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1.
N Engl J Med ; 390(23): 2156-2164, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38899694

RESUMEN

BACKGROUND: Variants in APOE and PSEN1 (encoding apolipoprotein E and presenilin 1, respectively) alter the risk of Alzheimer's disease. We previously reported a delay of cognitive impairment in a person with autosomal dominant Alzheimer's disease caused by the PSEN1 E280A variant who also had two copies of the apolipoprotein E3 Christchurch variant (APOE3 Ch). Heterozygosity for the APOE3 Ch variant may influence the age at which the onset of cognitive impairment occurs. We assessed this hypothesis in a population in which the PSEN1 E280A variant is prevalent. METHODS: We analyzed data from 27 participants with one copy of the APOE3 Ch variant among 1077 carriers of the PSEN1 E280A variant in a kindred from Antioquia, Colombia, to estimate the age at the onset of cognitive impairment and dementia in this group as compared with persons without the APOE3 Ch variant. Two participants underwent brain imaging, and autopsy was performed in four participants. RESULTS: Among carriers of PSEN1 E280A who were heterozygous for the APOE3 Ch variant, the median age at the onset of cognitive impairment was 52 years (95% confidence interval [CI], 51 to 58), in contrast to a matched group of PSEN1 E280A carriers without the APOE3 Ch variant, among whom the median age at the onset was 47 years (95% CI, 47 to 49). In two participants with the APOE3 Ch and PSEN1 E280A variants who underwent brain imaging, 18F-fluorodeoxyglucose positron-emission tomographic (PET) imaging showed relatively preserved metabolic activity in areas typically involved in Alzheimer's disease. In one of these participants, who underwent 18F-flortaucipir PET imaging, tau findings were limited as compared with persons with PSEN1 E280A in whom cognitive impairment occurred at the typical age in this kindred. Four studies of autopsy material obtained from persons with the APOE3 Ch and PSEN1 E280A variants showed fewer vascular amyloid pathologic features than were seen in material obtained from persons who had the PSEN1 E280A variant but not the APOE3 Ch variant. CONCLUSIONS: Clinical data supported a delayed onset of cognitive impairment in persons who were heterozygous for the APOE3 Ch variant in a kindred with a high prevalence of autosomal dominant Alzheimer's disease. (Funded by Good Ventures and others.).


Asunto(s)
Edad de Inicio , Enfermedad de Alzheimer , Apolipoproteína E3 , Heterocigoto , Presenilina-1 , Humanos , Enfermedad de Alzheimer/genética , Presenilina-1/genética , Femenino , Masculino , Persona de Mediana Edad , Apolipoproteína E3/genética , Tomografía de Emisión de Positrones , Anciano , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Adulto , Genes Dominantes , Colombia
2.
Alzheimers Dement ; 19(6): 2585-2594, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36571821

RESUMEN

INTRODUCTION: Plasma-measured tau phosphorylated at threonine 217 (p-tau217) is a potential non-invasive biomarker of Alzheimer's disease (AD). We investigated whether plasma p-tau217 predicts subsequent cognition and positron emission tomography (PET) markers of pathology in autosomal dominant AD. METHODS: We analyzed baseline levels of plasma p-tau217 and its associations with amyloid PET, tau PET, and word list delayed recall measured 7.61 years later in non-demented age- and education-matched presenilin-1 E280A carriers (n = 24) and non-carrier (n = 20) family members. RESULTS: Carriers had higher plasma p-tau217 levels than non-carriers. Baseline plasma p-tau217 was associated with subsequent amyloid and tau PET pathology levels and cognitive function. DISCUSSION: Our findings suggest that plasma p-tau217 predicts subsequent brain pathological burden and memory performance in presenilin-1 E280A carriers. These results provide support for plasma p-tau217 as a minimally invasive diagnostic and prognostic biomarker for AD, with potential utility in clinical practice and trials. HIGHLIGHTS: Non-demented presenilin-1 E280A carriers have higher plasma tau phosphorylated at threonine 217 (p-tau217) than do age-matched non-carriers. Higher baseline p-tau217 is associated with greater future amyloid positron emission tomography (PET) pathology burden. Higher baseline p-tau217 is associated with greater future tau PET pathology burden. Higher baseline p-tau217 is associated with worse future memory performance.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Amiloide/metabolismo , Péptidos beta-Amiloides/metabolismo , Proteínas Amiloidogénicas , Biomarcadores , Encéfalo/patología , Cognición , Tomografía de Emisión de Positrones/métodos , Presenilina-1/genética , Proteínas tau/metabolismo
3.
Int J Mol Sci ; 23(22)2022 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-36430188

RESUMEN

Cotton is the most important crop for fiber production worldwide. However, the cotton boll weevil (CBW) is an insect pest that causes significant economic losses in infested areas. Current control methods are costly, inefficient, and environmentally hazardous. Herein, we generated transgenic cotton lines expressing double-stranded RNA (dsRNA) molecules to trigger RNA interference-mediated gene silencing in CBW. Thus, we targeted three essential genes coding for chitin synthase 2, vitellogenin, and ecdysis-triggering hormone receptor. The stability of expressed dsRNAs was improved by designing a structured RNA based on a viroid genome architecture. We transformed cotton embryos by inserting a promoter-driven expression cassette that overexpressed the dsRNA into flower buds. The transgenic cotton plants were characterized, and positive PCR transformed events were detected with an average heritability of 80%. Expression of dsRNAs was confirmed in floral buds by RT-qPCR, and the T1 cotton plant generation was challenged with fertilized CBW females. After 30 days, data showed high mortality (around 70%) in oviposited yolks. In adult insects fed on transgenic lines, chitin synthase II and vitellogenin showed reduced expression in larvae and adults, respectively. Developmental delays and abnormalities were also observed in these individuals. Our data remark on the potential of transgenic cotton based on a viroid-structured dsRNA to control CBW.


Asunto(s)
Gorgojos , Humanos , Animales , Gorgojos/genética , ARN Bicatenario/genética , ARN Bicatenario/metabolismo , Gossypium/genética , Gossypium/metabolismo , Vitelogeninas/genética , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo
4.
RNA Biol ; 18(11): 1653-1681, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33302789

RESUMEN

RNA interference (RNAi)-mediated gene silencing can be used to control specific insect pest populations. Unfortunately, the variable efficiency in the knockdown levels of target genes has narrowed the applicability of this technology to a few species. Here, we examine the current state of knowledge regarding the miRNA (micro RNA) and siRNA (small interfering RNA) pathways in insects and investigate the structural variability at key protein domains of the RNAi machinery. Our goal was to correlate domain variability with mechanisms affecting the gene silencing efficiency. To this end, the protein domains of 168 insect species, encompassing the orders Coleoptera, Diptera, Hemiptera, Hymenoptera, and Lepidoptera, were analysed using our pipeline, which takes advantage of meticulous structure-based sequence alignments. We used phylogenetic inference and the evolutionary rate coefficient (K) to outline the variability across domain regions and surfaces. Our results show that four domains, namely dsrm, Helicase, PAZ and Ribonuclease III, are the main contributors of protein variability in the RNAi machinery across different insect orders. We discuss the potential roles of these domains in regulating RNAi-mediated gene silencing and the role of loop regions in fine-tuning RNAi efficiency. Additionally, we identified several order-specific singularities which indicate that lepidopterans have evolved differently from other insect orders, possibly due to constant coevolution with plants and viruses. In conclusion, our results highlight several variability hotspots that deserve further investigation in order to improve the application of RNAi technology in the control of insect pests.


Asunto(s)
Silenciador del Gen , Proteínas de Insectos/metabolismo , Insectos/clasificación , Insectos/genética , MicroARNs/genética , Interferencia de ARN , ARN Interferente Pequeño/genética , Animales , Proteínas de Insectos/genética , Insectos/metabolismo , Filogenia , Dominios Proteicos
5.
Neurol Sci ; 42(11): 4637-4645, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33675003

RESUMEN

PURPOSE: The present study aims to explore the association between the quality of life (QoL) score and the clinical and sociodemographic variables in patients with the PSEN1-E280A mutation. We also seek to evaluate the differences between the QoL reported by the patients (P-QoL) and the scores reported by the caregivers (C-QoL). METHODS: An analysis of 75 patients with the PSEN1-E280A mutation with mild cognitive impairment and dementia was performed. We used the Quality of Life in Alzheimer Disease (QoL-AD) survey to evaluate QoL as an outcome and evaluated its association with sociodemographic, lifestyle, clinical, and past medical history variables. RESULTS: The largest difference in the median of the QoL-AD score was in those who needed help to eat, those with moderate or severe dementia, those classified as frail or pre-frail, those with moderate social risk, and those with depression. Also, C-QoL was lower than the P-QoL, and the QoL-AD of individuals with severe dementia was lower than for milder forms of the disease. Not needing help to eat, not having a stressful situation in the past 3 months, and the years of education were positively correlated with QoL-AD in the linear model. CONCLUSION: As studies in similar populations with AD, factors with more impact on QoL are those related to loss of functionality and independence. These factors are also associated with variables related to the current literature with the burden of the disease for the caregivers.


Asunto(s)
Enfermedad de Alzheimer , Calidad de Vida , Enfermedad de Alzheimer/genética , Cuidadores , Humanos , Mutación/genética , Presenilina-1/genética
6.
Dement Geriatr Cogn Disord ; 49(6): 565-572, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33207340

RESUMEN

INTRODUCTION: Gait speed (GS) is a predictor of negative outcomes in older adults and in those in risk to develop cognitive impairment; as such, it has been associated with dementia. Studies in Latin-American older adults showing this association are scarce. This study aimed to evaluate the relationship between GS and dementia in a representative sample of Colombian older adults. METHODS: This study is a secondary analysis from the Survey on Health, Well-Being, and Aging, SABE (from initials in Spanish: Salud, Bienestar & Envejecimiento) Colombia's survey conducted in 2015 with a sample of 23,694 elderly adults aged 60 years or older. RESULTS: A total of 19,470 participants from the SABE Colombia survey were available for analysis. The multivariate analysis shows that dementia was associated with slow GS (PR 2.39; CI 1.91-3.01) independently to the other variables (p < 0.001). Similarly, GS as a continuous variable shows a statistically significant association with dementia in the adjusted analysis (OR 0.06; CI 0.04-0.09; p < 0.001). CONCLUSION: Dementia was associated with slow GS. This finding provides evidence to include GS as a complementary parameter in the assessment of Colombian elderly adults.


Asunto(s)
Demencia/fisiopatología , Marcha , Encuestas Epidemiológicas , Velocidad al Caminar , Anciano , Disfunción Cognitiva , Colombia , Femenino , Humanos , Masculino
7.
Anaerobe ; 62: 102163, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32007684

RESUMEN

Periodontitis pathogenesis involves activation of host immune responses triggered by microbial dysbiosis. Therefore, controlling periodontal pathogens in-vivo is a main goal of periodontal therapy. New antimicrobials might help to control periodontal infection and improve treatment outcomes at "the dark times" of increasing antibiotic resistance. Here, we determined the biological activity of collinin and isocollinin against 8 bacterial strains. Antimicrobial activity of collinin and isocollinin, chlorhexidine digluconate (CHX) and sodium hypochlorite (NaClO) was evaluated against clinically relevant periodontal bacteria, like Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum, Prevotella intermedia, Dialister pneumosintes strains and superinfectants like Escherichia coli, Staphylococcusaureus, and Pseudomonasaeruginosa strains. A broth microdilution test was carried out to determine the minimum inhibitory concentration of collinin and isocollinin against those strains, and bacterial viability was determined by resazurin assay at diverse concentration and exposure times. P. gingivalis was the most susceptible strain to collinin and isocollinin (MIC 2.1 µg/mL and 4.2 µg/mL respectively). Other periodontal pathogens showed MICs <17 µg/mL for collinin and MICs between 20 and 42 µg/mL for isocollinin, whereas CHX and NaClO showed MICs of 62 and 326 µg/mL, respectively. Collinin and isocollinin also exhibited antimicrobial activity against superinfectant bacteria (MIC < 21 and < 42 µg/mL, respectively). Overall, collinin and isocollinin showed a remarkable antibacterial activity against relevant periodontal and superinfective bacteria, especially against P. gingivalis (MIC 2.1 µg/mL and 4.2 µg/mL respectively) and the highly virulent P. aeruginosa (MIC 5.2 and 20.8 µg/mL, respectively).


Asunto(s)
Cumarinas/farmacología , Periodontitis/microbiología , Sobreinfección/microbiología , Cumarinas/química , Relación Dosis-Respuesta a Droga , Humanos , Técnicas In Vitro , Pruebas de Sensibilidad Microbiana , Periodontitis/tratamiento farmacológico
8.
Environ Manage ; 66(2): 149-161, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32468152

RESUMEN

The ecosystem services (ES) approach has been introduced in environmental policies and management to serve as a link between nature and society. Communication, education, and participation actions (CEPA) have the potential to facilitate this link. In this research, we evaluated how CEPA have been implemented in biodiversity conservation projects that consider ES. We used content analysis to review 182 biodiversity conservation projects executed by 33 environmental authorities in Colombia. We also used multiple correspondence analysis and cluster analysis to classify projects on the basis of the purpose of CEPA, type of CEPA, integration of CEPA, ES addressed, main stakeholders, and aim of conservation. We found that five aspects are key to fostering social engagement in environmental management projects: promoting explicit consideration of the ES approaches, increasing conservation efforts focused on the non-material benefits of the ES, integrating different types of CEPA, including overlooked key actors (e.g., indigenous communities and women), and developing and implementing social indicators. These considerations might lead environmental managers to revise their daily practices and, eventually, inform policies that foster an explicit link between CEPA and ES approaches.


Asunto(s)
Conservación de los Recursos Naturales , Ecosistema , Biodiversidad , Colombia , Política Ambiental , Humanos
9.
Artículo en Inglés | MEDLINE | ID: mdl-30939984

RESUMEN

This article presents a study that identifies the variables with greatest impact on the biogas and methane production over a process with thermal pretreatment, to accelerate anaerobic digestion process in sewage sludge in a water treatment plant, for a poultry processing factory, by using fuzzy logic. The designed fuzzy logic model includes 688 inference rules, with a correlation of 99.3% between prediction data against experimental data, for the biogas variable; and 97% for the methane variable. The predictions of the fuzzy logic model were analyzed with response surface models, and it is concluded that the temperature and operating time variables are mutually determining in the biogas and methane production. Likewise, this research provides a methodology for the design of an expert decision support system that allows to evaluate and optimize a mesophilic anaerobic digestion process through a previous thermal treatment in order to improve the yields of biogas and methane in the treatment of effluent sludge from agroindustry. These results propose to diffuse logic as a reliable tool to make comparisons, and predictions for operation variables management on the treatment of residual sludge with thermal pretreatment on anaerobic digestion.


Asunto(s)
Biocombustibles/análisis , Reactores Biológicos/microbiología , Metano/análisis , Modelos Teóricos , Aguas del Alcantarillado , Purificación del Agua/métodos , Anaerobiosis , Lógica Difusa , Metano/biosíntesis , Proyectos de Investigación , Aguas del Alcantarillado/química , Aguas del Alcantarillado/microbiología , Temperatura
10.
Artículo en Inglés | MEDLINE | ID: mdl-29672214

RESUMEN

This article focuses on the analysis of the behavior patterns of the variables involved in the anaerobic digestion process. The objective is to predict the impact factor and the behavior pattern of the variables, i.e., temperature, pH, volatile solids (VS), total solids, volumetric load, and hydraulic residence time, considering that these are the control variables for the conservation of the different groups of anaerobic microorganisms. To conduct the research, samples of physicochemical sludge were taken from a water treatment plant in a poultry processing factory, and, then, the substrate was characterized, and a thermal pretreatment was used to accelerate the hydrolysis process. The anaerobic digestion process was analyzed in order to obtain experimental data of the control variables and observe their impact on the production of biogas. The results showed that the thermal pre-hydrolysis applied at 90°C for 90 min accelerated the hydrolysis phase, allowing a significant 52% increase in the volume of methane produced. An artificial neural network was developed, and it was trained with the database obtained by monitoring the anaerobic digestion process. The results obtained from the artificial neural network showed that there is an adjustment between the real values and the prediction of validation based on 60 samples with a 96.4% coefficient of determination, and it was observed that the variables with the major impact on the process were the loading rate and VS, with impact factors of 36% and 23%, respectively.


Asunto(s)
Simulación por Computador , Industria de Procesamiento de Alimentos/métodos , Redes Neurales de la Computación , Aguas del Alcantarillado/química , Temperatura , Aguas Residuales/química , Purificación del Agua/métodos , Anaerobiosis , Animales , Biocombustibles , Predicción , Hidrólisis , Residuos Industriales , Metano , Aves de Corral , Aguas del Alcantarillado/microbiología , Aguas Residuales/microbiología
12.
J Oral Maxillofac Surg ; 74(4): 797-803, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26604048

RESUMEN

PURPOSE: Patients with unilateral complete cleft lip and palate (UCLP) have a characteristic bilateral septal deformity, and septal deviation can be associated with turbinate hyperplasia, leading to paradoxical nasal obstruction. The purpose of the present study was to measure and compare the bony and mucosal dimensions of the inferior turbinate on the cleft and non-cleft sides in patients with UCLP. PATIENTS AND METHODS: We implemented a retrospective cohort study of patients with UCLP who had undergone computed tomography (CT) scan between 2002 to 2013. Subjects who had undergone nasal revision, septoplasty, turbinectomy, or Le Fort I osteotomy before the imaging date were excluded. The primary predictor variable was the subject side (cleft vs noncleft side), and the primary outcome variable was the turbinate cross-sectional area. The secondary predictor variables included the site of measurement along the sagittal axis of the turbinate (anterior, middle, posterior) and tissue type (turbinate whole, bone, mucosa). The Wilcoxon signed rank test for paired samples compared the turbinate dimensions on the cleft and noncleft sides, with statistical significance set at P ≤ .05. RESULTS: The sample included 53 patients (32 females and 21 males). The inferior turbinates were measured bilaterally on CT images obtained at a mean age of 12.2 ± 0.8 years. The inferior turbinate on the noncleft side was significantly larger in both bone and mucosa (P = .003). This relationship did not change when controlling for age and gender. CONCLUSIONS: The results of the present study have confirmed bony and mucosal enlargement of the inferior turbinate on the noncleft side in patients with UCLP. This might contribute to bilateral nasal obstruction and should be considered during treatment planning for nasopharyngeal and orthognathic surgery.


Asunto(s)
Labio Leporino/patología , Fisura del Paladar/patología , Nariz/anomalías , Cornetes Nasales/anomalías , Adolescente , Anatomía Transversal/métodos , Cefalometría/métodos , Niño , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Hiperplasia , Hipertrofia , Masculino , Hueso Nasal/anomalías , Mucosa Nasal/patología , Tabique Nasal/anomalías , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos
13.
J Dent Educ ; 87(7): 939-945, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37052476

RESUMEN

PURPOSE: Oral and maxillofacial surgery (OMS) residencies commonly affiliate with Veterans Affairs Medical Centers (VAMC) to extend care for veterans. This study quantifies the surgical experience of residents at the Corporal Michael J. Crescenz (CMC) VAMC in Philadelphia, Pennsylvania and determines the number of programs affiliated with VA Medical Centers, to enumerate the educational benefits and improve veteran healthcare. METHODS: The dental project manager logs from 2012 through 2021 of the CMC VAMC operating room were analyzed, and cases were categorized into 12 groups. The implant cases from 2012 through 2021 were quantified. Program affiliations were determined using a VA Office of Academic Affiliation report. RESULTS: There were 1359 procedures (760 cases) performed. Dentoalveolar (n = 967) was the most common category, and extractions (n = 384) were the most common procedure. The least cases and procedures were performed in 2012 (n = 14; n = 23). The most cases were performed in 2019 (n = 137), and the most procedures were performed in 2019 and 2021 (n = 255). There were 3133 implants placed. There are 40 OMS programs affiliated with VA Medical Centers; more dual degree (n = 24) than single degree (n = 16) programs having an affiliation. CONCLUSION: The CMC VAMC offers robust dentoalveolar experience and is increasing in surgical volume, representing the expected needs of an aging veteran population. An increasing budget and millions of eligible veterans indicates VA medical centers nationally will continue to provide valuable surgical experiences.


Asunto(s)
Internado y Residencia , Cirugía Bucal , Veteranos , Estados Unidos , Humanos , United States Department of Veterans Affairs , Hospitales , Hospitales de Veteranos
14.
Front Mol Biosci ; 10: 1073721, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36950526

RESUMEN

The cotton boll weevil (CBW) (Anthonomus grandis) is one of the major insect pests of cotton in Brazil. Currently, CBW control is mainly achieved by insecticide application, which is costly and insufficient to ensure effective crop protection. RNA interference (RNAi) has been used in gene function analysis and the development of insect control methods. However, some insect species respond poorly to RNAi, limiting the widespread application of this approach. Therefore, nanoparticles have been explored as an option to increase RNAi efficiency in recalcitrant insects. Herein, we investigated the potential of chitosan-tripolyphosphate (CS-TPP) and polyethylenimine (PEI) nanoparticles as a dsRNA carrier system to improve RNAi efficiency in the CBW. Different formulations of the nanoparticles with dsRNAs targeting genes associated with juvenile hormone metabolism, such as juvenile hormone diol kinase (JHDK), juvenile hormone epoxide hydrolase (JHEH), and methyl farnesoate hydrolase (MFE), were tested. The formulations were delivered to CBW larvae through injection (0.05-2 µg), and the expression of the target genes was evaluated using RT-qPCR. PEI nanoparticles increased targeted gene silencing compared with naked dsRNAs (up to 80%), whereas CS-TPP-dsRNA nanoparticles decreased gene silencing (0%-20%) or led to the same level of gene silencing as the naked dsRNAs (up to 50%). We next evaluated the effects of targeting a single gene or simultaneously targeting two genes via the injection of naked dsRNAs or dsRNAs complexed with PEI (500 ng) on CBW survival and phenotypes. Overall, the gene expression analysis showed that the treatments with PEI targeting either a single gene or multiple genes induced greater gene silencing than naked dsRNA (∼60%). In addition, the injection of dsJHEH/JHDK, either naked or complexed with PEI, significantly affected CBW survival (18% for PEI nanoparticles and 47% for naked dsRNA) and metamorphosis. Phenotypic alterations, such as uncompleted pupation or malformed pupae, suggested that JHEH and JHDK are involved in developmental regulation. Moreover, CBW larvae treated with dsJHEH/JHDK + PEI (1,000 ng/g) exhibited significantly lower survival rate (55%) than those that were fed the same combination of naked dsRNAs (30%). Our findings demonstrated that PEI nanoparticles can be used as an effective tool for evaluating the biological role of target genes in the CBW as they increase the RNAi response.

15.
Rev Colomb Psiquiatr (Engl Ed) ; 52(4): 305-313, 2023.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38065663

RESUMEN

INTRODUCTION: Mild Cognitive Impairment (MCI) is common in Parkinson's Disease (PD). Few studies have compared the Health-Related Quality of Life (HRQoL) in patients with and without MCI due to PD (PD-MCI), and its correlation to patients' subjective cognitive and communicative difficulties has not been explored. OBJECTIVE: We aimed to compare HRQoL in PD-MCI and PD without MCI (PD-nMCI), and explore its possible relationship to subjective cognitive and communicative complaints. METHODS: We included 29 PD-nMCI and 11 PD-MCI patients. The HRQoL was assessed with the Parkinson's Disease Questionnaire-39 (PDQ-39): its Cognition dimension was used as a measure of subjective cognitive complaints, its Communication dimension for subjective communicative complaints, and the summary index (PDQ-39 SI) as an indicator of HRQoL. Non-parametric partial correlations between the Cognition and Communication dimensions, and the adjusted PDQ-39 SI were conducted. RESULTS: PD-MCI patients had greater subjective cognitive and communicative complaints and worse HRQoL than PD-nMCI patients. In the PD-MCI group, both subjective cognitive and communicative complaints exhibited significant direct correlations with the adjusted HRQoL scores. CONCLUSIONS: HRQoL seems to be affected in PD-MCI, and it might be influenced by greater subjective cognitive and communicative complaints. Including patient-reported outcome measures of HRQoL, and providing cognitive and speech rehabilitation, as well as psychotherapeutic strategies to face these deficits can enhance the patient-centred approach in PD.


Asunto(s)
Disfunción Cognitiva , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/psicología , Calidad de Vida/psicología , Pruebas Neuropsicológicas , Disfunción Cognitiva/etiología , Cognición , Comunicación
16.
Nat Commun ; 14(1): 5120, 2023 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-37612284

RESUMEN

Autosomal dominant Alzheimer's disease (ADAD) is genetically determined, but variability in age of symptom onset suggests additional factors may influence cognitive trajectories. Although apolipoprotein E (APOE) genotype and educational attainment both influence dementia onset in sporadic AD, evidence for these effects in ADAD is limited. To investigate the effects of APOE and educational attainment on age-related cognitive trajectories in ADAD, we analyzed data from 675 Presenilin-1 E280A mutation carriers and 594 non-carriers. Here we show that age-related cognitive decline is accelerated in ADAD mutation carriers who also have an APOE e4 allele compared to those who do not and delayed in mutation carriers who also have an APOE e2 allele compared to those who do not. Educational attainment is protective and moderates the effect of APOE on cognition. Despite ADAD mutation carriers being genetically determined to develop dementia, age-related cognitive decline may be influenced by other genetic and environmental factors.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/genética , Apolipoproteínas , Apolipoproteínas E/genética , Cognición , Escolaridad , Genotipo
17.
Mol Neurobiol ; 59(6): 3845-3858, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35420381

RESUMEN

Hereditary ataxias are a group of devastating neurological disorders that affect coordination of gait and are often associated with poor coordination of hands, speech, and eye movements. Ataxia with ocular apraxia type 1 (AOA1) (OMIM: 606,350.0006) is characterized by slowly progressive symptoms of childhood-onset and pathogenic mutations in APTX; the only known cause underpinning AOA1. APTX encodes the protein aprataxin, composed of three domains sharing homology with proteins involved in DNA damage, signaling, and repair. We present four siblings from an endogamic family in a rural, isolated town of Colombia with ataxia and ocular apraxia of childhood-onset and confirmed molecular diagnosis of AOA1, homozygous for the W279* p.Trp279Ter mutation. We predicted the mutated APTX with AlphaFold to demonstrate the effects of this stop-gain mutation that deletes three beta helices encoded by amino acid 270 to 339 rescinding the C2H2-type zinc fingers (Znf) (C2H2 Znf) DNA-binding, the DNA-repair domain, and the whole 3D structure of APTX. All siblings exhibited different ages of onset (4, 6, 8, and 11 years old) and heterogeneous patterns of dysarthria (ranging from absence to mild-moderate dysarthria). Neuropsychological evaluation showed no neurocognitive impairment in three siblings, but one sibling showed temporospatial disorientation, semantic and phonologic fluency impairment, episodic memory affection, constructional apraxia, moderate anomia, low executive function, and symptoms of depression. To our knowledge, this report represents the most extensive series of siblings affected with AOA1 in Latin America, and the genetic analysis completed adds important knowledge to outline this family's disease and general complex phenotype of hereditary ataxias.


Asunto(s)
Apraxias , Ataxia Cerebelosa , Degeneraciones Espinocerebelosas , Apraxias/complicaciones , Apraxias/genética , Ataxia/complicaciones , Ataxia/genética , Colombia , ADN , Proteínas de Unión al ADN/genética , Disartria/complicaciones , Humanos , Mutación/genética , Proteínas Nucleares/genética , Fenotipo , Hermanos , Degeneraciones Espinocerebelosas/complicaciones
18.
Plants (Basel) ; 11(20)2022 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-36297768

RESUMEN

The root-knot nematode (RKN), Meloidogyne incognita, is a devastating soybean pathogen worldwide. The use of resistant cultivars is the most effective method to prevent economic losses caused by RKNs. To elucidate the mechanisms involved in resistance to RKN, we determined the proteome and transcriptome profiles from roots of susceptible (BRS133) and highly tolerant (PI 595099) Glycine max genotypes 4, 12, and 30 days after RKN infestation. After in silico analysis, we described major defense molecules and mechanisms considered constitutive responses to nematode infestation, such as mTOR, PI3K-Akt, relaxin, and thermogenesis. The integrated data allowed us to identify protein families and metabolic pathways exclusively regulated in tolerant soybean genotypes. Among them, we highlighted the phenylpropanoid pathway as an early, robust, and systemic defense process capable of controlling M. incognita reproduction. Associated with this metabolic pathway, 29 differentially expressed genes encoding 11 different enzymes were identified, mainly from the flavonoid and derivative pathways. Based on differential expression in transcriptomic and proteomic data, as well as in the expression profile by RT-qPCR, and previous studies, we selected and overexpressed the GmPR10 gene in transgenic tobacco to assess its protective effect against M. incognita. Transgenic plants of the T2 generation showed up to 58% reduction in the M. incognita reproduction factor. Finally, data suggest that GmPR10 overexpression can be effective against the plant parasitic nematode M. incognita, but its mechanism of action remains unclear. These findings will help develop new engineered soybean genotypes with higher performance in response to RKN infections.

19.
Artículo en Inglés, Español | MEDLINE | ID: mdl-34489098

RESUMEN

INTRODUCTION: Mild Cognitive Impairment (MCI) is common in Parkinson's Disease (PD). Few studies have compared the Health-Related Quality of Life (HRQoL) in patients with and without MCI due to PD (PD-MCI), and its correlation to patients' subjective cognitive and communicative difficulties has not been explored. OBJECTIVE: We aimed to compare HRQoL in PD-MCI and PD without MCI (PD-nMCI), and explore its possible relationship to subjective cognitive and communicative complaints. METHODS: We included 29 PD-nMCI and 11 PD-MCI patients. The HRQoL was assessed with the Parkinson's Disease Questionnaire-39 (PDQ-39): its Cognition dimension was used as a measure of subjective cognitive complaints, its Communication dimension for subjective communicative complaints, and the summary index (PDQ-39 SI) as an indicator of HRQoL. Non-parametric partial correlations between the Cognition and Communication dimensions, and the adjusted PDQ-39 SI were conducted. RESULTS: PD-MCI patients had greater subjective cognitive and communicative complaints and worse HRQoL than PD-nMCI patients. In the PD-MCI group, both subjective cognitive and communicative complaints exhibited significant direct correlations with the adjusted HRQoL scores. CONCLUSIONS: HRQoL seems to be affected in PD-MCI, and it might be influenced by greater subjective cognitive and communicative complaints. Including patient-reported outcome measures of HRQoL, and providing cognitive and speech rehabilitation, as well as psychotherapeutic strategies to face these deficits can enhance the patient-centred approach in PD.

20.
Rev Soc Bras Med Trop ; 50(1): 52-60, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28327802

RESUMEN

INTRODUCTION:: Cutaneous leishmaniasis (CL) is a tropical disease that affects millions of individuals worldwide. The current drugs for CL may be effective but have serious side effects; hence, alternatives are urgently needed. Although plant-derived materials are used for the treatment of various diseases in 80% of the global population, the validation of these products is essential. Gelatin capsules containing dried Artemisia annua leaf powder were recently developed as a new herbal formulation (totum) for the oral treatment of malaria and other parasitic diseases. Here, we aimed to determine the usefulness of A. annua gel capsules in CL. METHODS:: The antileishmanial activity and cytotoxicity of A. annua L. capsules was determined via in vitro and in vivo studies. Moreover, a preliminary evaluation of its therapeutic potential as antileishmanial treatment in humans was conducted in 2 patients with uncomplicated CL. RESULTS:: Artemisia annua capsules showed moderate in vitro activity in amastigotes of Leishmania (Viannia) panamensis; no cytotoxicity in U-937 macrophages or genotoxicity in human lymphocytes was observed. Five of 6 (83.3%) hamsters treated with A. annua capsules (500mg/kg/day) for 30 days were cured, and the 2 examined patients were cured 45 days after initiation of treatment with 30g of A. annua capsules, without any adverse reactions. Both patients remained disease-free 26 and 24 months after treatment completion. CONCLUSION:: Capsules of A. annua L. represent an effective treatment for uncomplicated CL, although further randomized controlled trials are needed to validate its efficacy and safety.


Asunto(s)
Antiprotozoarios/farmacología , Antiprotozoarios/uso terapéutico , Artemisia annua/química , Leishmaniasis Cutánea/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Adulto , Animales , Cricetinae , Femenino , Humanos , Leishmania/efectos de los fármacos , Masculino , Pruebas de Sensibilidad Parasitaria , Hojas de la Planta/química , Resultado del Tratamiento
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