A protease and a lipoprotein jointly modulate the conserved ExoR-ExoS-ChvI signaling pathway critical in Sinorhizobium meliloti for symbiosis with legume hosts.

Sinorhizobium meliloti is a model alpha-proteobacterium for investigating microbe-host interactions, in particular nitrogen-fixing rhizobium-legume symbioses. Successful infection requires complex coordination between compatible host and endosymbiont, including bacterial production of succinoglycan, also known as exopolysaccharide-I (EPS-I). In S. meliloti EPS-I production is controlled by the conserved ExoS-ChvI two-component system. Periplasmic ExoR associates with the ExoS histidine kinase and negatively regulates ChvI-dependent expression of exo genes, necessary for EPS-I synthesis. We show that two extracytoplasmic proteins, LppA (a lipoprotein) and JspA (a lipoprotein and a metalloprotease), jointly influence EPS-I synthesis by modulating the ExoR-ExoS-ChvI pathway and expression of genes in the ChvI regulon. Deletions of jspA and lppA led to lower EPS-I production and competitive disadvantage during host colonization, for both S. meliloti with Medicago sativa and S. medicae with M. truncatula. Overexpression of jspA reduced steady-state levels of ExoR, suggesting that the JspA protease participates in ExoR degradation. This reduction in ExoR levels is dependent on LppA and can be replicated with ExoR, JspA, and LppA expressed exogenously in Caulobacter crescentus and Escherichia coli. Akin to signaling pathways that sense extracytoplasmic stress in other bacteria, JspA and LppA may monitor periplasmic conditions during interaction with the plant host to adjust accordingly expression of genes that contribute to efficient symbiosis. The molecular mechanisms underlying host colonization in our model system may have parallels in related alpha-proteobacteria.

Administration of silymarin in NAFLD/NASH: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with a high prevalence worldwide and poses serious harm to human health. There is growing evidence suggesting that the administration of specific supplements or nutrients may slow NAFLD progression. Silymarin is a hepatoprotective extract of milk thistle, but its efficacy in NAFLD remains unclear. MATERIALS AND METHODS: Relevant studies were searched in PubMed, Embase, the Cochrane Library, Web of Science, clinicaltrails.gov, and China National Knowledge Infrastructure and were screened according to the eligibility criteria. Data were analyzed using Revman 5.3. Continuous values and dichotomous values were pooled using the standard mean difference (SMD) and odds ratio (OR). Heterogeneity was evaluated using the Cochran's Q test (I2 statistic). A P<0.05 was considered statistically significant. RESULTS: A total of 26 randomized controlled trials involving 2,375 patients were included in this study. Administration of silymarin significantly reduced the levels of TC (SMD[95%CI]=-0.85[-1.23, -0.47]), TG (SMD[95%CI]=-0.62[-1.14, -0.10]), LDL-C (SMD[95%CI]=-0.81[-1.31, -0.31]), FI (SMD[95%CI]=-0.59[-0.91, -0.28]) and HOMA-IR (SMD[95%CI]=-0.37[-0.77, 0.04]), and increased the level of HDL-C (SMD[95%CI]=0.46[0.03, 0.89]). In addition, silymarin attenuated liver injury as indicated by the decreased levels of ALT (SMD[95%CI]=-12.39[-19.69, -5.08]) and AST (SMD[95% CI]=-10.97[-15.51, -6.43]). The levels of fatty liver index (SMD[95%CI]=-6.64[-10.59, -2.69]) and fatty liver score (SMD[95%CI]=-0.51[-0.69, -0.33]) were also decreased. Liver histology of the intervention group revealed significantly improved hepatic steatosis (OR[95%CI]=3.25[1.80, 5.87]). CONCLUSIONS: Silymarin can regulate energy metabolism, attenuate liver damage, and improve liver histology in NAFLD patients. However, the effects of silymarin will need to be confirmed by further research.

Egr2 and 3 maintain anti-tumour responses of exhausted tumour infiltrating CD8 + T cells.

Although T cells can develop into an exhausted state in the tumour microenvironment, tumour infiltrating T cells (TILs) are important to control tumour growth. By analysing single cell RNA-sequencing data from human tumours, we found that the transcription factors Early Growth Response 2 (EGR2) and 3 were highly induced in TILs, but not peripheral CD8 + T cells, in multiple patient cohorts. We found that deficiency of Egr2 and 3 in T cells resulted in enhanced tumour growth and fewer TILs in mouse models. Egr2 is highly expressed together with checkpoint molecules in a proportion of CD8 + TILs and Egr2high cells exhibit better survival and proliferation than Egr2-/-Egr3-/- and Egr2low TILs. Anti-PD-1 treatment increases Egr2 expression in CD8 + TILs and reduces tumour growth, while anti-PD-1 efficacy is abrogated in the absence of Egr2 and 3. Thus, Egr2 and 3 are important for maintaining anti-tumour responses of exhausted CD8 + TILs.

The transcription factors Egr2 and Egr3 are essential for the control of inflammation and antigen-induced proliferation of B and T cells.

Lymphocytes provide optimal responses against pathogens with minimal inflammatory pathology. However, the intrinsic mechanisms regulating these responses are unknown. Here, we report that deletion of both transcription factors Egr2 and Egr3 in lymphocytes resulted in a lethal autoimmune syndrome with excessive serum proinflammatory cytokines but also impaired antigen receptor-induced proliferation of B and T cells. Egr2- and Egr3-defective B and T cells had hyperactive signal transducer and activator of transcription-1 (STAT1) and STAT3 while antigen receptor-induced activation of transcription factor AP-1 was severely impaired. We discovered that Egr2 and/or Egr3 directly induced expression of suppressor of cytokine signaling-1 (SOCS1) and SOCS3, inhibitors of STAT1 and STAT3, and also blocked the function of Batf, an AP-1 inhibitor, in B and T cells. Thus, Egr2 and Egr3 regulate B and T cell function in adaptive immune responses and homeostasis by promoting antigen receptor signaling and controlling inflammation.

Examining effective communication in nursing practice during COVID-19: A large-scale qualitative study.

AIM: The aim of this study was to conduct a primary examination of the qualitative communication experiences of nurses during the first wave of the COVID-19 pandemic in the United States. BACKGROUND: Ambiguity in ever-evolving knowledge on how to provide care during COVID-19. Remaining safe has created a sense of urgency, which has in turn created the need for organizations to quickly alter their operational plans and protocols to support measures that increase capacity and establish a culture of safe care and clear communication. However, no known study has described communication in nursing practice during COVID-19. METHODS: Utilizing qualitative descriptive methodology, semi-structured interviews were conducted with 100 nurse participants from May to September 2020 and recorded for thematic analysis. The consolidated criteria for reporting qualitative studies (COREQ), a 32-item checklist, were used to ensure detailed and comprehensive reporting of this qualitative study protocol. FINDINGS: Study participants shared descriptions of how effective communication positively impacted patient care and nursing practice experiences during the first wave of the COVID-19 pandemic. The thematic network analyses identified the importance of effective communication across three levels: (1) organizational leadership, (2) unit leadership and (3) nurse-to-nurse communication. Within this structure, three organizing themes, essential to effective communication, were described including (a) presence, (b) education and (c) emotional support. CONCLUSION: Examining existing crisis communication policies and procedures across healthcare organizations is imperative to maintain highly relevant, innovative, and data-driven policies and strategies that are fundamental to preserving quality patient care and supporting optimal nursing practice. IMPLICATIONS FOR NURSING POLICY AND HEALTH POLICY: Effective communication is critical to support nurses through extended periods of crisis. COVID-19 represents a unique contemporary challenge to the nursing workforce given the high stress and prolonged strain it has created for both human and healthcare supply resources. There is value in nurses' presence at local, unit level and organizational leadership levels to convey critical information that directly informs leadership decision-making during unprecedented emergencies such as the COVID-19 pandemic.

[Mechanism of Gynostemma pentaphyllum in treatment of metabolism associated fatty liver disease based on network pharmacology and molecular docking].

The present study explored the mechanism of action of Gynostemma pentaphyllum in the treatment of metabolism associa-ted fatty liver disease(MAFLD) by network pharmacology and molecular docking. The main active components and action targets of G. pentaphyllum were collected from TCMSP. Disease-related targets were obtained from GeneCards, OMIM and TTD, and the common targets of the three databases were screened out, which were converted to the genes with standard names by UniProt. The drug-disease common target genes were obtained through Venn tool and uploaded to STRING for the construction of the protein-protein interaction(PPI) network. Cytoscape was used to construct and analyze the drug-active component-common target-disease network. The gene ontology(GO) analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed on the common targets by DAVID. Pymol was adopted to perform molecular docking of active components and the common targets and predict their binding ability. Twenty-four active components(such as gypenosides, quercetin and sitosterol) of G. pentaphyllum were screened out. Ninety-two targets were obtained and 54 common targets were identified. Key targets included TNF, IL6, PTGS2, TP53, CCL2 and VEGFA. GO analysis on biological processes, molecular functions and cellular components and KEGG pathway analysis were performed, and the results indicated that NF-κB, PI3 K-Akt, TNF and HIF-1 signaling pathways were mainly involved. Molecular docking results showed that gypenosides and quercetin had a strong binding ability to TNF, IL6 and PTGS2. The findings of this study revealed that the therapeutic efficacy of G. pentaphyllum on MAFLD might be achieved by resisting inflammation and oxidative stress and improving insulin resistance, providing ideas and a theoretical basis for the development and application of G. pentaphyllum in the treatment of MAFLD.

Egr2 and 3 Inhibit T-bet-Mediated IFN-γ Production in T Cells.

T-bet is important for differentiation of cytotoxic CD8 and Th1 CD4 T cells. We have discovered that Egr2 and 3 are potent inhibitors of T-bet function in CD4 and CD8 effector T cells. Egr2 and 3 were essential to suppress Th1 differentiation in Th2 and Th17 conditions in vitro and also to control IFN-γ-producing CD4 and CD8 T cells in response to virus infection. Together with Egr2 and 3, T-bet is induced in naive T cells by Ag stimulation, but Egr2 and 3 expression was inhibited by Th1-inducing cytokines. We found that Egr2 and 3 physically interact with the T-box domain of T-bet, blocking T-bet DNA binding and inhibiting T-bet-mediated production of IFN-γ. Thus, Egr2 and 3 are antagonists of T-bet function in effector T cells and are important for the control of inflammatory responses of T cells.

Early Growth Response Genes 2 and 3 Regulate the Expression of Bcl6 and Differentiation of T Follicular Helper Cells.

T follicular helper (Tfh) cells support differentiation of B cells to plasma cells and high affinity antibody production in germinal centers (GCs), and Tfh differentiation requires the function of B cell lymphoma 6 (BCL6). We have now discovered that early growth response gene 2 (EGR2) and EGR3 directly regulate the expression of Bcl6 in Tfh cells, which is required for their function in regulation of GC formation. In the absence of EGR2 and -3, the expression of BCL6 in Tfh cells is defective, leading to impaired differentiation of Tfh cells, resulting in a failure to form GCs following virus infection and defects in production of antiviral antibodies. Enforced expression of BCL6 in EGR2/3-deficient CD4 T cells partially restored Tfh differentiation and GC formation in response to virus infection. Our findings demonstrate a novel function of EGR2/3 that is important for Tfh cell development and Tfh cell-mediated B cell immune responses.

Early growth response gene-2 controls IL-17 expression and Th17 differentiation by negatively regulating Batf.

Early growth response gene (Egr)-2 is important for the maintenance of T cell homeostasis and controls the development of autoimmune disease. However, the underlying mechanisms are unknown. We have now discovered that Egr-2, which is induced by TGF-ß and IL-6, negatively regulates the expression of IL-17, but not IL-2 or IFN-γ, in effector T cells. In the absence of Egr-2, CD4 T cells produce high levels of Th17 cytokines, which renders mice susceptible to experimental autoimmune encephalomyelitis induction. T cells lacking Egr-2 show increased propensity for Th17, but not Th1 or Th2, differentiation. Control of IL-17 expression and Th17 differentiation by Egr-2 is due to inhibition of Batf, a transcription factor that regulates IL-17 expression and Th17 differentiation. Egr-2 interacts with Batf in CD4 T cells and suppresses its interaction with DNA sequences derived from the IL-17 promoter, whereas the activation of STAT3 and expression of retinoic acid-related orphan receptor γt are unchanged in Th17 cells in the absence of Egr-2. Thus, Egr-2 plays an important role to intrinsically control Th17 differentiation. We also found that CD4 T cells from multiple sclerosis patients have reduced expression of Egr-2 and increased expression of IL-17 following stimulation with anti-CD3 in vitro. Collectively, our results demonstrate that Egr-2 is an intrinsic regulator that controls Th17 differentiation by inhibiting Batf activation, which may be important for the control of multiple sclerosis development.

IL-2-engineered nano-APC effectively activates viral antigen-mediated T cell responses from chronic hepatitis B virus-infected patients.

Impaired function of virus-specific T cells resulting from virus persistence is one of the major mechanisms underlying the development of chronic hepatitis B viral infection. Previously, we found that IL-2 can restore the effector function of T cells rendered tolerant by Ag persistence. However, systemic administration of IL-2 induces organ pathology and expansion of T regulatory cells. In this study, we show that nano-APC with engineered HLA alleles and IL-2 deliver peptide-MHC complexes, costimulatory molecules, and IL-2 to Ag-responding T cells, resulting in enhanced expression of CD25 and activation of TCR signaling pathways, while suppressing PD-1 expression on viral-responding CD8 T cells from chronic hepatitis B virus patients. The enhanced activation of CD4 and CD8 T cells induced by IL-2-nano-APC was Ag dependent and IL-2-nano-APC did not affect T regulatory cells. At a size of 500 nm, the nano-APC effectively induce immune synapse formation on Ag-specific T cells and accumulate as free particles in the lymphoid organs. These attributes of IL-2-nano-APC or other bioadjuvant-engineered nano-APC have profound implications for their use as a therapeutic strategy in the treatment of chronic hepatitis B virus infection or other chronic viral diseases.

Depression and NAFLD risk: A meta-analysis and Mendelian randomization study.

BACKGROUND: Both depression and nonalcoholic fatty liver disease (NAFLD) have a high global prevalence. Growing evidence suggests an association between depression and NAFLD, while the association remains unclear. Thus, in this study, we aimed to explore the effect of depression on the risk of developing NAFLD. METHODS: The meta-analysis examined the association between depression and the risk of NAFLD by including observational studies. Relevant studies were searched in PubMed, Embase, the Cochrane Library, and Web of Science. Then a two-sample Mendelian randomization (MR) analysis was performed to explore causal association using genetic instruments identified from a genome-wide association study. RESULTS: Six eligible studies were included in the meta-analysis, involving 289,22 depression cases among 167,554 participants. Meta-analysis showed a significant association between depression and a higher risk of developing NAFLD (OR = 1.14, 95 % CI: [1.05, 1.24], P = 0.002). However, we found no convincing evidence supporting a causal role of genetically predicted depression with NAFLD risk (OR = 0.861, 95 % CI: [0.598, 1.238], P = 0.420). LIMITATIONS: The insufficient number of included studies, the use of summary-level data, and restrictions on population sources are the major limiting factors. CONCLUSIONS: Meta-analysis and MR analysis demonstrated inconsistent results on the relationship between depression and a high risk of developing NAFLD. Specifically, meta-analysis confirmed that depression increases the risk of developing NAFLD, while MR analysis did not support a causal association between genetically determined depression and the risk of NAFLD.

Motivators and Barriers to COVID-19 Vaccination in Young Adults Living in the USA.

High rates of COVID-19 infection and lower vaccination rates among young adults aged 18 to 26 in the United States prompted this study to examine motivating factors and barriers to COVID-19 vaccination and identify preferences in COVID-19 vaccine education. Three focus group discussions were completed. Transcribed data were analyzed using thematic analysis. Three key themes were identified including (1) motivating factors to vaccination, (2) barriers to vaccination, and (3) COVID-19 vaccination educational intervention design recommendations. Motivating factors included five relevant subthemes: civic duty, fear related to the disease process; fear related to emerging variants and breakthroughs; fear regarding the suffering of others; and freedom. Barriers included four subthemes: lack of trust, misinformation, politics, and pressure. Attempts to further educate young adults about the COVID-19 vaccine should consider strategies that target motivating factors and barriers while also making accurate information accessible through social media.

Design and Analysis of Intelligent Robot Based on Internet of Things Technology.

This research uses Auto-ID Labs radio frequency identification system to realize the information dissemination from the destination node to the nodes in its neighborhood. The purpose is to forward messages and explore typical applications. Realize the intelligent analysis and management of IoT devices and data. Design a set of edge video CDN system, in the G1 data set A = 9, p = 9, ℤp = 9, lℤp = 8, AES = 5, ES = 9. Distribute some hot content to public wireless hotspots closer to users in advance, A = 9, p = 7, ℤp = 9, lℤp = 9, AES = 9, ES = 8. At present, a large amount of research is mainly to deploy an edge node between the end node of the Internet of Things and the cloud computing center to provide high-quality services. By learning a stable dynamic system from human teaching to ensure the robustness of the controller to spatial disturbances. FPP-SCA plan FPP-SCA = 1.99, FPP-SCA = 1.86, FPP-SCA = 1.03, FPP-SCA = 1.18, FPP-SCA = 1.01, FPP-SCA = 1.46, FPP-SCA = 1.61.The more robots work in an unstructured environment, with different scenarios and tasks, the comparison shows that the FPP-SCA scheme is the optimal model F-S0 = 2.52, F-S5 = 2.38, F-S10 = 2.5, F- S15 = 2.09, F-S20 = 2.54, F-S25 = 2.8, F-S30 = 2.98.

Effect of Four-in-One Optimized Emergency Nursing Procedure on Symptoms and Vital Signs of Patients with Mushroom Poisoning.

Most members of the general public find it difficult to identify poisonous wild mushrooms, resulting in family food poisoning. Toxic mushroom poisoning can produce nausea, vomiting, abdominal pain, and other severe symptoms 30 minutes or more after ingestion that can even lead to death. Using a "four-in-one" optimized emergency nursing procedure to treat mushroom poisoning can reduce the rescue time and improve the survival rate of patients. This study aimed to analyze the influence of a "four-in-one" optimized emergency nursing procedure to treat patients with toadstool poisoning. A prospective randomized study was conducted. Sixteen cases of toadstool poisoning, corresponding to 78 patients admitted to our hospital from January 2017 to July 2020, were selected and divided into a study group and a control group of 39 cases each using a random number table. The control group was provided with routine emergency care, and the study group was given a "four-in-one" treatment that optimized the emergency care process; both groups were subjected to basic treatment + blood purification and other treatment measures, and the treatment time in the rescue room and the first blood purification time of the two groups were compared. Differences in routine blood tests, liver and kidney function indices, hospitalization time, coma time, treatment outcome, and nursing satisfaction before and after treatment were found. The treatment time and the first blood purification time of the study group were lower than those of the control group, and the difference was statistically significant (P < 0.05); ALT, AST, TBIL, TBA, and ALB were measured upon admission for the study and the control groups. The measured values of PT, APTT, CK, CK-MB, and BUN were compared for the two groups, but the difference in the values between the two groups was not statistically significant (P > 0.05); after 7 days of treatment, the ALT, TBA, and APTT indicators of the study group were lower than those of the control group, and the difference was statistically significant (P < 0.05); the measured values of ALT, AST, TBIL, TBA, ALB, PT, APTT, CK, CK-MB, BUN, and Scr after 7 days of treatment were significantly lower than those before treatment for both groups (P < 0.05). The length of stay for the study group was lower than that for the control group, and the difference was statistically significant (P < 0.05); the treatment efficiency was 87.18% for the study group, compared with 82.05% for the control group, but the difference was not statistically significant (P > 0.05). The study group rated nursing care as follows: very satisfactory, 79.49%; relatively satisfactory, 15.38%; and acceptable, 5.13%; the control group rated nursing care as follows: very satisfactory, 51.28%; relatively satisfactory, 30.77%; and acceptable, 12.82%; the results were statistically significant (P < 0.05). Using a "four-in-one" optimized emergency care process to treat patients with mushroom poisoning can significantly reduce the rescue room treatment time and the first blood purification time and improve nursing satisfaction, but has a limited effect on improving the treatment efficiency.

The promising role of probiotics/prebiotics/synbiotics in energy metabolism biomarkers in patients with NAFLD: A systematic review and meta-analysis.

Background: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with a high prevalence worldwide, seriously harming human health, and its pathogenesis remains unclear. In recent years, increasing evidence has indicated that intestinal microbiota plays an important role in the occurrence and development of NAFLD. The regulation method of probiotics/prebiotics/synbiotics can alter the intestinal microbiota and has been suggested as an option in the treatment of NAFLD. Methods: Five databases of PubMed, Embase, the Cochrane Library, clinicaltrails.gov, and China National Knowledge Infrastructure were searched initially, and then the eligible studies were screened. Finally, the data of included studieswere extracted, combined and analyzed. Results: A total of 29 randomized controlled trials involving 2,110 patients were included in this study. The results showed that using probiotics/prebiotics/synbiotics in the intervention group could reduce the levels of glucose (SMD = -0.23, 95% CI [-0.45, -0.01], P = 0.04), HOMA-IR (SMD = -0.47, 95% CI [-0.63, -0.31], P < 0.00001) and insulin (SMD = -0.46, 95% CI [-0.76, -0.16], P = 0.002) in sugar metabolism; in terms of lipid metabolism, the levels of TC (SMD = -0.62, 95%CI [-0.87, -0.36], P < 0.00001), and LDL-C (SMD = -0.57, 95%CI [-0.85, -0.28], P < 0.00001) were decreased; and the level of ALB was decreased in protein metabolism (SMD = -0.34, 95%CI [-0.61, -0.06], P = 0.02). Conclusions: Based on the current evidence, probiotics/prebiotics/synbiotics may improve energy metabolism biomarkers in the NAFLD population, but these effects still need to be confirmed by further research. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#aboutpage.

Barriers and perceived needs for understanding and using research among emergency nurses.

INTRODUCTION: Nurses are involved in conducting research and incorporating evidence into their practice. However, barriers exist at the individual, unit, and organizational level related to understanding, conducting, and evaluating the evidence. The Emergency Nurses Association (ENA) conducted a study to understand levels of education in research, the extent of experience, and needs and barriers to research at the individual and organizational levels in emergency nursing. METHODS: A cross-sectional survey design was used to poll members of the ENA. A 62-item survey instrument was designed to assess five areas: 1) nurses' research values, skills, experience, and awareness; 2) organizational settings' opportunities, barriers, and limitations to research; 3) nurses' understanding and comprehension of research and evidence; 4) presentation and accessibility of research; and 5) continuing educational topics to improve knowledge of the research process. RESULTS: Respondents (n = 948) identified barriers at the individual level that included lack of knowledge about critiquing research studies and familiarity with the research process. Barriers at the unit level included obtaining help from administrators and other staff in starting a project or having the authority to change practice. Barriers at the institution level included lack of support systems such as protected time to conduct research or implement changes in practice. DISCUSSION: Emergency nurses are highly motivated and interested in learning more about conducting and utilizing research to improve practice. Perceived personal, unit-based, and organizational barriers were identified through this research in an effort to highlight areas for improvement at the local and national levels.

Antigen-loaded ER microsomes from APC induce potent immune responses against viral infection.

Although matured DC are capable of inducing effective primary and secondary immune responses in vivo, it is difficult to control the maturation and antigen loading in vitro. In this study, we show that ER-enriched microsomal membranes (microsomes) isolated from DC contain more peptide-receptive MHC I and II molecules than, and a similar level of costimulatory molecules to, their parental DC. After loading with defined antigenic peptides, the microsomes deliver antigenic peptide-MHC complexes (pMHC) to both CD4 and CD8 T cells effectively in vivo. The peptide-loaded microsomes accumulate in peripheral lymphoid organs and induce stronger immune responses than peptide-pulsed DC. The microsomal vaccines protect against acute viral infection. Our data demonstrate that peptide-MHC complexes armed microsomes from DC can be an important alternative to DC-based vaccines for protection from viral infection.

Alcohol screening, brief intervention, and referral to treatment conducted by emergency nurses: an impact evaluation.

INTRODUCTION: In a quasi-experimental study, control and intervention group outcomes were compared following implementation of alcohol screening, brief intervention, and referral to treatment (SBIRT) by emergency nurses. The primary hypothesis was: Trauma patients who participate in nurse-delivered ED SBIRT will have greater reductions in alcohol consumption and fewer alcohol-related incidents than those who do not. METHODS: Patients were screened for alcohol use and those with risky drinking were randomly assigned to either the intervention or usual care group. Those in the intervention group received a brief motivational intervention and referral to appropriate follow-up services. Using medical and driving history records, subjects' alcohol consumption, alcohol-related traffic incidents, repeat injuries, and repeat ED visits were compared between groups at baseline and three-month follow-up. RESULTS: Alcohol consumption decreased by 70% in the intervention group compared to 20% in the usual care group. Drinking frequency also decreased in both groups. Fewer patients from the intervention group (20%) had recurring ED visits compared to patients in the usual care group (31%). DISCUSSION: The SBIRT procedure can impact alcohol consumption and potentially reduce injuries and ED visits when successfully implemented by staff nurses in the emergency department environment. Further research is needed to improve follow-up methods in this hard to reach, mobile patient population.

Egr2 regulation in T cells is mediated through IFNγ/STAT1 and IL-6/STAT3 signalling pathway.

The immune system is a host defence system to protect the body against foreign invaders. T cells are one of the major components of the immune cells and they are essential for immune responses. Early growth response gene (Egr2) in T cells is important for maintaining immune functions of T cells by promoting adaptive immune responses while controlling inflammation and preventing the development of autoimmune diseases. A study by our group demonstrated the function of Egr2 as a checkpoint regulator controlling the proliferation and differentiation of the T cells. In association, Egr2 and 3 play indispensable role in T cell immune response, but the mechanism regulating Egr2 expression in T cells is still unclear. In this study, we analysed the Egr2 expression mechanism in CD4 T cells under antigen stimulation. We found that Egr2 expression is regulated by different cytokines including IL-2 and IL-4, which increased Egr2 induction in activated T cells. However, inflammatory cytokines, including INFγ and IL-6, suppressed Egr2 expression through STAT1 and STAT3 signalling pathway respectively, highlighting a mechanism for tolergenic immune response on T cells.

Egr2 and 3 control inflammation, but maintain homeostasis, of PD-1high memory phenotype CD4 T cells.

The transcription factors Egr2 and 3 are essential for controlling inflammatory autoimmune responses of memory phenotype (MP) CD4 T cells. However, the mechanism is still unclear. We have now found that the Egr2+ subset (PD-1high MP) of MP CD4 T cells expresses high levels of checkpoint molecules (PD-1 and Lag3) and also markers of effector T cells (CXCR3 and ICAM-1). Egr2/3 are not required for PD-1high MP CD4 cell development but mediate a unique transcriptional programme that effectively controls their inflammatory responses, while promoting homeostatic proliferation and adaptive responses. Egr2 negative PD-1high MP CD4 T cells are impaired in homeostatic proliferation and adaptive responses against viral infection but display inflammatory responses to innate stimulation such as IL-12. PD-1high MP CD4 T cells have recently been implicated in rheumatoid arthritis pathogenesis, and we have now found that Egr2 expression is reduced in PD-1high MP CD4 T cells from patients with active rheumatoid arthritis compared with healthy controls. These findings demonstrate that Egr2/3 control the inflammatory responses of PD-1high MP CD4 T cells and maintain their adaptive immune fitness.