Displaying publications 1 - 20 of 43 in total

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  1. Khetan AK, Leong DP, Gupta R, Zhu Y, Li S, Liu W, et al.
    Int J Epidemiol, 2021 Dec 22.
    PMID: 34939099 DOI: 10.1093/ije/dyab268
    BACKGROUND: Final adult height is a useful proxy measure of childhood nutrition and disease burden. Tall stature has been previously associated with decreased risk of all-cause mortality, decreased risk of major cardiovascular events and an increased risk of cancer. However, these associations have primarily been derived from people of European and East Asian backgrounds, and there are sparse data from other regions of the world.

    METHODS: The Prospective Urban-Rural Epidemiology study is a large, longitudinal population study done in 21 countries of varying incomes and sociocultural settings. We enrolled an unbiased sample of households, which were eligible if at least one household member was aged 35-70 years. Height was measured in a standardized manner, without shoes, to the nearest 0.1 cm. During a median follow-up of 10.1 years (interquartile range 8.3-12.0), we assessed the risk of all-cause mortality, major cardiovascular events and cancer.

    RESULTS: A total of 154 610 participants, enrolled since January 2003, with known height and vital status, were included in this analysis. Follow-up event data until March 2021 were used; 11 487 (7.4%) participants died, whereas 9291 (6.0%) participants had a major cardiovascular event and 5873 (3.8%) participants had a new diagnosis of cancer. After adjustment, taller individuals had lower hazards of all-cause mortality [hazard ratio (HR) per 10-cm increase in height 0.93, 95% confidence interval (CI) 0.90-0.96] and major cardiovascular events (HR 0.97, 95% CI 0.94-1.00), whereas the hazard of cancer was higher in taller participants (HR 1.23, 95% CI 1.18-1.28). The interaction p-values between height and country-income level for all three outcomes were <0.001, suggesting that the association with height varied by country-income level for these outcomes. In low-income countries, height was inversely associated with all-cause mortality (HR 0.88, 95% CI 0.84-0.92) and major cardiovascular events (HR 0.87, 95% CI 0.82-0.93). There was no association of height with these outcomes in middle- and high-income countries. The respective HRs for cancer in low-, middle- and high-income countries were 1.14 (95% CI 0.99-1.32), 1.12 (95% CI 1.04-1.22) and 1.20 (95% CI 1.14-1.26).

    CONCLUSIONS: Unlike high- and middle-income countries, tall stature has a strong inverse association with all-cause mortality and major cardiovascular events in low-income countries. Improved childhood physical development and advances in population-wide cardiovascular treatments in high- and middle-income countries may contribute to this gap. From a life-course perspective, we hypothesize that optimizing maternal and child health in low-income countries may improve rates of premature mortality and cardiovascular events in these countries, at a population level.

  2. Jiang C, Zhu Y, Luo Y, Tan CS, Mastrotheodoros S, Costa P, et al.
    BMC Psychol, 2023 Oct 18;11(1):345.
    PMID: 37853499 DOI: 10.1186/s40359-023-01293-1
    BACKGROUND: The 10-item Rosenberg Self-Esteem Scale (RSES) is a widely used tool for individuals to self-report their self-esteem; however, the factorial structures of translated versions of the RSES vary across different languages. This study aimed to validate the Chinese version of the RSES in the Chinese mainland using a longitudinal design.

    METHODS: A group of healthcare university students completed the RSES across three waves: baseline, 1-week follow-up, and 15-week follow-up. A total of 481 valid responses were collected through the three-wave data collection process. Exploratory factor analysis (EFA) was performed on the baseline data to explore the potential factorial structure, while confirmatory factor analysis (CFA) was performed on the follow-up data to determine the best-fit model. Additionally, the cross-sectional and longitudinal measurement invariances were tested to assess the measurement properties of the RSES for different groups, such as gender and age, as well as across different time points. Convergent validity was assessed against the Self-Rated Health Questionnaire (SRHQ) using Spearman's correlation. Internal consistency was examined using Cronbach's alpha and McDonald's omega coefficients, while test-retest reliability was assessed using intraclass correlation coefficient.

    RESULTS: The results of EFA revealed that Items 5, 8, and 9 had inadequate or cross-factor loadings, leading to their removal from further analysis. Analysis of the remaining seven items using EFA suggested a two-factor solution. A comparison of several potential models for the 10-item and 7-item RSES using CFA showed a preference for the 7-item form (RSES-7) with two factors. Furthermore, the RSES-7 exhibited strict invariance across different groups and time points, indicating its stability and consistency. The RSES-7 also demonstrated adequate convergent validity, internal consistency, and test-retest reliability, which further supported its robustness as a measure of self-esteem.

    CONCLUSIONS: The findings suggest that the RSES-7 is a psychometrically sound and brief self-report scale for measuring self-esteem in the Chinese context. More studies are warranted to further verify its usability.

  3. Chen G, Zhou W, Guan D, Sunarso J, Zhu Y, Hu X, et al.
    Sci Adv, 2017 06;3(6):e1603206.
    PMID: 28691090 DOI: 10.1126/sciadv.1603206
    Perovskite oxides exhibit potential for use as electrocatalysts in the oxygen evolution reaction (OER). However, their low specific surface area is the main obstacle to realizing a high mass-specific activity that is required to be competitive against the state-of-the-art precious metal-based catalysts. We report the enhanced performance of Ba0.5Sr0.5Co0.8Fe0.2O3-δ (BSCF) for the OER with intrinsic activity that is significantly higher than that of the benchmark IrO2, and this result was achieved via fabrication of an amorphous BSCF nanofilm on a surface-oxidized nickel substrate by magnetron sputtering. The surface nickel oxide layer of the Ni substrate and the thickness of the BSCF film were further used to tune the intrinsic OER activity and stability of the BSCF catalyst by optimizing the electronic configuration of the transition metal cations in BSCF via the interaction between the nanofilm and the surface nickel oxide, which enables up to 315-fold enhanced mass-specific activity compared to the crystalline BSCF bulk phase. Moreover, the amorphous BSCF-Ni foam anode coupled with the Pt-Ni foam cathode demonstrated an attractive small overpotential of 0.34 V at 10 mA cm-2 for water electrolysis, with a BSCF loading as low as 154.8 μg cm-2.
  4. Zhu Y, Tan JK, Wong SK, Goon JA
    Int J Mol Sci, 2023 May 23;24(11).
    PMID: 37298120 DOI: 10.3390/ijms24119168
    Nonalcoholic fatty liver disease (NAFLD) has emerged as a global health problem that affects people even at young ages due to unhealthy lifestyles. Without intervention, NAFLD will develop into nonalcoholic steatohepatitis (NASH) and eventually liver cirrhosis and hepatocellular carcinoma. Although lifestyle interventions are therapeutic, effective implementation remains challenging. In the efforts to establish effective treatment for NAFLD/NASH, microRNA (miRNA)-based therapies began to evolve in the last decade. Therefore, this systematic review aims to summarize current knowledge on the promising miRNA-based approaches in NAFLD/NASH therapies. A current systematic evaluation and a meta-analysis were conducted according to the PRISMA statement. In addition, a comprehensive exploration of PubMed, Cochrane, and Scopus databases was conducted to perform article searches. A total of 56 different miRNAs were reported as potential therapeutic agents in these studies. miRNA-34a antagonist/inhibitor was found to be the most studied variant (n = 7), and it significantly improved the hepatic total cholesterol, total triglyceride, Aspartate Aminotransferase (AST), and Alanine Transaminase (ALT) levels based on a meta-analysis. The biological processes mediated by these miRNAs involved hepatic fat accumulation, inflammation, and fibrosis. miRNAs have shown enormous therapeutic potential in the management of NAFLD/NASH, wherein miRNA-34a antagonist has been found to be an exceptional potential agent for the treatment of NAFLD/NASH.
  5. Huang L, Liu Z, Li H, Wang Y, Li Y, Zhu Y, et al.
    Geohealth, 2020 Jul 07.
    PMID: 32838101 DOI: 10.1029/2020GH000272
    The outbreak of COVID-19 in China has led to massive lockdowns in order to reduce the spread of the epidemic and control human-to-human transmission. Subsequent reductions in various anthropogenic activities have led to improved air quality during the lockdown. In this study, we apply a widely used exposure-response function to estimate the short-term health impacts associated with PM2.5 changes over the Yangtze River Delta (YRD) region due to COVID-19 lockdown. Concentrations of PM2.5 during lockdown period reduced by 22.9% to 54.0% compared to pre-lockdown level. Estimated PM2.5-related daily premature mortality during lockdown period is 895 (95% confidential interval: 637-1081), which is 43.3% lower than pre-lockdown period and 46.5% lower compared with averages of 2017-2019. According to our calculation, total number of avoided premature death associated PM2.5 reduction during the lockdown is estimated to be 42.4 thousand over the YRD region, with Shanghai, Wenzhou, Suzhou (Jiangsu province), Nanjing, and Nantong being the top five cities with largest health benefits. Avoided premature mortality is mostly contributed by reduced death associated with stroke (16.9 thousand, accounting for 40.0%), ischemic heart disease (14.0 thousand, 33.2%) and chronic obstructive pulmonary disease (7.6 thousand, 18.0%). Our calculations do not support or advocate any idea that pandemics produce a positive note to community health. We simply present health benefits from air pollution improvement due to large emission reductions from lowered human and industrial activities. Our results show that continuous efforts to improve air quality are essential to protect public health, especially over city-clusters with dense population.
  6. Xia W, Tang N, Kord-Varkaneh H, Low TY, Tan SC, Wu X, et al.
    Pharmacol Res, 2020 11;161:105113.
    PMID: 32755613 DOI: 10.1016/j.phrs.2020.105113
    BACKGROUND AND AIM: Previous studies lack consistent conclusions as to whether astaxanthin is actually linked to various health benefits as claimed. Here, we attempt to unravel the association of astaxanthin consumption with selected health benefits by performing a systematic review and meta-analysis.

    METHODS: Online literature search databases including Scopus, Web of Science, PubMed/Medline, Embase and Google Scholar were searched to discover relevant articles available up to 17 March 2020. We used mean changes and SD of the outcomes to assess treatment response from baseline and mean difference, and 95 % CI were calculated to combined data and assessment effect sizes in astaxanthin and control groups.

    RESULTS: 14 eligible articles were included in the final quantitative analysis. Current study revealed that astaxanthin consumption was not associated with FBS, HbA1c, TC, LDL-C, TG, BMI, BW, DBP, and SBP. We did observe an overall increase in HDL-C (WMD: 1.473 mg/dl, 95 % CI: 0.319-2.627, p = 0.012). As for the levels of CRP, only when astaxanthin was administered (i) for relatively long periods (≥ 12 weeks) (WMD: -0.528 mg/l, 95 % CI: -0.990 to -0.066), and (ii) at high dose (> 12 mg/day) (WMD: -0.389 mg/dl, 95 % CI: -0.596 to -0.183), the levels of CRP would decrease.

    CONCLUSION: In summary, our systematic review and meta-analysis revealed that astaxanthin consumption was associated with increase in HDL-C and decrease in CRP. Significant associations were not observed for other outcomes.

  7. Schweiker M, Abdul-Zahra A, André M, Al-Atrash F, Al-Khatri H, Alprianti RR, et al.
    Sci Data, 2019 11 26;6(1):289.
    PMID: 31772199 DOI: 10.1038/s41597-019-0272-6
    Thermal discomfort is one of the main triggers for occupants' interactions with components of the built environment such as adjustments of thermostats and/or opening windows and strongly related to the energy use in buildings. Understanding causes for thermal (dis-)comfort is crucial for design and operation of any type of building. The assessment of human thermal perception through rating scales, for example in post-occupancy studies, has been applied for several decades; however, long-existing assumptions related to these rating scales had been questioned by several researchers. The aim of this study was to gain deeper knowledge on contextual influences on the interpretation of thermal perception scales and their verbal anchors by survey participants. A questionnaire was designed and consequently applied in 21 language versions. These surveys were conducted in 57 cities in 30 countries resulting in a dataset containing responses from 8225 participants. The database offers potential for further analysis in the areas of building design and operation, psycho-physical relationships between human perception and the built environment, and linguistic analyses.
  8. She S, Yu J, Tang W, Zhu Y, Chen Y, Sunarso J, et al.
    ACS Appl Mater Interfaces, 2018 Apr 11;10(14):11715-11721.
    PMID: 29546981 DOI: 10.1021/acsami.8b00682
    Perovskite oxide is an attractive low-cost alternative catalyst for oxygen evolution reaction (OER) relative to the precious metal oxide-based electrocatalysts (IrO2 and RuO2). In this work, a series of Sr-doped La-based perovskite oxide catalysts with compositions of La1- xSr xFeO3-δ ( x = 0, 0.2, 0.5, 0.8, and 1) are synthesized and characterized. The OER-specific activities in alkaline solution increase in the order of LaFeO3-δ (LF), La0.8Sr0.2FeO3-δ (LSF-0.2), La0.5Sr0.5FeO3-δ (LSF-0.5), SrFeO3-δ (SF), and La0.2Sr0.8FeO3-δ (LSF-0.8). We establish a direct correlation between the enhancement in the specific activity and the amount of surface oxygen vacancies as well as the surface Fe oxidation states. The improved specific activity for LSF-0.8 is clearly linked to the optimum amount of surface oxygen vacancies and surface Fe oxidation states. We also find that the OER performance stability is a function of the crystal structure and the deviation in the surface La and/or Sr composition(s) from their bulk stoichiometric compositions. The cubic structure and lower deviation, as is the case for LSF-0.8, led to a higher OER performance stability. These surface performance relations provide a promising guideline for constructing efficient water oxidation.
  9. Song P, Adeloye D, Acharya Y, Bojude DA, Ali S, Alibudbud R, et al.
    J Glob Health, 2024 Feb 16;14:04054.
    PMID: 38386716 DOI: 10.7189/jogh.14.04054
    BACKGROUND: In this priority-setting exercise, we sought to identify leading research priorities needed for strengthening future pandemic preparedness and response across countries.

    METHODS: The International Society of Global Health (ISoGH) used the Child Health and Nutrition Research Initiative (CHNRI) method to identify research priorities for future pandemic preparedness. Eighty experts in global health, translational and clinical research identified 163 research ideas, of which 42 experts then scored based on five pre-defined criteria. We calculated intermediate criterion-specific scores and overall research priority scores from the mean of individual scores for each research idea. We used a bootstrap (n = 1000) to compute the 95% confidence intervals.

    RESULTS: Key priorities included strengthening health systems, rapid vaccine and treatment production, improving international cooperation, and enhancing surveillance efficiency. Other priorities included learning from the coronavirus disease 2019 (COVID-19) pandemic, managing supply chains, identifying planning gaps, and promoting equitable interventions. We compared this CHNRI-based outcome with the 14 research priorities generated and ranked by ChatGPT, encountering both striking similarities and clear differences.

    CONCLUSIONS: Priority setting processes based on human crowdsourcing - such as the CHNRI method - and the output provided by ChatGPT are both valuable, as they complement and strengthen each other. The priorities identified by ChatGPT were more grounded in theory, while those identified by CHNRI were guided by recent practical experiences. Addressing these priorities, along with improvements in health planning, equitable community-based interventions, and the capacity of primary health care, is vital for better pandemic preparedness and response in many settings.

  10. Tobias DK, Merino J, Ahmad A, Aiken C, Benham JL, Bodhini D, et al.
    Nat Med, 2023 Oct;29(10):2438-2457.
    PMID: 37794253 DOI: 10.1038/s41591-023-02502-5
    Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
  11. Tao J, Chen J, Li J, Mathurin L, Zheng JC, Li Y, et al.
    Proc Natl Acad Sci U S A, 2017 09 12;114(37):9832-9837.
    PMID: 28855335 DOI: 10.1073/pnas.1709163114
    The optimal functionalities of materials often appear at phase transitions involving simultaneous changes in the electronic structure and the symmetry of the underlying lattice. It is experimentally challenging to disentangle which of the two effects--electronic or structural--is the driving force for the phase transition and to use the mechanism to control material properties. Here we report the concurrent pumping and probing of Cu2S nanoplates using an electron beam to directly manipulate the transition between two phases with distinctly different crystal symmetries and charge-carrier concentrations, and show that the transition is the result of charge generation for one phase and charge depletion for the other. We demonstrate that this manipulation is fully reversible and nonthermal in nature. Our observations reveal a phase-transition pathway in materials, where electron-induced changes in the electronic structure can lead to a macroscopic reconstruction of the crystal structure.
  12. Rao R, Bing Zhu Y, Alinejad T, Tiruvayipati S, Lin Thong K, Wang J, et al.
    Gut Pathog, 2015;7:6.
    PMID: 25922623 DOI: 10.1186/s13099-015-0052-6
    The Malaysian giant freshwater prawn, Macrobrachium rosenbergii, is an economically important crustacean worldwide. However, production of this prawn is facing a serious threat from Vibriosis disease caused by Vibrio species such as Vibrio parahaemolyticus. Unfortunately, the mechanisms involved in the immune response of this species to bacterial infection are not fully understood. We therefore used a high-throughput deep sequencing technology to investigate the transcriptome and comparative expression profiles of the hepatopancreas from this freshwater prawn infected with V. parahaemolyticus to gain an increased understanding of the molecular mechanisms underlying the species' immune response to this pathogenic bacteria.
  13. Schweiker M, Abdul-Zahra A, André M, Al-Atrash F, Al-Khatri H, Alprianti RR, et al.
    Sci Data, 2020 01 06;7(1):11.
    PMID: 31907360 DOI: 10.1038/s41597-019-0348-3
    An amendment to this paper has been published and can be accessed via a link at the top of the paper.
  14. McGrattan AM, Zhu Y, Richardson CD, Mohan D, Soh YC, Sajjad A, et al.
    J Alzheimers Dis, 2021;79(2):743-762.
    PMID: 33361599 DOI: 10.3233/JAD-201043
    BACKGROUND: Mild cognitive impairment (MCI) is a cognitive state associated with increased risk of dementia. Little research on MCI exists from low-and middle-income countries (LMICs), despite high prevalence of dementia in these settings.

    OBJECTIVE: This systematic review aimed to review epidemiological reports to determine the prevalence of MCI and its associated risk factors in LMICs.

    METHODS: Medline, Embase, and PsycINFO were searched from inception until November 2019. Eligible articles reported on MCI in population or community-based studies from LMICs and were included as long as MCI was clearly defined.

    RESULTS: 5,568 articles were screened, and 78 retained. In total, n = 23 different LMICs were represented; mostly from China (n = 55 studies). Few studies were from countries defined as lower-middle income (n = 14), low income (n = 4), or from population representative samples (n = 4). There was large heterogeneity in how MCI was diagnosed; with Petersen criteria the most commonly applied (n = 26). Prevalence of amnesic MCI (aMCI) (Petersen criteria) ranged from 0.6%to 22.3%. Similar variability existed across studies using the International Working Group Criteria for aMCI (range 4.5%to 18.3%) and all-MCI (range 6.1%to 30.4%). Risk of MCI was associated with demographic (e.g., age), health (e.g., cardio-metabolic disease), and lifestyle (e.g., social isolation, smoking, diet and physical activity) factors.

    CONCLUSION: Outside of China, few MCI studies have been conducted in LMIC settings. There is an urgent need for population representative epidemiological studies to determine MCI prevalence in LMICs. MCI diagnostic methodology also needs to be standardized. This will allow for cross-study comparison and future resource planning.

  15. Kanesvaran R, Castro E, Wong A, Fizazi K, Chua MLK, Zhu Y, et al.
    ESMO Open, 2022 Aug;7(4):100518.
    PMID: 35797737 DOI: 10.1016/j.esmoop.2022.100518
    The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of prostate cancer was published in 2020. It was therefore decided, by both the ESMO and the Singapore Society of Oncology (SSO), to convene a special, virtual guidelines meeting in November 2021 to adapt the ESMO 2020 guidelines to take into account the differences associated with the treatment of prostate cancer in Asia. These guidelines represent the consensus opinions reached by experts in the treatment of patients with prostate cancer representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with prostate cancer across the different regions of Asia.
  16. Li M, Zhang H, Zhang W, Cao Y, Sun B, Jiang Q, et al.
    Sci Total Environ, 2023 Mar 14;876:162807.
    PMID: 36921865 DOI: 10.1016/j.scitotenv.2023.162807
    In Shanghai, the prevalence of tet(X4) and tet(X4)-carrying plasmid from food-producing -animal Enterobacteriales has not been intensively investigated. Here, five tet(X4)-positive swine-origin E. coli strains were characterized among 652 food-producing-animal E. coli isolates in Shanghai during 2018-2021 using long-term surveillance among poultry, swine and cattle, antimicrobial susceptibility testing, and tet(X4)-specific PCR. A combination of short- and long-read sequencing technologies demonstrated that the five strains with 4 STs carried a nearly identical 193 kb tet(X4)-bearing plasmid (p193k-tetX4) belonging to the same IncFIA(HI1)/IncHI1A/IncHIB plasmid family (p193k). Surprisingly, 34 of the 151 global tet(X4)-positive plasmids was the p193k members and exclusively pandemic in China. Other p193k members harboring many critically important ARGs (mcr or blaNDM) with particular genetic environment are widespread throughout human-animal-environmental sources, with 33.77 % human origin. Significantly, phylogenetic analysis of 203 p193k-tetX4 sequences revealed that human- and animal-origin plasmids clustered within the same phylogenetic subgroups. The largest lineage (173/203) comprised 161 E. coli, 6 Klebsiella, 3 Enterobacter, 2 Citrobacter, and 1 Leclercia spp. from animals (n = 143), humans (n = 18), and the environment (n = 9). Intriguingly, the earliest 2015 E. coli strain YA_GR3 from Malaysian river water and 2016 S. enterica Chinese clinical strain GX1006 in another lineage demonstrated that p193k-tetX4 have been widely spread from S. enterica or E. coli to other Enterobacterales. Furthermore, 180 E. coli p193k-tetX4 strains were widespread cross-sectorial transmission among food animals, pets, migratory birds, human and ecosystems. Our findings proved the extensive transmission of the high-risk p193k harboring crucial ARGs across multiple interfaces and species. Therefore, one-health-based systemic surveillance of these similar high-risk plasmids across numerous sources and bacterial species is extremely essential.
  17. Chung WY, Zhu Y, Mahamad Maifiah MH, Shivashekaregowda NKH, Wong EH, Abdul Rahim N
    J Antibiot (Tokyo), 2021 02;74(2):95-104.
    PMID: 32901119 DOI: 10.1038/s41429-020-00366-2
    Antimicrobial resistance (AMR) threatens the effective prevention and treatment of a wide range of infections. Governments around the world are beginning to devote effort for innovative treatment development to treat these resistant bacteria. Systems biology methods have been applied extensively to provide valuable insights into metabolic processes at system level. Genome-scale metabolic models serve as platforms for constraint-based computational techniques which aid in novel drug discovery. Tools for automated reconstruction of metabolic models have been developed to support system level metabolic analysis. We discuss features of such software platforms for potential users to best fit their purpose of research. In this work, we focus to review the development of genome-scale metabolic models of Gram-negative pathogens and also metabolic network approach for identification of antimicrobial drugs targets.
  18. Lin YW, Abdul Rahim N, Zhao J, Han ML, Yu HH, Wickremasinghe H, et al.
    PMID: 30670431 DOI: 10.1128/AAC.02176-18
    Polymyxins are used as a last-line therapy against multidrug-resistant (MDR) New Delhi metallo-β-lactamase (NDM)-producing Klebsiella pneumoniae However, polymyxin resistance can emerge with monotherapy; therefore, novel strategies are urgently needed to minimize the resistance and maintain their clinical utility. This study aimed to investigate the pharmacodynamics of polymyxin B in combination with the antiretroviral drug zidovudine against K. pneumoniae Three isolates were evaluated in static time-kill studies (0 to 64 mg/liter) over 48 h. An in vitro one-compartment pharmacokinetic/pharmacodynamic (PK/PD) model (IVM) was used to simulate humanized dosage regimens of polymyxin B (4 mg/liter as continuous infusion) and zidovudine (as bolus dose thrice daily to achieve maximum concentration of drug in broth [Cmax] of 6 mg/liter) against K. pneumoniae BM1 over 72 h. The antimicrobial synergy of the combination was further evaluated in a murine thigh infection model against K. pneumoniae 02. In the static time-kill studies, polymyxin B monotherapy produced rapid and extensive killing against all three isolates followed by extensive regrowth, whereas zidovudine produced modest killing followed by significant regrowth at 24 h. Polymyxin B in combination with zidovudine significantly enhanced the antimicrobial activity (≥4 log10 CFU/ml) and minimized bacterial regrowth. In the IVM, the combination was synergistic and the total bacterial loads were below the limit of detection for up to 72 h. In the murine thigh infection model, the bacterial burden at 24 h in the combination group was ≥3 log10 CFU/thigh lower than each monotherapy against K. pneumoniae 02. Overall, the polymyxin B-zidovudine combination demonstrates superior antimicrobial efficacy and minimized emergence of resistance to polymyxins.
  19. Shen Y, Zhu Y, Sunarso J, Guan D, Liu B, Liu H, et al.
    Chemistry, 2018 May 11;24(27):6950-6957.
    PMID: 29411451 DOI: 10.1002/chem.201705675
    Because of their structural and compositional flexibility, perovskite oxides represent an attractive alternative electrocatalyst class to precious metals for the oxygen reduction reaction (ORR); an important reaction in fuel cells and metal-air batteries. Partial replacement of the original metal cation with another cation, namely, doping, can be used to tailor the ORR activity of perovskite, for which a metal has been exclusively used as the dopant component in the past. Herein, phosphorus is proposed as a non-metal dopant for the cation site to develop a new perovskite family with the formula of La0.8 Sr0.2 Mn1-x Px O3-δ (x=0, 0.02, 0.05, and 0.1; denoted as LSM, LSMP0.02, LSMP0.05, and LSMP0.1, respectively). Powder XRD patterns reveal that the solubility of phosphorus in the perovskite structure is around 0.05. Rotating ring-disk electrode experiments in the form of linear-sweep voltammetry scans demonstrated the best ORR performance for LSMP0.05, and also revealed close to a four-electron ORR pathway for all four compositions. A chronoamperometric test (9000 s) and 500 cycle accelerated durability test demonstrated higher durability for LSMP0.05 relative to that of LSM and the commercial 20 wt % Pt/C catalyst. The higher ORR activity for LSMP0.05 is attributed to the optimised average valence of Mn, as evidenced by combined X-ray photoelectron spectroscopy and soft X-ray absorption spectroscopy data. Doping phosphorus into perovskites is an effective way to develop high-performance electrocatalysts for ORR.
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