Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 307
Filtrar
1.
J Surg Res ; 302: 484-489, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39173524

RESUMO

INTRODUCTION: Patients with pectus excavatum (PE) often undergo cross-sectional imaging (CSI) to quantify severity for insurance authorization before surgical repair. The modified percent depth (MPD), an external caliper-based metric, was previously validated to be similar to the pectus index and correction index. This study explored family perceptions of CSI and MPD with respect to value and costs. METHODS: This is a cross-sectional survey study including families of patients enrolled in an ongoing prospective multicenter study evaluating the use of MPD as an alternative to CSI for quantifying PE severity. Families of PE patients who underwent both MPD and CSI completed a survey to determine their perceptions of MPD and costs of CSI. Responses were described and associations were evaluated using chi squared, Wilcoxon rank-sum test and logistic regression as appropriate. Statistical significance was set to 0.05. RESULTS: There were 136 surveys completed for a response rate of 88%. Respondents were confident in MPD (86%) and confident in its similarity to CSI (76%). Families of females were less confident in the measurements than males (55% versus 80%, P = 0.02; odds ratio 0.30 (0.11, 0.83). Obtaining CSI required time off work/school in 90% and a copay in 60%. Nearly half (49%) of respondents reported CSI was a time/financial hardship. Increasing copay led to decreased reassurance in CSI (55%: copay > $100 versus 77%: lower copay/75%: no copay; P = 0.04). CONCLUSIONS: From the family perspective, MPD is valuable in assessing the severity of PE. Obtaining CSI was financially burdensome, particularly for those with higher copays. MPD measurements provide high value at low cost in assessing the severity of PE.

2.
J Virol Methods ; 329: 115007, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39154937

RESUMO

In the employment of serodiagnostic methods for the detection of orthoflavivirus infections, neutralization tests are known to be more accurate than measurements of antibody binding properties employing enzyme-linked immunosorbent assays. However, neutralization tests require infectious virus and laboratories with an appropriate level of biosafety. Single-round infectious particles (SRIPs), which encode a reporter gene instead of the viral structural protein genes, are replication incompetent and represent a safe and reliable alternative to the diagnosis of pathogenic viruses in neutralization tests. The orthoflavivirus SRIPs are produced by co-transfection of plasmids expressing virus-like particles and replicons into mammalian cell lines preferably with high transfection efficacy, such as HEK293T cells. However, certain orthoflavivirus SRIPs have limitations in their efficient expression at 37°C, which is the optimal temperature for mammalian cell growth, resulting in insufficient yields for neutralization tests. Here, we demonstrate that the production of orthoflavivirus SRIPs increases at the lower temperature of 28°C compared to 37°C. Moreover, infections with 28°C-cultured SRIPs in microneutralization tests were specifically inhibited in the presence of serum from mice infected with homologous viruses, suggesting that these SRIPs preserved their neutralizing epitopes for antibodies. Our method to produce high titer SRIPs is anticipated to promote efficient and safe SRIPs neutralization tests as a general serodiagnostic method for detecting virus-specific neutralizing antibodies against orthoflaviviruses.


Assuntos
Anticorpos Antivirais , Testes de Neutralização , Temperatura , Animais , Camundongos , Humanos , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Testes de Neutralização/métodos , Flexiviridae/genética , Flexiviridae/imunologia , Flexiviridae/isolamento & purificação , Cultura de Vírus/métodos , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Células HEK293 , Camundongos Endogâmicos BALB C
3.
Eur J Med Chem ; 276: 116592, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39013357

RESUMO

A novel group of 5,6-dihydropyrido [2',1':2,3]imidazo [4,5-c]quinolines was prepared via a microwave assisted one-pot telescopic approach. The synthetic sequence involves the formation of an amine precursor of imidazo [1,2-a]pyridine via condensation and reduction under microwave irradiation. Subsequently, the Pictet-Spengler cyclisation reaction occurs with ketones (cyclic or acyclic) to obtain substituted 5,6-dihydropyrido [2',1':2,3]imidazo [4,5-c]quinolines in excellent yields. The compounds were tested as neuroprotective agents. Observed protection of neuron-like cells, SH-SY5Y differentiated with ATRA, in Parkinson's and Huntington's disease models inspired further mechanistic studies of protective activity against damage induced by 1-methyl-4-phenylpyridinium (MPP+), a compound causing Parkinson's disease. The novel compounds exhibit similar or higher potency than ebselen, an established drug with antioxidant activity, in the cells against MPP + -induced total cellular superoxide production and cell death. However, they exhibit a significantly higher capacity to reduce mitochondrial superoxide and preserve mitochondrial membrane potential. We also observed marked differences between a selected derivative and ebselen in terms of normalizing MPP + -induced phosphorylation of Akt and ERK1/2. The cytoprotective activity was abrogated when signaling through cannabinoid receptor CB2 was blocked. The compounds also inhibit both acetylcholine and butyrylcholine esterases. Overall the data show that novel 5,6-dihydropyrido [2',1':2,3]imidazo [4,5-c]quinoline have a broad cytoprotective activity which is mediated by several mechanisms including mitoprotection.


Assuntos
Inibidores da Colinesterase , Fármacos Neuroprotetores , Quinolinas , Receptor CB2 de Canabinoide , Transdução de Sinais , Humanos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/síntese química , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Inibidores da Colinesterase/síntese química , Quinolinas/farmacologia , Quinolinas/química , Quinolinas/síntese química , Relação Estrutura-Atividade , Transdução de Sinais/efeitos dos fármacos , Receptor CB2 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/antagonistas & inibidores , Estrutura Molecular , Relação Dose-Resposta a Droga , Linhagem Celular Tumoral , Animais
4.
Tuberculosis (Edinb) ; 148: 102544, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39018651

RESUMO

The PhoPR system is a master regulator in Mycobacterium tuberculosis. A key difference between M. tuberculosis and Mycobacterium bovis is a G71I substitution in the M. bovis PhoR orthologue. Functional studies of the M. bovis PhoPR system have generated conflicting findings, with some research suggesting that the M. bovis PhoPR is defective while others indicate it is functional. We sought to revisit the functionality of the M. bovis PhoPR system. To address this, we constructed a phoPR mutant in the reference strain M. bovis AF2122/97. We employed a combination of growth assays and transcriptomics analyses to assess the phenotype of the mutant vs wild type and complemented strains. We found that the M. bovis AF2122/97 ΔphoPR mutant showed a growth defect on solid and liquid media compared to the wild type and complemented strains. The transcriptome of the M. bovis AF2122/97 ΔphoPR mutant was also altered as compared to wild type, including differential expression of genes involved in lipid metabolism and secretion. Our work provides further insight into the activity of PhoPR in M. bovis and underlines the importance of the PhoPR system as a master regulator of gene expression in the Mycobacterium tuberculosis complex.

5.
Emerg Infect Dis ; 30(8): 1609-1620, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39043403

RESUMO

SARS-CoV-2 can infect wildlife, and SARS-CoV-2 variants of concern might expand into novel animal reservoirs, potentially by reverse zoonosis. White-tailed deer and mule deer of North America are the only deer species in which SARS-CoV-2 has been documented, raising the question of whether other reservoir species exist. We report cases of SARS-CoV-2 seropositivity in a fallow deer population located in Dublin, Ireland. Sampled deer were seronegative in 2020 when the Alpha variant was circulating in humans, 1 deer was seropositive for the Delta variant in 2021, and 12/21 (57%) sampled deer were seropositive for the Omicron variant in 2022, suggesting host tropism expansion as new variants emerged in humans. Omicron BA.1 was capable of infecting fallow deer lung type-2 pneumocytes and type-1-like pneumocytes or endothelial cells ex vivo. Ongoing surveillance to identify novel SARS-CoV-2 reservoirs is needed to prevent public health risks during human-animal interactions in periurban settings.


Assuntos
COVID-19 , Cervos , SARS-CoV-2 , Animais , SARS-CoV-2/imunologia , SARS-CoV-2/genética , COVID-19/epidemiologia , COVID-19/veterinária , Humanos , Cervos/virologia , Irlanda/epidemiologia , Estudos Soroepidemiológicos , População Urbana , Reservatórios de Doenças/virologia , Reservatórios de Doenças/veterinária , Animais Selvagens/virologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Feminino , Masculino
6.
Acta Neurochir (Wien) ; 166(1): 243, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822878

RESUMO

BACKGROUND: Trigeminal schwannoma is a rare type of tumor that arises from the Schwann cells of the trigeminal nerve. METHOD: We present a case of a patient with a giant V2 trigeminal schwannoma with painful swelling in the left maxilla. A complete resection using a combined open maxillectomy and endoscopic endonasal approach was performed. CONCLUSION: This case highlights the importance of a multidisciplinary approach to perform a combined open and endoscopic approach for safe resection while preserving adequate speech and swallowing.


Assuntos
Neoplasias dos Nervos Cranianos , Neurilemoma , Humanos , Neoplasias dos Nervos Cranianos/cirurgia , Neoplasias dos Nervos Cranianos/patologia , Neoplasias dos Nervos Cranianos/diagnóstico por imagem , Endoscopia/métodos , Maxila/cirurgia , Maxila/diagnóstico por imagem , Cirurgia Endoscópica por Orifício Natural/métodos , Neurilemoma/cirurgia , Neurilemoma/diagnóstico por imagem , Neurilemoma/patologia , Resultado do Tratamento , Nervo Trigêmeo/cirurgia , Nervo Trigêmeo/patologia , Doenças do Nervo Trigêmeo/cirurgia , Doenças do Nervo Trigêmeo/patologia
7.
Front Pediatr ; 12: 1379254, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38751748

RESUMO

Background: Neuronal Ceroid Lipofuscinosis (NCL) disorders, recognized as the primary cause of childhood dementia globally, constitute a spectrum of genetic abnormalities. CLN8, a subtype within NCL, is characterized by cognitive decline, motor impairment, and visual deterioration. This study focuses on an atypical case with congenital onset and a remarkably slow disease progression. Methods: Whole-genome sequencing at 30× coverage was employed as part of a national genomics program to investigate the genetic underpinnings of rare diseases. This genomic approach aimed to challenge established classifications (vLINCL and EPMR) and explore the presence of a continuous phenotypic spectrum associated with CLN8. Results: The whole-genome sequencing revealed two novel likely pathogenic mutations in the CLN8 gene on chromosome 8p23.3. These mutations were not previously associated with CLN8-related NCL. Contrary to established classifications (vLINCL and EPMR), our findings suggest a continuous phenotypic spectrum associated with CLN8. Pathological subcellular markers further validated the genomic insights. Discussion: The identification of two previously undescribed likely pathogenic CLN8 gene mutations challenges traditional classifications and highlights a more nuanced phenotypic spectrum associated with CLN8. Our findings underscore the significance of genetic modifiers and interactions with unrelated genes in shaping variable phenotypic outcomes. The inclusion of pathological subcellular markers further strengthens the validity of our genomic insights. This research enhances our understanding of CLN8 disorders, emphasizing the need for comprehensive genomic analyses to elucidate the complexity of phenotypic presentations and guide tailored therapeutic strategies. The identification of new likely pathogenic mutations underscores the dynamic nature of CLN8-related NCL and the importance of individualized approaches to patient management.

8.
J Surg Res ; 299: 353-358, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38795558

RESUMO

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is a common respiratory morbidity among premature infants. Nissen fundoplication may be performed on infants with BPD to protect the lungs from gastroesophageal reflux-related aspiration, but the indications and benefits associated with fundoplication are not well-defined. This study evaluated associations of Nissen with clinical outcomes in infants with severe BPD (sBPD), using propensity score matching to minimize bias and confounding. METHODS: Infants ≤31 wk gestational age with sBPD (grade 2-3) admitted to a single neonatal intensive care unit (NICU) between January 2016 and October 2021 were included. Patients with sBPD who underwent Nissen fundoplication during initial NICU admission were propensity score-matched at a 1:2 ratio with control patients who did not undergo Nissen (no-Nissen). Outcomes were compared, including time to freedom from respiratory support (defined as ≤2 L nasal cannula), time to initial NICU discharge, and incidence of hospital readmission or death within 1 y postdischarge. RESULTS: After propensity score matching, 18 Nissen infants were compared with 30 no-Nissen infants. The Nissen group trended toward longer time to freedom from respiratory support (median 105 versus 70 d, P = 0.09), and had longer initial hospital stays (188 versus 111 d, P = 0.002), more 1-y hospital readmissions (83% versus 50%, P = 0.04), and more tracheostomies (28% versus 0%, P = 0.005). Mortality during first-year postdischarge was similar (6% versus 10%, P = 1.0). CONCLUSIONS: Despite adjustment for confounding variables, Nissen fundoplication was associated with prolonged support and greater resource utilization among infants with sBPD. Prospective studies are needed to clarify indications for fundoplication in this population.


Assuntos
Displasia Broncopulmonar , Fundoplicatura , Refluxo Gastroesofágico , Pontuação de Propensão , Humanos , Fundoplicatura/métodos , Fundoplicatura/estatística & dados numéricos , Displasia Broncopulmonar/cirurgia , Recém-Nascido , Masculino , Feminino , Estudos Retrospectivos , Refluxo Gastroesofágico/cirurgia , Lactente , Resultado do Tratamento , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Índice de Gravidade de Doença
9.
Bol. latinoam. Caribe plantas med. aromát ; 23(3): 371-381, mayo 2024. tab, ilus, mapas
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
10.
Chemistry ; 30(36): e202400828, 2024 Jun 25.
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 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.

11.
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
12.
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
13.
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
14.
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.

15.
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.

16.
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
17.
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
18.
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.

19.
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.

20.
Viruses ; 16(1)2024 01 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
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA