IFNh and IRF9 influence the transcription of MHCII mediated by IFNγ to maintain immune balance in sea perch lateolabrax japonicus.

The major histocompatibility complex class II (MHCII) molecules are crucial elements of the adaptive immune system, essential for orchestrating immune responses against foreign pathogens. However, excessive expression of MHCII can disrupt normal physiological functions. Therefore, the host employs various mechanisms to regulate MHCII expression and maintain immune homeostasis. Despite this importance, limited studies have explored the negative regulation of MHCII transcription in bony fish. In this study, we found that interferon h (IFNh), a subtype of type I IFN in sea perch Lateolabrax japonicus, could inhibit the activation of IFNγ induced-MHCII expression by modulating the transcription of the class II major histocompatibility complex transactivator (CIITA). Transcriptome analysis revealed 57 up-regulated and 69 down-regulated genes in cells treated with both IFNγ and IFNh compared to those treated with IFNγ alone. To maintain cellular homeostasis, interferon regulatory factor 9 (IRF9) was up-regulated following IFNγ stimulation, thereby preventing MHCII overexpression. Mechanistically, IRF9 bound to the CIITA promoter and suppressed its expression activated by IRF1. Furthermore, IRF9 inhibited the promoter activity of both MHCII-α and MHCII-ß induced by CIITA. Our findings highlight the roles of IFNh and IRF9 as suppressors regulating MHCII expression at different hierarchical levels. This study provides insights into the intricate regulation of antigen presentation and the foundation for further exploration of the interaction mechanisms between aquatic virus and fish.

Ct-based diagnosis of sarcopenia as a prognostic factor for postoperative mortality after elective open-heart surgery in older patients: a cohort-based systematic review and meta-analysis.

Background: Cardiac open-heart surgery, which usually involves thoracotomy and cardiopulmonary bypass, is associated with a high incidence of postoperative mortality and adverse events. In recent years, sarcopenia, as a common condition in older patients, has been associated with an increased incidence of adverse prognosis. Methods: We conducted a search of databases including PubMed, Embase, and Cochrane, with the search date up to January 1, 2024, to identify all studies related to elective cardiac open-heart surgery in older patients. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence. Results: A total of 12 cohort studies were included in this meta-analysis for analysis. This meta-analysis revealed that patients with sarcopenia had a higher risk of postoperative mortality. Furthermore, the total length of hospital stay and ICU stay were longer after surgery. Moreover, there was a higher number of patients requiring further healthcare after discharge. Regarding postoperative complications, sarcopenia patients had an increased risk of developing renal failure and stroke. Conclusion: Sarcopenia served as a tool to identify high-risk older patients undergoing elective cardiac open-heart surgery. By identifying this risk factor early on, healthcare professionals took targeted steps to improve perioperative function and made informed clinical decisions.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023426026.

The impact of combined administration of ropivacaine and dexamethasone on postoperative analgesia in perianal surgery with pudendal nerve block under ultrasound guidance: a prospective randomized controlled study.

Background: In recent years, severe pain after perianal surgery has seriously affected the prognosis of hospitalized patients. How to maximize the improvement of postoperative pain and perioperative comfort becomes particularly important. Methods: This study was a double-blind randomized controlled trial (Registration No.: ChiCTR2100048760, Registration Date: 16 July 2021, Link: www.chictr.org.cn/showproj.html?proj=130226), and patients were randomly divided into two groups: one group underwent postoperative 20 mL bilateral pudendal nerve block with 0.5% ropivacaine (P group), and the other group underwent postoperative 20 mL bilateral pudendal nerve block with 0.5% ropivacaine + 8 mg dexamethasone (PD group). The primary outcome was the incidence of moderate to severe pain at the first postoperative dressing change. Secondary outcomes included Quality of recovery-15 (QoR-15) score at 3 days after surgery, sleep quality, pain score at 3 days after surgery, and incidence of adverse events. Results: In the main outcome indicators, the incidence was 41.7% in the P group and 24.2% in the PD group (p = 0.01). The QoR-15 score and sleep quality in PD group were better than those in P group 2 days before surgery. The incidence of postoperative urinary retention was significantly decreased in PD group (p = 0.01). Conclusion: Local anesthesia with dexamethasone combined with pudendal nerve block after perianal surgery can reduce the incidence of moderate to severe pain during the first dressing change. This may be one of the approaches to multimodal analgesia after perianal surgery. Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR2100048760.

A real-world study of antifibrotic drugs-related adverse events based on the United States food and drug administration adverse event reporting system and VigiAccess databases.

Objectives: This study aims to investigate adverse events (AEs) and adverse drug reactions (ADRs) associated with pirfenidone and nintedanib, two antifibrotic drugs used to treat idiopathic pulmonary fibrosis (IPF). Methods: Reporting odds ratio (ROR) and proportional reporting ratio (PRR) analyses were conducted to assess the association between these drugs and signals at both the preferred term (PT) and system organ class (SOC) levels. Results: 55,949 reports for pirfenidone and 35,884 reports for nintedanib were obtained from the FAERS database. The VigiAccess database provided 37,187 reports for pirfenidone and 23,134 reports for nintedanib. Male patients and individuals over the age of 65 were more likely to report AEs. Gastrointestinal disorders emerged as the most significant signal at SOC level for both drugs. Furthermore, nausea, diarrhoea, and decreased appetite were observed at the PT level. We further identified notable signals, including hemiplegic migraine for pirfenidone and asthenia, constipation, and flatulence for nintedanib, which were previously unknown or underestimated ADRs. Conclusion: This study has identified AEs and ADRs associated with pirfenidone and nintedanib, confirming that the majority of the corresponding label information indicates relative safety. However, it is essential to take unexpected risk signals seriously, necessitating further research to manage the safety profiles of these drugs.

Feedback loop regulation between viperin and viral hemorrhagic septicemia virus through competing protein degradation pathways.

Viperin is an antiviral protein that exhibits a remarkably broad spectrum of antiviral activity. Viperin-like proteins are found all kingdoms of life, suggesting it is an ancient component of the innate immune system. However, viruses have developed strategies to counteract viperin's effects. Here, we describe a feedback loop between viperin and viral hemorrhagic septicemia virus (VHSV), a common fish pathogen. We show that Lateolabrax japonicus viperin (Ljviperin) is induced by both IFN-independent and IFN-dependent pathways, with the C-terminal domain of Ljviperin being important for its anti-VHSV activity. Ljviperin exerts an antiviral effect by binding both the nucleoprotein (N) and phosphoprotein (P) of VHSV and induces their degradation through the autophagy pathway, which is an evolutionarily conserved antiviral mechanism. However, counteracting viperin's activity, N protein targets and degrades transcription factors that up-regulate Ljviperin expression, interferon regulatory factor (IRF) 1 and IRF9, through ubiquitin-proteasome pathway. Together, our results reveal a previously unknown feedback loop between viperin and virus, providing potential therapeutic targets for VHSV prevention. Importance: Viral hemorrhagic septicaemia (VHS) is a contagious disease caused by the viral hemorrhagic septicaemia virus (VHSV), which poses a threat to over 80 species of marine and freshwater fish. Currently, there are no effective treatments available for this disease. Understanding the mechanisms of VHSV-host interaction is crucial for preventing viral infections. Here, we found that, as an ancient antiviral protein, viperin degrades the N and P proteins of VHSV through the autophagy pathway. Additionally, the N protein also impacts the biological functions of IRF1 and IRF9 through the ubiquitin-proteasome pathway, leading to the suppression of viperin expression. Therefore, the N protein may serve as a potential virulence factor for the development of VHSV vaccines and screening of antiviral drugs. Our research will serve as a valuable reference for the development of strategies to prevent VHSV infections.

Effect of sarcopenia in predicting postoperative mortality in emergency laparotomy: a systematic review and meta-analysis.

BACKGROUND: While emergency laparotomy has been associated with high rates of postoperative mortality and adverse events, preoperative systematic evaluation of patients may improve perioperative outcomes. However, due to the critical condition of the patient and the limited operation time, it is challenging to conduct a comprehensive evaluation. In recent years, sarcopenia is considered a health problem associated with an increased incidence of poor prognosis. This study aimed to investigate the effect of sarcopenia on 30-day mortality and postoperative adverse events in patients undergoing emergency laparotomy. METHODS: We systematically searched databases including PubMed, Embase, and Cochrane for all studies comparing emergency laparotomy in patients with and without sarcopenia up to March 1, 2022. The primary outcome was of 30-day postoperative mortality. Secondary outcomes were the length of hospital stay, the incidence of adverse events, number of postoperative intensive care unit (ICU) admissions, and ICU length of stay. Study and outcome-specific risk of bias were assessed using the Quality in Prognosis Studies (QUIPS) tool. We rated the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE). RESULT: A total of 11 eligible studies were included in this study. The results showed that patients with sarcopenia had a higher risk of death 30 days after surgery (OR = 2.42, 95% CI = 1.93-3.05, P < 0.00001). More patients were admitted to ICU after surgery (OR = 1.58, 95% CI = 1.11-2.25, P = 0.01). Both the ICU length of stay (MD = 0.55, 95% CI = 0.05-1.06, P = 0.03) and hospital length of stay (MD = 2.33, 95% CI = 1.33-3.32, P < 0.00001) were longer in the sarcopenia group. The incidence of postoperative complications was also significantly higher in patients with sarcopenia (OR = 1.78, 95% CI = 1.41-2.26, P < 0.00001). CONCLUSION: In emergency laparotomy, sarcopenia was associated with increased 30-day postoperative mortality. Both the lengths of stay in the ICU and the total length of hospital stay were significantly higher than those in non-sarcopenic patients. Therefore, we concluded that sarcopenia can be used as a tool to identify preoperative high-risk patients, which can be considered to develop new postoperative risk prediction models. Registration number Registered on Prospero with the registration number of CRD42022300132.

Study on MEV90 of 0.5% ropivacaine for US-guided caudal epidural block in anorectal surgery.

Background: Choosing the appropriate concentration and volume of anesthetics is critical for a successful nerve block. The current study aimed to determine the minimum effective volume (MEV) of 0.5% ropivacaine for US-guided CEB in 90% of patients (MEV90) undergoing anorectal surgery. The aims were to reduce the occurrence of complications associated with a sacral blockade in anorectal surgery, broaden the indications for surgical procedures and treatment, and improve patient satisfaction. This study presents the groundwork for the development of individualized anesthetic programs. We believe that the study would serve as a reference for the use of caudal epidural block (CEB) in lower abdominal surgery for intraoperative and postoperative analgesia. Methods: This study used a biased coin design (BCD) up-and-down method (UDM). We divided the participants into two groups based on gender, and each group independently performed the biased coin design up-and-down method. We used 0.5% ropivacaine for the first patient in each group; however, the volume was 10 ml for men and 8 ml for women. Therefore, the dose of anesthetics given to each patient was determined by the response of the previous patient. If the block of the previous patient failed, the volume was increased by 2 ml in the following patient. Otherwise, the next subject had an 11% chance of receiving a volume of 2 ml less or an 89% chance of receiving no volume change. We defined a successful block as painless surgery with anal sphincter relaxation 15 min after the drug injection. Enrollment was completed after 45 successful caudal blocks for each group. Results: Caudal epidural block was successfully performed on 50 men and 49 women. The MEV90 of ropivacaine for CEB was calculated to be 12.88 ml (95% CI: 10.8-14 ml) for men and 10.73 ml (95% CI: 9.67-12 ml) for women. Men had a MEV99 of 13.88 ml (95% CI: 12.97-14 ml), and women had a MEV99 of 11.87 ml (95% CI: 11.72-12 ml). Conclusion: With operability and general applicability, it is possible to increase the success rate of CEB for anorectal surgery to 99% as well as decrease the incidence of anesthesia-related complications. CEB can meet the needs of patients for rapid postoperative rehabilitation, improve patient satisfaction, and lay a solid foundation for postoperative analgesia.

Adaptive Observer Based Fault Tolerant Control for Sensor and Actuator Faults in Wind Turbines.

The installed wind energy generation capacity has been increasing dramatically all over the world. However, most wind turbines are installed in hostile environments, where regular operation needs to be ensured by effective fault tolerant control methods. An adaptive observer-based fault tolerant control scheme is proposed in this article to address the sensor and actuator faults that usually occur on the core subsystems of wind turbines. The fast adaptive fault estimation (FAFE) algorithm is adopted in the adaptive observers to accurately and rapidly located the faults. Based on the states and faults estimated by the adaptive observers, the state feedback fault tolerant controllers are designed to stabilize the system and compensate for the faults. The gain matrices of the controllers are calculated by the pole placement method. Simulation results illustrate that the proposed fault tolerant control scheme with the FAFE algorithm stabilizes the faulty system effectively and performs better than the baseline on the benchmark model of wind turbines.

Intrathecal morphine versus transversus abdominis plane block for caesarean delivery: a systematic review and meta-analysis.

BACKGROUND: The number of caesarean deliveries has been increasing. Although intrathecal morphine (ITM) can relieve pain and is widely applied in caesarean deliveries, it is associated with many side effects. Transversus abdominis plane block (TAPB), a new analgesic technology, has also began playing a certain role after caesarean delivery, with fewer adverse effects. This study mainly compares the analgesic and adverse effects of ITM and TAPB in caesarean delivery. METHODS: We systematically searched PubMed, Cochrane Library, EMBASE, and Web of Science, for randomised controlled trials (RCTs) published before 9 October, 2020 to compare the effects of ITM and TAPB. Primary outcome of the study was the pain score at rest 24 h after caesarean delivery, whereas the secondary outcomes were the pain score at movement 24 h after operation, postoperative nausea and vomiting (PONV), itching, and morphine consumption. For the outcome assessment, we conducted a sensitivity analysis. RESULT: Six RCTs involving 563 patients and meeting the study inclusion criteria were included in this study. Results indicated no significant difference in the pain score between ITM and TAPB at 24 h of rest or movement. The sensitivity analysis results indicated that the resting pain score (95% CI = - 1.27 to - 0.28; P = 0.002) and 24-h moving pain score (95% CI = - 1.8 to - 0.07; P = 0.03) of the ITM group were lower than those of the TAPB group. The consumption of morphine in the ITM group was lower than in the TAPB group (95% CI = 1.92 to 4.87; P < 0.00001); however, in terms of adverse reactions, the incidence of pruritus (95% CI = 1.17 to 8.26; P = 0.02) and PONV (95% CI = 1.92 to 4.87, P < 0.00001) in the ITM group was higher than in the TAPB group. CONCLUSION: Parturients in the ITM and TAPB groups exhibited similar analgesic effects. However, in the sensitivity analysis performed by eliminating the studies causing heterogeneity, the ITM group was found to have superior analgesic effects compared with the TAPB group, with less morphine consumption. Differently, the TAPB group displayed less side effects such as PONV. Therefore, TAPB is still a valuable analgesia option for patients who cannot use ITM for analgesia after caesarean delivery or those having a high risk of PONV. TRIAL REGISTRATION: Registration number: Registered on Prospero with the registration number of CRD42020210135 .

Interventions that address institutional child maltreatment: An evidence and gap map.

Background: Child maltreatment has serious short and long-term negative impacts for those experiencing it. Child maltreatment occurring in institutional settings has recently received substantial attention. However, evidence about the effectiveness of interventions that prevent, disclose, respond to, or treat maltreatment that has occurred in these environments is fragmented and can be difficult to access. This evidence and gap map (EGM) collates this research evidence. It was developed as a resource for stakeholders operating in the child health, welfare and protection sectors, including practitioners, organisational leaders, policy developers and researchers, wanting to access high quality evidence on interventions addressing institutional child maltreatment. Objectives: The objectives of this EGM were twofold: (a) To provide a structured and accessible collection of existing evidence from finalised and ongoing overviews of systematic reviews, systematic reviews and effectiveness studies of interventions addressing institutional child maltreatment-for those who work to fund, develop, implement and evaluate interventions aimed at ensuring children's safety in institutional settings; (b) to identify gaps in the available evidence on interventions addressing institutional child maltreatment-thereby helping to inform the research agendas of funders and other organisations. Search Methods: A comprehensive search strategy identified relevant studies from published and grey literature, comprising: (1) 10 electronic academic databases; (2) five trial and systematic review registries; (3) nine organisational websites; (4) websites and reference lists of inquiry reports associated with seven international inquiries into child abuse and (4) the lists of included studies within systematic reviews identified by the search strategy. Members of this EGM's Subject Matter Experts group were also invited to forward relevant unpublished studies or grey literature. Selection Criteria: The selection criteria were developed to identify finalised and ongoing overviews of reviews, systematic reviews and primary studies that reported on the effectiveness of interventions addressing child maltreatment (including sexual abuse, physical abuse, neglect and emotional abuse) within institutional settings. Eligible effectiveness study designs included: randomised controlled trials (RCTs), nonrandomised trials, controlled before-and-after studies and quasi-experimental studies. Reviews were eligible if they reported a systematic literature search strategy. Data Collection and Analysis: All screening, data extraction, coding and critical appraisals were undertaken by two or more reviewers working independently, with discrepancies resolved via consensus or by a third reviewer. The titles and abstracts of studies identified by the search strategy were screened, and each full text of potentially relevant studies was further assessed for inclusion. Key data were extracted from all included studies and reviews. This included information about: publication details (e.g., year, author, country), inclusion/exclusion criteria (for reviews), study design, institutional setting, target population, type of maltreatment, intervention type and outcomes. Critical appraisal of included systematic reviews was achieved using the AMSTAR 2 tool, and completed RCTs were assessed using the updated Cochrane Risk of Bias 2.0 tool. Main Results: Number of studies The electronic database search yielded 6318 citations, and a further 2375 records were identified from additional sources. Following deduplication and title/abstract screening, 256 studies remained for full text review. A total of 73 eligible studies (reported across 84 publications) met the inclusion criteria, including: 11 systematic reviews (plus, one update); 62 primary studies (including, three protocols for primary studies). Study characteristics The studies were conducted across 18 countries, however more than half (52%) were undertaken in the United States. Overall, most studies evaluated curriculum-based interventions delivered in educational settings, primarily aimed at the prevention of sexual abuse. Institutional setting: Most studies evaluated interventions in school or early learning environments (n = 8 systematic reviews; n = 58 primary studies). Far fewer studies examined other organisational settings. Out of home care (including foster care, residential care and orphanages), and social service organisations servicing children were minimally represented. No studies were identified where the primary setting was sports clubs, churches/religious organisations, summer/vacation camps, detention centres/juvenile justice settings, or primary/secondary health care facilities. Target population: Most interventions targeted children rather than adults (n = 7 systematic reviews; n = 47 primary studies) from the general population. Fewer studies included populations known to be at an increased risk, or those already exposed to maltreatment. Just over a third of the primary studies conducted an analysis to ascertain differences in the effect of an intervention between the genders. Intervention type: Prevention interventions were the most studied (n = 5 systematic reviews; n = 57 primary studies), with additional studies including prevention approaches alongside other intervention types. Fewer studies evaluated interventions targeting disclosure, institutional responses, or treatment interventions. Type of maltreatment: The vast majority of the studies assessed interventions solely addressing the sexual abuse of children (n = 8 systematic reviews; n = 45 primary studies). The remaining studies addressed other forms of maltreatment, including physical and emotional abuse, or neglect, either in combination or as a sole focus. Outcomes: Primary reported outcomes reflected the bias toward child targeted interventions. Outcome measures captured child wellbeing and knowledge outcomes, including measures of mental health, children's knowledge retention and/or self-protective skills. Measures of maltreatment disclosure or maltreatment occurrence/reoccurrence were less common, and all other outcome categories included in the EGM were minimally or not reported. A third of studies reported on some measure of implementation. Study quality The overall quality of the studies was low to moderate. Most systematic reviews were low-quality (n = 10), with only one high quality review (and update) identified. Most completed RCTs had some concerns relating to the risk of bias (n = 30), and the remainder were considered to be at a high risk of bias (n = 19). Authors' Conclusions: This EGM has highlighted a substantial need for more high quality studies that evaluate interventions across a broader range of institutional contexts and maltreatment types. The current evidence base does not represent countries with large populations and the greatest incidence of child maltreatment. Few studies focussed on perpetrators or the organisational environment. Further evidence gaps were identified for interventions relating to disclosure, organisational responses and treatment, and few studies assessed interventions targeting perpetrators' maltreatment behaviours, recidivism or desistence. Future studies should also include measure of programme implementation.