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1.
Bol. latinoam. Caribe plantas med. aromát ; 23(3): 371-381, mayo 2024. tab, ilus
Artigo em Inglês | LILACS | ID: biblio-1538079

RESUMO

Mexican markets embody cultural diversity and offer a wide range of products, serving as hubs for local exchange.In our study at Mexico City's Sonora Market, the country's prominent medicinal market, we explored the use of plant remedies against witchcraft in an urban environment. Through interviews with plant vendors and extensive data collection, we identified 21 plant species from 16 botanical families renowned for their effectiveness in combating sorcery, attracting good luck, and promoting success. Additionally, we documented 14 ailments associated with envy and negative emotions. These remedies involved practices and applications such as cleansings, decoctions, baths, and incense burning, aimed at alleviating afflictions and fostering positive outcomes. Notably, the Sonora Market continues to uphold the tradition of using plant remedies against witchcraft, even in the bustling setting of one of the world's largest cities. This highlights the enduring significance of these practices within Mexican society


Los mercados mexicanos encarnan diversidad cultural y ofrecen numerosos productos, sirviendo como centros de intercambio local. En nuestro estudio en el Mercado de Sonora en la Ciudad de México, el sitio de plantas medicinales más relevante del país, exploramos el uso de plantas contra la brujería en un entorno urbano. A través de entrevistas con locatarios, identificamos 21 especies de plantas pertenecientes a 16 familias botánicas usadas en la lucha contra la brujería, atrayendo buena suerte y promoviendo el éxito. Además, documentamos 14 enfermedades asociadas con la envidia y emociones negativas. Los remedios involucraban prácticas y aplicaciones como limpias, decocciones, baños, incienso, con el objetivo de aliviar dolencias y fomentar resultados positivos. En el Mercado deSonora persiste la tradición de utilizar plantas contra la brujería, incluso en el marco de una de las mayores ciudades del mundo, resaltando la importancia de estas prácticas dentro de la sociedad mexicana.


Assuntos
Plantas Medicinais , Bruxaria , Etnobotânica , Medicina Tradicional , México
2.
Diagnostics (Basel) ; 14(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38611617

RESUMO

An improved understanding of the pathobiology of Alzheimer's disease (AD) should lead ultimately to an earlier and more accurate diagnosis of AD, providing the opportunity to intervene earlier in the disease process and to improve outcomes. The known hallmarks of Alzheimer's disease include amyloid-ß plaques and neurofibrillary tau tangles. It is now clear that an imbalance between production and clearance of the amyloid beta protein and related Aß peptides, especially Aß42, is a very early, initiating factor in Alzheimer's disease (AD) pathogenesis, leading to aggregates of hyperphosphorylation and misfolded tau protein, inflammation, and neurodegeneration. In this article, we review how the AD diagnostic process has been transformed in recent decades by our ability to measure these various elements of the pathological cascade through the use of imaging and fluid biomarkers. The more recently developed plasma biomarkers, especially phosphorylated-tau217 (p-tau217), have utility for screening and diagnosis of the earliest stages of AD. These biomarkers can also be used to measure target engagement by disease-modifying therapies and the response to treatment.

3.
Euro Surveill ; 29(16)2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38639093

RESUMO

BackgroundMpox, caused by monkeypox virus (MPXV), was considered a rare zoonotic disease before May 2022, when a global epidemic of cases in non-endemic countries led to the declaration of a Public Health Emergency of International Concern. Cases of mpox in Ireland, a country without previous mpox reports, could reflect extended local transmission or multiple epidemiological introductions.AimTo elucidate the origins and molecular characteristics of MPXV circulating in Ireland between May 2022 and October 2023.MethodsWhole genome sequencing of MPXV from 75% of all Irish mpox cases (182/242) was performed and compared to sequences retrieved from public databases (n = 3,362). Bayesian approaches were used to infer divergence time between sequences from different subclades and evaluate putative importation events from other countries.ResultsOf 242 detected mpox cases, 99% were males (median age: 35 years; range: 15-60). All 182 analysed genomes were assigned to Clade IIb and, presence of 12 distinguishable subclades suggests multiple introductions into Ireland. Estimation of time to divergence of subclades further supports the hypothesis for multiple importation events from numerous countries, indicative of extended and sustained international spread of mpox. Further analysis of sequences revealed that 92% of nucleotide mutations were from cytosine to thymine (or from guanine to adenine), leading to a high number of non-synonymous mutations across subclades; mutations associated with tecovirimat resistance were not observed.ConclusionWe provide insights into the international transmission dynamics supporting multiple introductions of MPXV into Ireland. Such information supported the implementation of evidence-informed public health control measures.


Assuntos
Monkeypox virus , Mpox , Masculino , Humanos , Adulto , Feminino , Irlanda/epidemiologia , Monkeypox virus/genética , Teorema de Bayes , Mpox/diagnóstico , Mpox/epidemiologia , Surtos de Doenças
4.
Chemistry ; : e202400828, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640462

RESUMO

Pyridoxal hydrochloride, a vitamin B6 vitamer, was synthetically converted to a series of diverse redox-active benzoyl pyridinium salts. Cyclic voltammetry studies demonstrated redox reversibility under basic conditions, and two of the most promising salts were subjected to laboratory-scale redox flow battery tests involving galvanostatic cycling at 10 mM in 0.1 M NaOH. In these tests, the battery was charged completely, corresponding to the transfer of two electrons to the electrolyte, but no discharge was observed. Both CV analysis and electrochemical simulations confirmed that the redox wave observed in the experimental voltammograms corresponds to a two-electron process. To explain the irreversibility in the battery tests, we conducted bulk electrolysis with the benzoyl pyridinium salts, affording the corresponding benzylic secondary alcohols. Computational studies suggest that the reduction proceeds in three consecutive steps: first electron transfer (ET), then proton-coupled electron transfer (PCET) and finally proton transfer (PT) to give the secondary alcohol. 1H NMR deuterium exchange studies indicated that the last PT step is not reversible in 0.1 M NaOH, rendering the entire redox process irreversible. The apparent reversibility observed in CV at the basic media likely arises from the slow rate of the PT step at the timescale of the measurement.

5.
Pediatr Surg Int ; 40(1): 102, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589706

RESUMO

PURPOSE: The utility of pulmonary function testing (PFT) in pectus excavatum (PE) has been subject to debate. Although some evidence shows improvement from preoperative to postoperative values, the clinical significance is uncertain. A high failure-to-completion rate for operative PFT (48%) was identified in our large institutional cohort. With such a high non-completion rate, we questioned the overall utility of PFT in the preoperative assessment of PE and sought to evaluate if other measures of PE severity or cardiopulmonary function could explain this finding. METHODS: Demographics, clinical findings, and results from cardiac MRI, PFT (spirometry and plethysmography), and cardiopulmonary exercise tests (CPET) were reviewed in 270 patients with PE evaluated preoperatively between 2015 and 2018. Regression modeling was used to measure associations between PFT completion and cardiopulmonary function. RESULTS: There were no differences in demographics, symptoms, connective tissue disorders, or multiple indices of pectus severity and cardiac deformation in PFT completers versus non-completers. While regression analysis revealed higher RVEF, LVEF, and LVEF-Z scores, lower RV-ESV/BSA, LV-ESV/BSA, and LV-ESV/BSA-Z scores, and abnormal breathing reserve in PFT completers vs. non-completers, these findings were not consistent across continuous and binary analyses. CONCLUSIONS: We found that PFT completers were not significantly different from non-completers in most structural and functional measures of pectus deformity and cardiopulmonary function. Inability to complete PFT is not an indicator of pectus severity.


Assuntos
Tórax em Funil , Humanos , Tórax em Funil/cirurgia , Espirometria
6.
J Alzheimers Dis ; 99(1): 1-20, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38640152

RESUMO

Alzheimer's disease (AD) is a chronic neurodegenerative disorder with a global impact. The past few decades have witnessed significant strides in comprehending the underlying pathophysiological mechanisms and developing diagnostic methodologies for AD, such as neuroimaging approaches. Neuroimaging techniques, including positron emission tomography and magnetic resonance imaging, have revolutionized the field by providing valuable insights into the structural and functional alterations in the brains of individuals with AD. These imaging modalities enable the detection of early biomarkers such as amyloid-ß plaques and tau protein tangles, facilitating early and precise diagnosis. Furthermore, the emerging technologies encompassing blood-based biomarkers and neurochemical profiling exhibit promising results in the identification of specific molecular signatures for AD. The integration of machine learning algorithms and artificial intelligence has enhanced the predictive capacity of these diagnostic tools when analyzing complex datasets. In this review article, we will highlight not only some of the most used diagnostic imaging approaches in neurodegeneration research but focus much more on new tools like artificial intelligence, emphasizing their application in the realm of AD. These advancements hold immense potential for early detection and intervention, thereby paving the way for personalized therapeutic strategies and ultimately augmenting the quality of life for individuals affected by AD.


Assuntos
Doença de Alzheimer , Inteligência Artificial , Diagnóstico Precoce , Neuroimagem , Humanos , Doença de Alzheimer/diagnóstico por imagem , Neuroimagem/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Biomarcadores/análise
7.
Int J Mol Sci ; 25(6)2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38542362

RESUMO

Indole alkaloids are the main bioactive molecules of the Gelsemium genus plants. Diverse reports have shown the beneficial actions of Gelsemium alkaloids on the pathological states of the central nervous system (CNS). Nevertheless, Gelsemium alkaloids are toxic for mammals. To date, the molecular targets underlying the biological actions of Gelsemium alkaloids at the CNS remain poorly defined. Functional studies have determined that gelsemine is a modulator of glycine receptors (GlyRs) and GABAA receptors (GABAARs), which are ligand-gated ion channels of the CNS. The molecular and physicochemical determinants involved in the interactions between Gelsemium alkaloids and these channels are still undefined. We used electrophysiological recordings and bioinformatic approaches to determine the pharmacological profile and the molecular interactions between koumine, gelsemine, gelsevirine, and humantenmine and these ion channels. GlyRs composed of α1 subunits were inhibited by koumine and gelsevirine (IC50 of 31.5 ± 1.7 and 40.6 ± 8.2 µM, respectively), while humantenmine did not display any detectable activity. The examination of GlyRs composed of α2 and α3 subunits showed similar results. Likewise, GABAARs were inhibited by koumine and were insensitive to humantenmine. Further assays with chimeric and mutated GlyRs showed that the extracellular domain and residues within the orthosteric site were critical for the alkaloid effects, while the pharmacophore modeling revealed the physicochemical features of the alkaloids for the functional modulation. Our study provides novel information about the molecular determinants and functional actions of four major Gelsemium indole alkaloids on inhibitory receptors, expanding our knowledge regarding the interaction of these types of compounds with protein targets of the CNS.


Assuntos
Alcaloides , Gelsemium , Animais , Gelsemium/química , Alcaloides/química , Extratos Vegetais/química , Alcaloides Indólicos/química , Ácido gama-Aminobutírico , Mamíferos/metabolismo
8.
Mol Genet Metab Rep ; 38: 101060, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38469103

RESUMO

Introduction: Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), is a neurodegenerative autosomal recessive disease caused by TPP1 gene variants, with a spectrum of classic and atypical phenotypes. The aim of treatment is to slow functional decline as early as possible in an attempt to improve quality of life and survival. This study describes the clinical characteristics as well as the response to treatment with cerliponase alfa. Materials and methods: A retrospective study was conducted in five Latin-American countries, using clinical records from patients with CLN2. Clinical follow-up and treatment variables are described. A descriptive and bivariate statistical analysis was performed. Results: A total of 36 patients were observed (range of follow-up of 61-110 weeks post-treatment). At presentation, patients with the classic phenotype (n = 16) exhibited regression in language (90%), while seizures were the predominant symptom (87%) in patients with the atypical phenotype (n = 20). Median age of symptom onset and time to first specialized consultation was 3 (classical) and 7 (atypical) years, while the median time interval between onset of symptoms and treatment initiation was 4 years (classical) and 7.5 (atypical). The most frequent variant was c.827 A > T in 17/72 alleles, followed by c.622C > T in 6/72 alleles. All patients were treated with cerliponase alfa, and either remained functionally stable or had a loss of 1 point on the CLN2 scale, or up to 2 points on the Wells Cornel and Hamburg scales, when compared to pretreatment values. Discussion and conclusion: This study reports the largest number of patients with CLN2 currently on treatment with cerliponase alfa in the world. Data show a higher frequency of patients with atypical phenotypes and a high allelic proportion of intron variants in our region. There was evidence of long intervals until first specialized consultation, diagnosis, and enzyme replacement therapy. Follow-up after the initiation of cerliponase alfa showed slower progression or stabilization of the disease, associated with adequate clinical outcomes and stable functional scores. These improvements were consistent in both clinical phenotypes.

9.
Chem Biodivers ; 21(4): e202400235, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38412304

RESUMO

Over the last decades, soft corals have been proven a rich source of biologically active compounds, featuring a wide range of chemical structures. Herein, we investigated the chemistry of an alcyonarian of the genus Lemnalia (Neptheidae), specimens of which were collected from the coral reefs near Al Lith, on the south-west coast of Saudi Arabia. A series of chromatographic separations led to the isolation of 31 sesquiterpenes, featuring mainly the nardosinane and neolemnane carbon skeletons, among which three (13, 14 and 28) are new natural products. The metabolites isolated in sufficient amounts were evaluated in vitro in human tumor and non-cancerous cell lines for a number of biological activities, including their cytotoxic, anti-inflammatory, anti-angiogenic, and neuroprotective activities, as well as for their effect on androgen receptor (AR)-regulated transcription. Among the tested metabolites, compound 12 showed comparable neuroprotective activity to the positive control N-acetylcysteine, albeit at a 10-fold lower concentration.


Assuntos
Antozoários , Antineoplásicos , Sesquiterpenos , Animais , Humanos , Arábia Saudita , Oceano Índico , Sesquiterpenos/química , Antozoários/química , Antineoplásicos/farmacologia , Antineoplásicos/metabolismo
10.
Sci Rep ; 14(1): 3400, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38336889

RESUMO

Enhancements in the structural and operational aspects of transportation are important for achieving high-quality mobility. Toll plazas are commonly known as a potential bottleneck stretch, as they tend to interfere with the normality of the flow due to the charging points. Focusing on the automation of toll plazas, this research presents the development of an axle counter to compose a free-flow toll collection system. The axle counter is responsible for the interpretation of images through algorithms based on computer vision to determine the number of axles of vehicles crossing in front of a camera. The You Only Look Once (YOLO) model was employed in the first step to identify vehicle wheels. Considering that several versions of this model are available, to select the best model, YOLOv5, YOLOv6, YOLOv7, and YOLOv8 were compared. The YOLOv5m achieved the best result with precision and recall of 99.40% and 98.20%, respectively. A passage manager was developed thereafter to verify when a vehicle passes in front of the camera and store the corresponding frames. These frames are then used by the image reconstruction module which creates an image of the complete vehicle containing all axles. From the sequence of frames, the proposed method is able to identify when a vehicle was passing through the scene, count the number of axles, and automatically generate the appropriate charge to be applied to the vehicle.

11.
Sensors (Basel) ; 24(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339684

RESUMO

This review delves into the critical role of automation and sensor technologies in optimizing parameters for thermal treatments within electrical power generation. The demand for efficient and sustainable power generation has led to a significant reliance on thermal treatments in power plants. However, ensuring precise control over these treatments remains challenging, necessitating the integration of advanced automation and sensor systems. This paper evaluates the pivotal aspects of automation, emphasizing its capacity to streamline operations, enhance safety, and optimize energy efficiency in thermal treatment processes. Additionally, it highlights the indispensable role of sensors in monitoring and regulating crucial parameters, such as temperature, pressure, and flow rates. These sensors enable real-time data acquisition, facilitating immediate adjustments to maintain optimal operating conditions and prevent system failures. It explores the recent technological advancements, including machine learning algorithms and IoT integration, which have revolutionized automation and sensor capabilities in thermal treatment control. Incorporating these innovations has significantly improved the precision and adaptability of control systems, resulting in heightened performance and reduced environmental impact. This review underscores the imperative nature of automation and sensor technologies in thermal treatments for electrical power generation, emphasizing their pivotal role in enhancing operational efficiency, ensuring reliability, and advancing sustainability in power generation processes.

12.
Viruses ; 16(1)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38257837

RESUMO

A 3-year-old male with X-linked lymphoproliferative syndrome type 1 underwent an unrelated umbilical cord blood transplant (UUCBT). The week prior to transplant the patient tested positive for adenovirus (HAdV) with a viral load of <190 copies/mL and was started on cidofovir. UUCBT proceeded as scheduled, and the patient engrafted on day +19. The patient's HAdV load in serum continued to rise with resulting hepatic dysfunction, despite ongoing therapy with cidofovir and HAdV specific T-cell infusions. The patient died 6 months after transplantation having never cleared the virus. Next generation whole genome sequencing and sequence data analyses identified an intertypic recombinant HAdV-C P1H2F2 closely related (99.6% similarity) to genotype C108 in the isolates from three blood specimens obtained during the last week of life. Incidentally, the de novo assembly strategy enabled the detection of an adeno-associated virus type 2 (AAV2) genome in the DNA purified from the plasma isolates. Proteotyping analysis revealed minor differences in the predicted amino acid sequences for E1A, E1B 19K, E1B 55K, DNA polymerase, penton base, and fiber. None of the mutations previously described for HAdV-C5 variants resistant to cidofovir were identified. In silico restriction enzyme analysis revealed a distinct Sac I profile for the identified virus, supporting its designation as a C108 variant.


Assuntos
Infecções por Adenoviridae , Transtornos Linfoproliferativos , Pré-Escolar , Humanos , Masculino , Adenoviridae , Infecções por Adenoviridae/diagnóstico , Infecções por Adenoviridae/tratamento farmacológico , Cidofovir/uso terapêutico , Genótipo , Transplante de Células-Tronco
13.
Front Psychol ; 14: 1192114, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38078274

RESUMO

Emotional processing is a cognitive function essential for the interaction of humans with their environment and the development of adaptive behaviors. Adolescent offenders (AOs) express difficulty in cognitive processes linked to emotional processing, which is a response consistently observed during the endogenous (i.e., controlled) control of attention. Less remains understood of the extent to which such atypical responses extend beyond controlled attention and influence exogenous mechanisms (i.e., automatic). This study explores this hypothesis using the recently devised emotional Flanker paradigm. It recruited a group of 39 male AOs and 39 nonoffenders from Barranquilla, Colombia. Assessment consists of an emotional Flanker paradigm administered along with traditional neurocognitive and social cognition tasks. The AOs displayed the well-known attentional bias to threat and a relatively atypical response to emotional targets in which they detected emotions, particularly negative ones, faster than did nonoffenders. Frontal lobe functions account for these effects but not sociodemographic variables nor general cognitive abilities. The results are interpreted in light of evidence suggesting that youngsters with high levels of antisocial behaviors (e.g., callous-unemotional traits) present an enhanced orientation toward distressing stimuli, which is explained by lifelong experiences (e.g., histories of abuse). The findings suggest that environmental influences seemingly exist in the development of these traits, but additional research is required to elucidate the role of cognitive and environmental factors in the development of antisocial behavior.

14.
An. R. Acad. Nac. Farm. (Internet) ; 89(4): 451-458, Oct-Dic, 2023. ilus
Artigo em Inglês | IBECS | ID: ibc-229817

RESUMO

Objetivo: Evaluar la actividad antimicrobiana de la bebida de Kéfir contra Escherichia coli, Salmonella typhimurium y Shigella flexneri. Método: El kéfir utilizado en la investigación fue adquirido en Toluca, Estado de México. Se realizó una reactivación del kéfir con leche pasteurizada y se analizaron 3 carbohidratos (miel, azúcar y piloncillo) en diferentes concentraciones y tiempos, 80, 100, 120% y 24, 48 y 72 horas respectivamente. Los microorganismos cultivables aislados se caracterizaron por técnicas fenotípicas, bioquímicas y de espectroscopia de masas. El pH inicial y final se determinaron durante el tiempo de estudio. La actividad antimicrobiana se realizó extrayendo los metabolitos presentes en el fermento con el método de Kirby-Bauer, además se evaluó el fermento directo, para determinar si hubo inhibición con las cepas de Escherichia coli ATCC 11229, Salmonella typhimurium ATCC 14028 y Shigella flexneri ATCC 12022. Resultados: Se observó que en los tres carbohidratos utilizados a una concentración de 120% y en un tiempo de 72 h, fue donde se obtuvo un pH menor (3,51 a 3,64) comparado con su concentración inicial (6,50 a 6,64). A partir de los metabolitos extraídos en los diferentes fermentos, no se obtuvo halo de inhibición con las cepas analizadas. Sin embargo, al usar fermentos directos, se observó que en los carbohidratos utilizados (azúcar, miel, piloncillo) existía la presencia de un halo de inhibición o el crecimiento de colonias distintas de las evaluadas. Los microorganismos cultivables aislados fueron: Pichia kudriavzevii (levadura); Enterococcus sp (coco grampositivo) y Lactobacillus sp (bacilo grampositivo). Conclusiones: Los fermentos de kéfir hechos con diferentes carbohidratos, llegaron a presentar un grado de inhibición solo como un consorcio contra microorganismos Gram-negativos analizados.Palabras Clave: Kéfir; fermentación microbiota; infección; actividad antimicrobiana.(AU)


Objective: Evaluate the antimicrobial activity of the Kefir drink against Escherichia coli, Salmonella typhimurium and Shigella flexneri. Method: The Kefir used in the investigation was acquired in Toluca, State of Mexico. We performed a reactivation of Kefir with pasteurized milk and analyzed 3 carbohydrates (honey, sugar and piloncillo) at different concentrations and times, 80, 100, 120% and 24, 48 and 72 hours respectively. Isolated cultivable microorganisms were characterized by phenotypic, biochemical and mass spectroscopy techniques. The initial and final pH were determined during the study time. The antimicrobial activity was carried out by extracting the metabolites present in the ferment with the Kirby-Bauer method, in addition the direct ferment was evaluated, to determine if there was inhibition with the Escherichia coli (ATCC 11229) strains, Salmonella typhimurium (ATCC 14028) and Shigella flexneri (ATCC 12022). Results: It was observed that in the three carbohydrates used at a concentration of 120% and at a time of 72 h, a lower pH was obtained (3.51 to 3.64) compared to their initial concentration (6.50 to 6.64). From the metabolites extracted in the different ferments, no inhibition halo was obtained with the strains analyzed. However, when using direct ferments, it was observed that in the carbohydrates used (sugar, honey, piloncillo) there was the presence of an inhibiting halo or the growth of colonies other than those evaluated. The isolated cultivable microorganisms were: Pichia kudriavzevii (yeast); Enterococcus sp (gram-positive coconut) and Lactobacillus sp (gram-positive bacillus). Conclusions : Kefir ferments made with different carbohydrates, came to present a degree of inhibition only as a consortium against Gram-negative microorganisms analyzed.(AU)


Assuntos
Humanos , Masculino , Feminino , Shigella flexneri , Salmonella typhimurium , Escherichia coli , Kefir/microbiologia , Produtos com Ação Antimicrobiana , Microbiota , México , Microbiologia , Técnicas Microbiológicas
15.
Arch Pharm (Weinheim) ; 356(12): e2300378, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37797174

RESUMO

A library of 3-aryl-3-azetidinyl acetic acid methyl ester derivatives was prepared from N-Boc-3-azetidinone employing the Horner-Wadsworth-Emmons reaction, rhodium(I)-catalyzed conjugate addition of arylboronic acids, and subsequent elaborations to obtain N-unprotected hydrochlorides, N-alkylated and N-acylated azetidine derivatives. The compounds were evaluated for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, revealing several derivatives to possess AChE inhibition comparable to that of the AChE inhibitor rivastigmine. The binding mode of the AChE inhibitor donepezil and selected active compounds 26 and 27 within the active site of AChE was studied using molecular docking. Furthermore, the neuroprotective activity of the prepared compounds was evaluated in models associated with Parkinson's disease (salsolinol-induced) and aspects of Alzheimer's disease (glutamate-induced oxidative damage). Compound 28 showed the highest neuroprotective effect in both salsolinol- and glutamate-induced neurodegeneration models, and its protective effect in the glutamate model was revealed to be driven by a reduction in oxidative stress and caspase-3/7 activity.


Assuntos
Doença de Alzheimer , Fármacos Neuroprotetores , Humanos , Butirilcolinesterase/metabolismo , Acetilcolinesterase/metabolismo , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Inibidores da Colinesterase/química , Doença de Alzheimer/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Glutamatos/uso terapêutico
16.
Medicina (B.Aires) ; 83(supl.4): 95-101, oct. 2023. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1521209

RESUMO

Resumen Introducción : La trombosis de venas y senos venosos cerebrales (TVSC) constituye una causa conocida, aun que subestimada de ictus en la infancia. Su diagnóstico requiere un alto índice de sospecha, una correcta in terpretación de la neuroimagen e interrelación entre el clínico y el radiólogo. Objetivo : Analizar las manifestaciones clínicas, fac tores de riesgo y neuroimagen de recién nacidos (RN) y niños menores de 15 años con TVSC. Métodos: Estudio descriptivo, retrospectivo, multi céntrico, de una serie consecutiva de casos de menores de 15 años que ingresaron por TVSC entre el 1 de enero del 2010 y el 1 de marzo de 2022. Resultados : El estudio incluyó 51 pacientes: 39% con síntomas agudos y 59% subagudos. En los RN predomi naron síntomas encefalopáticos y convulsiones, mien tras en los niños elementos de hipertensión endocranea na (HTEC). Se identificaron factores de riesgo en el 90% de los casos. La resonancia magnética con angiografía en tiempo venoso confirmó el diagnóstico en el 80%, siendo el seno recto el más afectado en RN y el seno lateral en niños. Se encontraron complicaciones hemorrágicas en 30.5%, siendo más frecuentes en los RN. Se inició anti coagulación en el 82% sin complicaciones. Las secuelas estuvieron presentes en 44.4% de RN y 37.9% de niños, siendo más frecuentes y graves en los RN. Conclusiones : Para realizar un diagnóstico precoz es fundamental pensar en TVSC en RN con síntomas en cefalopáticos y/o convulsiones y en mayores con clínica de HTEC en presencia de enfermedades predisponentes o desencadenantes.


Abstract Introduction : Cerebral venous sinus thrombosis (CVST) is a well-known, although underestimated, cause of stroke in childhood. Its diagnosis requires a high index of suspicion, a correct interpretation of neuroim aging studies and an interrelation between clinicians and radiologists. The clinical features, risk factors and neuroimaging of children under 15 years of age with CVST were analyzed. Methods : multicenter, retrospective, descriptive, study of a consecutive series of cases of children under 15 years of age, who were admitted due to CVST between January 1st, 2010, and March 1st, 2022. Results : The study included 51 patients: 39% with acute symptoms and 59% with subacute symptoms. Newborns predominantly presented encephalopathic symptoms and seizures, while children exhibited signs of intracranial hypertension (ICH). Risk factors were 96 identified in 90% of the cases. Magnetic resonance with angiography in venous time confirmed the diagnosis in 80% of the patients, with the straight sinus being the most affected in newborns and the lateral sinus in chil dren. Hemorrhagic complications were found in 30.5%, being more frequent in newborns. Anticoagulation was initiated in 82% without complications. Sequelae were present in 44.4% of newborns and 37.9% of children, being more frequent and severe in newborns. Conclusions : To make an early diagnosis, it is essen tial to consider CVST in newborns with encephalopathic symptoms and/or seizures, and in children with signs of ICH in the presence of predisposing or triggering conditions.

17.
J Surg Educ ; 80(12): 1789-1798, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37749001

RESUMO

OBJECTIVE: This study aims to evaluate if there is any significant linguistic difference in LoR based on applicant's race/ethnicity. DESIGN: Retrospective review of applications to pediatric surgery fellowship at a single institution (2016-2020). Race was self-reported by applicants. LoR were analyzed via the Linguistic Inquiry and Word Count (LIWC) software program. SETTING: Johns Hopkins All Children's Hospital, St. Petersburg, Florida USA. A free-standing tertiary pediatric hospital. PARTICIPANTS: Pediatric surgery fellowship applicants from 2016 to 2020. RESULTS: A total of 1086 LoR from 280 applicants (52% female) were analyzed. Racial distribution was Caucasians 62.1%, Asian 12.1%, Hispanics 7.1%, multiracial 6.4% African Americans 5%, and other/unknown 7.1%. Letter writers were largely male (84%), pediatric surgeons (63%) and professors (57%). There was no difference in LoR word count across races. LoR for female multiracial candidates contained higher use of affiliation and negative emotion terms compared to Hispanic females (p = 0.002 and 0.048, respectively), and past focus terms when compared to Caucasian and Asian female applicants (p < 0.001 and p = 0.003, respectively). Religion terms were more common in LoR for Asian females when compared to Caucasian females (p < 0.001). CONCLUSION: This study demonstrates linguistic differences in LoR for pediatric surgery training programs based on applicant race/ethnicity. While differences are present, these do not suggest overt bias based on applicants race or ethnicity.


Assuntos
Internato e Residência , Especialidades Cirúrgicas , Humanos , Masculino , Feminino , Criança , Seleção de Pessoal , Idioma , Linguística
18.
Clin Transplant ; 37(12): e15134, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37772613

RESUMO

BACKGROUND: Programmed cell death ligand 1 (PD-L1) expression on tumor cells engages the PD-1 receptor on T cells, inhibiting anti-tumor responses. PD-L1 has been detected in cases of post-transplant lymphoproliferative disorder (PTLD) but reports are limited. Here we examine PD-L1 expression and evaluate for clinical correlations. METHODS: Twenty-one cases of PTLD were identified among pediatric kidney transplant recipients at our institution from February 1996 to April 2017. Using paraffin-embedded tissue biopsies, we examined 21 primary tumors for expression using PD-L1 monoclonal antibody performed with PAX5 as a double stain. We scored expression of PD-L1 on lesional B-cells as a percentage of positive cells. Clinical course and outcome were obtained from retrospective chart review. RESULTS: Applying revised 2017 WHO PTLD classification showed five non-destructive, nine polymorphic, and seven monomorphic cases. Average PD-L1 expression based upon PTLD subtype was: non-destructive 11%, polymorphic 43%, and monomorphic 73% (p = .01). Two patients transferred shortly after diagnosis, five received chemotherapy, and three died from PTLD. Among the fatalities, all showed monomorphic PTLD and 90% of lesional B-cells expressed PD-L1. CONCLUSION: In this case series, significant differences in PD-L1 expression were seen among different subtypes, and monomorphic PTLD demonstrated the highest expression. Study of a larger cohort is needed, and if the correlation of PD-L1 expression and PTLD subtype is confirmed, this may highlight the potential utility of checkpoint inhibitor therapy in cases of severe or refractory disease among kidney transplant recipient in whom the risk of allograft loss is acceptable given the option of chronic dialysis.


Assuntos
Infecções por Vírus Epstein-Barr , Transplante de Rim , Transtornos Linfoproliferativos , Humanos , Criança , Estudos Retrospectivos , Transplante de Rim/efeitos adversos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/uso terapêutico , Ligantes , Infecções por Vírus Epstein-Barr/etiologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/etiologia , Apoptose
19.
Medicina (B Aires) ; 83 Suppl 4: 95-101, 2023 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-37714130

RESUMO

INTRODUCTION: Cerebral venous sinus thrombosis (CVST) is a well-known, although underestimated, cause of stroke in childhood. Its diagnosis requires a high index of suspicion, a correct interpretation of neuroimaging studies and an interrelation between clinicians and radiologists. The clinical features, risk factors and neuroimaging of children under 15 years of age with CVST were analyzed. METHODS: multicenter, retrospective, descriptive, study of a consecutive series of cases of children under 15 years of age, who were admitted due to CVST between January 1st, 2010, and March 1st, 2022. RESULTS: The study included 51 patients: 39% with acute symptoms and 59% with subacute symptoms. Newborns predominantly presented encephalopathic symptoms and seizures, while children exhibited signs of intracranial hypertension (ICH). Risk factors were identified in 90% of the cases. Magnetic resonance with angiography in venous time confirmed the diagnosis in 80% of the patients, with the straight sinus being the most affected in newborns and the lateral sinus in children. Hemorrhagic complications were found in 30.5%, being more frequent in newborns. Anticoagulation was initiated in 82% without complications. Sequelae were present in 44.4% of newborns and 37.9% of children, being more frequent and severe in newborns. CONCLUSIONS: To make an early diagnosis, it is essential to consider CVST in newborns with encephalopathic symptoms and/or seizures, and in children with signs of ICH in the presence of predisposing or triggering conditions.


Introducción: La trombosis de venas y senos venosos cerebrales (TVSC) constituye una causa conocida, aunque subestimada de ictus en la infancia. Su diagnóstico requiere un alto índice de sospecha, una correcta interpretación de la neuroimagen e interrelación entre el clínico y el radiólogo. OBJETIVO: Analizar las manifestaciones clínicas, factores de riesgo y neuroimagen de recién nacidos (RN) y niños menores de 15 años con TVSC. Métodos: Estudio descriptivo, retrospectivo, multicéntrico, de una serie consecutiva de casos de menores de 15 años que ingresaron por TVSC entre el 1 de enero del 2010 y el 1 de marzo de 2022. RESULTADOS: El estudio incluyó 51 pacientes: 39% con síntomas agudos y 59% subagudos. En los RN predominaron síntomas encefalopáticos y convulsiones, mientras en los niños elementos de hipertensión endocraneana (HTEC). Se identificaron factores de riesgo en el 90% de los casos. La resonancia magnética con angiografía en tiempo venoso confirmó el diagnóstico en el 80%, siendo el seno recto el más afectado en RN y el seno lateral en niños. Se encontraron complicaciones hemorrágicas en 30.5%, siendo más frecuentes en los RN. Se inició anticoagulación en el 82% sin complicaciones. Las secuelas estuvieron presentes en 44.4% de RN y 37.9% de niños, siendo más frecuentes y graves en los RN. CONCLUSIONES: Para realizar un diagnóstico precoz es fundamental pensar en TVSC en RN con síntomas encefalopáticos y/o convulsiones y en mayores con clínica de HTEC en presencia de enfermedades predisponentes o desencadenantes.


Assuntos
Encefalopatias , Trombose dos Seios Intracranianos , Recém-Nascido , Humanos , Criança , Estudos Retrospectivos , Trombose dos Seios Intracranianos/diagnóstico por imagem , Trombose dos Seios Intracranianos/etiologia , Convulsões/etiologia , Angiografia
20.
J Pediatr Surg ; 58(10): 2006-2011, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37393165

RESUMO

INTRODUCTION: Pediatric surgery applicants are increasingly pursuing research in non-traditional fields including surgical innovation. This study aims to evaluate the relative value that pediatric surgeons involved in fellow selection place on innovation experience compared to traditional research. METHODS: A cross-sectional web-based survey of American Pediatric Surgical Association members involved in the selection of pediatric surgical fellows was conducted. Respondents reported their own innovation experience and were asked to identify valuable traits of applicants who completed an innovation fellowship. They rated the value of traditional research metrics including publications, presentations, and advanced degrees compared to patents and other innovation-related metrics. Comparisons were made between those with and without innovation experience with respect to gender, years in practice, and institutional role. RESULTS: One hundred thirty respondents were involved in pediatric surgery fellow selection. Innovation work was felt to be equal to or more valuable than basic science by 75% of respondents (84% vs. clinical/outcomes, 93% vs. other non-traditional, 72% vs. other clinical fellowships). Commonly cited concerns included "fewer publications" (21%) and "preoccupation with financial reward" (19%). The most valuable innovation-related metrics were "developing a novel surgical procedure" (67%) and "developing a novel device" (58%). When asked if the respondent would advise a junior resident to pursue an innovation fellowship, 49% would, 9% would not, and 43% were unsure. Seventeen percent expressed concern for match success. CONCLUSION: Innovation experience is generally viewed positively by pediatric surgeons involved in fellow selection. However, applicants and mentors would benefit from focusing on traditional academic outputs to ensure competitiveness. TYPE OF STUDY: Cross-sectional observational study. LEVEL OF EVIDENCE: III.


Assuntos
Internato e Residência , Especialidades Cirúrgicas , Cirurgiões , Criança , Humanos , Estados Unidos , Bolsas de Estudo , Estudos Transversais , Atitude , Inquéritos e Questionários
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