Assessment of cefiderocol disk diffusion versus broth microdilution results when tested against Acinetobacter baumannii complex clinical isolates.

IMPORTANCE: Carbapenem-resistant Acinetobacter baumannii is a major global health concern due to its high prevalence and limited treatment options. Cefiderocol is the only novel Food and Drug Administration (FDA)-approved ß-lactam agent for the salvage treatment of carbapenem-resistant A. baumannii infection. Currently, a commercial automated susceptibility testing panel of cefiderocol is unavailable. Both the preparation of iron-depleted cation-adjusted Mueller-Hinton broth and the performance of broth microdilution are cumbersome in routine microbiology laboratories. A disk diffusion method is convenient for cefiderocol antimicrobial susceptibility testing, but limited data are available specifically for A. baumannii clinical isolates. Moreover, the Clinical and Laboratory Standards Institute published revisions to the A. baumannii cefiderocol disk diffusion breakpoints in 2022. Hence, we evaluated the performance of cefiderocol disk diffusion compared with the reference BMD against A. baumannii clinical isolates, especially those with cefiderocol zone diameters ≤ 14 mm.

Occurrence, spatial heterogeneity, and risk assessment of perfluoroalkyl acids (PFAAs) in the major rivers of the Tibetan Plateau.

The Tibetan Plateau (TP) is home to the headwaters of major rivers in Asia, yet their water quality security on a large spatial scale is scarcely studied, especially in regard to emerging organic pollutants. In this study, a systematic field campaign was carried out along Yarlung Tsangpo River, Nu River, Lancang River and Jinsha River, and 13 perfluoroalkyl acids (PFAAs) were analyzed. The total concentrations of PFAAs in the river waters of the TP were in the range of 0.58-7.46 ng/L, containing a high proportion of perfluorobutanoic acid (PFBA) and perfluorobutane sulfonate (PFBS) with average values of 56.7 %. Elevated PFAA loadings were found for the midstream of Yarlung Tsangpo River in central Tibet. Geodetector results indicated that precipitation, solar radiation and vegetation type were the top three influential factors contributing to the observed spatial heterogeneity. When interactions with human activities were taken into account, the explanatory power was significantly enhanced and rose above 0.70, highlighting the increased risks for TP rivers from the combined effects of natural environments and anthropogenic activities. Risk assessments suggest a low risk is posed to the alpine aquatic ecosystems and human health. The discharge fluxes of PFAAs via riverine export were estimated at 94-425 kg/year, which is one to two orders of magnitude lower than their mass loadings in major rivers worldwide. Our study underlined the need for further attention to the increased risk of water resource quality on the central TP in the context of long-range transport, increased cryosphere melting and local emission.

Spatial variations and social determinants of life expectancy in China, 2005-2020: A population-based spatial panel modelling study.

Background: Social determinants of health (SDOH) produce a broad range of life expectancy (LE) disparities. In China, limited literatures were found to report association between SDOH and LE at ecological level during a consecutive period of time from the spatial perspectives. This study aimed to determine the existence, quantify the magnitude, and interpret the association between SDOH and LE in China. Methods: Provincial-level LE were estimated from mortality records during 2005-2020 from National Mortality Surveillance System in China. A spatial panel Durbin model was used to investigate LE associated SDOH proxies. Spatial spillover effects were introduced to interpret direct and indirect effects caused by SDOH during long-term and short-term period on LE disparities. Findings: Nationwide, LE increased from 73.1 (95% confidence interval (CI): 71.3, 74.4) years to 77.7 (95%CI: 76.5, 78.7) years from 2005 to 2020. Unequally spatial distribution of LE with High-High clustering in coastal areas and Low-Low clustering in western regions were observed. Locally, it was estimated that SDOH proxies statistically significant related to an increase of LE, including GDP (coefficient: 0.02, 95%CI: 0.00, 0.03), Gini index (coefficient: 2.35, 95%CI: 1.82, 2.88), number of beds in health care institutions (coefficient: 0.02, 95%CI: 0.00, 0.05) and natural growth rate of resident population (coefficient: 0.02, 95%CI: 0.01, 0.02). Direct and indirect effects decomposition during long-term and short-term of LE associated SDOH proxies demonstrated that GDP, urbanization rate, unemployment rate, education attainment, Gini index, number of beds in health care institutions, sex ratio, gross dependence ratio and natural growth rate of resident population not only affected local LE, but also exerted spatial spillover effects towards geographical neighbors. Interpretation: Spatial variations of LE existed at provincial-level in China. SDOH regarding socioeconomic development and equity, healthcare resources, as well as population characteristics not only affected LE disparities at local scale but also among nearby provinces. Externalities of policy of those SDOH proxies should be took into consideration to promote health equity nationally. Comprehensive approaches on the basis of population strategy should be consolidated to optimize supportive socioeconomic environment and narrow the regional gap to reduce health disparities and increase LE. Funding: National Key Research & Development Program of China (Grant No.2018YFC1315301); Ministry of Education of China Humanities and Social Science General Program (Grant No.18YJC790138).

Spatiotemporal Evolution and Drivers of Total Health Expenditure across Mainland China in Recent Years.

A substantially growing health expenditure has become an important global issue. Thus, how and why health expenditure is rising should be urgently investigated in systematic research. The Bayesian space-time model and the Bayesian least absolute shrinkage and selection operator (LASSO) model were employed in this study to investigate the spatiotemporal trends and influence patterns of total health expenditure per capita (THEPC) and total health expenditure (THEE) as a share of the gross domestic product (GDP) on the Chinese mainland from 2009 to 2018. The spatial distribution of THEE as a share of GDP in mainland China has shaped a distinct geographical structure with the characteristic of 'west high/east low'. Its local increasing trends formed a geographical structure that exhibited a 'north high/south low' feature. The heterogeneity of the influence patterns of health expenditure was observed from east to west across China. Natural environmental factors, such as air pollution and green coverage, along with changes in dietary structures, have increasingly influenced the growth of health expenditures.

FN3 Domain Displaying Double Epitopes: A Cost-Effective Strategy for Producing Substitute Antigens.

Construction of substitute antigens based on alternative scaffold proteins is a promising strategy in bioassay technology. In this study, we proposed a strategy for constructing substitute antigens derived from 10th human fibronectin type III (FN3) using two peptide epitopes of terminal pro-brain natriuretic peptide (NT-proBNP) as an example. The base sequences encoding the two antigenic epitopes of NT-proBNP were recombined into the FG loop region and the C-terminus of FN3, fused by 4 GS or polyN linker. The fusion proteins (named FN3-epitopes-4GS and FN3-epitopes-polyN, respectively) were expressed and purified cost-effectively using an Escherichia coli expression system. The immunoreactivity of recombinant substitutes was preliminarily confirmed by western blot analysis using epitope-specific antibodies. The sandwich enzyme-linked immunosorbent assay demonstrated that either FN3-epitopes-polyN or FN3-epitopes-4GS was highly sensitive, and FN3-epitopes-polyN exhibited better kinetics to specific antibodies than FN3-epitopes-4GS, showing a linear dose-response relationship in the concentration range of 0.06-12.85 ng/ml, which suggest that the polyN linker was more suitable for constructing the FN3-based substitute antigens compared to the 4 GS linker. Furthermore, the serum stability test and differential scanning calorimetry analysis showed that the recombinant FN3-epitopes-polyN maintained the original stability of FN3. Therefore, it was confirmed that FN3 could be engineered to construct a stable biomacromolecular substitute for displaying double epitopes of antigen proteins, such as NT-proBNP. In summary, a cost-effective strategy to produce NT-proBNP substitute antigens with good immunoreactivity and physicochemical stability was established in this work, which may provide potential uses for the production of other substitute antigens in the future.

Determinant Powers of Socioeconomic Factors and Their Interactive Impacts on Particulate Matter Pollution in North China.

Severe air pollution has significantly impacted climate and human health worldwide. In this study, global and local Moran's I was used to examine the spatial autocorrelation of PM2.5 pollution in North China from 2000-2017, using data obtained from Atmospheric Composition Analysis Group of Dalhousie University. The determinant powers and their interactive effects of socioeconomic factors on this pollutant are then quantified using a non-linear model, GeoDetector. Our experiments show that between 2000 and 2017, PM2.5 pollution globally increased and exhibited a significant positive global and local autocorrelation. The greatest factor affecting PM2.5 pollution was population density. Population density, road density, and urbanization showed a tendency to first increase and then decrease, while the number of industries and industrial output revealed a tendency to increase continuously. From a long-term perspective, the interactive effects of road density and industrial output, road density, and the number of industries were amongst the highest. These findings can be used to develop the effective policy to reduce PM2.5 pollution, such as, due to the significant spatial autocorrelation between regions, the government should pay attention to the importance of regional joint management of PM2.5 pollution.

Spatiotemporal matching between medical resources and population ageing in China from 2008 to 2017.

BACKGROUND: Globally, the increasingly severe population ageing issue has been creating challenges in terms of medical resource allocation and public health policies. The aim of this study is to address the space-time trends of the population-ageing rate (PAR), the number of medical resources per thousand residents (NMRTR) in mainland China in the past 10 years, and to investigate the spatial and temporal matching between the PAR and NMRTR in mainland China. METHODS: The Bayesian space-time hierarchy model was employed to investigate the spatiotemporal variation of PAR and NMRTR in mainland China over the past 10 years. Subsequently, a Bayesian Geo-Detector model was developed to evaluate the spatial and temporal matching levels between PAR and NMRTR at national level. The matching odds ratio (OR) index proposed in this paper was applied to measure the matching levels between the two terms in each provincial area. RESULTS: The Chinese spatial and temporal matching q-statistic values between the PAR and three vital types of NMRTR were all less than 0.45. Only the spatial matching Bayesian q-statistic values between the PAR and the number of beds in hospital reached 0.42 (95% credible interval: 0.37, 0.48) nationwide. Chongqing and Guizhou located in southwest China had the highest spatial and temporal matching ORs, respectively, between the PAR and the three types of NMRTR. The spatial pattern of the spatial and temporal matching ORs between the PAR and NMRTR in mainland China exhibited distinct geographical features, but the geographical structure of the spatial matching differed from that of the temporal matching between the PAR and NMRTR. CONCLUSION: The spatial and temporal matching degrees between the PAR and NMRTR in mainland China were generally very low. The provincial regions with high PAR largely experienced relatively low spatial matching levels between the PAR and NMRTR, and vice versa. The geographical pattern of the temporal matching between the PAR and NMRTR exhibited the feature of north-south differentiation.

Spatiotemporal trends and ecological determinants in maternal mortality ratios in 2,205 Chinese counties, 2010-2013: A Bayesian modelling analysis.

BACKGROUND: As one of its Millennium Development Goals (MDGs), China has achieved a dramatic reduction in the maternal mortality ratio (MMR), although a distinct spatial heterogeneity still persists. Evidence of the quantitative effects of determinants on MMR in China is limited. A better understanding of the spatiotemporal heterogeneity and quantifying determinants of the MMR would support evidence-based policymaking to sustainably reduce the MMR in China and other developing areas worldwide. METHODS AND FINDINGS: We used data on MMR collected by the National Maternal and Child Health Surveillance System (NMCHSS) at the county level in China from 2010 to 2013. We employed a Bayesian space-time model to investigate the spatiotemporal trends in the MMR from 2010 to 2013. We used Bayesian multivariable regression and GeoDetector models to address 3 main ecological determinants of the MMR, including per capita income (PCI), the proportion of pregnant women who delivered in hospitals (PPWDH), and the proportion of pregnant women who had at least 5 check-ups (PPWFC). Among the 2,205 counties, there were 925 (42.0%) hotspot counties, located mostly in China's western and southwestern regions, with a higher MMR, and 764 (34.6%) coldspot counties with a lower MMR than the national level. China's westernmost regions, including Tibet and western Xinjiang, experienced a weak downward trend over the study period. Nationwide, medical intervention was the major determinant of the change in MMR. The MMR decreased by 1.787 (95% confidence interval [CI]: 1.424-2.142, p < 0.001) per 100,000 live births when PPWDH increased by 1% and decreased by 0.623 (95% CI 0.436-0.798, p < 0.001) per 100,000 live births when PPWFC increased by 1%. The major determinants for the MMR in China's western and southwestern regions were PCI and PPWFC, while that in China's eastern and southern coastlands was PCI. The MMR in western and southwestern regions decreased nonsignificantly by 1.111 (95% CI -1.485-3.655, p = 0.20) per 100,000 live births when PCI in these regions increased by 1,000 Chinese Yuan and decreased by 1.686 (95% CI 1.275-2.090, p < 0.001) when PPWFC increased by 1%. Additionally, the western and southwestern regions showed the strongest interactive effects between different factors, in which the corresponding explanatory power of any 2 interacting factors reached up to greater than 80.0% (p < 0.001) for the MMR. Limitations of this study include a relatively short study period and lack of full coverage of eastern coastlands with especially low MMR. CONCLUSIONS: Although China has accomplished a 75% reduction in the MMR, spatial heterogeneity still exists. In this study, we have identified 925 (hotspot) high-risk counties, mostly located in western and southwestern regions, and among which 332 counties are experiencing a slower pace of decrease than the national downward trend. Nationally, medical intervention is the major determinant. The major determinants for the MMR in western and southwestern regions, which are developing areas, are PCI and PPWFC, while that in China's developed areas is PCI. The interactive influence of any two of the three factors, PCI, PPWDH, and PPWFC, in western and southwestern regions was up to and in excess of 80% (p < 0.001).

Assessment of RANTES levels as the indicators of plaque vulnerability in rabbit models of atherosclerosis.

The aim of the present study was to determine the chemokine RANTES (regulated on activation, normal T-cell expressed, and secreted) levels in plasma and atherosclerotic plaques and to assess their diagnostic efficacy in the evaluation of vulnerable plaques. The rabbit models of vulnerable atherosclerotic plaque (VAP) were established by high fat diet and pharmaceutical triggering. The serum RANTES levels of VAP group (91.97 ± 8.51 ng/ml) were significantly higher than those of AS (atherosclerosis) group (50.03 ± 2.92 ng/ml). Consistently, the mRNA and protein of RANTES in vulnerable atherosclerotic plaques were also obviously up-regulated compared to AS group (P < 0.01). Moreover, corrected plaque area and vulnerability index of VAP group proved to be significantly higher than AS group. The correlation coefficient between RANTES and plaque vulnerability indicated that RANTES, especially plaque RANTES, was positively correlated with VAP. In addition, increased expression of nuclear factor kappa B p65 (NF-κB p65) was observed in VAP group compared to AS group (P < 0.05), which partly accounted for the increased RANTES levels. In conclusion, positive associations between RANTES and plaque vulnerability suggest that higher RANTES levels may be associated with atherosclerosis and high-risk plaques. Our study highlights the utility of both serum and plaque RANTES levels as indicators of plaque vulnerability in the field of preventive cardiology.