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1.
Invest Ophthalmol Vis Sci ; 65(4): 10, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38573620

RESUMO

Purpose: In a previous study, we documented that the Intravitreal injections (IVIs) of bevacizumab in rats caused a retinal inflammatory response. We now study whether the IVI of other humanized anti-VEGF: ranibizumab and aflibercept also cause an inflammatory reaction in the rat retina and if it depends on the dose administered. Finally, we study whether this reaction affects retinal ganglion cell (RGC) survival. Methods: Albino Sprague-Dawley rats received a single IVI of 5 µL of PBS or ranibizumab or aflibercept at the concentration used in clinical practice (10 µg/µL or 40 µg/µL) or at a lower concentration (0.38 µg/µL and 1.5 µg/µL) calculated to obtain within the rat eye the same concentration as in the human eye in clinical practice. Others received a single 5 µL IVI of a polyclonal goat anti-rat VEGF (0.015 µg/µL) or of vehicle (PBS). Animals were processed 7 days or 1 month later. Retinal whole mounts were immunolabeled for the detection of microglial, macroglial, RGCs, and intrinsically photosensitive RGCs (ipRGCs). Fluorescence and confocal microscopy were used to examine retinal changes, and RGCs and ipRGCs were quantified automatically or semiautomatically, respectively. Results: All the injected substances including the PBS induced detectable side effects, namely, retinal microglial cell activation and retinal astrocyte hypertrophy. However, there was a greater microglial and macroglial response when the higher concentrations of ranibizumab and aflibercept were injected than when PBS, the antibody anti-rat VEGF and the lower concentrations of ranibizumab or aflibercept were injected. The higher concentration of ranibizumab and aflibercept resulted also in significant RGC death, but did not cause appreciable ipRGC death. Conclusions: The IVI of all the substances had some retinal inflammatory effects. The IVI of humanized anti-VEGF to rats at high doses cause important side effects: severe inflammation and RGC death, but not ipRGC death.


Assuntos
Fatores de Crescimento Endotelial , Células Ganglionares da Retina , Humanos , Ratos , Animais , Injeções Intravítreas , Ranibizumab/toxicidade , Fator A de Crescimento do Endotélio Vascular , Ratos Sprague-Dawley , Cabras , Neuroglia
2.
Animals (Basel) ; 14(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38473127

RESUMO

A retrospective study of microbiological laboratory results from 2020 to 2022, obtained from a veterinary diagnostic laboratory of the island of Gran Canaria, Spain, focused on canine otitis cases, was performed. The objective of this study was to analyze the pathogen distribution, antimicrobial susceptibility, prevalence of multidrug resistant phenotypes and the role of coinfections in otitis cases in order to provide up-to-date evidence that could support effective control strategies for this prevalent pathology. A total of 604 submissions were processed for the diagnosis of canine external otitis. Of the samples analyzed, 472 were positive for bacterial or fungal growth (78.1%; 95% CI: 74.8-81.4%). A total of 558 microbiological diagnoses were obtained, divided in 421 bacterial (75.4%; 95% CI: 71.8-79.0%) and 137 fungal (24.6%; 95% CI: 20.9-28.1%) identifications. Staphylococcus pseudintermedius, Malassezia pachydermatis and Pseudomonas aeruginosa were the most prevalent microorganisms detected in clinical cases of otitis. High level antimicrobial resistance was found for Pseudomonas aeruginosa (30.7%), Proteus mirabilis (29.4%), Staphylococcus pseudintermedius (25.1%) and Escherichia coli (19%). Multidrug-resistant phenotypes were observed in 47% of the bacteria isolated. In addition, a 26.4% prevalence of methicillin-resistant Staphylococcus pseudintermedius was detected. The high prevalence of antimicrobial resistant phenotypes in these bacteria highlights the current necessity for constant up-to-date prevalence and antimicrobial susceptibility data that can support evidence-based strategies to effectively tackle this animal and public health concern.

3.
Biomedicines ; 12(3)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38540142

RESUMO

The murine models of Alzheimer's disease (AD) have advanced our understanding of the pathophysiology. In vivo studies of the retina using optical coherence tomography (OCT) have complemented histological methods; however, the lack of standardisation in OCT methodologies for murine models of AD has led to significant variations in the results of different studies. A literature search in PubMed and Scopus has been performed to review the different methods used in these models using OCT and to analyse the methodological characteristics of each study. In addition, some recommendations are offered to overcome the challenges of using OCT in murine models. The results reveal a lack of consensus on OCT device use, retinal area analysed, segmentation techniques, and analysis software. Although some studies use the same OCT device, variations in other parameters make the direct comparison of results difficult. Standardisation of retinal analysis criteria in murine models of AD using OCT is crucial to ensure consistent and comparable results. This implies the application of uniform measurement and segmentation protocols. Despite the absence of standardisation, OCT has proven valuable in advancing our understanding of the pathophysiology of AD.

4.
Biofilm ; 7: 100190, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38515541

RESUMO

Mycoplasmas are known as the minimalist microorganisms in the microbes' world. Their minimalist nature makes them highly sensitive to the environmental conditions and limits their ability to survive for extended periods outside their animal host. Nevertheless, there are documented instances of mycoplasma transmission over significant distances and this phenomenon may be linked to relatively unexplored abilities of mycoplasmas, such as their capacity to synthesize biofilm-the predominant mode of bacterial growth in nature. The authors decided to establish a method aimed at inducing the clustering of mycoplasma planktonic cells within a biofilm in vitro and subsequently assess the capacity of certain avian mycoplasmas to synthesize a biofilm. A total of 299 avian mycoplasma isolates were included in the study, encompassing both pathogenic (Mycoplasma gallisepticum, M. synoviae, M. meleagridis, M. iowae) and non-pathogenic species (M. gallinaceum, M. gallinarum, M. iners and M. pullorum). The authors successfully demonstrated the feasibility of inducing avian mycoplasmas to synthetize in vitro a biofilm, which can be visually quantified. The only species that did not produce any biofilm was M. iowae. In general, the pathogenic mycoplasmas produced greater quantities of biofilm compared to the non-pathogenic ones. Furthermore, it was observed that the ability to produce biofilm appeared to vary, both qualitatively and quantitatively, not only among different species but also among isolates of a single species. Future studies will be necessary to determine whether biofilm production plays a pivotal epidemiological role for the pathogenic avian mycoplasmas.

5.
Sci Rep ; 14(1): 6917, 2024 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519529

RESUMO

Variants in the CNNM2 gene are causative for hypomagnesaemia, seizures and intellectual disability, although the phenotypes can be variable. This study aims to understand the genotype-phenotype relationship in affected individuals with CNNM2 variants by phenotypic, functional and structural analysis of new as well as previously reported variants. This results in the identification of seven variants that significantly affect CNNM2-mediated Mg2+ transport. Pathogenicity of these variants is further supported by structural modelling, which predicts CNNM2 structure to be affected by all of them. Strikingly, seizures and intellectual disability are absent in 4 out of 7 cases, indicating these phenotypes are caused either by specific CNNM2 variant only or by additional risk factors. Moreover, in line with sporadic observations from previous reports, CNNM2 variants might be associated with disturbances in parathyroid hormone and Ca2+ homeostasis.


Assuntos
Proteínas de Transporte de Cátions , Deficiência Intelectual , Humanos , Deficiência Intelectual/genética , Magnésio/metabolismo , Convulsões/genética , Fenótipo , Proteínas de Transporte de Cátions/genética
6.
Int J Mol Sci ; 25(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38542089

RESUMO

Glaucoma is a neurodegenerative disease that causes blindness. In this study, we aimed to evaluate the protective role of cilastatin (CIL), generally used in the treatment of nephropathologies associated with inflammation, in an experimental mouse model based on unilateral (left) laser-induced ocular hypertension (OHT). Male Swiss mice were administered CIL daily (300 mg/kg, i.p.) two days before OHT surgery until sacrifice 3 or 7 days later. Intraocular Pressure (IOP), as well as retinal ganglion cell (RGC) survival, was registered, and the inflammatory responses of macroglial and microglial cells were studied via immunohistochemical techniques. Results from OHT eyes were compared to normotensive contralateral (CONTRA) and naïve control eyes considering nine retinal areas and all retinal layers. OHT successfully increased IOP values in OHT eyes but not in CONTRA eyes; CIL did not affect IOP values. Surgery induced a higher loss of RGCs in OHT eyes than in CONTRA eyes, while CIL attenuated this loss. Similarly, surgery increased macroglial and microglial activation in OHT eyes and to a lesser extent in CONTRA eyes; CIL prevented both macroglial and microglial activation in OHT and CONTRA eyes. Therefore, CIL arises as a potential effective strategy to reduce OHT-associated damage in the retina of experimental mice.


Assuntos
Glaucoma , Doenças Neurodegenerativas , Hipertensão Ocular , Masculino , Camundongos , Animais , Doenças Neurodegenerativas/complicações , Glaucoma/etiologia , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/patologia , Pressão Intraocular , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Cilastatina/uso terapêutico , Modelos Animais de Doenças
7.
J Lipid Res ; 65(3): 100516, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38320654

RESUMO

The gold-standard diagnostic test for peroxisomal disorders (PDs) is plasma concentration analysis of very long-chain fatty acids (VLCFAs). However, this method's time-consuming nature and limitations in cases which present normal VLCFA levels necessitates alternative approaches. The analysis of C26:0-lysophosphatydylcholine (C26:0-LPC) in dried blood spot samples by tandem-mass spectrometry (MS/MS) has successfully been implemented in certain newborn screening programs to diagnose X-linked adrenoleukodystrophy (ALD). However, the diagnostic potential of very long-chain LPCs concentrations in plasma remains poorly understood. This study sought to evaluate the diagnostic performance of C26:0-LPC and other very long-chain LPCs, comparing them to VLCFA analysis in plasma. The study, which included 330 individuals affected by a peroxisomal ß-oxidation deficiency and 407 control individuals, revealed that C26:0- and C24:0-LPC concentrations demonstrated the highest diagnostic accuracy (98.8% and 98.4%, respectively), outperforming VLCFA when C26:0/C22:0 and C24:0/C22:0 ratios were combined (98.1%). Combining C24:0- and C26:0-LPC gave the highest sensitivity (99.7%), with ALD females exhibiting notably higher sensitivity compared with the VLCFA ratio combination (98.7% vs. 93.5%, respectively). In contrast, C22:0-LPC exhibited suboptimal performance, primarily due to its low sensitivity (75%), but we identified a potential use to help distinguish between ALD and Zellweger spectrum disorders. In summary, MS/MS analysis of plasma C24:0- and C26:0-LPC concentrations represents a rapid and straightforward approach to diagnose PDs, demonstrating superior diagnostic accuracy, particularly in ALD females, compared with conventional VLCFA biomarkers. We strongly recommend integrating very-long chain LPC plasma analysis in the diagnostic evaluation of individuals suspected of having a PD.


Assuntos
Adrenoleucodistrofia , Lisofosfatidilcolinas , Recém-Nascido , Feminino , Humanos , Espectrometria de Massas em Tandem , Adrenoleucodistrofia/diagnóstico , Triagem Neonatal/métodos , Biomarcadores , Ácidos Graxos não Esterificados , Ácidos Graxos
9.
Nefrologia (Engl Ed) ; 44(1): 23-31, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38350738

RESUMO

Renal diseases associated with hypomagnesemia are a complex and diverse group of tubulopathies caused by mutations in genes encoding proteins that are expressed in the thick ascending limb of the loop of Henle and in the distal convoluted tubule. In this paper, we review the initial description, the clinical expressiveness and etiology of four of the first hypomagnesemic tubulopathies described: type 3 Bartter and Gitelman diseases, Autosomal recessive hypomagnesemia with secondary hypocalcemia and Familial hypomagnesemia with hypercalciuria and nephrocalcinosis. The basic biochemical patterns observed in renal tubular hypomagnesemias and the modalities of transport and interaction that occur between the transporters involved in the reabsorption of magnesium in the distal convoluted tubule are described below. Finally, the recent report of a new renal disease with hypomagnesemia, type 2 hypomagnesemia with secondary hypocalcemia caused by reduced TRPM7 channel activity is described.


Assuntos
Hipocalcemia , Deficiência de Magnésio/congênito , Nefrocalcinose , Canais de Cátion TRPM , Humanos , Magnésio , Nefrocalcinose/genética , Túbulos Renais , Proteínas Serina-Treonina Quinases , Canais de Cátion TRPM/genética
10.
Nefrología (Madrid) ; 44(1): 23-31, ene.- feb. 2024. ilus
Artigo em Espanhol | IBECS | ID: ibc-229418

RESUMO

Las enfermedades renales que cursan con hipomagnesemia son un grupo complejo y variopinto de tubulopatías producidas por mutaciones en genes que codifican proteínas que se expresan en la rama gruesa ascendente del asa de Henle y en el túbulo contorneado distal. En el presente artículo revisamos la descripción inicial, la expresividad clínica y la etiología de cuatro de las primeras causas de tubulopatías hipomagnesémicas que se describieron: las enfermedades de Bartter tipo 3 y Gitelman, la hipomagnesemia con hipocalcemia secundaria autosómica recesiva y la hipomagnesemia familiar con hipercalciuria y nefrocalcinosis. A continuación, se describen los patrones bioquímicos básicos que se observan en las hipomagnesemias tubulares renales y las modalidades de transporte e interacción que concurren entre los transportadores implicados en la reabsorción de magnesio en el túbulo contorneado distal. Finalmente, se comunica la reciente descripción de una nueva tubulopatía hipomagnesémica, la hipomagnesemia con hipocalcemia secundaria tipo 2 causada por una reducción de la actividad del canal TRPM7 (AU)


Renal diseases associated with hypomagnesemia are a complex and diverse group of tubulopathies caused by mutations in genes encoding proteins that are expressed in the thick ascending limb of the loop of Henle and in the distal convoluted tubule. In this paper, we review the initial description, the clinical expressiveness and etiology of four of the first hypomagnesemic tubulopathies described: Type 3 Bartter and Gitelman diseases,Autosomal recessive hypomagnesemia with secondary hypocalcemia and Familial hypomagnesemia with hypercalciuria and nephrocalcinosis. The basic biochemical patterns observed in renal tubular hypomagnesemias and the modalities of transport and interaction that occur between the transporters involved in the reabsorption of magnesium in the distal convoluted tubule are described below. Finally, the recent report of a new renal disease with hypomagnesemia, Type 2 hypomagnesemia with secondary hypocalcemia caused by reduced TRPM7 channel activity is described (AU)


Assuntos
Humanos , Deficiência de Magnésio/genética , Alça do Néfron/metabolismo , Túbulos Renais Distais/metabolismo
11.
Front Cell Neurosci ; 18: 1354569, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38333055

RESUMO

Glaucoma is a neurodegenerative disease of the retina characterized by the irreversible loss of retinal ganglion cells (RGCs) leading to visual loss. Degeneration of RGCs and loss of their axons, as well as damage and remodeling of the lamina cribrosa are the main events in the pathogenesis of glaucoma. Different molecular pathways are involved in RGC death, which are triggered and exacerbated as a consequence of a number of risk factors such as elevated intraocular pressure (IOP), age, ocular biomechanics, or low ocular perfusion pressure. Increased IOP is one of the most important risk factors associated with this pathology and the only one for which treatment is currently available, nevertheless, on many cases the progression of the disease continues, despite IOP control. Thus, the IOP elevation is not the only trigger of glaucomatous damage, showing the evidence that other factors can induce RGCs death in this pathology, would be involved in the advance of glaucomatous neurodegeneration. The underlying mechanisms driving the neurodegenerative process in glaucoma include ischemia/hypoxia, mitochondrial dysfunction, oxidative stress and neuroinflammation. In glaucoma, like as other neurodegenerative disorders, the immune system is involved and immunoregulation is conducted mainly by glial cells, microglia, astrocytes, and Müller cells. The increase in IOP produces the activation of glial cells in the retinal tissue. Chronic activation of glial cells in glaucoma may provoke a proinflammatory state at the retinal level inducing blood retinal barrier disruption and RGCs death. The modulation of the immune response in glaucoma as well as the activation of glial cells constitute an interesting new approach in the treatment of glaucoma.

12.
Int J Mol Sci ; 25(4)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38397059

RESUMO

This study explores the impact of plasma treatment on Lavandin Grosso flowers and its influence on the extraction of essential oils (EOs) via hydrodistillation. Short plasma treatment times enhance the yield of EO extraction from 3.19% in untreated samples to 3.44%, corresponding to 1 min of plasma treatment, while longer treatment times (10 min) show diminishing returns to 3.07% of yield extraction. Chemical characterization (GC/MS and ATR-FTIR) indicates that plasma treatments do not significantly alter the chemical composition of the extracted EOs, preserving their aromatic qualities. Investigations into plasma-surface interactions reveal changes at the nanometer level, with XPS confirming alterations in the surface chemistry of Lavandin Grosso flowers by reducing surface carbon and increasing oxygen content, ultimately resulting in an increased presence of hydrophilic groups. The presence of hydrophilic groups enhances the interaction between the surface membrane of the glandular trichomes on Lavandin Grosso flowers and water vapor, consequently increasing the extraction of EOs. Furthermore, microscopic SEM examinations demonstrate that plasma treatments do not affect the morphology of glandular trichomes, emphasizing that surface modifications primarily occur at the nanoscale. This study underscores the potential of plasma technology as a tool to enhance EO yields from botanical sources while maintaining their chemical integrity.


Assuntos
Óleos Voláteis , Óleos Voláteis/química , Cromatografia Gasosa-Espectrometria de Massas , Flores/química , Vapor , Tecnologia
13.
J Eat Disord ; 12(1): 13, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254246

RESUMO

Existing descriptions of the treatment of avoidant/restrictive food intake disorder (ARFID) at higher levels of care (HLOC) for eating disorders are limited, despite HLOC settings frequently serving patients with ARFID. The purpose of this commentary is to expand on the preliminary literature that describes pediatric ARFID treatment at HLOC by describing two specific components of our approach to treating pediatric ARFID that may not yet have traction in the current literature. Specifically, we highlight the utility of (1) treatment accommodations that appropriately account for patients' neurodevelopmental needs (e.g., executive functioning, sensory processing) and (2) the adjunctive use of Dialectical Behavior Therapy (DBT) elements within family-based pediatric ARFID treatment. We also describe necessary future directions for research in these domains to clarify if incorporating these considerations and approaches into pediatric ARFID treatment at HLOC does indeed improve treatment outcomes.

14.
Nat Commun ; 15(1): 544, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38228587

RESUMO

What a strain is and how many strains make up a natural bacterial population remain elusive concepts despite their apparent importance for assessing the role of intra-population diversity in disease emergence or response to environmental perturbations. To advance these concepts, we sequenced 138 randomly selected Salinibacter ruber isolates from two solar salterns and assessed these genomes against companion short-read metagenomes from the same samples. The distribution of genome-aggregate average nucleotide identity (ANI) values among these isolates revealed a bimodal distribution, with four-fold lower occurrence of values between 99.2% and 99.8% relative to ANI >99.8% or <99.2%, revealing a natural "gap" in the sequence space within species. Accordingly, we used this ANI gap to define genomovars and a higher ANI value of >99.99% and shared gene-content >99.0% to define strains. Using these thresholds and extrapolating from how many metagenomic reads each genomovar uniquely recruited, we estimated that -although our 138 isolates represented about 80% of the Sal. ruber population- the total population in one saltern pond is composed of 5,500 to 11,000 genomovars, the great majority of which appear to be rare in-situ. These data also revealed that the most frequently recovered isolate in lab media was often not the most abundant genomovar in-situ, suggesting that cultivation biases are significant, even in cases that cultivation procedures are thought to be robust. The methodology and ANI thresholds outlined here should represent a useful guide for future microdiversity surveys of additional microbial species.


Assuntos
Bactérias , Bacteroidetes , Bactérias/genética , Bacteroidetes/genética , Metagenômica/métodos , Metagenoma/genética , Filogenia , Genoma Bacteriano/genética
15.
Nutr Hosp ; 2024 Jan 15.
Artigo em Espanhol | MEDLINE | ID: mdl-38258653

RESUMO

INTRODUCTION: intestinal failure (IF) is an organic failure classified into three types (I-III); it conditions inability to absorb nutrients and water, so parenteral nutrition (PN) is required. OBJECTIVE: to evaluate the characteristics of hospitalized patients with IF, and their association with clinical and nutritional outcomes. METHODS: historical cohort of hospitalized adults with IF and PN. Variables of the nutritional care process (screening, anthropometric, biochemical, clinical, nutritional), mortality and hospital stay were recorded. RESULTS: six hundred and ninety-seven patients aged 56 (41-68) years, 327 women (46.8 %), with body mass index (BMI) 22.4 (18.3-25.9), were included. DIAGNOSIS: 577 patients with IF-I, 96 patients with IF-II, and 24 patients with IF-III. The most frequent causes were malignant neoplasms, IF-I (26.7 %) and surgical complications in IF-II (21.9 %) and IF-III (37.5 %). The most common pathophysiology in all types of IF was motility disorders (40.6 % in IF-I; 43.8 % in IF-II; 33.8 % in IF-III). The majority of patients had high nutritional risk (92.4 %) and refeeding syndrome (65.6 % high and very high). In acute IF (FI-I) compared to prolonged IF (If-II/IF-III) there is a higher BMI (p = 0.039), visceral fat (p = 0.041) and over-hydration (p = 0.014), but they have a smaller phase angle (p = 0.004), with a lower adequacy percentage than what is prescribed in relation to their energy expenditure (p < 0.001). CONCLUSIONS: during the nutritional care process there are differences between the types of IF, which are relevant to optimize their multidisciplinary management and avoid related complications.

16.
Chem Biodivers ; 21(2): e202301930, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38216544

RESUMO

The aim of this study was to screen sixteen meso-1 semi-synthetic derivatives bearing ether, esther, carbamate, phosphate or aminoether functional groups against five cancer cell lines: MCF-7 (breast), A549 (lung), HepG2 (liver), HeLa (cervix), and DU145 (prostate) at 25 µM using the MTT assay. Results from the screening showed that two derivatives had the lowest percentage of cell viability at 25 µM, the aminoether derivative meso-11 and the esther derivative meso-20 against A549 (44.15±0.78 %) and MCF-7 (41.60±0.92 %), respectively. Then, it was determined the IC50 value of each compound against their most sensitive cancer cell line. Results showed that aminoether derivative meso-11 showed potent cytotoxicity against A549 (IC50 =17.11±2.11 µM), whereas it resulted more cytotoxic against the LL-47 lung normal cell line (IC50 =9.49±1.19 µM) having a Selective Index (SI) of 0.55. On the other hand, the esther derivative meso-20 exhibited potent activity against MCF-7 (IC50 =18.20±1.98 µM), whereas it displayed moderate cytotoxicity against the MCF-10 breast normal cell line (IC50 =41.22±2.17 µM) with a SI of 2.2. Finally, studies on the mechanism of action of meso-20 indicated disruption of MCF-7 plasma membrane in vitro and the AMPK activation in silico.


Assuntos
Antineoplásicos , Guaiacol/análogos & derivados , Lignanas , Masculino , Humanos , Relação Estrutura-Atividade , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos/farmacologia , Lignanas/farmacologia , Proliferação de Células , Estrutura Molecular , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Células MCF-7
17.
Clin Chem Lab Med ; 62(3): 493-505, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-37794778

RESUMO

OBJECTIVES: Acylcarnitine and amino acid analyses of dried blood spot (DBS) samples using tandem mass spectrometry in newborn screening (NBS) programmes can generate false positive (FP) results. Therefore, implementation of second-tier tests (2TTs) using DBS samples has become increasingly important to avoid FPs. The most widely used 2TT metabolites include methylmalonic acid, 3-hydroxypropionic acid, methylcitric acid, and homocysteine. METHODS: We simultaneously measured 46 underivatised metabolites, including organic acids, acylglycine and acylcarnitine isomers, homocysteine, and orotic acid, in DBS samples using tandem mass spectrometry. To validate this method, we analysed samples from 147 healthy newborns, 160 patients with genetic disorders diagnosed via NBS, 20 patients with acquired vitamin B12 deficiency, 10 newborns receiving antibiotic treatment, and nine external quality control samples. RESULTS: The validation study revealed that 31 metabolites showed good analytical performance. Furthermore, this method detected key metabolites for all diseases associated with increased levels of the following acylcarnitines: C3, C4, C5, C4DC/C5OH, and C5DC. The sensitivity of this method to detect all diseases was 100 %, and the specificity was 74-99 %, except for glutaric aciduria type 1. This method can also be used to diagnose mitochondrial fatty acid ß-oxidation disorders (FAODs) and urea cycle defects (UCDs). CONCLUSIONS: We have described a 2TT panel of 31 metabolites in DBS samples based on an easy and rapid method without derivatisation. Its implementation allowed us to distinguish between different organic acidurias, some FAODs, and UCDs. This new strategy has increased the efficiency of our NBS programme by reducing FP and false negative results, second sample requests, and the time required for diagnosis.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Encefalopatias Metabólicas , Carnitina/análogos & derivados , Glutaril-CoA Desidrogenase/deficiência , Triagem Neonatal , Espectrometria de Massas em Tandem , Humanos , Recém-Nascido , Espectrometria de Massas em Tandem/métodos , Triagem Neonatal/métodos , Espanha , Cromatografia Líquida/métodos , Homocisteína , Teste em Amostras de Sangue Seco/métodos
18.
Transcult Psychiatry ; 61(1): 95-106, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37964582

RESUMO

It cannot be assumed that the experience of having an autistic child is the same across countries since demographic and systemic factors are as diverse as the manifestation of ASD symptomatology. This study explores the lived experiences of 20 Venezuelan parents after receiving an autism diagnosis for their child. Applied thematic analysis was used to analyze parental attitudes, challenges in identifying their child's delay, access to diagnostic services, beliefs towards autism, professional evaluations, family support, and perceptions toward health and educational services for autistic children. Venezuelan parents reported a generalized lack of autism awareness, an unsupportive school system, and judgment from their extended family. Despite the universal health coverage in the country, Venezuelan parents commented on the scarcity of services, as well as the lengthy and costly processes to receive an ASD diagnosis. The results support previous research findings showing that socioeconomic factors influence how parents experience the process of obtaining an autism diagnosis for their children. For most Venezuelan parents, it might imply a long journey in which limited resources and knowledge about autism will determine its route and length. For parents, cultural values and spiritual and religious beliefs will serve as both coping mechanisms and barriers to accessing services.


Assuntos
Transtorno Autístico , Criança , Humanos , Transtorno Autístico/diagnóstico , Pais , Fatores Socioeconômicos , Instituições Acadêmicas
19.
Autism ; 28(1): 58-72, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36602228

RESUMO

LAY ABSTRACT: An earlier diagnosis of autism spectrum disorder might lead to earlier intervention. However, people living in Latin American and Caribbean countries do not have much knowledge about autism spectrum disorder symptoms. It has been suggested that the older a child is when diagnosed, the fewer opportunities he or she will have to receive services. We asked 2520 caregivers of autistic children in six different Latin America and Caribbean Countries, the child's age when they noticed some developmental delays and their child's age when they received their first autism spectrum disorder diagnosis. Results indicate that, on average, caregivers were concerned about their child's development by 22 months of age; however, the diagnosis was received when the child was 46 months of age. In addition, older children with better language abilities and public health coverage (opposed to private health coverage) were diagnosed later. On the contrary, children with other medical problems and more severe behaviors received an earlier diagnosis. In our study, children were diagnosed around the time they entered formal schooling, delaying the access to early intervention programs. In summary, the characteristics of the autistic person and the type of health coverage influence the age of diagnosis in children living in Latin America and Caribbean Countries.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Criança , Feminino , Humanos , Adolescente , Transtorno Autístico/diagnóstico , América Latina , Transtorno do Espectro Autista/diagnóstico , Região do Caribe
20.
Repert. med. cir ; 33(1): 61-66, 2024. tab, graf
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1552533

RESUMO

Introducción: el ataque cerebrovascular (ACV) es común a nivel mundial, una de cada cuatro personas puede presentarlo a lo largo de la vida. Constituye la segunda causa de muerte y la tercera principal de discapacidad. Es importante la atención integral para lograr un impacto en la calidad de vida. Objetivo: determinar la calidad de atención en el manejo del ACV isquémico agudo de los pacientes que consultaron al servicio de neurología en los Hospitales de San José e Infantil Universitario de San José, Bogotá DC, entre enero 1/2019 y enero 1/2020. Metodología: estudio descriptivo de corte transversal. El criterio de inclusión fue pacientes mayores de 18 años con diagnóstico de ACV isquémico. La información se recolectó de las historias clínicas, se empleó estadística descriptiva para analizar los datos. Resultados: se incluyeron 411 pacientes, 88,8% sin alteración del estado de conciencia, 26,4% ingresaron antes de las 4,5 horas de ventana para trombólisis, se realizaron procedimientos de recanalización endovenosa a 11,4%. El tiempo puerta aguja tuvo una mediana de 37,2 minutos comparado con la mediana nacional de tiempo que fue 56,5 min según lo registrado en la plataforma ResQ. El 72% recibió terapia antiagregante y estatina 88.8%. Discusión y conclusiones: al identificar los síntomas es importante ser estrictos en el tiempo de atención y la implementación de plataformas para óptimos planes de atención. Se requieren campañas masivas de educación, así como que planes de mejora institucionales.


Introduction: cerebrovascular attack (CVA) is common worldwide. One in four people may have a stroke during their lifetime. It is the second leading cause of death and the third leading cause of disability. Thus, it is important to provide integrated care to achieve an impact on quality of life. Objective: to determine ischemic CVA management quality of care among patients seen at the neurology service of the San José and Infantil Universitario de San José hospitals in Bogotá DC, between January 1/2019 and January 1/2020. Methodology: a descriptive, cross-sectional study. The inclusion criteria included patients over 18 years of age diagnosed with ischemic CVA. Information was collected from clinical records. Data was analyzed using descriptive statistics. Results: 411 patients were included; 88.8% had an altered state of consciousness, 26.4% were admitted within the 4.5-hour window for thrombolysis; 11.4% underwent intravenous reperfusion procedures. Door-to-needle time: median was 37.2 minutes versus the national media of 56.5 min according to the ResQ records platform; 72% received anti-platelet therapy and 88.8% received statins. Discussion and conclusions: the establishment of a strict time to care and the implementation of platforms to improve care plans, is essential. Massive education campaigns are required, as well as, institutional improvement plans.


Assuntos
Humanos
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