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BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) and EEG-guided neurofeedback techniques can reduce motor symptoms in Parkinson's disease (PD). However, the effects of their combination are unknown. Our objective was to determine the immediate and short-term effects on motor and non-motor symptoms, and neurophysiological measures, of rTMS and EEG-guided neurofeedback, alone or combined, compared to no intervention, in people with PD. METHODS: A randomized, single-blinded controlled trial with 4 arms was conducted. Group A received eight bilateral, high-frequency (10 Hz) rTMS sessions over the Primary Motor Cortices; Group B received eight 30-minute EEG-guided neurofeedback sessions focused on reducing average bilateral alpha and beta bands; Group C received a combination of A and B; Group D did not receive any therapy. The primary outcome measure was the UPDRS-III at post-intervention and two weeks later. Secondary outcomes were functional mobility, limits of stability, depression, health-related quality-of-life and cortical silent periods. Treatment effects were obtained by longitudinal analysis of covariance mixed-effects models. RESULTS: Forty people with PD participated (27 males, age = 63 ± 8.26 years, baseline UPDRS-III = 15.63 ± 6.99 points, H&Y = 1-3). Group C showed the largest effect on motor symptoms, health-related quality-of-life and cortical silent periods, followed by Group A and Group B. Negligible differences between Groups A-C and Group D for functional mobility or limits of stability were found. CONCLUSIONS: The combination of rTMS and EEG-guided neurofeedback diminished overall motor symptoms and increased quality-of-life, but this was not reflected by changes in functional mobility, postural stability or depression levels. TRIAL REGISTRATION: NCT04017481.
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Eletroencefalografia , Neurorretroalimentação , Doença de Parkinson , Estimulação Magnética Transcraniana , Humanos , Doença de Parkinson/terapia , Doença de Parkinson/reabilitação , Doença de Parkinson/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Estimulação Magnética Transcraniana/métodos , Neurorretroalimentação/métodos , Idoso , Eletroencefalografia/métodos , Método Simples-Cego , Resultado do Tratamento , Córtex Motor/fisiologia , Córtex Motor/fisiopatologia , Qualidade de VidaRESUMO
BACKGROUND: Anemia is a common comorbidity in patients with diabetes mellitus (DM), particularly in older adults. However, there is a lack of data on the prevalence and the characteristics of anemia in this population in Spain. OBJECTIVE: To describe the prevalence and the characteristics of anemia in patients with DM aged 50 or older (PDM50) in a healthcare district in the province of Cádiz. METHODS: A retrospective cross-sectional study was conducted that included outpatient's laboratory tests (OLT) performed over 30 months at PDM50. RESULTS: The prevalence of anemia was 29.9% (95% CI: 28.7%-31.1%), predominating in women (33.3% vs 26.7%; Pâ¯<â¯0.01), in older people stratified by decades (61.7% in 9th decade vs 12% in 5th decade; Pâ¯<â¯0.01), and in those with kidney disease (44.7% vs 28%; Pâ¯<â¯0.01). Most cases were mild (68.3%), normocytic (78.7%), and hypochromic (52%). Similarly, moderate-to-severe anemia was more frequent in women (39% vs 23%), their prevalence increased with age (45% in the 9th decade vs 24% in the 5th decade), and with the progression of kidney damage, either measured by a decreased glomerular filtration rate (GFR) (49% in G4 vs 25% in G1), or the presence of albuminuria (Pâ¯<â¯0.01). No association was found between DM control, based on glycated hemoglobin (HbA1c), and anemia in either sex (Pâ¯=â¯0.887). CONCLUSION: This study describes a high prevalence of anemia in PDM50, particularly in women, in the most advantageous people and in the presence of kidney disease, even in early stages, highlighting the clinical importance of this coexistence.
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Anemia , Humanos , Feminino , Masculino , Anemia/epidemiologia , Prevalência , Espanha/epidemiologia , Estudos Transversais , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Diabetes Mellitus/epidemiologia , Complicações do Diabetes/epidemiologiaRESUMO
FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination.
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Leucemia Mieloide Aguda , Mutação , Proteínas Nucleares , Nucleofosmina , Tirosina Quinase 3 Semelhante a fms , Humanos , Tirosina Quinase 3 Semelhante a fms/genética , Idoso , Masculino , Feminino , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/diagnóstico , Proteínas Nucleares/genética , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Vidarabina/administração & dosagem , Adulto , Taxa de SobrevidaRESUMO
PURPOSE: Rett syndrome (RTT) is a rare multi-systemic disorder primarily linked to mutations in MECP2 gene. This study aims to describe the prevalence of orthopedic conditions in RTT patients, and examine their intricate interplay with functional capabilities, and MECP2 variant subtypes. METHODS: Conducted as a cross-sectional retrospective observational study, the research encompassed 55 patients meeting clinical RTT criteria and holding MECP2 mutations. A review of clinical records was performed to gather demographic data, mutation subtypes, orthopedic conditions, management strategies, and assessments of function. RESULTS: Mean age of the participants was 10.22 ± 4.64 years (range, 2.9-19.41). Prevalence rates of orthopedic conditions were as follows: kyphoscoliosis 63.6%, hip displacement 14.6%, knee problems 40%, and foot deformities 75.5%. Significant relationship emerged between spinal (p < 0.01) and knee deformities (p < 0.01) with reduced motor function across various domains. Hip displacement significantly affected sitting ability (p = 0.002), and foot deformities impacted standing and walking capabilities (p = 0.049). Mutation clusters analysis revealed significant correlations with spinal (p = 0.022) and knee deformities (p = 0.002). Linear models highlighted the critical importance of mutation clusters, spine deformities, age, and hip management concerning functional variables. CONCLUSIONS: In this study, foot deformities were the most frequent orthopedic manifestation, followed by spinal, knee, and hip deformities; and unveiled their relationships with functional status and groups of mutations in RTT patients. LEVEL OF EVIDENCE: Level IV, Case series.
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OBJECTIVE: To characterize and describe clinical experience with childhood-onset non-infectious uveitis. STUDY DESIGN: A multicenter retrospective multidisciplinary national web-based registry of 507 patients from 21 hospitals was analyzed. Cases were grouped as immune disease-associated (IMDu), idiopathic (IDIu) or ophthalmologically distinct. Characteristics of juvenile idiopathic arthritis-associated (non-HLA-B27-related) uveitis (JIAu), IDIu, and pars planitis (PP) were compared. RESULTS: IMDu (62.3%) and JIAu (51.9%) predominated in young females; and IDIu (22.7%) and PP (13.6%) in older children, without sex imbalance. Ocular complications occurred in 45.3% of cases (posterior synechiae [28%], cataracts [16%], band keratopathy [14%], ocular hypertension [11%] and cystoid macular edema [10%]) and were associated with synthetic (86%) and biologic (65%) disease-modifying antirheumatic drug (DMARD) use. Subgroups were significantly associated (p < 0.05) with different characteristics. JIAu was typically anterior (98%), insidious (75%), in ANA-positive (69%), young females (82%) with fewer complications (31%), better visual outcomes, and later use of uveitis-effective biologics. In contrast, IDIu was characteristically anterior (87%) or panuveitic (12.1%), with acute onset (60%) and more complications at onset (59%: synechiae [31%] and cataracts [9.6%]) and less DMARD use, while PP is intermediate, and was mostly bilateral (72.5%), persistent (86.5%) and chronic (86.8%), with more complications (70%; mainly posterior segment and cataracts at last visit), impaired visual acuity at onset, and greater systemic (81.2%), subtenon (29.1%) and intravitreal (10.1%) steroid use. CONCLUSION: Prognosis of childhood uveitis has improved in the "biologic era," particularly in JIAu. Early referral and DMARD therapy may reduce steroid use and improve outcomes, especially in PP and IDIu.
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The current demand on health services requires that nurses play a key role, by adapting their competencies to different fields and complexity levels. The approach of situations presented by critically ill patients underpins the need for development of specialised competencies in specific areas such as patient safety, prevention and control of healthcare-associated infections, performance of specific techniques and interventions, autonomous medication management or the use of technology, among others. Spain relies on a specialist training programme that is unique worldwide. Training admission is managed through a contract as a "Resident Nurse Intern" (EIR, Enfermera Interna Residente), provided by regional healthcare services. Only 6 specialities have been established and developed, in an uneven manner and with a short provision of places, annually. Given that the specialization in critical care nursing does not exist, nurses usually self-fund their postgraduate training to enhance their opportunities career development. The development of a speciality for critical care nursing is a priority. The models proposed advocate for creating nursing roles that could cover the systemic gaps through the expansion of their competencies and the introduction of procedures that fit nursing into advanced practice, which could be achieved through Advanced Accreditation Diplomas. Simultaneously, it would be convenient to analyse how and why such a dynamic discipline in some countries became stuck in anachronistic models of the Spanish healthcare system. This analysis might contribute to move forward on the development of areas of improvement in terms of service access and quality of care.
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Enfermagem de Cuidados Críticos , Enfermagem de Cuidados Críticos/educação , Humanos , Espanha , Necessidades e Demandas de Serviços de Saúde , Papel do Profissional de EnfermagemRESUMO
Ambient sound can mask acoustic signals. The current study addressed how echolocation in people is affected by masking sound, and the role played by type of sound and spatial (i.e. binaural) similarity. We also investigated the role played by blindness and long-term experience with echolocation, by testing echolocation experts, as well as blind and sighted people new to echolocation. Results were obtained in two echolocation tasks where participants listened to binaural recordings of echolocation and masking sounds, and either localized echoes in azimuth or discriminated echo audibility. Echolocation and masking sounds could be either clicks or broad band noise. An adaptive staircase method was used to adjust signal-to-noise ratios (SNRs) based on participants' responses. When target and masker had the same binaural cues (i.e. both were monoaural sounds), people performed better (i.e. had lower SNRs) when target and masker used different types of sound (e.g. clicks in noise-masker or noise in clicks-masker), as compared to when target and masker used the same type of sound (e.g. clicks in click-, or noise in noise-masker). A very different pattern of results was observed when masker and target differed in their binaural cues, in which case people always performed better when clicks were the masker, regardless of type of emission used. Further, direct comparison between conditions with and without binaural difference revealed binaural release from masking only when clicks were used as emissions and masker, but not otherwise (i.e. when noise was used as masker or emission). This suggests that echolocation with clicks or noise may differ in their sensitivity to binaural cues. We observed the same pattern of results for echolocation experts, and blind and sighted people new to echolocation, suggesting a limited role played by long-term experience or blindness. In addition to generating novel predictions for future work, the findings also inform instruction in echolocation for people who are blind or sighted.
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Localização de Som , Animais , Humanos , Localização de Som/fisiologia , Cegueira , Ruído , Acústica , Sinais (Psicologia) , Mascaramento Perceptivo , Estimulação Acústica/métodosRESUMO
Purpose: First, testing an intervention of neuromodulation based on motor imagery and action observation as a promoter of motor adaptation of a complex motor task involving balance. Second, determining what prior balance factors can affect the motor adaptation task. Methods: A double-blind randomized controlled trial was performed. Forty-eight healthy subjects were recruited. The balance of all participants during gait and standing was assessed before adapting to the complex, multi-limb motor task of riding an inverse steering bicycle (ISB). Two interventions were carried out interleaved among trials of adaptation to the motor task: the experimental group (n = 24) was asked to perform neuromodulation (EN) by watching first-person ISB riding through immersive VR glasses and, simultaneously, mentally mimicking the movements. The control group (CG) was asked to watch a slideshow video of steady landscape images. Results: The results showed that the EN group did not improve the motor adaptation rate and induced higher adaptation times with respect to the CG. However, while the motor adaptation success showed a significant dependence on the prior proprioceptive participation in balance in the CG, the EN group did not present any relationship between the prior balance profile and motor adaptation outcome. Conclusions: Results point to a benefit of the visually guided neuromodulation for the motor adaptation of the subjects with low participation of proprioception in balance. Moreover, the results from the control group would allow to disclose prognostic factors about the success of the motor adaptation, and also prescription criteria for the proposed neuromodulation based on the balance profile.
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I ntroducción Este estudio analiza la comparabilidad de las medidas tomadas por un autorefractómetro portátil Retinomax K-plus 3 en modo Quick (rápido) y un autorrefractómetro de sobremesa Topcon KR-800 en modo estándar sobre la población pediátrica, y establece su correlación. Método Es un estudio comparativo retrospectivo. Se midieron las variables potencia dióptrica esférica (SPH), potencia dióptrica cilíndrica (CYL), ángulo del eje cilíndrico (AX) y equivalente esférico (SE) con el Retinomax en modo Quick y con el Topcon en modo estándar. Cada paciente fue evaluado en condiciones ciclopléjicas y no ciclopléjicas por ambos autorefractómetros. Se realizó la prueba t de Student entre ambos instrumentos para SPH, CYL y SE. Se calculó el coeficiente de correlación de Pearson y se representó la dispersión mediante gráficas de Bland-Altman, evaluándose también el subgrupo de pacientes menores de 4 años. Se realizó un análisis descriptivo de los porcentajes de medidas que diferían. Resultados Incluyó 98 ojos de 49 sujetos (rango de edad: 3-16 años). Los datos de SPH sin cicloplejia son prácticamente idénticos, mientras que con cicloplejia hay un sesgo hipermetrópico de +0,5 dioptrías medidas con Retinomax. Los resultados de CYL son muy similares con y sin cicloplejia. Existe una gran correlación de Pearson para ambos instrumentos (>0,91) y un bajo grado de dispersión en los gráficos de Bland-Altman bajo cicloplejia. Conclusión Los datos del Retinomax fueron consistentes con los obtenidos por el Topcon. El Retinomax es un instrumento útil para detectar errores de refracción en niños de entre 3 y 16 años (AU)
Introduction This study analyzes the comparability of measurements taken by a Retinomax K-plus 3 handheld autorefractometer in quick mode and a Topcon KR-800 on-table autorefractometer in standard mode on the pediatric population, and establishes their correlation. Methods It is a retrospective comparative study. Spherical diopter power (SPH), cylindrical diopter power (CYL), angle of cylindrical axis (AX), and spherical equivalent (SE) were measured with the Retinomax in quick mode and with the Topcon in standard mode. Each patient was evaluated in cycloplegic and non-cycloplegic conditions by both autorefractometers. Student's t-test was performed between the two instruments for SPH, CYL, and SE. The Pearson correlation coefficient was calculated and the dispersion was represented using Bland-Altman graphs, also evaluating the subgroup of patients under 4 years of age. A descriptive analysis of the percentages of measures that differed was performed. Results It included 98 eyes of 49 subjects (age range: 3-16 years). The data for HPS without cycloplegia are virtually identical, whereas with cycloplegia there is a hyperopic bias of +0.5 diopters measured with Retinomax. CYL results are very similar with and without cycloplegia. There is a high Pearson correlation for both instruments (>0.91) and a low degree of dispersion in the Bland-Altman plots under cycloplegia. Conclusion The Retinomax data were consistent with those obtained by Topcon. The Retinomax is a useful instrument for detecting refractive errors in children between 3 and 16 years of age (AU)
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Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Técnicas de Diagnóstico Oftalmológico/instrumentação , Erros de Refração/diagnóstico , Estudos Retrospectivos , Correlação de DadosRESUMO
Antecedentes y objetivos: La hipertensión arterial (HTA) es un factor de riesgo clave para el ictus. Evaluamos si la importancia de la HTA sobre el riesgo de ictus isquémico ha aumentado en las últimas décadas. Métodos: Estudio retrospectivo de pacientes con ictus isquémico dados de alta en 3 hospitales de Sevilla (España), durante los periodos: 1999-2001, 2014-2016 y 2019-2020. Resultados: Se incluyeron 1.379 pacientes, 42,6% mujeres, edad media 69,1 (±11) años. La HTA fue el factor de riesgo vascular más prevalente en todos los periodos, con un aumento progresivo de pacientes hipertensos (65,9 vs. 69,6 vs. 74%; p=0,029). La HTA fue especialmente frecuente en pacientes≥80 años (73 vs. 81,9 vs. 85,2%; p=0,029). Al alta se utilizaron progresivamente más fármacos antihipertensivos (en el 65 vs. 85,1 vs. 90,2% de los pacientes; p=0,0001), con un claro aumento en el número de fármacos antihipertensivos utilizados (media 0,9±0,8 vs. 1,5±1 vs. 1,8±0,8 fármacos; p=0,0001). El uso de diuréticos (13,7-39,3-65,3%; p=0,0001), IECA (35,5-43,3-53,4%; p=0,0001) y bloqueadores de los receptores de angiotensina (12,2-24-32,4%; p=0,0001) aumentó progresivamente. Por el contrario, disminuyó el uso de antagonistas del calcio (24-19,9-13,7; p=0,0001). Conclusiones: En las últimas 2 décadas existe un mayor protagonismo de la HTA entre los pacientes con primer evento cerebrovascular isquémico. Es necesario un mayor y mejor control de la HTA para disminuir la enorme carga de la enfermedad cerebrovascular. (AU)
Background and objectives: Hypertension (HT) is a key risk factor for stroke. We evaluated whether the importance of hypertension on the risk of ischemic stroke has increased in recent decades. Methods: Retrospective study of patients with ischemic stroke discharged from 3 hospitals in Seville (Spain), during the periods: 1999-2001, 2014-2016 and 2019-2020. Results: 1,379 patients were included, 42.6% women, mean age 69.1 (±11) years. HT was the most prevalent vascular risk factor in all periods, with a progressive increase in hypertensive patients (65.9% vs 69.6% vs 74%; P=.029). HT was especially frequent in patients≥80 years (73% vs 81.9% vs 85.2%; P=.029). At discharge, progressively more antihypertensive drugs were used (in 65% vs 85.1 vs 90.2% of patients; P=.0001), with a clear increase in the number of antihypertensive drugs used (mean 0.9±0.8 vs 1.5±1 vs 1.8±0.8 drugs, P=.0001). The use of diuretics (13.7%-39.3%-65.3%; p=0.0001), ACE inhibitors (35.5%-43.3%-53.4%; P=.0001) and angiotensin receptor blockers (12.2%-24%-32.4%; P=.0001) increased progressively. On the contrary, the use of calcium antagonists decreased (24%-19.9%-13.7%; P=.0001). Conclusions: In the last 2 decades there has been a greater role for HT among patients with their first ischemic cerebrovascular event. Greater and better control of HT is necessary to reduce the enormous burden of cerebrovascular disease. (AU)
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Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Hipertensão , Acidente Vascular Cerebral/prevenção & controle , Estudos Retrospectivos , Fatores de Risco , Espanha , Anti-Hipertensivos/uso terapêuticoRESUMO
INTRODUCTION: This study analyzes the comparability of measurements taken by a Retinomax K-plus 3 handheld autorefractometer in Quick mode and a Topcon KR-800 on-table autorefractometer in standard mode on the pediatric population, and establishes their correlation. METHODS: It is a retrospective comparative study. Spherical diopter power (SPH), cylindrical diopter power (CYL), angle of cylindrical axis (AX), and spherical equivalent (SE) were measured with the Retinomax in Quick mode and with the Topcon in standard mode. Each patient was evaluated in cycloplegic and non-cycloplegic conditions by both autorefractometers. Student's t-test was performed between the two instruments for SPH, CYL, and SE. The Pearson correlation coefficient was calculated and the dispersion was represented using Bland-Altman graphs, also evaluating the subgroup of patients under 4 years of age. A descriptive analysis of the percentages of measures that differed was performed. RESULTS: It included 98 eyes of 49 subjects (age range: 3-16 years). The data for HPS without cycloplegia are virtually identical, whereas with cycloplegia there is a hyperopic bias of +0.5 diopters measured with Retinomax. CYL results are very similar with and without cycloplegia. There is a high Pearson correlation for both instruments (>0.91) and a low degree of dispersion in the Bland-Altman plots under cycloplegia. CONCLUSION: The Retinomax data were consistent with those obtained by Topcon. The Retinomax is a useful instrument for detecting refractive errors in children between 3 and 16 years of age.
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Hiperopia , Presbiopia , Distúrbios Pupilares , Criança , Humanos , Pré-Escolar , Adolescente , Estudos Retrospectivos , Correlação de Dados , Olho , MidriáticosRESUMO
The objectives of this study were to describe the personality traits of Portuguese skydivers and to study the differences in the 5 dimensions of personality traits: Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness. The variables were: experience, sex and age. One hundred and fourteen skydivers participated. We used the NEO-FFI questionnaire. The statistical tests used were the Chi-square, Pearson's correlation coefficient and multivariate data analysis (MANCOVA). The results show that the skydivers presented higher values in the Extraversion and Conscientiousness dimensions, and lower in the Neuroticism dimension. The multivariate analysis identified statistically significant differences in the Conscientiousness dimension based on experience, with the more experienced skydivers obtaining higher scores, although the effect size was small. The skydivers did not present significant differences, which allows us to conclude that they form a homogeneous group, with similar personality traits. (AU)
Los objetivos de este estudio fueron describir los rasgos de personalidad de los practicantes de paracaidismo portugueses y estudiar las diferencias en las 5 dimensiones del rasgo de personalidad: Neuroticismo, Extraversión, Apertura a la Experiencia, Amabilidad y Responsabilidad. Las variables fueron: experiencia, sexo y edad. Participaron 114 paracaidistas. Usamos el cuestionario NEO-FFI. Las pruebas estadísticas usadas fueran el Chi-cuadrado el coeficiente de correlación de Pearson y análisis multivariado de datos (MANCOVA). Los resultados muestran que los paracaidistas presentaron valores más altos en la dimensión Extroversión y Responsabilidad, y menores en la dimensión Neuroticismo. El análisis multivariado identifica diferencias estadísticamente significativas en la dimensión Responsabilidad en función de la experiencia, obteniendo puntuaciones más altas para los paracaidistas más experimentados, aunque el tamaño del efecto sea pequeño. Los paracaidistas no presentaron diferencias significativas, lo que nos permite concluir que se trata de un grupo homogéneo, con rasgos de personalidad similares. (AU)
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Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Aviação , Personalidade/classificação , Portugal , Inquéritos e Questionários , Distribuição de Qui-Quadrado , Análise MultivariadaRESUMO
Whether there exist finite-time blow-up solutions for the 2D Boussinesq and the 3D Euler equations are of fundamental importance to the field of fluid mechanics. We develop a new numerical framework, employing physics-informed neural networks, that discover, for the first time, a smooth self-similar blow-up profile for both equations. The solution itself could form the basis of a future computer-assisted proof of blow-up for both equations. In addition, we demonstrate physics-informed neural networks could be successfully applied to find unstable self-similar solutions to fluid equations by constructing the first example of an unstable self-similar solution to the Córdoba-Córdoba-Fontelos equation. We show that our numerical framework is both robust and adaptable to various other equations.
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Redes Neurais de Computação , FísicaRESUMO
The photoreceptor outer segment is a highly specialized primary cilium essential for phototransduction and vision. Biallelic pathogenic variants in the cilia-associated gene CEP290 cause non-syndromic Leber congenital amaurosis 10 (LCA10) and syndromic diseases, where the retina is also affected. While RNA antisense oligonucleotides and gene editing are potential treatment options for the common deep intronic variant c.2991+1655A>G in CEP290 , there is a need for variant-independent approaches that could be applied to a broader spectrum of ciliopathies. Here, we generated several distinct human models of CEP290 -related retinal disease and investigated the effects of the flavonoid eupatilin as a potential treatment. Eupatilin improved cilium formation and length in CEP290 LCA10 patient-derived fibroblasts, in gene-edited CEP290 knockout (CEP290 KO) RPE1 cells, and in both CEP290 LCA10 and CEP290 KO iPSCs-derived retinal organoids. Furthermore, eupatilin reduced rhodopsin retention in the outer nuclear layer of CEP290 LCA10 retinal organoids. Eupatilin altered gene transcription in retinal organoids, by modulating the expression of rhodopsin, and by targeting cilia and synaptic plasticity pathways. This work sheds light into the mechanism of action of eupatilin, and supports its potential as a variant-independent approach for CEP290 -associated ciliopathies.
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BACKGROUND AND OBJECTIVES: Hypertension (HT) is a key risk factor for stroke. We evaluated whether the importance of hypertension on the risk of ischemic stroke has increased in recent decades. METHODS: Retrospective study of patients with ischemic stroke discharged from 3 hospitals in Seville (Spain), during the periods: 1999-2001, 2014-2016 and 2019-2020. RESULTS: 1,379 patients were included, 42.6% women, mean age 69.1 (±11) years. HT was the most prevalent vascular risk factor in all periods, with a progressive increase in hypertensive patients (65.9% vs 69.6% vs 74%; P=.029). HT was especially frequent in patients≥80 years (73% vs 81.9% vs 85.2%; P=.029). At discharge, progressively more antihypertensive drugs were used (in 65% vs 85.1 vs 90.2% of patients; P=.0001), with a clear increase in the number of antihypertensive drugs used (mean 0.9±0.8 vs 1.5±1 vs 1.8±0.8 drugs, P=.0001). The use of diuretics (13.7%-39.3%-65.3%; p=0.0001), ACE inhibitors (35.5%-43.3%-53.4%; P=.0001) and angiotensin receptor blockers (12.2%-24%-32.4%; P=.0001) increased progressively. On the contrary, the use of calcium antagonists decreased (24%-19.9%-13.7%; P=.0001). CONCLUSIONS: In the last 2 decades there has been a greater role for HT among patients with their first ischemic cerebrovascular event. Greater and better control of HT is necessary to reduce the enormous burden of cerebrovascular disease.
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PURPOSE: Surgery of primary thyroid lymphoma (PTL) has been mostly limited to diagnostic work-up. This study aimed to further study its potential role. METHODS: This was a retrospective study from a multi-institutional registry of PTL patients. Clinical, diagnostic work-up (fine needle aspiration, FNA; core needle biopsy, CoreNB), contribution of surgery (open surgical biopsy, OpenSB; thyroidectomy), histology subtype, and outcome data were evaluated. RESULTS: Some 54 patients were studied. Diagnostic work-up included FNA in 47 patients, CoreNB in 11, and OpenSB in 21. CoreNB yielded the best sensitivity (90.9%). Thyroidectomy was performed in 14 patients with other diagnosis (incidental PTL), in 4 for diagnosis and in 4 for elective treatment of PTL. Incidental PTL was associated with not performed FNA nor CoreNB (OR 52.5; P = 0.008), mucosa-associated lymphoid tissue (MALT) subtype (OR 24.3; P = 0.012), and Hashimoto's thyroiditis (OR 11.1; P = 0.032). Lymphoma-related death (10 cases) mostly occurred within the first year after diagnosis and was associated with diffuse large B-cell (DLBC) subtype (OR 10.3; P = 0.018) and older patients (OR 1.08 for every 1-year increase; P = 0.010). There was a trend towards lower mortality rate in patients receiving thyroidectomy (2/22 versus 8/32, P = 0.172). CONCLUSION: Incidental PTL accounts for most of thyroid surgery cases and are associated with incomplete diagnostic work-up, Hashimoto's thyroiditis and MALT subtype. CoreNB appears to be the best tool for diagnosis. Most of PTL deaths occurred during the first year after diagnosis and mostly related to systemic treatment. Age and DLBC subtype are poor prognostic factors.
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Linfoma , Neoplasias da Glândula Tireoide , Tireoidite , Humanos , Estudos RetrospectivosRESUMO
Background: Since the state of alarm was declared due to the COVID-19 pandemic, hospitals have been the main ones in charge of registering the therapeutic follow-up of affected people. The analysis of these data has allowed those different biochemical markers have been identified as predictors of the severity of the disease, but most of the published studies tend to be eminently descriptive and do not propose a biochemical hypothesis to explain the alteration of the results they are showing. Our objective is to recognize the main metabolic processes that are occurring in COVID-19 patients, as well as the identification of clinical parameters that are decisive to predict the severity of the disease. Methods: A multivariate analysis was carried out from the clinical parameters collected in the database of the HM hospitals in Madrid, to determine the most relevant variables to predict the severity of the disease. Chemometric methods allow these variables to be obtained by applying a classification strategy with PLS-LDA. Findings and interpretation: The variables that most contribute to separation are age in men and, in both sexes, the concentration of lactate dehydrogenase, urea and C-reactive protein.Oxygen deficiency in the tissues, due to the loss of functionality of the lungs, could be affecting the muscle tissue with special severity. Inflammation and tissue damage is related to increased LDH and CRP. The loss of muscle mass and the increase in the concentration of urea and LDH is explained by the adaptation of muscle metabolism to this oxygen deficiency. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profits sectors.
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Introducción Las sociedades estadounidenses de nefrología recomiendan cambiar la ecuación CKD-EPI 2009 por la nueva CKD-EPI 2021, que no incluye el coeficiente de raza, para estimar la tasa de filtrado glomerular (TFGe). Se desconoce cómo podría afectar este cambio a la distribución de la enfermedad renal de la población española predominantemente caucásica. Métodos Se estudiaron dos cohortes de adultos de la provincia de Cádiz, BD-SIDICA (n=264.217 personas) y BD-PANDEMIA (n=64.217), que disponían de mediciones de creatinina plasmática entre 2017 y 2021. Se calcularon los cambios de la TFGe y la consecuente reclasificación en las diferentes categorías de la clasificación KDIGO-2012 al modificar la ecuación CKD-EPI 2009 por la de 2021. Resultados En comparación con la ecuación de 2009, CKD-EPI-21 arrojó una TFGe más alta, con una mediana de 3,8mL/min/1,73m2 (IQR: 2,98-4,48) en BD-SIDICA y de 3,89mL/min/1,73m2 (IQR: 3,05-4,55) en BD-PANDEMIA. Como primera consecuencia, del total de la población, el 15,3% en BD-SIDICA y el 15,1% en BD-PANDEMIA y el 28,1% y el 27,3%, respectivamente, de la población con enfermedad renal (G3-G5), se reclasificó a una categoría de TFGe más alta y ningún sujeto a una más grave. Como segunda consecuencia, la prevalencia de la enfermedad renal disminuyó del 9% al 7,5% en ambas cohortes. Conclusiones Implementar la ecuación CKD-EPI-21 en la población española, predominantemente caucásica, aumentaría la TFGe en una cantidad modesta (mayor en hombres y con mayor edad o TFG) y una proporción importante de la población se clasificaría en una categoría de TFGe superior, con la consiguiente disminución de la prevalencia de la enfermedad renal (AU)
Introduction United States nephrology societies recommend changing from the CKD-EPI 2009 equation to the new CKD-EPI 2021 equation, which does not include the race coefficient, for calculating estimated glomerular filtration rate (eGFR). It is unknown how this change might affect the distribution of kidney disease in the predominantly Caucasian Spanish population. Methods Two databases of adults from the province of Cádiz, DB-SIDICA (n=264,217) and BD-PANDEMIC (n=64,217), that had plasma creatinine measurements recorded between 2017 and 2021 were studied. Changes in eGFR and the consequent reclassification into different categories of the KDIGO2012 classification resulting from substituting the CKD-EPI 2009 equation for the 2021 equation were calculated. Results Compared to the 2009 equation, CKD-EPI 2021 yielded a higher eGFR, with a median of 3.8mL/min/1.73m2 (IQR: 2.98-4.48) in DB-SIDICA and 3.89mL/min/1.73m2 (IQR: 3.05-4.55) in DB-PANDEMIA. The first consequence was that 15.3% of the total population in DB-SIDICA and 15.1% of the total population in DB-PANDEMIA were reclassified into a higher category of eGFR, as were 28.1% and 27.3%, respectively, of the population with CKD (G3-G5); no subjects were classified into the more severe category. The second consequence was that the prevalence of kidney disease decreased from 9% to 7.5% in both cohorts. Conclusions Implementing the CKD-EPI 2021 equation in the Spanish population, which is predominantly Caucasian, would increase eGFR by a modest amount (greater in men and those who are older or have a higher GFR). A significant proportion of the population would be classified into a higher eGFR category, with a consequent decrease in the prevalence of kidney disease (AU)
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Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Insuficiência Renal Crônica/diagnóstico , Taxa de Filtração Glomerular , Creatinina/sangue , Testes de Função RenalRESUMO
INTRODUCTION: Planovalgus foot (PVF) is the most common orthopaedic abnormality in children with Down syndrome (DS), and as a result these patients rarely develop an adequate plantar arch in adulthood. The present study aims to evaluate the impact of PVF on activities of daily living and participation in sports among young adults with DS and determine whether this impact is related to the degree of foot deformity based on clinical and imaging studies. METHODS: Observational analytical study examining a database of 649 patients with DS from a pediatric referral center, identifying those individuals over age 20 years at the time of the study with a childhood diagnosis of PVF. Finally, 51 patients (102 feet) were evaluated based on clinical and imaging studies, and function was assessed using the The Foot and Ankle Outcome Score (FAOS) and the Visual Analogue Scale (VAS) pain scale. A correlation analysis was performed to determine the clinical and radiographic variables associated with functional outcomes. Linear regression models were obtained to quantify the impact of these variables on function. RESULTS: Patients had a mean age of 26.14±3.88 years and body mass index of 24.51±4.57. Clinically, 63.65% presented grade 3 or 4 PVF, and most were flexible. Radiographically, midfoot flattening was mild-moderate in 92.16%, 58.82% had medial talo-navicular uncoverage, and 30.39% had an increased hallux valgus (HV) angle. Mean scores for all FAOS subscales were between 65 and 71% and the mean VAS score was 1.45±1.96. An association analysis revealed a tendency toward lower scores on all FAOS subscales and greater pain according to the VAS scale in more severe PVF and in cases of moderate HV with asymmetry between feet. Linear regression models showed that major contributors to functional scores were radiographic evidence of hindfoot valgus, midfoot abduction, and flattening, and HV. CONCLUSIONS: Young adults with DS who are diagnosed with PVF in childhood have acceptable functional scores and low pain. Alteration of radiographic parameters toward flatter, more valgus and abducted feet and greater and asymmetric HV tend to be associated with worse long-term functional scores in activities of daily living and sports participation and increased pain. Therefore, non-operative management of these patients is justified, although individualized treatment is recommended. LEVEL OF EVIDENCE: Level IV, Case series.
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Síndrome de Down , Hallux Valgus , Ossos do Tarso , Criança , Adulto Jovem , Humanos , Adulto , Resultado do Tratamento , Atividades Cotidianas , Síndrome de Down/complicações , Dor , Hallux Valgus/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: The prevalence of hip dysplasia among patients with Down syndrome (DS) is higher than in the general population. We hypothesize that a relationship may exist between functional level and hip dysplasia in DS, but this has not been studied to date. The aim of this study is to evaluate whether there is a relationship between functional level and radiographic parameters of hip dysplasia or other measures. METHODS: Retrospective cross-sectional comparative study of 652 patients with DS from a pediatric referral center database. Patients over 8 years of age with an anteroposterior pelvis radiograph and with no exclusion criteria were selected, totaling 132 patients (264 hips; 54.55% females; mean age 12.96 ± 2.87 y). Several radiographic parameters of the acetabulum [Sharp angle (SA), Tönnis angle (TA), Wiberg center-edge angle (W-CEA), extrusion index (EI), and acetabular retroversion signs], the proximal femur [neck shaft angle (NSA)], and joint congruence [Shenton line (SL)] were assessed. Patients were classified into 2 levels based on functional skills. A multivariate association analysis was performed between radiographic parameters and functional level. RESULTS: Sixty-one patients were compatible with a functional level I and 71 with a level II. Forty-six hips were dysplastic and 60 were borderline according to the W-CEA. A statistically significant relationship was found between the categorical distribution of certain radiographic measurements of hip dysplasia (EI, SA, TA, W-CEA, SL, and classification by functional level ( P < 0.0005). A significant receiver operating characteristic curve was obtained for W-CEA with a cutt-off point at 26.4 degrees for level I (area under the curve = 0.763; P < 0.005; sensitivity = 0.800 and specificity = 0.644). There was a fairly high correlation between EI and TA (0.749; P < 0.0005), EI and W-CEA (-0.817; P < 0.0005), and TA and W-CEA (-0.748; P < 0.0005). Numerous hips showed signs of acetabular retroversion, with no significant differences found between functional levels or association with hip dysplasia measures. CONCLUSIONS: The present study reveals a relationship between an increased risk of hip dysplasia and reduced functional levels in DS children older than 8 years. These findings may guide individualized clinical follow-up of hip development in DS children considering their functional level. LEVEL OF EVIDENCE: Level III, retrospective comparative study.