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1.
bioRxiv ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-39005328

RESUMO

Alcohol consumption remains a significant global health challenge, causing millions of direct and indirect deaths annually. Intriguingly, recent work has highlighted the prefrontal cortex, a major brain area that regulates inhibitory control of behaviors, whose activity becomes dysregulated upon alcohol abuse. However, whether an endogenous mechanism exists within this brain area that limits alcohol consumption is unknown. Here we identify a discrete GABAergic neuronal ensemble in the medial orbitofrontal cortex (mOFC) that is selectively recruited during binge alcohol-drinking and intoxication. Upon alcohol intoxication, this neuronal ensemble suppresses binge drinking behavior. Optogenetically silencing of this population, or its ablation, results in uncontrolled binge alcohol consumption. We find that this neuronal ensemble is specific to alcohol and is not recruited by other rewarding substances. We further show, using brain-wide analysis, that this neuronal ensemble projects widely, and that its projections specifically to the mediodorsal thalamus are responsible for regulating binge alcohol drinking. Together, these results identify a brain circuit in the mOFC that serves to protect against binge drinking by halting alcohol intake. These results provide valuable insights into the complex nature of alcohol abuse and offers potential avenues for the development of mOFC neuronal ensemble-targeted interventions.

2.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38825089

RESUMO

INTRODUCTION: There is no generalized consensus regarding perioperative prophylaxis of venous thromboembolism (VTE), either on using or timing it in patients undergoing spine surgery. VTE is a current concern because, even though being an uncommon event, it can cause serious complications. The aim of the present study is to propose guidelines for the prevention of thrombotic events in posterior spinal surgery, either as deep vein thrombosis or pulmonary thromboembolism. If the number of patients getting prophylaxis drugs is reduced a subsequent reduction of the incidence of epidural hematoma can be expected. MATERIALS AND METHODS: A number of 235 patients who had undergone posterior spinal arthrodesis in the previous five years were studied. Mechanical thromboprophylaxis measures consisting of compression stockings were applied in all of them. Anticoagulant drugs were also applied whenever risk factors for thrombosis were observed. Early weight-bearing was resumed immediately after surgery. Demographic, clinical, and surgical variables were collected, as well as complications appearing during the follow-up period, that was scheduled at one, two, four, six and twelve months after the surgery. Thrombotic events, if present, were diagnosed by clinical and imaging tests such as ultrasound and CT angiography. RESULTS: From the total 235 patients of this series, one hundred and fifty-three cases met the study inclusion criteria. A total of four thrombotic events appeared, one in the form of deep vein thrombosis and other three in the form of pulmonary thromboembolism. These last patients suffering an embolism died because of it. None of the variables studied had statistical significance for the occurrence of a thrombotic event. All four patients who suffered thrombotic events were receiving anticoagulant drugs, in addition to mechanical compression stockings, because of the presence of risk factors for thrombosis. CONCLUSIONS: By applying the fore mentioned protocol, adequate prevention of thromboembolic events was achieved in this study population of patients undergoing posterior spinal surgery.

3.
Heliyon ; 10(4): e26283, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38434078

RESUMO

The human exhalation flow is characterized in this work from the three-dimensional velocimetry results obtained by using the stereo particle image velocimetry (SPIV) measurement technique on the flow emitted from a realistic airway model. For this purpose, the transient exhalation flow through the mouth of a person performing two different breaths corresponding to two metabolic rates, standing relaxed (SR) and walking active (WA), is emulated and studied. To reproduce the flow realistically, a detailed three-dimensional model obtained from computed tomography measurements on real subjects is used. To cope with the variability of the experimental data, a subsequent analysis of the results is performed using the TR-PIV (time resolved particle image velocimetry) technique. Exhalation produces a transient jet that becomes a puff when flow emission ends. Three-dimensional vector fields of the jet velocity are obtained in five equally spaced transverse planes up to a distance of Image 1 from the mouth at equally spaced time instants Image 2 which will be referred to as phases (φ), from the beginning to the end of exhalation. The time evolution during exhalation of the jet area of influence, the velocity field and the jet air entrainment have been characterized for each of the jet cross sections. The importance of the use of realistic airway models for the study of this type of flow and the influence of the metabolic rate on its development are also analyzed. The results obtained contribute to the characterization of the human exhalation as a pathway of the transmission of pathogens such as SARS-CoV-2 virus.

4.
Proc Natl Acad Sci U S A ; 121(14): e2313538121, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38527193

RESUMO

A major consequence of aging and stress, in yeast to humans, is an increased accumulation of protein aggregates at distinct sites within the cells. Using genetic screens, immunoelectron microscopy, and three-dimensional modeling in our efforts to elucidate the importance of aggregate annexation, we found that most aggregates in yeast accumulate near the surface of mitochondria. Further, we show that virus-like particles (VLPs), which are part of the retrotransposition cycle of Ty elements, are markedly enriched in these sites of protein aggregation. RNA interference-mediated silencing of Ty expression perturbed aggregate sequestration to mitochondria, reduced overall protein aggregation, mitigated toxicity of a Huntington's disease model, and expanded the replicative lifespan of yeast in a partially Hsp104-dependent manner. The results are in line with recent data demonstrating that VLPs might act as aging factors in mammals, including humans, and extend these findings by linking VLPs to a toxic accumulation of protein aggregates and raising the possibility that they might negatively influence neurological disease progression.


Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Humanos , Animais , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Agregados Proteicos , Longevidade , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Replicação do DNA , Mamíferos/metabolismo
5.
Eur J Health Econ ; 25(2): 257-267, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36995531

RESUMO

BACKGROUND: Our study aimed to assess whether there was a relationship between clinical benefits and reimbursement decisions as well as the inclusion of economic evaluations in  therapeutic positioning reports (IPTs) and to explore factors influencing reimbursement decisions. MATERIALS AND METHODS: We analysed all anti-cancer drugs approved in Spain from 2010 to September 2022. The clinical benefit of each drug were evaluated using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) 1.1. The characteristics of these drugs were obtained from the Spanish Agency of Medicines and Medical Devices. Reimbursement status information was obtained using BIFIMED, a web resource available in Spanish and consulted the agreements of the Interministerial Committee on Pricing of Medicines (CIPM). RESULTS: In total, 73 drugs were included involving 197 indications. Almost half of the indications had substantial clinical benefit (49.8% yes vs. 50.3% no). Of the 153 indications with a reimbursement decision, 61 (56.5%) reimbursed indications had substantial clinical benefit compared to 14 (31.1%) of the non-reimbursed (p < 0.01). The median gain of overall survival was 4.9 months (2.8-11.2) for reimbursed indications and 2.9 months (1.7-5) in non-reimbursed (p < 0.05). Only six (3%) indications had an economic evaluation in the IPT. CONCLUSION: Our study revealed that there is a relationship between substantial clinical benefit and the reimbursement decision in Spain. However, we also found that the overall survival gain was modest, and a significant proportion of the reimbursed indications had no substantial clinical benefit. Economic evaluations in IPTs are infrequent and cost-effectiveness analysis is not provided by CIPM.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Espanha , Antineoplásicos/uso terapêutico , Oncologia , Análise Custo-Benefício , Neoplasias/tratamento farmacológico
6.
Rev Neurol ; 77(9): 205-214, 2023 11 01.
Artigo em Espanhol | MEDLINE | ID: mdl-37889128

RESUMO

INTRODUCTION: Cognitive impairment secondary to cerebrovascular events is a common complication of aortic valve replacement interventions. Our aim is to study the deterioration profile of patients who have undergone surgical valve replacement or transcatheter valve implantation (TAVI) and whether it differs according to the intervention they underwent and their baseline risk factors. PATIENTS AND METHODS: We conducted a prospective observational study with two non-equivalent groups of patients (TAVI group and surgical group) Intergroup comparisons were carried out in several cognitive domains, with a baseline assessment and follow-up measurements six and 12 months after the intervention. RESULTS: The TAVI group performed less well than the surgical group in executive and visuospatial functions, with scores partially determined by age (p < 0.01) and prior intellectual level (Pearson prior intelligence quotient-scalar test means: 0.665; p < 0.001). Mean scores at the three measurement points indicate a decline in executive function performance at six months, which is restored at 12 months. Sustained increases in memory were recorded at both time points, while visuospatial function and naming showed no subsequent recovery of the baseline levels. These trends are similar in both groups. CONCLUSION: The results obtained do not confirm the appearance of a specific process of post-intervention neurocognitive impairment in complicated aortic stenosis. The deterioration profile does not show any significant differences between groups, but is more evident in TAVI patients, due to the influence of variables related to sample selection.


TITLE: Deterioro cognitivo tardío en pacientes con estenosis aórtica tratados con sustitución valvular quirúrgica y con implantación transcatéter de válvula aórtica: estudio comparativo.Introducción. El deterioro cognitivo secundario a eventos cerebrovasculares es una complicación frecuente en las intervenciones de reemplazo de válvula aórtica. Nuestro objetivo es el estudio del perfil de deterioro de los pacientes sometidos a reemplazo valvular quirúrgico o implantación de prótesis transcatéter (TAVI) y si éste resulta diferente según la intervención a la que son sometidos y los factores de riesgo basales. Pacientes y métodos. Estudio observacional prospectivo, con dos grupos no equivalentes de pacientes (grupo TAVI y grupo quirúrgico). Se realizaron comparaciones intergrupo en varios dominios cognitivos, con una evaluación basal y mediciones de seguimiento seis y 12 meses después la intervención. Resultados. El grupo TAVI presentó resultados inferiores al grupo quirúrgico en funciones ejecutivas y visuoespaciales, puntuaciones parcialmente determinadas por la edad (p < 0,01) y el nivel intelectual previo (Pearson cociente intelectual previo-medias escalares en los test: 0,665; p < 0,001). La media de puntuaciones en los tres momentos de medición indica una disminución del rendimiento en funciones ejecutivas a los seis meses, que se recupera a los 12 meses. En memoria se registraron incrementos sostenidos en ambos momentos, en tanto que la función visuoespacial y la denominación no mostraron recuperación posterior de los niveles basales. Estas tendencias son similares en los dos grupos. Conclusión. Los resultados obtenidos no confirman la instauración de un proceso específico de deterioro neurocognitivo postintervención en la estenosis aórtica complicada. El perfil de deterioro no presenta diferencias significativas entre los grupos, pero es más evidente en los pacientes con TAVI, debido a la influencia de las variables de selección de la muestra.


Assuntos
Estenose da Valva Aórtica , Disfunção Cognitiva , Implante de Prótese de Valva Cardíaca , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/métodos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/métodos , Medição de Risco , Resultado do Tratamento , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/cirurgia , Fatores de Risco , Disfunção Cognitiva/etiologia , Instrumentos Cirúrgicos
7.
Plant Biol (Stuttg) ; 25(6): 944-955, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37357019

RESUMO

A reduction in chemical N-based fertillizer was investigated in Citrus plants. As N and water uptake are connected, the relationship between the physiological response to reductions in N was studied in relation to N metabolism and water. We examined the response of new and mature leaves and roots of Citrus macrophylla, grown under controlled conditions, and given different concentrations of N: 16, 8 or 4 mM. Differences in growth and development were determined for biochemical (mineral content, photosynthetic pigments, proteins and nitrate and nitrite reductase activity), physiological (photosynthesis and transpiration), and molecular (relative expression of nitrate transporters and aquaporins) parameters. Only plants given 4 mM N showed a reduction in growth. Although there were changes in NR activity, protein synthesis, and chlorophyll content in both 8 and 4 mM N plants that were highly related to aquaporin and nitrate transporter expression. The results revealed new findings on the relationship between aquaporins and nitrate transporters in new leaves of Citrus, suggesting a mechanism for ensuring growth under low N when new tissues are being formed.


Assuntos
Aquaporinas , Citrus , Nitratos/metabolismo , Transportadores de Nitrato , Nitrogênio/metabolismo , Água/metabolismo , Folhas de Planta/metabolismo , Aquaporinas/metabolismo , Aquaporinas/farmacologia , Raízes de Plantas/metabolismo
9.
Phytopathology ; 113(9): 1761-1772, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37014099

RESUMO

Understanding the emergence and prevalence of viral diseases in crops requires the systematic epidemiological monitoring of viruses, as well as the analysis of how ecological and evolutionary processes combine to shape viral population dynamics. Here, we extensively monitored the occurrence of six aphid-transmitted viruses in melon and zucchini crops in Spain for 10 consecutive cropping seasons between 2011 and 2020. The most prevalent viruses were cucurbit aphid-borne yellows virus (CABYV) and watermelon mosaic virus (WMV), found in 31 and 26% of samples with yellowing and mosaic symptoms. Other viruses, such as zucchini yellow mosaic virus, cucumber mosaic virus, Moroccan watermelon mosaic virus, and papaya ring spot virus, were detected less frequently (<3%) and mostly in mixed infections. Notably, our statistical analysis showed a significant association between CABYV and WMV in melon and zucchini hosts, suggesting that mixed infections might be influencing the evolutionary epidemiology of these viral diseases. We then carried out a comprehensive genetic characterization of the full-length genome sequences from CABYV and WMV isolates by using the Pacific Biosciences single-molecule real-time (PacBio) high-throughput technology to assess the genetic variation and structure of their populations. Our results showed that the CABYV population displayed seven codons under positive selection, and although most isolates clustered in the Mediterranean clade, a subsequent analysis of molecular variance revealed a significant, fine-scale temporal structure, which was in part explained by the level of the variance between isolates from single and mixed infections. In contrast, the WMV population genetic analysis showed that most of the isolates grouped into the Emergent clade, with no genetic differentiation and under purifying selection. These results underlie the epidemiological relevance of mixed infections for CABYV and provide a link between genetic diversity and CABYV dynamics at the whole-genome level.


Assuntos
Afídeos , Coinfecção , Cucurbita , Cucurbitaceae , Luteoviridae , Viroses , Animais , Doenças das Plantas , Luteoviridae/genética , Produtos Agrícolas , Verduras , Variação Genética
11.
Nat Commun ; 13(1): 7741, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36517491

RESUMO

If neutrinos are their own antiparticles the otherwise-forbidden nuclear reaction known as neutrinoless double beta decay can occur. The very long lifetime expected for these exceptional events makes its detection a daunting task. In order to conduct an almost background-free experiment, the NEXT collaboration is investigating novel synthetic molecular sensors that may capture the Ba dication produced in the decay of certain Xe isotopes in a high-pressure gas experiment. The use of such molecular detectors immobilized on surfaces must be explored in the ultra-dry environment of a xenon gas chamber. Here, using a combination of highly sensitive surface science techniques in ultra-high vacuum, we demonstrate the possibility of employing the so-called Fluorescent Bicolor Indicator as the molecular component of the sensor. We unravel the ion capture process for these molecular indicators immobilized on a surface and explain the origin of the emission fluorescence shift associated to the ion trapping.

12.
Neurologia (Engl Ed) ; 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36216225

RESUMO

BACKGROUND: The Frontal Assessment Battery is a short bedside test used to assess executive functions (EF). The aims of the present study were, first, to evaluate the psychometric proprieties of the Spanish version of the FAB (FAB-E) in a representative sample, and second, to establish cut-off points for impairment in executive function according to age and education level. METHODS: A sample of 798 healthy Spanish adult subjects aged 19 to 91 participated in this study. Neuropsychological assessment of participants was conducted using the FAB-E, Mini-Mental State Examination (MMSE) and Trail Making Test (TMT). We examined internal consistency, intraclass correlation, test-retest reliability, and concurrent and divergent validity. In addition, we established a cut-off point for detecting executive function impairment based on the 5th percentile by age group and education level. RESULTS: The analysis of the psychometric properties of the FAB-E showed good internal consistency (Cronbach's α = 0.60), intraclass correlation (0.72), test-retest reliability (0.70) and concurrent and divergent validity between the TMT (r = -0.523), MMSE (r = 0.426) and the FAB-E. The cut-off points for each age group were 16 points for the ≤ 29 group, 15 points for the 30-39 group, 14 points for the 40-49 and 50-59 groups, 12 points for the 60-69 group, and 10 points for the ≥ 70 age group. CONCLUSIONS: The psychometric analysis showed that the FAB-E has good validity and reliability. Thus, FAB-E may be a helpful tool to evaluate EF in a healthy Spanish population. In addition, this study provides information on reference data that will be very valuable for clinicians and researchers.

13.
Cir Pediatr ; 35(3): 118-124, 2022 Jul 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-35796083

RESUMO

OBJECTIVE: The advances made in the surgical and postnatal treatment of congenital diaphragmatic hernia (CDH) have considerably improved patient survival, but morbidity remains significant. The objective of this study was to analyze the effect these sequels have on the health-related quality of life (HRQL) of adolescents and young adults who have survived CDH, and to compare it with that of the general population. MATERIALS AND METHODS: A transversal descriptive study of patients diagnosed with CDH in our institution from 1997 to 2004 was carried out. Survival, location, hernia size, herniated organs, need for extracorporeal membrane oxygenation, and mechanical ventilation time were analyzed. In addition, a comparative study of the current HRQL of survivors was conducted using the SF-36 survey (36-Item Health Survey Short Form), which assessed physical function, physical role, body pain, general health, vitality, social function, emotional role, and mental health. Data of 24 healthy adolescents was used as a control group. RESULTS: Of the 29 survivors (70.7%), 21 were successfully contacted, and 16 responded to the survey. They all claimed their overall quality of life was good or very good. The group of adolescents who underwent CDH surgical repair had better results in the vitality (p= 0.001) and mental health (p<0.05) areas, but the overall HRQL score and the remaining health areas were similar. No significant differences were found regarding diaphragmatic size or need for ECMO. CONCLUSION: According to adolescent survivors who underwent CDH surgical repair, their quality of life is similar to that of other individuals of their age. Our results are encouraging and may prove useful for future parents of CDH patients.


OBJETIVO: Los avances en el tratamiento quirúrgico y posnatal han mejorado significativamente la supervivencia de pacientes con hernia diafragmática congénita (HDC). La morbilidad asociada sigue siendo significativa. El objetivo del estudio es evaluar efecto de estas secuelas sobre la calidad de vida relacionada con la salud (CVRS) de adolescentes y adultos jóvenes supervivientes de HDC y compararla con la población general. MATERIAL Y METODOS: Estudio descriptivo transversal de pacientes diagnosticados de HDC entre 1997 y 2004. Supervivencia, localización, tamaño de la hernia, órganos herniados, necesidad de oxigenación por membrana extracorpórea, tiempo de ventilación mecánica. Estudio comparativo de CVRS actual de pacientes supervivientes mediante la encuesta SF-36 (36-Item Health Survey Short Form): función física, rol físico, dolor corporal, salud general, vitalidad, función social, rol emocional, salud mental. Utilizamos datos de 24 adolescentes sanos como grupo control. RESULTADOS: De los 29 supervivientes (70,7%), fueron localizados 21 y contestaron la encuesta 16, que consideraron tener una calidad de vida global buena o muy buena. El grupo de adolescentes intervenidos tuvieron mejores resultados en las esferas de vitalidad (p = 0,001) y salud mental (p<0,05), pero la puntuación de la CVRS global y el resto de dimensiones de salud fueron similares. No se objetivaron diferencias significativas en relación con el tamaño diafragmático ni la necesidad de ECMO. CONCLUSIONES: Los adolescentes supervivientes intervenidos de HDC consideran tener una calidad de vida similar a jóvenes de su misma edad. Los resultados de nuestro estudio son alentadores y permiten un mejor asesoramiento para futuros pacientes con HDC.


Assuntos
Oxigenação por Membrana Extracorpórea , Hérnias Diafragmáticas Congênitas , Adolescente , Diafragma , Hérnias Diafragmáticas Congênitas/cirurgia , Humanos , Qualidade de Vida , Estudos Retrospectivos
14.
J Endocrinol Invest ; 45(10): 1977-1990, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35718853

RESUMO

OBJECTIVES: Graves' disease induced by Alemtuzumab (GD-IA) is one of the most frequently observed adverse events in patients with multiple sclerosis (MS) treated with this drug. The aim of this study is the sequencing and description of these events, along with the identification of the risk factors leading to their development. MATERIALS AND METHODS: We conducted a retrospective observational study identifying patients with relapsing-remitting multiple sclerosis (RRMS) and GD-IA, studying their baseline clinical features and variables related to the natural history of the disease. RESULTS: A total of 121 participants treated with Alemtuzumab were included, of whom 41 developed GD-IA (33.9%). A higher percentage of first-degree relatives with autoimmune thyroid disease was documented in the subgroup who developed the abovementioned event (14.6% vs 1.5%; p < 0.01). A total of 70.7% of patients diagnosed with GD-IA (n = 29/41) had fluctuations in thyroid function during follow-up, and 24.4% (n = 10/41) required total thyroidectomy for resolution of the condition. In 54.8% of participants diagnosed with GD-IA, a pattern of significant TSH decline was identified in the month prior to diagnosis of the event, with high predictive ability and associated with a more favorable clinical course (fewer weeks to normalization of thyroid function, HR = 8.99; 95% CI [2.11-38.44]; p = 0.0003). CONCLUSION: GD-IA has an atypical course compared to classical forms of the disease. The identification of risk factors for the development of the disease before starting treatment with Alemtuzumab and early monitoring of thyroid function once this treatment is initiated prove to be useful strategies in the diagnosis and clinical management of this condition.


Assuntos
Doença de Graves , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Alemtuzumab/efeitos adversos , Doença de Graves/induzido quimicamente , Doença de Graves/tratamento farmacológico , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Tireoidectomia
15.
Rev Esp Quimioter ; 35(4): 362-369, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35614861

RESUMO

OBJECTIVE: Bacteriemia is a major cause of morbidity and mortality among hospitalized patients worldwide. Early identification of microorganisms from blood culture can lead to improvement of treatment and outcomes. METHODS: The study was divided into two phases. The first phase when a comparison of the methods was made to check the concordance between them, using as a reference the standard method implemented in the laboratory. In a second phase, both methods are combined. We used the rapid identification method and when it could not identify we used the standard method. The microorganisms that were not identified by either of the two methods were identified from colony at 24 hours. RESULTS: A total of 589 microbial positive blood cultures have been included in the present study. With the rapid method we obtained 96% and 88% identification results for Gram-negative bacilli (GNB) and Gram-positive cocci (GPC) respectively. In this study we observed that the combination of the rapid and standard method achieved identifications of 98% and 97% for GNB and GPC respectively. CONCLUSIONS: The data analysed shows that both methods combined perform better than individually. We achieved an optimization of the identification of microorganisms directly from positive blood cultures by MALDI-TOF. This combination identified 98% of the microorganisms in between ten minutes to one hour and a half since the blood culture flagged positive.


Assuntos
Anti-Infecciosos , Bacteriemia , Cocos Gram-Positivos , Antibacterianos/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Hemocultura , Bactérias Gram-Negativas , Humanos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
16.
Neurologia (Engl Ed) ; 37(4): 287-303, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35595404

RESUMO

INTRODUCTION: Alzheimer disease (AD) is the most common cause of dementia and is considered one of the main causes of disability and dependence affecting quality of life in elderly people and their families. Current pharmacological treatment includes acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine; however, only one-third of patients respond to treatment. Genetic factors have been shown to play a role in this inter-individual variability in drug response. DEVELOPMENT: We review pharmacogenetic reports of AD-modifying drugs, the pharmacogenetic biomarkers included, and the phenotypes evaluated. We also discuss relevant methodological considerations for the design of pharmacogenetic studies into AD. A total of 33 pharmacogenetic reports were found; the majority of these focused on the variability in response to and metabolism of donepezil. Most of the patients included were from Caucasian populations, although some studies also include Korean, Indian, and Brazilian patients. CYP2D6 and APOE are the most frequently studied biomarkers. The associations proposed are controversial. CONCLUSIONS: Potential pharmacogenetic biomarkers for AD have been identified; however, it is still necessary to conduct further research into other populations and to identify new biomarkers. This information could assist in predicting patient response to these drugs and contribute to better treatment decision-making in a context as complex as ageing.


Assuntos
Doença de Alzheimer , Testes Farmacogenômicos , Acetilcolinesterase/uso terapêutico , Idoso , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Biomarcadores , Donepezila/uso terapêutico , Humanos , Testes Farmacogenômicos/métodos
17.
Int J Neural Syst ; 32(3): 2250008, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34996341

RESUMO

As a neurodevelopmental pathology, Attention Deficit Hyperactivity Disorder (ADHD) mainly arises during childhood. Persistent patterns of generalized inattention, impulsivity, or hyperactivity characterize ADHD that may persist into adulthood. The conventional diagnosis relies on clinical observational processes yielding high rates of overdiagnosis due to varying interpretations among specialists or missing information. Although several studies have designed objective behavioral features to overcome such an issue, they lack significance. Despite electroencephalography (EEG) analyses extracting alternative biomarkers using signal processing techniques, the nonlinearity and nonstationarity of EEG signals restrain performance and generalization of hand-crafted features. This work proposes a methodology to support ADHD diagnosis by characterizing EEG signals from hidden Markov models (HMM), classifying subjects based on similarity measures for probability functions, and spatially interpreting the results using graphic embeddings of stochastic dynamic models. The methodology learns a single HMM for EEG signal from each patient, so favoring the inter-subject variability. Then, the Probability Product Kernel, specifically developed for assessing the similarity between HMMs, fed a support vector machine that classifies subjects according to their stochastic dynamics. Lastly, the kernel variant of Principal Component Analysis provided a means to visualize the EEG transitions in a two-dimensional space, evidencing dynamic differences between ADHD and Healthy Control children. From the electrophysiological perspective, we recorded EEG under the Stop Signal Task modified with reward levels, which considers cognitive features of interest as insufficient motivational circuits recruitment. The methodology compares the supported diagnosis in two EEG channel setups (whole channel set and channels of interest in frontocentral area) and four frequency bands (Theta, Alpha, Beta rhythms, and a wideband). Results evidence an accuracy rate of 97.0% in the Beta band and in the channels where previous works found error-related negativity events. Such accuracy rate strongly supports the dual pathway hypothesis and motivational deficit concerning the pathophysiology of ADHD. It also demonstrates the utility of joining inhibitory and motivational paradigms with dynamic EEG analysis into a noninvasive and affordable diagnostic tool for ADHD patients.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Ritmo beta/fisiologia , Criança , Eletroencefalografia/métodos , Humanos , Processamento de Sinais Assistido por Computador , Máquina de Vetores de Suporte
18.
Bull Entomol Res ; 112(4): 469-480, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34823612

RESUMO

Climate change has affected the geographical distributions of most species worldwide; in particular, insects of economic importance inhabiting tropical regions have been impacted. Current and future predictions of change in geographic distribution are frequently included in species distribution models (SDMs). The potential spatial distributions of the fruit fly Anastrepha striata Schiner, the main species of agricultural importance in guava crops, under current and possible future scenarios in Colombia were modeled, and the establishment risk was assessed for each guava-producing municipality in the country. SDMs were developed using 221 geographical records in conjunction with nine scenopoetic variables. The model for current climate conditions indicated an extensive suitable area for the establishment of A. striata in the Andean region, smaller areas in the Caribbean and Pacific, and almost no areas in the Orinoquia and Amazonian regions. A brief discussion regarding the area's suitability for the fly is offered. According to the results, altitude is one of the main factors that direct the distribution of A. striata in the tropics. The Colombian guava-producing municipalities were classified according to the degree of vulnerability to fly establishment as follows: 42 were high risk, 16 were intermediate risk, and 17 were low risk. The implementation of future integrated management plans must include optimal spatial data and must consider environmental aspects, such as those suggested by the models presented here. Control decisions should aim to mitigate the positive relationship between global warming and the increase in the dispersal area of the fruit fly.


Assuntos
Psidium , Tephritidae , Distribuição Animal , Animais , Mudança Climática , Colômbia , Geografia
19.
Acta Ortop Mex ; 35(3): 261-265, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-34921535

RESUMO

The objective of this study was to investigate the prevalence and epidemiology of knee cartilage lesions in the work environment, and to assess whether they increase the patient's work leave and thus also cost. We also analyzed the prevalence of concomitant pathology and how it affected recovery and final outcome. MATERIAL AND METHODS: Monocentric retrospective cohort of patients with occupational injuries who underwent knee arthroscopy during 2018. Demographic data, diagnosis, concomitant chondral pathology, treatment, symptoms and signs at discharge, work leave and total cost were collected. RESULTS: 123 patients were analyzed, with a mean age of 47 years. No differences were found between sexes or with respect to obesity. Asymptomatic chondral lesions were found in 35.25% of the patients, primarily the older ones (48-53 years). The presence of cartilaginous pathology did not increase days of work leave or total cost (p > 0.05). In patients with meniscopathy in whom meniscectomy is performed, the chondral lesion increased the number of days of work leave (p = 0.03). There were no differences in the number of days of work leave nor total cost for different treatments of chondral pathology. CONCLUSION: The management of a concomitant chondral knee lesion is still controversial. These lesions might convey poorer functional prognosis in patients with meniscopathy. Current therapies have not shown a clear benefit in work injuries.


El objetivo principal del estudio fue analizar la asociación entre la presencia de lesiones cartilaginosas asintomáticas en pacientes con lesiones traumáticas de rodilla y su tiempo de baja y gasto mutual. Los objetivos secundarios fueron describir la prevalencia y epidemiología de estas lesiones y analizar si se asocian con la presencia de obesidad y un peor resultado final. Material y métodos: Revisión retrospectiva de una cohorte de todos los pacientes a los que se les realizó una artroscopía de rodilla tras una lesión traumática en un centro mutual en el año 2018. Se recogieron datos demográficos, diagnóstico, patología condral concomitante, tratamiento, clínica al alta, tiempo total de baja y el gasto derivado de ésta. Resultados: Fueron analizados 123 pacientes con una media de edad de 47 años, no se encontraron diferencias entre sexos ni respecto a la obesidad entre los grupos con y sin lesión condral. Las lesiones cartilaginosas fueron diagnosticadas en más de un tercio de los pacientes valorados (35.25%), la mayoría entre 48 y 53 años. La presencia de patología condral no fue un condicionante que aumentara los días de baja o el gasto total (p > 0.05). En pacientes con meniscectomía, la lesión condral aumenta el tiempo de baja (p = 0.03). Los tratamientos enfocados en la lesión condral no produjeron diferencias en cuanto a la duración de la baja ni en el gasto. Conclusión: El manejo de una lesión condral concomitante a nivel de la rodilla sigue presentando controversia. Podría implicar un factor de mal pronóstico de recuperación en pacientes con meniscopatía y las terapias actuales no han mostrado un beneficio claro en estos pacientes del entorno laboral.


Assuntos
Artroscopia , Articulação do Joelho , Humanos , Pessoa de Meia-Idade , Obesidade , Estudos Retrospectivos
20.
Eur J Hum Genet ; 29(10): 1520-1526, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34267336

RESUMO

A subset of families with co-dominant or recessive inheritance has been described in several genes previously associated with dominant inheritance. Those recessive families displayed similar, more severe, or even completely different phenotypes to their dominant counterparts. We report the first patients harboring homozygous disease-related variants in three genes that were previously associated with dominant inheritance: a loss-of-function variant in the CACNA1A gene and two missense variants in the RET and SLC20A2 genes, respectively. All patients presented with a more severe clinical phenotype than the corresponding typical dominant form. We suggest that co-dominant or recessive inheritance for these three genes could explain the phenotypic differences from those documented in their cognate dominant phenotypes. Our results reinforce that geneticists should be aware of the possible different forms of inheritance in genes when WES variant interpretation is performed. We also evidence the need to refine phenotypes and inheritance patterns associated with genes in order to avoid failures during WES analysis and thus, raising the WES diagnostic capacity in the benefit of patients.


Assuntos
Canais de Cálcio/genética , Genes Dominantes , Mutação com Perda de Função , Fenótipo , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/genética , Adulto , Alelos , Feminino , Humanos , Recém-Nascido , Masculino , Linhagem
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