Global antimicrobial resistance: a system-wide comprehensive investigation using the Global One Health Index.

BACKGROUND: Antimicrobial resistance (AMR) is one of the top ten global public health challenges. However, given the lack of a comprehensive assessment of worldwide AMR status, our objective is to develop a One Health-based system-wide evaluation tool on global AMR. METHODS: We have further developed the three-hierarchical Global One Health Index (GOHI)-AMR indicator scheme, which consists of five key indicators, 17 indicators, and 49 sub-indicators, by incorporating 146 countries' data from diverse authoritative databases, including WHO's Global Antimicrobial Resistance and Use Surveillance System (GLASS) and the European CDC. We investigated the overall- or sub-rankings of GOHI-AMR at the international/regional/national levels for data preprocessing and score calculation utilizing the existing GOHI methodology. Additionally, a correlation analysis was conducted between the GOHI-AMR and other socioeconomic factors. RESULTS: The average GOHI-AMR score for 146 countries is 38.45. As expected, high-income countries (HICs) outperform the other three income groups on overall rankings and all five key indicators of GOHI-AMR, whereas low-income countries unexpectedly outperform upper-middle-income countries and lower-middle-income countries on the antibiotics-resistant key indicator (ARR) and ARR-subordinate indicators, including carbapenem-, ß-lactam-, and quinolone resistance, and even HICs on aminoglycoside resistance. There were no significant differences among the four groups on the environmental-monitoring indicator (P > 0.05). GOHI-AMR was positively correlated with gross domestic product, life expectancy, and AMR-related publications, but negatively with natural growth rate and chronic respiratory disease. In contrast to Cyprus, the remarkably lower prevalence of "ESKAPE pathogens" in high-scoring Sweden and Denmark highlights Europe's huge gaps. China and Russia outperformed the other three BRICS countries on all key indicators, particularly India's ARR and Brazil's AMR laboratory network and coordination capacity. Furthermore, significant internal disparities in carbapenem-resistant Klebsiella pneumoniae (CRKP) and methicillin-resistant Staphylococcus aureus (MRSA) prevalence were observed between China and the USA, with MRSA prevalence both gradually declining, whereas CRKP prevalence has been declining in the USA but increasing in China, consistent with higher carbapenems-related indicator' performance in USA. CONCLUSIONS: GOHI-AMR is the most comprehensive tool currently available for the assessment of AMR status worldwide. We discovered unique features impacting AMR in each country and offered precise recommendations to improve the capacity to tackle AMR in low-ranking countries.

A Plasmid With Conserved Phage Genes Helps Klebsiella pneumoniae Defend Against the Invasion of Transferable DNA Elements at the Cost of Reduced Virulence.

Klebsiella pneumoniae exhibits extensive phenotypic and genetic diversity. Higher plasmid loads in the cell were supposed to play an key role in its genome diversity. Although some plasmids are widely distributed in Kp populations, they are poorly recognized. A plasmid named p2 in strain Kp1604 was predicted to be an intact prophage like Salmonella phage SSU5. However, our study showed that p2 was specifically packaged into membrane vesicles (MVs) rather than phage particles triggered by mitomycin C and subinhibitory concentrations of antibiotics. p2-minus mutant Kp1604Δp2 did not affect MV production. Compared with Kp1604, the capacity of plasmid uptake and the amount of phage burst of Kp1604Δp2 were improved. Moreover, virulence of Kp1604Δp2 also increased. Our results indicated that p2 could contribute to the host defense against the invasion of transferable DNA elements at the cost of reduced virulence. Further study on the mechanism will help us understand how it provides adaptive phenotypes to host evolution.

What matters for regional economic resilience amid COVID-19? Evidence from cities in Northeast China.

This paper examines how the economies of old industrial cities in Northeast China respond to the on-going COVID-19 pandemic crisis. The notion of resistance in regional economic resilience is used to explore what impact factors shape the response to the early stage of the crisis. The analysis reveals significant differences in terms of regional economic impact between COVID-19 and the 2008 financial crisis. We find that large cities are more vulnerable and exposed to the pandemic at its early stage, state agency plays a crucial role in shaping the economic resistance in most cities. Going beyond the existing 2008 financial crisis-induced account on regional economic resilience, this paper argues that regional resistance amid COVID-19 is not merely shaped by economic structural factors but also influenced by state agency in terms of economic restriction and restoration measures. The study suggests that the nature of COVID-19 as a particular context of crisis itself needs to be taken seriously when exploring the determinants and outcomes of regional economic resilience.

Characterizing the patterns of China's policies against COVID-19: A bibliometric study.

Since the beginning of 2020, the Chinese government has implemented substantial policies to prevent and control the COVID-19 epidemic. This research attempts to reveal and characterize the patterns of China's policy against COVID-19. Bibliometric methods are applied for studying policy evolution, with the aim of discovering the transitions of the policies over time, the collaborations among policy makers, and the effects of the policies. A total of 366 policies of epidemic prevention are collected. Policy topic shifting, the cooperation of policy-issuing agencies, and the policy content of agencies are analyzed. According to the results, China's policies are implemented in four stages. Moreover, the policy's foci against COVID-19 shifted from medical support in the early stage to economic development in the late stage. Agencies involved in the policymaking can be categorized into three types: leading agencies, key agencies, and auxiliary agencies, with their corresponding administrative influence ranked in this order. Especially, the Chinese government adopted a multi-agency, joint epidemic prevention and control mechanism to ensure the efficiency of the policymaking cooperation. Furthermore, aside from ensuring cooperation among the policy-issuing agencies, they each had their own primary focus of policies in the early stage, but their foci were gradually shared as the epidemic situation changed. This research reveals how China responded to the public health emergency of COVID-19 from the perspective of policy making.

Investigation and assessment of micropollutants and associated biological effects in wastewater treatment processes.

Currently, the wastewater treatment plants (WWTPs) attempt to achieve the shifting from general pollution parameters control to reduction of organic micropollutants discharge. However, they have not been able to satisfy the increasing ecological safety needs. In this study, the removal of micropollutants was investigated, and the ecological safety was assessed for a local WWTP. Although the total concentration of 31 micropollutants detected was reduced by 83% using the traditional biological treatment processes, the results did not reflect chemicals that had poor removal efficiencies and low concentrations. Of the five categories of micropollutants, herbicides, insecticides, and bactericides were difficult to remove, pharmaceuticals and UV filters were effectively eliminated. The specific photosynthesis inhibition effect and non-specific bioluminescence inhibition effect from wastewater were detected and evaluated using hazardous concentration where 5% of aquatic organisms are affected. The photosynthesis inhibition effect from wastewater in the WWTP was negligible, even the untreated raw wastewater. However, the bioluminescence inhibition effect from wastewater which was defined as the priority biological effect, posed potential ecological risk. To decrease non-specific biological effects, especially of macromolecular dissolved organic matter, overall pollutant reduction strategy is necessary. Meanwhile, the ozonation process was used to further decrease the bioluminescence inhibition effects from the secondary effluent; ≥ 0.34 g O3/g DOC of ozone dose was recommended for micropollutants elimination control and ecological safety.

[Pathogen distribution, risk factors, and outcomes of nosocomial infection in very premature infants].

OBJECTIVE: To study the pathogen distribution and risk factors of nosocomial infection in very preterm infants, as well as the risk of adverse outcomes. METHODS: A retrospective analysis was performed for the clinical data of 111 very preterm infants who were born between January and December, 2016 and had a gestational age of <32 weeks and a birth weight of <1 500 g. According to the presence or absence of nosocomial infection after 72 hours of hospitalization, the infants were divided into infection group and non-infection group. The infection group was analyzed in terms of pathogenic bacteria which caused infection and their drug sensitivity. A multivariate logistic regression analysis was used to investigate the potential risk factors and risk of adverse outcomes of nosocomial infection in very preterm infants. RESULTS: Gram-negative bacteria were the main pathogens for nosocomial infection in very preterm infants and accounted for 54%, among which Pseudomonas aeruginosa was the most common one; the following pathogens were fungi (41%), among which Candida albicans was the most common one. The drug sensitivity test showed that Gram-negative bacteria were highly resistant to ß-lactam and carbapenems and highly sensitive to quinolones, while fungi had low sensitivity to itraconazole and high sensitivity to 5-fluorocytosine and amphotericin B. Early-onset sepsis, duration of peripherally inserted central catheter, steroid exposure, and duration of parenteral nutrition were risk factors for nosocomial infection in very preterm infants (P<0.05). Compared with the non-infection group, the infection group had significantly higher risks of pulmonary complications (P<0.05), as well as a significantly longer length of hospital stay and a significantly higher hospital cost (P<0.001). CONCLUSIONS: Nosocomial infection in very preterm infants is affected by various factors and may increase the risk of adverse outcomes. In clinical practice, reasonable preventive and treatment measures should be taken with reference to drug sensitivity, in order to improve the prognosis of very premature infants.

Economic Impacts of the Generic Drug User Fee Act Fee Structure.

BACKGROUND: A Food and Drug Administration (FDA) Generic Drug User system, Generic Drug User Fee Amendment of 2012 (GDUFA), started October 1, 2012, and has been in place for over 3 years. There is controversy about the GDUFA fee structure but no analysis of GDUFA data that we could find. OBJECTIVE: To look at the economic impact of the GDUFA fee structure. METHODS: We compared the structure of GDUFA with that of other FDA Human Drug User fees. We then, using FDA-published information, analyzed where GDUFA facility and Drug Master File fees are coming from. We used the Orange Book to identify the sponsors of all approved Abbreviated New Drug Applications (ANDAs) and the S&P Capital IQ database to find the ultimate parent companies of sponsors of approved ANDAs. RESULTS: The key differences between the previous structure for Human Drug User fees and the GDUFA are as follows: GDUFA has no approved product fee and no first-time or small business fee exemptions and GDUFA charges facility fees from the time of filing and charges a foreign facility levy. Most GDUFA fees are paid by or on behalf of foreign entities. The top 10 companies hold nearly 50% of all approved ANDAs but pay about 14% of GDUFA facility fees. CONCLUSIONS: We conclude that the regressive nature of the GDUFA fee structure penalizes small, new, and foreign firms while benefiting the large established firms. A progressive fee structure in line with other human drug user fees is needed to ensure a healthy generic drug industry.

Safety assessment of Staphylococcus phages of the family Myoviridae based on complete genome sequences.

Staphylococcus phages of the Myoviridae family have a wide host range and potential applications in phage therapy. In this report, safety assessments of these phages were conducted based on their complete genome sequences. The complete genomes of Staphylococcus phages of the Myoviridae family were analyzed, and the Open Reading Frame (ORFs) were compared with a pool of virulence and antibiotic resistance genes using the BLAST algorithm. In addition, the lifestyle of the phages (virulent or temperate) was also confirmed using PHACTS. The results showed that all phages were lytic and did not contain resistance or virulence genes based on bioinformatic analyses, excluding the possibility that they could be vectors for the dissemination of these undesirable genes. These findings suggest that the phages are safe at the genome level. The SceD-like transglycosylase, which is a biomarker for vancomycin-intermediate strains, was widely distributed in the phage genomes. Approximately 70% of the ORFs encoded in the phage genomes have unknown functions; therefore, their roles in the antibiotic resistance and virulence of Staphylococcus aureus are still unknown and require consideration before use in phage therapy.

Evidence for Dual Binding Sites for 1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) in Insect Sodium Channels.

1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), the first organochlorine insecticide, and pyrethroid insecticides are sodium channel agonists. Although the use of DDT is banned in most of the world due to its detrimental impact on the ecosystem, indoor residual spraying of DDT is still recommended for malaria control in Africa. Development of resistance to DDT and pyrethroids is a serious global obstacle for managing disease vectors. Mapping DDT binding sites is necessary for understanding mechanisms of resistance and modulation of sodium channels by structurally different ligands. The pioneering model of the housefly sodium channel visualized the first receptor for pyrethroids, PyR1, in the II/III domain interface and suggested that DDT binds within PyR1. Previously, we proposed the second pyrethroid receptor, PyR2, at the I/II domain interface. However, whether DDT binds to both pyrethroid receptor sites remains unknown. Here, using computational docking of DDT into the Kv1.2-based mosquito sodium channel model, we predict that two DDT molecules can bind simultaneously within PyR1 and PyR2. The bulky trichloromethyl group of each DDT molecule fits snugly between four helices in the bent domain interface, whereas two p-chlorophenyl rings extend into two wings of the interface. Model-driven mutagenesis and electrophysiological analysis confirmed these propositions and revealed 10 previously unknown DDT-sensing residues within PyR1 and PyR2. Our study proposes a dual DDT-receptor model and provides a structural background for rational development of new insecticides.

Risk assessment of deep-vein thrombosis after acute stroke: a prospective study using clinical factors.

AIMS: Deep-vein thrombosis (DVT) represents a serious complication in acute stroke patients with pulmonary embolus (PE) as a potential outcome. Prediction of DVT may help with formulating a proper prevention strategy. To assess of the risk of deep venous thrombosis (DVT) in acute stroke patients, we developed and validated a clinical score in a cohort study. METHODS: Incidence of Deep Venous Thrombosis after Acute Stroke in China (INVENT-China) is a multicenter prospective cohort study. The potential predictive variables for DVT at baseline were collected, and the presence of DVT was evaluated using ultrasonography on the 14 ± 3 days. Data were randomly assigned to either a training data set or a test data set. Multivariate logistic regression analysis was used to develop risk scores to predict DVT in the training data set and the area under the receiver operating characteristic curve to validate the score in the test data set. RESULTS: From 2006-2007, 862 hospital-based acute stroke patients were enrolled in China. The overall incidence of DVT after acute stroke within two weeks was 12.4% (95%CI 10.3-14.7%). A seven-point score derived in the training data set (age [≥65 years = 1], sex [female gender = 1]), obesity [BMI ≥ 25 kg/m(2) = 1], active cancer [yes = 2], stroke subtype [cerebral hemorraghe = 1], muscle weakness [≥2 on Lower limb NIHSS score = 1] was highly predictive of 14-day risk of DVT(c statistic = 0.70, 95% CI, 0.64-0.76, P < 0.001), in the overall study population(c statistic = 0.65, 95% CI 0.59-0.70, P < 0.001). CONCLUSIONS: This clinical score may help identify acute stroke patients with high risk of DVT. In addition, it also serves as a platform to develop further models of DVT prediction in stroke patients based on clinical factors.