Publications by authors named "Michelle Zhao"

6 Publications

  • Page 1 of 1

Completing the β,γ-CXY-dNTP Stereochemical Probe Toolkit: Synthetic Access to the dCTP Diastereomers and P and F NMR Correlations with Absolute Configurations.

J Org Chem 2020 11 30;85(22):14592-14609. Epub 2020 Oct 30.

Department of Chemistry, Dana and David Dornsife College of Letters, Arts and Sciences, University of Southern California, University Park Campus, Los Angeles, California 90089, United States.

Nucleoside 5'-triphosphate (dNTP) analogues in which the β,γ-oxygen is mimicked by a CXY group (β,γ-CXY-dNTPs) have provided information about DNA polymerase catalysis and fidelity. Definition of CXY stereochemistry is important to elucidate precise binding modes. We previously reported the ()- and ()-β,γ-CHX-dGTP diastereomers (X = F, Cl), prepared via P,C-dimorpholinamide CHCl (, ) and CHF (, ) bisphosphonates (BPs) equipped with an ()-mandelic acid as a chiral auxiliary, with final deprotection using H/Pd. This method also affords the β,γ-CHCl-dTTP (, ), β,γ-CHF (, ), and β,γ-CHCl (, ) dATP diastereomers as documented here, but the reductive deprotection step is not compatible with dCTP or the bromo substituent in β,γ-CHBr-dNTP analogues. To complete assembly of the toolkit, we describe an alternative synthetic strategy featuring ethylbenzylamine or phenylglycine-derived chiral BP synthons incorporating a photolabile protecting group. After acid-catalyzed removal of the ()-(+)-α-ethylbenzylamine auxiliary, coupling with activated dCMP and photochemical deprotection, the individual diastereomers of β,γ-CHBr- (, ), β,γ-CHCl- (, 3), β,γ-CHF-dCTP (, ) were obtained. The β,γ-CH(CH)-dATPs (, ) were obtained using a methyl ()-(-)-phenylglycinate auxiliary. P and F NMR Δδ values are correlated with CXY stereochemistry and p values for 13 CXY-bisphosphonic acids and imidodiphosphonic acid are tabulated.
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http://dx.doi.org/10.1021/acs.joc.0c01204DOI Listing
November 2020

Smoking, life expectancy, and chronic disease in South Korea, Singapore, and the United States: A microsimulation model.

Health Econ 2019 Dec 4. Epub 2019 Dec 4.

Shorenstein Asia Pacific Research Center, Stanford University, Stanford, California.

The substantial social and economic burden attributable to smoking is well-known, with heavy smokers at higher risk of chronic disease and premature mortality than light smokers and nonsmokers. In aging societies with high rates of male smoking such as in East Asia, smoking is a leading preventable risk factor for extending lives (including work-lives) and healthy aging. However, little is known about whether smoking interventions targeted at heavy smokers relative to light smokers lead to disproportionately larger improvements in life expectancy and prevalence of chronic diseases and how the effects vary across populations. Using a microsimulation model, we examined the health effects of smoking reduction by simulating an elimination of smoking among subgroups of smokers in South Korea, Singapore, and the United States. We found that life expectancy would increase by 0.2 to 1.5 years among light smokers and 2.5 to 3.7 years among heavy smokers. Whereas both interventions led to an increased life expectancy and decreased the prevalence of chronic diseases in all three countries, the life-extension benefits were greatest for those who would otherwise have been heavy smokers. Our findings illustrate how smoking interventions may have significant economic and social benefits, especially for life extension, that vary across countries.
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http://dx.doi.org/10.1002/hec.3978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269831PMC
December 2019

Quality of Life in Pediatric Neurosurgery: Comparing Parent and Patient Perceptions.

World Neurosurg 2020 Feb 23;134:e306-e310. Epub 2019 Oct 23.

Baylor College of Medicine Department of Neurosurgery, Houston, Texas, USA; Texas Children's Hospital Division of Neurosurgery, Houston, Texas, USA. Electronic address:

Background: In the pediatric neurosurgical population, understanding how to mitigate the effects of disease on children's physical ability, social and psychological well-being, and education can have lasting effects on their development and family. Understanding parents' perceptions of their children's health-related quality of life (HRQoL) is crucial in proper counseling, management of expectations, establishment of a healthy patient/parent-physician relationship, and understanding the role and impact of health care. In this study we sought to examine the differences between patient and parent perceptions of HRQoL and the factors that influence these differences.

Methods: A standardized survey (PedsQL Inventory) to assess physical, psychological, and social function and school performance was administered to both parents and patients in a general pediatric neurosurgery outpatient clinic from 2015-2018.

Results: 197 encounters with 179 patients occurred in the study period. There were 105 male and 92 female patients across various ethnic backgrounds. The most common diagnoses were tumor (23.4%) and vascular malformation (16.2%). Parent overall scores were lower than their children's (72.5 vs. 76.4, P < 0.01). Parent scores of physical function (74.3 vs. 78.7, P < 0.01) and overall psychosocial function (71.5 vs. 75.3, P < 0.01) were also lower. Parent scores in all domains of the PedsQL were correlated with overall score difference (P < 0.01), but only child scores of overall psychosocial (P < 0.03) and school function (P < 0.04) were correlated with overall score difference.

Conclusions: Parents have more negative assessments of their children's HRQoL compared with their children in all domains assessed by the PedsQL. Further research is needed to identify factors that contribute to these discrepancies.
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http://dx.doi.org/10.1016/j.wneu.2019.10.037DOI Listing
February 2020

Hepatitis C Virus Infection in the Dallas County Jail: Implications for Screening, Prevention, and Linkage to Care.

Public Health Rep 2019 Nov/Dec;134(6):626-633. Epub 2019 Sep 17.

Division of Infectious Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Objectives: Screening for hepatitis C virus (HCV) infection in jail provides an opportunity to educate and offer care to a high-risk population. We aimed to (1) estimate the prevalence of HCV infection in jail; (2) describe the demographic characteristics, risk factors, and pre-incarceration health insurance status associated with HCV infection; and (3) examine the implementation of HCV screening in jail.

Methods: We conducted a retrospective analysis of an opt-out HCV screening program with HCV RNA confirmation and patient education at the Dallas County Jail from April 1 through November 2, 2017. We extracted data on test results, demographic characteristics, and release destination from electronic medical records. A nurse navigator recorded data on patient self-reported risk factors and pre-incarceration health insurance status.

Results: Of 4089 incarcerated persons screened, 708 (17.3%) had a positive HCV antibody result. Of these, 641 (90.5%) had an HCV RNA test ordered; 576 (89.9%) had RNA tests completed, of whom 413 (71.7%) had a positive HCV RNA result. Of these 413, 352 (85.2%) received patient education. Half of HCV RNA-positive incarcerated persons (n = 207, 50.1%) were born outside the birth cohort (1945-1965). Among those with HCV infection, commonly reported risk factors were injection drug use (168 of 352; 47.8%) and tattoos (82 of 352; 23.4%). Most incarcerated persons with HCV infection (284 of 350; 81.1%) did not have health insurance. HCV antibody prevalence was higher among incarcerated persons released to prison (232 of 961; 24.1%) than to outside agencies (38 of 403; 9.4%) or the community (178 of 1026; 17.4%).

Conclusions: Screening for HCV with RNA confirmation in jail provides an opportunity for disease education, transmission prevention, and navigation to HCV treatment. Future efforts should examine post-incarceration linkage to care.
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http://dx.doi.org/10.1177/0033354919874081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832085PMC
February 2020

Comparing demographic and health characteristics of new and existing SNAP recipients: application of a machine learning algorithm.

Am J Clin Nutr 2019 04;109(4):1164-1172

Center for Primary Care and Outcomes Research/Center for Health Policy, Department of Medicine, Stanford University, Stanford, CA.

Background: The Supplemental Nutrition Assistance Program (SNAP) expanded significantly after the Great Recession of 2008-2009, but no studies have characterized this new group of recipients. Few data sets provide details on whether an individual is a new or established recipient of SNAP.

Objective: We sought to identify new and existing SNAP recipients, and to examine differences in sociodemographic characteristics, health, nutritional status, and food purchasing behavior between new and existing recipients of SNAP after the recession.

Methods: We created a probabilistic algorithm to identify new and existing SNAP recipients using the 1999-2013 waves of the Panel Study of Income Dynamics. We applied this algorithm to the National Household Food Acquisition and Purchase Survey (FoodAPS), fielded during 2012-2013, to predict which individuals were likely to be new SNAP recipients. We then compared health and nutrition characteristics between new, existing, and never recipients of SNAP in FoodAPS.

Results: New adult SNAP recipients had higher socioeconomic status, better self-reported health, and greater food security relative to existing recipients, and were more likely to smoke relative to never recipients. New child SNAP recipients were less likely to eat all meals and had lower BMI relative to existing recipients. New SNAP households exhibited differences in food access and expenditures, although dietary quality was similar to that of existing SNAP households.

Conclusion: We developed a novel algorithm for predicting new and existing SNAP recipiency that can be applied to other data sets, and subsequently demonstrated differences in health characteristics between new and existing recipients. The expansion of SNAP since the Great Recession enrolled a population that differed from the existing SNAP population and that may benefit from different types of nutritional and health services than those traditionally offered.
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http://dx.doi.org/10.1093/ajcn/nqy355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462432PMC
April 2019

Direct regulation of blood pressure by smooth muscle cell mineralocorticoid receptors.

Nat Med 2012 Sep;18(9):1429-33

Molecular Cardiology Research Institute, Tufts Medical Center, Boston, Massachusetts, USA.

Hypertension is a cardiovascular risk factor present in over two-thirds of people over age 60 in North America; elevated blood pressure correlates with increased risk of heart attack, stroke and progression to heart and kidney failure. Current therapies are insufficient to control blood pressure in almost half of these patients. The mineralocorticoid receptor (MR), acting in the kidney, is known to regulate blood pressure through aldosterone binding and stimulation of sodium retention. However, recent studies support the concept that the MR also has extrarenal actions and that defects in sodium handling alone do not fully explain the development of hypertension and associated cardiovascular mortality. We and others have identified functional MR in human vascular smooth muscle cells (SMCs), suggesting that vascular MR might directly regulate blood pressure. Here we show that mice with SMC-specific deficiency of the MR have decreased blood pressure as they age without defects in renal sodium handling or vascular structure. Aged mice lacking MR in SMCs (SMC-MR) have reduced vascular myogenic tone, agonist-dependent contraction and expression and activity of L-type calcium channels. Moreover, SMC-MR contributes to angiotensin II–induced vascular oxidative stress, vascular contraction and hypertension. This study identifies a new role for vascular MR in blood pressure control and in vascular aging and supports the emerging hypothesis that vascular tone contributes directly to systemic blood pressure.
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http://dx.doi.org/10.1038/nm.2891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491085PMC
September 2012