206 results on '"Tsai AL"'
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2. Patient Suicides in Psychiatric Residencies and Post-Vention Responses: A National Survey of Psychiatry Chief Residents and Program Directors
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Tsai, Al, Moran, Scott, and Shoemaker, Richard
- Abstract
Objectives: This report focuses on post-vention measures taken by U.S. psychiatry residencies when a resident-in-training experiences a patient suicide. Methods: A survey distributed to program directors and chief residents obtained an estimate of the frequency of psychiatric residents' experiencing a patient suicide and the frequency of numerous post-vention activities utilized by psychiatric residencies in 2008. The survey looked at the presence or absence of a post-vention protocol within a program and determined whether there was an effect on the number of patient suicides and the frequency of post-vention activities within a program. The data were compared with the results of a similar survey from 1994 to determine whether there had been significant progress in the practice of supportive post-vention activities within training institutions. Results: There was a 21% response rate from chief residents (N=54) and a 31.1% response rate from program directors (N=94). Chief residents reported 1.44 suicides per residency, and program directors reported 0.88 suicides per residency for the 2008 calendar year. This corresponded to approximately 1 in 20 residents' experiencing a patient suicide in the 12-month period. Both groups reported approximately 1 in 5 psychiatry residency programs with written post-vention protocols, which was unchanged from the 1994 survey. When a protocol was in place, chief residents reported a statistically significant increase in timely notification of the program director, process groups, therapy or counseling, and emergency leave, whereas program directors reported a statistically significant decrease in post-vention therapy or counseling. Further statistical analysis revealed a tendency for programs with post-vention protocols to have more reported suicides. Conclusions: Post-vention protocols may be developed by residencies as a need to address residents experiencing a patient suicide. Discrepancies in the reports of chief residents and program directors in post-vention activities may reflect a lack of consensus on post-vention training and education within psychiatric residencies. (Contains 1 table.) more...
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- 2012
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3. Delayed incubation of blood culture bottles
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ROBACK, MARK G., primary, TSAI, AL K., additional, and HANSON, KEVAN L., additional
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- 1994
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4. A 20-year prospective study of childbearing and incidence of diabetes in young women, controlling for glycemia before conception: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.
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Gunderson EP, Lewis CE, Tsai AL, Chiang V, Carnethon M, Quesenberry CP Jr, Sidney S, Gunderson, Erica P, Lewis, Cora E, Tsai, Ai-Lin, Chiang, Vicky, Carnethon, Mercedes, Quesenberry, Charles P Jr, and Sidney, Stephen more...
- Abstract
Objective: We sought to determine whether childbearing increases incidence of type 2 diabetes after accounting for preconception glycemia and gestational glucose intolerance.Research Design and Methods: A prospective, biracial cohort was examined up to five times during 1985-2006 in the multicenter, U.S. population-based Coronary Artery Risk Development in Young Adults Study. The analysis included 2,408 women (1,226 black and 1,182 white) aged 18-30 years who were free of diabetes and had a fasting plasma glucose (FPG) <126 mg/dl at baseline. Incident diabetes was diagnosed by self-report, diabetes medication use, FPG >or=126 mg/dl, and/or plasma glucose >or=200 mg/dl after a 2-h oral glucose load. Time-dependent interim birth groups were those with zero and those with one or more births with or without gestational diabetes mellitus (GDM), stratified by baseline parity. Complementary log-log models estimated relative hazards of incident diabetes by interim births adjusted for age, race, family history of diabetes, and baseline covariates (FPG, BMI, education, smoking, and physical activity).Results: Of 193 incident diabetes cases in 42,782 person-years (4.5 cases/1,000 person-years), 84 (44%) had one or more interim births. Among nulliparas at baseline, incident rates per 1,000 person-years were 3.2 (95% CI 2.4-4.1) for those with no births, 2.9 (1.8-3.9) for one or more births without GDM, and 18.4 (10.9-25.9) for one or more births with GDM; adjusted relative hazards (95% CI) were 0.9 (0.6-1.4) for one or more births without GDM and 3.8 (2.2-6.6) for one or more births with GDM versus no births.Conclusions: Childbearing did not elevate diabetes incidence among those with normal glucose tolerance during pregnancy (without GDM). GDM conferred the highest risk of developing diabetes independent of family history of diabetes and preconception glycemia and obesity. [ABSTRACT FROM AUTHOR] more...- Published
- 2007
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5. Mechanisms of chromosomal rearrangement in the human genome
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Lieber Michael R and Tsai Albert G
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Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Many human cancers are associated with characteristic chromosomal rearrangements, especially hematopoietic cancers such as leukemias and lymphomas. The first and most critical step in the rearrangement process is the induction of two DNA double-strand breaks (DSB). In all cases, at least one of the two DSBs is generated by a pathologic process, such as (1) randomly-positioned breaks due to ionizing radiation, free radical oxidative damage, or spontaneous hydrolysis; (2) breaks associated with topoisomerase inhibitor treatment; or (3) breaks at direct or inverted repeat sequences, mediated by unidentified strand breakage mechanisms. In lymphoid cells, one of the two requisite DSBs is often physiologic, the result of V(D)J recombination or class switch recombination (CSR) at the lymphoid antigen receptor loci. The RAG complex, which causes the DSBs in V(D)J recombination, can cause (4) sequence-specific, pathologic DSBs at sites that fit the consensus of their normal V(D)J recombination signal targets; or (5) structure-specific, pathologic DSBs at regions of single- to double-strand transition. CSR occurs specifically in the B-cell lineage, and requires (6) activation-induced cytidine deaminase (AID) action at sites of single-stranded DNA, which may occur pathologically outside of the normal target loci of class switch recombination regions and somatic hypermutation (SHM) zones. Recent work proposes a seventh mechanism: the sequential action of AID and the RAG complex at CpG sites provides a coherent model for the pathologic DSBs at some of the most common sites of translocation in human lymphoma – the bcl-2 gene in follicular lymphoma and diffuse large B-cell lymphoma, and the bcl-1 gene in mantle cell lymphoma. more...
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- 2010
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6. The use of mobile phones as a data collection tool: A report from a household survey in South Africa
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Ijumba Petrida, Chopra Mickey, Doherty Tanya, Singh Yages, Solomon Wesley, Tomlinson Mark, Tsai Alexander C, and Jackson Debra
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Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
Abstract Background To investigate the feasibility, the ease of implementation, and the extent to which community health workers with little experience of data collection could be trained and successfully supervised to collect data using mobile phones in a large baseline survey Methods A web-based system was developed to allow electronic surveys or questionnaires to be designed on a word processor, sent to, and conducted on standard entry level mobile phones. Results The web-based interface permitted comprehensive daily real-time supervision of CHW performance, with no data loss. The system permitted the early detection of data fabrication in combination with real-time quality control and data collector supervision. Conclusions The benefits of mobile technology, combined with the improvement that mobile phones offer over PDA's in terms of data loss and uploading difficulties, make mobile phones a feasible method of data collection that needs to be further explored. more...
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- 2009
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7. HbA 1c variability associated with dementia risk in people with type 2 diabetes.
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Moran C, Whitmer RA, Dove Z, Lacy ME, Soh Y, Tsai AL, Quesenberry CP, Karter AJ, Adams AS, and Gilsanz P
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- Humans, Female, Male, Middle Aged, Aged, Risk Factors, Blood Glucose, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 epidemiology, Diabetes Mellitus, Type 2 complications, Glycated Hemoglobin analysis, Glycated Hemoglobin metabolism, Dementia epidemiology, Dementia blood
- Abstract
Introduction: Although poor glycemic control is associated with dementia, it is unknown if variability in glycemic control, even in those with optimal glycosylated hemoglobin A
1cipt> (HbA 1c ) levels, increases dementia risk., Methods: Among 171,964 people with type 2 diabetes, we evaluated the hazard of dementia association with long-term HbA1c variability using five operationalizations, including standard deviation (SD), adjusting for demographics and comorbidities., Results: The mean baseline age was 61 years (48% women). Greater HbA1c SD was associated with greater dementia hazard (adjusted hazard ratio = 1.15 [95% confidence interval: 1.12, 1.17]). In stratified analyses, higher HbA1c SD quintiles were associated with greater dementia hazard among those with a mean HbA1c < 6% (P = 0.0004) or 6% to 8% (P < 0.0001) but not among those with mean HbA1c ≥ 8% (P = 0.42)., Discussion: Greater HbA1c variability is associated with greater dementia risk, even among those with HbA1c concentrations at ideal clinical targets. These findings add to the importance and clinical impact of recommendations to minimize glycemic variability., Highlights: We observed a cohort of 171,964 people with type 2 diabetes (mean age 61 years). This cohort was based in Northern California between 1996 and 2018. We examined the association between glycosylated hemoglobin A1c (HbA1c ) variability and dementia risk. Greater HbA1c variability was associated with greater dementia hazard. This was most evident among those with normal-low mean HbA1c concentrations., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.) more...- Published
- 2024
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8. Reduced-Dimensionality Al Nanocrystals: Nanowires, Nanobars, and Nanomoustaches.
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Solti D, Jacobson CR, Yates JAO, Hammel BF, Naidu GN, Arndt CE, Bayles A, Yuan Y, Dhindsa P, Luu JT, Farr C, Wu G, Everitt HO, Tsai AL, Yazdi S, Nordlander P, and Halas NJ
- Abstract
Aluminum nanocrystals created by catalyst-driven colloidal synthesis support excellent plasmonic properties, due to their high level of elemental purity, monocrystallinity, and controlled size and shape. Reduction in the rate of nanocrystal growth enables the synthesis of highly anisotropic Al nanowires, nanobars, and singly twinned "nanomoustaches". Electron energy loss spectroscopy was used to study the plasmonic properties of these nanocrystals, spanning the broad energy range needed to map their plasmonic modes. The coupling between these nanocrystals and other plasmonic metal nanostructures, specifically Ag nanocubes and Au films of controlled nanoscale thickness, was investigated. Al nanocrystals show excellent long-term stability under atmospheric conditions, providing a practical alternative to coinage metal-based nanowires in assembled nanoscale devices. more...
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- 2024
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9. Digital health outreach to promote postpartum screening after gestational diabetes: A randomized factorial pilot study.
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Brown SD, Garcia BL, Ritchie JL, Tsai AL, Millman A, Greenberg M, Quesenberry CP, and Ferrara A
- Abstract
Objective: We examined the acceptability and feasibility of a multi-component digital health outreach intervention to promote uptake of guideline-recommended postpartum screening for type 2 diabetes among patients with gestational diabetes (GDM)., Methods: We conducted a 2
4 randomized factorial experiment as part of the Multiphase Optimization Strategy (MOST) preparation phase for developing behavioral interventions. Participants with current or recent GDM in an integrated healthcare system were randomized to receive an outreach message with up to four intervention components, designed to be self-administered in about 10 min and efficiently delivered online via REDCap: a streamlined values affirmation, personalized information on diabetes risk, an interactive motivational interviewing-based component, and an interactive action planning component. Patient-reported acceptability and feasibility outcomes were assessed via survey., Results: Among 162 participants, 72% self-identified with a racial/ethnic minority group. Across components, acceptability scores averaged 3.9/5; ≥91% of participants read most or all of the outreach message; ≥89% perceived the amount of information as "about right"; and ≥ 87% completed ≥1 interactive prompt., Conclusion: Each intervention component was acceptable to diverse patients and feasible to deliver in a brief, self-directed, online format., Innovation: These novel components target unaddressed barriers to patient engagement in guideline-recommended postpartum diabetes screening and adapt theory-based behavior change techniques for large-scale use., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Susan D. Brown reports financial support was provided by the Kaiser Permanente Northern California Division of Research and the 10.13039/100000062National Institute of Diabetes and Digestive and Kidney Diseases., (© 2024 The Authors.) more...- Published
- 2024
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10. Mechanism of stepwise electron transfer in six-transmembrane epithelial antigen of the prostate (STEAP) 1 and 2.
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Chen K, Wang L, Shen J, Tsai AL, Zhou M, and Wu G
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- Male, Humans, NADP metabolism, Cryoelectron Microscopy, Oxidoreductases metabolism, Heme metabolism, Antigens, Neoplasm, Electrons, Prostate metabolism
- Abstract
Six transmembrane epithelial antigen of the prostate (STEAP) 1-4 are membrane-embedded hemoproteins that chelate a heme prosthetic group in a transmembrane domain (TMD). STEAP2-4, but not STEAP1, have an intracellular oxidoreductase domain (OxRD) and can mediate cross-membrane electron transfer from NADPH via FAD and heme. However, it is unknown whether STEAP1 can establish a physiologically relevant electron transfer chain. Here, we show that STEAP1 can be reduced by reduced FAD or soluble cytochrome b
5 reductase that serves as a surrogate OxRD, providing the first evidence that STEAP1 can support a cross-membrane electron transfer chain. It is not clear whether FAD, which relays electrons from NADPH in OxRD to heme in TMD, remains constantly bound to the STEAPs. We found that FAD reduced by STEAP2 can be utilized by STEAP1, suggesting that FAD is diffusible rather than staying bound to STEAP2. We determined the structure of human STEAP2 in complex with NADP+ and FAD to an overall resolution of 3.2 Å by cryo-electron microscopy and found that the two cofactors bind STEAP2 similarly as in STEAP4, suggesting that a diffusible FAD is a general feature of the electron transfer mechanism in the STEAPs. We also demonstrated that STEAP2 reduces ferric nitrilotriacetic acid (Fe3+ -NTA) significantly slower than STEAP1 and proposed that the slower reduction is due to the poor Fe3+ -NTA binding to the highly flexible extracellular region in STEAP2. These results establish a solid foundation for understanding the function and mechanisms of the STEAPs., Competing Interests: KC, LW, JS, AT, MZ, GW No competing interests declared, (© 2023, Chen, Wang et al.) more...- Published
- 2023
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11. Free ferrous ions sustain activity of mammalian stearoyl-CoA desaturase-1.
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Shen J, Wu G, Pierce BS, Tsai AL, and Zhou M
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- Animals, Fatty Acids chemistry, Fatty Acids metabolism, Mammals, Lipid Metabolism, Iron chemistry, Iron metabolism, Stearoyl-CoA Desaturase metabolism, Cations, Divalent chemistry, Cations, Divalent metabolism, Biocatalysis
- Abstract
Mammalian stearoyl-CoA desaturase-1 (SCD1) introduces a double-bond to a saturated long-chain fatty acid in a reaction catalyzed by a diiron center. The diiron center is well-coordinated by conserved histidine residues and is thought to remain with the enzyme. However, we find here that SCD1 progressively loses its activity during catalysis and becomes fully inactive after about nine turnovers. Further studies show that the inactivation of SCD1 is due to the loss of an iron (Fe) ion in the diiron center and that the addition of free ferrous ions (Fe
2+ ) sustains the enzymatic activity. Using SCD1 labeled with Fe isotope, we further show that free Fe2+ is incorporated into the diiron center only during catalysis. We also discover that the diiron center in SCD1 has prominent electron paramagnetic resonance signals in its diferric state, indicative of distinct coupling between the two ferric ions. These results reveal that the diiron center in SCD1 is structurally dynamic during catalysis and that labile Fe2+ in cells could regulate SCD1 activity and hence lipid metabolism., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.) more...- Published
- 2023
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12. Effects of Dextromethorphan on Nicotine-Induced Reward, Behavioral Sensitization, Withdrawal Signs, and Drug Seeking-Related Behavior in Rats.
- Author
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Huang EY, Hung HY, Chen YH, Kao JH, Tsai AL, and Chow LH
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- Rats, Animals, Nicotine adverse effects, Nicotine metabolism, Dextromethorphan pharmacology, Dextromethorphan metabolism, Rats, Sprague-Dawley, Reward, Nucleus Accumbens metabolism, Dopamine metabolism, Tobacco Use Disorder drug therapy, Tobacco Use Disorder metabolism, Substance Withdrawal Syndrome drug therapy, Substance Withdrawal Syndrome metabolism
- Abstract
Introduction: Tobacco products are addictive, with nicotine serving as the major addictive ingredient. Chronic tobacco use or chronic administration of nicotine alone results in both physiological and psychological dependence. Our previous studies indicated that dextromethorphan (DM) could effectively attenuate the dependence of morphine and methamphetamine. Thus, we further investigated the possible effects of DM on nicotine dependence., Aims and Methods: Conditioned place preference (CPP) test was used to examine nicotine-induced rewarding effects as well as the drug-seeking-related behavior in rats. Nicotine dependence was induced by continuous subcutaneous infusion of nicotine via an osmotic minipump for 7 days and abstinence was initiated by removal of the pump. Withdrawal signs were observed and quantified. Locomotor activity was measured to determine the behavioral sensitization induced by nicotine. To investigate the activity of mesolimbic dopaminergic neuronal activity in correlation with the effects of nicotine, the animals were sacrificed and the nucleus accumbens (NAc), dorsal striatum (DS), and medial prefrontal cortex (mPFC) were dissected and used to determine the contents of dopamine (DA) and its metabolites using high-performance liquid chromatography (HPLC)., Results: Our results showed that DM could suppress nicotine-induced rewarding effect and drug-seeking-related behavior. In addition, co-administration and post-treatment of DM could both attenuate nicotine withdrawal signs. Moreover, DM could suppress nicotine-induced behavioral sensitization. Neurochemical experiments show that co-administration and post-treatment of DM abolished nicotine-induced increase of the DA turnover rate in the mPFC, but not in the NAc and DS., Conclusions: The results suggest that DM has a great therapeutic potential in the treatment of nicotine dependence., Implications: Our results showed that DM could suppress nicotine-induced rewarding effect and drug-seeking-related behavior. In addition, co-administration and post-treatment of DM could both attenuate nicotine withdrawal signs. Moreover, DM could suppress nicotine-induced behavioral sensitization. Neurochemical experiments show that co-administration and post-treatment of DM abolished nicotine-induced increase of the DA turnover rate in the mPFC, but not in the NAc and DS. These results suggest that DM has a great therapeutic potential in the treatment of nicotine dependence., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.) more...
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- 2023
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13. Glycemic Control Over Multiple Decades and Dementia Risk in People With Type 2 Diabetes.
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Moran C, Lacy ME, Whitmer RA, Tsai AL, Quesenberry CP, Karter AJ, Adams AS, and Gilsanz P
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- Male, Adult, Humans, Aged, Female, Glycated Hemoglobin, Cohort Studies, Glycemic Control, Diabetes Mellitus, Type 2 complications, Dementia
- Abstract
Importance: The levels of glycemic control associated with the lowest risk of dementia in people with type 2 diabetes are unknown. This knowledge is critical to inform patient-centered glycemic target setting., Objective: To examine the associations between cumulative exposure to various ranges of glycated hemoglobin (HbA1c) concentrations with dementia risk across sex and racial and ethnic groups and the association of current therapeutic glycemic targets with dementia risk., Design, Setting, and Participants: This cohort study included members of the Kaiser Permanente Northern California integrated health care system with type 2 diabetes who were aged 50 years or older during the study period from January 1, 1996, to September 30, 2015. Individuals with fewer than 2 HbA1c measurements during the study period, prevalent dementia at baseline, or less than 3 years of follow-up were excluded. Data were analyzed from February 2020 to January 2023., Exposures: Time-updated cumulative exposure to HbA1c thresholds. At each HbA1c measurement, participants were categorized based on the percentage of their HbA1c measurements that fell into the following categories: less than 6%, 6% to less than 7%, 7% to less than 8%, 8% to less than 9%, 9% to less than 10%, and 10% or more of total hemoglobin (to convert percentage of total hemoglobin to proportion of total hemoglobin, multiply by 0.01)., Main Outcomes and Measures: Dementia diagnosis was identified using International Classification of Diseases, Ninth Revision codes from inpatient and outpatient encounters. Cox proportional hazards regression models estimated the association of time-varying cumulative glycemic exposure with dementia, adjusting for age, race and ethnicity, baseline health conditions, and number of HbA1c measurements., Results: A total of 253 211 participants were included. The mean (SD) age of participants was 61.5 (9.4) years, and 53.1% were men. The mean (SD) duration of follow-up was 5.9 (4.5) years. Participants with more than 50% of HbA1c measurements at 9% to less than 10% or 10% or more had greater risk of dementia compared with those who had 50% or less of measurements in those categories (HbA1c 9% to <10%: adjusted hazard ratio [aHR], 1.31 [95% CI, 1.15-1.51]; HbA1c≥10%: aHR, 1.74 [95% CI, 1.62-1.86]). By contrast, participants with more than 50% of HbA1c concentrations less than 6%, 6% to less than 7%, or 7% to less than 8% had lower risk of dementia (HbA1c<6%: aHR, 0.92 [95% CI, 0.88-0.97]; HbA1c 6% to <7%: aHR, 0.79 [95% CI, 0.77-0.81]; HbA1c 7% to <8%: aHR, 0.93 [95% CI, 0.89-0.97])., Conclusions and Relevance: In this study dementia risk was greatest among adults with cumulative HbA1c concentrations of 9% or more. These results support currently recommended relaxed glycemic targets for older people with type 2 diabetes. more...
- Published
- 2023
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14. Unprecedented outbreak of respiratory syncytial virus in Taiwan associated with ON1 variant emergence between 2010 and 2020.
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Lin WH, Wu FT, Chen YY, Wang CW, Lin HC, Kuo CC, Lai WC, Lin FJ, Tiew WT, Tsai AL, Ho KT, Kuo TY, Li CH, Wu CY, Pan YJ, Tsao KC, and Hsieh YC
- Subjects
- Child, Preschool, Humans, Phylogeny, Retrospective Studies, Taiwan epidemiology, Epidemics, Respiratory Syncytial Virus, Human genetics
- Abstract
An outbreak of respiratory syncytial virus (RSV) has been observed in Taiwan since August 2020. We reviewed a central laboratory-based surveillance network established over 20 years by Taiwan Centres for Disease Control for respiratory viral pathogens between 2010 and 2020.A retrospective study of children <5 years old hospitalized with RSV infection at Chang Gung Memorial Hospital between 2018 and 2020 was conducted, and samples positive for RSV-A were sequenced. Clinical data were obtained and stratified by genotype and year.Data from 2020 showed an approximately 4-fold surge in RSV cases compared to 2010 in Taiwan, surpassing previous years during which ON1 was prevalent. Phylogenetic analysis of G protein showed that novel ON1 variants were clustered separately from those of 2018 and 2019 seasons and ON1 reference strains. The variant G protein carried six amino acid changes that emerged gradually in 2019; high consistency was observed in 2020. A unique substitution, E257K, was observed in 2020 exclusively. The F protein of the variant carried T12I and H514N substitutions, which weren't at antigenic sites. In terms of multivariate analysis, age (OR: 0.97; 95% CI: 0.94-0.99; p = 0.02) and 2020 ON1 variant (OR:2.52; 95% CI:1.13-5.63; p = 0.025) were independently associated with oxygen saturation <94% during hospitalization.The 2020 ON1 variant didn't show higher replication or virulence compared with those in 2018 in our study. The unprecedented 2020 RSV epidemic may attribute to antigenic changes and lack of interferon-stimulated immunity induced by seasonal circulating virus under non-pharmaceutical intervention. more...
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- 2022
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15. Plasmon-Generated Solvated Electrons for Chemical Transformations.
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Solti D, Chapkin KD, Renard D, Bayles A, Clark BD, Wu G, Zhou J, Tsai AL, Kürti L, Nordlander P, and Halas NJ
- Subjects
- Electrons, Light
- Abstract
Methods for generating solvated electrons─free electrons in solution─have focused primarily on alkali metal ionization or high-energy electrons or photons. Here we report the generation of solvated electrons by exciting the plasmon resonance of Al nanocrystals suspended in solution with visible light. Two chemical reactions were performed: a radical-addition reaction with the spin-trap 2-methyl-2-nitrosopropane, and a model cyclization reaction with the radical clock 6-bromohex-1-ene. A quantum efficiency of at least ∼1.1% for plasmon absorbed photon to solvated electron generation can be inferred from the measured radical clock reaction concentration. This study demonstrates a simple way to generate solvated electrons for driving reductive organic chemical reactions in a quantifiable and controlled manner. more...
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- 2022
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16. Transmembrane helices mediate the formation of a stable ternary complex of b 5 R, cyt b 5 , and SCD1.
- Author
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Shen J, Wu G, Tsai AL, and Zhou M
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- Animals, Electron Transport, Mammals, Oxidoreductases, Cytochromes b, Electrons
- Abstract
Mammalian cytochrome b
5 (cyt b5 ) and cytochrome b5 reductase (b5 R) are electron carrier proteins for membrane-embedded oxidoreductases. Both b5 R and cyt b5 have a cytosolic domain and a single transmembrane (TM) helix. The cytosolic domains of b5 R and cyt b5 contain cofactors required for electron transfer, but it is not clear if the TM helix has function beyond being an anchor to the membrane. Here we show that b5 R and cyt b5 form a stable binary complex, and so do cyt b5 and stearoyl-CoA desaturase-1 (SCD1). We also show that b5 R, cyt b5 and SCD1 form a stable ternary complex. We demonstrate that the TM helices are required for the assembly of stable binary and ternary complexes where electron transfer rates are greatly enhanced. These results reveal a role of the TM helix in cyt b5 and b5 R, and suggest that an electron transport chain composed of a stable ternary complex may be a general feature in membrane-embedded oxidoreductases that require cyt b5 and b5 R., (© 2022. The Author(s).) more...- Published
- 2022
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17. Reach, acceptability, and perceived success of a telehealth diabetes prevention program among racially and ethnically diverse patients with gestational diabetes: the GEM cluster-randomized trial.
- Author
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Brown SD, Hedderson MM, Gordon N, Albright CL, Tsai AL, Quesenberry CP, and Ferrara A
- Subjects
- Ethnicity, Female, Humans, Minority Groups, Pregnancy, United States, Diabetes Mellitus, Type 2 prevention & control, Diabetes, Gestational prevention & control, Telemedicine
- Abstract
Patients with gestational diabetes mellitus and from racial/ethnic minority groups face disproportionate risk for type 2 diabetes. Lifestyle interventions, if accessible and acceptable to diverse patients, could advance diabetes prevention and mitigate racial/ethnic disparities. Here we describe overall and race/ethnicity-specific reach, acceptability, and perceived success from an effective telehealth diabetes prevention lifestyle program for patients with gestational diabetes mellitus, implemented in the Gestational Diabetes Effects on Moms (GEM) cluster-randomized controlled trial. GEM tested a program of 13 telephone sessions and behavior change techniques (BCTs, e.g., goal setting) in a healthcare system. We evaluated participation (completing ≥1 session), acceptability of BCTs, and perceived success reaching program goals. Among 1,087 patients (75.2% from minority groups), 50.3% participated. Participation rates were 61.7% among Black, 56.4% among Hispanic, 55.6% among multiracial/other, 53.0% among White, and 43.7% among Asian/Pacific Islander patients. Evaluation survey respondents (n = 433/547; 79.2%) largely rated BCTs as very helpful (range 40.9%-58.4%) or moderately helpful (27.3%-34.9%). Respondents from minority groups largely rated goal setting for weight management as very or moderately helpful, with fewer minority respondents rating it as only a little/not at all helpful than White respondents (p = .02). Black and White respondents reported more limited success reaching a healthy weight than Asian/Pacific Islander, Hispanic, and multiracial/other women (p = .005). A telehealth diabetes prevention lifestyle program demonstrated reach and acceptability across racial/ethnic groups. While perceived success can be improved among Black and White participants, such programs could promote access to preventive care and help mitigate disparities in diabetes risk., (© Society of Behavioral Medicine 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.) more...
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- 2022
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18. A Dual Catalyst Strategy for Controlling Aluminum Nanocrystal Growth.
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Jacobson CR, Wu G, Alemany LB, Naidu GN, Lou M, Yuan Y, Bayles A, Clark BD, Cheng Y, Ali A, Tsai AL, Tonks IA, Nordlander P, and Halas NJ
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- Catalysis, Ligands, Aluminum, Nanoparticles chemistry
- Abstract
The synthesis of Al nanocrystals (Al NCs) is a rapidly expanding field, but there are few strategies for size and morphology control. Here we introduce a dual catalyst approach for the synthesis of Al NCs to control both NC size and shape. By using one catalyst that nucleates growth more rapidly than a second catalyst whose ligands affect NC morphology during growth, one can obtain both size and shape control of the resulting Al NCs. The combination of the two catalysts (1) titanium isopropoxide (TIP), for rapid nucleation, and (2) Tebbe's reagent, for specific facet-promoting growth, yields {100}-faceted Al NCs with tunable diameters between 35 and 65 nm. This dual-catalyst strategy could dramatically expand the possible outcomes for Al NC growth, opening the door to new controlled morphologies and a deeper understanding of earth-abundant plasmonic nanocrystal synthesis. more...
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- 2022
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19. Perspectives on postpartum diabetes screening among patients with gestational diabetes in an integrated healthcare system.
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Glaser K, Ferrara A, Ritchie JL, Tsai AL, Greenberg M, Quesenberry CP, and Brown SD
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- Blood Glucose, Female, Glucose Tolerance Test, Humans, Mass Screening, Postpartum Period, Pregnancy, Delivery of Health Care, Integrated, Diabetes Mellitus, Type 2 diagnosis, Diabetes, Gestational diagnosis, Diabetes, Gestational epidemiology
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- 2022
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20. Investigation of a cluster of Bacillus cereus bacteremia in neonatal care units.
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Tsai AL, Hsieh YC, Chen CJ, Huang KY, Chiu CH, Kuo CY, Lin TY, Lai MY, Chiang MC, and Huang YC
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- Bacillus cereus genetics, Disease Outbreaks, Humans, Infant, Newborn, Infant, Premature, Multilocus Sequence Typing, Bacteremia epidemiology, Cross Infection epidemiology
- Abstract
Background: Bacillus cereus is a well-known pathogen for self-limited foodborne illness, and rarely an opportunistic pathogen associated with invasive infections among immunocompromised patients. Nosocomial outbreaks have been rarely reported., Methods: Between August and November 2019, four preterm neonates in neonatal care units of a medical center developed late-onset B. cereus bacteremia. An investigation was carried out. Forty-eight environmental specimens were obtained from these neonatal units, skin surface and environmental objects of Patient 4 for the detection of this organism 19 days after the onset of illness of Patient 4. B. cereus isolates from Patient 4, five unrelated patients and environmental objects if identified were further characterized by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST)., Results: All four infants survived after vancomycin-containing treatment. Patient 4 developed diffuse cerebritis, brain abscess with severe neurologic sequelae. Of the 48 environmental samplings, 26 specimens showed positive for B. cereus, with one major clone (sequence type 365) accounting for 73%. The isolate from Patient 4 (ST427) was identical to one isolate collected from environmental objects in the same unit. After extensive cleaning of the environment and re-institution of the sterilization procedure of hospital linens, which was ceased since two months before the outbreak, no more cases was identified in these units for at least one year., Conclusions: We documented a cluster of B. cereus bacteremia involving four preterm infants, which might be associated with cessation of the procedure for linen sterilization and was successfully controlled by re-institution of this procedure., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021. Published by Elsevier B.V.) more...
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- 2022
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21. Uptake of guideline-recommended postpartum diabetes screening among diverse women with gestational diabetes: associations with patient factors in an integrated health system in USA.
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Brown SD, Hedderson MM, Zhu Y, Tsai AL, Feng J, Quesenberry CP, and Ferrara A
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- Child, Female, Glucose Tolerance Test, Humans, Infant, Newborn, Postpartum Period, Pregnancy, Delivery of Health Care, Integrated, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 epidemiology, Diabetes, Gestational diagnosis, Diabetes, Gestational epidemiology
- Abstract
Introduction: Clinical guidelines urge timely postpartum screening for diabetes among women with gestational diabetes mellitus (GDM), yet patient factors associated with screening uptake remain unclear. We aimed to identify patient factors associated with completed postpartum diabetes screening (2-hour oral glucose tolerance test within 4-12 weeks postpartum), as recommended by the American Diabetes Association (ADA)., Research Design and Methods: Within the context of Gestational Diabetes' Effects on Moms (GEM), a pragmatic cluster randomized trial (2011-2012), we examined survey and electronic health record data to assess clinical and sociodemographic factors associated with uptake of ADA-recommended postpartum screening. Participants included 1642 women (76% racial/ethnic minorities) identified with GDM according to the Carpenter and Coustan criteria in a health system that deploys population-level strategies to promote screening. To contextualize these analyses, screening rates derived from the GEM trial were compared with those in the health system overall using registry data from a concurrent 10-year period (2007-2016, n=21 974)., Results: Overall 52% (n=857) completed recommended postpartum screening in the analytic sample, comparable to 45.7% (n=10 040) in the registry. Screening in the analytic sample was less likely among women at elevated risk for type 2 diabetes, assessed using items from an ADA risk test (vs non-elevated; adjusted rate ratio (aRR)=0.86 (95% CI 0.75 to 0.98)); perinatal depression (0.88 (0.79 to 0.98)); preterm delivery (0.84 (0.72 to 0.98)); parity ≥2 children (vs 0; 0.80 (0.69 to 0.93)); or less than college education (0.79 (0.72 to 0.86)). Screening was more likely among Chinese Americans (vs White; 1.31 (1.15 to 1.49)); women who attended a routine postpartum visit (5.28 (2.99 to 9.32)); or women who recalled receiving healthcare provider advice about screening (1.31 (1.03 to 1.67))., Conclusions: Guideline-recommended postpartum diabetes screening varied by patient clinical and sociodemographic factors. Findings have implications for developing future strategies to improve postpartum care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.) more...
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- 2022
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22. Methods-Motivational Interviewing Approach for Enhanced Retention and Attendance.
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Jake-Schoffman DE, Brown SD, Baiocchi M, Bibeau JL, Daubenmier J, Ferrara A, Galarce MN, Hartogensis W, Hecht FM, Hedderson MM, Moran PJ, Pagoto SL, Tsai AL, Waring ME, and Kiernan M
- Subjects
- Exercise, Humans, Outcome Assessment, Health Care, Motivational Interviewing
- Abstract
Introduction: Suboptimal and differential participant engagement in randomized trials-including retention at primary outcome assessments and attendance at intervention sessions-undermines rigor, internal validity, and trial conclusions., Methods: First, this study describes Methods-Motivational Interviewing approach and strategies for implementation. This approach engages potential participants before randomization through interactive, prerequisite orientation sessions that illustrate the scientific rationale behind trial methods in accessible language and use motivational interviewing to diffuse ambivalence about participation. Then, this study examines the potential improvements in retention (proportion of participants assessed at follow-up visits) and attendance (e.g., mean percentage of intervention sessions attended, percentage of participants who attended 0 sessions) in 3 randomized weight-management trials that quickly added prerequisite orientations to their protocols following early signs of suboptimal or differential participant engagement (Supporting Health by Integrating Nutrition and Exercise [2009-2013, n=194]; Get Social [2016-2020, n=217]; GestationaL Weight Gain and Optimal Wellness [2014-2018, n=389]). Using a pre-post analytical design, adjusted estimates from regression models controlling for condition and assessment timepoint (analyses from 2020) are reported., Results: After adding prerequisite orientations, all 3 trials attained higher participant engagement. Retention at assessments was 11.4% and 17.3% higher (Get Social and Supporting Health by Integrating Nutrition and Exercise, respectively). Mean percentage of attendance at intervention sessions was 8.8% higher (GestationaL Weight Gain and Optimal Wellness), and 10.1% fewer participants attended 0 intervention sessions (Get Social). Descriptively, all the remaining retention and attendance outcomes were consistently higher but were nonsignificant. Across the trials, adding prerequisite orientations did not impact the proportion of eligible participants enrolled or the baseline demographics., Conclusions: The Methods-Motivational Interviewing approach shows promise for increasing the rigor of randomized trials and is readily adaptable to in-person, webinar, and conference call formats., Trial Registration: All 3 trials are registered at www.clinicaltrials.gov (Supporting Health by Integrating Nutrition and Exercise: NCT00960414; Get Social: NCT02646618; and GestationaL Weight Gain and Optimal Wellness: NCT02130232)., (Copyright © 2021 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2021
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23. A new paradigm for gaseous ligand selectivity of hemoproteins highlighted by soluble guanylate cyclase.
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Wu G, Martin E, Berka V, Liu W, Garcin ED, and Tsai AL
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- Carbon Monoxide chemistry, Hemeproteins chemistry, Nitric Oxide chemistry, Oxygen chemistry, Soluble Guanylyl Cyclase chemistry, Carbon Monoxide metabolism, Hemeproteins metabolism, Nitric Oxide metabolism, Oxygen metabolism, Soluble Guanylyl Cyclase metabolism
- Abstract
Nitric oxide (NO), carbon monoxide (CO), and oxygen (O
2 ) are important physiological messengers whose concentrations vary in a remarkable range, [NO] typically from nM to several μM while [O2 ] reaching to hundreds of μM. One of the machineries evolved in living organisms for gas sensing is sensor hemoproteins whose conformational change upon gas binding triggers downstream response cascades. The recently proposed "sliding scale rule" hypothesis provides a general interpretation for gaseous ligand selectivity of hemoproteins, identifying five factors that govern gaseous ligand selectivity. Hemoproteins have intrinsic selectivity for the three gases due to a neutral proximal histidine ligand while proximal strain of heme and distal steric hindrance indiscriminately adjust the affinity of these three gases for heme. On the other hand, multiple-step NO binding and distal hydrogen bond donor(s) specifically enhance affinity for NO and O2 , respectively. The "sliding scale rule" hypothesis provides clear interpretation for dramatic selectivity for NO over O2 in soluble guanylate cyclase (sGC) which is an important example of sensor hemoproteins and plays vital roles in a wide range of physiological functions. The "sliding scale rule" hypothesis has so far been validated by all experimental data and it may guide future designs for heme-based gas sensors., (Copyright © 2020 Elsevier Inc. All rights reserved.) more...- Published
- 2021
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24. The Chemical Basis of Intracerebral Hemorrhage and Cell Toxicity With Contributions From Eryptosis and Ferroptosis.
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Derry PJ, Vo ATT, Gnanansekaran A, Mitra J, Liopo AV, Hegde ML, Tsai AL, Tour JM, and Kent TA
- Abstract
Intracerebral hemorrhage (ICH) is a particularly devastating event both because of the direct injury from space-occupying blood to the sequelae of the brain exposed to free blood components from which it is normally protected. Not surprisingly, the usual metabolic and energy pathways are overwhelmed in this situation. In this review article, we detail the complexity of red blood cell degradation, the contribution of eryptosis leading to hemoglobin breakdown into its constituents, the participants in that process, and the points at which injury can be propagated such as elaboration of toxic radicals through the metabolism of the breakdown products. Two prominent products of this breakdown sequence, hemin, and iron, induce a variety of pathologies including free radical damage and DNA breakage, which appear to include events independent from typical oxidative DNA injury. As a result of this confluence of damaging elements, multiple pathways of injury, cell death, and survival are likely engaged including ferroptosis (which may be the same as oxytosis but viewed from a different perspective) and senescence, suggesting that targeting any single cause will likely not be a sufficient strategy to maximally improve outcome. Combination therapies in addition to safe methods to reduce blood burden should be pursued., Competing Interests: TK, PD, A-LT, JT, JM, and MH hold patents pending for the PEG-HCC and DEF-PEG-HCC particles described herein. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Derry, Vo, Gnanansekaran, Mitra, Liopo, Hegde, Tsai, Tour and Kent.) more...
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- 2020
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25. Association Between Topical Calcineurin Inhibitor Use and Keratinocyte Carcinoma Risk Among Adults With Atopic Dermatitis.
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Asgari MM, Tsai AL, Avalos L, Sokil M, and Quesenberry CP Jr
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- Adult, Aged, Calcineurin Inhibitors administration & dosage, Carcinoma, Basal Cell chemically induced, Carcinoma, Basal Cell pathology, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell pathology, Female, Follow-Up Studies, Glucocorticoids administration & dosage, Humans, Incidence, Keratinocytes drug effects, Keratinocytes pathology, Male, Middle Aged, Product Surveillance, Postmarketing statistics & numerical data, Retrospective Studies, Risk Assessment statistics & numerical data, Skin Neoplasms chemically induced, Skin Neoplasms pathology, Calcineurin Inhibitors adverse effects, Carcinoma, Basal Cell epidemiology, Carcinoma, Squamous Cell epidemiology, Dermatitis, Atopic drug therapy, Glucocorticoids adverse effects, Skin Neoplasms epidemiology
- Abstract
Importance: Topical calcineurin inhibitors (TCIs), primarily used to treat atopic dermatitis (AD), carry a black box label warning users about the potential for increased skin cancer risk. The risk associated with keratinocyte carcinoma (KC), the most common cancer, defined as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), remains poorly defined because findings from large-scale postmarketing surveillance studies have not been reported., Objectives: To examine KC risk overall and by subtype (BCC and SCC) among adults with AD exposed to TCIs compared with those exposed to topical corticosteroids (primary comparator group) and those unexposed to TCIs or topical corticosteroids (alternative comparator group) as well as alterations in risk with TCI dose, frequency, and duration of exposure., Design, Setting, and Participants: A retrospective cohort study was conducted at Kaiser Permanente Northern California, a large, integrated health care delivery system, of adults 40 years or older (n = 93 746) with a physician-rendered diagnosis of AD or dermatitis. Patients who were diagnosed from January 1, 2002, to December 31, 2013, were included, with follow-up through December 31, 2017. Data analysis was conducted from June 1, 2016, to October 1, 2018., Exposures: Time-varying pharmacy-dispensed TCI exposure (n = 7033) over the study period was compared with topical corticosteroids (n = 73 674) and no TCI or topical corticosteroid exposure (n = 46 141)., Main Outcomes and Measures: Electronic pathologic testing-validated incident KCs (n = 7744)., Results: Among a cohort of 93 746 members, the mean (SD) age was 58.5 (12.7) years, and 55 023 patients (58.7%) were women. Multivariable Cox proportional hazards regression revealed no association between TCI exposure and KC risk (adjusted hazard ratio [aHR], 1.02; 95% CI, 0.93-1.13) compared with topical corticosteroid exposure. Similarly, there were no significant differences in BCC risk (aHR, 1.01; 95% CI, 0.90-1.14, TCI vs topical corticosteroids) or SCC risk (aHR, 0.94; 95% CI, 0.82-1.08, TCI vs topical corticosteroids). Changing the comparator group to unexposed individuals yielded similar findings (aHR, 1.04; 95% CI, 0.91-1.19, TCI vs unexposed for basal cell carcinoma). There were no associations between TCI dose, frequency, and duration of use and BCC, SCC, or overall KC risk., Conclusions and Relevance: The results of this postmarketing surveillance study of adult health plan members with AD revealed no apparent association between TCI exposure and overall KC, BCC, or SCC risk. Secondary analyses examining dose, frequency, and duration of TCI exposure revealed no associations. These findings suggest that use of TCIs may be safe with respect to KC risk among adults with AD. more...
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- 2020
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26. Structure and Mechanism of a Unique Diiron Center in Mammalian Stearoyl-CoA Desaturase.
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Shen J, Wu G, Tsai AL, and Zhou M
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- Animals, Catalytic Domain, Crystallography, X-Ray, HEK293 Cells, Humans, Iron metabolism, Mice, Models, Molecular, Protein Conformation, Protein Domains, Sf9 Cells, Stearoyl-CoA Desaturase genetics, Zinc metabolism, Cytochrome-B(5) Reductase metabolism, Cytochromes b5 metabolism, Stearoyl-CoA Desaturase chemistry, Stearoyl-CoA Desaturase metabolism
- Abstract
Stearoyl-CoA desaturase 1 (SCD1) is a membrane-embedded metalloenzyme that catalyzes the formation of a double bond on a saturated acyl-CoA. SCD1 has a diiron center and its proper function requires an electron transport chain composed of NADH (or NADPH), cytochrome b
5 reductase (b5 R), and cytochrome b5 (cyt b5 ). Since SCD1 is a key regulator in fat metabolism and is required for survival of cancer cells, there is intense interest in targeting SCD1 for various metabolic diseases and cancers. Crystal structures of human and mouse SCD1 were reported recently; however, both proteins have two zinc ions instead of two iron ions in the catalytic center, and as a result, the enzymes are inactive. Here we report a general approach for incorporating iron into heterologously expressed proteins in HEK293 cells. We produced mouse SCD1 that contains a diiron center and visualized its diiron center by solving its crystal structure to 3.5 Å. We assembled the entire electron transport chain using the purified soluble domains of cyt b5 and b5 R, and the purified mouse SCD1, and we showed that three proteins coordinate to produce proper products. These results established an in vitro system that allows precise perturbations of the electron transport chain for the understanding of the catalytic mechanism in SCD1., (Copyright © 2020 Elsevier Ltd. All rights reserved.) more...- Published
- 2020
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27. A telehealth lifestyle intervention to reduce excess gestational weight gain in pregnant women with overweight or obesity (GLOW): a randomised, parallel-group, controlled trial.
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Ferrara A, Hedderson MM, Brown SD, Ehrlich SF, Tsai AL, Feng J, Galarce M, Marcovina S, Catalano P, and Quesenberry CP
- Subjects
- Adult, Exercise physiology, Female, Follow-Up Studies, Humans, Obesity blood, Obesity diagnosis, Obesity therapy, Overweight blood, Overweight diagnosis, Pregnancy, Weight Loss physiology, Young Adult, Gestational Weight Gain physiology, Overweight therapy, Prenatal Care methods, Risk Reduction Behavior, Telemedicine methods
- Abstract
Background: Excess gestational weight gain (GWG) among women with overweight or obesity synergistically increases their already elevated risk of having gestational diabetes, a caesarean delivery, a large for gestational age infant, and post-partum weight retention, and increases their child's risk of obesity. We investigated whether a primarily telehealth lifestyle intervention reduced excess GWG among women with overweight or obesity., Methods: We did a randomised controlled trial in five antenatal clinics of Kaiser Permanente; Oakland, San Leandro, Walnut Creek, Fremont, and Santa Clara, CA, USA. Women at 8-15 weeks' gestation with singletons, pre-pregnancy BMI 25·0-40·0 kg/m
2 , and aged 18 years or older were randomly assigned (1:1) to receive the telehealth lifestyle intervention or usual antenatal care. Randomisation was adaptively balanced for age, BMI, and race and ethnicity. Data collectors and investigators were masked to group assignments. The core lifestyle intervention consisted of two in-person and 11 telephone sessions on behavioural strategies to improve weight, diet, and physical activity, and stress management to help women meet a trial goal of gaining at the lower limit of the Institute of Medicine (IOM) guidelines range for total GWG: 7 kg for women with overweight and 5 kg for women with obesity. Usual antenatal care included an antenatal visit at 7-10 weeks' gestation, an additional seven antenatal visits, on average, and periodic health education newsletters, including the IOM GWG guidelines and information on healthy eating and physical activity in pregnancy. The primary outcome was weekly rate of GWG expressed as excess GWG, per Institute of Medicine guidelines and mean assessed in the intention-to-treat population. The trial is registered at ClinicalTrials.gov, NCT02130232., Findings: Between March 24, 2014, and Sept 26, 2017, 5329 women were assessed for eligibility and 200 were randomly assigned to the lifestyle intervention group and 198 to the usual care group. Analyses included 199 women in the lifestyle intervention group (one lost to follow-up) and 195 in the usual care group (three lost to follow-up). 96 (48%) women in the lifestyle intervention group and 134 (69%) women in the usual care group exceeded Institute of Medicine guidelines for rate of GWG per week (relative risk 0·70, 95% CI 0·59 to 0·83). Compared with usual care, women in the lifestyle intervention had reduced weekly rate of GWG (mean 0·26 kg per week [SD 0·15] vs 0·32 kg per week [0·13]; mean between-group difference -0·07 kg per week, 95% CI -0·09 to -0·04). No between-group differences in perinatal complications were observed., Interpretation: Our evidence-based programme showed that health-care delivery systems could further adapt to meet the needs of their clinical settings to prevent excess GWG and improve healthy behaviours and markers of insulin resistance among women with overweight or obesity by using telehealth lifestyle interventions., Funding: US National Institutes of Health., (Copyright © 2020 Elsevier Ltd. All rights reserved.) more...- Published
- 2020
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28. Discriminating α-synuclein strains in Parkinson's disease and multiple system atrophy.
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Shahnawaz M, Mukherjee A, Pritzkow S, Mendez N, Rabadia P, Liu X, Hu B, Schmeichel A, Singer W, Wu G, Tsai AL, Shirani H, Nilsson KPR, Low PA, and Soto C
- Subjects
- Amyloid chemistry, Brain Chemistry, Circular Dichroism, Endopeptidase K metabolism, Humans, Multiple System Atrophy cerebrospinal fluid, Parkinson Disease cerebrospinal fluid, Protein Conformation, Protein Denaturation, Protein Folding, Spectroscopy, Fourier Transform Infrared, alpha-Synuclein classification, alpha-Synuclein toxicity, Multiple System Atrophy diagnosis, Parkinson Disease diagnosis, alpha-Synuclein cerebrospinal fluid, alpha-Synuclein chemistry
- Abstract
Synucleinopathies are neurodegenerative diseases that are associated with the misfolding and aggregation of α-synuclein, including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy
1 . Clinically, it is challenging to differentiate Parkinson's disease and multiple system atrophy, especially at the early stages of disease2 . Aggregates of α-synuclein in distinct synucleinopathies have been proposed to represent different conformational strains of α-synuclein that can self-propagate and spread from cell to cell3-6 . Protein misfolding cyclic amplification (PMCA) is a technique that has previously been used to detect α-synuclein aggregates in samples of cerebrospinal fluid with high sensitivity and specificity7,8 . Here we show that the α-synuclein-PMCA assay can discriminate between samples of cerebrospinal fluid from patients diagnosed with Parkinson's disease and samples from patients with multiple system atrophy, with an overall sensitivity of 95.4%. We used a combination of biochemical, biophysical and biological methods to analyse the product of α-synuclein-PMCA, and found that the characteristics of the α-synuclein aggregates in the cerebrospinal fluid could be used to readily distinguish between Parkinson's disease and multiple system atrophy. We also found that the properties of aggregates that were amplified from the cerebrospinal fluid were similar to those of aggregates that were amplified from the brain. These findings suggest that α-synuclein aggregates that are associated with Parkinson's disease and multiple system atrophy correspond to different conformational strains of α-synuclein, which can be amplified and detected by α-synuclein-PMCA. Our results may help to improve our understanding of the mechanism of α-synuclein misfolding and the structures of the aggregates that are implicated in different synucleinopathies, and may also enable the development of a biochemical assay to discriminate between Parkinson's disease and multiple system atrophy. more...- Published
- 2020
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29. The Coexistence of Oculocutaneous Albinism with Schizophrenia.
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Tsai AL and Agustines D
- Abstract
Oculocutaneous albinism (OCA) is an extremely rare skin disorder which occurs in 0.005% of the world population, whereas schizophrenia is a rare mental illness which affects 1% of the world population. Researchers have spent much time searching for the causes of schizophrenia, as they are still largely unknown. It was previously hypothesized that schizophrenia could be caused by a defect in melatonin metabolism, leading to increased melanin production and the production of hallucinogenic agent. However, this implies that albinos would be protected against schizophrenia (since they have little to no melanin production), and although rare, there have been several case reports of albinos with schizophrenia, refuting this hypothesis. Following their discovery of schizophrenic albinos, several researchers have instead wondered whether schizophrenia and albinism could actually be genetically linked. To further this discussion, we present a case report of a 25-year-old African-American male with OCA2 and schizophrenia. He was hospitalized after his mother discovered the existence of a BB that was lodged in his forehead from a failed suicide attempt in response to command auditory hallucinations. The BB was removed during his hospitalization, and he was psychiatrically stabilized on a combination of risperidone, lithium, and escitalopram., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Tsai et al.) more...
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- 2020
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30. Revisiting the intersection of amyloid, pathologically modified tau and iron in Alzheimer's disease from a ferroptosis perspective.
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Derry PJ, Hegde ML, Jackson GR, Kayed R, Tour JM, Tsai AL, and Kent TA
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- Alzheimer Disease drug therapy, Amyloid beta-Peptides drug effects, Animals, Cellular Senescence drug effects, Ferroptosis drug effects, Humans, Iron toxicity, tau Proteins drug effects, Alzheimer Disease metabolism, Amyloid beta-Peptides metabolism, Cellular Senescence physiology, Ferroptosis physiology, Iron metabolism, Iron Chelating Agents therapeutic use, Reactive Oxygen Species metabolism, tau Proteins metabolism
- Abstract
The complexity of Alzheimer's disease (AD) complicates the search for effective treatments. While the key roles of pathologically modified proteins has occupied a central role in hypotheses of the pathophysiology, less attention has been paid to the potential role for transition metals overload, subsequent oxidative stress, and tissue injury. The association of transition metals, the major focus heretofore iron and amyloid, the same can now be said for the likely pathogenic microtubular associated tau (MAPT). This review discusses the interplay between iron, pathologically modified tau and oxidative stress, and connects many related discoveries. Basic principles of the transition to pathological MAPT are discussed. Iron, its homeostatic mechanisms, the recently described phenomenon of ferroptosis and purported, although still controversial roles in AD are reviewed as well as considerations to overcome existing hurdles of iron-targeted therapeutic avenues that have been attempted in AD. We summarize the involvement of multiple pathological pathways at different disease stages of disease progression that supports the potential for a combinatorial treatment strategy targeting multiple factors., (Copyright © 2019 Elsevier Ltd. All rights reserved.) more...
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- 2020
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31. Critical Comparison of the Superoxide Dismutase-like Activity of Carbon Antioxidant Nanozymes by Direct Superoxide Consumption Kinetic Measurements.
- Author
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Wu G, Berka V, Derry PJ, Mendoza K, Kakadiaris E, Roy T, Kent TA, Tour JM, and Tsai AL
- Subjects
- Carbon chemistry, Catalysis, Fullerenes, Graphite chemistry, Hydrophobic and Hydrophilic Interactions, Kinetics, Polyethylene Glycols chemistry, Antioxidants chemistry, Nanocomposites chemistry, Superoxide Dismutase chemistry, Superoxides metabolism
- Abstract
The superoxide dismutase-like activity of poly(ethylene glycolated) hydrophilic carbon clusters (PEG-HCCs), anthracite and bituminous graphene quantum dots (PEG-aGQDs and PEG-bGQDs, respectively), and two fullerene carbon nanozymes, tris malonyl-C
60 fullerene (C3) and polyhydroxylated-C60 fullerene (C60 -OHn ), were compared using direct optical stopped-flow kinetic measurements, together with three native superoxide dismutases (SODs), CuZnSOD, MnSOD, and FeSOD, at both pH 12.7 and 8.5. Computer modeling including both SOD catalytic steps and superoxide self-dismutation enabled the best choice of catalyst concentration with minimal contribution to the observed kinetic change from the substrate self-dismutation. Biexponential fitting to the kinetic data ranks the rate constant (M-1 s-1 ) in the order of PEG-HCCs > CuZnSOD ≈ MnSOD ≈ PEG-aGQDs ≈ PEG-bGQDs > FeSOD ≫ C3 > C60 -OHn at pH 12.7 and MnSOD > CuZnSOD ≈ PEG-HCCs > FeSOD > PEG-aGQDs ≈ PEG-bGQDs ≫ C3 ≈ C60 -OHn at pH 8.5. Nonlinear regression of the kinetic model above yielded the same ranking as the biexponential fit, but provided better mechanistic insight. The data obtained by freeze-quench EPR direct assay at pH 12.7 also yield the same ranking as stopped-flow data. This is a necessary assessment of a panel of proclaimed carbon nano SOD mimetics using the same two direct methods, revealing a dramatic, 3-4 orders of magnitude difference in SOD activity between PEG-HCCs/PEG-GQDs from soluble fullerenes. more...- Published
- 2019
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32. Effectiveness of metal oxide catalysts for the degradation of 1,4-dioxane.
- Author
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Heck KN, Wang Y, Wu G, Wang F, Tsai AL, Adamson DT, and Wong MS
- Abstract
1,4-dioxane, commonly used as a solvent stabilizer and industrial solvent, is an environmental contaminant and probable carcinogen. In this study, we explored the concept of using metal oxides to activate H
2 O2 catalytically at neutral pH in the dark for 1,4-dioxane degradation. Based on batch kinetics measurements, materials that displayed the most suitable characteristics (high 1,4-dioxane degradation activity and high H2 O2 consumption efficiency) were ZrO2 , WOx /ZrO2 , and CuO. In contrast, materials like TiO2 , WO3 , and aluminosilicate zeolite Y exhibited both low 1,4-dioxane degradation and H2 O2 consumption activities. Other materials ( e.g. , Fe2 O3 and CeO2 ) consumed H2 O2 rapidly, however 1,4-dioxane degradation was negligible. The supported metal oxide WOx /ZrO2 was the most active for 1,4-dioxane degradation and had higher H2 O2 consumption efficiency compared to ZrO2 . In situ acetonitrile poisoning and FTIR spectroscopy results indicate different surface acid sites for 1,4-dioxane and H2 O2 adsorption and reaction. Electron paramagnetic resonance measurements indicate that H2 O2 forms hydroxyl radicals (˙OH) in the presence of CuO, and unusually, forms superoxide/peroxyl radicals (˙O2 - ) in the presence of WOx /ZrO2 . The identified material properties suggest metal oxides/H2 O2 as a potential advanced oxidation process in the treatment of 1,4-dioxane and other recalcitrant organic compounds., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.) more...- Published
- 2019
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33. Aluminum Nanocubes Have Sharp Corners.
- Author
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Clark BD, Jacobson CR, Lou M, Renard D, Wu G, Bursi L, Ali AS, Swearer DF, Tsai AL, Nordlander P, and Halas NJ
- Abstract
Of the many plasmonic nanoparticle geometries that have been synthesized, nanocubes have been of particular interest for creating nanocavities, facilitating plasmon coupling, and enhancing phenomena dependent upon local electromagnetic fields. Here we report the straightforward colloidal synthesis of single-crystalline {100} terminated Al nanocubes by decomposing AlH
3 with Tebbe's reagent in tetrahydrofuran. The size and shape of the Al nanocubes is controlled by the reaction time and the ratio of AlH3 to Tebbe's reagent, which, together with reaction temperature, establish kinetic control over Al nanocube growth. Al nanocubes possess strong localized field enhancements at their sharp corners and resonances highly amenable to coupling with metallic substrates. Their native oxide surface renders them extremely air stable. Chemically synthesized Al nanocubes provide an earth-abundant alternative to noble metal nanocubes for plasmonics and nanophotonics applications. more...- Published
- 2019
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34. A Randomized Study of Values Affirmation to Promote Interest in Diabetes Prevention Among Women With a History of Gestational Diabetes.
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Brown SD, Fotuhi O, Grijalva CS, Tsai AL, Quesenberry CP Jr, Ritchie JL, Cohen GL, and Ferrara A
- Subjects
- Adult, Body Mass Index, Electronic Mail, Female, Humans, Life Style, Pregnancy, Program Development, Diabetes Mellitus, Type 2 prevention & control, Diabetes, Gestational, Health Promotion organization & administration, Social Values
- Abstract
Objective: The objective of this study was to test whether 2 interventions promote interest in diabetes prevention among women with a history of gestational diabetes mellitus, who face high lifetime risk for diabetes., Research Design and Methods: We designed an email outreach message promoting an existing preventive lifestyle program. The message incorporated values affirmation, a theory-based intervention that can improve openness to health information but typically relies on a writing exercise less practical in health care settings. In a 3-arm randomized study, 237 women with elevated body mass index and a history of gestational diabetes mellitus were randomized to read an outreach message containing either no affirmation (control) or 1 of 2 affirmations, streamlined to remove the typical writing exercise: either a values affirmation prompting reflection on any personal value, or a parenting affirmation prompting reflection on caregiving-related values. Outcomes included demonstrating interest in the lifestyle program (seeking information about it or intending to join) and seeking publicly-available health information about diabetes prevention., Results: Compared with control, participants randomized to the values affirmation more frequently demonstrated interest in the lifestyle program (59.0% vs. 74.4%; adjusted relative risk: 1.31; 95% confidence interval: 1.04-1.66) and sought information about diabetes prevention (59.0% vs. 73.4%; adjusted relative risk: 1.22; 95% confidence interval: 0.97-1.54). The parenting affirmation yielded no significant differences in either outcome., Conclusions: A streamlined values affirmation, designed for feasibility in a health care setting, can promote interest in diabetes prevention among women at high risk. Research is needed to evaluate its effects on diabetes prevention program enrollment and clinical outcomes. more...
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- 2019
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35. Catalytic oxidation and reduction reactions of hydrophilic carbon clusters with NADH and cytochrome C: features of an electron transport nanozyme.
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Derry PJ, Nilewski LG, Sikkema WKA, Mendoza K, Jalilov A, Berka V, McHugh EA, Tsai AL, Tour JM, and Kent TA
- Subjects
- Ascorbic Acid pharmacology, Catalysis, Electron Spin Resonance Spectroscopy, Electron Transport drug effects, Humans, Oxidation-Reduction drug effects, Polyethylene Glycols chemistry, Polyethylene Glycols pharmacology, Cytochromes c metabolism, Hydrogen Peroxide metabolism, Mitochondria metabolism, NAD metabolism, Nanotubes, Carbon chemistry
- Abstract
Previously, our group reported on the promising efficacy of poly(ethylene glycol)-hydrophilic carbon clusters (PEG-HCCs) to work as broadly active and high capacity antioxidants in brain ischemia and injury models including stroke and traumatic brain injury coupled with hemorrhagic shock. PEG-HCCs are a carbon nanomaterial derived from harsh oxidation of single wall carbon nanotubes and covalently modified with poly(ethylene glycol). They retain no tubular remnants and are composed of a highly oxidized carbon core functionalized with epoxy, peroxyl, quinone, ketone, carboxylate, and hydroxyl groups. HCCs are the redox active carbon core of PEG-HCCs, which have a broad reduction potential range starting at +200 mV and extending to -2 V. Here we describe a new property of these materials: the ability to catalytically transfer electrons between key surrogates and proteins of the mitochondrial electron transport complex in a catalytic fashion consistent with the concept of a nanozyme. The estimated reduction potential of PEG-HCCs is similar to that of ubiquinone and they enabled the catalytic transfer of electrons from low reduction potential species to higher reduction electron transport complex constituents. PEG-HCCs accelerated the reduction of resazurin (a test indicator of mitochondrial viability) and cytochrome c by NADH and ascorbic acid in solution. Kinetic experiments suggested a transient tertiary complex. Electron paramagnetic resonance demonstrated NADH increased the magnitude of PEG-HCCs' intrinsic radical, which then reduced upon subsequent addition of cytochrome c or resazurin. Deconvolution microscopy identified PEG-HCCs in close proximity to mitochondria after brief incubation with cultured SHSY-5Y human neuroblastoma cells. Compared to methylene blue (MB), considered a prototypical small molecule electron transport shuttle, PEG-HCCs were more protective against toxic effects of hydrogen peroxide in vitro and did not demonstrate impaired cell viability as did MB. PEG-HCCs were protective in vitro when cells were exposed to sodium cyanide, a mitochondrial complex IV poison. Because mitochondria are a major source of free radicals in pathology, we suggest that this newly described nanozyme action helps explain their in vivo efficacy in a range of injury models. These findings may also extend their use to mitochondrial disorders. more...
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- 2019
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36. Highly Oxidized Graphene Quantum Dots from Coal as Efficient Antioxidants.
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Nilewski L, Mendoza K, Jalilov AS, Berka V, Wu G, Sikkema WKA, Metzger A, Ye R, Zhang R, Luong DX, Wang T, McHugh E, Derry PJ, Samuel EL, Kent TA, Tsai AL, and Tour JM
- Subjects
- Antioxidants pharmacology, Biocompatible Materials pharmacology, Graphite pharmacology, Humans, Oxidation-Reduction, Polyethylene Glycols chemistry, Quantum Dots chemistry, Superoxide Dismutase chemistry, Antioxidants chemistry, Biocompatible Materials chemistry, Coal, Graphite chemistry
- Abstract
Graphene quantum dots (GQDs) have recently been employed in various fields including medicine as antioxidants, primarily because of favorable biocompatibility in comparison to common inorganic quantum dots, although the structural features that lead to the biological activities of GQDs are poorly understood. Here, we report that coal-derived GQDs and their poly(ethylene glycol)-functionalized derivatives serve as efficient antioxidants, and we evaluate their electrochemical, chemical, and in vitro biological activities. more...
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- 2019
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37. Gestational weight gain and optimal wellness (GLOW): rationale and methods for a randomized controlled trial of a lifestyle intervention among pregnant women with overweight or obesity.
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Brown SD, Hedderson MM, Ehrlich SF, Galarce MN, Tsai AL, Quesenberry CP, and Ferrara A
- Subjects
- Adult, California, Counseling methods, Diet, Healthy methods, Female, Gestational Weight Gain, Humans, Life Style, Obesity complications, Overweight complications, Pregnancy, Pregnancy Complications etiology, Randomized Controlled Trials as Topic, Young Adult, Obesity therapy, Overweight therapy, Pregnancy Complications prevention & control, Prenatal Care methods, Weight Reduction Programs methods
- Abstract
Background: Excess gestational weight gain (GWG) is common among women with overweight or obesity, increasing their risks for pregnancy complications, delivering a large infant, and postpartum weight retention. To date, only intensive interventions have had success and few interventions have been designed for implementation in healthcare settings., Methods: We describe the development, rationale, and methods of GLOW (GestationaL Weight Gain and Optimal Wellness), a randomized controlled trial evaluating the efficacy of a lifestyle intervention to prevent excess GWG among racially/ethnically diverse women with overweight or obesity in an integrated healthcare delivery system. Participants in Kaiser Permanente Northern California will be randomized, within 2 weeks of completing a study baseline clinic visit at 10 weeks' gestation, to either usual medical care or a multi-component pregnancy lifestyle intervention adapted from the Diabetes Prevention Program (target N = 400). Informed by focus groups with patients and designed to be feasible in a clinical setting, the intervention will include 13 weekly individual sessions (11 delivered by telephone) focused on behavior change for weight management, healthy eating, physical activity, and stress management. Outcomes will be assessed in women and their infants from randomization to 12 months postpartum. The primary outcome is GWG. Secondary outcomes include changes in diet and physical activity during pregnancy and infant birthweight. Exploratory outcomes include cardiometabolic profile assessed via pregnancy blood samples and cord blood samples; and postpartum weight retention and infant anthropometrics up to 12 months of age. The trial includes systematic approaches to enhance intervention fidelity, intervention adherence, and participant retention in trial assessments., Discussion: GLOW is among few trials targeting excess GWG among diverse women with overweight or obesity in a healthcare setting, with long-term maternal and infant outcomes assessed up to 12 months after delivery. This evaluation of a multi-component intervention is designed to produce generalizable results to inform potential adoption of the intervention in clinical settings., Trial Registration: ClinicalTrials.gov ( NCT02130232 ): submitted April 30, 2014; posted May 5, 2014. more...
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- 2019
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38. Ligand-Dependent Colloidal Stability Controls the Growth of Aluminum Nanocrystals.
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Clark BD, DeSantis CJ, Wu G, Renard D, McClain MJ, Bursi L, Tsai AL, Nordlander P, and Halas NJ
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- Colloids, Ligands, Models, Molecular, Molecular Conformation, Solvents chemistry, Aluminum chemistry, Metal Nanoparticles chemistry
- Abstract
The precise size- and shape-controlled synthesis of monodisperse Al nanocrystals remains an open challenge, limiting their utility for numerous applications that would take advantage of their size and shape-dependent optical properties. Here we pursue a molecular-level understanding of the formation of Al nanocrystals by titanium(IV) isopropoxide-catalyzed decomposition of AlH
3 in Lewis base solvents. As determined by electron paramagnetic resonance spectroscopy of intermediates, the reaction begins with the formation of Ti3+ -AlH3 complexes. Proton nuclear magnetic resonance spectroscopy indicates isopropoxy ligands are removed from Ti by Al, producing aluminum(III) isopropoxide and low-valent Ti3+ catalysts. These Ti3+ species catalyze elimination of H2 from AlH3 inducing the polymerization of AlH3 into colloidally unstable low-valent aluminum hydride clusters. These clusters coalesce and grow while expelling H2 to form colloidally stable Al nanocrystals. The colloidal stability of the Al nanocrystals and their size is determined by the molecular structure and density of coordinating atoms in the reaction, which is controlled by choice of solvent composition. more...- Published
- 2019
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39. Suppressing Li Metal Dendrites Through a Solid Li-Ion Backup Layer.
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Salvatierra RV, López-Silva GA, Jalilov AS, Yoon J, Wu G, Tsai AL, and Tour JM
- Abstract
The growing demand for sustainable and off-grid energy storage is reviving the attempts to use Li metal as the anode in the next generation of batteries. However, the use of Li anodes is hampered due to the growth of Li dendrites upon charging and discharging, which compromises the life and safety of the battery. Here, it is shown that lithiated multiwall carbon nanotubes (Li-MWCNTs) act as a controlled Li diffusion interface that suppresses the growth of Li dendrites by regulating the Li
+ ion flux during charge/discharge cycling at current densities between 2 and 4 mA cm-2 . A full Li-S cell is fabricated to showcase the versatility of the protected Li anode with the Li-MWCNT interface, where the full cells could support pulse discharges at high currents and over 450 cycles at different rates with coulombic efficiencies close to 99.9%. This work indicates that carbon materials in lithiated forms can be an effective and simple approach to the stabilization of Li metal anodes., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.) more...- Published
- 2018
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40. A Tailored Letter Based on Electronic Health Record Data Improves Gestational Weight Gain Among Women With Gestational Diabetes Mellitus: The Gestational Diabetes' Effects on Moms (GEM) Cluster-Randomized Controlled Trial.
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Hedderson MM, Brown SD, Ehrlich SF, Tsai AL, Zhu Y, Quesenberry CP, Crites Y, and Ferrara A
- Subjects
- Adolescent, Adult, Body Mass Index, Cluster Analysis, Female, Humans, Postpartum Period physiology, Pregnancy, Pregnancy Complications prevention & control, Risk Reduction Behavior, Weight Loss, Young Adult, Diabetes, Gestational therapy, Electronic Health Records, Life Style, Obesity prevention & control, Precision Medicine methods, Weight Gain, Weight Reduction Programs methods
- Abstract
Objective: Evaluate whether a tailored letter improved gestational weight gain (GWG) and whether GWG mediated a multicomponent intervention's effect on postpartum weight retention among women with gestational diabetes mellitus (GDM)., Research Design and Methods: A cluster-randomized controlled trial of 44 medical facilities ( n = 2,014 women) randomized to usual care or a multicomponent lifestyle intervention delivered during pregnancy (tailored letter) and postpartum (13 telephone sessions) to reduce postpartum weight retention. The tailored letter, using electronic health record (EHR) data, recommended an end-of-pregnancy weight goal tailored to prepregnancy BMI and GWG trajectory at GDM diagnosis: total GWG at the lower limit of the IOM range if BMI ≥18.5 kg/m
2 or the midpoint if <18.5 kg/m2 and weight maintenance if women had exceeded this. The outcomes for this study were the proportion of women meeting the Institute of Medicine (IOM) guidelines for weekly rate of GWG from GDM diagnosis to delivery and meeting the end-of-pregnancy weight goal., Results: The tailored letter significantly increased the proportion of women meeting the IOM guidelines (72.6% vs. 67.1%; relative risk 1.08 [95% CI 1.01-1.17]); results were similar among women with BMI <25.0 kg/m2 (1.07 [1.00-1.15]) and ≥25.0 kg/m2 (1.08 [0.98-1.18]). Thirty-six percent in the intervention vs. 33.0% in usual care met the end-of-pregnancy weight goal (1.08 [0.99-1.18]); the difference was statistically significant among women with BMI <25.0 kg/m2 (1.28 [1.05-1.57]) but not ≥25.0 kg/m2 (0.99 [0.87-1.13]). Meeting the IOM guidelines mediated the effect of the multicomponent intervention in reducing postpartum weight retention by 24.6% (11.3-37.8%)., Conclusions: A tailored EHR-based letter improved GWG, which mediated the effect of a multicomponent intervention in reducing postpartum weight retention., (© 2018 by the American Diabetes Association.) more...- Published
- 2018
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41. Efficacy of Novel Carbon Nanoparticle Antioxidant Therapy in a Severe Model of Reversible Middle Cerebral Artery Stroke in Acutely Hyperglycemic Rats.
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Fabian RH, Derry PJ, Rea HC, Dalmeida WV, Nilewski LG, Sikkema WKA, Mandava P, Tsai AL, Mendoza K, Berka V, Tour JM, and Kent TA
- Abstract
Introduction: While oxidative stress can be measured during transient cerebral ischemia, antioxidant therapies for ischemic stroke have been clinically unsuccessful. Many antioxidants are limited in their range and/or capacity for quenching radicals and can generate toxic intermediates overwhelming depleted endogenous protection. We developed a new antioxidant class, 40 nm × 2 nm carbon nanoparticles, hydrophilic carbon clusters, conjugated to poly(ethylene glycol) termed PEG-HCCs. These particles are high-capacity superoxide dismutase mimics, are effective against hydroxyl radical, and restore the balance between nitric oxide and superoxide in the vasculature. Here, we report the effects of PEG-HCCs administered during reperfusion after transient middle cerebral artery occlusion (tMCAO) by suture in the rat under hyperglycemic conditions. Hyperglycemia occurs in one-third of stroke patients and worsens clinical outcome. In animal models, this worsening occurs largely by accelerating elaboration of reactive oxygen species (ROS) during reperfusion., Methods: PEG-HCCs were studied for their protective ability against hydrogen peroxide in b.End3 brain endothelial cell line and E17 primary cortical neuron cultures. In vivo , hyperglycemia was induced by streptozotocin injection 2 days before tMCAO. 58 Male Sprague-Dawley rats were analyzed. They were injected IV with PBS or PEG-HCCs (4 mg/kg 2×) at the time of recanalization after either 90- or 120-min occlusion. Rats were survived for up to 3 days, and infarct volume characteristics and neurological functional outcome (modified Bederson Score) were assessed., Results: PEG-HCCs were protective against hydrogen peroxide in both culture models. In vivo improvement was found after PEG-HCCs with 90-min ischemia with reduction in infarct size (42%), hemisphere swelling (46%), hemorrhage score (53%), and improvement in Bederson score (70%) ( p = 0.068-0.001). Early high mortality in the 2-h in the PBS control group precluded detailed analysis, but a trend was found in improvement in all factors, e.g., reduction in infarct volume (48%; p = 0.034) and a 56% improvement in Bederson score ( p = 0.055) with PEG-HCCs., Conclusion: This nano-antioxidant showed some improvement in several outcome measures in a severe model of tMCAO when administered at a clinically relevant time point. Long-term studies and additional models are required to assess potential for clinical use, especially for patients hyperglycemic at the time of their stroke, as these patients have the worst outcomes. more...
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- 2018
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42. Elevated Red Cell Distribution Width Is Associated With Decreased Ventilator-Free Days in Critically Ill Patients.
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Otero TMN, Yeh DD, Bajwa EK, Azocar RJ, Tsai AL, Belcher DM, and Quraishi SA
- Subjects
- APACHE, Boston, Critical Illness mortality, Female, Hospital Mortality, Humans, Intensive Care Units, Male, Middle Aged, Predictive Value of Tests, Prospective Studies, Respiratory Insufficiency mortality, Respiratory Insufficiency therapy, Retrospective Studies, Risk Factors, Critical Care, Critical Illness therapy, Erythrocyte Indices, Respiration, Artificial statistics & numerical data, Respiratory Insufficiency blood, Respiratory Insufficiency physiopathology
- Abstract
Introduction: Elevated red cell distribution width (RDW) is associated with mortality in a variety of respiratory conditions. Recent data also suggest that RDW is associated with mortality in intensive care unit (ICU) patients. Although respiratory failure is common in the ICU, the relationship between RDW and pulmonary outcomes in the ICU has not been previously explored. Therefore, our goal was to investigate the association of admission RDW with 30-day ventilator-free days (VFDs) in ICU patients., Methods: We performed a retrospective analysis from an ongoing prospective, observational study. Patients were recruited from medical and surgical ICUs of a large teaching hospital in Boston, Massachusetts. The RDW was assessed within 1 hour of ICU admission. Poisson regression analysis was used to investigate the association of RDW (normal: 11.5%-14.5% vs elevated: >14.5%) with 30-day VFD, while controlling for age, sex, race, body mass index, Nutrition Risk in the Critically Ill score, the presence of chronic lung disease, Pao
2 /Fio2 ratio, and admission levels of hemoglobin, mean corpuscular volume, phosphate, albumin, C-reactive protein, and creatinine., Results: A total of 637 patients comprised the analytic cohort. Mean RDW was 15 (standard deviation 4%), with 53% of patients in the normal range and 47% with elevated levels. Median VFD was 16 (interquartile range: 6-25) days. Poisson regression analysis demonstrated that ICU patients with elevated admission RDW were likely to have 32% lower 30-day VFDs compared to their counterparts with RDW in the normal range (incidence rate ratio: 0.68; 95% confidence interval: 0.55-0.83: P < .001)., Conclusions: We observed an inverse association of RDW and 30-day VFD, despite controlling for demographics, nutritional factors, and severity of illness. This supports the need for future studies to validate our findings, understand the physiologic processes that lead to elevated RDW in patients with respiratory failure, and determine whether changes in RDW may be used to support clinical decision-making. more...- Published
- 2018
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43. Herpes Zoster Rates in a Large Cohort of Patients With Systemically Treated Psoriasis.
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Levandoski KA, Quesenberry CP, Tsai AL, and Asgari MM
- Subjects
- Adult, Age Factors, Aged, Cohort Studies, Comorbidity, Dermatologic Agents pharmacology, Female, Follow-Up Studies, Herpes Zoster diagnosis, Herpes Zoster drug therapy, Humans, Incidence, Injections, Subcutaneous, Male, Middle Aged, Psoriasis diagnosis, Risk Assessment, Severity of Illness Index, Sex Factors, Treatment Outcome, Biological Products therapeutic use, Dermatologic Agents therapeutic use, Herpes Zoster epidemiology, Psoriasis drug therapy, Psoriasis epidemiology
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- 2018
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44. Structural and Functional Insight of Sphingosine 1-Phosphate-Mediated Pathogenic Metabolic Reprogramming in Sickle Cell Disease.
- Author
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Sun K, D'Alessandro A, Ahmed MH, Zhang Y, Song A, Ko TP, Nemkov T, Reisz JA, Wu H, Adebiyi M, Peng Z, Gong J, Liu H, Huang A, Wen YE, Wen AQ, Berka V, Bogdanov MV, Abdulmalik O, Han L, Tsai AL, Idowu M, Juneja HS, Kellems RE, Dowhan W, Hansen KC, Safo MK, and Xia Y more...
- Subjects
- 2,3-Diphosphoglycerate chemistry, 2,3-Diphosphoglycerate metabolism, Anemia, Sickle Cell pathology, Animals, Erythrocytes, Abnormal pathology, Female, Hemoglobin A chemistry, Hemoglobin, Sickle chemistry, Hemolysis, Humans, Lysophospholipids chemistry, Male, Mice, Mice, Transgenic, Oxidative Stress, Pentose Phosphate Pathway, Sphingosine chemistry, Sphingosine metabolism, Anemia, Sickle Cell metabolism, Erythrocytes, Abnormal metabolism, Hemoglobin A metabolism, Hemoglobin, Sickle metabolism, Lysophospholipids metabolism, Sphingosine analogs & derivatives
- Abstract
Elevated sphingosine 1-phosphate (S1P) is detrimental in Sickle Cell Disease (SCD), but the mechanistic basis remains obscure. Here, we report that increased erythrocyte S1P binds to deoxygenated sickle Hb (deoxyHbS), facilitates deoxyHbS anchoring to the membrane, induces release of membrane-bound glycolytic enzymes and in turn switches glucose flux towards glycolysis relative to the pentose phosphate pathway (PPP). Suppressed PPP causes compromised glutathione homeostasis and increased oxidative stress, while enhanced glycolysis induces production of 2,3-bisphosphoglycerate (2,3-BPG) and thus increases deoxyHbS polymerization, sickling, hemolysis and disease progression. Functional studies revealed that S1P and 2,3-BPG work synergistically to decrease both HbA and HbS oxygen binding affinity. The crystal structure at 1.9 Å resolution deciphered that S1P binds to the surface of 2,3-BPG-deoxyHbA and causes additional conformation changes to the T-state Hb. Phosphate moiety of the surface bound S1P engages in a highly positive region close to α1-heme while its aliphatic chain snakes along a shallow cavity making hydrophobic interactions in the "switch region", as well as with α2-heme like a molecular "sticky tape" with the last 3-4 carbon atoms sticking out into bulk solvent. Altogether, our findings provide functional and structural bases underlying S1P-mediated pathogenic metabolic reprogramming in SCD and novel therapeutic avenues. more...
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- 2017
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45. Bindings of NO, CO, and O 2 to multifunctional globin type dehaloperoxidase follow the 'sliding scale rule'.
- Author
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Wu G, Zhao J, Franzen S, and Tsai AL
- Subjects
- Hemoglobins metabolism, Carbon Monoxide metabolism, Globins metabolism, Nitric Oxide metabolism, Oxygen metabolism, Peroxidases metabolism
- Abstract
Dehaloperoxidase-hemoglobin (DHP), a multifunctional globin protein, not only functions as an oxygen carrier as typical globins such as myoglobin and hemoglobin, but also as a peroxidase, a mono- and dioxygenase, peroxygenase, and an oxidase. Kinetics of DHP binding to NO, CO, and O
2 were characterized for wild-type DHP A and B and the H55D and H55V DHP A mutants using stopped-flow methods. All three gaseous ligands bind to DHP significantly more weakly than sperm whale myoglobin (SWMb). Both CO and NO bind to DHP in a one-step process to form a stable six-coordinate complex. Multiple-step NO binding is not observed in DHP, which is similar to observations in SWMb, but in contrast with many heme sensor proteins. The weak affinity of DHP for O2 is mainly due to a fast O2 dissociation rate, in accordance with a longerε N-Fe distance between the heme iron and distal histidine in DHP than that in Mb, and an open-distal pocket that permits ligand escape. Binding affinities in DHP show the same 3-4 orders separation between the pairs NO/CO and CO/O2 , consistent with the 'sliding scale rule' hypothesis. Strong gaseous ligand discrimination by DHP is very different from that observed in typical peroxidases, which show poor gaseous ligand selectivity, correlating with a neutral proximal imidazole ligand rather than an imidazolate. The present study provides useful insights into the rationale for DHP to function both as mono-oxygenase and oxidase, and is the first example of a globin peroxidase shown to follow the 'sliding scale rule' hypothesis in gaseous ligand discrimination., (© 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.) more...- Published
- 2017
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46. Association between Lithium Use and Melanoma Risk and Mortality: A Population-Based Study.
- Author
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Asgari MM, Chien AJ, Tsai AL, Fireman B, and Quesenberry CP Jr
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, California epidemiology, Cause of Death trends, Disease Progression, Female, Follow-Up Studies, Humans, Incidence, Lithium pharmacokinetics, Male, Melanoma blood, Melanoma chemically induced, Middle Aged, Retrospective Studies, Risk Factors, Skin Neoplasms blood, Skin Neoplasms chemically induced, Survival Rate trends, Young Adult, Melanoma, Cutaneous Malignant, Lithium adverse effects, Melanoma epidemiology, Risk Assessment methods, SEER Program, Skin Neoplasms epidemiology
- Abstract
Laboratory studies show that lithium, an activator of the Wnt/ß-catenin signaling pathway, slows melanoma progression, but to our knowledge no published epidemiologic studies have explored this association. We conducted a retrospective cohort study of adult white Kaiser Permanente Northern California members (n = 2,213,848) from 1997-2012 to examine the association between lithium use and melanoma risk. Lithium exposure (n = 11,317) was assessed from pharmacy databases, serum lithium levels were obtained from electronic laboratory databases, and incident cutaneous melanomas (n = 14,056) were identified from an established cancer registry. In addition to examining melanoma incidence, melanoma hazard ratios and 95% confidence intervals for lithium exposure were estimated using Cox proportional hazards models, adjusted for potential confounders. Melanoma incidence per 100,000 person-years among lithium-exposed individuals was 67.4, compared with 92.5 in unexposed individuals (P = 0.027). Lithium-exposed individuals had a 32% lower risk of melanoma (hazard ratio = 0.68, 95% confidence interval = 0.51-0.90) in unadjusted analysis, but the estimate was attenuated and nonsignificant in adjusted analysis (adjusted hazard ratio = 0.77, 95% confidence interval = 0.58-1.02). No lithium-exposed individuals presented with thick (>4 mm) or advanced-stage melanoma at diagnosis. Among melanoma patients, lithium-exposed individuals were less likely to suffer melanoma-associated mortality (rate = 4.68/1,000 person-years) compared with the unexposed (rate = 7.21/1,000 person-years). Our findings suggest that lithium may reduce melanoma risk and associated mortality., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2017
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47. Gaseous ligand selectivity of the H-NOX sensor protein from Shewanella oneidensis and comparison to those of other bacterial H-NOXs and soluble guanylyl cyclase.
- Author
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Wu G, Liu W, Berka V, and Tsai AL
- Subjects
- Humans, Bacterial Proteins chemistry, Carbon Monoxide chemistry, Nitric Oxide chemistry, Oxygen chemistry, Protein Folding, Shewanella enzymology, Soluble Guanylyl Cyclase chemistry
- Abstract
To delineate the commonalities and differences in gaseous ligand discrimination among the heme-based sensors with Heme Nitric oxide/OXygen binding protein (H-NOX) scaffold, the binding kinetic parameters for gaseous ligands NO, CO, and O
2 , including KD , kon , and koff , of Shewanella oneidensis H-NOX (So H-NOX) were characterized in detail in this study and compared to those of previously characterized H-NOXs from Clostridium botulinum (Cb H-NOX), Nostoc sp. (Ns H-NOX), Thermoanaerobacter tengcongensis (Tt H-NOX), Vibrio cholera (Vc H-NOX), and human soluble guanylyl cyclase (sGC), an H-NOX analogue. The KD (NO) and KD (CO) of each bacterial H-NOX or sGC follow the "sliding scale rule"; the affinities of the bacterial H-NOXs for NO and CO vary in a small range but stronger than those of sGC by at least two orders of magnitude. On the other hand, each bacterial H-NOX exhibits different characters in the stability of its 6c NO complex, reactivity with secondary NO, stability of oxyferrous heme and autoxidation to ferric heme. A facile access channel for gaseous ligands is also identified, implying that ligand access has only minimal effect on gaseous ligand selectivity of H-NOXs or sGC. This comparative study of the binding parameters of the bacterial H-NOXs and sGC provides a basis to guide future new structural and functional studies of each specific heme sensor with the H-NOX protein fold., (Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.) more...- Published
- 2017
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48. Perceived psychosocial stress and gestational weight gain among women with gestational diabetes.
- Author
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Kubo A, Ferrara A, Brown SD, Ehrlich SF, Tsai AL, Quesenberry CP Jr, Crites Y, and Hedderson MM
- Subjects
- Adolescent, Adult, Cross-Sectional Studies, Diabetes, Gestational physiopathology, Female, Humans, Middle Aged, Obesity physiopathology, Pregnancy, Young Adult, Diabetes, Gestational psychology, Obesity etiology, Obesity psychology, Stress, Psychological, Weight Gain
- Abstract
Growing evidence links perceived stress-a potentially modifiable psychosocial risk factor-with health behaviors and obesity. Yet little is known about the relationship between stress during pregnancy and gestational weight gain, particularly among women with pregnancy complications. We conducted a cross-sectional analysis to examine associations between psychosocial stress during pregnancy and gestational weight gain among women with gestational diabetes. We used baseline data from the Gestational Diabetes's Effects on Moms (GEM) study: 1,353 women with gestational diabetes who delivered a term singleton within Kaiser Permanente Northern California were included. Perceived stress near the time of gestational diabetes diagnosis was measured using the validated Perceived Stress Scale (PSS10). Gestational weight gain was categorized according to the 2009 Institute of Medicine recommendations. Binomial regression analyses adjusted for gestational age and maternal age at the time of gestational diabetes diagnosis, and race/ethnicity and estimated rate ratios (RR) and their 95% confidence interval (CI). Among women with a normal pregravid Body Mass Index (BMI 18.5-24.9 kg/m2), there was a significant association between high (Q4) PSS score and risk of both exceeding and gaining below the Institute of Medicine recommendations compared to those with lower stress (Q1) [adjusted RR = 2.16 95% CI 1.45-3.21; RR = 1.39 95% CI 1.01-1.91, respectively.] Among women with pregravid overweight/obesity (BMI≥25 kg/m2), there was no association. Although the temporal relationship could not be established from this study, there may be a complex interplay between psychosocial stress and gestational weight gain among women with gestational diabetes. Further studies examining stress earlier in pregnancy, risk of developing gestational diabetes and excess/inadequate gestational weight gain are warranted to clarify these complex relationships. more...
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- 2017
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49. Perylene Diimide as a Precise Graphene-like Superoxide Dismutase Mimetic.
- Author
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Jalilov AS, Nilewski LG, Berka V, Zhang C, Yakovenko AA, Wu G, Kent TA, Tsai AL, and Tour JM
- Subjects
- Graphite metabolism, Hydrogen Peroxide chemistry, Hydrogen Peroxide metabolism, Hydrophobic and Hydrophilic Interactions, Imides metabolism, Molecular Structure, Oxides chemistry, Oxides metabolism, Perylene chemistry, Perylene metabolism, Polyethylene Glycols chemistry, Polyethylene Glycols metabolism, Superoxide Dismutase metabolism, Graphite chemistry, Imides chemistry, Nanoparticles chemistry, Perylene analogs & derivatives, Superoxide Dismutase chemistry
- Abstract
Here we show that the active portion of a graphitic nanoparticle can be mimicked by a perylene diimide (PDI) to explain the otherwise elusive biological and electrocatalytic activity of the nanoparticle construct. Development of molecular analogues that mimic the antioxidant properties of oxidized graphenes, in this case the poly(ethylene glycolated) hydrophilic carbon clusters (PEG-HCCs), will afford important insights into the highly efficient activity of PEG-HCCs and their graphitic analogues. PEGylated perylene diimides (PEG
n -PDI) serve as well-defined molecular analogues of PEG-HCCs and oxidized graphenes in general, and their antioxidant and superoxide dismutase-like (SOD-like) properties were studied. PEGn -PDIs have two reversible reduction peaks, which are more positive than the oxidation peak of superoxide (O2 •- ). This is similar to the reduction peak of the HCCs. Thus, as with PEG-HCCs, PEGn -PDIs are also strong single-electron oxidants of O2 •- . Furthermore, reduced PEGn -PDI, PEGn -PDI•- , in the presence of protons, was shown to reduce O2 •- to H2 O2 to complete the catalytic cycle in this SOD analogue. The kinetics of the conversion of O2 •- to O2 and H2 O2 by PEG8 -PDI was measured using freeze-trap EPR experiments to provide a turnover number of 133 s-1 ; the similarity in kinetics further supports that PEG8 -PDI is a true SOD mimetic. Finally, PDIs can be used as catalysts in the electrochemical oxygen reduction reaction in water, which proceeds by a two-electron process with the production of H2 O2 , mimicking graphene oxide nanoparticles that are otherwise difficult to study spectroscopically. more...- Published
- 2017
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50. Endothelial differentiation of bone marrow mesenchyme stem cells applicable to hypoxia and increased migration through Akt and NFκB signals.
- Author
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Liu C, Tsai AL, Li PC, Huang CW, and Wu CC
- Subjects
- Animals, Bone Marrow Cells cytology, Bone Marrow Cells drug effects, Cell Differentiation drug effects, Cell Hypoxia genetics, Cell Movement drug effects, Culture Media chemistry, Culture Media pharmacology, Deferoxamine pharmacology, Endothelial Progenitor Cells cytology, Endothelial Progenitor Cells drug effects, Gene Expression Regulation, Mesenchymal Stem Cells cytology, Mesenchymal Stem Cells drug effects, NF-KappaB Inhibitor alpha genetics, NF-KappaB Inhibitor alpha metabolism, NF-kappa B metabolism, Phosphorylation, Proto-Oncogene Proteins c-akt metabolism, Rats, Rats, Sprague-Dawley, Receptors, CXCR4 genetics, Receptors, CXCR4 metabolism, Signal Transduction, Stress, Mechanical, Bone Marrow Cells metabolism, Endothelial Progenitor Cells metabolism, Mesenchymal Stem Cells metabolism, NF-kappa B genetics, Oxygen pharmacology, Proto-Oncogene Proteins c-akt genetics
- Abstract
Background: Bone marrow mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) are used to repair hypoxic or ischemic tissue. However, the underlining mechanism of resistance in the hypoxic microenvironment and the efficacy of migration to the injured tissue are still unknown. The current study aims to understand the hypoxia resistance and migration ability of MSCs during differentiation toward endothelial lineages by biochemical and mechanical stimuli., Method: MSCs were harvested from the bone marrow of 6-8-week-old Sprague-Dawley rats. The endothelial growth medium (EGM) was added to MSCs for 3 days to initiate endothelial differentiation. Laminar shear stress was used as the fluid mechanical stimulation., Results: Application of EGM facilitated the early endothelial lineage cells (eELCs) to express EPC markers. When treating the hypoxic mimetic desferrioxamine, both MSCs and eELCs showed resistance to hypoxia as compared with the occurrence of apoptosis in rat fibroblasts. The eELCs under hypoxia increased the wound closure and C-X-C chemokine receptor type 4 (CXCR4) gene expression. Although the shear stress promoted eELC maturation and aligned cells parallel to the flow direction, their migration ability was not superior to that of eELCs either under normoxia or hypoxia. The eELCs showed higher protein expressions of CXCR4, phosphorylated Akt (pAkt), and endogenous NFκB and IκBα than MSCs under both normoxia and hypoxia conditions. The potential migratory signals were discovered by inhibiting either Akt or NFκB using specific inhibitors and revealed decreases of wound closure and transmigration ability in eELCs., Conclusion: The Akt and NFκB pathways are important to regulate the early endothelial differentiation and its migratory ability under a hypoxic microenvironment. more...
- Published
- 2017
- Full Text
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