Article
Immunology
Ross M. Boyce, Brandon D. Hollingsworth, Emma Baguma, Erin Xu, Varun Goel, Amanda Brown-Marusiak, Rabbison Muhindo, Raquel Reyes, Moses Ntaro, Mark J. Siedner, Sarah G. Staedke, Jonathan J. Juliano, Edgar M. Mulogo
Summary: Three rounds of chemoprevention with dihydroartemisinin-piperaquine delivered under pragmatic conditions reduced the incidence of malaria after severe flooding in western Uganda. These findings provide a proof-of-concept for the use of chemoprevention to reduce excess disease burden associated with severe flooding.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Brodie L. Bailey, William Nguyen, Anna Ngo, Christopher D. Goodman, Maria R. Gancheva, Paola Favuzza, Laura M. Sanz, Francisco-Javier Gamo, Kym N. Lowes, Geoffrey I. McFadden, Danny W. Wilson, Benoit Laleu, Stephen Brand, Paul F. Jackson, Alan F. Cowman, Brad E. Sleebs
Summary: The study identified a triazolopyrimidine compound with good activity against Plasmodium falciparum and high selectivity against human cells, but faced challenges such as slow onset of action and low aqueous solubility. Further optimization is needed for its development as a potential partner in anti-malarial treatment.
BIOORGANIC CHEMISTRY
(2021)
Article
Medicine, General & Internal
Matthew Cairns, Amadou Barry, Issaka Zongo, Issaka Sagara, Serge R. Yerbanga, Modibo Diarra, Charles Zoungrana, Djibrilla Issiaka, Abdoul Aziz Sienou, Amadou Tapily, Koualy Sanogo, Mahamadou Kaya, Seydou Traore, Kalifa Diarra, Hama Yalcouye, Youssoufa Sidibe, Alassane Haro, Ismaila Thera, Paul Snell, Jane Grant, Halidou Tinto, Paul Milligan, Daniel Chandramohan, Brian Greenwood, Alassane Dicko, Jean Bosco Ouedraogo
Summary: A trial in Burkina Faso and Mali showed that combining the seasonal vaccination with RTS,S/AS01E malaria vaccine and seasonal malaria chemoprevention was more effective in preventing malaria compared to using each intervention alone. The efficacy of both interventions was highest immediately post-administration, but declined over time.
Article
Biochemistry & Molecular Biology
Trent D. Ashton, Anna Ngo, Paola Favuzza, Hayley E. Bullen, Maria R. Gancheva, Ornella Romeo, Molly Parkyn Schneider, Nghi Nguyen, Ryan W. J. Steel, Sandra Duffy, Kym N. Lowes, Helene Jousset Sabroux, Vicky M. Avery, Justin A. Boddey, Danny W. Wilson, Alan F. Cowman, Paul R. Gilson, Brad E. Sleebs
Summary: This study focuses on refining the physicochemical properties of a new antimalarial class, with the aim to improve aqueous solubility, metabolism, and reduce adverse effects. Although the optimized compounds show potent activity against asexual parasites, they exhibit modest activity against early-stage gametocytes and no activity against pre-erythrocytic liver parasites. Surprisingly, the refined physicochemical properties did not lead to improved oral efficacy in a mouse model of malaria compared to previous studies.
BIOORGANIC CHEMISTRY
(2021)
Editorial Material
Microbiology
Amit Sharma
Summary: Two recent publications highlight highly potent inhibitors as potential candidates for HIV pre-exposure prophylaxis (PrEP). They provide solid evidence that long-acting capsid or fusion inhibitors administered as PrEP can offer robust protection against simian-human immunodeficiency virus in the rhesus macaque model of HIV infection.
CELL HOST & MICROBE
(2022)
Review
Infectious Diseases
Joerg J. Moehrle
Summary: Traditional malaria drug discovery has focused on orally available drugs. However, there is now interest in injectable medicines, such as monoclonal antibodies (mAbs) with long-lasting plasma half-lives or long-lasting depot formulations of small molecules. These drugs could act as prophylactics targeting earlier parasitic stages or as interventions against infectious gametocytes. Compared to small-molecule drugs, the development of mAbs is less risky and they have a good safety profile. This could provide faster access to new malaria treatments for vulnerable populations.
TROPICAL MEDICINE AND INFECTIOUS DISEASE
(2022)
Article
Multidisciplinary Sciences
Suyash Deodhar, Brady Sillman, Aditya N. Bade, Sean N. Avedissian, Anthony T. Podany, JoEllyn M. McMillan, Nagsen Gautam, Brandon Hanson, Bhagya L. Dyavar Shetty, Adam Szlachetka, Morgan Johnston, Michellie Thurman, Daniel J. Munt, Alekha K. Dash, Milica Markovic, Arik Dahan, Yazen Alnouti, Alborz Yazdi, Bhavesh D. Kevadiya, Siddappa N. Byrareddy, Samuel M. Cohen, Benson Edagwa, Howard E. Gendelman
Summary: Ultra-long-acting integrase strand transfer inhibitors were developed through screening a library of nanoformulations. One particular nanocrystal showed potential for yearly dosing, releasing drugs slowly at the injection site and adjacent tissues. Significant plasma drug levels were maintained up to a year after injection.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Zunkai Xu, Tao Liu, Yaoyao Jiang, Zhixia Chen, Xiaoguang Shi, Yang Xu, Na Yu, Xia Hua, Xing-Jie Liang, Xiaoyong Yuan, Shutao Guo
Summary: Injectable long-acting prodrug-based microcrystals with an acid-sensitive ketal linker were synthesized for developing extended-release antipsychotic drugs. The drug exposure was prolonged in rats treated with the prodrug-based microcrystals, and the release rate decreased with increasing microcrystal size. Moreover, the drug release from the microcrystals was considerably decreased in an inflammation model, indicating an immune-mediated boost in release post-injection.
MOLECULAR PHARMACEUTICS
(2022)
Article
Multidisciplinary Sciences
Samuel J. Vidal, Elena Bekerman, Derek Hansen, Bing Lu, Kelly Wang, Judy Mwangi, William Rowe, Federico Campigotto, Jim Zheng, Darryl Kato, Abishek Chandrashekar, Julia Barrett, Shivani Patel, Huahua Wan, Tochi Anioke, Noe B. Mercado, Joseph P. Nkolola, Melissa J. Ferguson, William J. Rinaldi, Christian Callebaut, Wade Blair, Tomas Cihlar, Romas Geleziunas, Stephen R. Yant, Dan H. Barouch
Summary: The study shows that a single subcutaneous injection of GS-CA1 can provide long-term protection against repeated rectal simian-human immunodeficiency virus (SHIV) challenges in rhesus macaques. Pharmacokinetic analysis indicates a correlation between GS-CA1 plasma concentration and protection from SHIV challenges. These proof-of-concept data support the development of capsid inhibitors as a novel long-acting PrEP strategy in humans.
Article
Pharmacology & Pharmacy
Tahir Khuroo, Sathish Dharani, Eman M. Mohamed, Sujana Immadi, Zhixing Wu, Mansoor A. Khan, Dai Lu, Pramod Nehete, Ziyaur Rahman
Summary: The study focused on characterizing the ultra-long acting prodrug of dolutegravir (DTG) and developing a biodegradable microparticle formulation. The prodrug DTG-Palmitate showed similar physicochemical properties and stability to DTG, but demonstrated a slower in-vitro release rate and potential for sustained drug release compared to DTG. Pharmacokinetic evaluation in rabbits showed significantly increased plasma half-life, area under the curve, and mean-residence time for DTG-Palmitate compared to DTG.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Microbiology
Nelson V. Simwela, W. Armand Guiguemde, Judith Straimer, Clement Regnault, Barbara H. Stokes, Luis E. Tavernelli, Fumiaki Yokokawa, Benjamin Taft, Thierry T. Diagana, Michael P. Barrett, Andrew P. Waters
Summary: This study used metabolomics technologies to characterize the potential targets of anti-malarial drug candidates and found that fast-acting leads induce a common biochemical theme in drug-exposed malaria parasites. These findings provide insights into the mode of action of fast drug candidates in future drug discovery programs.
MICROBIOLOGY SPECTRUM
(2023)
Review
Pharmacology & Pharmacy
Arnau Guasch-Girbau, Xavier Fernandez-Busquets
Summary: Malaria eradication has been a longstanding goal on the global health agenda, but the causative agents of the disease have developed mechanisms to evade immunity and drug resistance. Nanomedicine is considered a new strategy in the fight against malaria, and is already making an impact in diagnosis, prevention, and therapy. Next generation antimalarial drugs in development are being assessed for their potential use of nanotechnology.
Article
Pharmacology & Pharmacy
Paul Curley, James J. Hobson, Neill J. Liptrott, Edward Makarov, Amer Al-khouja, Lee Tatham, Christopher A. W. David, Helen Box, Megan Neary, Joanne Sharp, Henry Pertinez, David Meyers, Charles Flexner, Caren L. Freel Meyers, Larisa Poluektova, Steve Rannard, Andrew Owen
Summary: The study reports the feasibility and predicted antiviral activity of the semi-solid prodrug nanoparticle (SSPN) long-acting injectable (LAI) formulation for the prevention of HIV infection. Preclinical assessments show that the formulation has a prolonged pharmacokinetic half-life in animal models and can effectively suppress viral loads to prevent and control HIV infection.
Article
Infectious Diseases
Abdullahi Ahmad, Aurelia Prom, John Bradley, Mamadou Ndiath, Blessed Etoketim, Mamadou Bah, Jean-Pierre Van Geertruyden, Chris Drakeley, Teun Bousema, Jane Achan, Umberto D'Alessandro
Summary: The study assessed the impact of seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) on gametocyte carriage in asymptomatic P. falciparum infected children, with no evidence of increased gametocyte carriage before and after SMC treatment.
Article
Medicine, General & Internal
Adrienne E. Swanstrom, Robert J. Gorelick, Jorden L. Welker, Fabian Schmidt, Bing Lu, Kelly Wang, William Rowe, Matthew W. Breed, Kristin E. Killoran, Joshua A. Kramer, Duncan Donohue, James D. Roser, Paul D. Bieniasz, Theodora Hatziioannou, Cathi Pyle, James A. Thomas, Charles M. Trubey, Jim Zheng, Wade Blair, Stephen R. Yant, Jeffrey D. Lifson, Gregory Q. Del Prete
Summary: This study demonstrates that LEN has potent antiviral activity against stHIV-A19 and can prevent HIV-1 infection in a nonhuman primate model. The sustained plasma drug exposures of subcutaneous LEN support its potential as a long-acting PrEP for humans.
Review
Emergency Medicine
Brandon C. Maughan, Lisa Frueh, Marian S. McDonagh, Bryan Casciere, Jeffrey A. Kline
Summary: Studies show that outpatient management of low-risk PE patients leads to favorable outcomes, with few experiencing major adverse events such as mortality, recurrent VTE, or major bleeding within 90 days.
ACADEMIC EMERGENCY MEDICINE
(2021)
Article
Oncology
Oana A. Zeleznik, Raji Balasubramanian, Yibai Zhao, Lisa Frueh, Sarah Jeanfavre, Julian Avila-Pacheco, Clary B. Clish, Shelley S. Tworoger, A. Heather Eliassen
Summary: In a study primarily among premenopausal women, 11 metabolites were found to be associated with breast cancer risk, with 7 of them remaining significant even after adjustment for established risk factors.
Meeting Abstract
Oncology
Tengteng Wang, Yujing J. Heng, Gabrielle M. Baker, Vanessa C. Bret-Mounet, Susan E. Hankinson, Michelle D. Holmes, Wendy Y. Chen, Walter C. Willett, Bernard A. Rosner, Rulla M. Tamimi, A. Heather Eliassen
Article
Immunology
Anasuya C. Pal, Isaline Renard, Pallavi Singh, Pratap Vydyam, Joy E. Chiu, Sovitj Pou, Rolf W. Winter, Rozalia Dodean, Lisa Frueh, Aaron C. Nilsen, Michael K. Riscoe, J. Stone Doggett, Choukri Ben Mamoun
Summary: This study describes an optimized method for culturing Babesia duncani in a mouse model, which can be used to study the virulence of Babesia and develop new therapies for human babesiosis. The model combines continuous parasite replication in human erythrocytes with lethal infection in mice.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Environmental Sciences
Lidia Minguez-Alarcon, Lisa Frueh, Paige L. Williams, Tamarra James-Todd, Irene Souter, Jennifer B. Ford, Kathryn M. Rexrode, Antonia M. Calafat, Russ Hauser, Jorge E. Chavarro
Summary: This study investigates the association between urinary phenol concentrations and serum lipid levels in pregnant women. The results suggest that pregnant women with higher concentrations of urinary propylparaben and bisphenol A have higher levels of total cholesterol, non-HDL cholesterol, and LDL cholesterol in their serum.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Ophthalmology
Jae H. Kang, Mengyu Wang, Lisa Frueh, Bernard Rosner, Janey L. Wiggs, Tobias Elze, Louis R. Pasquale
Summary: This study evaluated racial/ethnic differences in primary open-angle glaucoma (POAG) using machine learning algorithms to identify regional visual field loss patterns. It found that black participants had higher risks of early and advanced visual field loss compared to non-Hispanic whites, while no differences were observed for Asians or Hispanic whites.
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
(2022)
Article
Substance Abuse
Alexandria Macmadu, Lisa Frueh, Alexandra B. Collins, Roxxanne Newman, Nancy P. Barnett, Josiah D. Rich, Melissa A. Clark, Brandon D. L. Marshall
Summary: This study examines the influence of overdoses occurring in social networks on individual overdose risk and characterizes drug use behaviors following the overdose of someone in the network. The findings show that some individuals increase their drug use following the overdose event, while others reduce their drug use and engage in protective behaviors. The study highlights the importance of enhancing network-based overdose prevention interventions and integrating bereavement support and mental health services for people who use drugs.
INTERNATIONAL JOURNAL OF DRUG POLICY
(2022)
Article
Substance Abuse
Alexandria Macmadu, Annajane Yolken, Lisa Frueh, Jai'el R. Toussaint, Roxxanne Newman, Brendan P. Jacka, Alexandra B. Collins, Brandon D. L. Marshall
Summary: The lack of Good Samaritan Law protections and harsh drug selling statutes in the USA hinders bystanders from seeking medical assistance for overdoses. This study found that police administered naloxone in approximately 10% of overdose incidents, with naloxone most often administered by others. Arrests at overdose events and incidents involving combative persons were rare.
HARM REDUCTION JOURNAL
(2022)
Article
Substance Abuse
Lisa Frueh, Alexandra B. B. Collins, Roxxanne Newman, Nancy P. P. Barnett, Josiah D. D. Rich, Melissa A. A. Clark, Brandon D. L. Marshall, Alexandria Macmadu
Summary: This study examines the impact of the COVID-19 pandemic on drug use behaviors among people who use drugs (PWUD) in Rhode Island. The findings highlight the multi-level influences of individual, network, institutional, and policy factors on drug use behaviors and overdose risk.
HARM REDUCTION JOURNAL
(2023)
Article
Multidisciplinary Sciences
Oana A. Zeleznik, Jae H. Kang, Jessica Lasky-Su, A. Heather Eliassen, Lisa Frueh, Clary B. Clish, Bernard A. Rosner, Tobias Elze, Pirro Hysi, Anthony Khawaja, Janey L. Wiggs, Louis R. Pasquale
Summary: Glaucoma is a leading cause of irreversible blindness worldwide, but its etiology is poorly understood. This study aimed to identify plasma metabolites associated with the risk of primary open-angle glaucoma (POAG) using case-control studies and cross-sectional studies. The results showed that higher levels of diglycerides and triglycerides were adversely associated with glaucoma, indicating their important role in glaucoma pathogenesis.
NATURE COMMUNICATIONS
(2023)
Article
Otorhinolaryngology
Oana A. Zeleznik, D. Bradley Welling, Konstantina Stankovic, Lisa Frueh, Raji Balasubramanian, Gary C. Curhan, Sharon G. Curhan
Summary: This case-control study investigated the association between circulating metabolites and persistent tinnitus. The study identified certain plasma metabolites and metabolite classes that were significantly associated with persistent tinnitus, providing insights into its pathophysiology and potential therapeutic targets.
JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY
(2023)
Article
Environmental Sciences
Rachit Sharma, Jamie L. Humphrey, Lisa Frueh, Ellen J. Kinnee, Perry E. Sheffield, Jane E. Clougherty
Summary: This study explores the association between asthma morbidity among children aged 5-17 years and exposures to pollution, temperature, social stressors, and neighborhood violent crime and socioeconomic deprivation. Results indicate that different pollutants and temperature exposures have varying effects on asthma morbidity depending on season and lag days, and the effects are modified by violent crime and socioeconomic deprivation in a non-linear manner.
ENVIRONMENTAL RESEARCH
(2023)
Article
Ophthalmology
Jae H. Kang, Oana Zeleznik, Lisa Frueh, Jessica Lasky-Su, A. Heather Eliassen, Clary Clish, Bernard A. Rosner, Louis R. Pasquale, Janey L. Wiggs
Summary: This study aimed to identify a prediagnostic plasma metabolomic signature associated with exfoliation glaucoma (XFG). Through the analysis of blood samples, lysophosphatidylcholines and phosphatidylethanolamine plasmalogens were found to be positively associated with XFG risk, while triacylglycerols and steroids (such as cortisone) were inversely associated with XFG risk.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Oncology
Oana A. Zeleznik, Raji Balasubramanian, Yumeng Ren, Deirdre K. Tobias, Bernard A. Rosner, Cheng Peng, Alaina M. Bever, Lisa Frueh, Sarah Jeanfavre, Julian Avila-Pacheco, Clary B. Clish, Samia Mora, Frank B. Hu, A. Heather Eliassen
Summary: The study found complex associations between circulating branched-chain amino acid (BCAA) levels and breast cancer risk, with menopausal status and timing influencing the relationship. Further research is needed to fully understand this complex relationship.
JNCI CANCER SPECTRUM
(2021)
Article
Microbiology
Heather J. Painter, Joanne M. Morrisey, Michael W. Mather, Lindsey M. Orchard, Cuyler Luck, Martin J. Smilkstein, Michael K. Riscoe, Akhil B. Vaidya, Manuel Llinas
Summary: The emergence of drug-resistant Plasmodium falciparum parasites poses a challenge to global malaria eradication efforts, highlighting the importance of identifying new antimalarial drugs. Studying the molecular mechanism of drug resistance has revealed a novel resistance mechanism that could potentially guide the development of future antimalarial combination therapies.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)