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Background: Interactions between parasitic insects and their hosts demonstrate the complexity of evolutionary processes. Specifically, the parasitoid wasp Aphidius ervi manipulates its host, the pea aphid Acyrthosiphon pisum, through strategic venom injection to enhance mummification. This study explores how this venom affects the aphid's immune system, particularly targeting the activity of the phenoloxidase (PO) enzyme.

Results: Following the injection of venom from A. ervi, significant changes were observed in the expression of immune-related genes in A. pisum, especially notable expression changes of ApPPOs and a reduction of PO activity. Multi-omics sequencing identified 74 potential venom proteins in the venom gland of A. ervi, including serine protease homolog 1 (AeSPH1) and serine protease inhibitor (AeSPN1), hypothesized to regulate PO activity. The injection of recombinant protein AeSPH1 and AeSPN1 into the A. pisum hemocoel selectively reduced the expression of ApPPO1, without affecting ApPPO2, and effectively suppressed melanization. Moreover, RNAi targeting AeSPH1 significantly reduced the mummification rate in A. pisum population parasitized by A. ervi.

Conclusion: Our findings clarify the complex biochemical mechanisms underlying host-wasp interactions and highlight potential avenues for developing targeted biological control strategies. © 2024 Society of Chemical Industry.

Background and aims: Patient initiated transport refusal during Emergency Medical Service (EMS) opioid overdose encounters has become an endemic problem. This study aimed to quantify circumstantial and environmental factors which predict refusal of further care.

Design: In this cross-sectional analysis, a case definition for opioid overdose was applied retrospectively to EMS encounters. Selected cases had sociodemographic and situational/incident variables extracted using patient information and free text searches of case narratives. 50 unique binary variables were used to build a logistic model.

Setting: Prehospital EMS overdose encounters in Washington, DC, USA, from July 2017 to July 2023.

Participants: Of EMS encounters in the study timeframe, 14 587 cases were selected as opioid overdoses.

Measurements: Predicted probability for covariates was the outcome variable. Model performance was assessed using Stratified K-Fold Cross-Validation and scored with positive predictive value, sensitivity and F1. Prediction accuracy and McFadden's pseudo-R squared are also determined.

Findings: The model achieved a predictive accuracy of 78% with a high positive predictive value (0.83) and moderate sensitivity (0.68). Bystander type influenced the refusal outcome, with decreased refusal probability associated with family (nondescript) (-28%) and parents (-16%), while presence of a girlfriend increased it (+28%). Negative situational factors like noted physical trauma (-62%), poor weather (-14%) and lack of housing (-14%) decreased refusal probability. Characteristics of the emergency response team, like a prior crew member encounter (+20%) or crew experience <1 year (-36%), had a variable association with transport.

Conclusions: Refusal of emergency transport for opioid overdose cases in Washington, DC, USA, has expanded by 43.8% since 2017. Several social, environmental and systematic factors can predict this refusal. Logistic regression models can be used to quantify broad categories of behavior in surveillance medical research.

Objective: This study examined cross-level interaction between parental education and neighbourhood SES in predicting overweight including obesity among school-aged children.

Methods: This analysis used data from 19 984 children aged 5-6 years participating in the school-entry examination of the years 2015 to 2019 in the Aachen city region in Germany. We employed multilevel logistic regression models to predict overweight based on parental education and neighbourhood SES, along with their cross-level interaction, while controlling for several characteristics of the child.

Results: Children from families with intermediate (OR: 1.99; 95% CI, 1.65-2.40) and low parental education (OR: 2.55; 95% CI, 1.92-3.39) and from neighbourhoods with intermediate (OR: 1.25; 95% CI, 1.02-1.53) and low SES (OR: 1.61; 95% CI, 1.29-2.02) were at significantly higher odds for overweight. There was an indication of a cross-level interaction effect (p-value <0.10) to the disadvantage of children with higher parental education, suggesting that inequalities in overweight decrease in more deprived neighbourhoods. The predicted probability of overweight for children with high parental education increased from 6.4% in high SES neighbourhoods to 7.8% in intermediate and 9.9% in low SES neighbourhoods. Sensitivity analyses for obesity and a higher context level of spatial SES confirmed the results.

Conclusions: The results highlight the crucial role of both individual and contextual socioeconomic conditions in predicting childhood overweight. They also suggest that the impact of neighbourhood socioeconomic status on childhood overweight varies by parental education, particularly disadvantaging children with higher parental education, indicating a social contagion of overweight through spatial disadvantage.

Background: An increasing human population, the emergence of resistances against pesticides and their potential impact on the environment call for the development of new eco-friendly pest control strategies. RNA interference (RNAi)-based pesticides have emerged as a new option with the first products entering the market. Essentially, double-stranded RNAs targeting essential genes of pests are either expressed in the plants or sprayed on their surface. Upon feeding, pests mount an RNAi response and die. However, it has remained unclear whether RNAi-based insecticides should target the same pathways as classic pesticides or whether the different mode-of-action would favor other processes. Moreover, there is no consensus on the best genes to be targeted.

Results: We performed a genome-wide screen in the red flour beetle to identify 905 RNAi target genes. Based on a validation screen and clustering, we identified the 192 most effective target genes in that species. The transfer to oral application in other beetle pests revealed a list of 34 superior target genes, which are an excellent starting point for application in other pests. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses of our genome-wide dataset revealed that genes with high efficacy belonged mainly to basic cellular processes such as gene expression and protein homeostasis - processes not targeted by classic insecticides.

Conclusion: Our work revealed the best target genes and target processes for RNAi-based pest control and we propose a procedure to transfer our short list of superior target genes to other pests. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

We conducted a systematic review and meta-analysis to determine the efficacy of interventions aimed at reducing weight bias in healthcare students, and to explore factors that may impact intervention success. A systematic review and random-effects meta-analyses were conducted by including studies that examined the efficacy of weight bias reduction interventions for healthcare students. Of the 3463 journal articles and dissertations screened, 67 studies (within 64 records) met inclusion criteria, with 35 studies included in the meta-analyses (explicit = 35, implicit [and explicit] = 10) and 32 studies included in the narrative synthesis (explicit = 34, implicit [and explicit] = 3). Weight bias interventions had a small but positive impact, g = -0.31 (95% CI = -0.43 to -0.19, p < 0.001), in reducing students' explicit weight bias but there was no intervention effect on implicit weight bias, g = -0.12 (95% CI = -0.26 to 0.02, p = 0.105). There was considerable heterogeneity in the pooled effect for explicit bias (I² = 74.28, Q = 132.21, df = 34, p < 0.001). All subgroup comparisons were not significant (p > 0.05) and were unable to explain the observed heterogeneity. Narrative synthesis supported meta-analytic findings. The small but significant reduction of explicit weight bias encourages the continued testing of interventions, irrespective of variation in individual intervention components. Contrarily, reductions in implicit weight bias may only be possible from a large societal shift in negative beliefs and attitudes held towards people living in larger bodies.

Arterial media calcification is a severe cardiovascular complication commonly manifesting in patients with chronic kidney disease (CKD). Patients with CKD frequently undergo intravenous iron therapy to address iron deficiency. Iron is suggested to be sequestered in vascular cells, potentially leading to oxidative (lipid) stress and cell death, which are recognized as key contributors to arterial calcification. The objective of this study was to investigate the effect of intravenous iron administration on CKD-induced arterial media calcification. Therefore, adenine-induced CKD rats were treated intravenously with iron and checked for arterial iron deposition and calcification, as well as for ferritin and lipid peroxidation markers. Additionally, arterial sections from patients with CKD who were dialysis dependent were analyzed for these parameters. This study showed that intravenous iron administration in CKD rats led to arterial iron deposition and a lipid peroxidation signature. CKD-induced arterial calcification was increased upon iron treatment and correlated with arterial iron accumulation and lipid peroxidation markers. Patients with CKD who were dialysis dependent showed arterial iron accumulation and elevated lipid peroxidation, but a direct correlation with arterial calcification was lacking. Taken together, iron treatment is suggested as a potential contributor to the calcification process, instead of being a predominant factor, thereby emphasizing the complexity of arterial calcification as a multifactorial disease. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Objective: This study aimed to evaluate the cardiorenal effect of combining sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) when compared with monotherapy of either agent in patients with type 2 diabetes (T2D).

Methods: PubMed, Web of Science, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrial.gov were systematically searched from inception to June 2024. Eligible studies included randomised controlled trials and observational studies assessing that compared with SGLT2i or GLP-1RA monotherapy, the risk of cardiorenal outcomes in patients with T2D who treated with combination therapy. Pooled relative risk (RR) and 95% confidence intervals (CIs) were computed in random-effects model.

Results: In all, five RCTs, 10 post hoc analyses and one observational study were included. The reduced risk of the composite cardiovascular outcome was observed in patients receiving combination therapy of SGLT2i and GLP-1RA when compared with SGLT2i monotherapy (RR = 0.57, 95% CI 0.38-0.86, p = 0.008) or GLP-1RA monotherapy (RR = 0.77, 95% CI 0.65-0.91, p = 0.002). Likewise, the composite renal adverse events were less frequent in patients receiving combination therapy of SGLT2i and GLP-1RA when compared with SGLT2i monotherapy (RR = 0.69, 95% CI 0.59-0.82, p < 0.001) or GLP-1RA monotherapy (RR = 0.66, 95% CI 0.53-0.83, p < 0.001). Compared with GLP-1RA monotherapy, the combination therapy of SGLT2i and GLP-1RA was associated with lower risks of heart failure-related outcomes (RR = 0.63, 95% CI 0.51-0.77, p < 0.001) and all-cause mortality (RR = 0.66, 95% CI 0.50-0.88, p = 0.004) in patients with T2D.

Conclusion: The cardiorenal benefits might be magnified with the combination therapy of SGLT2i and GLP-1RA when compared with monotherapy of either agent. Further investigations are needed to validate the findings.

Background: The Stress Hyperglycemia Ratio (SHR), a new biomarker calculated from glucose and HbA1c levels, has been linked to significant clinical outcomes in diabetes. This study investigates the potential of the SHR to predict End-Stage Renal Disease (ESRD) among patients with Diabetic Kidney Disease (DKD).

Methods: We included 316 participants from the West China Hospital T2DM-DKD cohort (January 2008-September 2020), divided into three SHR tertiles: T1 (SHR <0.7), T2 (SHR ≥0.7 to <0.94) and T3 (SHR ≥0.94). A second retrospective cohort of 625 DKD patients was recruited from Sichuan University Hospital (January 2019-May 2022), with similar inclusion criteria. SHR was analysed using Restricted Cubic Spline, Kaplan-Meier curves and Cox proportional hazards models. Key confounders such as eGFR, proteinuria, hypoalbuminemia and glucose-lowering medications were adjusted for in the analysis.

Results: In Cohort 1 (median follow-up 42 months), 38.6% developed ESRD. Kaplan-Meier curves showed a higher incidence of ESRD in the lowest and highest SHR tertiles compared to the middle group (p < 0.01). Multivariate analysis confirmed that SHR <0.7 (HR 1.71, 95% CI: 1.01-2.90) and SHR ≥0.94 (HR 1.93, 95% CI: 1.16-3.20) were significantly associated with ESRD. In Cohort 2 (median follow-up 18.6 months), patients with SHR <0.7 and ≥0.94 had significantly higher risks of ≥30% eGFR decline or ESRD, with adjusted HRs of 2.18 (95% CI: 1.15-4.11) and 2.68 (95% CI: 1.38-5.23), respectively.

Conclusion: This study observed a U-shaped relationship between SHR and ESRD in patients with DKD. Both very high and very low SHR values correlate with increased risks, highlighting the critical importance of glucose management in chronic diabetes care.