Restoring a balanced pool of host-derived and microbiota-derived ligands of the aryl hydrocarbon receptor is beneficial after stroke.

Background: Stroke is a major cause of morbidity and mortality, and its incidence increases with age. While acute therapies for stroke are currently limited to intravenous thrombolytics and endovascular thrombectomy, recent studies have implicated an important role for the gut microbiome in post-stroke neuroinflammation. After stroke, several immuno-regulatory pathways, including the aryl hydrocarbon receptor (AHR) pathway, become activated. AHR is a master regulatory pathway that mediates neuroinflammation. Among various cell types, microglia (MG), as the resident immune cells of the brain, play a vital role in regulating post-stroke neuroinflammation and antigen presentation. Activation of AHR is dependent on a dynamic balance between host-derived and microbiota-derived ligands. While previous studies have shown that activation of MG AHR by host-derived ligands, such as kynurenine, is detrimental after stroke, the effects of post-stroke changes in microbiota-derived ligands of AHR, such as indoles, is unknown. Our study builds on the concept that differential activation of MG AHR by host-derived versus microbiome-derived metabolites affects outcomes after ischemic stroke. We examined the link between stroke-induced dysbiosis and loss of essential microbiota-derived AHR ligands. We hypothesize that restoring the balance between host-derived (kynurenine) and microbiota-derived (indoles) ligands of AHR is beneficial after stroke, offering a new potential avenue for therapeutic intervention in post-stroke neuroinflammation. Method: We performed immunohistochemical analysis of brain samples from stroke patients to assess MG AHR expression after stroke. We used metabolomics analysis of plasma samples from stroke and non-stroke control patients with matched comorbidities to determine the levels of indole-based AHR ligands after stroke. We performed transient middle cerebral artery occlusion (MCAO) in aged (18 months) wild-type (WT) and germ-free (GF) mice to investigate the effects of post-stroke treatment with microbiota-derived indoles on outcome. To generate our results, we employed a range of methodologies, including flow cytometry, metabolomics, and 16S microbiome sequencing. Results: We found that MG AHR expression is increased in human brain after stroke and after ex vivo oxygen-glucose deprivation and reperfusion (OGD/R). Microbiota-derived ligands of AHR are decreased in the human plasma at 24 hours after ischemic stroke. Kynurenine and indoles exhibited differential effects on aged WT MG survival after ex vivoOGD/R. We found that specific indole-based ligands of AHR (indole-3-propionic acid and indole-3-aldehyde) were absent in GF mice, thus their production depends on the presence of a functional gut microbiota. Additionally, a time-dependent decrease in the concentration of these indole-based AHR ligands occurred in the brain within the first 24 hours after stroke in aged WT mice. Post-stroke treatment of GF mice with a cocktail of microbiota-derived indole-based ligands of AHR regulated MG-mediated neuroinflammation and molecules involved in antigen presentation (increased CD80, MHC-II, and CD11b). Post-stroke treatment of aged WT mice with microbiota-derived indole-based ligands of AHR reduced both infarct volume and neurological deficits at 24 hours. Conclusion: Our novel findings provide compelling evidence that the restoration of a well-balanced pool of host-derived kynurenine-based and microbiota-derived indole-based ligands of AHR holds considerable therapeutic potential for the treatment of ischemic stroke.

Calcifilaxis en una paciente en hemodiálisis: complicación grave con elevada mortalidad / Calciphylaxis in a hemodialysis patient: a serious complication with high mortality

Descripción del caso: Paciente con enfermedad renal crónica terminal en tratamiento de hemodiálisis desde hace 1 año. Acude a sesión de hemodiálisis refiriendo lesiones cutáneas muy dolorosas con aspecto necrótico de 2 semanas de evolu-ción en extremidades inferiores distales sugestivas de calcifi-laxis. Dados los antecedentes clínicos de fibrilación auricular paroxística, anticoagulada con acenocumarol y los factores de riesgo que presenta, se inician medidas inmediatas dado el mal pronóstico de dicha enfermedad. Descripción/evaluación del plan de cuidados: Se suspende tratamiento con acenocumarol iniciando anticoagulación con heparina de bajo peso molecular, también se suspenden los suplementos de vitamina D. Se inicia administración de bifos-fonatos como inhibidores del calcio, de tiosulfato de sodio como vasodilatador y quelante del fósforo. Se instaura pauta de analgesia siendo uno de los objetivos más importantes del plan de cuidados, el control del dolor, con la administración de opiáceos, antiinflamatorios no esteroideos o mórficos. Aunque fue de difícil manejo, el papel de enfermería ha sido fundamental para procurar el máximo confort. También fue muy importante la vigilancia y el cuidado de las lesiones para prevenir infecciones y controlar la enfermedad observándose una adversa y rápida evolución a pesar de las terapias coad-yuvantes, puesto que cuando se diagnosticó ya presentaba lesiones necróticas. Conclusiones: La calcifilaxis es una complicación poco fre-cuente pero grave que suele observarse en pacientes con enfermedad renal crónica, sobre todo en hemodiálisis. Eltratamiento es multidisciplinar y es importante identificar precozmente a estos pacientes. Desgraciadamente, como en nuestro caso, los resultados no son siempre favorables.(AU)

Case description: Patient with end-stage renal disease undergoing hemodialysis treatment for 1 year. The patient presents to the hemodialysis session with extremely painful necrotic-looking skin lesions on the distal lower extremities, suggestive of calciphylaxis, which have been present for 2 weeks. Given the patient’s medical history of paroxysmal atrial fibrillation and anticoagulation with acenocoumarol, along with the risk factors present, immediate measures are initiated due to the poor prognosis of this condition. Description/evaluation of the care plan: Acenocoumarol treatment is discontinued, and anticoagulation with low molecular weight heparin is initiated. Vitamin D supplements are also discontinued. Bisphosphonates are started as calcium inhibitors, sodium thiosulfate is administered as a vasodilator, and phosphate binder. An analgesic regimen is established, with pain control being one of the most important goals of he care plan. This includes the administration of opioids, nonsteroidal anti-inflammatory drugs, or morphine. Although challenging, the nursing role has been crucial in providing maximum comfort. Close monitoring and wound care are also important to prevent infections and control the disease, although an adverse and rapid progression was observed despite the adjunctive therapies, as necrotic lesions were already present at the time of diagnosis. Conclusions: Calciphylaxis is a rare but serious complication often observed in patients with chronic kidney disease, especially in those undergoing hemodialysis. Treatment is multidisciplinary, and early identification of these patients is important. Unfortunately, as in our case, the outcomes are not always favorable.(AU)

Polyurethane Adhesives with Chemically Debondable Properties via Diels-Alder Bonds.

Covalent adaptable networks (CANs) represent a pioneering advance in polymer science, offering unprecedented versatility in materials design. Unlike conventional adhesives with irreversible bonds, CAN-based polyurethane adhesives have the unique ability to undergo chemical restructuring through reversible bonds. One of the strategies for incorporating these types of reactions in polyurethanes is by functionalisation with Diels-Alder (DA) adducts. By taking advantage of the reversible nature of the DA chemistry, the adhesive undergoes controlled crosslinking and decrosslinking processes, allowing for precise modulation of bond strength. This adaptability is critical in applications requiring reworkability or recyclability, as it allows for easy disassembly and reassembly of bonded components without compromising the integrity of the material. This study focuses on the sustainable synthesis and characterisation of a solvent-based polyurethane adhesive, obtained by functionalising a polyurethane prepolymer with DA diene and dienophiles. The characterisation of the adhesives was carried out using different experimental techniques: nuclear magnetic resonance spectroscopy (NMR), Brookfield viscosity, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and T-peel strength testing of leather/adhesive/rubber joints to determine the adhesive properties, both before and after the application of external stimuli. The conversion of both the DA and retro-Diels-Alder (r-DA) reactions was confirmed by 1H-NMR. The adhesive properties were not altered by the functionalisation of the adhesive prepolymer, showing similar thermal resistance and good rheological and adhesive properties, even exceeding the most demanding technical requirements for upper-to-sole joints in footwear. After the application of an external thermal stimuli, the bonded materials separated without difficulty and without damage, thus facilitating their separation, recovery and recycling.

Organosilicon-Based Plasma Nanocoating on Crust Leather for Water-Repellent Footwear.

In this study, functional nanocoatings for water-repellent footwear leather materials were investigated by chemical plasma polymerisation by implanting and depositing the organosilicon compound hexamethyldisiloxane (HMDSO) using a low-pressure plasma system. To this end, the effect of monomers on leather plasma deposition time was evaluated and both the resulting plasma polymers and the deposited leather samples were characterised using different experimental techniques, such as: Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). In addition, leather samples were tested by standard tests for color change, water resistance, surface wetting resistance and dynamic water contact angle (DWCA). The resulting polysiloxane polymers exhibited hydrophobic properties on leather. Furthermore, these chemical surface modifications created on the substrate can produce water repellent effects without altering the visual leather appearance and physical properties. Both plasma coating treatments and nanocoatings with developed water-repellency properties can be considered as a more sustainable, automated and less polluting alternative to chemical conventional processing that can be introduced into product-finishing processes in the footwear industry.

Hiperpotasemia severa tras realización de ileostomía en un paciente en hemodiálisis crónica / Severe hyperkalaemia after ileostomy in a patient on chronic hemodialysis

Descripción del caso: Paciente que ingresa por anemia y de-terioro de la función renal. Se diagnostica neoplasia de recto infiltrante tras realización de colonoscopia e inicia tratamiento renal sustitutivo tras colocación de catéter temporal. Previa-mente a la realización de la ileostomía se somete a radiotera-pia neoadyuvante. Tres meses después presenta hiperpotase-mia severa persistente. Encontramos pocos casos descritos en la literatura al respecto, pero parece estar relacionado con la interrupción del tránsito intestinal.Descripción/evaluación del plan de cuidados: Se hace refuer-zo dietético, se modifican los parámetros de la hemodiálisis (HD) y se inicia tratamiento con resinas, pero no se norma-liza el potasio hasta el cierre de la ileostomía. Resolver la hi-perpotasemia fue el objetivo imperioso del plan de cuidados, además del manejo de la ansiedad y el apoyo al paciente en el autocuidado de su estoma. Parece ser que la alteración de la homeostasia se debió al déficit de secreción intestinal de potasio en el colon. Se aceleró el proceso de restauración de la continuidad intestinal con el cierre de la ileostomía, confir-mándose la sospecha. Conclusiones: La hiperpotasemia en los pacientes en tratamien-to en hemodiálisis puede estar relacionada con la cirugía de co-lon. Nuestro caso demuestra la importancia de la secreción de potasio en el tracto intestinal para mantener la homeostasis en los pacientes con insuficiencia renal crónica terminal. (AU)

Case description: Patient admitted for anaemia and deterioration of renal function. Infiltrating rectal neoplasia was diagnosed after colonoscopy. Renal replacement therapy was started after placing a tunneled venous catheter. Prior to ileostomy, neoadjuvant radiotherapy was performed. Three months later, persistent severe hyperkalaemia appeared. Few cases have been described in the literature, but there seems to be a relationship with the interruption of intestinal transit.Description/evaluation of the care plan: Dietary reinforce-ment was performed, hemodialysis parameters were modi-fied and treatment with resins was started, but potassium did not normalise until the ileostomy was closed. Resolving the hyperkalaemia was the main focus of the care plan, in addition to anxiety management and supporting the patient in stoma self-care. It was suggested that the alteration of homeosta-sis was due to a deficit of intestinal potassium secretion in the colon. The process of restoring intestinal continuity was accelerated with the closure of the ileostomy, confirming the suspicion.Material and Method: Hyperkalaemia in hemodialysis patients may be related to colon surgery. Our case demonstrates the importance of potassium secretion in the intestinal tract to maintain homeostasis in patients with end-stage renal failure. (AU)

Sustainable Reactive Polyurethane Hot Melt Adhesives Based on Vegetable Polyols for Footwear Industry.

The aim of this work is to develop sustainable reactive polyurethane hot melt adhesives (HMPUR) for footwear applications based on biobased polyols as renewable resources, where ma-croglycol mixtures of polyadipate of 1,4-butanediol, polypropylene and different biobased polyols were employed and further reacted with 4-4'-diphenylmethane diisocyanate. The different reactive polyurethane hot melt adhesives obtained were characterized with different experimental techniques, such as Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), softening temperature and melting viscosity. Finally, their adhesion properties were measured from T-peel tests on leather/HMPUR adhesives/SBR rubber joints in order to establish the viability of the used biobased polyols and the amount of these polyols that could be added to reactive polyurethane hot melt adhesives satisfactorily to meet the quality requirements of footwear joints. All biobased polyols and percentages added to the polyurethane adhesive formulations successfully met the quality requirements of footwear, being comparable to traditional adhesives currently used in footwear joints in terms of final strength. Therefore, these new sustainable polyurethane adhesives can be considered as suitable and sustainable alternatives to the adhesives commonly used in footwear joints.

Hydrophobic Leather Coating for Footwear Applications by a Low-Pressure Plasma Polymerisation Process.

The aim of this work is to develop hydrophobic coatings on leather materials by plasma polymerisation with a low-pressure plasma system using an organosilicon compound, such as hexamethyldisiloxane (HMDSO), as chemical precursor. The hydrophobic coatings obtained by this plasma process were evaluated with different experimental techniques such as Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and standardised tests including colour measurements of the samples, surface coating thickness and water contact angle (WCA) measurements. The results obtained indicated that the monomer had polymerised correctly and completely on the leather surface creating an ultra-thin layer based on polysiloxane. The surface modification produced a water repellent effect on the leather that does not alter the visual appearance and haptic properties. Therefore, the application of the plasma deposition process showed promising results that makes it a more sustainable alternative to conventional functional coatings, thus helping to reduce the use of hazardous chemicals in the finishing process of footwear manufacturing.

Age-dependent involvement of gut mast cells and histamine in post-stroke inflammation.

BACKGROUND: Risk of stroke-related morbidity and mortality increases significantly with age. Aging is associated with chronic, low-grade inflammation, which is thought to contribute to the poorer outcomes after stroke seen in the elderly. Histamine (HA) is a major molecular mediator of inflammation, and mast cells residing in the gut are a primary source of histamine. METHODS: Stroke was induced in male C57BL/6 J mice at 3 months (young) and 20 months (aged) of age. Role of histamine after stroke was examined using young (Yg) and aged (Ag) mice; mice underwent MCAO surgery and were euthanized at 6 h, 24 h, and 7 days post-ischemia; sham mice received the same surgery but no MCAO. In this work, we evaluated whether worsened outcomes after experimental stroke in aged mice were associated with age-related changes in mast cells, histamine levels, and histamine receptor expression in the gut, brain, and plasma. RESULTS: We found increased numbers of mast cells in the gut and the brain with aging. Using the middle cerebral artery occlusion (MCAO) model of ischemic stroke, we demonstrate that stroke leads to increased numbers of gut mast cells and gut histamine receptor expression levels. These gut-centric changes are associated with elevated levels of HA and other pro-inflammatory cytokines including IL-6, G-CSF, TNF-α, and IFN-γ in the peripheral circulation. Our data also shows that post-stroke gut inflammation led to a significant reduction of mucin-producing goblet cells and a loss of gut barrier integrity. Lastly, gut inflammation after stroke is associated with changes in the composition of the gut microbiota as early as 24-h post-stroke. CONCLUSION: An important theme emerging from our results is that acute inflammatory events following ischemic insults in the brain persist longer in the aged mice when compared to younger animals. Taken together, our findings implicate mast cell activation and histamine signaling as a part of peripheral inflammatory response after ischemic stroke, which are profound in aged animals. Interfering with histamine signaling orally might provide translational value to improve stroke outcome.