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The consumption of poultry products contaminated with Salmonella species is one of the most common causes of Salmonella infections. In vivo studies demonstrated the potential application of peanut skins (PS) as an antimicrobial poultry feed additive to help mitigate the proliferation of Salmonella in poultry environments. Tons of PS, a waste by-product of the peanut industry, are generated and disposed in U.S. landfills annually. Peanut skins and extracts have been shown to possess antimicrobial and antioxidant properties. Hence, we aimed to determine the effect of PS as a feed additive on the gut microbiota of broilers fed a control or PS supplemented (4% inclusion) diet and inoculated with or without Salmonella enterica Enteritidis (SE). At hatch 160 male broilers were randomly assigned to 4 treatments: 1) CON-control diet without SE, 2) PS-PS diet without SE, 3) CONSE-control diet with SE, 4) PSSE-PS diet with SE. On d 3, birds from CONSE and PSSE treatments were inoculated with 4.2 × 10 9 CFU/mL SE. At termination (4 wk), 10 birds/treatment were euthanized and ileal and cecal contents were collected for 16S rRNA analysis using standard methodologies. Sequencing data were analyzed using QIIME2. No effect of PS or SE was observed on ileal alpha and beta diversity, while evenness, richness, number of amplicon sequence variants (ASV) and Shannon, as well as beta diversity were significantly (P < 0.05) affected in ceca. Similarly, more differentially abundant taxa between treatment groups were identified in ceca than in ileum. However, more microbiota functional changes, based on the PICRUST2 prediction, were observed in ileum. Overall, relatively minor changes in microbiota were observed during SE infection and PS treatment, suggesting that PS addition may not attenuate the SE proliferation, as shown previously, through modulation of microbiota in gastrointestinal tract. However, while further studies are warranted, these results suggest that PS may potentially serve as a functional feed additive for poultry for improvement of animal health., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Published by Elsevier Inc.)

In multicellular organisms, a variety of lipid-protein particles control the systemic flow of triacylglycerides, cholesterol, and fatty acids between cells in different tissues. The chemical modification by oxidation of these particles can trigger pathological responses, mediated by a group of membrane proteins termed scavenger receptors. The lectin-like oxidized low-density lipoprotein (LOX-1) scavenger receptor binds to oxidized low-density lipoprotein (oxLDL) and mediates both signaling and trafficking outcomes. Here, we identified five synthetic proteins termed Affimers from a phage display library, each capable of binding recombinant LOX-1 extracellular (oxLDL-binding) domain with high specificity. These Affimers, based on a phytocystatin scaffold with loop regions of variable sequence, were able to bind to the plasma membrane of HEK293T cells exclusively when human LOX-1 was expressed. Binding and uptake of fluorescently labeled oxLDL by the LOX-1-expressing cell model was inhibited with subnanomolar potency by all 5 Affimers. ERK1/2 activation, stimulated by oxLDL binding to LOX-1, was also significantly inhibited (p < 0.01) by preincubation with LOX-1-specific Affimers, but these Affimers had no direct agonistic effect. Molecular modeling indicated that the LOX-1-specific Affimers bound predominantly via their variable loop regions to the surface of the LOX-1 lectin-like domain that contains a distinctive arrangement of arginine residues previously implicated in oxLDL binding, involving interactions with both subunits of the native, stable scavenger receptor homodimer. These data provide a new class of synthetic tools to probe and potentially modulate the oxLDL/LOX-1 interaction that plays an important role in vascular disease., Competing Interests: Conflicts of interest M. J. M. and D. C. T. are named inventors of the Affimer technology and this is filed under U.S. patent number #10,844,370 assigned to the University of Leeds on “Scaffold proteins derived from plant cystatins”., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Previous studies have attributed the prominent analgesic, hallucinogenic, sedative, and anxiolytic properties of Salvia divinorum to Salvinorin A. However, the overall pharmacological profile of this isolate limits its clinical applications. To address these limitations, our study evaluates the C(22)-fused-heteroaromatic analogue of salvinorin A [2-O-salvinorin B benzofuran-2-carboxylate] (P-3l) in mice nociception and anxiety models while assessing possible mechanism of action. In comparison with the control group, orally administered P-3l (1, 3, 10, and 30 mg/kg) attenuates acetic acid-induced abdominal writhing, formalin-induced hind paw licking, the thermal reaction to the hotplate, and/or aversive response in the elevated plus-maze, open field, and light-dark box; and potentiates the effect of morphine and diazepam at sub-effective doses (1.25 and 0.25 mg/kg, respectively) without eliciting significant alterations in relative organ weight, or haematological or biochemical parameters. The in vivo blockade of P-3 l effects by naloxone (non-selective opioid receptor antagonist), naloxonazine (antagonist of specific subtypes mu 1 of μ-OR), and nor-binaltorphimine (selective ĸ-OR antagonist) supports initial results from binding assays and the interpretations made possible from computational modeling of the interactions of P-3 l with the opioid receptor subtypes. In addition to the opioidergic mechanism, the blockade of the P-3 l effect by flumazenil suggests benzodiazepine binding site involvement in its biological activities. These results support P-3 l potentially possessing clinical utility and substantiate the need for additional pharmacological characterization., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest for this study., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Vascular endothelial growth factors (VEGFs) bind to membrane receptors on a wide variety of cells to regulate diverse biological responses. The VEGF-A family member promotes vasculogenesis and angiogenesis, processes which are essential for vascular development and physiology. As angiogenesis can be subverted in many disease states, including tumour development and progression, there is much interest in understanding the mechanistic basis for how VEGF-A regulates cell and tissue function. VEGF-A binds with high affinity to two VEGF receptor tyrosine kinases (VEGFR1, VEGFR2) and with lower affinity to co-receptors called neuropilin-1 and neuropilin-2 (NRP1, NRP2). Here, we use a structural viewpoint to summarise our current knowledge of VEGF-VEGFR activation and signal transduction. As targeting VEGF-VEGFR activation holds much therapeutic promise, we examine the structural basis for anti-angiogenic therapy using small-molecule compounds such as tyrosine kinase inhibitors that block VEGFR activation and downstream signalling. This review provides a rational basis towards reconciling VEGF and VEGFR structure and function in developing new therapeutics for a diverse range of ailments.

The process of atherosclerosis leads to the formation of plaques in the arterial wall, resulting in a decreased blood supply to tissues and organs and its sequelae: morbidity and mortality. A class of membrane-bound proteins termed scavenger receptors (SRs) are closely linked to the initiation and progression of atherosclerosis. Increasing interest in understanding SR structure and function has led to the idea that these proteins could provide new routes for cardiovascular disease diagnosis, management, and treatment. In this review, we consider the main classes of SRs that are implicated in arterial disease. We consider how our understanding of SR-mediated recognition of diverse ligands, including modified lipid particles, lipids, and carbohydrates, has enabled us to better target SR-linked functionality in disease. We also link clinical studies on vascular disease to our current understanding of SR biology and highlight potential areas that are relevant to cardiovascular disease management and therapy.

Aim: To present the authors' experience of endovascular treatment of confirmed and presumed (microbiology negative) mycotic aortic aneurysms (MAA)., Materials and Methods: Patients undergoing endovascular aortic repair were identified retrospectively from 1998 using the radiology information system and an internally kept database until 2018. The primary aim was to assess the technical success and peri-operative morbidity and mortality. The secondary aim was to assess progression of infection, re-interventions, late mortality, and correlation to antibiotic duration pre- and post-procedure., Results: Thirty-four endovascular aortic procedures were performed for MAA, excluding aorto-enteric fistulas, inflammatory aneurysms, and infected grafts without a new aneurysm. Seventy-six percent of these were thoracic and 24% abdominal. The technical success was 100%. Additional procedures were undertaken in four patients with two requiring a further endovascular procedure. There were two inpatient aneurysm-related mortalities and no inpatient conversions to open repair. The 30-day re-admission and re-intervention rate was 0%. Blood cultures were positive in 45%. There were no secondary graft infections., Conclusion: This is the largest European single-centre study. It supports endovascular management of MAA as a lower-risk alternative to open surgery with the majority of patients presenting acutely, later in life and requiring emergency management., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Objective : To review the outcomes of central venoplasty in the treatment of symptomatic central vein stenosis in patients undergoing haemodialysis via an ipsilateral arteriovenous fistula (AVF). Methods : Data were collected retrospectively, and included all the consecutive cases of central venoplasty between January 2008 and December 2015. Results : A total of 132 central venoplasties in 76 patients were performed, with incidence of symptomatic central vein stenosis at 7.4%. Of the patients, 66% were male and the mean age was 61 years. The most frequent indication was decreased dialysis access flow rates (58%) and 52% of all the patients had symptoms of upper limb swelling. The patients who had previous ipsilateral tunneled internal jugular vein dialysis catheters made up 58% of the patients. The mean time from AVF creation to first central venoplasty was 24 months, and 74% of the cases required a second central venoplasty and the mean time to second venoplasty was 7 months. The overall post intervention assisted primary patency rate was 87%, 74%, 63%, and 42% at 6, 12, 18, and 24 months respectively. Statistically significant differences were found in primary assisted patency (p=0.025) and time to second procedure (p=0.039) comparing those with and without a history of ipsilateral tunneled dialysis catheter. Conclusion : Central venoplasty is technically feasible with low procedural risk. The maintenance of the AVF patency usually requires multiple procedures at average interval of 7 months. Patients with a history of upper limb tunneled dialysis catheter ipsilateral to the side of central vein stenosis or AVF have a less favorable outcome compared to those without.

Multidrug resistance (MDR) represents a major hindrance to the efficacy of cancer chemotherapeutics. While surgical resection, radiation, and chemotherapy can be used to reduce tumor size, the subsequent appearance of drug resistant cells is a frequent problem. One of the main contributors to the development of MDR is increased expression of multi-drug resistant protein 1 (MDR1), also known as P-glycoprotein (P-gp). P-gp is a membrane-associated efflux pump that can efficiently remove internalized taxane-base chemotherapeutics thus preventing drug accumulation and maintaining cellular viability. Consequently, investigation into the molecular mechanisms responsible for regulation of P-gp expression is necessary to facilitate treatment of MDR tumors. Using molecular and biochemical approaches, we identified that the micro-RNA, miRNA149, contributes to the development of MDR within malignant mesothelioma cells by regulating the expression of MDR1.

Internal herniation following laparoscopic surgery is rare. We present a case of small bowel obstruction secondary to internal herniation in a 76-year-old male patient. Presentation was on postoperative day 28 following transperitoneal laparoscopic radical left nephrectomy for suspected renal carcinoma. The herniation was through a defect in the large bowel mesentery identified at exploratory laparotomy. To date, 10 cases of internal herniation following laparoscopic nephrectomy have been described in the literature. Two cases were managed laparoscopically and the remainder by laparotomy. One case required resection of an ischaemic portion small bowel and the remainder were managed by reduction of the hernia and closure of the defect. Internal herniation is rare but carries significant morbidity. It must be considered in cases presenting with obstructive symptoms after laparoscopic nephrectomy. Early CT scanning and prompt surgical management are hallmarks of best management.

Omental torsion is a rare cause of acute abdominal pain. We report a case of omental torsion in a 7-year-old girl, who presented with right iliac fossa pain. The patient underwent an open appendicectomy, during which a normal appendix was identified and a diagnosis of omental torsion was made. The affected segment of omentum was resected along with the appendix. The patient made an uncomplicated recovery and was discharged on day 1 postoperatively. A normal appendix in the presence of omental torsion is found in 0.1% of all appendicectomies in children. We suggest routine visualisation of the omentum in the presence of a normal appendix during appendicectomy., (2016 BMJ Publishing Group Ltd.)

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether dialysis-dependent patients with upper limb arterio-venous fistulae (AVFs) undergoing coronary artery bypass grafting should avoid having ipsilateral in situ internal mammary artery (IMA) grafts. A literature search performed yielded 28 peer reviewed articles, of which 21 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The papers identified included 478 patients, of whom 219 had in situ IMA grafts with ipsilateral upper limb arterio-venous fistulae. There was a substantial variation between the papers, from single case reports to small retrospective cohort studies, but no randomized, controlled trials. The largest retrospective study included 155 patients and followed up for up to 5 years. Methods used to determine coronary steal included clinical assessment, electrocardiogram or echocardiographic changes, Doppler ultrasound of mammary arteries and angiography. The aggregate evidence suggested that 61 of the 219 patients with ipsilateral IMA grafts developed some clinical or physiological evidence of malperfusion during the use of the AVFs for dialysis. Comparisons with the contralateral IMA suggested that 27 of the 61 patients suffered similar problems when dialysis was applied. A number of studies used controls, including in situ right internal mammary artery (RIMA) flow and patients not on dialysis. In total, 32 patients had their in situ RIMA flow measurements studied, of which none showed any statistically significant flow alteration. While further strong evidence to demonstrate long-term outcomes is required, we recommend the avoidance, where possible, of ipsilateral in situ IMA grafts in patients with an upper limb AVF. There is sufficient experimental and anecdotal evidence to suggest that steal occurs and that in some patients, this has clinical implications on both morbidity and mortality. In this scenario, the use of the contralateral mammary is strongly advocated to maximize the patency of grafts in an already high-risk population.