The rise of antibiotic resistance in Campylobacter.

PURPOSE OF REVIEW: Campylobacter is a major foodborne pathogen that infects the human intestinal tract. This review discusses the current status of antibiotic resistance, transmission of antibiotic resistance genes, and strategies to combat the global Campylobacter epidemic. RECENT FINDINGS: Over the past 18 months, articles on Campylobacter antibiotic resistance have been published in ∼39 countries. Antibiotic-resistant Campylobacter have been detected in humans, livestock, poultry, wild animals, the environment, and food. Campylobacter spp. are resistant to a wide spectrum of antimicrobial agents, including the antibiotics quinolones, macrolides, tetracyclines, aminoglycosides, and chloramphenicols. Multidrug resistance is a globally emerging problem. Continuous antibiotic pressure promotes the spread of drug-resistant Campylobacter spp. Additionally, Campylobacter is well adapted to acquiring foreign drug resistance genes, including ermB, optrA, fexA, and cfrC, which are usually acquired from gram-positive bacteria. SUMMARY: The widespread use of antibiotics has caused a global epidemic of drug-resistant Campylobacter infections. Many countries are actively reducing the use of antibiotics and adopting alternatives in the livestock and poultry industries to control the spread of drug-resistant Campylobacter spp.

Telithromycin resistance in Campylobacter mediated by 23S rRNA A2075G mutation and erm(B).

OBJECTIVES: Recently, epidemiological research has shown an unusually high prevalence of telithromycin-resistant Campylobacter. This study was designed to investigate the potential resistance mechanism of telithromycin resistance in Campylobacter. METHODS: A total of 122 Campylobacter isolates of chicken origin collected in 2019 from three regions of China were tested for susceptibility to telithromycin. The potential mechanism of resistance to telithromycin in Campylobacter was revealed through WGS analysis and natural transformation. RESULTS: In this study, 51.3% (61/119) of Campylobacter coli and 100.0% (3/3) of Campylobacter jejuni were resistant to telithromycin. erm(B) or A2075G mutation in 23S rRNA (23S_A2075G) was identified in the telithromycin-resistant C. coli. Cloning of the erm(B) or 23S_A2075G into C. jejuni NCTC 11168 resulted in a 256-fold increase in the MIC of telithromycin. MLST results indicated that various STs were involved in the dissemination of 23S_A2075G and erm(B). Phylogenetic analysis showed that the C. coli isolates with 23S_A2075G and erm(B) from chickens and humans were closely related. CONCLUSIONS: 23S_A2075G and erm(B), which have been widely spread in different genotypes of C. coli isolated from animals and humans, could mediate high levels of resistance to telithromycin in C. coli. C. coli containing 23S_A2075G or erm(B) are clonally related and have the potential to spread zoonotic diseases.

Conformationally selective RNA aptamers allosterically modulate the ß2-adrenoceptor.

G-protein-coupled receptor (GPCR) ligands function by stabilizing multiple, functionally distinct receptor conformations. This property underlies the ability of 'biased agonists' to activate specific subsets of a given receptor's signaling profile. However, stabilizing distinct active GPCR conformations to enable structural characterization of mechanisms underlying GPCR activation remains difficult. These challenges have accentuated the need for receptor tools that allosterically stabilize and regulate receptor function through unique, previously unappreciated mechanisms. Here, using a highly diverse RNA library combined with advanced selection strategies involving state-of-the-art next-generation sequencing and bioinformatics analyses, we identify RNA aptamers that bind a prototypical GPCR, the ß2-adrenoceptor (ß2AR). Using biochemical, pharmacological, and biophysical approaches, we demonstrate that these aptamers bind with nanomolar affinity at defined surfaces of the receptor, allosterically stabilizing active, inactive, and ligand-specific receptor conformations. The discovery of RNA aptamers as allosteric GPCR modulators significantly expands the diversity of ligands available to study the structural and functional regulation of GPCRs.

Personality traits and suicide attempts with and without psychiatric disorders: analysis of impulsivity and neuroticism.

BACKGROUND: There is a critical need for empirical data concerning the association of personality traits and attempted suicide with and without psychiatric disorders in mainland China. The objective of the present study is to provide such data by determining the prevalence of psychiatric disorders and analyzing the levels of impulsivity and neuroticism among people who have attempted suicide, and to examine the association between these personality traits and suicide attempt in people with or without psychiatric disorders. METHODS: We administered self-reported tests and clinical interviews to 196 people who have attempted suicide who were admitted to a hospital emergency room or our psychiatric settings after a suicide attempt. RESULTS: One hundred and fifty-six subjects (79.6%) met the criteria for Axis I disorders and eleven (6.6%) met the criteria Axis II personality disorders. Those who have attempted suicide who did not have psychiatric disorders exhibited a greater degree of background characteristics (e.g., high lethality, more interpersonal conflicts and more alcohol use), lower levels of suicidality (suicide risk, depressive symptoms) and differences of personality traits (e.g., more impulsive and less neuroticism) as compared to those who do have psychiatric disorders. Profile differences existed even after control for the stressful life event. CONCLUSION: Our findings suggest that some personality traits differ between people who have attempted suicide depending on whether or not they have psychiatric disorders. Based on these findings, investigating the impact of personality traits on suicidal behavior in therapeutic settings would provide critical data to improve patient treatment and outcomes.

Comparison of the characteristics of suicide attempters with major depressive disorder and those with no psychiatric diagnosis in emergency departments of general hospitals in China.

BACKGROUND: Major depressive disorder (MDD) is a known major risk factor for suicide due to the high suicide mortality. However, studies comparing the characteristics of suicide attempters with major depressive disorder and those with no psychiatric diagnosis in China are very limited. This study examined and compared the sociodemographic and psychological characteristics of suicide attempters with MDD and those with no psychiatric diagnosis in emergency departments of general hospitals to better understand the risk factors for suicide attempts in China. METHODS: All subjects were enrolled in the study between June 2007 and January 2008. A total of 127 suicide attempters-54 with MDD and 73 with no psychiatric diagnosis-were enrolled. The sociodemographic and clinical characteristics were compared between two groups using the statistical analysis performed using frequency distribution, Student's t test, Chi-square test, and Fisher's exact test and a logistic regression model. RESULTS: Suicide attempters with MDD were more likely to be more depressive, older, divorced or separated, unemployed, and living alone, and more likely to write a suicide note, have suicide ideation, and be motivated by reducing pain and burden. Suicide attempters with no psychiatric diagnosis were more likely to be younger and more impulsive, have self-rescue, and be motivated by threatening or taking revenge on others. Multivariate logistic regression analysis identified the following independent predictors of suicide attempts in individuals with MDD: a lower score on the quality of life scale, more years of education, and suicide ideation. CONCLUSIONS: The present study found both similarities and differences in the sociodemographic and clinical characteristics of suicide attempters with MDD and those with no psychiatric diagnosis in the emergency departments of general hospitals in China. These findings will help us to recognize the characteristics of suicide attempters in both groups and develop specific interventions for the two types of suicide attempters to prevent future suicide in China. For example, the suicide attempters with MDD in the emergency departments must be advised to the psychological clinic.

Musculoskeletal Ultrasound: A Novel Approach for Luschka's Joint and Vertebral Artery.

BACKGROUND: Cervical vertigo has been a controversial diagnosis for several years, and the lack of a diagnostic test is a critical problem. Musculoskeletal ultrasound (MSUS) is a real-time dynamic approach that is used to investigate the musculoskeletal and vascular systems. MATERIAL/METHODS: In this study, MSUS was used to examine whether there is a relationship among vertigo, the vertebral artery (VA), and Luschka's joint proliferation in patients with cervical vertigo. RESULTS: MSUS clearly revealed the size, shape, and characteristics of the Luschka's joint, the VA, and the surrounding structures. The Luschka's joint proliferation was not distributed uniformly, but the predilection sites were C4/5 (50.5%) and C5/6 (32.3%). The proliferation from C4/5 and C5/6 Luschka's joints was the major cause of the grade 2/3 VA tortuosity. Moreover, there was a significant correlation between VA compression from Luschka's joint proliferation and the symptoms of cervical vertigo. CONCLUSIONS: MSUS is a real-time and noninvasive technique that can be used to locate and observe Luschka's joint and the VA during research and clinical applications. In future practice MSUS could be used as a diagnostic approach for patients with suspected cervical vertigo.

Global identification of MLL2-targeted loci reveals MLL2's role in diverse signaling pathways.

Myeloid/lymphoid or mixed-lineage leukemia (MLL)-family genes encode histone lysine methyltransferases that play important roles in epigenetic regulation of gene transcription. MLL genes are frequently mutated in human cancers. Unlike MLL1, MLL2 (also known as ALR/MLL4) and its homolog MLL3 are not well-understood. Specifically, little is known regarding the extent of global MLL2 involvement in the regulation of gene expression and the mechanism underlying its alterations in driving tumorigenesis. Here we profile the global loci targeted by MLL2. A combinatorial analysis of the MLL2 binding profile and gene expression in MLL2 wild-type versus MLL2-null isogenic cell lines identified direct transcriptional target genes and revealed the connection of MLL2 to multiple cellular signaling pathways, including the p53 pathway, cAMP-mediated signaling, and cholestasis signaling. In particular, we demonstrate that MLL2 participates in retinoic acid receptor signaling by promoting retinoic acid-responsive gene transcription. Our results present a genome-wide integrative analysis of the MLL2 target loci and suggest potential mechanisms underlying tumorigenesis driven by MLL2 alterations.

Reading frame correction by targeted genome editing restores dystrophin expression in cells from Duchenne muscular dystrophy patients.

Genome editing with engineered nucleases has recently emerged as an approach to correct genetic mutations by enhancing homologous recombination with a DNA repair template. However, many genetic diseases, such as Duchenne muscular dystrophy (DMD), can be treated simply by correcting a disrupted reading frame. We show that genome editing with transcription activator-like effector nucleases (TALENs), without a repair template, can efficiently correct the reading frame and restore the expression of a functional dystrophin protein that is mutated in DMD. TALENs were engineered to mediate highly efficient gene editing at exon 51 of the dystrophin gene. This led to restoration of dystrophin protein expression in cells from Duchenne patients, including skeletal myoblasts and dermal fibroblasts that were reprogrammed to the myogenic lineage by MyoD. Finally, exome sequencing of cells with targeted modifications of the dystrophin locus showed no TALEN-mediated off-target changes to the protein-coding regions of the genome, as predicted by in silico target site analysis. This strategy integrates the rapid and robust assembly of active TALENs with an efficient gene-editing method for the correction of genetic diseases caused by mutations in non-essential coding regions that cause frameshifts or premature stop codons.

Screening for colorectal cancer: Study on the shedding cells of feces.

Objective: The objective of this study was to explore the enrichment efficiency of an improved fecal exfoliated cell enrichment method and its application in colorectal cancer screening. Material and Methods: Samples were collected from a cohort of 100 colorectal cancer patients being treated at the First Hospital of Hebei Medical University from January 2021 to June 2022. Patient samples were equally divided between control and experimental groups corresponding to the enrichment method being applied to the fecal exfoliated cells. Samples consisted of natural stool and bowel cleansing enema solution samples. The control group received the traditional three-layer integrated screen method, and the experimental group used nano-Fe3O4 folic acid magnetic beads to enrich the fecal exfoliated cells. The morphology of the extracted cells was observed by light microscopy through hematoxylin and eosin staining, and the positive rate of fecal occult blood test (FOBT) and the detection rate of colorectal cancer was compared between the two groups. Results: The FOBT-positive rates of natural feces and intestinal cleansing liquid in the control group were 74.00% and 90.00%, respectively, and the FOBT-positive rates of natural feces and intestinal cleansing liquid in the experimental group were 76.00% and 92.00%, respectively. The positive FOBT rate was high, and the difference was statistically significant (P = 0.037 and P = 0.029). The sensitivities of natural fecal exfoliation cytology in the control and experimental groups were 82.00% and 92.00%, respectively. The sensitivity of the experimental group was higher than that of the control group, and the difference was not statistically significant (P = 0.137). The sensitivities of the exfoliated cytology examination of the intestinal cleansing liquid in the control and experimental groups were 88.00% and 98.00%, respectively. The sensitivity of the experimental group was significantly higher than that of the control group, and the difference was statistically significant (P = 0.050). Cell smear results show that the exfoliated cells collected by the three-layer integrated sieve method are unevenly distributed, with overlapping cells and a large number of impurities blurring the background, seriously affecting the observation of cell morphology. The cell structure is blurred, stained unevenly, and arranged in a disorderly manner. The exfoliated cells collected by the nanofolic acid magnetic bead enrichment method are relatively evenly distributed, with no overlapping of cells in patches. The background is clear, and the morphology of each cell can be clearly observed. The cell structure is relatively clear, stained evenly, and distributed evenly. Conclusion: In the cytological examination of fecal exfoliation of colorectal cancer, the nano-Fe3O4 folic acid magnetic bead enrichment method can enrich more target cells compared with the traditional three-layer integrated screen method, improve the detection rate of colorectal cancer, and ensure the exfoliation The cell smears are of higher quality, providing a better sample for clinical assessment of the exfoliated cells. Nano-Fe3O4 folic acid magnetic beads enrichment method can become a simple, efficient, and relatively safe screening method for colorectal cancer, positively affecting early screening developments and diagnosis of colorectal cancer.

Distribution and Transmission of Colistin Resistance Genes mcr-1 and mcr-3 among Nontyphoidal Salmonella Isolates in China from 2011 to 2020.

Mobile colistin resistance (mcr) genes are present mainly in plasmids and can disseminate clonally or horizontally via either plasmids or insertion sequences in different genomic locations among the Enterobacteriaceae. A nationwide large-scale study on mcr prevalence and transmission in nontyphoidal Salmonella isolates is still lacking. Here, we identified 140 mcr-positive Salmonella isolates out of 7,106 isolates from 29 provinces in China from 2011 to 2020. We aligned short reads to putative plasmids from long-read hybrid assemblies and predicted the plasmid backbones of non-long-read sequencing isolates to elucidate mcr transmission patterns. The mcr-1 and mcr-3 genes are transmitted on similar high-risk clones (sequence type 34 [ST34]) but through plasmids of various replicon types. Furthermore, the ban on colistin use in food animals can lead to a decrease in the mcr-positive Salmonella prevalence among diarrheal patients, related mainly to IncHI2A_IncHI2 plasmids. We provide a framework for plasmid data incorporation into genomic surveillance systems, contributing to a better understanding of mcr spread and transmission. IMPORTANCE Nontyphoidal Salmonella is one of four major causative agents of diarrheal diseases globally, with most cases of salmonellosis being mild. Antimicrobial treatments are required for cases of life-threatening infections, and colistin is one of the last-line antibiotics for the treatment of multidrug-resistant Salmonella infections. However, the efficacy of colistin has been compromised by the emergence of various mcr genes. To elucidate the transmission of mcr genes in Salmonella isolates, our study analyzed 7,106 Salmonella strains from 29 provinces in China from 2011 to 2020. The results showed that mcr genes are transmitted on similar high-risk clones (ST34) but through plasmids of various replicon types. In addition, our data illustrated that the ban on the use of colistin in food animals led to a significant decrease in mcr-positive isolates. Our findings offer an essential step toward a more comprehensive understanding of the spread and transmission of mcr genes.

Genomic Insights into the Increased Occurrence of Campylobacteriosis Caused by Antimicrobial-Resistant Campylobacter coli.

Campylobacter is the leading bacterial cause of diarrheal illnesses worldwide. Campylobacter jejuni and C. coli are the most common species accounting for campylobacteriosis. Although the proportion of campylobacteriosis caused by C. coli is increasing rapidly in China, the underlying mechanisms of this emergence remain unclear. In this study, we analyzed the whole-genome sequences and associated environments of 1,195 C. coli isolates with human, poultry, or porcine origins from 1980 to 2021. C. coli isolates of human origin were closely related to those from poultry, suggesting that poultry was the main source of C. coli infection in humans. Analysis of antimicrobial resistance determinants indicated that the prevalence of multidrug-resistant C. coli has increased dramatically since the 2010s, coinciding with the shift in abundance from C. jejuni to C. coli in Chinese poultry. Compared with C. jejuni, drug-resistant C. coli strains were better adapted and showed increased proliferation in the poultry production environment, where multiple antimicrobial agents were frequently used. This study provides an empirical basis for the molecular mechanisms that have enabled C. coli to become the dominant Campylobacter species in poultry; we also emphasize the importance of poultry products as sources of campylobacteriosis caused by C. coli in human patients. IMPORTANCE The proportion of campylobacteriosis caused by C. coli is increasing rapidly in China. Coincidentally, the dominant species of Campylobacter occurring in poultry products has shifted from C. jejuni to C. coli. Here, we analyzed the whole-genome sequences of 1,195 C. coli isolates from different origins. The phylogenetic relationship among C. coli isolates suggests that poultry was the main source of C. coli infection in humans. Further analysis indicated that antimicrobial resistance in C. coli strains has increased dramatically since the 2010s, which could facilitate their adaptation in the poultry production environment, where multiple antimicrobial agents are frequently used. Thus, our findings suggest that the judicious use of antimicrobial agents could mitigate the emergence of multidrug-resistant C. coli strains and enhance clinical outcomes by restoring drug sensitivity in Campylobacter.

Coexistence of optrA and fexA in Campylobacter.

Previous studies indicated that Campylobacter has developed several mechanisms that confer resistance to florfenicol, which is used in food animal production. This study describes the coexistence of optrA and fexA in Campylobacter jejuni and Campylobacter coli isolates from pigs and poultry. Moreover, whole-genome sequencing data showed that the two genes are located in various multidrug resistance genomic islands within different regions of the Campylobacter genomes. The emergence of optrA and fexA may support the spread of florfenicol-resistant Campylobacter strains of animal origin.IMPORTANCE Florfenicol is widely used for the treatment of respiratory infections and as a feed additive in food animal production. As a foodborne pathogen, Campylobacter is constantly exposed to florfenicol, and resistance to this antimicrobial agent has increased in recent years. Previous studies indicated that Campylobacter has developed several mechanisms that confer resistance to florfenicol. This study describes for the first time the coexistence of the florfenicol exporter FexA and the ribosomal protective protein OptrA in Campylobacter jejuni isolated from pigs. The two genes were located in various multidrug resistance genomic islands within different regions of the Campylobacter genomes. Although phenicols are not commonly used for the treatment of Campylobacter infections, the extensive use of florfenicol in food animals may play a role in the coselection of multidrug resistance genomic island (MDRGI)-carrying Campylobacter isolates which also exhibited resistance to critically important antimicrobial agents (macrolides, aminoglycosides, and tetracyclines) commonly used for the treatment of human campylobacteriosis.

[Analysis of features for suicide attempters at emergency departments in general hospitals].

OBJECTIVE: To investigate the prevalence of various mental disorders of suicide attempters and analyze the clinical features of suicide attempters with mental disorders. METHODS: The investigators randomly selected four Class III general hospitals from different parts of Shenyang and collected 239 suicide attempters over 15 years old at emergency room. When the conditions of suicide attempters improved after rescue, the investigators studied by suicide general table, self-injury questionnaire, Hamilton Depression Rating Scale for Depression-24 and Structure Clinical Interview for DSM-IV Axis I Disorders-Patient Edition. RESULTS: The overall prevalence of mental disorders in attempted suicides was 69.46% while self-injury, one of the highest prevalent mood disorders, accounted for 48.12%. During the year before suicide, only 7.23% of the suicide attempters with mental disorders consulted a psychologist or psychiatrist, and took anti-psychosis drugs, anti-depression or anti-anxiety drugs. Suicide attempters with mental disorders often committed suicide less impulsively. And their purpose was to relieve themselves and reduce the burden of others so that the rate of self-help was lower after their injuries occurred; suicide attempters with mental disorders had more obvious symptoms. And their degrees of depression were greater (P < 0.05) than ones without mental disorders. CONCLUSION: The prevalence of mental disorders at emergency rooms in general hospitals is high in suicide attempts, but the pre-suicide consulting rate remains so low. The depressive components of mental disorders are most directly related to suicidal behaviors of suicide attempters.

MLKL deficiency inhibits DSS-induced colitis independent of intestinal microbiota.

The maintenance of intestinal tissue homeostasis is vital for the resistance against inflammatory bowel diseases (IBDs). Necroptosis is identified as an alternative mode of regulated cell death, which plays a pivotal role in tissue homeostasis. Thus, the roles of RIP3-mediated necroptosis in intestinal inflammation have been extensively studied. However, the biological implications of the mixed lineage kinase-like protein (MLKL), a molecule downstream of RIP3 in gut remain unclear. In this study, the role of MLKL in DSS-induced colitis was examined, and the contribution of gut microbiota was also determined. Compared with non-littermate WT mice, the survival rate, clinical score, intestinal damage and intestinal mucosal barrier integrity of non-littermate MLKL-deficient mice are significantly improved. MLKL deficiency prevents inflammatory cytokines production and MAPK signaling activation. Hence, MLKL deficiency inhibits DSS-induced colitis. Moreover, we proved that DSS susceptibility difference between two genotypes is not driven by intestinal microbiota based on the co-housing of two non-littermate genotypes and qPCR detection of fecal dominant bacterial taxa.

Salmonella Outer Protein B Suppresses Colitis Development via Protecting Cell From Necroptosis.

Salmonella effectors translocated into epithelial cells contribute to the pathogenesis of infection. They mediate epithelial cell invasion and subsequent intracellular replication. However, their functions in vivo have not been well-identified. In this study, we uncovered a role for Salmonella outer protein B (SopB) in modulating necroptosis to facilitate bacteria escape epithelial cell and spread to systemic sites through a Salmonella-induced colitis model. Mice infected with SopB deleted strain ΔsopB displayed increased severity to colitis, reduced mucin expression and increased bacterial translocation. In vitro study, we found there was an increased goblet cell necroptosis following ΔsopB infection. Consistently, mice infected with ΔsopB had a strong upregulation of mixed lineage kinase domain-like (MLKL) phosphorylation. Deletion of MLKL rescued severity of tissue inflammatory, improved mucin2 expression and abolished the increased bacterial translocation in mice infected with ΔsopB. Intriguingly, the expression of sopB in LS174T cells was downregulated. The temporally regulated SopB expression potentially switched the role from epithelial cell invasion to bacterial transmission. Collectively, these results indicated a role for SopB in modulating the onset of necroptosis to increased bacteria pathogenesis and translocated to systemic sites.

Prevalence and rates of recognition of depressive disorders in internal medicine outpatient departments of 23 general hospitals in Shenyang, China.

BACKGROUND: One important approach to increasing recognition and treatment rates for depression in urban China is to identify persons with depression who have contact with primary health care services, most of which are provided in the outpatient departments of general hospitals. We aim to assess the prevalence, risk factors and rates of recognition of depressive disorders in internal medicine outpatient departments of general hospitals. METHODS: Outpatients with depression among 5312 consecutive attendees at outpatient internal medicine departments of 23 randomly selected general hospitals in Shenyang are identified by a two-stage screening process using the General Health Questionnaire and the Structured Clinical Interview for DSM-IV-TR Axis I Disorders. Charts of subjects with DSM-IV depressive disorders are reviewed to determine if treating clinicians made a diagnosis of depression or prescribed anti-depressant medications. RESULTS: The current prevalence of any type of depressive disorder was 11.0% (95% CI: 10.1%-12.1%); and those of major depressive disorder, dysthymia, and depression not otherwise specified were 3.6% (3.1%-4.2%), 2.8% (2.4%-3.4%), and 4.1% (3.5%-4.8%) respectively. Only 4.0% (2.5%-6.1%) of the depressed patients were identified by the treating clinician and only 3.0% (1.6%-4.9%) were provided with antidepressant medication. Older age, female gender, reporting religious beliefs, low educational level, low income level and widowhood were independently associated with the occurrence of depression. CONCLUSIONS: The prevalence of depression in primary care settings in urban China is lower than that reported in most western countries but the risk factors for depression are similar. The very low rates of recognition and treatment are related both to the low rates of care seeking for psychological problems and to the high-volume collective model of hospital-based primary care delivery. Increasing the recognition and treatment of depression in Chinese general hospitals will require changing the attitudes of patients and clinicians and, more importantly, altering the structure of care delivery.

Comparing characteristics of suicide attempters with suicidal ideation and those without suicidal ideation treated in the emergency departments of general hospitals in China.

Suicide attempts are more frequent than suicides, and suicidal ideation has been identified as an important precursor of both attempted and completed suicide. In this study, we compare the characteristics of suicide attempters with suicidal ideation and suicide attempters without suicidal ideation who were treated in the emergency departments of general hospitals in China. We identified 166 people as having suicidal ideation and 73 people who did not have suicidal ideation. The suicide attempters with suicidal ideation were more likely to be more depressed, older, have a lower score on life quality, female, divorced and unemployed, report having religious beliefs, have a suicide attempt history and a psychiatric diagnosis, and intend to reduce pain as motives. However, the suicide attempters without suicidal ideation were more likely to have a more self-rescue ideation and were more impulsive, and to threaten or intend revenge on others as motives. Multivariate logistic regression analysis identified the following independent predictors of suicidal ideation in the suicide attempters: a higher score on Hamilton Depression Rating Scale, religious beliefs, non-impulsive suicide attempts, and a psychiatric diagnosis. The results indicate the importance of developing different interventions for the two groups to prevent future suicide in China.

Non-Hematopoietic MLKL Protects Against Salmonella Mucosal Infection by Enhancing Inflammasome Activation.

The intestinal mucosal barrier is critical for host defense against pathogens infection. Here, we demonstrate that the mixed lineage kinase-like protein (MLKL), a necroptosis effector, promotes intestinal epithelial barrier function by enhancing inflammasome activation. MLKL-/- mice were more susceptible to Salmonella infection compared with wild-type counterparts, with higher mortality rates, increased body weight loss, exacerbated intestinal inflammation, more bacterial colonization, and severe epithelial barrier disruption. MLKL deficiency promoted early epithelial colonization of Salmonella prior to developing apparent intestinal pathology. Active MLKL was predominantly expressed in crypt epithelial cells, and experiments using bone marrow chimeras found that the protective effects of MLKL were dependent on its expression in non-hematopoietic cells. Intestinal mucosa of MLKL-/- mice had impaired caspase-1 and gasdermin D cleavages and decreased interleukin (IL)-18 release. Moreover, administration of exogenous recombinant IL-18 rescued the phenotype of increased bacterial colonization in MLKL-/- mice. Thus, our results uncover the role of MLKL in enhancing inflammasome activation in intestinal epithelial cells to inhibit early bacterial colonization.

Comparative Efficacy and Safety of Antihypertensive Agents for Adult Diabetic Patients with Microalbuminuric Kidney Disease: A Network Meta-Analysis.

BACKGROUND: Antihypertensive treatment mitigates the progression of chronic kidney disease. Here, we comparatively assessed the effects of antihypertensive agents in normotensive and hypertensive diabetic patients with microalbuminuric kidney disease. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs) comparing oral antihypertensive agents in adult diabetic patients with microalbuminuria. The primary efficacy outcome was reduction in albuminuria, and the primary safety outcomes were dry cough, presyncope, and edema. Random-effects pairwise and Bayesian network meta-analyses were performed to produce outcome estimates for all RCTs, only hypertensive RCTs, or only normotensive RCTs. Surface under the cumulative ranking (SUCRA) probability rankings were calculated for all outcomes. Sensitivity analyses on type 2 diabetes status, age, or follow-up duration were also performed. RESULTS: A total of 38 RCTs were included in the meta-analyses. The angiotensin-converting enzyme inhibitor-calcium channel blocker (ACEI-CCB) combination therapy of captopril+diltiazem was most efficacious in reducing albuminuria irrespective of blood pressure status. However, the ACEI-angiotensin receptor blocker (ACEI-ARB) combination therapy of trandolapril+candesartan was the most efficacious in reducing albuminuria for normotensive patients, while the ACEI-CCB combination therapy of fosinopril+amlodipine was the most efficacious in reducing albuminuria for hypertensive patients. The foregoing combination therapies displayed inferior safety profiles relative to ACEI monotherapy with respect to dry cough, presyncope, and edema. With respect to type 2 diabetic patients with microalbuminuria, the Chinese herbal medicine Tangshen formula followed by the ACEI ramipril were the most efficacious in reducing albuminuria. CONCLUSIONS: Trandolapril+candesartan appears to be the most efficacious intervention for reducing albuminuria for normotensive patients, while fosinopril+amlodipine appears to be the most efficacious intervention for reducing albuminuria for hypertensive patients. For practitioners opting for monotherapy, our SUCRA analysis supports the use of trandolapril and fosinopril in normotensive and hypertensive adult diabetic patients with microalbuminuria, respectively.

Capturing Parent-Child Interactions With Social Media: Comment on Zhang et al. (2015).

Zhang et al. conducted a qualitative study of children presented with 19 parental structuring behaviors of parental control and were asked to attribute the parent's intent behind the behaviors. The authors developed several conceptual categories, "parent-centered," "child-centered," or "social" interests. Here, we describe how their 12 propositions could be empirically tested in further studies using social media.