Now showing items 1-20 of 1243

    • Bridging Curriculum Gaps In Pediatric and Adolescent Gender-Affirming Care Through Interprofessional Education

      Kruger Howard, Amy; Morgan, Jill A.; Castile, Tiernan Connor; Westgate, Lee; Gold, Sara; Nikita, Maria Eleni (2022-03)
    • Patient-Informed Value Assessment of Telehealth Care Services: Conceptualization to Implementation

      Amill-Rosario, Alejandro; Jegede, Abidemi; Slejko, Julia F.; dosReis, Susan (2022)
    • Evidence for a Patient-Informed Approach to Value Assessment of Major Depressive Disorder Treatments

      Nasroodin, Simone; Nguyen, Karen; Namvar, Tarlan; Xie, Richard; Chapman, Richard; Slejko, Julia F.; dosReis, Susan (2022-05)
    • Economic Burden of Interstitial Lung Disease in a Commercially Insured Population with Sjögren’s Syndrome in the United States

      Lee, Tsung-Ying, M.S.; Slejko, Julia F.; Davies-Teye, Bernard Bright; Onukwugha, Eberechukwu (2022-05)
    • Iron-dependent differential regulation of T6SS in Pseudomonas aeruginosa

      Chourashi, Rhishita; Oglesby, Amanda G. (2022-04)
      Differential iron regulation of RsmY/Z sRNA in shaking versus static cultures. -- AQ dependent expression of rsmY/Z genes as well as HS2-T6SS genes (type six secretion system). -- AQ mediated iron regulation of RsmY/Z and HS2-T6SS genes is promoter dependent
    • Crowdfunding investigative journalism at The BMJ

      Coombes, Rebecca (Magazine editor); Doshi, Peter (BMJ Publishing Group, 2022-03-29)
      The BMJ is now more than a scholarly journal, and for the past decade we have pursued investigative journalism as a powerful lever for improving health by exposing failings in the system. Over the past year we have substantially expanded our coverage, publishing 16 investigative stories (, including a series that won a British Journalism Award, and worked with a greater number of international journalists. We have reported the disclosures of a whistleblower working on the Pfizer covid-19 vaccine trial, a story that unexpectedly led us to confront Facebook over the way it deals with misinformation on its platform. We have probed the implications of mRNA instability in vaccines and asked serious questions about Russia’s Sputnik vaccine. Beyond covid, we have tackled concerns in global health, including polio eradication, and asked whether health institutions should still be investing in fossil fuels.
    • Synthesizing α-helix mimetics with CADD-positioned electrophilic warheads to inhibit the BFL-1 antiapoptotic protein

      Goodis, Christopher Craig; Zhao, Mingtian; Conlon, Ivie L.; Li, Amanda; MacKerell, Alexander D., Jr.; Fletcher, Steven (2022)
    • Phenobarbital Induces SLC13A5 Expression through Activation of PXR but Not CAR in Human Primary Hepatocytes

      Li, Zhihui; Li, Linhao; Heyward, Scott; Men, Shuaiqian; Xu, Meishu; Sueyoshi, Tatsuya; Wang, Hongbing, Ph.D. (2022-04-05)
      Phenobarbital (PB), a widely used antiepileptic drug, is known to upregulate the expression of numerous drug-metabolizing enzymes and transporters in the liver primarily via activation of the constitutive androstane receptor (CAR, NR1I3). The solute carrier family 13 member 5 (SLC13A5), a sodium-coupled citrate transporter, plays an important role in intracellular citrate homeostasis that is associated with a number of metabolic syndromes and neurological disorders. Here, we show that PB markedly elevates the expression of SLC13A5 through a pregnane X receptor (PXR)-dependent but CARindependent signaling pathway. In human primary hepatocytes (HPH), the mRNA and protein expression of SLC13A5 was robustly induced by PB treatment, while genetic knockdown or pharmacological inhibition of PXR significantly attenuated this induction. Utilizing genetically modified HepaRG cells, we found that PB induces SLC13A5 expression in both wild type and CAR-knockout HepaRG cells, whereas such induction was fully abolished in the PXR-knockout HepaRG cells. Mechanistically, we identified and functionally characterized three enhancer modules located upstream from the transcription start site or introns of the SLC13A5 gene that are associated with the regulation of PXR-mediated SLC13A5 induction. Moreover, metformin, a deactivator of PXR, dramatically suppressed PB-mediated induction of hepatic SLC13A5 as well as its activation of the SLC13A5 luciferase reporter activity via PXR. Collectively, these data reveal PB as a potent inducer of SLC13A5 through the activation of PXR but not CAR in human primary hepatocytes.
    • Maryland Mentor: 2022

      University of Maryland, Baltimore. School of Pharmacy. Experiential Learning Program, 2022
    • Assessing Muscle-Related Adverse Events in Randomized Trials of Statins.

      Doshi, Peter; Hong, Kyungwan; Tanveer, Sarah; Jefferson, Tom (Springer Nature, 2022-03-16)
    • Evaluating novel pilot pharmacokinetic bioequivalence study for inhalation powder drug products exhibiting batch-to-batch variability

      Li, Shuhui; Feng, Kairui; Lee, Jieon; Gong, Yuqing; Wu, Fang; Newman, Bryan; Yoon, Miyoung; Fang, Lanyan; Zhao, Liang; Gobburu, Jogarao (2022-03-11)
    • Challenges and Successes of Deprescribing Networks Across the Globe: A Qualitative Key Informant Study

      Kim, Catherine; Thompson, Allison; Kim, Grace; Keller, Michelle; Marcum, Zachary A.; Brandt, Nicole J. (2022-02)
    • Deciphering the contents of electronic nicotine delivery systems (ENDS) aerosol from model e-liquids and commercial products and determining their toxicological effects on cells

      Eng, Bryan; Lee, Angela; Li, Haoju; Ma, Tao, Ph.D.; Pilli, Nageswara; Brandis, Joel; Liu, Tian; Dalby, Richard N.; Kane, Maureen A.; Michel, Sarah L. J.; et al. (2022-03-11)
    • The "Common" Chemical Universe

      Sharif, Suliman; Chow, Elena Yi; Orr, Asuka; Liu, Ruibin; Romany, Aarion; Frank, Aziza; Burke, Chris; Jo, Sunhwan; Zhao, Shaoqi; MacKerell, Alexander D., Jr. (2022-03-04)
    • Nanotherapeutic targeting of the Fn14 receptor for TNBC brain metastases

      Carney, Christine; Kapur, Anshika; Anastasiadis, Pavlos; Chen, Chixiang; Woodworth, Graeme; Winkles, Jeffrey Allan; Kim, Anthony J. (2022-03-04)
    • Patterns, Factors and Outcomes associated with Gabapentin use in Combination with Opioids and Benzodiazepines among Social Security Disability Insurance (SSDI)-eligible Medicare Beneficiaries

      Olopoenia, Abisola; Simoni-Wastila, Linda (2021)
      Background: Little is known about the patterns, factors, and public health outcomes associated with concurrent utilization of gabapentin, opioids, and benzodiazepines (GABA+OP+BZD) Objective: To examine the patterns, factors, and public health outcomes associated with concurrent utilization of GABA+OP+BZD among Social Security Disability Insurance (SSDI) eligible beneficiaries. Methods: Using a 5% sample of 2013-2016 Medicare data, we utilized a retrospective cohort design to examine the following patterns of concurrent utilization: monotherapy, dual therapy, tri-therapy, switching, augmentation, discontinuation, and continuation. Similarly, a retrospective cohort design was utilized to examine the sociodemographic and clinical factors associated with the longest concurrent medication utilization episode, defined based on the overlap of prescriptions for GABA+OP+BZD. We used a nested case control design to examine the association between concurrent utilization of GABA+OP+BZD and adverse outcomes (respiratory depression, substance and opioid related overdose, and adverse drug-related events) among disabled beneficiaries with acute pain [AP], chronic pain [CP], and mental health conditions [MH]. Results: Among disabled beneficiaries, gabapentin initiators were significantly more likely to become dual and tri-therapy users (p<0.01) and to augment therapy (50.1%) when compared to opioid (28.7%) and benzodiazepine (38.7%) users; the majority augmented within 2-months after initiating therapy. Back pain [AOR(95%CI): 1.23(1.07-1.41)], chronic pain [1.27 (1.07-1.51)], mental health [1.16 (1.02-1.33)], opioid dose [1.05 (1.03-1.06)] and duration [1.07 (1.06-1.07)], and benzodiazepine duration [1.06 (1.05-1.06)] were positive predictors of having longest concurrent use involving GABA+OP+BZD. Concurrent GABA+OP+BZD use was associated with increased odds of respiratory depression [AP: 1.35 (1.19-1.52), CP:1.24 (1.11-1.38) and MH: 1.16 (1.02-1.32)], opioid related overdose [AP: 1.43 (1.04-1.98), CP: 1.47 (1.07-2.00) and MH: 1.44 (1.04-2.00)], substance related overdose[AP: 1.77 (1.26-2.50), CP: 1.70 (1.24-2.34) and MH: 1.92 (1.31-2.82)] and adverse drug related events[AP: 1.36 (1.22-1.50), CP: 1.23 (1.10-1.36) and MH: 1.15 (1.02-1.30)]. Conclusion: Our study provides the first evidence of patterns, factors, and outcomes associated with concurrent utilization of GABA+OP+BZD. Given noted adverse outcomes associated with GABA+OP+BZD, it is imperative that the benefits and risks of co-prescribing these medications be examined comprehensively, especially for those at the greatest risk of being prescribed these medications.
    • Exploiting Vulnerabilities in Cancers with Activated Extracellular Signal-Regulated Kinase (ERK1/2)

      Martinez, Ramon; Shapiro, Paul, Ph.D.; 0000-0002-0050-3172 (2021)
      Constitutively active extracellular signal–regulated kinase (ERK) 1/2 signaling promotes cancer cell proliferation and survival. ERK1/2 pathway inhibitors are important therapies for treating many cancers, however, acquired resistance to most protein kinase inhibitors limit their ability to provide durable responses. Few studies have looked at the adaptive proteome responses of BRAF/MEK dual inhibitor resistant cells, and fewer still have established the utility of allosteric inhibitors targeting the ERK2 protein. The overall goal of the current study was to identify signaling mechanisms of therapeutic resistance and further investigate a previously identified inhibitor of melanoma cell growth with putative activity with the protein ERK2. To test this, we hypothesize that vulnerable targets can be identified for therapeutic intervention, and test if alternative inhibitors exhibit clinical potential for melanoma treatment in two specific aims. In Aim 1, we characterized the global protein changes happening in constitutively-activeERK1/2 melanoma cells models that developed resistance to BRAF (PLX4032) and MEK1/2 (AZD6244) inhibitors using mass spectrometry. We additionally identified putative targets for treatment and analyzed the potential for a metabolic inhibitor, niclosamide. In Aim 2, studies were focused on elucidating the structure-activity relationship and binding mechanism of a ERK2-specific inhibitor developed in house, SF-3-030. We identified chemical features required for biologic activity and global effects on gene and protein levels in A375 melanoma cells containing mutant BRAF(V600E). We then identified the mechanism of action of the inhibitor in preventing melanoma growth using mass spectrometry analysis. Overall, these studies help to elucidate how cells overcome currently used clinical therapies, what vulnerable markers can be identified and used for therapeutic intervention, and that inhibitors alternative to the clinical standard can show potential for melanoma treatment.
    • Association of Patient Cost Sharing and Area Deprivation with Multiple Myeloma Treatment Receipt and Outcomes

      Hong, Yoon Duk; Slejko, Julia F; 0000-0002-9548-5770 (2021)
      Introduction: Advances in multiple myeloma (MM) treatment have improved survival, but there are increased concerns about treatment affordability and access. This study assessed 1) how cost-sharing assistance and area deprivation affect treatment receipt, 2) changes in the patient cost responsibility and disparities in treatment over time, and 3) how the low-income subsidy (LIS), which lowers Part D cost sharing, and area deprivation affect treatment access and survival. Methods: Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified patients diagnosed with MM. The effect of cost-sharing assistance and area deprivation on treatment was estimated using multilevel logistic regression. We estimated the monthly incremental patient cost responsibility among MM patients compared to non-cancer controls and examined changes over time (2007-2011, 2012-2016). The effect of diagnosis period and area deprivation on treatment was estimated using multilevel logistic regression. The association between LIS, area deprivation, and mortality was estimated from a mixed-effects Cox proportional hazards model. We assessed whether treatment mediates the association between LIS and mortality. Results: Individuals receiving Medicare Parts A, B and D cost-sharing assistance had higher odds of receiving treatment compared with non-recipients (OR=1.21; 95%CI: 1.01–1.45). Living in the most deprived area (Quintile 5) was associated with lower odds of receiving treatment compared with the least deprived area (Quintile 1; OR=0.81; 95%CI: 0.65–0.99), but there was no difference in the other quintiles. The difference in the estimated monthly incremental patient cost responsibility between 2012-2015 and 2007-2011 was $58 [average marginal cost; 95%CI: $12–$105]). The difference in the likelihood of any treatment receipt between Quintile 1 and 5 decreased, but the difference in the likelihood of receiving a novel agent-based regimen increased. The mortality hazard was higher for LIS recipients relative to non-recipients in Quintiles 1, 3 and 4 (HR=1.50, 1.38, 1.28; p=0.0001), and there was no difference in the other two quintiles. This association was partially mediated by treatment receipt. Conclusions: The patient cost responsibility for MM care increased over time. The type of cost-sharing assistance and area deprivation affect treatment receipt, although not across all quintiles. LIS receipt did not confer a survival benefit.