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A Potent Antimalarial Benzoxaborole Targets A Plasmodium Falciparum Cleavage And Polyadenylation Specificity Factor Homologue., Ebere Sonoiki, Caroline L. Ng, Marcus C. S. Lee, Denghui Guo, Yong-Kang Zhang, Yasheen Zhou, M. R. K. Alley, Vida Ahyong, Laura M. Sanz, Maria Jose Lafuente-Monasterio, Chen Dong, Patrick G. Schupp, Jiri Gut, Jenny Legac, Roland A. Cooper, Francisco-Javier Gamo, Joseph Derisi, Yvonne R. Freund, David A. Fidock, Philip J. Rosenthal

Natural Sciences and Mathematics | Faculty Scholarship

Benzoxaboroles are effective against bacterial, fungal and protozoan pathogens. We report potent activity of the benzoxaborole AN3661 against Plasmodium falciparum laboratory-adapted strains (mean IC50 32 nM), Ugandan field isolates (mean ex vivo IC50 64 nM), and murine P. berghei and P. falciparum infections (day 4 ED90 0.34 and 0.57 mg kg-1, respectively). Multiple P. falciparum lines selected in vitro for resistance to AN3661 harboured point mutations in pfcpsf3, which encodes a homologue of mammalian cleavage and polyadenylation specificity factor subunit 3 (CPSF-73 or CPSF3). CRISPR-Cas9-mediated introduction of pfcpsf3 mutations into parental lines recapitulated AN3661 resistance. PfCPSF3 homology models placed these …

Cytomegalovirus Serostatus, Inflammation, And Antibody Response To Influenza Vaccination In Older Adults: The Moderating Effect Of Beta Blockade, Rebecca G. Reed, Richard N. Greenberg, Suzanne C. Segerstrom

Psychology Faculty Publications

Cytomegalovirus (CMV) has been implicated as a factor in immunosenescence, including poor antibody response to vaccination and higher immune activation and inflammation. Some people may be more or less vulnerable to the negative effects of CMV. The present investigation tested the effects of beta-blocker use and chronological age on the associations between CMV and immunity in adults aged 60–91 (N=98; 69% CMV seropositive) who were administered the trivalent influenza vaccine for up to 5 years. Peak antibody response, corrected for baseline, and spring (persistent) antibody response, corrected for peak, were assessed, as well as beta-2 microglobulin (β2μ) and interleukin-6 (IL-6). …

Mice With Infectious Colitis Exhibit Linear Growth Failure And Subsequent Catch-Up Growth Related To Systemic Inflammation And Igf-1, Mark D. Deboer, Vidhya Vijayakumar, Meiqing Gong, John L. Fowlkes, Rachel M. Smith, Fernando Ruiz-Perez, James P. Nataro

Barnstable Brown Diabetes Center Faculty Publications

In developing communities, intestinal infection is associated with poor weight gain and linear-growth failure. Prior translational animal models have focused on weight gain investigations into key contributors to linear growth failure have been lacking. We hypothesized that murine intestinal infection with Citrobacter-rodentium would induce linear-growth failure associated with systemic inflammation and suppressed serum levels of insulin-like growth factor-1 (IGF-1). We evaluated 4 groups of mice infected or sham-infected on day-of-life 28: uninfected-controls, wild-type C.-rodentium-infected, partially-attenuated C. rodentium-infected (with deletion of 3 serine protease genes involved in colonization), and pair-fed (given the amount of daily food consumed by the …

Parvovirus B19 Ns1 Protein Induces Cell Cycle Arrest At G2-Phase By Activating The Atr-Cdc25c-Cdk1 Pathway., Peng Xu, Zhe Zhou, Min Xiong, Wei Zou, Xuefeng Deng, Safder S. Ganaie, Steve Kleiboeker, Jianxin Peng, Kaiyu Liu, Shengqi Wang, Shui Qing Ye, Jianming Qiu

Manuscripts, Articles, Book Chapters and Other Papers

Human parvovirus B19 (B19V) infection of primary human erythroid progenitor cells (EPCs) arrests infected cells at both late S-phase and G2-phase, which contain 4N DNA. B19V infection induces a DNA damage response (DDR) that facilitates viral DNA replication but is dispensable for cell cycle arrest at G2-phase; however, a putative C-terminal transactivation domain (TAD2) within NS1 is responsible for G2-phase arrest. To fully understand the mechanism underlying B19V NS1-induced G2-phase arrest, we established two doxycycline-inducible B19V-permissive UT7/Epo-S1 cell lines that express NS1 or NS1mTAD2, and examined the function of the TAD2 domain during G2-phase arrest. The results confirm that the …

Outpatient Parenteral Antimicrobial Therapy In Pediatric Medicaid Enrollees., Jennifer Goldman, Troy Richardson, Jason G. Newland, Brian R. Lee, Jeffrey S. Gerber, Matt Hall, Matthew Kronman, Adam L. Hersh

Manuscripts, Articles, Book Chapters and Other Papers

Background: Outpatient parenteral antimicrobial therapy (OPAT) is overused in cases where highly bioavailable oral alternatives would be equally effective. However, the scope of OPAT use for children nationwide is poorly understood. Our objective was to characterize OPAT use and clinical outcomes for a large population of pediatric Medicaid enrollees treated with OPAT.

Methods: We analyzed the Truven MarketScan Medicaid claims database between 2009 and 2012. An OPAT episode was identified by capturing children with claims data indicating home infusion therapy for an intravenous antimicrobial. We characterized OPAT use by describing patient demographics, diagnoses, and antimicrobials prescribed. We categorized an antimicrobial …

Respiratory Syncytial Virus Hospitalization Risk In The Second Year Of Life By Specific Congenital Heart Disease Diagnoses, Deborah Friedman, J Fryzek, X Jiang, A Bloomfield, C Ambrose, P Wong

NYMC Faculty Publications

Children with hemodynamically significant congenital heart disease (CHD) are at elevated risk of morbidity and mortality due to respiratory syncytial virus (RSV) disease compared to their healthy peers. Previous studies have demonstrated lower RSV hospitalization risk among all children with CHD at 12-23 months of age versus 0-11 months of age. However, RSV hospitalization risk at 12-23 months of age by specific CHD diagnosis has not been characterized. Both case-control and cohort studies were conducted using data from the US National Inpatient Sample from 1997 to 2013 to characterize relative risk of RSV hospitalization among children 12-23 months of age …

Gvhd After Umbilical Cord Blood Transplantation For Acute Leukemia: An Analysis Of Risk Factors And Effect On Outcomes, Y Chen, T Wang, Michael T. Hemmer, A Alousi, J Pidala, Mitchell Cairo, C Cutler

NYMC Faculty Publications

Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed 1404 umbilical cord bloodtransplantation (UCBT) patients (single (<18 years)=810, double (⩾18 years)=594) with acute leukemia to define the incidence of acuteGvHD (aGvHD) and chronic GvHD (cGvHD), analyze clinical risk factors and investigate outcomes. After single UCBT, 100-day incidence of grade II-IV aGvHD was 39% (95% confidence interval (CI), 36-43%), grade III-IV aGvHD was 18% (95% CI, 15-20%) and 1-year cGvHD was 27% (95% CI, 24-30%). After double UCBT, 100-day incidence of grade II-IV aGvHD was 45% (95% CI, 41-49%), grade III-IV aGvHD was 22% (95% CI, 19-26%) and …

High-Dose Immunosuppressive Therapy And Autologous Hct For Relapsing-Remitting Ms., Richard A Nash, George J Hutton, Michael K Racke, Uday Popat, Steven M Devine, Kaitlyn C Steinmiller, Linda M Griffith, Paolo A Muraro, Harry Openshaw, Peter H Sayre, Olaf Stuve, Douglas L Arnold, Mark H Wener, George E Georges, Annette Wundes, George H Kraft, J D Bowen

Articles, Abstracts, and Reports

OBJECTIVE: To evaluate the safety, efficacy, and durability of multiple sclerosis (MS) disease stabilization after high-dose immunosuppressive therapy (HDIT) and autologous hematopoietic cell transplantation (HCT).

METHODS: High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT-MS) is a phase II clinical trial of HDIT/HCT for patients with relapsing-remitting (RR) MS who experienced relapses with disability progression (Expanded Disability Status Scale [EDSS] 3.0-5.5) while on MS disease-modifying therapy. The primary endpoint was event-free survival (EFS), defined as survival without death or disease activity from any one of: disability progression, relapse, or new lesions on MRI. Participants were evaluated through 5 years posttransplant. …

Risk Factors For Poor Multidrug-Resistant Tuberculosis Treatment Outcomes In Kyiv Oblast, Ukraine, Omowunmi Aibana, Mariya Bachmaha, Viatcheslav Krasiuk, Natasha Rybak, Timothy P Flanigan, Vasyl Petrenko, Megan B Murray

Faculty, Staff and Student Publications

BACKGROUND: Ukraine is among ten countries with the highest burden of multidrug- resistant TB (MDR-TB) worldwide. Treatment success rates for MDR-TB in Ukraine remain below global success rates as reported by the World Health Organization. Few studies have evaluated predictors of poor MDR-TB outcomes in Ukraine.

METHODS: We conducted a retrospective analysis of patients initiated on MDR-TB treatment in the Kyiv Oblast of Ukraine between January 01, 2012 and March 31st, 2015. We defined good treatment outcomes as cure or completion and categorized poor outcomes among those who died, failed treatment or defaulted. We used logistic regression analyses to identify …

Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial Of Rg7667, A Combination Monoclonal Antibody, For Prevention Of Cytomegalovirus Infection In High-Risk Kidney Transplant Recipients, Julie H. Ishida, Anita Patel, Aneesh K. Mehta, Philippe Gatault, Jacqueline M. Mcbride, Tracy Burgess, Michael A. Derby, David R. Snydman, Brinda Emu, Becket Feierbach, Ashley E. Fouts, Mauricio Maia, Rong Deng, Carrie M. Rosenberger, Lynn A. Gennaro, Natalee S. Striano, X C. Liao, Jorge A. Tavel

Nephrology Articles

Cytomegalovirus (CMV) infection is a significant complication after kidney transplantation. We examined the ability of RG7667, a combination of two monoclonal antibodies, to prevent CMV infection in high-risk kidney transplant recipients in a randomized, double-blind, placebo-controlled trial. CMV-seronegative recipients of a kidney transplant from a CMV-seropositive donor (D+R-) were randomized to receive RG7667 (n = 60) or placebo (n = 60) at the time of transplant and 1, 4, and 8 weeks posttransplant. Patients were monitored for CMV viremia every 1 to 2 weeks posttransplant for 24 weeks. Patients who had seroconverted (D+R+) or withdrawn before dosing were excluded from …

Acceptability Of Hiv Testing Sites Among Rural And Urban African Americans Who Use Cocaine, D. Keith Branham, Tyrone F. Borders, Katharine E. Stewart, Geoffrey M. Curran, Brenda M. Booth

Health Management and Policy Faculty Publications

African Americans (AAs) who use cocaine in the Southern region of the U.S. have a relatively high risk of HIV and need for HIV testing. Among this group, those residing in rural areas may have less favorable opinions about common HIV testing sites, which could inhibit HIV testing. We examined rural/urban variations in their acceptability of multiple HIV testing sites (private physician clinic, local health department, community health center, community HIV fair, hospital emergency department, blood plasma donation center, drug abuse treatment facility, and mobile van or community outreach worker). Results from partial proportional odds and logistic regression analyses indicate …

Nephrotoxicity During Vancomycin Therapy In Combination With Piperacillin-Tazobactam Or Cefepime, Wilbur Cliff Rutter, Jessica N. Cox, Craig A. Martin, Donna R. Burgess, David S. Burgess

Pharmacy Practice and Science Faculty Publications

Recent reports have demonstrated that vancomycin (VAN) may lead to an increase in the incidence of acute kidney injury (AKI) when it is combined with antipseudomonal beta-lactams. This study compared the incidence of AKI associated with VAN plus piperacillin-tazobactam (TZP) or cefepime (FEP). This was a retrospective, matched cohort study that was conducted at an academic medical center between September 2010 and September 2014 and that included adult patients without severe chronic or structural kidney disease, dialysis, pregnancy, cystic fibrosis, or a hospital transfer receiving TZP-VAN or FEP-VAN for at least 48 h. The primary outcome was the difference in …

Metronidazole Metabolism In Neonates And The Interplay Between Ontogeny And Genetic Variation., Laura A. Wang, Daniel Gonzalez, J Steven Leeder, Rachel F. Tyndale, Robin E. Pearce, Daniel K. Benjamin, Gregory L. Kearns, Michael Cohen-Wolkowiez, Best Pharmaceuticals For Children Act-Pediatric Trials Network Steering Committee

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Metronidazole Metabolism In Neonates And The Interplay Between Ontogeny And Genetic Variation., Laura A. Wang, Daniel Gonzalez, J Steven Leeder, Rachel F. Tyndale, Robin E. Pearce, Daniel K. Benjamin, Gregory L. Kearns, Michael Cohen-Wolkowiez, Best Pharmaceuticals For Children Act-Pediatric Trials Network Steering Committee

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Clinical Risk Factors For Infective Endocarditis In Staphylococcus Aureus Bacteremia, Vincent Bryan D Salvador, Bikash Chapagain, Astha Joshi, Debra J Brennessel

The Texas Heart Institute Journal

Crucial to the management of staphylococcal bacteremia is an accurate evaluation of associated endocarditis, which has both therapeutic and prognostic implications. Because the clinical presentation of endocarditis can be nonspecific, the judicious use of echocardiography is important in distinguishing patients at high risk of developing endocarditis. In the presence of high-risk clinical features, an early transesophageal echocardiogram is warranted without prior transthoracic echocardiography.

The purpose of this study was to investigate the clinical risk factors for staphylococcal infective endocarditis that might warrant earlier transesophageal echocardiography and to describe the incidence of endocarditis in cases of methicillin-resistant and methicillin-sensitive Staphylococcus aureus …

Qualitative Study Of Primary Care Clinicians' Views On Point-Of-Care Testing For C-Reactive Protein For Acute Respiratory Tract Infections In Family Medicine., Victoria Hardy, Matthew Thompson, Gina A Keppel, William Alto, M Ashworth Dirac, Jon Neher, Christopher Sanford, Jaime Hornecker, Allison Cole

Articles, Abstracts, and Reports

OBJECTIVE: To explore clinicians views of the barriers and facilitators to use of C-reactive protein (CRP) point-of-care tests (POCT) in US family medicine clinics for the management of acute respiratory tract infections (ARTIs) in adults.

SETTING: Five family medicine clinics across two US states.

PARTICIPANTS: 30 clinicians including 18 physicians, 9 physician residents, 2 physician assistants and 1 nurse practitioner, took part in the study.

DESIGN: A qualitative study using a grounded theory approach to thematically analyse focus group interviews.

RESULTS: These clinicians had limited access to diagnostic tests for patients with ARTI, and very little knowledge of CRP POCT. …

A Cationic Amphiphilic Random Copolymer With Ph-Responsive Activity Against Methicillin-Resistant Staphylococcus Aureus., Sungyoup Hong, Haruko Takahashi, Enrico T Nadres, Hamid Mortazavian, Gregory Caputo, John G Younger, Kenichi Kuroda

College of Science & Mathematics Departmental Research

In this report, we demonstrate the pH-dependent, in vitro antimicrobial activity of a cationic, amphiphilic random copolymer against clinical isolates of drug-resistant Staphylococcus aureus. The polymer was developed toward a long-term goal of potential utility in the treatment of skin infections. The proposed mechanism of action of the polymer is through selectively binding to bacterial membranes and subsequent disruption of the membrane structure/integrity, ultimately resulting in bacterial cell death. The polymer showed bactericidal activity against clinical isolates of methicillin-resistant or vancomycin-intermediate S. aureus. The polymer was effective in killing S. aureus at neutral pH, but inactive under acidic conditions (pH …

Addendum Guidelines For The Prevention Of Peanut Allergy In The United States: Report Of The National Institute Of Allergy And Infectious Diseases–Sponsored Expert Panel, Alkis Togias, Susan F. Cooper, Maria L. Acebal, Amal Assa'ad, James R. Baker, Lisa A. Beck, Julie Block, Carol Byrd-Bredbenner, Edmond S. Chan, Lawrence F. Eichenfield, David M Fleischer, George J. Fuchs Iii, Glenn T. Furuta, Matthew J. Greenhawt, Ruchi S. Gupta, Michele Habich, Stacie M. Jones, Kari Keaton, Antonella Muraro, Marshall Plaut, Lanny J. Rosenwasser, Daniel Rotrosen, Hugh A. Sampson, Lynda C. Schneider, Scott H. Sicherer, Robert Sidbury, Jonathan Spergel, David R. Stukus, Carina Venter, Joshua A. Boyce

Pediatrics Faculty Publications

Background: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy.

Objectives: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy …

Improving Adolescent Hpv Vaccination In A Randomized Controlled Cluster Trial Using The 4 Pillars™ Practice Transformation Program., Richard K. Zimmerman, Krissy K. Moehling, Chyongchiou J. Lin, Song Zhang, Jonathan M. Raviotta, Evelyn C. Reis, Sharon Humiston, Mary Patricia Nowalk

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Uptake of meningococcal vaccine (MCV) and tetanus, diphtheria and pertussis (Tdap) vaccine among adolescents has approached Healthy People 2020 goals, but human papillomavirus (HPV) vaccination has not. This study evaluated an intervention using the 4 Pillars™ Practice Transformation Program to increase HPV, MCV and Tdap uptake among adolescents in primary care practices.

METHODS: Practices with at least 50 patients 11-17years old with estimated vaccination rates less than national goals, were assigned to intervention (n=11) and control (n=11) groups in a randomized controlled cluster trial; 9 intervention and 11 control sites completed the study. The baseline and active study periods …

Sustained Nitric Oxide-Releasing Nanoparticles Interfere With Methicillin-Resistant Staphylococcus Aureus Adhesion And Biofilm Formation In A Rat Central Venous Catheter Model., Mircea Radu Mihu, Vitor Cabral, Rodney Pattabhi, Moses T Tar, Kelvin P Davies, Adam J Friedman, Luis R Martinez, Joshua D Nosanchuk

Dermatology Faculty Publications

Staphylococcus aureus is frequently isolated in the setting of infections of indwelling medical devices, which are mediated by the microbe's ability to form biofilms on a variety of surfaces. Biofilm-embedded bacteria are more resistant to antimicrobial agents than their planktonic counterparts and often cause chronic infections and sepsis, particularly in patients with prolonged hospitalizations. In this study, we demonstrate that sustained nitric oxide-releasing nanoparticles (NO-np) interfere with S. aureus adhesion and prevent biofilm formation on a rat central venous catheter (CVC) model of infection. Confocal and scanning electron microscopy showed that NO-np-treated staphylococcal biofilms displayed considerably reduced thicknesses and bacterial …

Sting Expression And Response To Treatment With Sting Ligands In Premalignant And Malignant Disease., Jason R Baird, Zipei Feng, Hong D Xiao, David Friedman, Ben Cottam, Bernard A Fox, Gwen Kramer, Rom S Leidner, Richard Bryan Bell, Kristina H Young, Marka R Crittenden, Michael J Gough

Articles, Abstracts, and Reports

Human papilloma virus positive (HPV+) tumors represent a large proportion of anal, vulvar, vaginal, cervical and head and neck squamous carcinomas (HNSCC) and late stage invasive disease is thought to originate from a premalignant state. Cyclic dinucleotides that activate STimulator of INterferon Genes (STING) have been shown to cause rapid regression of a range of advanced tumors. We aimed to investigate STING ligands as a novel treatment for papilloma. We tested therapies in a spontaneous mouse model of papilloma of the face and anogenital region that histologically resembles human HPV-associated papilloma. We demonstrate that STING ligands cause rapid regression of …

Bid-Induced Release Of Aif/Endog From Mitochondria Causes Apoptosis Of Macrophages During Infection With, Wei-Lin Hu, Hai-Yan Dong, Yang Li, David M. Ojcius, Shi-Jun Li, Jie Yan

All Dugoni School of Dentistry Faculty Articles

Leptospirosis is a global zoonotic infectious disease caused by pathogenic Leptospira species. Leptospire-induced macrophage apoptosis through the Fas/FasL-caspase-8/3 pathway plays an important role in the survival and proliferation of the pathogen in hosts. Although, the release of mitochondrial apoptosis-inducing factor (AIF) and endonuclease G (EndoG) in leptospire-infected macrophages has been described, the mechanisms linking caspase and mitochondrion-related host-cell apoptosis has not been determined. Here, we demonstrated that leptospire-infection induced apoptosis through mitochondrial damages in macrophages. Apoptosis was caused by the mitochondrial release and nuclear translocation of AIF and/or EndoG, leading to nuclear DNA fragmentation. However, the mitochondrion-related CytC-caspase-9/3 pathway was …

Mononuclear-Macrophages But Not Neutrophils Act As Major Infiltrating Anti-Leptospiral Phagocytes During Leptospirosis., Xu Chen, Shi-Jun Li, David M. Ojcius, Ai-Hua Sun, Wei-Lin Hu, Xu'ai Lin, Jie Yan

All Dugoni School of Dentistry Faculty Articles

OBJECTIVE: To identify the major infiltrating phagocytes during leptospirosis and examine the killing mechanism used by the host to eliminate Leptospira interrogans.

METHODS: Major infiltrating phagocytes in Leptospira-infected C3H/HeJ mice were detected by immunohistochemistry. Chemokines and vascular endothelial cell adhesion molecules (VECAMs) of Leptospira-infected mice and leptospirosis patients were detected by microarray and immunohistochemistry. Leptospira-phagocytosing and -killing abilities of human or mouse macrophages and neutrophils, and the roles of intracellular ROS, NO and [Ca2+]i in Leptospira-killing process were evaluated by confocal microscopy and spectrofluorimetry.

RESULTS: Peripheral blood mononuclear-macrophages rather than neutrophils were the main infiltrating phagocytes in the lungs, liver …

Differential Phenotypes Of Memory Cd4 And Cd8 T Cells In The Spleen And Peripheral Tissues Following Immunostimulatory Therapy., Gail D Sckisel, Annie Mirsoian, Christine M Minnar, Marka R Crittenden, Brendan Curti, Jane Q Chen, Bruce R Blazar, Alexander D Borowsky, Arta M Monjazeb, William J Murphy

Articles, Abstracts, and Reports

BACKGROUND: Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis. In this study we expand upon our previous work by evaluating CD4 and CD8-T cell phenotype and distribution in peripheral organs which are more representative …

An Indicator Cell Assay For Blood-Based Diagnostics., Samuel A Danziger, Leslie R Miller, Karanbir Singh, G Adam Whitney, Elaine R Peskind, Ge Li, Robert J Lipshutz, John D Aitchison, Jennifer J Smith

Articles, Abstracts, and Reports

We have established proof of principle for the Indicator Cell Assay Platform™ (iCAP™), a broadly applicable tool for blood-based diagnostics that uses specifically-selected, standardized cells as biosensors, relying on their innate ability to integrate and respond to diverse signals present in patients' blood. To develop an assay, indicator cells are exposed in vitro to serum from case or control subjects and their global differential response patterns are used to train reliable, disease classifiers based on a small number of features. In a feasibility study, the iCAP detected pre-symptomatic disease in a murine model of amyotrophic lateral sclerosis (ALS) with 94% …

Bis(N-Amidinohydrazones) And N-(Amidino)-N'-Aryl-Bishydrazones: New Classes Of Antibacterial/Antifungal Agents, Sanjib K. Shrestha, Liliia M. Kril, Keith D. Green, Stefan Kwiatkowski, Vitaliy M. Sviripa, Justin Robert Nickell, Linda Phyliss Dwoskin, David S. Watt, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

The emergence of multidrug-resistant bacterial and fungal strains poses a threat to human health that requires the design and synthesis of new classes of antimicr obial agents. We evaluated bis(N-amidinohydrazones) and N-(amidino)-N'-aryl-bishydrazones for their antibacterial and antifungal activities against panels of Gram-positive/Gram-negative bacteria as well as fungi. We investigated their potential to develop resistance against both bacteria and fungi by a multi-step, resistance-selection method, explored their potential to induce the production of reactive oxygen species, and assessed their toxicity. In summary, we found that these compounds exhibited broad-spectrum antibacterial and antifungal activities against most of …

Impact Of Simultaneous Exposure To Arboviruses On Infection And Transmission By Aedes Aegypti Mosquitoes, Claudia Rückert, James Weger-Lucarelli, Selene M. Garcia-Luna, Michael C. Young, Alex D. Byas, Reyes A. Murrieta, Joseph R. Fauver, Gregory D. Ebel

Journal Articles: Epidemiology

The recent emergence of both chikungunya and Zika viruses in the Americas has significantly expanded their distribution and has thus increased the possibility that individuals may become infected by more than one Aedes aegypti-borne virus at a time. Recent clinical data support an increase in the frequency of coinfection in human patients, raising the likelihood that mosquitoes could be exposed to multiple arboviruses during one feeding episode. The impact of coinfection on the ability of relevant vector species to transmit any of these viruses (that is, their vector competence) has not been determined. Thus, we here expose Ae. aegypti mosquitoes …

Next Generation Sequencing Reveals The Antibiotic Resistant Variants In The Genome Of Pseudomonas Aeruginosa, B. Ramanathan, H.M. Jindal, C.F. Le, R. Gudimella, A. Anwar, R. Razali, J. Poole-Johnson, R. Manikam, S.D. Sekaran

Research Publications (2016 to 2020)

Rapid progress in next generation sequencing and allied computational tools have aided in identification of single nucleotide variants in genomes of several organisms. In the present study, we have investigated single nucleotide polymorphism (SNP) in ten multi-antibiotic resistant Pseudomonas aeruginosa clinical isolates. All the draft genomes were submitted to Rapid Annotations using Subsystems Technology (RAST) web server and the predicted protein sequences were used for comparison. Non-synonymous single nucleotide polymorphism (nsSNP) found in the clinical isolates compared to the reference genome (PAO1), and the comparison of nsSNPs between antibiotic resistant and susceptible clinical isolates revealed insights into the genome variation. …

Neglected Intestinal Parasites, Malnutrition And Associated Key Factors: A Population Based Cross-Sectional Study Among Indigenous Communities In Sarawak, Malaysia, Y. Rajoo, S. Ambu, Y.A.L. Lim, K. Rajoo, S.C. Tey, C.W. Lu, R. Ngui

Research Publications (2016 to 2020)

Intestinal parasitic infections (IPIs) have been recognized as one of the most significant causes of illness among disadvantaged communities. Many studies have been conducted on the prevalence of IPIs in Malaysia. However, these studies mostly focused on the indigenous groups in Peninsular Malaysia. The present study was conducted to provide the current baseline data on prevalence of IPIs, anaemia, malnutrition and associated risk factors among the indigenous communities in Sarawak, situation at northwest Borneo island of Malaysia. A cross sectional study was conducted among the longhouses communities. Stool samples were obtained and examined for the presence of IPIs using microscopy …

Cellular And Molecular Mechanisms Underlying Alcohol-Induced Aggressiveness Of Breast Cancer, Yongchao Wang, Mei Xu, Zun-Ji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Breast cancer is a leading cause of morbidity and mortality in women. Both Epidemiological and experimental studies indicate a positive correlation between alcohol consumption and the risk of breast cancer. While alcohol exposure may promote the carcinogenesis or onset of breast cancer, it may as well enhance the progression and aggressiveness of existing mammary tumors. Recent progress in this line of research suggests that alcohol exposure is associated with invasive breast cancer and promotes the growth and metastasis of mammary tumors. There are multiple potential mechanisms involved in alcohol-stimulated progression and aggressiveness of breast cancer. Alcohol may increase the mobility …