Ritmo circadiano y presión arterial en pacientes con monitorización ambulatoria de la presión arterial y su relación con el riesgo de evento cardiovascular / Circadian rhythm and blood pressure in patients with ambulatory blood pressure monitoring and its relationship with the risk of cardiovascular events

Introducción: Las enfermedades cardiovasculares son el conjunto de afecciones que más muertes produce globalmente, siendo la hipertensión arterial uno de los principales factores de riesgo. En este sentido, la monitorización de la presión arterial ambulatoria (MAPA) permite detectar los diferentes cambios de presión arterial a lo largo de 24h, denominados patrones circadianos: dipper, no dipper,riser o dipper extremo. Existe una posible asociación entre los diferentes patrones y el riesgo cardiovascular. En este estudio se pretende comparar el riesgo cardiovascular usando las escalas validadas REGICOR y SCORE en los pacientes con diferentes patrones circadianos usando la MAPA. Material y métodos: Estudio retrospectivo de pacientes hipertensos con registro MAPA entre 2015 y 2021 en Alcázar de San Juan y Madridejos. Se recogieron variables sociodemográficas, clínicas, antecedentes (hipertensión arterial, IMC, comorbilidades, hábitos de tabaquismo), analíticas, escalas REGICOR y SCORE, y ritmos circadianos. Resultados: Se han incluido un total de 269 pacientes (el 46,5% mujeres, 64,3±12,6 años), de los cuales un 38,3% presentaron patrón dipper, 10% dipper extremo, 33,1% no dipper y un 18,6% riser. Los pacientes con patrón riser tuvieron una puntuación significativamente mayor en las escalas REGICOR y SCORE (34 y 68%, respectivamente). Se observó una correlación significativa entre ambas escalas (rho Spearman: 0,589; p<0,001), aunque con baja concordancia (kappa de 0,348 [IC 95% 0,271-0,425]).Conclusión: La MAPA se ha convertido en una herramienta útil en el diagnóstico y tratamiento de la hipertensión arterial. Adicionalmente, conocer los patrones circadianos de estos pacientes podría favorecer el seguimiento y la elección del tratamiento adecuado.(AU)

Introduction: Cardiovascular diseases are the group of diseases that cause most deaths worldwide, being arterial hypertension the modifiable risk factor that mostly predisposes to other cardiovascular diseases development. In this regard, ambulatory blood pressure monitoring (ABPM) lets to detect the different changes in blood pressure throughout 24h, known as circadian patterns (dipper, non-dipper, riser or extreme dipper). There may be an association between these patterns and cardiovascular risk, so this study aims to compare cardiovascular risk using the 2 validated scales REGICOR and SCORE in patients with different circadian patterns using ABMP. Material and methods: Retrospective study of hypertensive patients with ABMP registered between 2015 and 2021 in Alcázar de San Juan and Madridejos. Data were collected from clinical history (arterial hypertension, BMI, comorbidities, and smoking habits) and ABPM records, as well as sociodemographic and analytical variables, cardiovascular risk scales (REGICOR and SCORE) and circadian rhythm variables (dipper, extreme dipper, non-dipper and rise pattern). Results: Two hundred and sixty-nine patients (46.5% female, 64.3±12.6 years old) were included. There were 38.3% with dipper pattern, 10% extreme dipper, 33.1% non-dipper and 18.6% riser. Patients with riser pattern showed higher score on the REGICOR and SCORE scales (34 and 68%, respectively). A significant correlation was established between both scales (Spearman rho: 0.589; p<0.001), but with poor concordance (kappa=0.348 [95% CI 0.271–0.425]). Conclusion: ABMP has turned into a very useful tool in the diagnosis and treatment of arterial hypertension. In addition, the circadian patterns of these patients may correlate to the choice of an adequate treatment and correct follow-up.(AU)

Quercetin improved hepatic circadian rhythm dysfunction in middle-aged mice fed with vitamin D-deficient diet

We aimed to determine whether quercetin is capable of improving circadian rhythm and metabolism disorder under vitamin D-deficient condition. Middle-aged mice were randomly divided into four groups, namely, control (CON), vitamin D-deficient diet (VDD), quercetin (Q), and quercetin intervention in vitamin D-deficient diet (VDQ), with a total of 12 weeks’ intervention. Mice were sacrificed at zeitgeber time1 (ZT1) and ZT13 time points. At ZT1, circadian locomotor output cycle kaput (CLOCK) protein expression from VDD, Q, and VDQ groups; CRY1 from Q group; and CRY2 from VDD group were significantly lower compared to CON group. The mRNA expression of Sirt1, Bmal1, Clock, Cry1, and Cry2 in VDQ groups, also Bmal1, Clock, and Cry1 from Q group, were significantly decreased compared to CON group. At ZT13, compared to CON group, fasting insulin and homeostasis model assessment-insulin resistance (HOMA-IR) were higher in VDD group; BMAL1 was significantly increased, while CLOCK and CRY1 protein were significantly decreased from VDD group; CLOCK protein from VDQ group was significantly higher compared to CON, VDD, and Q groups, and also, BMAL1 protein expression from VDQ group was elevated compared to CON group. The mRNA expression of Bmal1, Clock, Per2, Cry1, and Cry2 in VDQ groups were significantly increased compared to CON groups. The mRNA expression of Bmal1 from VDQ group was decreased compared to both VDD and Q group. In conclusion, vitamin D-deficient diet resulted in a disordered liver circadian rhythm, and quercetin improved the hepatic circadian desynchronization. Quercetin supplementation might be effective for balancing circadian rhythm under vitamin D-deficient condition. (AU)

Quercetin improved hepatic circadian rhythm dysfunction in middle-aged mice fed with vitamin D-deficient diet

We aimed to determine whether quercetin is capable of improving circadian rhythm and metabolism disorder under vitamin D-deficient condition. Middle-aged mice were randomly divided into four groups, namely, control (CON), vitamin D-deficient diet (VDD), quercetin (Q), and quercetin intervention in vitamin D-deficient diet (VDQ), with a total of 12 weeks’ intervention. Mice were sacrificed at zeitgeber time1 (ZT1) and ZT13 time points. At ZT1, circadian locomotor output cycle kaput (CLOCK) protein expression from VDD, Q, and VDQ groups; CRY1 from Q group; and CRY2 from VDD group were significantly lower compared to CON group. The mRNA expression of Sirt1, Bmal1, Clock, Cry1, and Cry2 in VDQ groups, also Bmal1, Clock, and Cry1 from Q group, were significantly decreased compared to CON group. At ZT13, compared to CON group, fasting insulin and homeostasis model assessment-insulin resistance (HOMA-IR) were higher in VDD group; BMAL1 was significantly increased, while CLOCK and CRY1 protein were significantly decreased from VDD group; CLOCK protein from VDQ group was significantly higher compared to CON, VDD, and Q groups, and also, BMAL1 protein expression from VDQ group was elevated compared to CON group. The mRNA expression of Bmal1, Clock, Per2, Cry1, and Cry2 in VDQ groups were significantly increased compared to CON groups. The mRNA expression of Bmal1 from VDQ group was decreased compared to both VDD and Q group. In conclusion, vitamin D-deficient diet resulted in a disordered liver circadian rhythm, and quercetin improved the hepatic circadian desynchronization. Quercetin supplementation might be effective for balancing circadian rhythm under vitamin D-deficient condition. (AU)

A new border for circadian rhythm gene NFIL3 in diverse fields of cancer

The circadian rhythm disorder and abnormal expression of rhythm genes are related to many diseases, especially cancer. Rhythm gene NFIL3 is involved in energy metabolism and immune cell differentiation, and its aberrant expression is associated with metabolic diseases and inflammation. Previously, numerous studies have shown that aberrant NFIL3 expression is associated with tumorigenesis, progression, and chemotherapy resistance. For instance, NFIL3 performs as a nuclear transcription factor, impacts cell proliferation, represses apoptosis, and promotes cancer cell invasion and metastasis by regulating the transcription of target genes. In addition, NFIL3 expressed in cancer cells influences the type and proportion of infiltrated immune cells in the tumor microenvironment. Increased expression of NFIL3 induces the chemotherapy and immunotherapy resistance in cancer. In this review, we summarized the pathological functions of NFIL3 in tumorigenesis, cancer development, and treatment. The rhythm gene NFIL3 can be used as a promising target in cancer therapy in the future (AU)

Sleep patterns in childhood: a longitudinal assessment from the Generation XXI birth cohort / Patrones de sueño en la infancia: evaluación longitudinal de la cohorte de nacimiento Generación XXI

Objective: To describe sleep-wake patterns in young children, based on sleep characteristics in early infancy and preschool ages, identifying their main sociodemographic characteristics, and to assess the association between different sleep characteristics at both ages. Method: We included 1092 children from the Generation XXI birth cohort, evaluated at six months and four years of age, by face-to-face interviews. Sleep patterns were constructed through latent class analysis and structured equation modeling, including data on wake-up time and bedtime, afternoon naps, locale of nighttime sleep and night awakenings. To estimate the association between sociodemographic characteristics and sleep patterns, odds ratios and 95% confidence intervals were computed using logistic regression. Results: Two sleep patterns were identified through latent class analysis: pattern 1 was characterized by earlier bedtime and wake-up times, while pattern 2 was defined by later times. When compared with pattern 1, pattern 2 was more frequent among children whose mothers had changed from partnered to not partnered until preschool age and those who did not stay at the kindergarten, and was less common among those with siblings. Through structured equation modeling, an aggregating factor was identified at preschool age, which was mainly correlated with bedtime and wake-up time. A positive association between sleep characteristics evaluated in early infancy and in preschool ages was observed. Conclusions: Sleep patterns and circadian sleep preferences seem to be developed early in life, which highlight the importance of promoting an adequate sleep hygiene from infancy, assuming its impact on sleep quality during the life course. (AU)

Objetivo: Describir los patrones de sueño en niños, a partir de las características del sueño en la primera infancia y preescolar, identificando sus características sociodemográficas, y evaluar la asociación entre las características del sueño en ambas edades. Método: Se incluyeron 1092 niños de la cohorte Generación XXI, evaluados a los 6 meses y los 4 años de edad, mediante entrevistas en persona. Los patrones de sueño se identificaron mediante análisis de clases latentes y modelos de ecuaciones estructuradas, utilizando datos sobre la hora de despertarse y acostarse, las siestas de la tarde, el lugar del sueño nocturno y los despertares nocturnos. Para estimar la asociación entre las características sociodemográficas y los patrones de sueño se calcularon odds ratio con intervalos de confianza del 95% mediante regresión logística. Resultados: Se identificaron dos patrones de sueño: el patrón 1 se caracterizó por acostarse y levantarse más temprano; el patrón 2, por tiempos más tardíos. El patrón 2 fue más frecuente entre los niños con madres que cambiaron de pareja a no pareja y que no permanecieron en el jardín de infancia, y menos común entre aquellos con hermanos. Se identificó un factor agregante en la edad preescolar, correlacionado con la hora de acostarse y despertarse. Se observó una asociación positiva entre las características del sueño evaluadas en la primera infancia y en edades preescolares. Conclusiones: Los patrones del sueño parecen desarrollarse temprano en la vida, lo que destaca la importancia de promover una adecuada higiene del sueño desde la infancia. (AU)

Endocrine biomarkers related to sleep-wake cycle and sleep disturbances in patients with bipolar disorder: A systematic review

Background and objectives: Sleep and circadian disturbances have been widely studied in patients with bipolar disorder. However, there is no clear evidence about the role of peripheral biomarkers of the circadian cycle in this population. This systematic review aims to identify potential endocrine blood biomarkers of circadian rhythms and study their relationship with sleep problems in these patients.MethodsAn electronic search was performed of PubMed and PsycINFO databases. It included articles about the topic from 1991 through 2021. The search strategy was: ("peripheral biomarkers" OR "biological markers" OR biomarker OR cortisol OR melatonin OR orexin OR hypocretin) AND (blood OR serum OR plasma) AND (“sleep-wake” OR "circadian rhythm" OR sleep OR insomnia) AND "bipolar."ResultsAfter excluding duplicates, 92 records were obtained. Only 5 studies met the inclusion criteria (n=499; bipolar disorder=125; unipolar depression=148; schizophrenia=80; controls=146). The endocrine parameters analyzed were: cortisol (3 studies), melatonin (1 study), and orexin-A (1 study). Overall, no significant associations were detected between these biomarkers and sleep disturbances, assessed with subjective (psychometric evaluation) and/or objective (polysomnography) measures.ConclusionThis review highlights the lack of studies exploring the role of endocrine biomarkers related to circadian function in the pathophysiology of sleep disturbances in bipolar disorder. (AU)

Variabilidad del marcador genético CLOCK rs3749474 y su impacto en investigaciones y pruebas clínicas sobre obesidad y ritmo circadiano / Variability of the genetic marker CLOCK rs3749474 and its impact on research and clinical trials on obesity and circadian rhythm

Introducción: los ritmos circadianos influyen en la conducta alimentaria, siendo el gen CLOCK uno de los encargados de su regulación. El rs3749474T/C del gen CLOCK ha sido asociado a un mayor riesgo de obesidad y quienes portan el alelo T presentan una mayor pérdida de peso ante una dieta baja en carbohidratos y lípidos que quienes poseen la forma CC. Material y métodos: usando la base de datos 1000 Genomes se obtuvo el genotipo del polimorfismo de nucleótido único (SNP) rs3749474 de 2.504 individuos, abarcando cinco macropoblaciones (África, Este Asiático, Sur Asiático, Europa y Latinoamérica) y 26 poblaciones. CT y TT fueron tratados como genotipos de no riesgo y CC, como de riesgo. Se utilizó la prueba exacta de Fisher para comparar las frecuencias de los genotipos de riesgo y no riesgo. Resultados: existe una alta diferenciación para la frecuencia de genotipos portadores del alelo T entre las macropoblaciones: África alcanzó solo el 31,47 %; Europa, un 56,86 %; Latinoamérica, un 66,28 %; el Sur Asiático, un 68,3 %; y el Este Asiático, un 81,15 %, con diferencias significativas (pFisher < 0,05) en todas las comparaciones, excepto entre Latinoamérica y Sur Asiático. Se observó una baja heterogeneidad entre poblaciones dentro de cada macropoblación. Conclusiones: la alta heterogeneidad para las frecuencias genotípicas de CLOCK rs3749474 en las macropoblaciones estudiadas indica que la disminución del consumo de carbohidratos y lípidos tendrá un impacto heterogéneo desde el punto de vista epidemiológico. Esto sugiere incluir la ancestría genética en posteriores estudios de asociación entre ciclos circadianos, conducta alimentaria y obesidad, con el objeto de desarrollar pruebas clínicas personalizadas. (AU)

Introduction: circadian rhythms influence eating behavior, with the CLOCK gene being one of those responsible for its regulation. The rs3749474T/C of the CLOCK gene has been associated with an increased risk of obesity. Those who carry the T allele have greater weight loss on a diet low in carbohydrates and lipids than those who have the CC form. Methodology: using the 1000 Genomes database, the genotype of the single nucleotide polymorphism (SNP) rs3749474 was obtained from 2,504 individuals, covering five macro-populations (Africa, East Asia, South Asia, Europe and Latin America) and 26 populations. CT and TT were treated as non-risk genotypes and CC as risk. Fisher's exact test was used to compare the frequencies of risk and non-risk genotypes among the five macro populations. Results: there is a high differentiation for the frequency of genotypes carrying the T allele among the macro-populations: Africa reached only 31.47 %, Europe 56.86 %; Latin America 66.28 %; South Asia 68.3 % and East Asia 81.15 %, with significant differences (pFisher < 0.05) in all comparisons, except between Latin America and South Asia. Low heterogeneity was observed between populations within each macro population. Conclusions: the high heterogeneity for the genotypic frequencies of CLOCK rs3749474 in the studied macro-populations indicates that the decrease in the consumption of carbohydrates and lipids will have a heterogeneous impact, from the epidemiological point of view. This suggests including the genetic ancestry in later studies of association between circadian cycles, eating behavior and obesity, in order to develop personalized clinical tests. (AU)

Trastorno por Déficit de Atención con Hiperactividad: Ritmo Circanual en el Mes de Nacimiento / Attention Deficit Hyperactivity Disorder: Circannual Rhythm in the Month of Birth

Estudiamos la existencia de ritmo circanual en el mes de nacimiento en participantes con trastorno de déficit de atención e hiperactividad (TDAH)y analizamos la asociación entre meses de nacimiento y TDAH. La muestra incluye 10978 participantes (1778 TDAH / 9200 no TDAH), entre 3 y18 años, reclutados mediante muestreo consecutivo de primeras consultas atendidas en salud mental entre 1992 y 2021. Los participantes conTDAH presentan un ritmo circanual significativo en los meses de nacimiento, con una acrofase en octubre. Nacer en el último cuatrimestre del añoincrementa significativamente la probabilidad de ser diagnosticado TDAH, controlando el efecto de sexo y edad. Con el transcurso de los meses delaño, existe una tendencia lineal creciente significativa de ser diagnosticado de TDAH, no observada en población general, ni en casos sin TDAH.Es necesario tener precaución en el diagnóstico y tratamiento de los niños nacidos en los últimos meses del año, que, por su mayor inmadurez encomparación con los demás niños de la clase, pudieran ser diagnosticados y tratados erróneamente como TDAH. (AU)

We studied the existence of circanual rhythm in the month of birthin participants with attention deficit hyperactivity disorder (ADHD) and analyzed the association between months of birth and ADHD. We analyzed10,978 participants (1,778 ADHD/9,200 non-ADHD), aged 3 to 18 years. A consecutive sample of first visits to mental health between 1992 and2021 is used. Participants with ADHD exhibit a significant circannual rhythm in the months of birth, with an acrophase in October. Being born in thelast quarter of the year significantly increases the probability of being diagnosed with ADHD, controlling for the effect of sex and age. As the monthsof the year go by, there is a significant increasing linear trend of being diagnosed with ADHD, which is not observed neither in general populationnor in cases without ADHD. Caution is necessary in diagnosis and treatment of children born in the last months of year, who, due to their greaterimmaturity compared to the other children in class, could be misdiagnosed and treated as ADHD. (AU)

Melatonina en los trastornos de sueño / Melatonin in sleep disorders

La melatonina es la principal hormona implicada en la regulación de la oscilación entre sueño y vigilia. Es fácilmente sintetizable y administrable por vía oral, lo que ha propiciado el interés para usarla en el tratamiento de una de las patologías humanas más prevalentes, el insomnio. Además, el hecho de que su producción se reduzca con la edad, en una relación inversamente proporcional a la frecuencia de mala calidad de sueño, ha reforzado la idea de que su déficit es, al menos en parte, responsable de estos trastornos. En esta línea de pensamiento, remontar el déficit que se va instaurando a medida que transcurre la vida sería un modo natural de restaurar la integridad del sueño, que se va perdiendo con la edad. Sin embargo, a pesar del innegable atractivo teórico de esta aproximación al problema del insomnio, la evidencia científica que sustenta el posible beneficio de esta terapia sustitutiva es escasa. Ni siquiera están bien definidos los rangos de dosis a los que administrarla o la formulación farmacológica más adecuada. En la presente revisión se repasa la fisiología de la melatonina, se revisan las características farmacológicas de su administración exógena y se analizan los datos existentes sobre su utilidad clínica. (AU)

Melatonin is the main hormone involved in the control of the sleep-wake cycle. It is easily synthesisable and can be administered orally, which has led to interest in its use as a treatment for insomnia. Moreover, as production of the hormone decreases with age, in inverse correlation with the frequency of poor sleep quality, it has been suggested that melatonin deficit is at least partly responsible for sleep disorders. Treating this age-related deficit would therefore appear to be a natural way of restoring sleep quality, which is lost as patients age. However, despite the undeniable theoretical appeal of this approach to insomnia, little scientific evidence is available that supports any benefit of this substitutive therapy. Furthermore, the most suitable dose ranges and pharmaceutical preparations for melatonin administration are yet to be clearly defined. This review addresses the physiology of melatonin, the different pharmaceutical preparations, and data on its clinical usefulness. (AU)

The intrinsically photosensitive retinal ganglion cell (ipRGC) mediated pupil response in young adult humans with refractive errors

Purpose: The intrinsically photosensitive retinal ganglion cells (ipRGCs) signal environmental light, with axons projected to the midbrain that control pupil size and circadian rhythms. Post-illumination pupil response (PIPR), a sustained pupil constriction after short-wavelength light stimulation, is an indirect measure of ipRGC activity. Here, we measured the PIPR in young adults with various refractive errors using a custom-made optical system.Methods: PIPR was measured on myopic (−3.50 ± 1.82 D, n = 20) and non-myopic (+0.28 ± 0.23 D, n = 19) participants (mean age, 23.36 ± 3.06 years). The right eye was dilated and presented with long-wavelength (red, 625 nm, 3.68 × 1014 photons/cm2/s) and short-wavelength (blue, 470 nm, 3.24 × 1014 photons/cm2/s) 1 s and 5 s pulses of light, and the consensual response was measured in the left eye for 60 s following light offset. The 6 s and 30 s PIPR and early and late area under the curve (AUC) for 1 and 5 s stimuli were calculated.Results: For most subjects, the 6 s and 30 s PIPR were significantly lower (p < 0.001), and the early and late AUC were significantly larger for 1 s blue light compared to red light (p < 0.001), suggesting a strong ipRGC response. The 5 s blue stimulation induced a slightly stronger melanopsin response, compared to 1 s stimulation with the same wavelength. However, none of the PIPR metrics were different between myopes and non-myopes for either stimulus duration (p > 0.05).Conclusions: We confirm previous research that there is no effect of refractive error on the PIPR. (AU)

Pacientes ingresados por recaída aguda de esquizofrenia paranoide: cambios estacionales, pero no circadianos, en los niveles séricos deproteína S100B / Patients admitted for acute relapse of paranoid schizophrenia: seasonal, but not circadian, changes in serum levels of S100B protein

Introducción: El objetivo de esta investigación es estudiar si los pacientes esquizofrénicos presentan niveles másaltos de proteína S100B en verano que en invierno, como seha descrito en sujetos sanos.Método. Se estudiaron 52 pacientes caucásicos que ingresaron por recaída aguda y que cumplían con los criteriosDSM-IV de esquizofrenia paranoide. La proteína S100B ensuero se midió a las 12:00 y las 00:00 horas el día despuésdel ingreso. Los pacientes fueron reclutados durante nuevemeses (julio-marzo) y se agruparon por estación, según lafecha de ingreso, como grupo de verano, otoño o invierno.Los niveles séricos de S100B se midieron con un ELISA.Resultados. Los pacientes ingresados en invierno presentaron niveles séricos de proteína S100B significativamentemás altos a las 12:00 y 00:00 horas que los pacientes ingresados en verano (12:00, invierno: 287,5 ± 264,9 vs. verano: 33,7 ± 22,6, p < 0,05; 00:00, invierno: 171,2 ± 143,8 vs.verano: 23,3 ± 18,6, p < 0,05). Las concentraciones séricasde S100B en otoño no fueron significativamente diferentesde las concentraciones de verano o invierno (12:00: 128,7 ±208,8, 00:00: 102,2 ± 153,2). No hubo diferencias significativas por estación entre las concentraciones diurnas y nocturnas de proteína S100B.Conclusiones. Los pacientes esquizofrénicos hospitalizados por una descompensación aguda presentan concentraciones séricas de proteína S100B significativamente másaltas en invierno que en verano, al contrario de lo descritoen sujetos sanos, tanto a las 12:00 horas como a las 00:00horas. Al estudiar este biomarcador en la esquizofrenia esrecomendable controlar el cambio de estación como fuentede sesgo en los diseños experimentales. (AU)

Introduction: Healthy subjects present higher summerthan winter S100B protein concentrations. There is no available information regarding if schizophrenia patients presentthe same pattern. The aim of this research is to study if patients with schizophrenia present seasonal changes in serumS100B concentrations.Methods. In fifty-two Caucasian schizophrenia paranoidinpatients meeting DSM-IV criteria, serum S100B protein wasmeasured at 12:00 h and 00:00 h the next day after admission.Patients were recruited for a period of nine months (July-March)and were grouped as summer, autumn or winter group according to the date of admission. Serum S100B levels were measuredwith an enzyme-linked immunoassay (ELISA) kit.Results. Patients admitted in winter had significantly higher serum S100B concentrations at 12:00 h and 00:00 h than patients admitted in summer (12:00, winter: 287.5±264.9 vs.summer: 33.7±22.6, p < 0.05; 00:00, winter: 171.2±143.8 vs.summer: 23.3±18.6, p < 0.05). Autumn serum S100B concentrations were not significantly different from the summer or winter concentrations (12:00: 128.7±208.8, 00:00:102.2±153.2). There were no significant differences between12:00 and 00:00 serum S100B concentrations in any season.Conclusions. Acutely relapsed paranoid schizophreniainpatients present significantly higher serum S100B concentrations in winter than summer, the opposite pattern described in healthy subjects, both at midday and midnight.Controlling this seasonal change as source of bias in experimental designs is strongly advisable. (AU)

Time-restricted feeding in dark phase of circadian cycle and/or westernized diet cause mixed hyperlipidemia in rats / La alimentación con restricción de tiempo en la fase oscura del ciclo circadiano y/o la dieta occidentalizada causan hiperlipidemia mixta en las ratas

BACKGROUND: the dietary pattern that characterizes western diet is strongly associated with metabolic diseases and excess weight, as well as chronic illnesses. Misaligned feeding schedules can lead to or aggravate the development of such conditions. AIM: this study evaluated the influence of dietary composition and/or time-restricted feeding on the anthropometric and biochemical profile of adult rats. METHODS: forty male rats, at 60 days of life, were divided into the following groups: Control (C), Restricted Control (RC), Westernized (W), and Restricted Westernized (RW). RESULTS: westernized groups, in spite of a low energy intake (C = 5399 ± 401.2 kcal; RC = 4279.0 ± 476.2 kcal; W = 4302 ± 619.8 kcal; RW = 4081.0 ± 404.4 kcal, p < 0.001), had a higher body weight (C = 404.6 ± 39.1 g; RC = 335.1 ± 36.5 g; W = 488.9 ± 51.2 g; RW = 438.8 ± 36.5 g, p < 0.001) as compared to their paired controls (RC and C) - around 30 % and 20 % more for RW and W, respectively. The westernized diet caused glucose intolerance and mixed hyperlipidemia, characterized by higher concentrations of cholesterol (C = 40.8 ± 7.4 mg/dL; RC = 76.7 ± 10.8 mg/dL; W = 61.3 ± 20.2 mg/dL; RW = 42.2 ± 8.2 mg/dL), LDLc (C = 17.4 ± 7.5 mg/dL; RC = 38.8 ± 7.2 mg/dL ; W = 45.3 ± 15.8 mg/dL; RW = 11.0 ± 5.8 mg/dL), and triacylglycerol (C = 45.2 ± 15.0 mg/dL; RC = 73.2 ± 21.5 mg/dL ; W = 83.6 ± 23.4 mg/dL; RW = 57.5 ± 13.6 mg/dL) in the serum (p < 0.05). CONCLUSION: the effect of time-restricted feeding on body weight was strongly dependent on diet composition. The glucose tolerance test showed an influence of the circadian cycle phase. Mixed hyperlipidemia varied according to the presence of westernized diet and/or time-restricted food

ANTECEDENTES: el patrón dietético que caracteriza a la dieta occidental está fuertemente asociado con las enfermedades metabólicas, así como con el sobrepeso y las enfermedades crónicas. Los horarios de alimentación desorganizados pueden conducir o agravar el desarrollo de tales trastornos. OBJETIVO: este estudio evaluó la influencia de la composición dietética y/o la alimentación restringida en el perfil antropométrico y bioquímico de ratas adultas. MÉTODOS: cuarenta ratas macho, a los 60 días de vida, se dividieron en los seguientes grupos: control (C); control restringido (RC); occidentalizado (W) y occidentalizado restringido (RW). RESULTADOS: los grupos occidentalizados, a pesar de la baja ingesta energética (C = 5399 ± 401,2 kcal; RC = 4279,0 ± 476,2 kcal; W = 4302 ± 619,8 kcal; RW = 4081,0 ± 404,4 kcal, p < 0,001), tuvieron mayor peso corporal (C = 404,6 ± 39,1 g; RC = 335,1 ± 36,5 g; W = 488,9 ± 51,2 g; RW = 438,8 ± 36,5 g, p < 0,001) que los respectivos grupos de control (RC y C): alrededor de un 30 % y un 20 % más para RW y W, respectivamente. La dieta occidentalizada provocó intolerancia a la glucosa e hiperlipidemia mixta, caracterizada por una mayor concentración de colesterol (C = 40,8 ± 7,4 mg/dL; RC = 76,7 ± 10,8 mg/dL; W = 61,3 ± 20,2 mg/dL; RW = 42,2 ± 8,2 mg/dL), cLDL (C = 17,4 ± 7,5 mg/dL; RC = 38,8 ± 7,2 mg/dL; W = 45,3 ± 15,8 mg/dL; RW = 11,0 ± 5,8 mg/dL) y triacilglicerol (C = 45,2 ± 15,0 mg/dL; RC = 73,2 ± 21,5 mg/dL; W = 83,6 ± 23,4 mg/dL; RW = 57,5 ± 13,6 mg/dL) en el suero (p < 0,05). CONCLUSIÓN: el efecto de la alimentación restringida en el tiempo sobre el peso corporal fue muy dependiente de la composición de la dieta. La prueba de tolerancia a la glucosa mostró la influencia de la fase del ciclo circadiano. La hiperlipidemia mixta varió según la presencia de la dieta occidentalizada y/o la comida con restricción de tiempo

Efectos del tratamiento farmacológico estimulante sobre los patrones de actividad circadiana en niños con trastorno por déficit de atención/hiperactividad / The effects of pharmacological treatment with stimulants on circadian activity patterns in children with attention deficit hyperactivity disorder

INTRODUCCIÓN: El trastorno por déficit de atención/hiperactividad (TDAH) es uno de los trastornos mentales más comunes en la infancia. Los síntomas nucleares del TDAH se tratan con estimulantes como el metilfenidato; aun así, existe mucha controversia respecto a sus efectos secundarios. OBJETIVOS: Analizar los patrones de actividad en niños con TDAH durante un período de 24 horas durante siete días, antes y después de tomar tratamiento farmacológico estimulante (metilfenidato), y observar si existen diferencias entre las diferentes presentaciones del trastorno (subtipo inatento y combinado). PACIENTES Y MÉTODOS: Un total de 30 niños y adolescentes (recién diagnosticados de TDAH según los criterios diagnósticos del DSM-IV) fueron evaluados a través de un actígrafo, un instrumento que permite monitorizar los movimientos corporales analizando los patrones de movimiento y las diferencias entre sueño y vigilia. RESULTADOS: Existen diferencias significativas antes y después de realizar el tratamiento, con niveles de actividad más altos en los pacientes con TDAH antes de empezar el tratamiento y un decrecimiento de esta actividad tras el tratamiento farmacológico. También existen diferencias entre los subtipos inatento y combinado, y el último grupo muestra un nivel de actividad mayor. CONCLUSIONES: El nivel de activación que presentan los sujetos con TDAH es mayor antes de tomar tratamiento, e influye en los patrones circadianos, el sueño y la calidad de vida. El tratamiento farmacológico ayuda a disminuir el nivel de activación

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders in childhood. The nuclear symptoms of ADHD are treated with stimulant medication such as methylphenidate; however, there's a lot of controversy regarding its side effects. AIMS. To analyse the activity patterns in children with ADHD during a period of 24 hours for seven days, before and after taking pharmacological treatment with stimulants (methylphenidate) and observe the differences between the different presentations of ADHD (inattentive and combined subtype). PATIENTS AND METHODS: A total of 30 children and adolescents (newly diagnosed with ADHD according to DSM-IV). Analyses were carried out through actigraphy, an instrument that allows us to monitor body movements by analysing movement patterns and differences between sleep and wakefulness. RESULTS: There were significant differences before and after treatment showing higher activity levels in patients with ADHD before treatment, and a decrease in this situation after taking pharmacological treatment. There are also differences between inattentive and combined subtype, showing the last group, higher activity levels. CONCLUSIONS: The level of activation presented by ADHD subjects is higher before taking stimulant treatment, influencing circadian patterns, sleep and quality of life. Pharmacological treatments help to decrease the level of activation

A circadian rhythm-related MTNR1B genetic variant (rs10830963) modulates glucose metabolism and insulin resistance after body weight loss secondary to biliopancreatic diversion surgery / La variante genética MTNR1B (rs10830963), relacionada con el ritmo circadiano, modula el metabolismo de la glucosa y la resistencia a la insulina después de la pérdida de peso corporal secundaria a una cirugía de derivación biliopancreática

OBJECTIVE: the rs10830963 SNP of the MTNR1B gene may be related with biochemical changes after weight loss induced by caloric restriction. We investigated the role of this SNP on biochemical parameters after biliopancreatic diversion (BPD) surgery in morbid obese subjects. PATIENTS AND METHODS: one hundred and fifty-four patients with morbid obesity, without diabetes mellitus type 2, were enrolled. Their biochemical and anthropometric parameters were recorded before the procedure and after one, two, and three years of follow-up. All subjects were genotyped (rs10830963) at baseline. RESULTS: the decrease in fasting insulin levels seen after the first year (delta: -3.9 ± 1.2 mIU/L vs. -1.8 ± 1.1 mIU/L; p = 0.03), the second year (delta: -5.0 ± 0.3 mIU/L vs. -2.3 ± 0.2 mIU/L; p = 0.01) and the third year (delta: -5.1 ± 1.9 mIU/L vs. -2.8 ± 1.1 mIU/L; p = 0.02) was higher in non-G-allele carriers than in G-allele carriers. Additionally, the improvement of HOMA-IR levels at year one (delta: -0.7 ± 0.2 mIU/L vs. -0.2 ± 0.2 mIU/L; p = 0.03), year two (delta: -1.0 ± 0.3 mIU/L vs. -0.5 ± 0.2 mIU/L; p = 0.01) and year three (delta: -1.2 ± 0.3 mIU/L vs. -0.4 ± 0.2 mIU/L; p = 0.03) was also higher in non-G-allele carriers than in G-allele carriers. Finally, basal glucose levels after the first year (delta: -10.1 ± 2.4 mg/dL vs. -3.6 ± 1.8 mg/dL; p = 0.02), the second year (delta: -16.0 ± 2.3 mg/dL vs. -8.4 ± 2.2 mg/dL; p = 0.01) and the third year (delta: -17.4 ± 3.1 mg/dL vs. -8.8 ± 2.9 mg/dL; p = 0.03) were higher in non-G-allele carriers than in G-allele carriers, too. Improvements seen in comorbidities were similar in both genotype groups. CONCLUSION: our study showed an association of the rs10830963 MTNR1B polymorphism after massive weight loss with lower glucose response, insulin resistance, and fasting insulin levels in G-allele carriers

OBJETIVO: la variante SNP rs10830963 del gen MTNR1B podría estar relacionada con cambios bioquímicos tras la pérdida de peso inducida por una restricción calórica. El objetivo de este trabajo es evaluar el papel de este SNP en los parámetros bioquímicos después de la cirugía de derivación biliopancreática (DBP). PACIENTES Y MÉTODOS: se reclutaron un total de 154 pacientes con obesidad mórbida sin diabetes mellitus de tipo 2. La valoración bioquímica y antropométrica se realizó antes de la intervención y tras 1, 2 y 3 años de seguimiento. Todos los sujetos fueron genotipados (rs10830963) en el momento basal. RESULTADOS: la disminución de los niveles de insulina en ayunas después del primer año (delta: -3,9 ± 1,2 mUI/L vs. -1,8 ± 1,1 mUI/L; p = 0,03), el segundo año (delta: -5,0 ± 0,3 mUI/L vs. -2,3 ± 0,2 mUI/L; p = 0,01) y el tercer año (delta: -5,1 ± 1,9 mUI/L vs. -2,8 ± 1,1 mUI/L; p = 0,02) fueron mayores en los no portadores del alelo G que en los portadores. Además, la mejora de los niveles de HOMA-IR en el primer año (delta: -0,7 ± 0,2 mUI/L ± -0,2 ± 0,2 mUI/L; p = 0,03), segundo año (delta: -1,0 ± 0,3 mUI/L vs. -0,5 ± 0,2 mUI/L; p = 0,01) y en el tercer año (delta: -1,2 ± 0,3 mUI/L vs. -0,4 ± 0,2 mUI/L; p = 0,03) también fueron mayores en los no portadores del alelo G. Finalmente, los niveles basales de glucosa después del primer año (delta: -10,1 ± 2,4 mg/dL vs. -3,6 ± 1,8 mg/dL; p = 0,02), el segundo año (delta: -16,0 ± 2,3 mg/dL vs. - 8,4 ± 2,2 mg/dL; p = 0,01) y el tercer año (delta: -17,4 ± 3,1 mg/dL vs. -8,8 ± 2,9 mg/dL; p = 0.03) fueron mayores en los no portadores del alelo G. Las comorbilidades mejoraron en ambos genotipos de manera similar. CONCLUSIÓN: nuestro estudio mostró una asociación del polimorfismo rs10830963 MTNR1B tras una pérdida de peso posquirúrgica con una menor respuesta de los niveles de glucosa, resistencia a la insulina e insulina en ayunas en portadores del alelo G

Presión arterial central en la obesidad mórbida y tras la cirugía bariátrica / Central blood pressure in morbid obesity and after bariatric surgery

La obesidad está asociada con la hipertensión arterial por mecanismos diversos. La presión arterial (PA) central parece estar más correlacionada que la PA periférica con el riesgo cardiovascular futuro. La cirugía bariátrica constituye un método eficaz para disminuir la PA paralelamente a una pérdida de peso significativa en pacientes con obesidad severa. El estudio de la relación entre la modificación de peso tras cirugía bariátrica y la medición ambulatoria de PA, no solo a nivel periférico, sino también a nivel central, podría aportar información respecto a los mecanismos del daño orgánico asociado a la PA elevada en la obesidad. En esta revisión analizamos la evidencia disponible respecto a la asociación entre la PA central con la obesidad y sus modificaciones tras la cirugía bariátrica

Various mechanisms are related to arterial hypertension in obesity. Central blood pressure (BP) seems to correlate more than peripheral BP with future cardiovascular risk. Bariatric surgery is an effective method to reduce BP along with weight loss in patients with morbid obesity. The study of the relationship between weight modification after bariatric surgery and ambulatory BP measurement, not only peripheral BP, but also central BP, could provide information regarding the mechanisms of organic damage associated with elevated BP in obesity. In this review we analyze the available evidence regarding the association between central BP with obesity and its modifications after bariatric surgery

Sleep-wake cycle of elite athletes prior to the Rio 2016 Olympic Games / Ciclo de vigilia-sueño de atletas de élite antes de los Juegos Olímpicos de Río 2016 / Ciclo de vigília-sono de atletas de elite antes dos Jogos Olímpicos Rio 2016

OBJECTIVE: To analyze chronotype, duration and quality of sleep among elite athletes, to compare differences in sleep variables between sex, and to compare differences between athletes of individual and team sports. METHOD: The sample included 70 Brazilian elite athletes of both sex (male=37; female=33) with a mean age 23.0 ± 4.0 years old. To measure sleep-wake cycle, athletes wore an actigraph on the wrist for 10 days. Moreover, athletes answered the chronotype questionnaire of Horne and Östberg. RESULTS: The most athletes are intermediate-type (n=55, 78.6%), with a mean of 07h:18min of sleep per night. The athletes demonstrated higher sleep fragmentation (39.26 ± 23.66 minutes) and higher sleep latency (30.88 ± 16.19 minutes) during pre-competition training days. Additionally, the athletes of individual sports demonstrated more fragmentation (p < 0.001) and less sleep efficiency (p < 0.001) compared athletes of team sports. However, there was no significant difference in all sleep variables between the male and female sex. CONCLUSION: The overall elite athletes presented poor sleep quality during the training periods prior to the Rio 2016 Olympic Games, and individual athletes showed higher fragmentation and poorer sleep efficiency compared to team athletes

OBJETIVO: Analizar el cronotipo, la duración y la calidad del sueño entre los atletas de élite, comparar las diferencias en las variables de sueño entre los sexos y comparar las diferencias entre los atletas de los deportes individuales y de equipo. MÉTODO: La muestra incluyó a 70 atletas de élite brasileños de ambos sexos (hombre = 37; mujer = 33) con una edad media de 23.0 ± 4.0 años. Para medir lo ciclo de vigilia-sueño, los atletas usaron un actígrafo en la muñeca durante 10 días. Además, los atletas respondieron el cuestionario cronotipo de Horne y Östberg. RESULTADOS: La mayoría de los atletas son de tipo intermedio (n = 55, 78.6%), con una media de 07h: 18min de sueño por noche. Los atletas demostraron una mayor fragmentación del sueño (39.26 ± 23.66 minutos) y una mayor latencia del sueño (30.88 ± 16.19 minutos) durante los días de entrenamiento previo a la competencia. Además, los atletas de deportes individuales demostraron más fragmentación (p <0.001) y menos eficiencia del sueño (p <0.001) en comparación con los atletas de deportes de equipo. Sin embargo, no hubo diferencias significativas en todas las variables de sueño entre el sexo masculino y el femenino. CONCLUSIÓN: Los atletas de élite en general presentaron mala calidad del sueño durante los períodos de entrenamiento previos a los Juegos Olímpicos de Río 2016, y los atletas individuales mostraron una mayor fragmentación y una menor eficiencia del sueño en comparación con los atletas del equipo

OBJETIVO: Analisar o cronotipo, a duração e a qualidade do sono de atletas de elite, comparar as diferenças nas variáveis do sono entre os sexos e as diferenças entre atletas de esportes individuais e coletivos. MÉTODO: A amostra incluiu 70 atletas de elite brasileiros de ambos os sexos (masculino = 37; feminino = 33) com idade média de 23.0 ± 4.0 anos. Para mensurar o ciclo vigília-sono, os atletas usaram um actígrafo no punho por 10 dias. Além disso, os atletas responderam ao questionário de cronotipo de Horne e Östberg. RESULTADOS: A maioria dos atletas é do tipo intermediário (n = 55, 78.6%), com média de 07h:18min de sono por noite. Os atletas demonstraram maior fragmentação do sono (39.26 ± 23.66 minutos) e maior latência do sono (30.88 ± 16.19 minutos) durante os dias de treinamento pré-competição. Além disso, os atletas de esportes individuais demonstraram maior fragmentação (p <0.001) e menor eficiência do sono (p <0.001) em comparação aos atletas de esportes coletivos. No entanto, não houve diferença significativa em todas as variáveis de sono entre os sexos masculino e feminino. CONCLUSÃO: Os atletas de elite em geral apresentaram baixa qualidade do sono durante os períodos de treinamento antes dos Jogos Olímpicos Rio 2016, e os atletas de esportes individuais apresentaram maior fragmentação e menor eficiência do sono em comparação aos atletas de esportivos coletivos

Comparación del estado nutricional, cronotipo y conducta alimentaria en estudiantes universitarios chilenos que presentan el polimorfismo rs3749474T/C o rs4864548A/G del gen CLOCK / Comparison of nutritional status, chronotype and eating behavior in Chilean university students presenting the polymorphism rs3749474T / C or rs4864548A / G of the CLOCK gene

FUNDAMENTOS: El estado nutricional puede verse afectado por la conducta alimentaria y los ritmos circadianos. Estos se encuentran regulados por el gen CLOCK, cuyos alelos T del SNP rs3749474T/C y A del SNP rs4864548A/G, han sido asociados con la obesidad en adultos. MÉTODOS: Se evaluó a 65 sujetos usando la técnica PCR en tiempo real para determinar si era portadores del alelo T del SNP rs3749474T/C o del A del SNP rs4864548A/G. Se realizaron mediciones antropométricas, y se aplicó los cuestionarios TFEQ y el Horne-Östberg. RESULTADOS: De los 65 sujetos estudiados, 8 eran portadores del alelo T del SNP rs3749474T/C y 7 del A del SNP rs4864548A/G. Los portadores del alelo A presentaron mayores valores promedio de IMC (26,58), circunferencia de cintura (89,57cm) y porcentaje de grasa (31,56%) no existiendo diferencias estadísticamente significativas entre ellos. No se encontraron diferencias estadísticamente significativas en cuanto a la conducta alimentaria. El 66,67% del total de los sujetos presentó un cronotipo de tipo intermedio. CONCLUSIONES: Los portadores del alelo A del SNP rs4864548A/G presentarían un mayor potencial de sufrir problemas asociados a la obesidad, pero es necesario realizar estudios con poblaciones más grandes y con mejor paridad de género, que permita corroborar esta aseveración

BACKGROUND: Nutritional status may be affected by eating behavior and circadian rhythms. These are regulated by the CLOCK gene, whose T alleles of SNP rs3749474T / C and A of SNP rs4864548A / G, have been associated with obesity in adults. METHODS: 65 subjects were evaluated using the real-time PCR technique to determine whether they were carriers of the T allele of the SNP rs3749474T/C or the A of the SNP rs4864548A/G. Anthropometric measurements were made, and the TFEQ and Horne-Östberg questionnaires were applied. RESULTS: Of the 65 subjects studied, 8 were carriers of the T allele of the SNP rs3749474T / C and 7 of the A of the SNP rs4864548A/G. The carriers of the A allele had higher average BMI values (26.58), waist circumference (89.57cm) and fat percentage (31.56%), with no statistically significant differences between them. No statistically significant differences were found regarding eating behavior. 66.67% of the total subjects presented an intermediate type chronotype. CONCLUSIONS: The carriers of the A allele of SNP rs4864548A/G would have a greater potential to suffer problems associated with obesity, but studies with larger populations and with better gender parity are necessary, which allows to confirm this assertion

Cardioversión en la fibrilación auricular de reciente comienzo / Cardioversion in recent onset atrial fibrillation

Objetivos: Este estudio analiza el control del ritmo en los servicios de urgencias (SUH) y sus resultados en pacientes con fibrilación auricular (FA) de reciente comienzo, para identificar áreas de mejora en el manejo. Método: Estudio multicéntrico, observacional, prospectivo y transversal desarrollado en 124 SUH representativos del sistema sanitario español basado en el registro HERMES-AF (estrategias de manejo en el servicio de urgencias hospitalario de la FA) del 23 de mayo al 5 de junio de 2011. Se incluyeron pacientes con FA sintomática con menos de 48 h de evolución en los cuales se tomó la decisión de restaurar el ritmo sinusal. Resultados: Se incluyeron 337 pacientes, se optó por cardioversión farmacológica en 311 pacientes (92,3%), y por cardioversión eléctrica en 52 (15%), la mitad de los casos tras fracaso de los fármacos. Se obtuvo ritmo sinusal (RS) en 278 pacientes (82,5%) y el alivio de los síntomas en 297 (94%), con una tasa de efectos adversos del 0,9%, ninguno grave. Amiodarona se asoció de manera independiente a una menor tasa de RS al alta (OR = 0,442; IC 95% 0,238-0,823; p = 0,01), al contrario que la cardioversión eléctrica (OR = 4,0; IC 95% 1,2-13,3; p = 0,024). Los fármacos I-C se asociaron con una mayor proporción de altas en < 6 h (OR 2,6; IC 95% 1,6-4,3; p < 0,001) y amiodarona con más estancias prolongadas de > 24 h (OR 2,7, IC 95% 1,5-4,8; p < 0,003). Conclusiones: En los SUH, la restauración del RS en la FA de reciente comienzo es segura, efectiva y asocia beneficios clínicos para los pacientes. Reemplazar amiodarona por técnicas más efectivas y rápidas como la cardioversión eléctrica o los fármacos I-C es un área de mejora de la calidad asistencial

Objectives: To analyze heart rate control in hospital emergency departments and outcomes in patients with recent onset atrial fibrillation (AF) so that targets for improvement can be identified. Methods: Multicenter, prospective observational cross-sectional study in a representative sample of 124 hospitals of the Spanish health services, based on records in the HERMES-AF database (Hospital Emergency Department Management Strategies for AF) for May 23 to June 5, 2011. Patients with symptomatic AF within 48 hours of onset were enrolled when the decision was made to attempt restoration of sinus rhythm. Results: We included 337 patients. Chemical cardioversion was used in 311 (92.3%) and electrical cardioversion in 52 (15%), after drugs had failed in half the cases. Sinus rhythm was restored in 278 patients (82.5%), and symptoms resolved in 94%. Adverse effects were recorded in 0.9% but none were serious. Amiodarone was independently associated with a lower rate of restored sinus rhythm (odds ratio [OR], 0.442; 95% CI, 0.238-0.823; P=.01) than electrical cardioversion (OR, 4.0; 95% CI, 1.2-13.3; P=.024). The use of class Ic antiarrhythmic agents was associated with a higher percentage of discharges in less than 6 hours (OR, 2.6; 95% CI, 1.6-4.3; P<.001), and amiodarone was associated with hospital stays longer than 24 hours (OR, 2.7; 95% CI, 1.5-4.8; P<.003). Conclusions: Emergency department restoration of sinus rhythm in patients with AF is safe, effective, and associated with clinical benefits. Quality of care could be improved by replacing the use of amiodarone with faster and more effective treatments such as electrical cardioversion or the use of class Ic agents