Knowledge, attitudes and practices relating to antibiotic use and antibiotic resistance among backyard pig farmers in rural Shandong province, China

China is among the world's largest consumers of antibiotics for livestock, and the demand for meat protein continues to rise. Pig production takes place at a range of facilities, including backyard pig farms. The aim of this study was to describe the knowledge, attitudes and practices of backyard pig farmers concerning antibiotic use and resistance, and to observe household storage of antibiotics for use in pigs. We conducted a cross-sectional questionnaire survey among 271 rural residents with backyard pig farms in 12 villages in one town in Shandong province. The median number of pigs per backyard farm was 14, and 82 % (222/271) of participants reported not having had any training about raising pigs. Eighteen percent of participants (48/271) reported always or often adding antibiotics to feed to keep pigs healthy and prevent diseases, and a third (88/271) of participants believed that pigs should be given antibiotics when they stop eating. Thirty percent (82/271) reported having bought antibiotics in the previous year without having first spoken with a veterinarian. Antibiotics accounted for over half of all medicines stored (55 %, 197/358), and were observed in 31 % of all households (83/271). Less than half of participants (45 %, 37/83) from households in which antibiotics for pig use were found knew that they were storing antibiotics. The most common class of antibiotics stored for use in pigs was (Q)J01C betalactam antibiotics, penicillins (19 %, 37/197), followed by (Q)J01F macrolides, lincosamides and streptogramins (14 %, 28/197), and (Q)J01M quinolones (12 %, 25/197). These results provide important insights into how backyard pig farmers are using antibiotics in rural China and suggest potential targets for interventions to reduce unnecessary and inappropriate use

Carbapenemase-Producing Escherichia coli among Humans and Backyard Animals

Background: The rapidly increasing dissemination of carbapenem-resistant Enterobacteriaceae (CRE) in both humans and animals poses a global threat to public health. However, the transmission of CRE between humans and animals has not yet been well studied. Objectives: We investigated the prevalence, risk factors, and drivers of CRE transmission between humans and their backyard animals in rural China. Methods: We conducted a comprehensive sampling strategy in 12 villages in Shandong, China. Using the household [residents and their backyard animals (farm and companion animals)] as a single surveillance unit, we assessed the prevalence of CRE at the household level and examined the factors associated with CRE carriage through a detailed questionnaire. Genetic relationships among human- and animal-derived CRE were assessed using whole-genome sequencing–based molecular methods. Results: A total of 88 New Delhi metallo-β-lactamases –type carbapenem-resistant Escherichia coli (NDM-EC), including 17 from humans, 44 from pigs, 12 from chickens, 1 from cattle, and 2 from dogs, were isolated from 65 of the 746 households examined. The remaining 12 NDM-EC were from flies in the immediate backyard environment. The NDM-EC colonization in households was significantly associated with a) the number of species of backyard animals raised/kept in the same household, and b) the use of human and/or animal feces as fertilizer. Discriminant analysis of principal components (DAPC) revealed that a large proportion of the core genomes of the NDM-EC belonged to strains from hosts other than their own, and several human isolates shared closely related core single-nucleotide polymorphisms and blaNDM genetic contexts with isolates from backyard animals. Conclusions: To our knowledge, we are the first to report evidence of direct transmission of NDM-EC between humans and animals. Given the rise of NDM-EC in community and hospital infections, combating NDM-EC transmission in backyard farm systems is needed. https://doi.org/10.1289/EHP525

Agrimol B inhibits colon carcinoma progression by blocking mitochondrial function through the PGC-1α/NRF1/TFAM signaling pathway

BackgroundThe activation of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) stimulates the transcription of the downstream target proteins, mitochondrial transcription factor A (TFAM) and nuclear respiratory factor 1 (NRF1), which induces mitochondrial biogenesis and promotes colorectal tumorigenesis. Agrimol B (Agr) is a constituent of Agrimonia pilosa Ledeb. that exerts anticancer effects. Herein, we aimed to investigate the antitumor activity of Agr and its mechanism of action.MethodsThe interaction between Agr and PGC-1α was predicted by molecular docking. After the treatment with different concentrations of Agr (0, 144, 288, and 576 nM), the cell viability, migration rate, proliferation rate, and apoptosis rate of human colon cancer HCT116 cells were determined. Mitochondrial activity, cellular reactive oxygen species (ROS), and mitochondrial membrane potential were assessed to measure the regulatory effect of Agr on mitochondrial function. Western blotting (WB) assay was used to examine the expression of PGC-1α, NRF1, and TFAM, as well as of the pro-apoptotic proteins, Bax and Caspase-3, and the antiapoptotic protein (Bcl-2). Finally, subcutaneous tumor xenograft model mice were used to evaluate the effect of Agr on colorectal cancer (CRC) in vivo.ResultsThe molecular docking results revealed a high likelihood of Agr interacting with PGC-1α. Agr inhibited the proliferation and migration of HCT116 cells, promoted ROS production and mitochondrial oxidative stress, inhibited mitochondrial activity, and decreased mitochondrial membrane potential. Agr induced cell apoptosis and, in combination with PGC-1α, impaired mitochondrial biogenesis and suppressed the expression of NRF1 and TFAM. Agr also suppressed the expression of Bcl-2 and Cleaved-Caspase-3 and increased the expression of Bax and Caspase-3. In addition, the in vivo antitumor effect and mechanism of Agr were confirmed by using a subcutaneous tumor xenograft mouse model.ConclusionsOur findings demonstrated that Agr regulates the expression of PGC-1α, thereby inducing mitochondrial dysfunction and promoting tumor cell apoptosis. This work highlights the potential of Agr as a promising therapeutic candidate in CRC

Effectiveness of chemotherapy using bortezomib combined with homoharringtonine and cytarabine in refractory or relapsed acute myeloid leukemia: a phase II, multicenter, prospective clinical trial

BackgroundRefractory/relapsed acute myeloid leukemia (R/R AML) has unsatisfactory outcomes even after allogeneic hematopoietic stem cell transplantation. Long-term survival is mainly influenced by complete remission (CR) rates after induction therapies.ObjectivesTo investigate CR/CR with incomplete hematologic recovery (CRi) rates and adverse events with a new induction therapy (bortezomib, homoharringtonine, and cytarabine [BHA]) for patients with R/R AML.MethodsWe enrolled 21 patients with R/R AML (median age, 42 [range, 30–62] years), who received BHA for remission induction (bortezomib, 1.3 mg/m2/day on days 1 and 4; homoharringtonine, 4 mg/m2/day for 5 days, and cytarabine, 1.5 g/m2/day for 5 days). CR and adverse events were assessed.ResultsAfter one course of BHA, the CR/CRi and partial remission rates were 38.1% and 14.3%, respectively, with an overall response rate (ORR) of 52.4% in 21 patients. 9 of 21 patients harbored FLT3-ITD or FLT3-TKD mutations, and achieved either CR/CRi or ORR of 66.7% (P=0.03) by comparison with that in R/R AML without FLT3 mutation. After induction therapy, consolidation chemotherapy or allogeneic hematopoietic stem cell transplantation led to a one-year overall survival of 27.8% in all patients. One-year relapse-free survival was 50% in 8 patients who had achieved CR/CRi after one course of BHA. During induction, non-hematologic adverse events (grade 3/4) commonly were infection (90.5%), hypokalemia (14.4%), hypocalcemia (14.3%), and mucositis (9.5%). In patients achieving CR, the median time to neutrophil count >0.5×109/L and time to platelet count >20×109/L were 15 (13–17) days and 13 (13–18) days, respectively.ConclusionBHA chemotherapy regimen was safe and tolerable to serve as an induction therapy for R/R AML, particularly with FLT3 mutation. The higher CR/CRi rate will give a clue to determine a potentialeffectiveness of BHA for AML patients carrying FLT3 mutation in a further investigation.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2000029841

Effects of artemisinin on ventricular arrhythmias in response to left ventricular afterload increase and microRNA expression profiles in Wistar rats

Background Patients with dilated cardiomyopathy, increased ventricular volume, pressure overload or dysynergistic ventricular contraction and relaxation are susceptible to develop serious ventricular arrhythmias (VA). These phenomena are primarily based on a theory of mechanoelectric feedback, which reflects mechanical changes that produce alterations in electrical activity. However, very few systematic studies have provided evidence of the preventive effects of artemisinin (ART) on VA in response to left ventricle (LV) afterload increases. MicroRNAs (miRNAs) are endogenous small non-coding RNAs that regulate expression of multiple genes by suppressing mRNAs post-transcriptionally. Aims The aims of this study were to investigate preventive effects of ART on mechanical VA and the underling molecular mechanisms of differentially expressed miRNAs (DEMs). Methods For the study, 70 male Wistar rats were randomly divided into seven groups: group 1 was a control group (sham surgery); group 2 was a model group that underwent transverse aortic constriction (TAC) surgery; groups 3, 4, 5 and 6 were administered ART 75, 150, 300 and 600 mg/kg before TAC surgery, respectively; and group 7 was administered verapamil (VER) 1 mg/kg before TAC surgery. A ventricular arrhythmia score (VAS) was calculated to evaluate preventive effects of ART and VER on mechanical VA. The high throughput sequencing-based approach provided DEMs that were altered by ART pretreatment between group 2 and group 4. All predicted mRNAs of DEMs were enriched by gene ontology (GO) and Kyoto Encyclopedia annotation of Genes and Genomes (KEGG) databases. These DEMs were validated by a real time quantitative polymerase chain reaction (RT-qPCR). Results The average VASs of groups 3, 4, 5, 6 and 7 were significantly reduced compared with those of group 2 (2.70 ± 0.48, 1.70 ± 0.95, 2.80 ± 0.79, 2.60 ± 0.97, 1.40 ± 0.52, vs 3.70 ± 0.67, p < 0.01, respectively). The three top GO terms were neuron projection, organ morphogenesis and protein domain specific binding. KEGG enrichment of the 16 DEMs revealed that MAPK, Wnt and Hippo signaling pathways were likely to play a substantial role in the preventive effects of ART on mechanical VA in response to LV afterload increases. All candidate DEMs with the exception of rno-miR-370-3p, rno-miR-6319, rno-miR-21-3p and rno-miR-204-5p showed high expression levels validated by RT-qPCR. Conclusions Artemisinin could prevent mechanical VA in response to LV afterload increases. Validated DEMs could be biomarkers and therapeutic targets of ART regarding its prevention of VA induced by pressure overload. The KEGG pathway and GO annotation analyses of the target mRNAs could indicate the potential functions of candidate DEMs. These results will help to elucidate the functional and regulatory roles of candidate DEMs associated with antiarrhythmic effects of ART

Knockout of the BK β2 subunit abolishes inactivation of BK currents in mouse adrenal chromaffin cells and results in slow-wave burst activity

Rat and mouse adrenal medullary chromaffin cells (CCs) express an inactivating BK current. This inactivation is thought to arise from the assembly of up to four β2 auxiliary subunits (encoded by the kcnmb2 gene) with a tetramer of pore-forming Slo1 α subunits. Although the physiological consequences of inactivation remain unclear, differences in depolarization-evoked firing among CCs have been proposed to arise from the ability of β2 subunits to shift the range of BK channel activation. To investigate the role of BK channels containing β2 subunits, we generated mice in which the gene encoding β2 was deleted (β2 knockout [KO]). Comparison of proteins from wild-type (WT) and β2 KO mice allowed unambiguous demonstration of the presence of β2 subunit in various tissues and its coassembly with the Slo1 α subunit. We compared current properties and cell firing properties of WT and β2 KO CCs in slices and found that β2 KO abolished inactivation, slowed action potential (AP) repolarization, and, during constant current injection, decreased AP firing. These results support the idea that the β2-mediated shift of the BK channel activation range affects repetitive firing and AP properties. Unexpectedly, CCs from β2 KO mice show an increased tendency toward spontaneous burst firing, suggesting that the particular properties of BK channels in the absence of β2 subunits may predispose to burst firing

Air pollution and elite college graduates’ job location choice: evidence from China

In this paper, we examine the impact of air pollution on the job location choice of a highly educated labor force. Using the administrative job contract records of all graduates from Tsinghua University from 2005 to 2016, we find that air pollution significantly reduces the probability of elite graduates accepting job offers in a polluted city. Specifically, all else equal, if a city’s PM2.5 level increases by 10 μg/m3, the share of Tsinghua graduates choosing that city will decrease by 0.23 percentage point (9% of the mean value). This “crowding-out” effect is larger for master’s and doctoral graduates, but insignificant for undergraduates. A placebo test finds this effect does not exist for individuals who had signed a job contract prior to university admission, which strengthens our finding. Heterogeneity analysis indicates that males, students who grew up in cleaner provinces, and students graduating from school of the environment are more sensitive to air pollution. Different levels of preference for clean air and tolerance to pollution, as well as whether having the knowledge of pollution’s harms, can effectively explain the heterogeneous effect of air pollution’s impacts on job location choices of those elites

Effects of Bioactive Packaging Films Incorporated with Bifidocin A on Microbial Reduction and Quality Parameters of Chill-Stored Spanish Mackerel (Scomberomorus niphonius) Fillets

To evaluate the potential of bifidocin A for preservation of fresh Spanish mackerel fillets, the bioactive packaging films incorporated with bifidocin A (1 × minimal inhibition concentration (MIC), 2 × MIC and 4 × MIC) were developed, and their effects on the microbiological and physicochemical properties and sensory profile of mackerel fillets at refrigerated storage were investigated. Results showed that the incorporation of bifidocin A in cellulosic matrix films did not affect the thickness and elongation of the films, but reduced slightly the tension strength. The films incorporated with 2 × MIC and 4 × MIC bifidocin A presented a broad spectrum of activity against most tested bacteria, including some fish-borne specific spoilage bacteria such as Pseudomonas fluorescens, Shewanella putrefaciens, Brochothrix thermosphacta, and Micrococcus luteus, and maintained their 100% activity for 28 days during storage at 4°C. The bioactive packaging films incorporated with bifidocin A could generally suppress the growth of microflora, especially Pseudomonas and Enterobacteriaceae, as well as substantially inhibit the accumulation of total volatile basic nitrogen (TVB-N), thiobarbituric acid reactive substances (TBARS) and hypoxanthine, during chilled mackerel fillets storage. Overall, from a microbiological and physicochemical point of view, a much more effective treatment was achieved with 4 × MIC bifidocin A, extending the shelf life to 12 days and maintaining the relatively low TVB-N value (≤13.2 mg/100 g), TBARS value (≤0.45 mg MDA/kg), and K-value (≤32.8%), as well as a relatively high sensory score (≥7.1) during the whole storage. Hence, the bioactive packaging films incorporated with bifidocin A could be a promising hurdle technology and alternative to conventional processes used for improving the safety and quality of chilled mackerel fillets