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1.
Vet Pathol ; : 3009858241270000, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39143918

RESUMEN

Polyglucosan bodies are accumulations of insoluble glucose polymers and proteins that form intracytoplasmic inclusions in the brain, large numbers of which can be indicative of neurodegenerative diseases such as Lafora disease. Montserrat orioles (Icterus oberi) are an icterid passerine endemic to Montserrat with conservation populations maintained in captivity abroad. We demonstrate that polyglucosan bodies are unusually abundant in the cerebellar molecular and Purkinje cell layers and cerebellar peduncles of captive-bred and wild-caught Montserrat orioles. The bodies are periodic acid-Schiff positive and diastase resistant and label with concanavalin A and for ubiquitin, consistent with those seen in humans. We found no association of the polyglucosan bodies with concurrent neurological lesions or clinical signs, nor with EPM2A and EPM2B gene mutations associated with Lafora disease. We conclude that an abundance of cerebellar polyglucosan bodies may be a normal finding in aged Montserrat orioles and not a threat to the captive breeding population.

2.
Glomerular Dis ; 4(1): 129-136, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39144474

RESUMEN

Introduction: Rituximab (RTX) has been reported as an effective treatment alternative in primary forms of minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) associated with steroid dependence and frequent relapses. However, the optimal RTX regimen and the outcomes of further doses of RTX remain unclear. This study aimed to evaluate the use of induction and maintenance RTX therapy for adults with primary podocytopathies. Methods: We performed a retrospective case series on adult patients with steroid-dependent podocytopathies who received an induction RTX therapy. Maintenance therapy was performed at physician's discretion. Remission and relapse rates, concomitant corticosteroids and immunosuppressants use, B-cell depletion and adverse events were analyzed. Results: Fourteen patients (mean age at start of RTX 29.1 ± 21.9 years) with MCD (n = 7) or FSGS (n = 7) were treated with 2 doses of 1,000 mg 2 weeks apart (n = 13) or four doses of 375 mg/m2 (n = 1) of RTX. At last follow-up (mean 47.3 ± 101.7 months), 10 patients were in complete remission and two remained in partial remission. A reduction in the number of relapses, number of patients under corticosteroids and immunosuppressants, and dose of prednisolone was observed when compared to baseline (14 [100%] vs. 5 [35.7%]; 8/14 [57.1%] vs. 4/12 [33.3%]; 13/14 [92.9%] vs. 7/12 [58.3%]; 20 mg/day vs. 5.25 mg/day, respectively). Maintenance RTX therapy was used in 6 patients, with sustained complete remission. Infusion reactions were observed in 4 patients (one required treatment withdrawal). Conclusions: Our findings support the use of RTX for a steroid-free remission in podocytopathies and suggest that maintenance RTX is well-tolerated and associated with prolonged remission. Further studies are needed to confirm its efficacy and safety and establish the optimal induction and maintenance RTX regimen in steroid-dependent podocytopathies.


Rituximab (RTX) seems to be an effective treatment alternative in primary forms of MCD and FSGS, particularly in cases of steroid dependence and frequent relapses. Our findings support the use of RTX for a steroid-free remission in podocytopathies and suggest that maintenance RTX is well-tolerated and associated with prolonged remission. Further studies are needed to confirm its efficacy and safety and establish the optimal induction and maintenance RTX regimen in steroid-dependent podocytopathies.

3.
Nurse Educ Today ; 141: 106310, 2024 10.
Artículo en Inglés | MEDLINE | ID: mdl-39029414

RESUMEN

BACKGROUND: Entrepreneurship education is commonly incorporated into areas beyond nursing. However, advocating for curricular changes is necessary in a generation that seeks new learning styles and has different preferences and needs. Entrepreneurship has been identified as a valuable subject to be incorporated into nursing education, as it aligns with the foundational principles of Nursing as a science. AIM: To examine the state of knowledge regarding the entrepreneurship education of undergraduate nursing students. DESIGN: A scoping review was conducted following JBI and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. METHODS: The searches were performed on July 19th, 2023, in MEDLINE via PubMed; ISI Web of Science; EBSCOhost CINAHL; Embase; Scopus; BVShost LILACS; and ProQuest. Grey literature was searched on Google Scholar. Records examining the entrepreneurship education of nursing students were included. RESULTS: The searches resulted in 17 records, 15 of which were from databases and two of which were identified via other methods. Although entrepreneurship education has increased over the years, the incorporation of diverse teaching modalities as a transformative and innovative educational strategy is still not a reality for many undergraduate nursing students worldwide. The findings highlight that entrepreneurship education is incorporated theoretically into mandatory courses with curricular components related to administration and health services management. CONCLUSIONS: Entrepreneurship education can pivot nursing education and drive change in educational strategy while maintaining the fundamentals of nursing education. With entrepreneurship education, nursing students envision professional identity values, such as leadership, critical thinking, and political development. When understanding their political role, nursing students can exercise leadership to think critically outside the box and challenge the status quo.


Asunto(s)
Curriculum , Bachillerato en Enfermería , Emprendimiento , Estudiantes de Enfermería , Emprendimiento/tendencias , Humanos , Bachillerato en Enfermería/tendencias , Bachillerato en Enfermería/métodos , Curriculum/tendencias
4.
Omega (Westport) ; : 302228241259647, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38844415

RESUMEN

Background: Research has predominantly focused on the post-traumatic consequences of grief. Less is known about the factors associated with the capacity for recovery and growth. Objective: The main goal of this study is to analyse the mediating role of coping strategies in the relationship between the impact of the event and posttraumatic growth, considering the degree of kinship and the cause of death. Methods: This exploratory and correlational study, which used a cross-sectional design, involved a community sample of 889 adults who had lost a loved one. Results: Emotion and problem-focused coping strategies mediate the relationship between the impact of loss and posttraumatic growth, specifically when a spouse or a child dies. Conclusions: Individuals who experience greater suffering also undergo higher levels of post-traumatic growth. Coping strategies are crucial in post-trauma reconstruction and growth. Furthermore, the degree of kinship and the cause of death are decisive factors.

5.
Sci Rep ; 14(1): 12484, 2024 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-38816497

RESUMEN

Autism spectrum disorders (ASDs) are known to present sex-specific differences. At the same time, understanding how maternal behaviours are affected by pathogenic mutations is crucial to translate research efforts since rearing may recursively modulate neurodevelopment phenotype of the progeny. In this work, we focused on the effects of Gprasp2 deletion in females and its impact in progeny care and development. Female mice, wild-type (WT), Gprasp2+/- (HET) or Gprasp2-/- (KO) mutants and their progeny were used and behavioural paradigms targeting anxiety, memory, maternal care, and other social behaviours were performed. Analysis of communication was carried out through daily recordings of ultrasonic vocalizations in isolated pups and cross-fostering experiments were performed to understand the effect of maternal genotype in pup development. We found that Gprasp2-/- females presented striking impairments in social and working memory. Females also showed disruptions in maternal care, as well as physiological and molecular alterations in the reproductive system and hypothalamus, such as the structure of the mammary gland and the expression levels of oxytocin receptor (OxtR) in nulliparous versus primiparous females. We observed alterations in pup communication, particularly a reduced number of calls in Gprasp2 KO pups, which resulted from an interaction effect of the dam and pup genotype. Cross-fostering mutant pups with wild-type dams rescued some of the early defects shown in vocalizations, however, this effect was not bidirectional, as rearing WT pups with Gprasp2-/- dams was not sufficient to induce significant phenotypical alterations. Our results suggest Gprasp2 mutations perturb social and working memory in a sex-independent manner, but impact female-specific behaviours towards progeny care, female physiology, and gene expression. These changes in mutant dams contribute to a disruption in early stages of progeny development. More generally, our results highlight the need to better understand GxE interactions in the context of ASDs, when female behaviour may present a contributing factor in postnatal neurodevelopmental trajectory.


Asunto(s)
Conducta Materna , Conducta Social , Animales , Femenino , Masculino , Ratones , Trastorno del Espectro Autista/genética , Conducta Animal , Eliminación de Gen , Conducta Materna/fisiología , Ratones Noqueados , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Oxitocina/genética , Vocalización Animal/fisiología , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo
6.
J Vet Intern Med ; 38(4): 2368-2372, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38662636

RESUMEN

Granuloprival degeneration is an uncommon form of cerebellar cortical degeneration (CCD). A 3-month-old Yorkshire Terrier and a 7-month-old Lagotto Romagnolo dog were presented with a history of progressive cerebellar dysfunction including wide-based stance, cerebellar ataxia, intention tremors, and loss of menace response despite normal vision. Magnetic resonance imaging of the brain identified marked diffuse decrease of the cerebellum size. Euthanasia was performed in both cases because of progression of clinical signs. Histopathological examination identified marked diffuse thinning of the granular cell layer with almost complete loss of the granular cell neurons, providing a definitive diagnosis of granuloprival CCD. Granuloprival CCD should be considered as a differential diagnosis in Yorkshire Terrier and Lagotto Romagnolo dogs with post-natal progressive clinical signs of cerebellar dysfunction.


Asunto(s)
Enfermedades de los Perros , Animales , Perros , Enfermedades de los Perros/patología , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/diagnóstico por imagen , Imagen por Resonancia Magnética/veterinaria , Masculino , Corteza Cerebelosa/patología , Femenino
8.
Neurochem Res ; 49(7): 1677-1686, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38451434

RESUMEN

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease and the most common movement disorder. Although PD etiology is not fully understood, alpha (α)-synuclein is a key protein involved in PD pathology. MicroRNAs (miRNA), small gene regulatory RNAs that control gene expression, have been identified as biomarkers and potential therapeutic targets for brain diseases, including PD. In particular, miR-124 is downregulated in the plasma and brain samples of PD patients. Recently we showed that the brain delivery of miR-124 counteracts 6-hydroxydopamine-induced motor deficits. However, its role in α-synuclein pathology has never been addressed. Here we used paraquat (PQ)-induced rat PD model to evaluate the role of miR-124-3p in α-synuclein accumulation and dopaminergic neuroprotection. Our results showed that an intranigral administration of miR-124-3p reduced the expression and aggregation of α-synuclein in the substantia nigra (SN) of rats exposed to PQ. NADPH oxidases (NOX), responsible for reactive oxygen species generation, have been considered major players in the development of α-synuclein pathology. Accordingly, miR-124-3p decreased protein expression levels of NOX1 and its activator, small GTPase Rac1, in the SN of PQ-lesioned rats. Moreover, miR-124-3p was able to counteract the reduced levels of pituitary homeobox 3 (PITX3), a protein required for the dopaminergic phenotype, induced by PQ in the SN. This is the first study showing that miR-124-3p decreases PQ-induced α-synuclein levels and the associated NOX1/Rac1 signaling pathway, and impacts PITX3 protein levels, supporting the potential of miR-124-3p as a disease-modifying agent for PD and related α-synucleinopathies.


Asunto(s)
MicroARNs , Paraquat , alfa-Sinucleína , Animales , MicroARNs/metabolismo , alfa-Sinucleína/metabolismo , Paraquat/toxicidad , Masculino , Ratas , Ratas Wistar , Enfermedad de Parkinson/metabolismo , Sustancia Negra/metabolismo , Sustancia Negra/efectos de los fármacos , Modelos Animales de Enfermedad , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson Secundaria/metabolismo , Ratas Sprague-Dawley
9.
Gels ; 10(2)2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38391453

RESUMEN

This study deals with the preparation of adsorbents from a commercial xerogel by chemically modifying its surface with concentrated mineral acids and alkali metal chlorides, their physicochemical characterization, and their use as adsorbents for gallic acid in aqueous solution. Although there are publications on the use of carbon xerogels as adsorbents, we propose and study simple modifications that can change their chemical properties and, therefore, their performance as adsorbents. The adsorbate of choice is gallic acid and, to our knowledge, there is no history of its adsorption with carbon xerogels. The prepared adsorbents have a high specific surface area (347-563 m2 g-1), better pore development for samples treated with alkali metal chlorides than with mineral acids, and are more acidic than the initial xerogel (p.z.c range 2.49-6.87 vs. 7.20). The adsorption equilibrium is reached in <16 h with a kinetic constant between 0.018 and 0.035 h-1 for the pseudo-second-order model. The adsorption capacity, according to the Langmuir model, reaches 62.89 to 83.33 mg g-1. The adsorption properties of the commercial xerogel improved over a wide range of pH values and temperatures. The experimental results indicate that the adsorption process is thermodynamically favored.

10.
Sci Total Environ ; 920: 170989, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38365038

RESUMEN

Pentabromodiphenyl ether (BDE-99) and bisphenol A (BPA) are synthetic organic compounds present in several daily use products. Due to their physicochemical properties, they are ubiquitously present in aquatic ecosystems and considered highly persistent. Recent evidence has confirmed that both emerging compounds are toxic to humans and terrestrial mammals eliciting a wide range of detrimental effects at endocrine and immune levels. However, the ecotoxicological responses that they can trigger in vertebrate marine species have not yet been established. Hence, this study aimed to investigate the ecotoxicological responses of juvenile Sparus aurata upon chronic (28 days) dietary exposure to BDE-99 and BPA (alone and combined) following an integrated multi-biomarker approach that combined fitness indicators (Fulton's K and splenosomatic indexes) with endocrine [cortisol, 17ß-estradiol (E2), 11-ketotestosterone (11-KT) concentrations] and immune (peroxidase and antiprotease activities) endpoints in fish plasma, and oxidative stress [superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) activities, and lipid peroxidation (LPO)] endpoints in the fish spleen. The mixture of BDE-99 and BPA yielded the highest IBR index value in both plasma and spleen biomarkers, therefore, suggesting that the effects of these compounds are more severe when they act together. Endocrine biomarkers were the most responsive in the three contaminated treatments. Fitness indicators were not affected by the individual nor the interactive effects of BDE-99 and BPA. These findings highlight the relevance of accounting for the interactive effects of emerging chemical contaminants and integrating responses associated with distinct biological pathways when investigating their impacts on marine life, as such a multi-biomarker approach provides a broader, more realistic and adequate perspective of challenges faced by fish in a contaminated environment.


Asunto(s)
Compuestos de Bencidrilo , Éteres Difenilos Halogenados , Fenoles , Dorada , Animales , Humanos , Dorada/metabolismo , Ecosistema , Estrés Oxidativo , Biomarcadores/metabolismo , Mamíferos/metabolismo
11.
Contemp Clin Trials Commun ; 37: 101255, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38292216

RESUMEN

Background: Despite efforts to increase diversity in neuroscience trials, racial and ethnic minority groups remain underrepresented. Disparities in clinical trial participation could reflect unequal opportunities to participate and may contribute to decreased generalizability of findings and failure to identify important differences in efficacy and safety outcomes. Methods: We retrospectively reviewed the F. Hoffmann-La Roche database for global, multicenter, neuroscience clinical trials from February 2016 to February 2021 and summarized and stratified race and ethnicity distributions by clinical trial therapeutic area and by country. These data were then compared to national population data for each study's targeted age group (available for studies conducted in the US, Canada, and the UK). The underrepresentation or overrepresentation of each racial and ethnic group was summarized. Results: The analysis population included 8015 participants from 47 countries. Globally, 85.6 % of participants were White, 7.1 % were Asian, 1.6 % were Black, 1.3 % were American Indian or Alaska Native, less than 0.1 % were Native Hawaiian or other Pacific Islander, 0.7 % were of multiple races, and 3.6 % were of other/unknown race. White individuals predominated in all but one trial. Black individuals were underrepresented in all trials but one. Asian individuals were overrepresented in approximately 20 % of trials. In the US, 7.3 % of participants were of Hispanic or Latino ethnicity vs 16.4 % of the US population. Conclusion: The findings and learnings from this summary and analysis demonstrate the need for continued awareness and new approaches in designing studies that reflect population diversity.

12.
J Neurosurg ; 141(1): 79-88, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38181499

RESUMEN

OBJECTIVE: The use of intraoperative techniques to detect residual tumors has recently become increasingly important. Intraoperative MRI has long been considered the gold standard; however, it is not widely used because of high equipment costs and long acquisition times. Consequently, real-time intraoperative ultrasound (ioUS), which is much less expensive than MRI, has gained popularity. The aim of the present study was to evaluate the capacity of ioUS to accurately determine the primary tumor volume and detect residual tumors. METHODS: A prospective study of adult patients who underwent surgery for intra-axial brain tumors between November 2017 and October 2020 was performed. Navigated intraoperative ultrasound (nioUS) of the brain was used to guide tumor resection and to detect the presence of residual disease. Both convex (5-8 MHz) and linear array (6-13 MHz) probes were used. Tumor volume and residual disease were measured with nioUS and compared with MR images. A linear regression model based on a machine learning pipeline and a Bland-Altman analysis were used to assess the accuracy of nioUS versus MRI. RESULTS: Eighty patients (35 females and 45 males) were included. The mean age was 58 years (range 25-80 years). A total of 88 lesions were evaluated; there were 64 (73%) gliomas, 19 (21.6%) metastases, and 5 (5.7%) other tumors, mostly located in the frontal (41%) and temporal (27%) lobes. Most of the tumors (75%) were perfectly visible on ioUS (grade 3, Mair grading system), except for those located in the insular lobe (grade 2). The regression model showed a nearly perfect correlation (R2 = 0.97, p < 0.001) between preoperative tumor volumes from both MRI and nioUS. Ultrasonographic visibility significantly influenced this correlation, which was stronger for highly visible (grade 3) tumors (p = 0.01). For residual tumors, the correlation between postoperative MRI and nioUS was weaker (R2 = 0.78, p < 0.001) but statistically significant. The Bland-Altman analysis showed minimal bias between the two techniques for pre- and postoperative scenarios, with statistically significant results for the preoperative concordance. CONCLUSIONS: The authors' findings show that most brain tumors are well delineated by nioUS and almost perfectly correlated with MRI-based measurements both pre- and postoperatively. These data support the hypothesis that nioUS is a reliable intraoperative technique that can be used for real-time monitoring of brain tumor resections and to perform volumetric analysis of residual disease.


Asunto(s)
Neoplasias Encefálicas , Imagen por Resonancia Magnética , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Adulto , Imagen por Resonancia Magnética/métodos , Estudios Prospectivos , Anciano de 80 o más Años , Carga Tumoral , Neoplasia Residual/diagnóstico por imagen , Neuronavegación/métodos , Glioma/diagnóstico por imagen , Glioma/cirugía , Glioma/patología , Procedimientos Neuroquirúrgicos/métodos , Monitoreo Intraoperatorio/métodos
13.
Neuron ; 111(21): 3435-3449.e8, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37918358

RESUMEN

Interleukin-4 (IL-4) is a type 2 cytokine with pleiotropic functions in adaptive immunity, allergies, and cognitive processes. Here, we show that low levels of IL-4 in the early postnatal stage delineate a critical period in which microglia extensively prune cerebellar neurons. Elevating the levels of this cytokine via peripheral injection, or using a mouse model of allergic asthma, leads to defective pruning, permanent increase in cerebellar granule cells, and circuit alterations. These animals also show a hyperkinetic and impulsive-like phenotype, reminiscent of attention-deficit hyperactivity disorder (ADHD). These alterations are blocked in Il4rαfl/fl::Cx3cr1-CreER mice, which are deficient in IL-4 receptor signaling in microglia. These findings demonstrate a previously unknown role for IL-4 during a neuroimmune critical period of cerebellar maturation and provide a first putative mechanism for the comorbidity between allergic disease and ADHD observed in humans.


Asunto(s)
Interleucina-4 , Microglía , Animales , Humanos , Cerebelo , Encéfalo , Citocinas
14.
Am J Bot ; 110(11): e16249, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37792319

RESUMEN

PREMISE: Bryophytes form a major component of terrestrial plant biomass, structuring ecological communities in all biomes. Our understanding of the evolutionary history of hornworts, liverworts, and mosses has been significantly reshaped by inferences from molecular data, which have highlighted extensive homoplasy in various traits and repeated bursts of diversification. However, the timing of key events in the phylogeny, patterns, and processes of diversification across bryophytes remain unclear. METHODS: Using the GoFlag probe set, we sequenced 405 exons representing 228 nuclear genes for 531 species from 52 of the 54 orders of bryophytes. We inferred the species phylogeny from gene tree analyses using concatenated and coalescence approaches, assessed gene conflict, and estimated the timing of divergences based on 29 fossil calibrations. RESULTS: The phylogeny resolves many relationships across the bryophytes, enabling us to resurrect five liverwort orders and recognize three more and propose 10 new orders of mosses. Most orders originated in the Jurassic and diversified in the Cretaceous or later. The phylogenomic data also highlight topological conflict in parts of the tree, suggesting complex processes of diversification that cannot be adequately captured in a single gene-tree topology. CONCLUSIONS: We sampled hundreds of loci across a broad phylogenetic spectrum spanning at least 450 Ma of evolution; these data resolved many of the critical nodes of the diversification of bryophytes. The data also highlight the need to explore the mechanisms underlying the phylogenetic ambiguity at specific nodes. The phylogenomic data provide an expandable framework toward reconstructing a comprehensive phylogeny of this important group of plants.


Asunto(s)
Briófitas , Hepatophyta , Filogenia , Briófitas/genética , Plantas/genética , Hepatophyta/genética
15.
Brain Circ ; 9(2): 94-98, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37576580

RESUMEN

BACKGROUND: The incidence of spontaneous intracerebral hemorrhage (SICH) is highest in very old elderlies (≥75 years). The increasing use of antithrombotic drugs is shifting the epidemiology of SICH towards predominance of lobar subtype, suggesting an incremented propensity of bleeding associated with underlying cerebral amyloid angiopathy. With population aging and antithrombotic use, a parallel raise of proportion of lobar SICH is occurring. Improvement of prognostication in this specific age group and SICH type is needed. Routine blood biomarkers can contribute to prediction of short-term mortality after SICH. OBJECTIVE: Our aim was to investigate the contribution of routine blood biomarkers for short-term mortality (30-days) in elderly patients with lobar SICH. METHODS: Retrospective analysis of consecutive 130 patients with ≥ 75 years and lobar SICH. The outcome was 30-day mortality. Logistic regression analysis was used to investigate whether admission routine biomarkers can be used as predictors. RESULTS: The case fatality was 40.8%. Admission glycaemia level, neutrophil to lymphocyte ratio and mean platelet volume were significantly different between groups (p = 0.001, p = 0.024, p = 0.038, respectively). There was no significant difference in all other routine biomarkers. On multivariate analysis, admission higher mean BG level (odds ratio [OR]: 1.010, 95% confidence interval [CI]: 1.001-1.019, p = 0.026) and neutrophil to lymphocyte ratio (OR: 1.070, 95% CI: 1.008-1.136, p = 0.027) emerged as predictors. CONCLUSION: In very old patients with lobar SICH, higher BG level and neutrophil to lymphocyte ratio are associated with increased risk of short-term death.

16.
Front Mol Neurosci ; 16: 1231659, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37588057

RESUMEN

Introduction: In Krabbe disease (KD), mutations in ß-galactosylceramidase (GALC), a lysosomal enzyme responsible for the catabolism of galactolipids, leads to the accumulation of its substrates galactocerebroside and psychosine. This neurologic condition is characterized by a severe and progressive demyelination together with neuron-autonomous defects and degeneration. Twitcher mice mimic the infantile form of KD, which is the most common form of the human disease. The Twitcher CNS and PNS present demyelination, axonal loss and neuronal defects including decreased levels of acetylated tubulin, decreased microtubule stability and impaired axonal transport. Methods: We tested whether inhibiting the α-tubulin deacetylase HDAC6 with a specific inhibitor, ACY-738, was able to counteract the early neuropathology and neuronal defects of Twitcher mice. Results: Our data show that delivery of ACY-738 corrects the low levels of acetylated tubulin in the Twitcher nervous system. Furthermore, it reverts the loss myelinated axons in the sciatic nerve and in the optic nerve when administered from birth to postnatal day 9, suggesting that the drug holds neuroprotective properties. The extended delivery of ACY-738 to Twitcher mice delayed axonal degeneration in the CNS and ameliorated the general presentation of the disease. ACY-738 was effective in rescuing neuronal defects of Twitcher neurons, stabilizing microtubule dynamics and increasing the axonal transport of mitochondria. Discussion: Overall, our results support that ACY-738 has a neuroprotective effect in KD and should be considered as an add-on therapy combined with strategies targeting metabolic correction.

17.
J Vasc Access ; : 11297298231186373, 2023 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-37475542

RESUMEN

BACKGROUND: Planning for vascular access (VA) creation is essential in pre-dialysis patients although optimal timing for VA referral and placement is debatable. Guidelines suggest referral when eGFR is 15-20 mL/min/1.73 m2. This study aimed to validate the use of kidney failure risk equation (KFRE) in VA planning. METHODS: Retrospective analysis of all adult patients with CKD who were referred for first VA placement, namely AVF or AVG, at a tertiary center, between January 2018 and December 2019. The four-variable KFRE was calculated. Start of KRT, mortality, and VA placement were assessed in a 2-year follow-up. We used Cox regression to predict KRT start and calculated the ROC curve. RESULTS: 256 patients were included and 64.5% were male, mean age was 70.4 ± 12.9 years and mean eGFR was 16.09 ± 10.43 mL/min/1.73 m2. One hundred fifty-nine patients required KRT (62.1%) and 72 (28.1%) died in the 2-year follow-up. The KFRE accurately predicted KRT start within 2-years (38.3 ± 23.8% vs 17.6 ± 20.9%, p < 0.001; HR 1.05 95% CI (1.06-1.12), p < 0.001), with an auROC of 0.788 (p < 0.001, 95% CI (0.733-0.837)). The optimal KFRE cut-off was >20%, with a HR of 9.2 (95% CI (5.06-16.60), p < 0.001). Patients with KFRE ⩾ 20% had a significant lower mean time from VA consult to KRT initiation (10.8 ± 9.4 vs 15.6 ± 10.3 months, p < 0.001). On a sub-analysis of patients with an eGFR < 20 mL/min/1.73 m2, a KFRE ⩾ 20% was also a significant predictor of 2-year start of KRT, with an HR of 6.61 (95% CI (3.49-12.52), p < 0.001). CONCLUSION: KFRE accurately predicted 2-year KRT start in this cohort of patients. A KFRE ⩾ 20% can help to establish higher priority patients for VA placement. The authors suggest referral for VA creation when eGFR < 20 mL/min/1.73 m2 and KFRE ⩾ 20%.

18.
Molecules ; 28(12)2023 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-37375324

RESUMEN

A new adsorbent material was prepared by coating an activated carbon with hydrothermal carbon obtained from sucrose. The material obtained has different properties from the sum of the properties of the activated carbon and the hydrothermal carbon, which shows that a new material was obtained. It has a high specific surface area (1051.9 m2 g-1) and is slightly more acidic than the starting activated carbon (p.z.c.-point of zero charge 8.71 vs. 9.09). The adsorptive properties of a commercial carbon (Norit RX-3 Extra) were improved over a wide pH and temperature range. The capacity values of the monolayer according to Langmuir's model reached 588 mg g-1 for the commercial product and 769 mg g-1 for the new adsorbent.

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