Attending Physician in Cardiology (Fee-Basis) at VA Palo Alto Healthcare System, Post-doctoral Research Fellow at Stanford Cardiovascular Institute, PhD Candidate in Epidemiology and Population Health Sciences. Graduate of Stanford Internal Medicine / Global Health Residency / Chief Resident, and Cardiology Fellowship Programs.
My professional interests include epidemiology and health services research focused on heart disease and environmental determinants of cardiovascular disorders, particularly in global vulnerable populations. I also have a longstanding interest in studying and improving the quality of care for neglected tropical heart diseases of low- and middle-income countries, chief among them rheumatic heart disease. I consider myself methodologically agnostic, and incorporate classic descriptive/analytic epidemiology, big data/outcomes analysis, health systems modeling, and geographic information services techniques in my work.
Member (Postdoc), Cardiovascular Institute
Honors & Awards
Alpha Omega Alpha Medical Honor Society, AOA, Stanford University Chapter (2017)
Gold Humanism Honor Society, Arnold P. Gold Foundation (2012)
TL1 Gold Ribbon Presentation, Association for Clinical and Translational Science (2018)
Stanford Cardiovascular Institute Travel Award, Stanford Cardiovascular Institute (2018)
Johnson and Johnson Global Health Scholar, Yale/Stanford Johnson & Johnson Global Health Scholars Program (2015)
Johnson and Johnson Global Health Scholar, Yale/Stanford Johnson & Johnson Global Health Scholars Program (2014)
Asian Pacific American Medical Student Association Global Health Fellowship, Asian Pacific American Medical Student Association (2012)
Stanford Medical Scholars Research Fellowship, Stanford University School of Medicine (2009-2011)
The John E. Linck III Memorial Graduation Prize, Yale University (2008)
Yale College Dean’s Research Fellowship in the Sciences, Yale University (2007)
Yale Science and Engineering Research Presentation Travel Prize, Yale University (2007)
1st Place Presentation, Yale Undergraduate Research Symposium in the Biological Sciences, Yale University (2007)
The Paul K. and Evalyn Elizabeth Cook Richter Summer Fellowship, Yale University (2007)
The Gary Stein Memorial Internship, Yale University (2006)
Robert C. Byrd Congressional Honors Scholarship, United States Department of Education (2005)
Professional Affiliations and Activities
Scientific Subcommittee Member; Council on Rheumatic Fever, Endocarditis, and Kawasaki Disease, American Heart Association (2020 - Present)
Faculty Fellow, Stanford Center for Innovation in Global Health (2016 - Present)
Representative, Chief Resident's Council, Department of Graduate Medical Education, Stanford University Medical Center (2016 - 2017)
Representative,Committee on Residency Reform, Department of Medicine, Stanford University Medical Center (2014 - 2016)
Resident Member, American College of Cardiology (2015 - 2017)
Resident Member, American College of Physicians (2013 - 2016)
Member, Stanford Center for Population Health Sciences (2015 - Present)
Member, Stanford Society of Physician Scholars (2013 - Present)
Education & Certifications
Fellowship, Stanford Hospitals & Clinics, Cardiology (2021)
Chief Resident, Stanford Hospitals & Clinics, Internal Medicine (2017)
Residency, Stanford Hospital & Clinics, Internal Medicine (2016)
MS, Stanford University, Epidemiology, Clinical Research (2018)
MD, Stanford University, Clinical Research, Immunology, Global Health (2013)
BS, Yale University, Molecular, Cellular & Developmental Biology (2008)
Non-degree Program, American Heart Association (AHA) Ten-Day Seminar on the Epidemiology and Prevention of Cardiovascular Disease, Epidemiology (2017)
Non-degree Program, Hasso Plattner Institute of Design at Stanford University, Entrepreneurial Design for Extreme Affordability Program (2012)
Service, Volunteer and Community Work
Hepatitis B Clinic Coordinator, Pacific Free Clinic (2009 - 2009)
- Created protocols, staffed, and managed the Hepatitis B program at Pacific Free Clinic,a student-run health clinic providing medical care for uninsured and underserved populations in the San Jose, CA area.
- Screened and vaccinated at-risk individuals against Hepatitis B virus, monitored infected patients, and reported epidemiological data to the Santa Clara Department of Public Health.
San Jose, CA
Clinical Volunteer, Arbor Free Clinic (2008 - 2013)
- Provided medical care at student-run clinic delivering health care for uninsured and underserved populations in the East Palo Alto, CA area.
Menlo Park, CA
Intern, Nyaya Health (2006 - 2008)
- Developed information sharing infrastructure for nonprofit NGO collaborating with the Nepali government to construct and run a hospital in rural Nepal.
- Traveled to Kathmandu and Sanfebagar to recruit clinic staff, test telecommunications devices for telemedicine opportunities, and perform administrative duties on behalf of the clinic with UNICEF and the Nepali National Center for STD and AIDS Control.
Health Educator, Yale University (2004 - 2005)
Teaching member of initiative to write, teach, and test a health education curriculum for New Haven, CT high school students
New Haven, CT
Community Associate, Stanford University (2009 - 2011)
Residential advisor in charge of maintaining graduate student safety and wellness through workshops, mentoring, social programming, and mental health initiatives
Johnson & Johnson Global Health Scholar, Yale-Stanford Johnson & Johnson Global Health Scholars Program (2015)
Delivered care for patients and taught medical students and interns at the University Central Hospital of Kigali (CHUK) in Kigali, Rwanda.
Andrew Chang, Carey Lee, Pamela Pavkov, Karen Lee, Michael Strasser. "United States Patent Attorney docket number: S11-190 Provisional Patent: “Low Cost Bubble CPAP Device”", Jun 1, 2011
Travel, History, Anthroplogy, Writing, Art Appreciation, Cooking, Football, Hiking
Current Research and Scholarly Interests
My research interests center around the epidemiology, environmental determinants, and health services dimensions of heart disease, with an emphasis on vulnerable populations, both international and domestic. Current projects include the development of novel care quality metrics for use in rheumatic heart disease in East Africa, testing of low sodium salt substitutes in South Asia, describing the global patterns of cardiovascular multimorbidity, and assessing the cardiovascular impacts of cyclical climate change-associated major environmental events. Other research interests include cost-effectiveness analysis, health economics, and device/service innovation for low-resource settings.
Current Clinical Interests
- Cardiovascular Disease
- Rheumatic Heart Disease
- Valvular Heart Disease
- Atrial Fibrillation
Researcher, Stanford University School of Medicine, Department of Hematology (2009 - 2012)
- Primary Investigator: Peter Lee, M.D.
- Project: Perturbations of immune cell (dendritic cell and T-cell) spatial distribution within tumor-draining lymph nodes of breast cancer patients
- Relevant Skills: Human pathology specimen handling, immunohistochemistry, and computational imaging
Teaching Assistant, Stanford University School of Medicine (2010 - 2011)
- Course Directors: Dr. Andrew Connolly and Dr. Julie Theriot
- Lectured and supervised laboratory exercises for core first-year medical student cell biology and histology class
Community Associate, Stanford University Graduate Life Office (2009 - 2011)
- Residential advisor in charge of maintaining graduate student safety and wellness through workshops, mentoring, social programming, and mental health initiatives
Research Assistant, Yale University School of Medicine, Department of Neurobiology (2005 - 2008)
- Primary Investigator: Gordon M. Shepherd, M.D., Ph.D.
- Project: Information coding in the murine brain and construction of odotypic maps in the olfactory bulb via localization of pseudorabies virus tracing vector
- Relevant Skills: Mouse stereotactic microsurgery, fluorescent microscopy, histology, and computational imaging
New Haven, CT
Clinical Profile and Outcomes of Rheumatic Heart Disease Patients Undergoing Surgical Valve Procedures in Uganda.
2023; 18 (1): 62
Chronic valvular heart disease is a well-known, long-term complication of acute rheumatic fever (ARF), which remains a major public health problem in low- and middle-income countries. Access to surgical management remains limited. Outcomes of the minority proportion of patients that access surgery have not been described in Uganda.To describe the volume and type of rheumatic heart disease (RHD) valvular interventions and the outcomes of operated patients in the Uganda RHD registry.We performed a retrospective cohort study of all valve surgery procedures identified in the Uganda RHD registry through December 2021.Three hundred and sixty-seven surgical procedures were performed among 359 patients. More than half were among young (55.9% were ≤20 years of age), female (59.9%) patients. All patients were censored at 15 years. The median (IQR) follow up period was 43 (22,79) months. Nearly half of surgeries (46.9%) included interventions on multiple valves, and most valvular operations were replacements with mechanical prostheses (96.6%). Over 70% of the procedures were sponsored by charity organizations. The overall mortality of patients who underwent surgery was 13% (47/359), with over half of the mortalities occurring within the first year following surgery (27/47; 57.4%). Fifteen-year survival or freedom from re-operation was not significantly different between those receiving valve replacements and those receiving valve repair (log-rank p = 0.76).There has been increasing access to valve surgery among Ugandan patients with RHD. Post-operative survival is similar to regionally reported rates. The growing cohort of patients living with prosthetic valves necessitates national expansion and decentralization of post-operative care services. Major reliance on charity funding of surgery is unsustainable, thus calling for locally generated and controlled support mechanisms such as a national health insurance scheme. The central illustration (Figure 1) provides a summary of our findings and recommendations.
View details for DOI 10.5334/gh.1260
View details for PubMedID 38028964
View details for PubMedCentralID PMC10655755
Healthcare provider-targeted mobile applications to diagnose, screen, or monitor communicable diseases of public health importance in low- and middle-income countries: A systematic review.
PLOS digital health
2023; 2 (10): e0000156
Communicable diseases remain a leading cause of death and disability in low- and middle-income countries (LMICs). mHealth technologies carry considerable promise for managing these disorders within resource-poor settings, but many existing applications exclusively represent digital versions of existing guidelines or clinical calculators, communication facilitators, or patient self-management tools. We thus systematically searched PubMed, Web of Science, and Cochrane Central for studies published between January 2007 and October 2019 involving technologies that were mobile phone- or tablet-based; able to screen for, diagnose, or monitor a communicable disease of importance in LMICs; and targeted health professionals as primary users. We excluded technologies that digitized existing paper-based tools or facilitated communication (i.e., knowledge-based algorithms). Extracted data included disease category, pathogen type, diagnostic method, intervention purpose, study/target population, sample size, study methodology, development stage, accessory requirement, country of development, operating system, and cost. Given the search timeline, studies involving COVID-19 were not included in the analysis. Of 13,262 studies identified by the screen, 33 met inclusion criteria. 12% were randomized clinical trials (RCTs), with 58% of publications representing technical descriptions. 62% of studies had 100 or fewer subjects. All studied technologies involved diagnosis or screening steps; none addressed the monitoring of infections. 52% focused on priority diseases (HIV, malaria, tuberculosis), but only 12% addressed a neglected tropical disease. Although most reported studies were priced under 20USD at time of publication, two thirds of the records did not yet specify a cost for the study technology. We conclude that there are only a small number of mHealth technologies focusing on innovative methods of screening and diagnosing communicable diseases potentially of use in LMICs. Rigorous RCTs, analyses with large sample size, and technologies assisting in the monitoring of diseases are needed.
View details for DOI 10.1371/journal.pdig.0000156
View details for PubMedID 37801442
Effectiveness of a community health worker-led low-sodium salt intervention to reduce blood pressure in rural Bangladesh: protocol for a cluster randomized controlled trial.
2023; 24 (1): 480
High blood pressure is a major public health problem in low- and middle-income countries. Low-sodium salt substitute (LSSS) is a promising population-level blood pressure-lowering intervention requiring minimal behavioral change. The optimal method of delivering LSSS to individuals, however, is currently unknown. Community health workers (CHWs) have successfully been used to implement health interventions in Bangladesh and may provide a venue for the dissemination of LSSS.We aim to conduct a cluster-randomized controlled trial involving 309 households in rural Bangladesh previously identified and characterized by the BRAC James P Grant School of Public Health, BRAC University (BRAC JPGSPH). These households will be randomly assigned to three arms: (1) control, i.e., no intervention; (2) information only, i.e., community health workers will provide basic information on high blood pressure, the health consequences of excessive salt consumption, and feedback to the participant on the likely quantity of salt s/he consumes (estimated using a questionnaire); (3) free LSSS arm: the same information as in arm 2 will be provided, but participants will receive 6 months of free low-sodium salt along with education on the benefits of LSSS. One male and one female adult (age ≥ 18 years) in each household will be invited to participate, the exclusion criteria being households with members known to have high serum potassium levels, are taking medications known to elevate potassium levels (e.g., ACE inhibitors, ARBs, potassium-sparing diuretics), are already taking potassium supplements, or those who have known kidney disease or abnormal serum creatinine at baseline. The primary endpoint will be blood pressure at 6 months post-intervention.Recent large clinical trials of LSSS in China and India have shown not only blood pressure improvements, but also stroke, major cardiac event, and all-cause mortality reductions. Nevertheless, how to best translate this intervention to population-level effectiveness remains unclear. Our study would test whether a community health worker-based program could be effectively used to disseminate LSSS and achieve measurable blood pressure benefits.ClinicalTrials.gov NCT05425030. Registered on June 21, 2022.
View details for DOI 10.1186/s13063-023-07518-3
View details for PubMedID 37501102
View details for PubMedCentralID PMC10375753
Impact of a Multidisciplinary Curriculum Training Students and Residents in Tobacco Cessation Strategies for Adult Caregivers of Children.
MedEdPORTAL : the journal of teaching and learning resources
2023; 19: 11313
Children's exposure to secondhand smoke is an underaddressed public health threat. The Clinical Effort Against Secondhand Smoke Exposure (CEASE) is a validated framework that trains pediatric providers to screen, counsel, refer to quitlines, and prescribe tobacco cessation medications to adult caregivers of children.A physician champion at a major urban academic center delivered a longitudinal didactic curriculum of CEASE principles to medical and nurse practitioner students and pediatrics and family medicine residents. At the end of each session, participants completed an anonymous survey measuring changes in self-perceived knowledge, comfort, and familiarity with smoking cessation skills and concepts. Using a separate end-of-year questionnaire, we also surveyed a group of pediatric residents to compare the impact of CEASE training on clinical practice. Finally, we tracked the number of referrals to the state's quitline for the duration of the training.Fifty-two trainees (55% students, 45% residents) responded to the evaluation survey administered immediately following training. There were statistically significant improvements in median scores after CEASE training for comfort in screening, counseling, motivational interviewing, referring to smokers' helplines, and providing caregivers with nicotine replacement therapy (NRT) prescriptions. Fifty-one percent of pediatric residents (41 of 80) responded to the end-of-year survey, which showed statistically significant differences in the number of patients/caregivers offered a referral to California's quitline and prescription of NRT according to completion of CEASE training.CEASE training successfully improved the self-efficacy of health professions students and residents in smoking cessation techniques for adult caregivers of children.
View details for DOI 10.15766/mep_2374-8265.11313
View details for PubMedID 37228253
View details for PubMedCentralID PMC10203095
What We Lost in the Fire: Endemic Tropical Heart Diseases in the Time of COVID-19.
The American journal of tropical medicine and hygiene
The COVID-19 pandemic has profoundly influenced the effort to achieve global health equity. This has been particularly the case for HIV/AIDS, tuberculosis, and malaria control initiatives in low- and middle-income countries, with significant outcome setbacks seen for the first time in decades. Lost in the calls for compensatory funding increases for such programs, however, is the plight of endemic tropical heart diseases, a group of disorders that includes rheumatic heart disease, Chagas disease, and endomyocardial fibrosis. Such endemic illnesses affect millions of people around the globe and remain a source of substantial mortality, morbidity, and health disparity. Unfortunately, these conditions were already neglected before the pandemic, and thus those living with them have disproportionately suffered during the time of COVID-19. In this perspective, we briefly define endemic tropical heart diseases, summarizing their prepandemic epidemiology, funding, and control statuses. We then describe the ways in which people living with these disorders, along with the healthcare providers and researchers working to improve their outcomes, have been harmed by the ongoing COVID-19 pandemic. We conclude by proposing the path forward, including approaches we may use to leverage lessons learned from the pandemic to strengthen care systems for these neglected diseases.
View details for DOI 10.4269/ajtmh.22-0514
View details for PubMedID 36746666
Association between Obesity and Length of COVID-19 Hospitalization: Unexpected Insights from the American Heart Association National COVID-19 Registry.
Journal of obesity & metabolic syndrome
Background: Observational analyses have noted an association between obesity and poor clinical outcome from Coronavirus Disease 2019 (COVID-19). The mechanism for this finding remains unclear.Methods: We analyzed data from 22,915 COVID-19 patients hospitalized in non-intensive care units using the American Heart Association National COVID Registry of adult COVID-19 admissions from March 2020 to April 2021. A multivariable Poisson model adjusted for age, sex, medical history, admission respiratory status, hospitalization characteristics, and select laboratory findings was used to calculate length of stay (LOS) as a function of body mass index (BMI) category. Additionally, 5,327 patients admitted to intensive care units were similarly analyzed for comparison.Results: Relative to normal BMI subjects, overweight, class I obese, and class II obese patients had approximately half-day reductions in LOS (-0.469 days, P<0.01; -0.480 days, P<0.01; -0.578 days, P<0.01, respectively).Conclusion: The model identified a dose-dependent, inverse relationship between BMI category and LOS for COVID-19, which was not seen when the model was applied to critically ill patients.
View details for DOI 10.7570/jomes22042
View details for PubMedID 36058896
Impacts of a Multicenter Medical Education Curriculum for Training Pediatric Residents on Tobacco Cessation for Adult Caregivers of Pediatric Patients.
The Clinical Effort Against Secondhand Smoke Exposure (CEASE) is an evidence-based framework that increases pediatric providers' ability to address secondhand smoke exposure of minors. Physician champions at 4 University of California sites conducted regular 1-hour didactic trainings on CEASE principles to pediatric residents as part of a longitudinal curriculum. At the conclusion of the academic year, 111 of 284 residents (39%) completed an anonymous survey. CEASE-trained residents reported significantly higher rates than untrained residents of counseling on smoking cessation (adjusted odds ratio [OR] = 4.50, P = .009), and referring to the smokers' quitline (adjusted OR 3.6, P = .007) to 50% or more of their patients' caregivers who smoked. In addition, among CEASE-trained residents, there were significant increases in multiple post-training knowledge and self-efficacy items. Our results show that a brief educational curriculum can be helpful in changing pediatric residents' attitudes and behavior toward assisting adult caregivers to pediatric patients in smoking cessation.
View details for DOI 10.1177/00099228221113783
View details for PubMedID 35891607
A systematic review of healthcare provider-targeted mobile applications for non-communicable diseases in low- and middle-income countries.
NPJ digital medicine
2022; 5 (1): 99
Mobile health (mHealth) interventions hold promise for addressing the epidemic of noncommunicable diseases (NCDs) in low- and middle-income countries (LMICs) by assisting healthcare providers managing these disorders in low-resource settings. We aimed to systematically identify and assess provider-facing mHealth applications used to screen for, diagnose, or monitor NCDs in LMICs. In this systematic review, we searched the indexing databases of PubMed, Web of Science, and Cochrane Central for studies published between January 2007 and October 2019. We included studies of technologies that were: (i) mobile phone- or tablet-based, (ii) able to screen for, diagnose, or monitor an NCD of public health importance in LMICs, and (iii) targeting health professionals as users. We extracted disease type, intervention purpose, target population, study population, sample size, study methodology, technology stage, country of development, operating system, and cost. Our initial search retrieved 13,262 studies, 315 of which met inclusion criteria and were analyzed. Cardiology was the most common clinical domain of the technologies evaluated, with 89 publications. mHealth innovations were predominantly developed using Apple's iOS operating system. Cost data were provided in only 50 studies, but most technologies for which this information was available cost less than 20 USD. Only 24 innovations targeted the ten NCDs responsible for the greatest number of disability-adjusted life years lost globally. Most publications evaluated products created in high-income countries. Reported mHealth technologies are well-developed, but their implementation in LMICs faces operating system incompatibility and a relative neglect of NCDs causing the greatest disease burden.
View details for DOI 10.1038/s41746-022-00644-3
View details for PubMedID 35853936
Aging Hearts in a Hotter, More Turbulent World: The Impacts of Climate Change on the Cardiovascular Health of Older Adults.
Current cardiology reports
PURPOSE OF REVIEW: Climate change has manifested itself in multiple environmental hazards to human health. Older adults and those living with cardiovascular diseases are particularly susceptible to poor outcomes due to unique social, economic, and physiologic vulnerabilities. This review aims to summarize those vulnerabilities and the resultant impacts of climate-mediated disasters on the heart health of the aging population.RECENT FINDINGS: Analyses incorporating a wide variety of environmental data sources have identified increases in cardiovascular risk factors, hospitalizations, and mortality from intensified air pollution, wildfires, heat waves, extreme weather events, rising sea levels, and pandemic disease. Older adults, especially those of low socioeconomic status or belonging to ethnic minority groups, bear a disproportionate health burden from these hazards. The worldwide trends responsible for global warming continue to worsen climate change-mediated natural disasters. As such, additional investigation will be necessary to develop personal and policy-level interventions to protect the cardiovascular wellbeing of our aging population.
View details for DOI 10.1007/s11886-022-01693-6
View details for PubMedID 35438387
- Mortality Along the Rheumatic Heart Disease Cascade of Care in Uganda. Circulation. Cardiovascular quality and outcomes 1800; 15 (1): e008445
EACVI Handbook of Cardiovascular CT
edited by Gaemperli, O., Maurovich-Horvat, P., Nieman, o., Pontone, G. K., Pugliese, F.
Oxford University Press. 2022; 1: 155–C2.8.P58
View details for DOI https://doi.org/10.1093/med/9780192884459.003.0019
Recent Advances in the Rheumatic Fever and Rheumatic Heart Disease Continuum
2022; 11 (2): 179
View details for DOI 10.3390/pathogens11020179
- Scientific Advances in Rheumatic Fever/Rheumatic Heart Disease Control Multidisciplinary Digital Publishing Institute. 2022 ; Encyclopedia.pub
Preoperative Computed Tomography Angiography Reveals Leaflet-Specific Calcification and Excursion Patterns in Aortic Stenosis.
Circulation. Cardiovascular imaging
BACKGROUND: Computed tomography-based evaluation of aortic stenosis (AS) by calcium scoring does not consider interleaflet differences in leaflet characteristics. Here, we sought to examine the functional implications of these differences.METHODS: We retrospectively reviewed the computed tomography angiograms of 200 male patients with degenerative calcific AS undergoing transcatheter aortic valve replacement and 20 male patients with normal aortic valves. We compared the computed tomography angiography (CTA)-derived aortic valve leaflet calcification load (AVLCCTA), appearance, and systolic leaflet excursion (LEsys) of individual leaflets. We performed computer simulations of normal valves to investigate how interleaflet differences in LEsys affect aortic valve area. We used linear regression to identify predictors of leaflet-specific calcification in patients with AS.RESULTS: In patients with AS, the noncoronary cusp (NCC) carried the greatest AVLCCTA (365.9 [237.3-595.4] Agatston unit), compared to the left coronary cusp (LCC, 278.5 [169.2-478.8] Agatston unit) and the right coronary cusp (RCC, 240.6 [137.3-439.0] Agatston unit; both P<0.001). However, LCC conferred the least LEsys (42.8 [38.8-49.0]) compared to NCC (44.8 [41.1-49.78], P=0.001) and RCC (47.7 [42.0-52.3], P<0.001) and was more often characterized as predominantly thickened (23.5%) compared to NCC (12.5%) and RCC (16.5%). Computer simulations of normal valves revealed greater reductions in aortic valve area following closures of NCC (-32.2 [-38.4 to -25.8]%) and RCC (-35.7 [-40.2 to -32.9]%) than LCC (-24.5 [-28.5 to -18.3]%; both P<0.001). By linear regression, the AVLCCTA of NCC and RCC, but not LCC, predicted LEsys (both P<0.001) in patients with AS. Both ostial occlusion and ostial height of the right coronary artery predicted AVLCCTA, RCC (P=0.005 and P=0.001).CONCLUSIONS: In male patients, the AVLCCTA of NCC and RCC contribute more to AS than that of LCC. LCC's propensity for noncalcific leaflet thickening and worse LEsys, however, should not be underestimated when using calcium scores to assess AS severity.
View details for DOI 10.1161/CIRCIMAGING.121.012884
View details for PubMedID 34915729
N-Terminal Pro-B-Type Natriuretic Peptide as a Biomarker for the Severity and Outcomes With COVID-19 in a Nationwide Hospitalized Cohort.
Journal of the American Heart Association
Background Currently, there is limited research on the prognostic value of NT-proBNP (N-terminal pro-B-type natriuretic peptide) as a biomarker in COVID-19. We proposed the a priori hypothesis that an elevated NT-proBNP concentration at admission is associated with increased in-hospital mortality. Methods and Results In this prospective, observational cohort study of the American Heart Association's COVID-19 Cardiovascular Disease Registry, 4675 patients hospitalized with COVID-19 were divided into normal and elevated NT-proBNP cohorts by standard age-adjusted heart failure thresholds, as well as separated by quintiles. Patients with elevated NT-proBNP (n=1344; 28.7%) were older, with more cardiovascular risk factors, and had a significantly higher rate of in-hospital mortality (37% versus 16%; P<0.001) and shorter median time to death (7 versus 9days; P<0.001) than those with normal values. Analysis by quintile of NT-proBNP revealed a steep graded relationship with mortality (7.1%-40.2%; P<0.001). NT-proBNP was also associated with major adverse cardiac events, intensive care unit admission, intubation, shock, and cardiac arrest (P<0.001 for each). In subgroup analyses, NT-proBNP, but not prior heart failure, was associated with increased risk of in-hospital mortality. Adjusting for cardiovascular risk factors with presenting vital signs, an elevated NT-proBNP was associated with 2-fold higher adjusted odds of death (adjusted odds ratio [OR], 2.23; 95% CI, 1.80-2.76), and the log-transformed NT-proBNP with other biomarkers projected a 21% increased risk of death for each 2-fold increase (adjusted OR, 1.21; 95% CI, 1.08-1.34). Conclusions Elevated NT-proBNP levels on admission for COVID-19 are associated with an increased risk of in-hospital mortality and other complications in patients with and without heart failure.
View details for DOI 10.1161/JAHA.121.022913
View details for PubMedID 34889112
Health system and patient-level factors serving as facilitators and barriers to rheumatic heart disease care in Sudan.
Global health research and policy
2021; 6 (1): 35
BACKGROUND: Rheumatic heart disease (RHD) remains a leading cause of morbidity and mortality in Sub-Saharan Africa despite widely available preventive therapies such as prophylactic benzathine penicillin G (BPG). In this study, we sought to characterize facilitators and barriers to optimal RHD treatment with BPG in Sudan.METHODS: We conducted a mixed-methods study, collecting survey data from 397 patients who were enrolled in a national RHD registry between July and November 2017. The cross-sectional surveys included information on demographics, healthcare access, and patient perspectives on treatment barriers and facilitators. Factors associated with increased likelihood of RHD treatment adherence to prophylactic BPG were assessed by using adjusted logistic regression. These data were enhanced by focus group discussions with 20 participants, to further explore health system factors impacting RHD care.RESULTS: Our quantitative analysis revealed that only 32% of the study cohort reported optimal prophylaxis adherence. Younger age, reduced primary RHD healthcare facility wait time, perception of adequate health facility staffing, increased treatment costs, and high patient knowledge about RHD were significantly associated with increased odds of treatment adherence. Qualitative data revealed significant barriers to RHD treatment arising from health services factors at the health system level, including lack of access due to inadequate healthcare staffing, lack of faith in local healthcare systems, poor ancillary services, and patient lack of understanding of disease. Facilitators of RHD treatment included strong interpersonal support.CONCLUSIONS: Multiple patient and system-level barriers to RHD prophylaxis adherence were identified in Khartoum, Sudan. These included patient self-efficacy and participant perception of healthcare facility quality. Strengthening local health system infrastructure, while enhancing RHD patient education, may help to improve treatment adherence in this vulnerable population.
View details for DOI 10.1186/s41256-021-00222-2
View details for PubMedID 34598719
Clinical Outcomes, Echocardiographic Findings, and Care Quality Metrics for People Living with HIV and Rheumatic Heart Disease in Uganda.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Rheumatic Heart Disease (RHD) affects 41 million people worldwide, mostly in low- and middle-income countries, where it is co-endemic with HIV. HIV is also a chronic inflammatory disorder associated with cardiovascular complications, yet the epidemiology of patients affected by both diseases is poorly understood.Utilizing the Uganda National RHD Registry, we described the echocardiographic findings, clinical characteristics, medication prescription rates, and outcomes of all 73 people carrying concurrent diagnoses of HIV and RHD between 2009 and 2018. These individuals were compared to an age- and sex-matched cohort of 365 subjects with RHD only.The median age of the HIV-RHD group was 36 years (IQR 15) and 86% were women. The HIV-RHD cohort had higher rates of prior stroke/transient ischemic attack (12% vs 5%, p=0.02) than the RHD-only group, with this association persisting following multivariable adjustment (OR 3.08, p=0.03). Prevalence of other comorbidities, echocardiographic findings, prophylactic penicillin prescription rates, retention in clinical care, and mortality were similar between the two groups.Patients living with RHD and HIV in Uganda are a relatively young, predominantly female group. Although RHD-HIV comorbid individuals have higher rates of stroke, their similar all-cause mortality and RHD care quality metrics (such as retention in care) compared to those with RHD alone suggest rheumatic heart disease defines their clinical outcome more than HIV does. We believe this study to be one of the first reports of the epidemiologic profile and longitudinal outcomes of patients who carry diagnoses of both conditions.
View details for DOI 10.1093/cid/ciab681
View details for PubMedID 34382644
- The Need to Expand the Framework of Environmental Determinants of Cardiovascular Health From Climate Change to Planetary Health: Trial by Wildfire. Circulation 2021; 143 (21): 2029-2031
The Impact of Novel Coronavirus COVID-19 on Non-Communicable Disease Patients and Health Systems: A Review.
Journal of internal medicine
Coronavirus Disease 2019 (COVID-19) is an ongoing global pandemic affecting all levels of health systems. This includes the care of patients with noncommunicable diseases (NCDs) who bear a disproportionate burden of both COVID-19 itself and the public health measures enacted to combat it. In this review, we summarize major COVID-19 related considerations for NCD patients and their care providers, focusing on cardiovascular, pulmonary, renal, hematologic, oncologic, traumatic, obstetric/gynecologic, operative, psychiatric, rheumatologic/immunologic, neurologic, gastrointestinal, ophthalmologic, and endocrine disorders. Additionally, we offer a general framework for categorizing the pandemic's disruptions by disease-specific factors, direct health system factors, and indirect health system factors. We also provide references to major NCD medical specialty professional society statements and guidelines on COVID-19. COVID-19 and its control policies have already resulted in major disruptions to the screening, treatment, and surveillance of NCD patients. In addition, it differentially impacts those with pre-existing NCDs and may lead to de novo NCD sequelae. Likely, there will be long-term effects from this pandemic that will continue to affect practitioners and patients in this field for years to come.
View details for DOI 10.1111/joim.13184
View details for PubMedID 33020988
Outcomes and Care Quality Metrics for Women of Reproductive Age Living With Rheumatic Heart Disease in Uganda.
Journal of the American Heart Association
Background Rheumatic heart disease disproportionately affects women of reproductive age, as it increases the risk of cardiovascular complications and death during pregnancy and childbirth. In sub-Saharan Africa, clinical outcomes and adherence to guideline-based therapies are not well characterized for this population. Methods and Results In a retrospective cohort study of the Uganda rheumatic heart disease registry between June 2009 and May 2018, we used multivariable regression and Cox proportional hazards models to compare comorbidities, mortality, anticoagulation use, and treatment cascade metrics among women versus men aged 15 to 44 with clinical rheumatic heart disease. We included 575 women and 252 men with a median age of 27 years. Twenty percent had New York Heart Association Class III-IV heart failure. Among patients who had an indication for anticoagulation, women were less likely than men to receive a prescription of warfarin (66% versus 81%; adjusted odds ratio, 0.37; 95% CI, 0.14-0.96). Retention in care (defined as a clinic visit within the preceding year) was poor among both sexes in this age group (27% for men, 24% for women), but penicillin adherence rates were high among those retained (89% for men, 92% for women). Mortality was higher in men than women (26% versus 19% over a median follow-up of 2.7 years; adjusted hazard ratio, 1.66; 95% CI, 1.18-2.33). Conclusions Compared with men, women of reproductive age with rheumatic heart disease in Uganda have lower rates of appropriate anticoagulant prescription but also lower mortality rates. Retention in care is poor among both men and women in this age range, representing a key target for improvement.
View details for DOI 10.1161/JAHA.119.015562
View details for PubMedID 32295465
Breast cancer induces systemic immune changes on cytokine signaling in peripheral blood monocytes and lymphocytes.
2020; 52: 102631
It is increasingly recognized that cancer progression induces systemic immune changes in the host. Alterations in number and function of immune cells have been identified in cancer patients' peripheral blood and lymphoid organs. Recently, we found dysregulated cytokine signaling in peripheral blood T cells from breast cancer (BC) patients, even those with localized disease.We used phosphoflow cytometry to determine the clinical significance of cytokine signaling responsiveness in peripheral blood monocytes from non-metastatic BC patients at diagnosis. We also examined the correlation between cytokine signaling in peripheral monocytes and the number of tumor-infiltrating macrophages in paired breast tumors.Our results show that cytokine (IFNγ) signaling may also be dysregulated in peripheral blood monocytes at diagnosis, specifically in BC patients who later relapsed. Some patients exhibited concurrent cytokine signaling defects in monocytes and lymphocytes at diagnosis, which predict the risk of future relapse in two independent cohorts of BC patients. Moreover, IFNγ signaling negatively correlates with expression of CSF1R on monocytes, thus modulating their ability to infiltrate into tumors.Our results demonstrate that tumor-induced systemic immune changes are evident in peripheral blood immune cells for both myeloid and lymphoid lineages, and point to cytokine signaling responsiveness as important biomarkers to evaluate the overall immune status of BC patients.This study was supported by the Department of Defense Breast Cancer Research Program (BCRP), The V Foundation, Stand Up to Cancer (SU2C), and Breast Cancer Research Foundation (BCRF).
View details for DOI 10.1016/j.ebiom.2020.102631
View details for PubMedID 31981982
Cost-effectiveness of Canakinumab for Prevention of Recurrent Cardiovascular Events.
Importance: In the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial, the anti-inflammatory monoclonal antibody canakinumab significantly reduced the risk of recurrent cardiovascular events in patients with previous myocardial infarction (MI) and high-sensitivity C-reactive protein (hs-CRP) levels of 2 mg/L or greater.Objective: To estimate the cost-effectiveness of adding canakinumab to standard of care for the secondary prevention of major cardiovascular events over a range of potential prices.Design, Setting, and Participants: A state-transition Markov model was constructed to estimate costs and outcomes over a lifetime horizon by projecting rates of recurrent MI, coronary revascularization, infection, and lung cancer with and without canakinumab treatment. We used a US health care sector perspective, and the base case used the current US market price of canakinumab of $73 000 per year. A hypothetical cohort of patients after MI aged 61 years with an hs-CRP level of 2 mg/L or greater was constructed.Interventions: Canakinumab, 150 mg, administered every 3 months plus standard of care compared with standard of care alone.Main Outcomes and Measures: Lifetime costs and quality-adjusted life-years (QALYs), discounted at 3% annually.Results: Adding canakinumab to standard of care increased life expectancy from 11.31 to 11.36 years, QALYs from 9.37 to 9.50, and costs from $242 000 to $1 074 000, yielding an incremental cost-effectiveness ratio of $6.4 million per QALY gained. The price would have to be reduced by more than 98% (to $1150 per year or less) to meet the $100 000 per QALY willingness-to-pay threshold. These results were generally robust across alternative assumptions, eg, substantially lower health-related quality of life after recurrent cardiovascular events, lower infection rates while receiving canakinumab, and reduced all-cause mortality while receiving canakinumab. Including a potential beneficial effect of canakinumab on lung cancer incidence improved the incremental cost-effectiveness ratio to $3.5 million per QALY gained. A strategy of continuing canakinumab selectively in patients with reduction in hs-CRP levels to less than 2 mg/L would have a cost-effectiveness ratio of $819 000 per QALY gained.Conclusions and Relevance: Canakinumab is not cost-effective at current US prices for prevention of recurrent cardiovascular events in patients with a prior MI. Substantial price reductions would be needed for canakinumab to be considered cost-effective.
View details for PubMedID 30649147
Interventions to Reduce Ethnic and Racial Disparities in Dyslipidemia Management.
Current treatment options in cardiovascular medicine
2019; 21 (5): 24
Race and ethnicity are associated with disparities in risk assessment, screening, patient awareness, treatment, and control of dyslipidemia and can contribute to worsened cardiovascular outcomes. This review summarizes these gaps in care and highlights recent interventions aimed at reducing them.Disparities in dyslipidemia diagnosis and treatment are well documented among certain racial and ethnic minority groups. Less is known about dyslipidemia among Hispanics, Asians, and Native Americans/Pacific Islanders, who have significant heterogeneity in cardiovascular risk and outcomes. Programs to reduce inequalities have focused on targeted risk assessment, improved screening practices, statin adherence-enhancing policies, culturally inclusive risk factor modification campaigns, and multidisciplinary treatment teams, with variable success. Interventions to reduce racial/ethnic disparities in dyslipidemia are important at all phases of care. Nevertheless, initiatives concentrating on single elements of the lipid treatment cascade were generally less effective at improving clinical endpoints than those that comprehensively addressed multiple phases. Moreover, there was a disproportionately greater number of published studies analyzing patient-facing lifestyle-based risk factor modifications than other types of interventions. Future investigations should focus on understudied populations such as disaggregated Hispanic, Asian, and Native American populations. Additionally, innovative strategies utilizing information technology and provider-facing programs are needed.
View details for PubMedID 31065884
Association of Healthcare Plan with Atrial Fibrillation Prescription Patterns.
Atrial fibrillation (AF) is treated by many types of physician specialists, including primary care physicians (PCPs). Health plans have different policies for how patients encounter these providers, and these may affect selection of AF treatment strategy.We hypothesized that healthcare plans with PCP-gatekeeping to specialist access may be associated with different pharmacologic treatments for AF.We performed a retrospective cohort study using a commercial pharmaceutical claims database. We utilized logistic regression models to compare odds of prescription of oral anticoagulant (OAC), non-vitamin K-dependent oral anticoagulant (NOAC), rate control, and rhythm control medications used to treat AF between patients with PCP-gated healthcare plans (e.g. HMO, EPO, POS) and patients with non-PCP-gated healthcare plans (e.g. PPO, CHDP, HDHP, Comprehensive) between 2007 and 2012. We also calculated median time to receipt of therapy within 90 days of index AF diagnosis.We found similar odds of OAC prescription at 90 days following new AF diagnosis in patients with PCP-gated plans compared to those with non-PCP-gated plans (OR: OAC 1.01, p=0.84; warfarin 1.05, p=0.08). Relative odds were similar for rate control (1.17, p<0.01) and rhythm control agents (0.93, p=0.03). However, PCP-gated plan patients had slightly lower likelihood of being prescribed NOACs (0.82, p=0.001) than non-gated plan patients. Elapsed time until receipt of medication was similar between PCP-gated and non-gated groups across drug classes.Pharmaceutical claims data do not suggest that PCP-gatekeeping by healthcare plans is a structural barrier to AF therapy, although it was associated with lower use of NOACs.
View details for PubMedID 30098034
Patient and facility variation in costs of catheter ablation for atrial fibrillation.
Journal of cardiovascular electrophysiology
Cost-effectiveness or value of cardiovascular therapies may be undermined by unwarranted cost variation, particularly for heterogeneous procedures such as catheter ablation for atrial fibrillation (AF). We sought to characterize cost variation of AF ablation in the U.S. health care system and the relationship between cost and outcomes.We performed a retrospective cohort study using data from the MarketScan® commercial claims and Medicare supplemental databases including patients who received an AF ablation from 2007 through 2011. We aggregated encounter cost, reflecting total payments received for the encounter, to the facility level to calculate median facility cost. We classified procedures as outpatient or inpatient and assessed for association between cost and 30-day and one-year outcomes. The analysis cohort included 9,415 AF ablations (59±11 years; 28% female; 52% outpatient) occurring at 327 facilities, with large cost variation across facilities (median: $25,100; 25th percentile: $18,900, 75th percentile: $35,600, 95th percentile: $57,800). Among outpatient procedures, there was reduced health care utilization in higher cost quintiles with reductions in rehospitalization at 30-days (Quintile 1: 16.1%, Quintile 5: 8.8%, p < 0.001) and one-year (Quintile 1: 34.8%, Quintile 5: 25.6%, p < 0.001), which remained significant in multivariate analysis.Although median costs of AF ablation are below amounts used in prior cost-effectiveness studies that demonstrated good value, large facility variation in cost suggests opportunities for cost reduction. However, for outpatient encounters, association of cost to modestly improved outcomes suggests cost containment strategies could have variable effects. This article is protected by copyright. All rights reserved.
View details for PubMedID 29864193
Motivations of women in Uganda living with rheumatic heart disease: A mixed methods study of experiences in stigma, childbearing, anticoagulation, and contraception.
2018; 13 (3): e0194030
Rheumatic heart disease (RHD) is a leading cause of premature mortality in low- and middle-income countries (LMICs). Women of reproductive age are a unique and vulnerable group of RHD patients, due to increased risk of cardiovascular complications and death during pregnancy. Yet, less than 5% of women of childbearing age with RHD in LMICs use contraceptives, and one in five pregnant women with RHD take warfarin despite known teratogenicity. It is unclear whether this suboptimal contraception and anticoagulant use during pregnancy is due to lack of health system resources, limited health literacy, or social pressure to bear children.We conducted a mixed methods study of 75 women living with RHD in Uganda. Questionnaires were administered to 50 patients. Transcripts from three focus groups with 25 participants were analyzed using qualitative description methodology.Several themes emerged from the focus groups, including pregnancy as a calculated risk; misconceptions about side-effects of contraceptives and anticoagulation; reproductive decision-making control by male partners, in-laws, or physicians; abandonment of patients by male partners; and considerable stigma against heart disease patients for both their reproductive and financial limitations (often worse than that directed against HIV patients). All questionnaire respondents were told by physicians that their hearts were not strong enough to support a pregnancy. Only 14% used contraception while taking warfarin. All participants felt that society would look poorly on a woman who cannot have children due to a heart condition.To our knowledge, this is the first qualitative study of female RHD patients and their attitudes toward cardiovascular disorders and reproduction. Our results suggest that health programs targeting heart disease in LMICs must pay special attention to the needs of women of childbearing age. There are opportunities for improved family/societal education programs and community engagement, leading to better outcomes and patient empowerment.
View details for PubMedID 29590159
View details for PubMedCentralID PMC5874006
IL6 Signaling in Peripheral Blood T Cells Predicts Clinical Outcome in Breast Cancer.
2017; 77 (5): 1119-1126
IL6 is a pleiotropic cytokine with both pro- and anti-inflammatory properties, which acts directly on cancer cells to promote their survival and proliferation. Elevated serum IL6 levels negatively correlate with survival of cancer patients, which is generally attributed to the direct effects of IL6 on cancer cells. How IL6 modulates the host immune response in cancer patients is unclear. Here, we show the IL6 signaling response in peripheral blood T cells is impaired in breast cancer patients and is associated with blunted Th17 differentiation. The mechanism identified involved downregulation of gp130 and IL6Rα in breast cancer patients and was independent of plasma IL6 levels. Importantly, defective IL6 signaling in peripheral blood T cells at diagnosis correlated with worse relapse-free survival. These results indicate that intact IL6 signaling in T cells is important for controlling cancer progression. Furthermore, they highlight a potential for IL6 signaling response in peripheral blood T cells at diagnosis as a predictive biomarker for clinical outcome of breast cancer patients. Cancer Res; 77(5); 1119-26. ©2016 AACR.
View details for DOI 10.1158/0008-5472.CAN-16-1373
View details for PubMedID 27879265
Regenerative Medicine: Potential Mechanisms of Cardiac Recovery in Takotsubo Cardiomyopathy.
Current treatment options in cardiovascular medicine
2016; 18 (3): 20-?
Takotsubo cardiomyopathy is an increasingly reported cause of acute chest pain and acute heart failure and is often associated with significant hemodynamic compromise. The illness is remarkable for the reversibility in systolic dysfunction seen in the disease course. While the pathophysiology of takotsubo syndrome is not completely elucidated, research suggests the presence of a cytoprotective process that allows the myocardium to recover following the inciting insult. Here, we summarize molecular and histologic studies exploring the response to injury in takotsubo disease and provide some discussion on how they may contribute to further investigations in cardiac recovery and regeneration.
View details for DOI 10.1007/s11936-016-0443-0
View details for PubMedID 26874708
- The Global Health Implications of e-Cigarettes. JAMA 2015; 314 (7): 663-664
Evaluating the Cost-effectiveness of Catheter Ablation of Atrial Fibrillation.
Arrhythmia & electrophysiology review
2014; 3 (3): 177-183
Atrial fibrillation (AF) is one of the most common cardiac conditions treated in primary care and specialty cardiology settings, and is associated with considerable morbidity, mortality and cost. Catheter ablation, typically by electrically isolating the pulmonary veins and surrounding tissue, is more effective at maintaining sinus rhythm than conventional antiarrhythmic drug therapy and is now recommended as first-line therapy. From a value standpoint, the cost-effectiveness of ablation must incorporate the upfront procedural costs and risks with the benefits of longer term improvements in quality of life (QOL) and healthcare utilisation. Here, we present a primer on cost-effectiveness analysis (CEA), review the data on cost-effectiveness of AF ablation and outline key areas for further investigation.
View details for DOI 10.15420/aer.2014.3.3.177
View details for PubMedID 26835088
- Trial of Zolpidem, Eszopiclone, and Other GABA Agonists in a Patient with Progressive Supranuclear Palsy Case Reports in Medicine 2014; 2014: 5
Trial of Zolpidem, Eszopiclone, and Other GABA Agonists in a Patient with Progressive Supranuclear Palsy
CASE REPORTS IN MEDICINE
Progressive supranuclear palsy (PSP) is a progressive, debilitating neurodegenerative disease of the Parkinson-plus family of syndromes. Unfortunately, there are no pharmacologic treatments for this condition, as most sufferers of the classic variant respond poorly to Parkinson medications such as levodopa. Zolpidem, a gamma aminobutyric acid (GABA) agonist specific to the α-1 receptor subtype, has been reported to show improvements in symptoms of PSP patients, including motor dysfunction, dysarthria, and ocular disturbances. We observed a 73-year-old woman with a six-year history of PSP, who, upon administration of a single 12.5 mg dose of sustained-release zolpidem, exhibited marked enhancements in speech, facial expressions, and fine motor skills for five hours. These results were reproduced upon subsequent clinic visits. In an effort to find a sustainable medication that maximized these beneficial effects while minimizing side effects and addressing some of her comorbid neuropsychological conditions, a trial of five other GABA receptor agonists was performed with the patient's consent, while she and her caregivers were blinded to the specific medications. She and her caretakers subsequently reported improvements, especially visual, while on eszopiclone, and, to a lesser degree, temazepam and flurazepam.
View details for PubMedID 25371679
View details for PubMedCentralID PMC4209775
Spatial organization of dendritic cells within tumor draining lymph nodes impacts clinical outcome in breast cancer patients
JOURNAL OF TRANSLATIONAL MEDICINE
Dendritic cells (DCs) are important mediators of anti-tumor immune responses. We hypothesized that an in-depth analysis of dendritic cells and their spatial relationships to each other as well as to other immune cells within tumor draining lymph nodes (TDLNs) could provide a better understanding of immune function and dysregulation in cancer.We analyzed immune cells within TDLNs from 59 breast cancer patients with at least 5 years of clinical follow-up using immunohistochemical staining with a novel quantitative image analysis system. We developed algorithms to analyze spatial distribution patterns of immune cells in cancer versus healthy intra-mammary lymph nodes (HLNs) to derive information about possible mechanisms underlying immune-dysregulation in breast cancer. We used the non-parametric Mann-Whitney test for inter-group comparisons, Wilcoxon Matched-Pairs Signed Ranks test for intra-group comparisons and log-rank (Mantel-Cox) test for Kaplan Maier analyses.Degree of clustering of DCs (in terms of spatial proximity of the cells to each other) was reduced in TDLNs compared to HLNs. While there were more numerous DC clusters in TDLNs compared to HLNs,DC clusters within TDLNs tended to have fewer member DCs and also consisted of fewer cells displaying the DC maturity marker CD83. The average number of T cells within a standardized radius of a clustered DC was increased compared to that of an unclustered DC, suggesting that DC clustering was associated with T cell interaction. Furthermore, the number of T cells within the radius of a clustered DC was reduced in tumor-positive TDLNs compared to HLNs. Importantly, clinical outcome analysis revealed that DC clustering in tumor-positive TDLNs correlated with the duration of disease-free survival in breast cancer patients.These findings are the first to describe the spatial organization of DCs within TDLNs and their association with survival outcome. In addition, we characterized specific changes in number, size, maturity, and T cell co-localization of such clusters. Strategies to enhance DC function in-vivo, including maturation and clustering, may provide additional tools for developing more efficacious DC cancer vaccines.
View details for DOI 10.1186/1479-5876-11-242
View details for Web of Science ID 000326447100001
View details for PubMedID 24088396
View details for PubMedCentralID PMC3852260
Center-surround vs. distance-independent lateral connectivity in the olfactory bulb
FRONTIERS IN NEURAL CIRCUITS
Lateral neuronal interactions are known to play important roles in sensory information processing. A center-on surround-off local circuit arrangement has been shown to play a role in mediating contrast enhancement in the visual, auditory, and somatosensory systems. The lateral connectivity and the influence of those connections have been less clear for the olfactory system. A critical question is whether the synaptic connections between the primary projection neurons, mitral and tufted (M/T) cells, and their main inhibitory interneurons, the granule cells (GCs), can support a center-surround motif. Here, we study this question by injecting a "center" in the glomerular layer of the olfactory bulb (OB) with a marker of synaptic connectivity, the pseudorabies virus (PRV), then examines the distribution of labeling in the "surround" of GCs. We use a novel method to score the degree to which the data fits a center-surround model vs. distance-independent connectivity. Data from 22 injections show that M/T cells generally form lateral connections with GCs in patterns that lie between the two extremes.
View details for DOI 10.3389/fncir.2012.00034
View details for Web of Science ID 000304625700001
View details for PubMedID 22666190
View details for PubMedCentralID PMC3364486
Learning to live together: harnessing regulatory T cells to induce organ transplant tolerance.
Yale journal of biology and medicine
2011; 84 (4): 345-351
The discovery of immune cells with regulatory effects has created considerable excitement for their potential use in inducing tolerance to transplanted tissues. Despite the fact that these cells possess essential functions in vivo, attempts to translate them into effective clinical therapies has proved challenging due to a number of unanticipated complexities in their behavior. This article provides a broad summary of research done to understand the largest of the regulatory cell subtypes, namely CD4+Foxp3+ Regulatory T cells (T(Regs)). Special attention will be paid to current and future difficulties in using T(Regs) clinically, as well as room for improvement and innovation in this field.
View details for PubMedID 22180672
Lateral connectivity in the olfactory bulb is sparse and segregated
FRONTIERS IN NEURAL CIRCUITS
Lateral connections in the olfactory bulb were previously thought to be organized for center-surround inhibition. However, recent anatomical and physiological studies showed sparse and distributed interactions of inhibitory granule cells (GCs) which tended to be organized in columnar clusters. Little is known about how these distributed clusters are interconnected. In this study, we use transsynaptic tracing viruses bearing green or red fluorescent proteins to further elucidate mitral- and tufted-to-GC connectivity. Separate sites in the glomerular layer were injected with each virus. Columns with labeling from both viruses after transsynaptic spread show sparse red or green GCs which tended to be segregated. However, there was a higher incidence of co-labeled cells than chance would predict. Similar segregation of labeling is observed from dual injections into olfactory cortex. Collectively, these results suggest that neighboring mitral and tufted cells receive inhibitory inputs from segregated subsets of GCs, enabling inhibition of a center by specific and discontinuous lateral elements.
View details for DOI 10.3389/fncir.2011.00005
View details for Web of Science ID 000290153700001
View details for PubMedID 21559072
- Hydrophilic Graft Modification of a Commercial Crystalline Polyolefin J. Polym. Sci. Part A: Polym. Chem. 2008; 46: 3533-3545
- Regioselective functionalization of high-molecular-weight crystalline polyolefins via C-H activation of methyl side group Polymer Preprints 2006; 47: 247-248