RESUMEN
Diamond-Blackfan anaemia (DBA) is a rare, inherited bone marrow failure syndrome with a ribosomal defect causing slowed globin chain production with normal haem synthesis, causing an overabundance of reactive iron/haem and erythroid-specific cellular toxicity. Eltrombopag, a non-peptide thrombopoietin receptor agonist, is a potent intracellular iron chelator and induced a robust durable response in an RPS19-mutated DBA patient on another trial. We hypothesized eltrombopag would improve RBC production in DBA patients. We conducted a single-centre, single-arm pilot study (NCT04269889) assessing safety and erythroid response of 6 months of daily, fixed-dose eltrombopag for DBA patients. Fifteen transfusion-dependent (every 3-5 weeks) patients (median age 18 [range 2-56]) were treated. One responder had sustained haemoglobin improvement and >50% reduction in RBC transfusion frequency. Of note, 7/15 (41%) patients required dose reductions or sustained discontinuation of eltrombopag due to asymptomatic thrombocytosis. Despite the low response rate, eltrombopag has now improved erythropoiesis in several patients with DBA with a favourable safety profile. Dosing restrictions due to thrombocytosis may cause insufficient iron chelation to decrease haem production and improve anaemia in most patients. Future work will focus on erythropoiesis dynamics in patients and use of haem synthesis inhibitors without an impact on other haematopoietic lineages.
Asunto(s)
Anemia de Diamond-Blackfan , Benzoatos , Hidrazinas , Pirazoles , Humanos , Anemia de Diamond-Blackfan/tratamiento farmacológico , Pirazoles/uso terapéutico , Hidrazinas/uso terapéutico , Hidrazinas/administración & dosificación , Hidrazinas/efectos adversos , Benzoatos/uso terapéutico , Benzoatos/administración & dosificación , Benzoatos/efectos adversos , Adulto , Masculino , Femenino , Niño , Adolescente , Persona de Mediana Edad , Adulto Joven , Preescolar , Proyectos Piloto , Resultado del Tratamiento , Receptores de Trombopoyetina/agonistas , Recurrencia , Eritropoyesis/efectos de los fármacosRESUMEN
Newborn visual fixation abilities predict future cognitive, perceptive, and motor skills. However, little is known about the factors associated with the newborn visual fixation, which is an indicator of neurocognitive abilities. We analyzed maternal biological and environmental characteristics associated with fine motor skills (visual tracking) in 1 month old infants. Fifty-one infants were tested on visual tracking tasks (Infant Visuomotor Behavior Assessment Scale/ Guide for the Assessment of Visual Ability in Infants) and classified according to visual conducts scores. Differences between groups were compared considering motor development (Alberta Infant Motor Scale) maternal mental health (Edinburgh Postnatal Depression Scale and Hamilton Anxiety Scale); home environment (Affordances in the Home Environment for Development Scale); maternal care (Coding Interactive Behavior); breastmilk composition (total fatty acids, proteins, and cortisol); and maternal metabolic profile (serum hormones and interleukins). Mothers of infants with lower visual fixation scores had higher levels of protein in breastmilk at 3 months. Mothers of infants with better visual conduct scores had higher serum levels of T4 (at 1 month) and prolactin (at 3 months). There were no associations between visual ability and motor development, home environment, or maternal care. Early newborn neuromotor development, especially visual and fine motor skills, is associated with maternal biological characteristics (metabolic factors and breastmilk composition), highlighting the importance of early detection of maternal metabolic changes for the healthy neurodevelopment of newborns.
RESUMEN
While classically linked to memory, the hippocampus is also a feeding behavior modulator due to its multiple interconnected pathways with other brain regions and expression of receptors for metabolic hormones. Here we tested whether variations in insulin sensitivity would be correlated with differential brain activation following exposure to palatable food cues, as well as with variations in implicit food memory in a cohort of healthy adolescents, some of whom were born small for gestational age (SGA). Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was positively correlated with activation in the cuneus, and negatively correlated with activation in the middle frontal lobe, superior frontal gyrus and precuneus when presented with palatable food images versus non-food images in healthy adolescents. Additionally, HOMA-IR and insulinemia were higher in participants with impaired food memory. SGA individuals had higher snack caloric density and greater chance for impaired food memory. There was also an interaction between the HOMA-IR and birth weight ratio influencing external eating behavior. We suggest that diminished insulin sensitivity correlates with activation in visual attention areas and inactivation in inhibitory control areas in healthy adolescents. Insulin resistance also associated with less consistency in implicit memory for a consumed meal, which may suggest lower ability to establish a dietary pattern, and can contribute to obesity. Differences in feeding behavior in SGA individuals were associated with insulin sensitivity and hippocampal alterations, suggesting that cognition and hormonal regulation are important components involved in their food intake modifications throughout life.
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Resistencia a la Insulina , Adolescente , Glucemia/metabolismo , Encéfalo/fisiología , Señales (Psicología) , Edad Gestacional , Humanos , Insulina , Comidas , Obesidad/complicacionesRESUMEN
BACKGROUND: The A3669G single nucleotide polymorphism (SNP) of the glucocorticoid receptor (GR) gene NR3C1 is associated with altered tissue sensitivity to glucocorticoids (GCs). GCs modulate the food reward circuitry and are implicated in increased intake of palatable foods, which can lead to the metabolic syndrome and obesity. We hypothesized that presence of the G variant of the A3669G SNP would affect preferences for palatable foods and alter metabolic, behavioural, and neural outcomes. METHODS: One hundred thirty-one adolescents were genotyped for the A3669G polymorphism, underwent anthropometric assessment and nutritional evaluations, and completed behavioural measures. A subsample of 74 subjects was followed for 5 years and performed a brain functional magnetic resonance imaging (fMRI) paradigm to verify brain activity in response to food cues. RESULTS: Sugar and total energy consumption were lower in A3669G G allele variant carriers. On follow-up, this group also had reduced serum insulin concentrations, increased insulin sensitivity, and lower anxiety scores. Because of our unbalanced sample sizes (31/37 participants non-G allele carriers/total), our imaging data analysis failed to find whole brain-corrected significant results in between-group t-tests. CONCLUSION: These results highlight that a genetic variation in the GR gene is associated, at the cellular level, with significant reduction in GC sensitivity, which, at cognitive and behavioural levels, translates to altered food intake and emotional stress response. This genetic variant might play a major role in decreasing risk for metabolic and psychiatric diseases.
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Alostasis , Regulación del Apetito , Ingestión de Energía , Preferencias Alimentarias , Polimorfismo de Nucleótido Simple , Adolescente , Fenómenos Fisiológicos Nutricionales de los Adolescentes , Alelos , Ansiedad/genética , Ansiedad/metabolismo , Ansiedad/psicología , Brasil , Niño , Fenómenos Fisiológicos Nutricionales Infantiles , Estudios de Cohortes , Femenino , Estudios de Asociación Genética , Humanos , Resistencia a la Insulina , Estudios Longitudinales , Masculino , Estudios Prospectivos , Estrés Psicológico/genética , Estrés Psicológico/metabolismo , Estrés Psicológico/psicologíaRESUMEN
Studies in rodents have shown that early life trauma leads to anxiety, increased stress responses to threatening situations, and modifies food intake in a new environment. However, these associations are still to be tested in humans. This study aimed to verify complex interactions among anxiety diagnosis, maternal care, and baseline cortisol on food intake in a new environment in humans. A community sample of 32 adolescents and young adults was evaluated for: psychiatric diagnosis using standardized interviews, maternal care using the Parental Bonding Inventory (PBI), caloric consumption in a new environment (meal choice at a snack bar), and salivary cortisol. They also performed a brain fMRI task including the visualization of palatable foods vs. neutral items. The study found a three-way interaction between anxiety diagnosis, maternal care, and baseline cortisol levels on the total calories consumed (snacks) in a new environment. This interaction means that for those with high maternal care, there were no significant associations between cortisol levels and food intake in a new environment. However, for those with low maternal care and who have an anxiety disorder (affected), cortisol was associated with higher food intake; whereas for those with low maternal care and who did not have an anxiety disorder (resilient), cortisol was negatively associated with lower food intake. In addition, higher anxiety symptoms were associated with decreased activation in the superior and middle frontal gyrus when visualizing palatable vs. neutral items in those reporting high maternal care. These results in humans mimic experimental research findings and demonstrate that a combination of anxiety diagnosis and maternal care moderate the relationship between the HPA axis functioning, anxiety, and feeding behavior in adolescents and young adults.
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Ansiedad/fisiopatología , Conducta Alimentaria/fisiología , Hidrocortisona/análisis , Sistema Hipotálamo-Hipofisario/fisiopatología , Relaciones Madre-Hijo , Sistema Hipófiso-Suprarrenal/fisiopatología , Adolescente , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Ingestión de Alimentos/fisiología , Ingestión de Alimentos/psicología , Conducta Alimentaria/psicología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Apego a Objetos , Padres , Saliva/química , Bocadillos , Adulto JovenRESUMEN
The home prothrombin time/international normalized ratio (PT/INR) self-management could be convenient for patients, enhancing treatment compliance and improving the quality of the oral anticoagulation. However, patient self-management (PSM) of oral anticoagulation may not be feasible for up to half of the patients due to cognitive or educational issues. In the present study, we aimed to evaluate the feasibility of a PSM program in a public health medical center that provides care for low-income patients. We also aimed to determine the accuracy of individual point-of-care devices (CoaguChek XS(®)) during long-term of home manipulation. Patients' time-in-therapeutic range (TTR) and perception of quality of life, were evaluated at scheduled study-visits to the center. Additionally, the accuracy of individual CoaguChek XS(®) was evaluated in comparison to the standard automated coagulometer at scheduled study-visits to the center. Twenty-five patients were included in the PSM program. The median TTR of patients was 75 % before inclusion, 72 % at 3 months, 75 % at 6 months and 100 % at 12 months after the beginning of self-management (P = 0.14).The median DASS scores were 64, 63, 61.5 and 71.5 before inclusion and at 3, 6 and 12 months, respectively (P = 0.09). One hundred paired INR values were obtained. Correlation between INR values delivered by individual CoaguChek XS(®) and the automated coagulometer was 94 % and the mean result bias was 0.07 INR units. The coefficient of correlation and the mean bias between methods was stable during 24 months of follow-up. The present study suggests that PSM is feasible for patients treated in the public health system and that the results delivered by CoaguChek XS(®) have long-term reliability.
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Anticoagulantes/uso terapéutico , Servicios de Atención de Salud a Domicilio/normas , Relación Normalizada Internacional , Sistemas de Atención de Punto/normas , Autocuidado/normas , Administración Oral , Anticoagulantes/administración & dosificación , Monitoreo de Drogas/métodos , Estudios de Factibilidad , Humanos , Salud Pública , Calidad de Vida , Reproducibilidad de los ResultadosAsunto(s)
Celecoxib/administración & dosificación , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Linfangioleiomiomatosis/tratamiento farmacológico , Adulto , Celecoxib/efectos adversos , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Función RespiratoriaAsunto(s)
Angiomiolipoma/genética , Neoplasias Renales/genética , Neoplasias Pulmonares/genética , Linfangioleiomiomatosis/genética , Mosaicismo , Neoplasias Primarias Múltiples/genética , Neoplasias Retroperitoneales/genética , Proteína 2 del Complejo de la Esclerosis Tuberosa/genética , Adulto , Anciano , Ácidos Nucleicos Libres de Células/genética , Femenino , Humanos , Linfangioleiomiomatosis/sangre , Persona de Mediana Edad , Neumotórax , Factor D de Crecimiento Endotelial Vascular/sangre , Adulto JovenRESUMEN
Chronic stress increases anxiety and encourages intake of palatable foods as "comfort foods". This effect seems to be mediated by altered function of the hypothalamic-pituitary-adrenal axis. In the current study, litters of Wistar rats were subjected to limited access to nesting material (Early-Life Stress group - ELS) or standard care (Control group) from postnatal day 2 to 9. In adult life, anxiety was assessed using the novelty-suppressed feeding test (NSFT), and acute stress responsivity by measurement of plasma corticosterone and ACTH levels. Preference for palatable foods was monitored by a computerized system (BioDAQ, Research Diets(®)) in rats receiving only regular chow or given the choice of regular and palatable diet for 30 days. ELS-augmented adulthood anxiety in the NSFT (increased latency to eat in a new environment; decreased chow intake upon return to the home cage) and increased corticosterone (but not ACTH) secretion in response to stress. Despite being lighter and consuming less rat chow, ELS animals ate more palatable foods during chronic exposure compared with controls. During preference testing, controls receiving long-term access to palatable diet exhibited reduced preference for the diet relative to controls exposed to regular chow only, whereas ELS rats demonstrated no such reduction in preference after prolonged palatable diet exposure. The increased preference for palatable foods showed by ELS animals may result from a habit of using this type of food to ameliorate anxiety.
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Ansiedad/etiología , Preferencias Alimentarias/psicología , Estrés Psicológico/complicaciones , Grasa Abdominal/anatomía & histología , Hormona Adrenocorticotrópica/sangre , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Corticosterona/sangre , Dieta , Ingestión de Alimentos/fisiología , Conducta Alimentaria , Femenino , Sistema Hipotálamo-Hipofisario , Sistema Hipófiso-Suprarrenal , Ratas , Ratas Wistar , Restricción FísicaRESUMEN
Objective: To set cutoff points for the triglyceride and glucose index (TyG) as a marker of insulin resistance (IR) for the pediatric population. Subjects and methods: This was a cross-sectional study with schoolchildren population-based data using data of 377 schoolchildren age 10 to 17 years of both sexes. We studied metabolic variables associated with IR indicators, such as fasting insulin and blood glucose, to calculate the homeostatic model assessment (HOMA-IR), and we studied triglycerides (TG) to determine the TyG index. We obtained TyG cutoff values for IR using the receiver operation characteristic (ROC), with definitions of sensitivity (Sen), specificity (Spe), and area under the ROC curve (AUC), with the HOMA-IR as reference. Results: The cutoff points of the TyG index for IR in adolescents are 7.94 for both sexes, 7.91 for boys, and 7.94 for girls, indicating moderate discriminatory power. When we also considered anthropometric variables of excess weight [TyG-BMI (body mass index)] and visceral fat [TyG-WC (waist circumference)], these indexes reached AUC values higher than 0.72, enhancing their potential use for a good diagnosis. Conclusion: TyG has proven to be a useful instrument for identifying IR in adolescent health screening, with high discrimination capacity when added to anthropometric variables, making it a feasible and inexpensive option.
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Enfermedades Cardiovasculares , Resistencia a la Insulina , Masculino , Femenino , Humanos , Adolescente , Niño , Glucosa , Triglicéridos , Brasil , Estudios Transversales , Biomarcadores , Glucemia/metabolismoRESUMEN
Fetal restriction (FR) alters insulin sensitivity, but it is unknown how the metabolic profile associated with restriction affects development of the dopamine (DA) system and DA-related behaviors. The Netrin-1/DCC guidance cue system participates in maturation of the mesocorticolimbic DA circuitry. Therefore, our objective was to identify if FR modifies Netrin-1/DCC receptor protein expression in the prefrontal cortex (PFC) at birth and mRNA in adulthood in rodent males. We used cultured HEK293 cells to assess if levels of miR-218, microRNA regulator of DCC, are sensitive to insulin. To assess this, pregnant dams were subjected to a 50% FR diet from gestational day 10 until birth. Medial PFC (mPFC) DCC/Netrin-1 protein expression was measured at P0 at baseline and Dcc/Netrin-1 mRNA levels were quantified in adults 15 min after a saline/insulin injection. miR-218 levels in HEK-293 cells were measured in response to insulin exposure. At P0, Netrin-1 levels are downregulated in FR animals in comparison to controls. In adult rodents, insulin administration results in an increase in Dcc mRNA levels in control but not FR rats. In HEK293 cells, there is a positive correlation between insulin concentration and miR-218 levels. Since miR-218 is a Dcc gene expression regulator and our in vitro results show that insulin regulates miR-218 levels, we suggest that FR-induced changes in insulin sensitivity could be affecting Dcc expression via miR-218, impacting DA system maturation and organization. As fetal adversity is linked to nonadaptive behaviors later in life, this may contribute to early identification of vulnerability to chronic diseases associated with fetal adversity.
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Resistencia a la Insulina , MicroARNs , Humanos , Masculino , Embarazo , Femenino , Ratas , Animales , Netrina-1/genética , Netrina-1/metabolismo , Células HEK293 , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Insulina/metabolismo , Roedores/genética , Roedores/metabolismo , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Señales (Psicología) , Corteza Prefrontal/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Mensajero/metabolismo , Receptor DCC/metabolismoRESUMEN
OBJECTIVES: Contemporary lower-field magnetic resonance imaging (MRI) may offer advantages for lung imaging by virtue of the improved field homogeneity. The aim of this study was to evaluate the utility of lower-field MRI for combined morphologic imaging and regional lung function assessment. We evaluate low-field MRI in patients with lymphangioleiomyomatosis (LAM), a rare lung disease associated with parenchymal cysts and respiratory failure. MATERIALS AND METHODS: We performed lung imaging on a prototype low-field (0.55 T) MRI system in 65 patients with LAM. T2-weighted imaging was used for assessment of lung morphology and to derive cyst scores, the percent of lung parenchyma occupied by cysts. Regional lung function was assessed using oxygen-enhanced MRI with breath-held ultrashort echo time imaging and inhaled 100% oxygen as a T1-shortening MR contrast agent. Measurements of percent signal enhancement from oxygen inhalation and percentage of lung with low oxygen enhancement, indicating functional deficits, were correlated with global pulmonary function test measurements taken within 2 days. RESULTS: We were able to image cystic abnormalities using T2-weighted MRI in this patient population and calculate cyst score with strong correlation to computed tomography measurements (R = 0.86, P < 0.0001). Oxygen-enhancement maps demonstrated regional deficits in lung function of patients with LAM. Heterogeneity of oxygen enhancement between cysts was observed within individual patients. The percent low-enhancement regions showed modest, but significant, correlation with FEV1 (R = -0.37, P = 0.007), FEV1/FVC (R = -0.33, P = 0.02), and cyst score (R = 0.40, P = 0.02). The measured arterial blood ΔT1 between normoxia and hyperoxia, used as a surrogate for dissolved oxygen in blood, correlated with DLCO (R = -0.28, P = 0.03). CONCLUSIONS: Using high-performance 0.55 T MRI, we were able to perform simultaneous imaging of pulmonary structure and regional function in patients with LAM.
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Quistes , Linfangioleiomiomatosis , Quistes/complicaciones , Humanos , Pulmón/diagnóstico por imagen , Linfangioleiomiomatosis/complicaciones , Linfangioleiomiomatosis/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Oxígeno/químicaRESUMEN
Introduction: Prenatal growth impairment leads to higher preference for palatable foods in comparison to normal prenatal growth subjects, which can contribute to increased body fat mass and a higher risk for developing chronic diseases in small-for-gestational-age (SGA) individuals throughout life. This study aimed to investigate the effect of SGA on feeding behavior in children and adolescents, as well as resting-state connectivity between areas related to reward, self-control, and value determination, such as orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DL-PFC), amygdala and dorsal striatum (DS). Methods: Caregivers and their offspring were recruited from two independent cohorts in Brazil (PROTAIA) and Canada (MAVAN). Both cohorts included anthropometric measurements, food choice tasks, and resting-state functional magnetic resonance imaging (fMRI) data. Results: In the Brazilian sample (17 ± 0.28 years, n=70), 21.4% of adolescents were classified as SGA. They exhibited lower monetary-related expenditure to buy a snack compared to controls in the food choice test. Decreased functional connectivity (n=40) between left OFC and left DL-PFC; and between right OFC and: left amygdala, right DS, and left DS were observed in the Brazilian SGA participants. Canadian SGA participants (14.9%) had non-significant differences in comparison with controls in a food choice task at 4 years old ( ± 0.01, n=315). At a follow-up brain scan visit (10.21 ± 0.140 years, n=49), SGA participants (28.6%) exhibited higher connectivity between the left OFC and left DL-PFC, also higher connectivity between the left OFC and right DL-PFC. We did not observe significant anthropometric neither nutrients' intake differences between groups in both samples. Conclusions: Resting-state fMRI results showed that SGA individuals had altered connectivity between areas involved in encoding the subjective value for available goods and decision-making in both samples, which can pose them in disadvantage when facing food options daily. Over the years, the cumulative exposure to particular food cues together with the altered behavior towards food, such as food purchasing, as seen in the adolescent cohort, can play a role in the long-term risk for developing chronic non-communicable diseases.
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Conducta Alimentaria , Preferencias Alimentarias , Adolescente , Canadá , Humanos , Fenotipo , RecompensaRESUMEN
BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare lung disease found primarily in women of childbearing age, characterized by the formation of air-filled cysts, which may be associated with reductions in lung function. An experimental, regional ultra-high resolution CT scan identified an additional volume of cysts relative to standard chest CT imaging, which consisted primarily of ultra-small cysts. RESEARCH QUESTION: What is the impact of these ultra-small cysts on the pulmonary function of patients with LAM? STUDY DESIGN AND METHODS: A group of 103 patients with LAM received pulmonary function tests and a CT examination in the same visit. Cyst score, the percentage lung volume occupied by cysts, was measured by using commercial software approved by the US Food and Drug Administration. The association between cyst scores and pulmonary function tests of diffusing capacity of the lungs for carbon monoxide (Dlco) (% predicted), FEV1 (% predicted), and FEV1/FVC (% predicted) was assessed with statistical analysis adjusted for demographic variables. The distributions of average cyst size and ultra-small cyst fraction among the patients were evaluated. RESULTS: The additional cyst volume identified by the experimental, higher resolution scan consisted of cysts of 2.2 ± 0.8 mm diameter on average and are thus labeled the "ultra-small cyst fraction." It accounted for 27.9 ± 19.0% of the total cyst volume among the patients. The resulting adjusted, whole-lung cyst scores better explained the variance of Dlco (P < .001 adjusted for multiple comparisons) but not FEV1 and FEV1/FVC (P = 1.00). The ultra-small cyst fraction contributed to the reduction in Dlco (P < .001) but not to FEV1 and FEV1/FVC (P = .760 and .575, respectively). The ultra-small cyst fraction and average cyst size were correlated with cyst burden, FEV1, and FEV1/FVC but less with Dlco. INTERPRETATION: The ultra-small cysts primarily contributed to the reduction in Dlco, with minimal effects on FEV1 and FEV1/FVC. Patients with lower cyst burden and better FEV1 and FEV1/FVC tended to have smaller average cyst size and higher ultra-small cyst fraction. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT00001465; URL: www.clinicaltrials.gov.
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Obstrucción de las Vías Aéreas/etiología , Órganos Artificiales , Neoplasias Pulmonares/complicaciones , Linfangioleiomiomatosis/complicaciones , Impresión Tridimensional , Tomografía Computarizada por Rayos X/métodos , Trabajo Respiratorio/fisiología , Obstrucción de las Vías Aéreas/fisiopatología , Quistes/fisiopatología , Difusión , Humanos , Pulmón , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/fisiopatología , Linfangioleiomiomatosis/diagnóstico , Linfangioleiomiomatosis/fisiopatología , Pruebas de Función RespiratoriaRESUMEN
OBJECTIVES: To measure the prevalence of vitamin D deficiency (through the 25-hydroxyvitamin D metabolite) in pediatric patients using antiepileptic drugs. SOURCE OF DATA: Meta-analysis of studies identified through search in the PubMed, Embase, LILACS, and Cochrane Library databases, on February 19, 2019. SUMMARY OF DATA: A total of 748 articles were identified, 29 of which were relevant to the objectives of this study. The prevalence of vitamin D deficiency found was 0.32 (95% CI=0.25-0.41; I2=92%, p<0.01). In the subgroup analyses, the most significant results were observed in the group of patients using cytochrome P450-inducing antiepileptic drugs, with a prevalence of 0.33 (95% CI=0.21-0.47; I2=86%, p<0.01) and, considering the study design, in the subgroup of cohort studies, with a prevalence of 0.52 (95% CI=0.40-0.64; I2=76%, p<0.01). CONCLUSIONS: Taking into account the deleterious effects of vitamin D deficiency on the bone health of individuals using antiepileptic drugs, it is suggested to include in their care 25-hydroxyvitamin D monitoring, cholecalciferol supplementation, and treatment of the deficiency, when present.
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Deficiencia de Vitamina D , Anticonvulsivantes/efectos adversos , Niño , Colecalciferol , Bases de Datos Factuales , Suplementos Dietéticos , Humanos , Prevalencia , Vitamina D , Deficiencia de Vitamina D/epidemiologíaRESUMEN
PURPOSE: To evaluate the accuracy of cyst score measurements by standard high-resolution helical volume chest CT (HRCT) in patients with lymphangioleiomyomatosis (LAM), using a short z-length ultra-high resolution re-scan (UH re-scan) as the reference. In cystic lung diseases, cyst score is derived from CT scans and defined as the percentage of the total lung parenchymal volume occupied by cysts, a biomarker which measures the severity of the disease. METHODS: In a prospective study of 73 LAM patients, each patient received the standard HRCT chest scan and a short z-length UH re-scan. Cyst scores were acquired from both scans using a standard FDA-approved scoring software on the CT scanner. RESULTS: The limited UH re-scan resolved small cysts that were not resolved in the HRCT. The HRCT-derived cyst scores were on average 59.6% of the reference values from the UH re-scan (p = 4.7e-25). The amount of under-estimation by HRCT varied from patient to patient, with an inter-quartile range of 29.8% and standard deviation of 20.7%. The overall trend was more pronounced underestimation for patients with lower cyst scores. For patients whose reference cyst scores were below 15 (n = 29), the HRCT cyst scores were 46.9 ± 21.6% of reference values (p = 7.4e-12), while for the rest of the patients (n = 44) the HRCT cyst scores were 68.0 ± 15.3% of reference values (p = 1.2E-19). Reconstructing the HRCT images to the resolution of the UH re-scan further widened the spread of the discrepancy between HRCT and reference values due to increased image noise, and did not provide accurate cyst scores. CONCLUSION: Cyst scores derived from standard high-resolution helical volume chest CT significantly underestimates the percentage lung volume occupied by cysts. This inaccuracy needs to be taken into consideration when cyst score is used as part of the CT assessment of the patient's condition.
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Linfangioleiomiomatosis/diagnóstico por imagen , Tomografía Computarizada Espiral/métodos , Adulto , Anciano , Quistes/diagnóstico por imagen , Femenino , Humanos , Pulmón/diagnóstico por imagen , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
Increased coagulation factor levels have been demonstrated to be a risk factor for venous thromboembolism in patients of Caucasian origin. Coagulation factors, hereditary thrombophilia, and ABO blood group were evaluated for venous thrombosis risk in a heterogeneous Brazilian population consisting of 122 women and 53 men, with a median age of 36 years (range 13-63), matched to a control group by age, sex, and ethnicity. Increased levels of factor VIII (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.6-6.0), von Willebrand factor (OR, 2.8; 95% CI, 1.4-5.4), non-O blood group (OR, 2.1; 95% CI, 1.3-3.4), and thrombophilia (OR, 3.4; 95% CI, 1.6-7.1) emerged as independent risk factors for venous thromboembolism. The interaction of high levels of factor IX and factor XI with other independent variables increased the potential for thrombosis synergistically. Therefore, the ability of identifying underlying thrombophilia risk factors in our population was enhanced by the inclusion of these factors in the prothrombotic laboratory workup.
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Sistema del Grupo Sanguíneo ABO , Factores de Coagulación Sanguínea/metabolismo , Trombofilia/sangre , Trombofilia/epidemiología , Trombosis de la Vena/sangre , Trombosis de la Vena/epidemiología , Adolescente , Adulto , Brasil/epidemiología , Factor IX/metabolismo , Factor VII/metabolismo , Factor VIII/metabolismo , Factor X/metabolismo , Factor XI/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Población Blanca/genética , Población Blanca/estadística & datos numéricos , Adulto Joven , Factor de von Willebrand/metabolismoRESUMEN
Recent studies have implicated a role for impulsivity in the altered eating behaviors and the increased risk for obesity consistently associated with intrauterine growth restriction (IUGR). Changes in dopamine transmission within prefrontal areas are believed to contribute to these adverse outcomes. Here we investigated the impulsive behavior toward a delayed reward and evaluated dopamine levels and its receptors in the medial prefrontal (mPFC) and orbitofrontal (OFC) cortex of female adult rats exposed to IUGR. From day 10 of pregnancy and until birth, Sprague-Dawley dams received either an ad libitum (Adlib) or a 50% food-restricted (FR) diet. At birth, all pups were adopted by Adlib mothers, generating the groups Adlib/Adlib (control) and FR/Adlib (intrauterine growth-restricted). Adult impulsive behavior was evaluated using a Tolerance to Delay of Reward Task. In vivo dopamine responses to sweet food intake were measured by voltammetry, and D1, D2 and DAT levels were accessed by Western Blot. Animals from FR group showed a pronounced aversion to delayed rewards. DA response to sweet food was found to be blunted in the mPFC of FR animals, whereas in the OFC, the DA levels appear to be unaffected by reward consumption. Moreover, FR animals presented reduced D1 receptors in the OFC and a later increase in the mPFC D2 levels. These findings suggest that IUGR female rats are more impulsive and that the associated mechanism involves changes in the dopamine signaling in both the mPFC and OFC.
Asunto(s)
Dopamina/metabolismo , Retardo del Crecimiento Fetal/metabolismo , Conducta Impulsiva/fisiología , Corteza Prefrontal/metabolismo , Transmisión Sináptica/fisiología , Animales , Conducta Animal/fisiología , Femenino , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Given the rising utilization of medical imaging and the risks of radiation, there is increased interest in reducing radiation exposure. The objective of this study was to evaluate, as a proof of principle, CT scans performed at radiation doses equivalent to that of a posteroanterior and lateral chest radiograph series in the cystic lung disease lymphangioleiomyomatosis (LAM). METHODS: From November 2016 to May 2018, 105 consecutive subjects with LAM received chest CT scans at standard and ultra-low radiation doses. Standard and ultra-low-dose images, respectively, were reconstructed with routine iterative and newer model-based iterative reconstruction. LAM severity can be quantified as cyst score (percentage of lung occupied by cysts), an ideal benchmark for validating CT scans performed at a reduced dose compared with a standard dose. Cyst scores were quantified using semi-automated software and evaluated by linear correlation and Bland-Altman analysis. RESULTS: Overall, ultra-low-dose CT scans represented a 96% dose reduction, with a median dose equivalent to 1 vs 22 posteroanterior and lateral chest radiograph series (0.14 mSv; 5th-95th percentile, 0.10-0.20 vs standard dose 3.4 mSv; 5th-95th percentile, 1.5-7.4; P < .0001). The mean difference in cyst scores between ultra-low- and standard-dose CT scans was 1.1% ± 2.0%, with a relative difference in cyst score of 11%. Linear correlation coefficient was excellent at 0.97 (P < .0001). CONCLUSIONS: In LAM chest CT scan at substantial radiation reduction to doses equivalent to that of a posteroanterior and lateral chest radiograph series provides cyst score quantification similar to that of standard-dose CT scan. TRIAL REGISTRY: ClinicalTrials.gov; Nos.: NCT00001465 and NCT00001532; URL: www.clinicaltrials.gov.
Asunto(s)
Pulmón/diagnóstico por imagen , Linfangioleiomiomatosis/diagnóstico , Tomografía Computarizada Multidetector/métodos , Exposición a la Radiación , Salud Radiológica , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Procesos y Resultados en Atención de Salud , Dosis de Radiación , Exposición a la Radiación/prevención & control , Exposición a la Radiación/estadística & datos numéricos , Radiografía Torácica/métodos , Radiografía Torácica/normas , Salud Radiológica/métodos , Salud Radiológica/normasRESUMEN
INTRODUCTION: Early life adversity, including the perception of poor quality of maternal care, is associated with long-term metabolic and psychosocial consequences. The negative quality of mother/child relationship is associated with emotional overeating in young children, which is defined by eating in response to emotional arousal states such as fear, anger or anxiety. However, it is not known if this association persists through adolescence. Therefore, we aimed at verifying if maternal care during infancy can influence emotional eating in young adults. METHODS: Seventy-five adolescents, residents of Porto Alegre, who participated in the PROTAIA Program (anxiety disorder in childhood and adolescence program), answered the Parental Bonding Instrument (PBI - assessment of perceived maternal care), and the Dutch Eating Behavior Questionnaire (DEBQ). Regression analysis models were built to predict Emotional Eating, a domain of the DEBQ, using maternal care, gender, and anxiety as independent variables. RESULTS: The model was statistically significant when adjusted for potential confounders (r2â¯=â¯0.272; pâ¯<â¯0.0001). Emotional eating was significantly predicted by levels of maternal care, anxiety and gender (betaâ¯=â¯-0.316; pâ¯=â¯0.006). CONCLUSION: The results demonstrated a negative association between the quality of maternal care and emotional eating in young adults, suggesting that the early environment could be involved on the development of eating disorders or on the differential eating behavior in adolescents with emotional disorders.