Objective: High blood pressure and proteinuria play major roles in chronic kidney disease (CKD), a high-mortality condition that affects millions of people. Reactive oxygen species (ROS) produced by NADPH oxidases are implicated in many pathophysiological processes including hypertension and CKD. Apocynin (APO) shows the anti-oxidative activity by inhibiting the assembly of NADPH oxidase and overproduction of ROS. The aim of this study was to investigate the effects of apocynin on oxidative stress, blood pressure and kidney function in normotensive rats with CKD induced by 5/6 nephrectomy through ligation of renal poles (Nx-L). Design and method: Male Wistar rats were divided into three groups. One group was control (sham surgery) and two other groups underwent two-step surgical procedure of 5/6 nephrectomy induced by ligation of renal poles. Unlike conventional Nx which leads to high mortality due to hemorrhage in or after surgery, here we induced Nx by ligation of the upper and lower poles (leads to necrosis of these poles) of left kidney after removal the right kidney one week later. After 4 weeks from this procedure, control and model group (Nx-L) received vehicle, while Nx-L+APO received apocynin 20 mg/kg/day (i.p.) for 4-week-period. Mean blood pressure (MAP), proteinuria, and oxidative stress marker (thiobarbituric acid reactive species-TBARS) in plasma and urine were measured. Results: In model group we observed significantly increased MAP (121,13±2,01vs.94,88±4,13mmHg, p<0.001), plasma creatinine (55,4±1,3vs. 41,3±2,3μmol/l, p<0.001), and proteinuria (0,036±0,006vs.0,017±0,001mg/min/kg, p<0.01) levels compared to those in control. Furthermore, significant increase of plasma TBARS level (5,47±0,77vs.2,75±0,52nmol/ml, p<0.01) and urine TBARS excretion (1,10±0,06vs.0,86±0,04nmol/min/kg, p<0.01) were detected in model compared to control. Interestingly, APO treatment significantly reduced blood pressure to the level of control (83,88±5,14vs.94,88±4,13mmHg). APO significantly reduced urine protein loss (0,024±0,002vs.0,036±0,006mg/min/kg, p<0.05) and plasma creatinine level (49,9±1,5vs.55,4±1,3μmol/l, p<0.05) as well as reduced plasma lipid peroxidation (2,19±0,26vs.5,47±0,77nmol/ml, p<0.001) in comparison to model group. Conclusions: Our results show that APO treatment prevents blood pressure rising and ameliorates kidney function in rats with 5/6 nephrectomy trough improvement of systemic oxidative status. Therefore, NADPH oxidase presents a potential therapeutic target in this form of kidney disease.

This article focuses on the parameter estimation problem in wireless sensor networks (WSNs) under adversarial attacks, considering the complexities of sensing and communication in challenging environments. In order to mitigate the impact of these attacks on the network, we propose a novel AP-DLMS algorithm with adaptive threshold attack detection and malicious punishment mechanism. The adaptive threshold is constructed using the observation matrix and network topology to detect the location of malicious attacks, while the standard reference estimation is designed to obtain the estimated deviation of each node. To mitigate the impact of data tampering on network performance, we introduce the honesty factor and punishment factor to combine the weights of normal nodes and malicious nodes respectively. Additionally, we propose a new probabilistic random attack model. Simulations are conducted to investigate the influence of key parameters in the adaptive threshold on the performance of the proposed AP-DLMS algorithm, and the mean square performance of the algorithm is analyzed under various attack models. The results demonstrate that the proposed algorithm exhibits strong robustness in adversarial networks, and the proposed attack model effectively demonstrates the impact of attacks.

Vesicoureteral reflux (VUR) is defined as the urine backflow from the urinary bladder to the pyelo-caliceal system. In contrast, intrarenal reflux (IRR) is the backflow of urine from the renal calyces into the tubulointerstitial space. VURs, particularly those associated with IRR can result in reflux nephropathy when accompanied by urinary tract infection (UTI). The prevalence of IRR in patients with diagnosed VUR is 1–11% when using voiding cystourethrography (VCUG), while 11.9–61% when applying the contrast-enhanced voiding urosonography (ceVUS). The presence of IRR diagnosed by VCUG often correlates with parenchymal scars, when diagnosed by a 99mTc dimercaptosuccinic acid scan (DMSA scan), mostly in kidneys with high-grade VURs, and when diagnosed by ceVUS, it correlates with the wide spectrum of parenchymal changes on DMSA scan. The study performed by both ceVUS and DMSA scans showed IRRs associated with non-dilated VURs in 21% of all detected VURs. A significant difference regarding the existence of parenchymal damage was disclosed between the IRR-associated and IRR-non-associated VURs. A higher portion of parenchymal changes existed in the IRR-associated VURs, regardless of the VUR grade. That means that kidneys with IRR-associated VURs represent the high-risk group of VURs, which must be considered in the future classification of VURs. When using ceVUS, 62% of places where IRR was found were still unaffected by parenchymal changes. That was the basis for our recommendation of preventive use of long-term antibiotic prophylaxis until the IRR disappearance, regardless of the VUR grade. We propose a new classification of VURs using the ceVUS method, in which each VUR grade is subdivided based on the presence of an IRR.

BACKGROUND The global coronavirus 2019 (COVID-19) pandemic began in early 2020, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In mid-2020 the CIAO (Modelling the Pathogenesis of COVID-19 Using the Adverse Outcome Pathway Framework) project was established, bringing together over 75 interdisciplinary scientists worldwide to collaboratively investigate the underlying biological mechanisms of COVID-19 and consolidate the data using the Adverse Outcome Pathway (AOP) Framework. Neurological symptoms such as anosmia and encephalitis have been frequently reported to be associated with infection with SARS-CoV-2. OBJECTIVE Within CIAO, a working group was formed to conduct a systematic scoping review of COVID-19 and its related neurological symptoms to determine which key events and modulating factors are most commonly reported and to identify knowledge gaps. DESIGN LitCOVID was used to retrieve 86,075 papers of which 10,244 contained relevant keywords. After title and abstract screening, 2,328 remained and their full texts were reviewed based on predefined inclusion and exclusion criteria. 991 studies fulfilled the inclusion criteria and were retrieved to conduct knowledge synthesis. RESULTS The majority of publications reported human observational studies. Early key events were less likely to be reported compared to middle and late key events/adverse outcomes. The majority of modulating factors described related to age or sex. Less recognised COVID-19 associated AO or neurological effects of COVID-19 were also identified including multiple sclerosis/demyelination, neurodegeneration/cognitive effects and peripheral neuronal effects. CONCLUSION There were many methodological and reporting issues noted in the reviewed studies. In particular, publication abstracts would benefit from clearer reporting of the methods and endpoints used and the key findings, to ensure relevant papers are included when systematic reviews are conducted. The information extracted from the scoping review may be useful in understanding the mechanisms of neurological effects of COVID-19 and to further develop or support existing AOPs linking COVID-19 and its neurological key events and adverse outcomes. Further evaluation of the less recognised COVID-19 effects is needed.

Background: Peripheral arterial disease (PAD) is highly prevalent and has a well-known association with diabetes. It is still unknown if diabetes worsens clinical outcomes after lower extremity revascularization (LER). Research question: What is the impact of diabetes on clinical outcomes in patients with PAD undergoing LER. Goals: In this meta-analysis, we assessed the effect of diabetes on mortality, major limb amputation, and major adverse cardiovascular events (MACE) in patients with PAD following endovascular or open LER during the perioperative period and within 30 days of follow-up. Methods: We performed a systematic search of PubMed, Embase, and Cochrane databases to December 2023, including studies that compared the clinical outcomes of patients with diabetes and without diabetes following LER procedure. Review Manager 5.4 was used for statistical analysis. I 2 statistics were used to examine heterogeneity. A random-effects model was applied to all analyses. Results: Of the 3,810 articles screened, five observational studies with 55,444 patients were included. A total of 51.13 % had diabetes. There was no significant association between diabetes and mortality (RR 0.96; 95 % confidence interval (CI) 0.74 - 1.26; I 2 = 69%; P = 0.79; Figure 1A). However, diabetes was associated with a significantly increased risk of major limb amputation by 50% (RR 1.50; 95 % CI 1.03 - 2.21; I 2 = 94%; P = 0.04; Figure 1B), and an 18% significantly higher risk of experiencing MACE (RR 1.18; 95 % CI 1.08 - 1.29; I 2 = 0%; P = 0.0005; Figure 1C). Conclusion: Our findings suggest that diabetes is associated with an increased risk of major amputation and MACE but not with mortality in patients following LER.

Abstract International education is Australia’s largest services export, and third largest export altogether, generating between $22 billion and $40 billion per year over the last few years. Higher education represents half of this ‘market’ with over 25 % of students being from overseas. Despite the important role that international students play in the fabric of Australian society and specifically in higher education, the findings from our linguistic ethnographic study of international students at an Australian university showed that the English language learning needs of these students were frequently unmet. Using James Scott’s theory of official and hidden transcripts, we reveal that students reported feeling that their “English is not good enough” and assumed personal ‘(ir)responsibility’ for this outcome. In this broad English Medium Instruction (EMI) context, where English is not the first language, but it is used as the language of instruction and as the lingua franca amongst international students, English-dominant perspectives acted to marginalise international students, impacting their academic performance and confidence for social networking. In this paper, we describe the shifts in higher educational policy in Australia over the last few decades to provide context to the current neoliberal educational climate for international students. We draw on principles of social justice to examine the present-day system and argue that Australian universities need to shift from an EMI by default model to a genuine EMI offering.

BACKGROUND Timely and safe elective health care facilitates return to normal activities for patients and prevents emergency admissions. Surgery is a cornerstone of elective care and relies on complex pathways. This study aimed to take a whole-system approach to evaluating access to and quality of elective health care globally, using inguinal hernia as a tracer condition. METHODS This was a prospective, international, cohort study conducted between Jan 30 and May 21, 2023, in which any hospital performing inguinal hernia repairs was eligible to take part. Consecutive patients of any age undergoing primary inguinal hernia repair were included. A measurement set mapped to the attributes of WHO's Health System Building Blocks was defined to evaluate access (emergency surgery rates, bowel resection rates, and waiting times) and quality (mesh use, day-case rates, and postoperative complications). These were compared across World Bank income groups (high-income, upper-middle-income, lower-middle-income, and low-income countries), adjusted for hospital and country. Factors associated with postoperative complications were explored with a three-level multilevel logistic regression model. FINDINGS 18 058 patients from 640 hospitals in 83 countries were included, of whom 1287 (7·1%) underwent emergency surgery. Emergency surgery rates increased from high-income to low-income countries (6·8%, 9·7%, 11·4%, 14·2%), accompanied by an increase in bowel resection rates (1·2%, 1·4%, 2·3%, 4·2%). Overall waiting times for elective surgery were similar around the world (median 8·0 months from symptoms to surgery), largely because of delays between symptom onset and diagnosis rather than waiting for treatment. In 14 768 elective operations in adults, mesh use decreased from high-income to low-income countries (97·6%, 94·3%, 80·6%, 61·0%). In patients eligible for day-case surgery (n=12 658), day-case rates were low and variable (50·0%, 38·0%, 42·1%, 44·5%). Complications occurred in 2415 (13·4%) of 18 018 patients and were more common after emergency surgery (adjusted odds ratio 2·06, 95% CI 1·72-2·46) and bowel resection (1·85, 1·31-2·63), and less common after day-case surgery (0·39, 0·34-0·44). INTERPRETATION This study demonstrates that elective health care is essential to preventing over-reliance on emergency systems. We identified actionable targets for system strengthening: clear referral pathways and increasing mesh repair in lower-income settings, and boosting day-case surgery in all income settings. These measures might strengthen non-surgical pathways too, reducing the burden on society and health services. FUNDING NIHR Global Health Research Unit on Global Surgery and Portuguese Hernia and Abdominal Wall Society (Sociedade Portuguesa de Hernia e Parede Abdominal).

Background and Purpose Posterior cerebral artery occlusion (PCAo) can cause long-term disability, yet randomized controlled trials to guide optimal reperfusion strategy are lacking. We compared the outcomes of PCAo patients treated with endovascular thrombectomy (EVT) with or without intravenous thrombolysis (IVT) to patients treated with IVT alone. Methods From the multicenter retrospective Posterior cerebraL ArTery Occlusion (PLATO) registry, we included patients with isolated PCAo treated with reperfusion therapy within 24 hours of onset between January 2015 and August 2022. The primary outcome was the distribution of the modified Rankin Scale (mRS) at 3 months. Other outcomes comprised 3-month excellent (mRS 0–1) and independent outcome (mRS 0–2), early neurological improvement (ENI), mortality, and symptomatic intracranial hemorrhage (sICH). The treatments were compared using inverse probability weighted regression adjustment. Results Among 724 patients, 400 received EVT+/-IVT and 324 IVT alone (median age 74 years, 57.7% men). The median National Institutes of Health Stroke Scale score on admission was 7, and the occluded segment was P1 (43.9%), P2 (48.3%), P3–P4 (6.1%), bilateral (1.0%), or fetal posterior cerebral artery (0.7%). Compared to IVT alone, EVT+/-IVT was not associated with improved functional outcome (adjusted common odds ratio [OR] 1.07, 95% confidence interval [CI] 0.79–1.43). EVT increased the odds for ENI (adjusted OR [aOR] 1.49, 95% CI 1.05–2.12), sICH (aOR 2.87, 95% CI 1.23–6.72), and mortality (aOR 1.77, 95% CI 1.07–2.95). Conclusion Despite higher odds for early improvement, EVT+/-IVT did not affect functional outcome compared to IVT alone after PCAo. This may be driven by the increased risk of sICH and mortality after EVT.

Conditioning before allogeneic hematopoietic stem cell transplantation (AlloHSCT) increases the tissue injury signal IL-33 in fibroblastic reticular cells (FRC). Released IL-33 directly stimulates donor CD4 T cells to prime IL-12-independent Type 1 T helper cell (Th1) differentiation and expansion. Tissue stroma upregulates IL-33, but a role for IL-33 in sustaining the pathogenic donor Th1 responses causing GVHD is unclear. We compared B6 mice with inducible ST2 deletion (R26-CreERT2xSt2fl/fl) to wildtype (WT) R26-CreERT2 as T cell donors in a lethal GVHD model (B6 to BALB/c). Donor ST2 deletion at days 10-14 post AlloHSCT increased CD4 T cells Foxp3 expression with reciprocal decreases in Tbet expression in both the lymphoid organs and target tissues. Sustained IL-33 signaling also maintained donor T cell TCF1 expression. Ablating ST2 after GVHD development improved clinical scores and promoted recipient weight gain. How bioactive IL-33 is released from nuclear sequestration remains undefined. RNAseq analysis suggested that IL-33 stimulates T cell granzyme B (GzmB) expression and B6 GzmB deficient (Gzmb-/-) donor T cells displayed reduced activation and expansion similar to ST2 deficient CD4 T cells. In contrast to GzmBWT, anti-IL-33 antibodies had no impact on GzmBKO T cell responses. Thus, cross-talk between donor T cells and IL-33+ stroma orchestrates the T cell identities that are critical to sustain the pathogenic CD4 T cell responses causing GVHD.

Due to their advantages—longer internal force delay compared to bulk materials, resistance to harsh conditions, damping of a wide frequency spectrum, insensitivity to ambient temperature, high reliability and low cost—granular materials are seen as an opportunity for the development of high-performance, lightweight vibration-damping elements (particle dampers). The performance of particle dampers is affected by numerous parameters, such as the base material, the size of the granules, the flowability, the initial prestress, etc. In this work, a series of experiments were performed on specimens with different combinations of influencing parameters. Energy-based design parameters were used to describe the overall vibration-damping performance. The results provided information for a deeper understanding of the dissipation mechanisms and their mutual correlation, as well as the influence of different parameters (base material, granule size and flowability) on the overall damping performance. A comparison of the performance of particle dampers with carbon steel and polyoxymethylene granules and conventional rubber dampers is given. The results show that the damping performance of particle dampers can be up to 4 times higher compared to conventional bulk material-based rubber dampers, even though rubber as a material has better vibration-damping properties than the two granular materials in particle dampers. However, when additional design features such as mass and stiffness are introduced, the results show that the overall performance of particle dampers with polyoxymethylene granules can be up to 3 times higher compared to particle dampers with carbon steel granules and conventional bulk material-based rubber dampers.