Circadian Transcriptome Oscillations In Human Adipose Tissue Depend On Napping Status And Link To Metabolic And Inflammatory Pathways.

STUDY OBJECTIVES: Napping is a common habit in many countries. Nevertheless, studies about the chronic effects of napping on obesity are contradictory, and the molecular link between napping and metabolic alterations has yet to be studied. We aim to identify molecular mechanisms in adipose tissue (AT) that may connect napping and abdominal obesity. METHODS: In this cross-sectional study, we extracted the RNA repeatedly across 24h from cultured AT explants and performed RNA sequencing. Circadian rhythms were analyzed using 6 consecutive time points across 24 hours. We also assessed global gene expression in each group (nappers vs. non-nappers). RESULTS: With napping, there was a loss of rhythmicity in 88% of genes that showed circadian rhythmicity among non-nappers, a reduction in rhythm amplitudes of 29%, and significant phase changes from a coherent unimodal acrophase in non-nappers, towards a scattered and bimodal acrophase in nappers. Those genes that lost rhythmicity with napping were mainly involved in pathways of glucose and lipid metabolism, and of the circadian clock. Additionally, we found differential global gene expression between nappers and non-nappers with 34 genes down- and 32 genes up-regulated in nappers. The top up-regulated gene (IER3) and top down-regulated pseudogene (VDAC2P2) in nappers have been previously shown to be involved in inflammation. CONCLUSION: These new findings may have implications for our understanding of napping's effects on obesity and metabolic disorders.

Melatonin decreases human adipose tissue insulin sensitivity.

Melatonin is a pineal hormone that modulates the circadian system and exerts soporific and phase-shifting effects. It is also involved in many other physiological processes, such as those implicated in cardiovascular, endocrine, immune, and metabolic functions. However, the role of melatonin in glucose metabolism remains contradictory, and its action on human adipose tissue (AT) explants has not been demonstrated. We aimed to assess whether melatonin (a pharmacological dose) influences insulin sensitivity in human AT. This will help better understand melatonin administration's effect on glucose metabolism. Abdominal AT (subcutaneous and visceral) biopsies were obtained from 19 participants with severe obesity (age: 42.84 ± 12.48 years; body mass index: 43.14 ± 8.26 kg/m2) who underwent a laparoscopic gastric bypass. AT biopsies were exposed to four different treatments: control (C), insulin alone (I) (10 nM), melatonin alone (M) (5000 pg/mL), and insulin plus melatonin combined (I + M). All four conditions were repeated in both subcutaneous and visceral AT, and all were performed in the morning at 8 a.m. (n = 19) and the evening at 8 p.m. (in a subsample of n = 12). We used western blot analysis to determine insulin signaling (using the pAKT/tAKT ratio). Furthermore, RNAseq analyses were performed to better understand the metabolic pathways involved in the effect of melatonin on insulin signaling. As expected, insulin treatment (I) increased the pAKT/tAKT ratio compared with control (p < .0001). Furthermore, the addition of melatonin (I + M) resulted in a decrease in insulin signaling as compared with insulin alone (I); this effect was significant only during the evening time (not in the morning time). Further, RNAseq analyses in visceral AT during the evening condition (at 8 p.m.) showed that melatonin resulted in a prompt transcriptome response (around 1 h after melatonin addition), particularly by downregulating the insulin signaling pathway. Our results show that melatonin reduces insulin sensitivity in human AT during the evening. These results may partly explain the previous studies showing a decrease in glucose tolerance after oral melatonin administration in the evening or when eating late when endogenous melatonin is present.

Habitual nappers and non-nappers differ in circadian rhythms of LIPE expression in abdominal adipose tissue explants.

Background and purpose: Napping is a widespread practice worldwide and has in recent years been linked to increased abdominal adiposity. Lipase E or LIPE encodes the protein hormone-sensitive lipase (HSL), an enzyme that plays an important role in lipid mobilization and exhibits a circadian expression rhythm in human adipose tissue. We hypothesized that habitual napping may impact the circadian expression pattern of LIPE, which in turn may attenuate lipid mobilization and induce abdominal fat accumulation. Methods: Abdominal adipose tissue explants from participants with obesity (n = 17) were cultured for a 24-h duration and analyzed every 4 h. Habitual nappers (n = 8) were selected to match non-nappers (n = 9) in age, sex, BMI, adiposity, and metabolic syndrome traits. Circadian LIPE expression rhythmicity was analyzed using the cosinor method. Results: Adipose tissue explants exhibited robust circadian rhythms in LIPE expression in non-nappers. In contrast, nappers had a flattened rhythm. LIPE amplitude was decreased in nappers as compared with non-nappers (71% lower). The decrease in amplitude among nappers was related to the frequency of napping (times per week) where a lower rhythm amplitude was associated with a higher napping frequency (r = -0.80; P = 0.018). Confirmatory analyses in the activity of LIPE's protein (i.e., HSL) also showed a significant rhythm in non-nappers, whereas significance in the activity of HSL was lost among nappers. Conclusion: Our results suggest that nappers display dysregulated circadian LIPE expression as well as dysregulated circadian HSL activity, which may alter lipid mobilization and contribute to increased abdominal obesity in habitual nappers.

Caracterización clínica y sociodemográfica del intento suicida en la Región de Los Ríos, Chile

Introducción: El intento suicida es uno de los factores de riesgo suicida más relevantes, conocer variables asociadas y estrategias de seguimiento post-intento suicida contribuye a prevenir el suicidio. Objetivos: el objetivo de este trabajo fue describir características clínico-sociodemográfica de las personas que presentan intento de suicidio, y dar a conocer una estrategia de vigilancia clínicoepidemiológica que se activa posterior al intento suicida. Método: Se utilizó un diseño transversal, participaron 170 personas de 15 y más años ingresados a la Unidad para Personas con Intento suicida entre los años 2015 al 2018 en la Región De Los Ríos, Chile. Se evaluaron estadísticamente datos de carácter sociodemográfico y clínicos, previos y posterior al intento suicida. Resultado: Los resultados sociodemográficos muestran predominancia de intentos de mujeres, con una muestra que tiene su lugar de residencia principalmente en sectores urbanos. Además, se observó que la pertenencia religiosa católica o evangélica, podría asociarse a mayor riesgo de reintento suicida (p=0,014). Conclusiones: Los factores clínicos muestran que presentar intentos suicidas previos, depresión en curso al momento del intento suicida y los conflictos de pareja son factores relevantes a considerar. La frecuencia de suicidio y los reintentos suicida en vigilancia fue baja, por lo que fortalecer la continuidad de cuidados podría tener un rol preventivo en el fenómeno suicida.

Introduction: Suicidal attempt is one of the most relevant suicide risk factors, knowing associated variables and post-suicide attempt follow-up strategies contributes to preventing suicide. Objective: the objective of this work was to describe the clinical-sociodemographic characteristics of people who present a suicide attempt, and to present a strategy of clinical-epidemiological surveillance that is activated after the suicide attempt. Methods: A cross-sectional design was carried out, involving 170 subjects aged 15 and over admitted to the Unit for People with a suicide attempt between 2015 and 2018 in the Los Ríos region, Chile. Sociodemographic and clinical data, before and after the suicide attempt, were statistically evaluated. Results: The sociodemographic results show a predominance of attempts by women, with a sample that has its place of residence mainly in urban areas. In addition, it was observed that Catholic or evangelical religious affiliation could be associated with a higher risk of suicidal retry (p = 0.014). Conclusions: The clinical factors show that having previous suicide attempts, ongoing depression at the time of the suicide attempt, and partner conflicts are relevant factors to consider. The frequency of suicide and suicide retries in surveillance was low, so strengthening the continuity of care could play a preventive role in the suicide phenomenon.

Circadian Rhythms in Hormone-sensitive Lipase in Human Adipose Tissue: Relationship to Meal Timing and Fasting Duration.

BACKGROUND: Fat mobilization in adipose tissue (AT) has a specific timing. However, circadian rhythms in the activity of the major enzyme responsible for fat mobilization, hormone-sensitive lipase (HSL), have not been demonstrated in humans. OBJECTIVE: To analyze in a cross-sectional study whether there is an endogenous circadian rhythm in HSL activity in human AT ex vivo and whether rhythm characteristics are related to food timing or fasting duration. METHODS: Abdominal AT biopsies were obtained from 18 severely obese participants (age: 46 ± 11 years; body mass index 42 ± 6 kg/m2) who underwent laparoscopic gastric bypass. Twenty-four-hour rhythms of HSL activity and LIPE (HSL transcript in humans) expression in subcutaneous AT were analyzed together with habitual food timing and night fasting duration. RESULTS: HSL activity exhibited a circadian rhythm (P = .023) and reached the maximum value at circadian time 16 (CT) that corresponded to around midnight (relative local clock time. Similarly, LIPE displayed a circadian rhythm with acrophase also at night (P = .0002). Participants with longer night fasting duration >11.20 hours displayed almost double the amplitude (1.91 times) in HSL activity rhythm than those with short duration (P = .013); while habitual early diners (before 21:52 hours) had 1.60 times higher amplitude than late diners (P = .035). CONCLUSIONS: Our results demonstrate circadian rhythms in HSL activity and may lead to a better understanding of the intricate relationships between food timing, fasting duration and body fat regulation.

Plant Phenolics and Phenolic-Enriched Extracts as Antimicrobial Agents against Food-Contaminating Microorganisms.

Phenolic compounds and extracts with bioactive properties can be obtained from many kinds of plant materials. These natural substances have gained attention in the food research as possible growth inhibitors of foodborne pathogenic and spoilage bacteria. Many phenolic-enriched plant extracts and individual phenolics have promising anti-quorum sensing potential as well and can suppress the biofilm formation and toxin production of food-related pathogens. Various studies have shown that plant phenolics can substitute or support the activity of synthetic food preservatives and disinfectants, which, by the way, can provoke serious concerns in consumers. In this review, we will provide a brief insight into the bioactive properties, i.e., the antimicrobial, anti-quorum sensing, anti-biofilm and anti-enterotoxin activities, of plant phenolic extracts and compounds, with special attention to pathogen microorganisms that have food relation. Carbohydrase aided applications to improve the antimicrobial properties of phenolic extracts are also discussed.

An Organic Solvent-Tolerant Lipase with Both Hydrolytic and Synthetic Activities from the Oleaginous Fungus Mortierella echinosphaera.

Lipase enzymes of the oleaginous fungal group Mortierella are rarely studied. However, considering that most commercial lipases are derived from filamentous fungal sources, their investigation can contribute to the cost-effective development of new biotechnological processes. Here, an extracellular lipase with a molecular mass of 30 kDa was isolated from Mortierella echinosphaera CBS 575.75 and characterized. The purified lipase exhibited an optimal p-nitrophenyl palmitate (pNPP)-hydrolyzing activity at 25 °C and pH 6.6-7.0 and proved to be highly stable at temperatures up to 40 °C and under broad pH conditions. The enzyme was active under low temperatures, retaining 32.5% of its activity at 10 °C, and was significantly stable in polar and non-polar organic solvents. The Km, Vmax, and kcat for pNPP were 0.336 mM, 30.4 µM/min, and 45.7 1/min for pNPP and 0.333 mM, 36.9 µM/min, and 55.6 1/min for pNP-decanoate, respectively. The pNPP hydrolysis was inhibited by Hg2+, N-bromosuccinimide, and sodium dodecyl sulfate, while ethylenediaminetetraacetic acid and metal ions, such as Ca2+, Mg2+, Na⁺, and K⁺ enhanced the activity. The purified lipase had non-regioselective activity and wide substrate specificity, showing a clear preference for medium-chained p-nitrophenyl esters. Besides its good transesterification activity, the enzyme appeared as a suitable biocatalyst to operate selective esterification reactions to long-chained alkyl esters. Adsorption to Accurel MP1000 improved the storage stability of the enzyme at 5 °C. The immobilized lipase displayed tolerance to a non-aqueous environment and was reusable for up to five cycles without significant loss in its synthetic and hydrolytic activities. These findings confirm the applicability of both the free and the immobilized enzyme preparations in future research.

Efecto de la sinusitis en la severidad del asma en pacientes pediatrícos / Effect of the sinusitis in the severity of the asthma in patients pediatrics

La asociación asma-sinusitis se conoce desde hace tiempo, estando bien comprobado que el tratamiento adecuado de la sinusitis en pacientes asmáticos mejora los síntomas respiratorios. Determinar la correlación entre severidad de crisis e intercrisis asmática y rinusopatía en pacientes pediátricos. Estudio retrospectivo, muestra, pacientes hospitalizados por crisis asmática, entre 1995-2001, a los cuales por estudios imagenológicos se halla diagnósticado Sinusopatia, variable estudiada: severidad de crisis e intercrisis asmática. Se revisaron 355 historias, siendo estudiados con imágenes el 28.17 por ciento, resultando con sinusopatía el 50 por ciento para un total de 50 pacientes incluidos. Distribución según intercrisis: Leve persistente 40 por ciento, leve intermitente 40 por ciento, moderada 12 por ciento y severa 8 por ciento. Conclusiones: no podemos afirmar una relación entre la presencia de sinusopatía y la severidad del asma, ya que la distribución de pacientes según intercrisis encontrada se asemeja a la reportada en la población general de asmáticos. Se debe solicitar con mayor frecuencia estudios de imágenes tipo TAC de senos paranasales en pacientes asmáticos