Dopamine ß-hydroxylase shapes intestinal inflammation through modulating T cell activation.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic and relapsing disease characterized by immune-mediated dysfunction of intestinal homeostasis. Alteration of the enteric nervous system and the subsequent neuro-immune interaction are thought to contribute to the initiation and progression of IBD. However, the role of dopamine beta-hydroxylase (DBH), an enzyme converting dopamine into norepinephrine, in modulating intestinal inflammation is not well defined. METHODS: CD4+CD45RBhighT cell adoptive transfer, and 2,4-dinitrobenzene sulfonic acid (DNBS) or dextran sodium sulfate (DSS)-induced colitis were collectively conducted to uncover the effects of DBH inhibition by nepicastat, a DBH inhibitor, in mucosal ulceration, disease severity, and T cell function. RESULTS: Inhibition of DBH by nepicastat triggered therapeutic effects on T cell adoptive transfer induced chronic mouse colitis model, which was consistent with the gene expression of DBH in multiple cell populations including T cells. Furthermore, DBH inhibition dramatically ameliorated the disease activity and colon shortening in chemically induced acute and chronic IBD models, as evidenced by morphological and histological examinations. The reshaped systemic inflammatory status was largely associated with decreased pro-inflammatory mediators, such as TNF-α, IL-6 and IFN-γ in plasma and re-balanced Th1, Th17 and Tregs in mesenteric lymph nodes (MLNs) upon colitis progression. Additionally, the conversion from dopamine (DA) to norepinephrine (NE) was inhibited resulting in increase in DA level and decrease in NE level and DA/NE showed immune-modulatory effects on the activation of immune cells. CONCLUSION: Modulation of neurotransmitter levels via inhibition of DBH exerted protective effects on progression of murine colitis by modulating the neuro-immune axis. These findings suggested a promising new therapeutic strategy for attenuating intestinal inflammation.

Brain structural alterations associated with impulsiveness in male violent patients with schizophrenia.

BACKGROUND: Violence in schizophrenia (SCZ) is a phenomenon associated with neurobiological factors. However, the neural mechanisms of violence in patients with SCZ are not yet sufficiently understood. Thus, this study aimed to explore the structural changes associated with the high risk of violence and its association with impulsiveness in patients with SCZ to reveal the possible neurobiological basis. METHOD: The voxel-based morphometry approach and whole-brain analyses were used to measure the alteration of gray matter volume (GMV) for 45 schizophrenia patients with violence (VSC), 45 schizophrenia patients without violence (NSC), and 53 healthy controls (HC). Correlation analyses were used to examine the association of impulsiveness and brain regions associated with violence. RESULTS: The results demonstrated reduced GMV in the right insula within the VSC group compared with the NSC group, and decreased GMV in the right temporal pole and left orbital part of superior frontal gyrus only in the VSC group compared to the HC group. Spearman correlation analyses further revealed a positive correlation between impulsiveness and GMV of the left superior temporal gyrus, bilateral insula and left medial orbital part of the superior frontal gyrus in the VSC group. CONCLUSION: Our findings have provided further evidence for structural alterations in patients with SCZ who had engaged in severe violence, as well as the relationship between the specific brain alterations and impulsiveness. This work provides neural biomarkers and improves our insight into the neural underpinnings of violence in patients with SCZ.

The association of childhood adversities and mental health problems with dual-harm in individuals with serious aggressive behaviors.

BACKGROUND: The coexistence of self-harm and aggression, which is referred to as dual-harm, is commonly seen in forensic population. Self-harm and aggression have often been studied separately, previous studies on risk factors of aggression or self-harm mainly focused on childhood adversities, emotional regulation, impulsivity and psychopathology, given their importance in the two behaviors. However, the factors associated with dual-harm remain unclear. This study aimed to explore potential risk factors associated with co-occurring self-harm among individuals with serious aggressive behaviors. METHODS: This multi-center, cross-sectional case-control study was conducted from May 2013 to January 2016 and involved seven qualified forensic institutes located in seven provinces in China. Participants were individuals with serious aggressive behaviors and were suspected to have mental disorders. Lifetime history of self-harm was obtained by a self-report questionnaire, and serious aggressive behaviors were assessed with the use of participants' forensic archive. Sociodemographic and clinical information were collected using a self-designed standardized data collection form, and childhood adversities was assessed using a clinician-rated scale designed by our research team. The Psychopathy Checklist-Revised (PCL-R) was used to assess psychopathic traits and the Brief Psychiatric Rating Scale (BPRS) was used to assess psychiatric symptoms of the participants. Univariate and multivariate logistic regression analyses were performed to analyze the relevant factors for dual-harm. RESULTS: A total of 423 individuals with serious aggressive behaviors were enrolled in the current study. Of them, 74 (17.5%) with self-harm history assigned into the dual-harm group (D-H) and 349 (82.5%) without self-harm history assigned into the aggression-only group (A-O). According to the binary logistic regression analysis, current diagnosis of mood disorder (OR = 3.2, 95%CI: 1.2-8.5), child abuse (OR = 2.8, 95%CI: 1.3-6.2), parental death (OR = 3.0, 95%CI: 1.2-7.5), and the score of the affective subscale in BPRS (OR = 1.7, 95%CI: 1.3-2.4) were significantly associated with dual-harm. CONCLUSIONS: Our study suggested the necessity of integrated evaluation of self-harm among individuals with serious aggressive behaviors. Childhood adversities and psychiatric symptoms in this population require special attention.

Microplastics can affect soil properties and chemical speciation of metals in yellow-brown soil.

Although the influence of microplastics (MPs) in different soil environments has been investigated, their effects on the physiochemical properties and chemical speciation of heavy metals in yellow-brown soil remains unknown. This study aimed to determine the effects of various concentrations of linear low-density polyethylene (LLDPE), polyamide (PA), polyurethane (PU), polystyrene (PS), and low-density polyethylene (LDPE) MPs on the yellow-brown soil environment and chemical speciation of the heavy metals cadmium (Cd), copper (Cu), lead (Pb), and zinc (Zn). MPs influenced the physicochemical properties and chemical speciation of heavy metals in yellow-brown soil. The physicochemical properties of yellow-brown soil can be altered by changing the concentrations of LDPE MP. The relationship between changes in field capacity (FC) and LDPE concentrations was approximately linear. The physiochemical properties of yellow-brown soil containing added PA, PU, and LDPE MPs were substantially improved (control vs. MPs): FC, 39 % vs. 42.50 % for PU, cation exchange capacity (CEC) 45.77, 56.65, and 57.44 cmol.kg-1 for PA, PU, and LDPE respectively, and organic matter (OM) content, 40.16 vs. 51.68 g.kg-1 for PA. The LLDPE and PU MPs also simultaneously affected the chemical speciation of heavy metals in yellow-brown soil. The LLDPE MPs increased the acid-soluble (45.17-54.67 % (Cd-F1), 7.24-11.30 % (Cu-F1), 4.20-7.23 % (Pb-F1), 21.21-31.47 % (Zn-F1)) and reducible (24.02-29.41 % (Cd-F2), 25.69-34.95 % (Cu-F2), 74.29-81.07 % (Pb-F2), 28.77-34.19 % (Zn-F2)) fractions of heavy metals, which increased their bioavailability. However, PU MPs reduced the ecological risk of heavy metals in yellow-brown soil by increasing the content of the residual fraction (26.11-40.21 % (Cd-F4), 47.63-59.67 % (Cu-F4), 17.25-26.76 % (Pb-F4), 32.63-50.46 % (Zn-F4)). Changes in the properties of yellow-brown soil and the impact of MPs on heavy metals, might change the chemical speciation of heavy metals. The impact of MPs on heavy metals in yellow-brown soil requires further investigation.

Effectiveness of a double-carbapenem combinations against carbapenem-resistant Gram-negative bacteria.

The emergence of carbapenem-resistant organisms posed considerable threat to global health while only limited treatment options are available and led to efforts to discover a novel way to treat them. To evaluate in vitro synergistic activity of meropenem plus ertapenem, a total of 203 carbapenem-resistant strains, collected from 12 provinces and municipalities in China, were examined with a dual carbapenem combination therapy. The statistical software R was used for analysis. Two hundred and one (201) of carbapenem-resistant strains mainly produced four types of carbapenemase: KPC-2 (n = 142, 69.95%), OXA-232 (n = 7, 3.45%), NDM (n = 38, 18.72%; 36 NDM-1, 1 NDM-4, 1 NDM-5), and IMP (n = 15, 7.39%; 1 IMP-26, 10 IMP-30, 4 IMP-4). Fifty-one out of two hundred and three (51/203 or 25.12%) of the examined strains showed a synergistic effect for the meropenem plus ertapenem combination throughout the checkerboard method, while only three isolates showed potential clinically relevant synergy (3/203, 1.48%). An additive effect was observed in 55/203 (27.09%) of the examined strains. Ninety-seven of the examined isolates (47.78%) showed fractional inhibitory concentration (FIC) greater or equal to 2 (indicating antagonism). The synergistic activity of meropenem plus ertapenem combination suggests this combination can be a possible way to treat the infection caused by the carbapenem-resistant organisms, especially for IMP or NDM producer with a lesser minimum inhibitory concentration (MIC) and the infected individual who was not recommended to use colistin or tigecycline.

Uromodulin aggravates renal tubulointerstitial injury through activation of the complement pathway in rats.

Uromodulin (Umod) is the most abundant constituent of urine in humans and exclusively found in the kidney tubular epithelium. However, the specific role of Umod in renal tubulointerstitial injury is yet to be understood. The present study was conducted with aim of investigating the potential therapeutic mechanism of Umod in the regulation of renal tubulointerstitial injury. Protein expression of Umod in renal tubular epithelial cells was measured with the conduction of Western blot analysis. Enzyme-linked immunosorbent assay and immunofluorescence assay were performed to detect the complement activation products and the activation products of surface deposition. The expression of C1q, C2, C4, B factor, C3, C5, H factor, CD46, CD55, C3aR, and C5aR were determined with the use of reverse-transcription quantitative polymerase chain reaction and Western blot analyses. Subsequently, the unilateral ureteral obstruction (UUO) rat model was established. Renal tubulointerstitial injury was assessed with the application of hematoxylin-eosin staining and Masson staining in rats. UUO rats and normal rats were injected with si-NC or si-Umod and complement inhibitor. UUO rats were observed to have serious impairment of kidney tubule, renal tubular dilation, and epithelial atrophy, with downregulated Umod and activated complement pathway. Silencing of Umod resulted in the activation of complement system while promoting interstitial fibrosis in renal tubules. Moreover, addition of complement inhibitor significantly alleviated the renal tubule injury and fibrosis. Collectively, our study suggests that silencing of Umod mediates the complement pathway, exacerbating renal tubulointerstitial injury in rats, which provides insight into the development of novel therapeutic agents for renal tubulointerstitial injury.

Incomplete homicide-suicide in Hunan China from 2010 to 2019: characteristics of surviving perpetrators.

BACKGROUND: The mental and psychological conditions of the individuals involved in homicide followed by suicide (H-S) are still unclear, especially in China. Information on these aspects cannot be accurately obtained due to the death of perpetrators. This study aims to demonstrate the characteristics of incomplete H-S with surviving perpetrators, which provide the possibility to obtain detailed mental and psychological information. METHODS: This study explores incomplete H-S events occurred in Hunan, China from 2010 to 2019, in which the surviving perpetrators received a forensic psychiatric assessment. Three aspects of information, i.e., the subject's demographic, clinical and criminal information, were recorded and analysed. RESULTS: 125 incomplete H-S incidents involved 166 victims were found in the current study. A total of 112 (89.6%) perpetrators were diagnosed with mental disorders, but only 56 of them had a history of consultation due to mental problems, and only one of them adhered to treatment. In most cases, the motivation is related to the psychopathological states, with the most common diagnosis being major depression, followed by schizophrenia. Gender difference was significant among the subjects: females were more likely to have a suicidal history, to be diagnosed as major depression and to be motivated by delirious altruism and family problems. CONCLUSIONS: This study indicated that psychopathology might be a predisposing factor, which highlighted the importance of mental state assessment for the population involved in incomplete H-S. A clearer understanding of the role of mental disorders might be helpful for the intervention of H-S.

Chromosomal and Plasmid-Borne Tigecycline Resistance Genes tet(X3) and tet(X4) in Dairy Cows on a Chinese Farm.

We isolated 47 Acinetobacter strains carrying tet(X3) and 4 ST767 E. coli strains carrying tet(X4) from 296 rectal swab samples from dairy cows on a Chinese farm. tet(X3) was located on chromosomes or diverse plasmids, and tet(X4) was located on IncFIBκ/FIA(HI1)/X1 nontransferable plasmid. The coexistence of tet(X3) and carbapenemase genes, including blaOXA-58 and blaNDM-1, was detected in 9 Acinetobacter spp. These findings suggested that the use of tetracycline and other antibiotics in food production warrants urgent attention.

Emergence of an Empedobacter falsenii strain harbouring a tet(X)-variant-bearing novel plasmid conferring resistance to tigecycline.

OBJECTIVES: To investigate the genomic and phenotypic characteristics of an MDR Empedobacter falsenii strain isolated from a Chinese patient, which was phenotypically resistant to all last-line antibiotics (carbapenems, colistin and tigecycline). METHODS: Species identity was determined by MALDI-TOF MS analysis. The complete genome sequence of the isolate was determined by WGS and the genetic elements conferring antimicrobial resistance were determined. The origin of this strain was tracked by phylogenetic analysis. RESULTS: The E. falsenii strain was genetically most closely related to an Empedobacter sp. strain isolated from the USA. Members of E. falsenii are speculated to be intrinsically resistant to colistin. The carbapenem resistance of this strain was conferred by a chromosomal blaEBR-2 variant gene. Phylogenetic analysis indicated that the gene encoding the EBR ß-lactamase was widely distributed in Empedobacter spp. Tigecycline resistance was mediated by a tet(X) variant gene encoded by a non-conjugative and non-typeable plasmid. CONCLUSIONS: The MDR phenotype of the E. falsenii isolate was conferred by different mechanisms. Findings from us and others indicate that E. falsenii may serve as a reservoir for carbapenem and tigecycline resistance determinants.

Prevalence and molecular epidemiology of mcr-1-positive Klebsiella pneumoniae in healthy adults from China.

OBJECTIVES: To investigate the nationwide prevalence of mcr-1-positive Klebsiella pneumoniae (MCRPKP) strains among healthy adults in China and identify their phenotypic and genomic characterizations. METHODS: A total of 7401 rectal swab samples were collected from healthy individuals in 30 hospitals located in 30 provinces and municipalities of mainland China in 2016. Colistin-resistant bacteria were enriched in colistin-supplemented lysogeny broth. MCRPKP strains were isolated and characterized with MALDI-TOF MS, PCR analysis and antimicrobial susceptibility testing. The genomic characteristics of MCRPKP strains were determined by WGS and bioinformatics analysis. RESULTS: Seven MCRPKP strains and one mcr-1-positive Klebsiella variicola strain were selectively isolated from six locales (three from Henan and one from each of Tianjin, Jiangxi, Yunnan, Gansu and Tibet). Antimicrobial susceptibility testing results indicated that all mcr-1-positive strains were susceptible to meropenem, aztreonam and ceftazidime/avibactam. WGS analysis suggested these strains belonged to seven distinct STs: ST15, ST1425, ST1462, ST273, ST307, ST391 and ST37-SLV. mcr-1 genes were carried by diverse plasmids, including IncHI2 (n = 3), IncX4 (n = 2), IncHI2/IncN (n = 1), IncFIB (n = 1) and one other plasmid type. Two ST15 strains harboured both mcr-1 and mcr-8 genes, which has not been reported before. CONCLUSIONS: Our data indicated a low prevalence of mcr-1-positive Klebsiella strains (0.11%, 8/7401) in healthy individuals in mainland China and most of these strains remained susceptible to clinically important antibiotics. The prevalence and coexistence of mcr-1 and mcr-8 in K. pneumoniae may further threaten public health through either the food chain or environmental routes.

Evolution of Carbapenem-Resistant Serotype K1 Hypervirulent Klebsiella pneumoniae by Acquisition of blaVIM-1-Bearing Plasmid.

We report the identification of a carbapenem-resistant, hypervirulent Klebsiella pneumoniae (hvKp) strain which produced the carbapenemase VIM-1. Genomic analysis showed that the strain belonged to sequence type ST23 and serotype K1, a major hvKp clone, and harbored three resistance-encoding plasmids. Among them, a blaVIM-1-bearing plasmid was found to possess a mosaic structure presumably generated by multiple gene mobilization events. This finding indicates that hvKp actively acquires mobile resistance-encoding elements, facilitating simultaneous expression of hypervirulence and carbapenem-resistance.

Application of CRISPR/Cas9-Based Genome Editing in Studying the Mechanism of Pandrug Resistance in Klebsiella pneumoniae.

In this study, a CRISPR/Cas9-mediated genome editing method was used to study the functions of the mgrB, tetA, and ramR genes in mediating colistin and tigecycline resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP). Inactivation of the tetA or ramR gene or the mgrB gene by CRISPR/Cas9 affected bacterial susceptibility to tigecycline or colistin, respectively. This study proved that the CRISPR/Cas9-based genome editing method could be effectively applied to K. pneumoniae and should be further utilized for genetic characterization.

Emergence of OXA-232 Carbapenemase-Producing Klebsiella pneumoniae That Carries a pLVPK-Like Virulence Plasmid among Elderly Patients in China.

This study reported the clonal dissemination of OXA-232-producing sequence type 15 (ST15) carbapenem-resistant Klebsiella pneumoniae among elderly patients in China. All patients were immunocompromised, suffered from multiple underlying diseases, and were hospitalized for a prolonged period; however, they slowly recovered on antimicrobial therapy. The blaOXA-232 gene was in a 6.1-kb ColKP3-type nonconjugative plasmid. The strains displayed a multidrug resistance phenotype and were not hypervirulent despite harboring a virulence plasmid. Active surveillance should be enforced to control further transmission.

Prevalence and Genetic Analysis of mcr-3-Positive Aeromonas Species from Humans, Retail Meat, and Environmental Water Samples.

The mobile colistin resistance gene mcr-3 is globally disseminated in both Enterobacteriaceae and Aeromonas species, with the latter potentially serving as a reservoir for this gene. Here, we investigated the prevalence of mcr-3 in rectal swabs from humans, in food-producing animals and their products, and in the aquatic environment, and we investigated the genetic relationships between the mcr-3-positive isolates. An enriched broth screening method was used to detect mcr-3 in samples, and species identification of isolates from positive samples was carried out by matrix-assisted laser desorption ionization-time of flight mass spectrometry and shotgun sequencing. All mcr-3-positive isolates were subjected to antimicrobial susceptibility testing, conjugation, and whole-genome sequencing. Ten Aeromonas isolates, including 2 from human rectal swabs, 1 from pork, 3 from chicken meat, and 4 from the aquatic environment, were positive for mcr-3, but only 2 showed resistance to colistin. In addition to the mcr-3 variants identified previously (the novel variants were termed mcr-3.13 to mcr-3.18), all isolates harbored mcr-3-like genes downstream of the mcr-3 variants. The MCR-3.13 to MCR-3.18 proteins exhibited only 89.2% to 96.1% amino acid identity to the original MCR-3 protein. Whole-genome sequence analysis indicated diversity within the genetic environments of mcr-3-positive Aeromonas isolates and possible transmission between different sources in China and even worldwide. Close relationships between mcr-3-positive and mcr-3-negative Aeromonas isolates suggested that mcr-3 might be common in Aeromonas species, which are not inherent hosts of mcr-3 but may act as an important reservoir of this mobile colistin resistance gene.

Rapid Increase in Prevalence of Carbapenem-Resistant Enterobacteriaceae (CRE) and Emergence of Colistin Resistance Gene mcr-1 in CRE in a Hospital in Henan, China.

The global spread of carbapenem-resistant Enterobacteriaceae (CRE) is one of the most severe threats to human health in a clinical setting. The recent emergence of plasmid-mediated colistin resistance gene mcr-1 among CRE strains greatly compromises the use of colistin as a last resort for the treatment of infections caused by CRE. This study aimed to understand the current epidemiological trends and characteristics of CRE from a large hospital in Henan, the most populous province in China. From 2014 to 2016, a total of 7,249 Enterobacteriaceae isolates were collected from clinical samples, among which 18.1% (1,311/7,249) were carbapenem resistant. Carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Escherichia coli were the two most common CRE species, with Klebsiella pneumoniae carbapenemases (KPC) and New Delhi metallo-ß-lactamases (NDM), respectively, responsible for the carbapenem resistance of the two species. Notably, >57.0% (n = 589) of the K. pneumoniae isolates from the intensive care unit were carbapenem resistant. Furthermore, blaNDM-5 and mcr-1 were found to coexist in one E. coli isolate, which exhibited resistance to almost all tested antibiotics. Overall, we observed a significant increase in the prevalence of CRE isolates during the study period and suggest that carbapenems may no longer be considered to be an effective treatment for infections caused by K. pneumoniae in the studied hospital.

[Factors influencing the quality of life of 104 children with phenylketonuria in Anhui Province, China].

OBJECTIVE: To investigate the factors influencing the quality of life (QOL) of children with phenylketonuria (PKU) in Anhui Province, China. METHODS: A total of 104 PKU children who were diagnosed and treated in three major maternal and child health hospitals in Anhui Province were enrolled as study subjects. The PedsQL™ 4.0 Generic Core Scales were used to evaluate the quality of life of these children. The multivariate logistic regression analysis was used to evaluate the factors influencing the QOL. RESULTS: The 104 PKU children had significantly lower overall QOL score and scores on the subscales of physiological functioning, emotional functioning, and social functioning than the general school-age children (P<0.01). They also had a significantly lower score on the physiological domain consisting of emotional functioning, social functioning, and role functioning than the general school-age children (P<0.01). The multivariate logistic regression analysis showed that an older age (≥4 years) of PKU children was the risk factor for poor QOL (OR=8.569, P<0.01), and guardians' engagement at enterprises or institutions was the protective factor for QOL (OR=0.206, P<0.05). CONCLUSIONS: PKU children have a low level of QOL, and age and guardians' occupation are factors influencing the QOL.

Effect of lanthanum carbonate versus calcium-based phosphate binders in dialysis patients: a meta-analysis.

BACKGROUND: The effects of lanthanum carbonate (LC) vs. calciumbased phosphate binders in dialysis patients have been a matter of debate. METHODS: We electronically searched PubMed, Embase, CENTRAL, and CBM for all randomized controlled trials comparing LC with calcium-based phosphate binders in adult dialysis patients. Quality assessment was performed using the Cochrane risk of bias tool. Metaanalysis was conducted by RevMan 5.2. RESULTS: Nine studies were eligible for our meta-analysis. There was no significant difference in all-cause mortality (RR 0.84, 95% CI 0.25 - 2.83) and cardiovascular events (RR 0.84, 95% CI 0.55 - 1.29) between LC and calcium-based phosphate binders. LC was associated with similar proportions of phosphate-controlled patients (RR 0.63, 95% CI 0.27 - 1.44) and lower incidence of hypercalcemia (RR 0.13, 95% CI 0.05 - 0.35) in comparison to calcium-based phosphate binders. Compared with calcium salts, LC was associated with significantly lower serum calcium, similar serum Ca x P product and higher serum iPTH. CONCLUSION: Despite the trends observed, we found no statistically significant differences in all-cause mortality and cardiovascular events between LC and calcium-based phosphate binders in dialysis patients. The conclusion was limited by lack of large sample and long-term trials. LC could reduce the incidence of hypercalcemia while comparable with calcium-based phosphate binders in reducing serum phosphorus level.

Phenotypic and genomic characteristics of clinical IMP-producing Klebsiella spp. Isolates in China.

BACKGROUND: IMP-producing Klebsiella spp. (IMPKsp) strains have spread globally, including in China. Currently, the prevalence and genomic characterization of IMPKsp is largely unknown nationwide. Here we aimed to provide a general overview of the phenotypic and genomic characteristics of IMPKsp strains. METHODS: 61 IMPKsp strains were obtained from 13 provinces in China during 2016-2021. All strains were tested for their susceptibility to antimicrobial agents by the microdilution broth method and sequenced with Illumina next-generation sequencing. We performed conjugation experiments on thirteen representative strains which were also sequenced by Oxford nanopore sequencing technology to characterize blaIMP-encoding plasmids. RESULTS: We find that all IMPKsp strains display multidrug-resistant (MDR) phenotypes. All strains belong to 27 different STs. ST307 emerges as a principal IMP-producing sublineage. blaIMP-4 is found to be the major isoform, followed by blaIMP-38. Seven incompatibility types of blaIMP-encoding plasmids are identified, including IncHI5 (32/61, 52.5%), IncN-IncR (10/61, 16.4%), IncFIB(K)-HI1B (7/61, 11.5%), IncN (5/61, 8.2%), IncN-IncFII (2/61, 3.3%), IncFII (1/61, 1.6%) and IncP (1/61, 1.6%). The strains carrying IncHI5 and IncN plasmids belong to diverse ST types, indicating that these two plasmids may play an important role in the transmission of blaIMP genes among Klebsiella spp. strains. CONCLUSIONS: Our results highlight that multi-clonal transmission, multiple genetic environments and plasmid types play a major role in the dissemination process of blaIMP genes among Klebsiella spp. IncHI5 type plasmids have the potential to be the main vectors mediating the spread of the blaIMP genes in Klebsiella spp.

Antibiotic resistance occurs when bacteria evolve to withstand antibiotic drugs. We are aware that a bacteria called Klebsiella is rapidly becoming resistant to carbapenems, a class of broad-spectrum antibiotics. In this study, we conducted a genetic and microbiological surveillance study across 13 provinces of China to understand factors that contribute to the growing bacterial drug resistance. We find that the way the multiple bacterial types interact with each other and swap certain genetic material may be the main cause of growing resistance. These findings call for close monitoring of genetic evolution as a matter of public health management strategy.

Trends in violent offending among people with schizophrenia: A 10-year ecological study.

Violent offending committed by people with schizophrenia has been a public concern. The present study aims to examine the incidence of violent offending among people with schizophrenia and its correlations with mental health resources and economic factors. In this study, an examination of violent offending by people with schizophrenia and those identified as not criminally responsible on account of mental disorder (NCRMD) between 2010 and 2019 in China's Hunan province was undertaken. Principal component analysis (PCA) and regression analyses were used to explore the association of violent offending in people with schizophrenia and those identified as NCRMD with violent offending in the general population, mental health medical resources, and provincial GDP. Between 2010 and 2019, a total of 2,093 people with schizophrenia committed violent offending in Hunan province, including 1,374 (65.6%) cases identified as NCRMD. Over the period, the incidence of violent offending in people with schizophrenia and those identified as NCRMD has been decreasing. The incidences were positively correlated with the incidence of violent offending in the general population and negatively associated with mental health resources and provincial GDP. These findings may be valuable in helping to develop strategies for violence prevention and risk management for people with schizophrenia.

Effect of Waiting Time for Radioactive Iodine Therapy on Outcome in N1 Stage Papillary Thyroid Cancer.

CONTEXT: The waiting time for radioactive iodine therapy (WRAIT) after total thyroidectomy (TT) in patients with papillary thyroid cancer (PTC) and lymph node metastases (N1) has not been sufficiently investigated for risk of adverse outcomes. OBJECTIVE: This work aimed to estimate the effect of WRAIT on the outcomes of disease persistence and recurrence among patients with N1 PTC and investigate factors predictive of delayed radioactive iodine therapy (RAIT). METHODS: This retrospective cohort study was conducted in a university hospital. A total of 909 patients with N1 PTC were referred for RAIT between 2014 and 2018. WRAIT is the duration between TT and initial RAIT. The optimal WRAIT threshold determined using recursive partitioning analysis was used to define early and delayed RAIT. The primary end point was tumor persistence/recurrence. We compared the outcomes of patients with early and delayed RAIT using inverse probability weighting based on the propensity score. RESULTS: The WRAIT threshold that optimally differentiated worse long-term remission/excellent response outcomes was greater than 88 days (51% of our cohort; n = 464). WRAIT exceeding 88 days was associated with an augmented risk of disease persistence/recurrence (odds ratio, 2.47; 95% CI, 1.60-3.82) after adjustment. Predictors of delayed RAIT included residence in lower-income areas, reoperation before the initial RAIT, TT at a nonuniversity-affiliated hospital, multifocality, extrathyroidal extension, N1b disease, and pre-RAIT-stimulated thyroglobulin level less than 1 ng/mL. CONCLUSION: Delayed RAIT beyond 88 days after TT in patients with N1 PTC independently increased the risk of disease persistence/recurrence. Evaluation of the predictive determinants of prolonged WRAIT may help target at-risk patients and facilitate interventions.