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2.
Sensors (Basel) ; 24(12)2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38931552

RESUMO

Electric power systems with a high penetration of photovoltaic generation and a relevant fleet of electric vehicles face significant stability challenges, particularly in mountainous areas where the variability of photovoltaic resources is pronounced. This study presents a novel methodology to strategically place electric vehicle aggregators along a feeder. This approach considers electrical variables and the dynamics of cloud movements within the study area. This innovative methodology reduces the substation's power load demand and significantly improves the end user's voltage levels. The improvements in voltage regulation and reduced demand on the substation provide clear benefits, including increased system resilience, better integration of renewable energy sources, and enhanced overall efficiency of the electric grid. These advantages are particularly critical in regions with high levels of photovoltaic generation and are important in promoting sustainable electric vehicle charging infrastructure. When analyzing different load scenarios for the IEEE European Low Voltage Test Feeder system, the consideration of distributed aggregators based on cloud movements decreased the power required at the substation by 21.25%, and the voltage drop in loads was reduced from 6.9% to 4.29%. This research underscores the critical need to consider both the variability and geographical distribution of PV resources in the planning and operation of electrical systems with extensive PV generation.

3.
Transplant Cell Ther ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38851323

RESUMO

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication after both autologous and allogeneic hematopoietic stem cell transplantation (HSCT). However, its characterization after haploidentical HSCT (haplo-HSCT) with post-transplantation cyclophosphamide (PT-Cy) is scarce. This study aimed to describe characteristics and outcomes of patients with SOS/VOD after haplo-HSCT with PT-Cy. We conducted a retrospective study of 797 patients undergoing a haplo-HSCT with PT-Cy between 2007 and 2019 in 9 centers in Spain. SOS/VOD was defined according to modified Seattle, Baltimore, or revised European Society for Blood and Marrow Transplantation (EBMT) criteria. Severity was graded retrospectively according to revised EBMT severity criteria into 4 categories: mild, moderate, severe, and very severe. From a total of 797 haplo-HSCTs performed, 46 patients (5.77%) were diagnosed with SOS/VOD at a median of 19 days (range, 4 to 84 days) after transplantation. Based on revised EBMT severity criteria, the SOS/VOD cases were classified as mild (n = 4; 8.7%), moderate (n = 10; 21.7%), severe (n = 12; 26.1%), and very severe (n = 20; 43.5%). Overall, 30 patients (65%) achieved SOS/VOD complete response, 25 (83%) of whom were treated with defibrotide. Twenty patients (43%) died before day +100 post-HSCT. Death was attributed to SOS/VOD in 11 patients, and 5 patients died of other causes without resolution of SOS/VOD. The incidence of SOS/VOD after haplo-HSCT with PT-Cy was comparable to those reported after HLA-identical HSCT series. Most of the patients developed very severe SOS/VOD according to revised EBMT severity criteria. Despite a promising SOS/VOD complete response (CR) rate (65%), 100-day mortality remained high (43%), indicating that further improvement in the management of this potentially fatal complication is needed.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38686811

RESUMO

BACKGROUND: Postoperative stroke is a potentially devastating neurological complication following surgical revascularization for Moyamoya disease. We sought to evaluate whether peri-operative hemoglobin levels were associated with the risk of early post-operative stroke following revascularization surgery in adult Moyamoya patients. METHODS: Adult patients having revascularization surgeries for Moyamoya disease between 1999-2022 were identified through single institutional retrospective review. Logistic regression analysis was used to test for the association between hemoglobin drop and early postoperative stroke. RESULTS: In all, 106 revascularization surgeries were included in the study. A stroke occurred within 7 days after surgery in 9.4% of cases. There were no significant associations between the occurrence of an early postoperative stroke and patient age, gender, or race. Mean postoperative hemoglobin drop was greater in patients who suffered an early postoperative stroke compared with patients who did not (2.3±1.1 g/dL vs. 1.3±1.1 g/dL, respectively; P=0.034). Patients who experienced a hemoglobin drop post-operatively had 2.03 times greater odds (95% confidence interval, 1.06-4.23; P=0.040) of having a stroke than those whose hemoglobin levels were stable. Early postoperative stroke was also associated with an increase in length of hospital stay (P<0.001), discharge to a rehabilitation facility (P=0.014), and worse modified Rankin scale at 1 month (P=0.001). CONCLUSION: This study found a significant association between hemoglobin drop and early postoperative stroke following revascularization surgery in adult patients with Moyamoya disease. Based on our findings, it may be prudent to avoid hemoglobin drops in Moyamoya patients undergoing surgical revascularization.

9.
J Neurointerv Surg ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38471762

RESUMO

BACKGROUND: Poor venous outflow (VO) profiles are associated with unfavorable outcomes in patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO), despite achieving successful reperfusion. The objective of this study is to assess the association between mortality and prolonged venous transit (PVT), a novel visual qualitative VO marker on CT perfusion (CTP) time to maximum (Tmax) maps. METHODS: We performed a retrospective analysis of prospectively collected data from consecutive adult patients with AIS-LVO with successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b/2c/3). PVT+ was defined as Tmax ≥10 s timing on CTP Tmax maps in at least one of the following: superior sagittal sinus (proximal venous drainage) and/or torcula (deep venous drainage). PVT- was defined as lacking this in both regions. The primary outcome was mortality at 90 days. In a 1:1 propensity score-matched cohort, regressions were performed to determine the effect of PVT on 90-day mortality. RESULTS: In 127 patients of median (IQR) age 71 (64-81) years, mortality occurred in a significantly greater proportion of PVT+ patients than PVT- patients (32.5% vs 12.6%, P=0.01). This significant difference persisted after matching (P=0.03). PVT+ was associated with a significantly increased likelihood of 90-day mortality (OR 1.22 (95% CI 1.02 to 1.46), P=0.03) in the matched cohort. CONCLUSIONS: PVT+ was significantly associated with 90-day mortality despite successful reperfusion therapy in patients with AIS-LVO. PVT is a simple VO profile marker with potential as an adjunctive metric during acute evaluation of AIS-LVO patients. Future studies will expand our understanding of using PVT in the evaluation of patients with AIS-LVO.

10.
Anal Chem ; 96(8): 3389-3401, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38353412

RESUMO

Methyl branching on the carbon chains of fatty acids and fatty esters is among the structural variations encountered with fatty acids and fatty esters. Branching in fatty acid/ester chains is particularly prominent in bacterial species and, for example, in vernix caseosa and sebum. The distinction of branched chains from isomeric straight-chain species and the localization of branching can be challenging to determine by mass spectrometry (MS). Condensed-phase derivatization strategies, often used in conjunction with separations, are most commonly used to address the identification and characterization of branched fatty acids. In this work, a gas-phase ion/ion strategy is presented that obviates condensed-phase derivatization and introduces a radical site into fatty acid ions to facilitate radical-directed dissociation (RDD). The gas-phase approach is also directly amenable to fatty acid anions generated via collision-induced dissociation from lipid classes that contain fatty esters. Specifically, divalent magnesium complexes bound to two terpyridine ligands that each incorporate a ((2,2,6,6-tetramethyl-1-piperidine-1-yl)oxy) (TEMPO) moiety are used to charge-invert fatty acid anions. Following the facile loss of one of the ligands and the TEMPO group of the remaining ligand, a radical site is introduced into the complex. Subsequent collision-induced dissociation (CID) of the complex exhibits preferred cleavages that localize the site(s) of branching. The approach is illustrated with iso-, anteiso-, and isoprenoid branched-chain fatty acids and an intact glycerophospholipid and is applied to a mixture of branched- and straight-chain fatty acids derived from Bacillus subtilis.


Assuntos
Ácidos Graxos , Lipídeos , Humanos , Ácidos Graxos/análise , Espectrometria de Massas , Ésteres/química , Íons/química , Ânions
11.
Rev Neurol ; 78(4): 109-116, 2024 Feb 16.
Artigo em Espanhol | MEDLINE | ID: mdl-38349319

RESUMO

INTRODUCTION: Neurocysticercosis (NCC), a possible cause of epilepsy with limited epidemiological data in the Dominican Republic, is endemic in four provinces in the country's south-western region. This study aimed to determine the association between NCC and epilepsy among people living in these endemic regions, and to obtain preliminary data on the prevalence of NCC in these provinces. PATIENTS AND METHODS: A case-control design was used, consisting of 111 patients with epilepsy with unknown causes, and 60 controls without epilepsy or NCC. The diagnosis of NCC was based on computed tomography and magnetic resonance imaging of the skull, as well as Western immunoblotting for serum antibodies using Taenia solium, following the criteria of Del Brutto et al. RESULTS. NCC was found in 27% of the epileptic patients (n = 30/111) and in 5% of the controls (n = 3/60); the probability of the epileptic patients having NCC was seven times higher than the controls (odds ratio = 7.04, 95% confidence interval: 2.04-24.18; p < 0.001). The participants' sociodemographic characteristics, including their age, sex, level of education, occupation, and province of residence presented no statistical significance in terms of their association with NCC. CONCLUSIONS: This study suggests that NCC is strongly associated with epilepsy in the south-western region of the Dominican Republic, and highlights the need for public health measures to improve the prevention, diagnosis and treatment of both diseases.


TITLE: Diagnóstico de neurocisticercosis en pacientes con epilepsia residentes en el suroeste de la República Dominicana.Introducción. La neurocisticercosis (NCC), una posible causa de epilepsia con datos epidemiológicos limitados en la República Dominicana, es endémica en cuatro provincias de la región suroeste. El objetivo de este estudio fue determinar la asociación entre la NCC y la epilepsia en personas que viven en estas regiones endémicas, así como obtener datos preliminares sobre la prevalencia de NCC en estas provincias. Sujetos y métodos. Se utilizó un diseño de casos y controles compuesto por 111 pacientes con epilepsia de causa desconocida y 60 controles sin epilepsia ni NCC. El diagnóstico de NCC se basó en la tomografía computarizada y la resonancia magnética del cráneo, así como en el inmunotransferencia de Western para anticuerpos séricos contra Taenia solium, siguiendo los criterios de Del Brutto et al. Resultados. Se encontró NCC en el 27% de los pacientes con epilepsia (n = 30/111) y en el 5% de los controles (n = 3/60); los casos de epilepsia tenían siete veces más probabilidades de tener NCC que los controles (odds ratio = 7,04, intervalo de confianza al 95%: 2,04-24,18; p < 0,001). Las características sociodemográficas de los participantes, como la edad, el sexo, el nivel de escolaridad, la ocupación y la provincia de residencia no mostraron significación estadística en cuanto a la asociación con NCC. Conclusiones. Este estudio sugiere que la NCC está fuertemente asociada con la epilepsia en la región suroeste de la República Dominicana, y destaca la necesidad de medidas de salud pública para mejorar la prevención, el diagnóstico y el tratamiento de ambas enfermedades.


Assuntos
Epilepsia , Neurocisticercose , Humanos , Neurocisticercose/complicações , Neurocisticercose/diagnóstico , Neurocisticercose/epidemiologia , República Dominicana/epidemiologia , Anticorpos , Escolaridade , Epilepsia/epidemiologia , Epilepsia/etiologia
12.
Actas Urol Esp (Engl Ed) ; 48(5): 398-403, 2024 Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38373482

RESUMO

INTRODUCTION AND OBJECTIVE: Generative artificial intelligence makes it possible to ask about medical pathologies in dialog boxes. Our objective was to analyze the quality of information about the most common urological pathologies provided by ChatGPT (OpenIA), BARD (Google), and Copilot (Microsoft). METHODS: We analyzed information on the following pathologies and their treatments as provided by AI: prostate cancer, kidney cancer, bladder cancer, urinary lithiasis, and benign prostatic hypertrophy (BPH). Questions in English and Spanish were posed in dialog boxes; the answers were collected and analyzed with DISCERN questionnaires and the overall appropriateness of the response. Surgical procedures were performed with an informed consent questionnaire. RESULTS: The responses from the three chatbots explained the pathology, detailed risk factors, and described treatments. The difference is that BARD and Copilot provide external information citations, which ChatGPT does not. The highest DISCERN scores, in absolute numbers, were obtained in Copilot; however, on the appropriacy scale it was noted that their responses were not the most appropriate. The best surgical treatment scores were obtained by BARD, followed by ChatGPT, and finally Copilot. CONCLUSIONS: The answers obtained from generative AI on urological diseases depended on the formulation of the question. The information provided had significant biases, depending on pathology, language, and above all, the dialog box consulted.


Assuntos
Idioma , Doenças Urológicas , Humanos , Inteligência Artificial , Inquéritos e Questionários , Internet
13.
J Prev Alzheimers Dis ; 11(2): 463-468, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38374753

RESUMO

Contextual memory, the ability to remember spatial or temporal features related to an event, is affected in Alzheimer's disease (AD). There is a shortfall of tests that measure contextual memory. To evaluate visuospatial contextual memory, we developed a computerized cognitive test, the MAPP Room Memory Test, which requires participants to identify in which visual scene target items were previously presented. We hypothesized that cognitively-unimpaired carriers of an autosomal dominant AD mutation (Presenilin-1 E280A, n=15) would perform more poorly on this test than non-carrier family members (n=31). Compared to non-carriers, the carriers had significantly worse delayed room recognition. The results indicate that the MAPP Room Memory Test may be sensitive to subtle cognitive changes associated with risk of AD. Future studies with larger samples using the MAPP Room Memory Test and biomarkers are needed to examine whether this test may also be sensitive to the earliest pathological changes in preclinical AD.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Mutação , Testes Neuropsicológicos
14.
Actas dermo-sifiliogr. (Ed. impr.) ; 115(1): 36-47, jan. 2024. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-229336

RESUMO

Antecedentes Diversos trabajos apoyan la hipótesis de que en España se está produciendo un aumento de incidencia de la escabiosis, y existen dudas sobre el posible desarrollo de resistencias y el incremento de formas clínicas atípicas. Los objetivos de este estudio fueron caracterizar el perfil demográfico y clínico de los pacientes de escabiosis atendidos por dermatólogos en España, identificar la posible aparición de escabiosis atípicas, así como describir la frecuencia y los posibles factores de riesgo de los fracasos terapéuticos previos. Métodos Realizamos un estudio observacional, transversal, multicéntrico con recogida de datos prospectiva, en abril y mayo de 2023 dentro de la plataforma CLINI-AEDVp de la Academia Española de Dermatología y Venereología. Resultados Se reclutaron 186 casos de escabiosis activa (51% mujeres) en 31 centros participantes de 15 comunidades autónomas. Se requirió un nivel A, B o C de los criterios de consenso de la International Alliance for the Control of Scabies (IACS) para el diagnóstico. El 92% de los pacientes presentaron formas clínicas típicas de escabiosis y un 66% había recibido tratamiento escabicida previo para el episodio en curso. De los pacientes previamente tratados, solo un 36% había recibido y cumplimentado una pauta terapéutica adecuada que incluyera el tratamiento simultáneo de convivientes, y un 50% careció de un documento escrito y claro con las recomendaciones. Conclusiones Una elevada proporción de los casos de escabiosis atendidos actualmente ha recibido tratamiento previo. En estos se observan defectos corregibles que pueden justificar parte de los fracasos terapéuticos. Trabajar en la mejora de las deficiencias encontradas ayudará a un mejor control de la enfermedad y a evaluar la efectividad actual de los escabicidas disponibles (AU)


Background Several studies support the hypothesis that scabies is on the rise in Spain. There are also concerns about the possible development of resistance to treatment and an increase in atypical presentations. The aims of this study were to describe the demographic and clinical characteristics of patients with scabies seen by dermatologists in Spain, to identify the possible emergence of atypical forms of scabies, and to explore the frequency of treatment failures and associated risk factors. Methods We conducted an observational, cross-sectional, multicenter study of data collected prospectively in April and May 2023 using the CLINI-AEDVp platform created by the Spanish Academy of Dermatology and Venereology (AEDV). Results Participating dermatologists from 31 hospitals in 15 of Spain's autonomous communities recorded 186 cases of active scabies (51% in women) during the study period. A diagnostic certainty level of A, B or C as per the International Alliance for the Control of Scabies Consensus Criteria was required for diagnosis. Overall, 92% of patients had typical scabies and 66% had already been treated with a scabicide for the current episode. Of the treated patients, only 36% had received and completed adequate treatment (including the simultaneous treatment of all household members) and 50% had not received clear written recommendations. Conclusions In a high proportion of the cases of scabies studied, the patient had already received treatment. In those cases, we observed several remediable shortcomings that could explain why some of these treatments had failed. Remedying these deficiencies should lead to better control of scabies and an improved assessment of the actual effectiveness of currently available scabicides (AU)


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Escabiose/epidemiologia , Escabiose/tratamento farmacológico , Estudos Transversais , Espanha/epidemiologia , Incidência
15.
Actas dermo-sifiliogr. (Ed. impr.) ; 115(1): t36-t47, jan. 2024. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-229337

RESUMO

Background Several studies support the hypothesis that scabies is on the rise in Spain. There are also concerns about the possible development of resistance to treatment and an increase in atypical presentations. The aims of this study were to describe the demographic and clinical characteristics of patients with scabies seen by dermatologists in Spain, to identify the possible emergence of atypical forms of scabies, and to explore the frequency of treatment failures and associated risk factors. Methods We conducted an observational, cross-sectional, multicenter study of data collected prospectively in April and May 2023 using the CLINI-AEDVp platform created by the Spanish Academy of Dermatology and Venereology (AEDV). Results Participating dermatologists from 31 hospitals in 15 of Spain's autonomous communities recorded 186 cases of active scabies (51% in women) during the study period. A diagnostic certainty level of A, B or C as per the International Alliance for the Control of Scabies Consensus Criteria was required for diagnosis. Overall, 92% of patients had typical scabies and 66% had already been treated with a scabicide for the current episode. Of the treated patients, only 36% had received and completed adequate treatment (including the simultaneous treatment of all household members) and 50% had not received clear written recommendations. Conclusions In a high proportion of the cases of scabies studied, the patient had already received treatment. In those cases, we observed several remediable shortcomings that could explain why some of these treatments had failed. Remedying these deficiencies should lead to better control of scabies and an improved assessment of the actual effectiveness of currently available scabicides (AU)


Antecedentes Diversos trabajos apoyan la hipótesis de que en España se está produciendo un aumento de incidencia de la escabiosis, y existen dudas sobre el posible desarrollo de resistencias y el incremento de formas clínicas atípicas. Los objetivos de este estudio fueron caracterizar el perfil demográfico y clínico de los pacientes de escabiosis atendidos por dermatólogos en España, identificar la posible aparición de escabiosis atípicas, así como describir la frecuencia y los posibles factores de riesgo de los fracasos terapéuticos previos. Métodos Realizamos un estudio observacional, transversal, multicéntrico con recogida de datos prospectiva, en abril y mayo de 2023 dentro de la plataforma CLINI-AEDVp de la Academia Española de Dermatología y Venereología. Resultados Se reclutaron 186 casos de escabiosis activa (51% mujeres) en 31 centros participantes de 15 comunidades autónomas. Se requirió un nivel A, B o C de los criterios de consenso de la International Alliance for the Control of Scabies (IACS) para el diagnóstico. El 92% de los pacientes presentaron formas clínicas típicas de escabiosis y un 66% había recibido tratamiento escabicida previo para el episodio en curso. De los pacientes previamente tratados, solo un 36% había recibido y cumplimentado una pauta terapéutica adecuada que incluyera el tratamiento simultáneo de convivientes, y un 50% careció de un documento escrito y claro con las recomendaciones. Conclusiones Una elevada proporción de los casos de escabiosis atendidos actualmente ha recibido tratamiento previo. En estos se observan defectos corregibles que pueden justificar parte de los fracasos terapéuticos. Trabajar en la mejora de las deficiencias encontradas ayudará a un mejor control de la enfermedad y a evaluar la efectividad actual de los escabicidas disponibles (AU)


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Escabiose/epidemiologia , Escabiose/tratamento farmacológico , Estudos Transversais , Espanha/epidemiologia , Incidência
18.
Actas Urol Esp (Engl Ed) ; 48(2): 177-183, 2024 Mar.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37574014

RESUMO

INTRODUCTION AND OBJECTIVES: Transplant renal artery stenosis (TRAS) is a vascular complication after kidney transplantation which estimated incidence is 13%. It could cause refractory arterial hypertension, kidney dysfunction and premature death in transplant recipients. METHODS: We carried out a retrospective study including every patient who underwent renal transplantation between 2014 and 2020. They were evaluated with a systematic post-transplant renal Doppler ultrasound. To identify independent risk factors for transplant renal artery stenosis we performed a multivariate analysis. RESULTS: Seven hundred twenty-four kidney transplants were included, 12% ​​were living donors and 88% were deceased donors. The mean age was 54.8 in recipients and 53 in donors. Transplant renal artery stenosis was diagnosed in 70 (10%) recipients, the majority in the first 6 months after surgery. 51% of patients with transplant renal artery stenosis were managed conservatively. The multivariate analysis showed diabetes mellitus, graft rejection, arterial resuture and donor body mass index as independent risk factors for transplant renal artery stenosis. Survival of the grafts with transplant renal artery stenosis was 98% at 6 months and 95% at two years. CONCLUSIONS: The systematic performance of Doppler ultrasound in the immediate post-transplant period diagnosed 10% of transplant renal artery stenosis in our cohort. Despite the above risk factors, an adequate monitoring and treatment could avoid the increased risk of graft loss in patients with transplant renal artery stenosis.


Assuntos
Obstrução da Artéria Renal , Humanos , Pessoa de Meia-Idade , Obstrução da Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/epidemiologia , Obstrução da Artéria Renal/etiologia , Incidência , Estudos Retrospectivos , Resultado do Tratamento , Fatores de Risco , Ultrassonografia Doppler/efeitos adversos
19.
Actas Dermosifiliogr ; 115(1): 36-47, 2024 Jan.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37678633

RESUMO

BACKGROUND: Several studies support the hypothesis that scabies is on the rise in Spain. There are also concerns about the possible development of resistance to treatment and an increase in atypical presentations. The aims of this study were to describe the demographic and clinical characteristics of patients with scabies seen by dermatologists in Spain, to identify the possible emergence of atypical forms of scabies, and to explore the frequency of treatment failures and associated risk factors. METHODS: We conducted an observational, cross-sectional, multicenter study of data collected prospectively in April and May 2023 using the CLINI-AEDVp platform created by the Spanish Academy of Dermatology and Venereology (AEDV). RESULTS: Participating dermatologists from 31 hospitals in 15 of Spain's autonomous communities recorded 186 cases of active scabies (51% in women) during the study period. A diagnostic certainty level of A, B or C as per the International Alliance for the Control of Scabies Consensus Criteria was required for diagnosis. Overall, 92% of patients had typical scabies and 66% had already been treated with a scabicide for the current episode. Of the treated patients, only 36% had received and completed adequate treatment (including the simultaneous treatment of all household members) and 50% had not received clear written recommendations. CONCLUSIONS: In a high proportion of the cases of scabies studied, the patient had already received treatment. In those cases, we observed several remediable shortcomings that could explain why some of these treatments had failed. Remedying these deficiencies should lead to better control of scabies and an improved assessment of the actual effectiveness of currently available scabicides.


Assuntos
Escabiose , Humanos , Feminino , Escabiose/tratamento farmacológico , Escabiose/epidemiologia , Espanha/epidemiologia , Estudos Transversais , Falha de Tratamento , Academias e Institutos
20.
Brain Behav Immun ; 116: 160-174, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38070624

RESUMO

Acute cerebral ischemia triggers a profound inflammatory response. While macrophages polarized to an M2-like phenotype clear debris and facilitate tissue repair, aberrant or prolonged macrophage activation is counterproductive to recovery. The inhibitory immune checkpoint Programmed Cell Death Protein 1 (PD-1) is upregulated on macrophage precursors (monocytes) in the blood after acute cerebrovascular injury. To investigate the therapeutic potential of PD-1 activation, we immunophenotyped circulating monocytes from patients and found that PD-1 expression was upregulated in the acute period after stroke. Murine studies using a temporary middle cerebral artery (MCA) occlusion (MCAO) model showed that intraperitoneal administration of soluble Programmed Death Ligand-1 (sPD-L1) significantly decreased brain edema and improved overall survival. Mice receiving sPD-L1 also had higher performance scores short-term, and more closely resembled sham animals on assessments of long-term functional recovery. These clinical and radiographic benefits were abrogated in global and myeloid-specific PD-1 knockout animals, confirming PD-1+ monocytes as the therapeutic target of sPD-L1. Single-cell RNA sequencing revealed that treatment skewed monocyte maturation to a non-classical Ly6Clo, CD43hi, PD-L1+ phenotype. These data support peripheral activation of PD-1 on inflammatory monocytes as a therapeutic strategy to treat neuroinflammation after acute ischemic stroke.


Assuntos
Edema Encefálico , AVC Isquêmico , Humanos , Camundongos , Animais , Monócitos/metabolismo , Edema Encefálico/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Antígeno B7-H1/metabolismo , Infarto da Artéria Cerebral Média/metabolismo
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