% pre-pregnancy to 7.5% by late pregnancy. Pregnancy-associated cessation rates were 53.7% for cigarettes, 81.0% for e-cigarettes, and 48.1% for dual-use. Primiparity was associated with higher odds of quitting across all groups: cigarettes [1.8 (1.6‒2.0)], e-cigarettes [1.6 (1.2‒2.1)], and dual-use [2.3 (95% CI: 1.7‒3.1)]. Black race and Hispanic ethnicity were positively associated with cessation of cigarettes and dual-use, while Black race was also associated with higher odds of EC cessation. A higher smoking frequency was associated with reduced cessation odds of cigarette [0.2 (0.2‒0.3)] and dual-use [0.3 (0.2‒0.4)], while a higher vaping frequency was associated with reduced e-cigarette cessation [0.3 (0.2‒0.5)]. Inadequate APNCU Index was associated with lower odds of quitting cigarettes [0.6 (0.5‒0.7)] and dual-use [0.6 (0.4‒0.9)], but showed no significant association with e-cigarette cessation [0.9 (0.6‒1.5)]. Distinct socio-demographic and PNC factors influence cessation patterns by product type. Findings underscore potential opportunities to integrate PNC with targeted cessation support, particularly for high-risk groups amid rising e-cigarette and dual use during pregnancy.

Abstract Estrogen receptor (ER) drives approximately 75% of all breast cancers and serves as the primary target for endocrine therapies. However, resistance to these therapies remains a major clinical hurdle, especially in metastatic ER-positive breast cancers harboring activating ESR1 mutations (e.g., Y537S, D538G) within the ligand-binding domain. These mutations are commonly detected in metastatic lesions and circulating tumor DNA (ctDNA) from patients undergoing endocrine treatment. While combination therapies with CDK4/6 inhibitors have shown promise, the mechanisms driving resistance in ESR1-mutant tumors and their associated therapeutic vulnerabilities remain poorly defined. To address this gap, we investigated the interaction between endocrine-resistant breast cancer (ERBC) cells and the tumor microenvironment. Using co-culture systems involving seven ERBC cell lines—including genome-edited ESR1 mutants—and four stromal cell types, we profiled 28 tumor-stroma secretome combinations via cytokine antibody arrays. This approach identified CCL5 and endoglin as significantly upregulated in resistant tumor-stroma interactions. We hypothesized that CCL5 promotes endocrine resistance and metastatic progression through paracrine signaling with stromal components. To test this, we generated CCL5 knockout EO771 cells using CRISPR-Cas9 and confirmed CCL5 loss through qRT-PCR and ELISA. CCL5-deficient cells exhibited markedly reduced proliferation and migration in vitro. In vivo, orthotopic mouse models demonstrated that CCL5 knockout tumors had significantly decreased growth and metastasis. Moreover, treatment with maraviroc, a CCR5 antagonist, selectively impaired the viability of wild-type but not CCL5-deficient cells. Together, these findings identify CCL5 as a key driver of endocrine resistance and metastatic potential in ERBC, highlighting it as a promising target for therapeutic intervention. This study lays the groundwork for future clinical strategies aimed at overcoming resistance in ESR1-mutant breast cancers by disrupting CCL5 signaling. Citation Format: D. Lomonaco, K. Jin. Ccl5 and endoglin as a therapeutic target in er positive breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-11-12.

Critical care pharmacists (CCPs) are recognized as essential members of the intensive care unit (ICU) multidisciplinary patient care team, yet still find it necessary to justify their presence. Therefore, it is important to understand which CCP activities provide the most value to patient outcomes to inform discussions about CCP practice and guide development of quality measures (QM) and key performance indicators (KPI). We aimed to conduct a scoping review of studies that assessed the effect of CCP patient care activities on clinically relevant outcomes in an intensive care unit (ICU) to guide development of QM/KPI. The Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Healthcare Administration Databases (via ProQuest), PubMed, and Web of Science from 1980 through October 1, 2025 were searched using the following search terms: "pharmacist," "critical care," "critically ill," "intensive care units," and "ICU." The search strategy retrieved 5971 articles of which 71 studies were included. Most studies were single-center evaluations, and the most common areas of CCP activity were antimicrobial stewardship (17 studies, 24%), sedation optimization (11 studies, 15%), pharmacotherapy management (10 studies, 14%), and medication safety (8 studies, 11%). The most common outcomes assessed were ICU length of stay (LOS) (55 studies, 77%), mortality (44 studies, 62%), hospital LOS (29 studies, 41%), duration of mechanical ventilation (20 studies, 28%), and medication errors (11 studies, 15%). Forty-two studies (59%) showed a statistically significant difference in the outcomes assessed favoring the CCP activity. Multiple QM/KPI were derived from specific CCP activities performed in these studies. Many studies documented improvements in clinically relevant outcomes because of the care provided by a CCP. QM/KPI derived from CCP activities performed in these studies may be useful in standardizing CCP practice and workflow and further establish CCP value.

We examined the cross-sectional relationship between cardiovascular disease (CVD) risk, history of falls, and the number of falls in the past year in the US multicenter MACS/WIHS Combined Cohort Study (2020-2022) of men and women without HIV (MWOH/WWOH) and men and women with HIV (MWH/WWH). CVD risk was assessed by pooled cohort equation 10-year risk scores and categorized into 4 levels. Self-reported falls outcomes (recent fall, not recent fall, one fall, multiple falls) were assessed using a standardized protocol. Odds ratios of falls were measured using multinomial regression models stratified by sex and adjusted for ethnicity, education attainment, alcohol consumption, body-mass index, fall-risk medications, physical activity, and HIV serostatus. There were 2723 participants, 35% were men (577 MWH, 360 MWOH) with a median age of 58 (IQR: 14) years. Women represented 65% (1271 WWH, 515 WWOH) with a median age of 55 (IQR: 11) years. In sex stratified multinomial adjusted models, among men, high CVD risk (vs. low risk) was significantly associated with a recent fall (vs. never fall) (aOR: 3.12, 95% CI: 1.59 to 6.13) and one fall (vs. no fall) in past year (aOR: 3.66; 95% CI: 1.45 to 9.21). Among women, high CVD risk was only significantly associated with multiple falls (vs. no fall) in past year (aOR: 2.06; 95% CI: 1.24 to 3.43). Our findings highlight the importance of integrating fall-risk assessments into CVD management, particularly for men and women with living with HIV and high CVD risk, and the need for targeted, gender-responsive fall prevention strategies in clinical practice.

Abstract Description Francisella tularensis (Ft) is a Gram-negative, intracellular bacterium and the causative agent of tularemia, a disease with a 30–60% fatality rate if untreated. Due to its low infectious dose and high mortality, Ft is considered a potential bioterrorism agent. Previous studies demonstrated that Ft suppresses host innate immune responses, including inflammasome-mediated signaling, resulting in reduced cytokine production, innate immune cell recruitment, and bacterial clearance. The absent in melanoma 2 (Aim2) inflammasome, activated by double-stranded DNA, promotes secretion of IL-1β and IL-18, key cytokines required for Ft clearance. However, Ft suppresses Aim2 activation through unknown mechanisms. We hypothesized that Ft modulates the intracellular redox environment to inhibit Aim2 inflammasome activation. Using an Ft mutant deficient in the oxidative stress regulator OxyR (ΔoxyR), we observed elevated IL-1β secretion and Aim2-dependent caspase-1 activation in infected macrophages compared to those infected with the wild-type Ft. Increased expression of IRF1 and GBP2, upstream components of Aim2 signaling, was also detected in ΔoxyR-infected macrophages. These effects were abolished in NADPH oxidase-deficient macrophages, highlighting a role for reactive oxygen species in this pathway. Our findings reveal that OxyR suppresses Aim2 inflammasome activation by regulating redox homeostasis, providing new insights into Ft pathogenesis. Funding Sources This work was funded by NIH/NIAID Grant 1R15AI107698. Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)