Gestational Diabetes Mellitus and its Effects on the Developing Cerebellum: A Narrative Review on Experimental Studies.

Diabetes mellitus during pregnancy is a common complication of gestation, but its effects on the offspring's development are poorly understood. Recently, some studies reported that gestational diabetes mellitus (GDM) impairs cerebellar development, and some genetic alterations have been described as consequences. Cerebellum, one of the hindbrain derived structures in the posterior cranial fossa, plays a crucial role in cognition and behavioral functions. In recent years, some surveys stated that gestational diabetes has adverse effects on the fetus's cerebellum. Disruption of cerebellar cortex morphogenesis, reduce the volume of the cerebellum, reduce the thickness of cerebellar cortex layers, and its neuronal cells and effects on the expression of synaptophysin, insulin, and insulin-like growth factor -1 receptors are some of the maternal diabetes effects on developing cerebellum. On other hand, GDM, as a neurotoxic agent, impaired cerebellar development and could be a cause for the behavioral, functional, and structural anomalies observed in pups of diabetic mothers. Based on the literature review, most studies have pointed out that administering insulin in patients with GDM decreased the cellular and molecular alterations that induced by GDM in the developing cerebellum. Undoubtedly, screening strategies for all pregnant women are necessary.

Insufficient sleep and weekend recovery sleep: classification by a metabolomics-based machine learning ensemble.

Although weekend recovery sleep is common, the physiological responses to weekend recovery sleep are not fully elucidated. Identifying molecular biomarkers that represent adequate versus insufficient sleep could help advance our understanding of weekend recovery sleep. Here, we identified potential molecular biomarkers of insufficient sleep and defined the impact of weekend recovery sleep on these biomarkers using metabolomics in a randomized controlled trial. Healthy adults (n = 34) were randomized into three groups: control (CON: 9-h sleep opportunities); sleep restriction (SR: 5-h sleep opportunities); or weekend recovery (WR: simulated workweek of 5-h sleep opportunities followed by ad libitum weekend recovery sleep and then 2 days with 5-h sleep opportunities). Blood for metabolomics was collected on the simulated Monday immediately following the weekend. Nine machine learning models, including a machine learning ensemble, were built to classify samples from SR versus CON. Notably, SR showed decreased glycerophospholipids and sphingolipids versus CON. The machine learning ensemble showed the highest G-mean performance and classified 50% of the WR samples as insufficient sleep. Our findings show insufficient sleep and recovery sleep influence the plasma metabolome and suggest more than one weekend of recovery sleep may be necessary for the identified biomarkers to return to healthy adequate sleep levels.

Association of the rs17782313, rs17773430 and rs34114122 Polymorphisms of/near MC4R Gene with Obesity-Related Biomarkers in a Spanish Pediatric Cohort.

Obesity is a multifactorial disease whose onset and development are shaped by the individual genetic background. The melanocortin 4 receptor gene (MC4R) is involved in the regulation of food intake and energy expenditure. Some of the single nucleotide polymorphisms (SNPs) of this gene are related to obesity and metabolic risk factors. The present study was undertaken to assess the relationship between three polymorphism SNPs, namely, rs17782313, rs17773430 and rs34114122, and obesity and metabolic risk factors. One hundred seventy-eight children with obesity aged between 7 and 16 years were studied to determine anthropometric variables and biochemical and inflammatory parameters. Our results highlight that metabolic risk factors, especially alterations in carbohydrate metabolism, were related to rs17782313. The presence of the minor C allele in the three variants (C-C-C) was significantly associated with anthropometric measures indicative of obesity, such as the body mass and fat mass indexes, and increased the values of insulinemia to 21.91 µIU/mL with respect to the wild type values. Our study suggests that the C-C-C haplotype of the SNPs rs17782313, rs17773430 and rs34114122 of the MC4R gene potentiates metabolic risk factors at early ages in children with obesity.

Circadian Disruption and Mental Health: The Chronotherapeutic Potential of Microbiome-Based and Dietary Strategies.

Mental illness is alarmingly on the rise, and circadian disruptions linked to a modern lifestyle may largely explain this trend. Impaired circadian rhythms are associated with mental disorders. The evening chronotype, which is linked to circadian misalignment, is a risk factor for severe psychiatric symptoms and psychiatric metabolic comorbidities. Resynchronization of circadian rhythms commonly improves psychiatric symptoms. Furthermore, evidence indicates that preventing circadian misalignment may help reduce the risk of psychiatric disorders and the impact of neuro-immuno-metabolic disturbances in psychiatry. The gut microbiota exhibits diurnal rhythmicity, as largely governed by meal timing, which regulates the host's circadian rhythms. Temporal circadian regulation of feeding has emerged as a promising chronotherapeutic strategy to prevent and/or help with the treatment of mental illnesses, largely through the modulation of gut microbiota. Here, we provide an overview of the link between circadian disruption and mental illness. We summarize the connection between gut microbiota and circadian rhythms, supporting the idea that gut microbiota modulation may aid in preventing circadian misalignment and in the resynchronization of disrupted circadian rhythms. We describe diurnal microbiome rhythmicity and its related factors, highlighting the role of meal timing. Lastly, we emphasize the necessity and rationale for further research to develop effective and safe microbiome and dietary strategies based on chrononutrition to combat mental illness.

Melatonin Levels in Children with Obesity Are Associated with Metabolic Risk and Inflammatory Parameters.

Melatonin, the hormone of circadian rhythm regulation, is involved in the modulation of mitochondrial activity through its antioxidant and anti-inflammatory properties. Alteration of circadian rhythms such as sleep is related to obesity and metabolic pathogenesis in adulthood, but studies during childhood are scarce. The present study investigated the association of melatonin with metabolic and inflammatory markers in children with (n = 113) and without obesity (n = 117). Melatonin was measured in saliva four and two hours before bedtime, and after one hour of sleep. Cardiometabolic factors, high sensitivity C-reactive protein, immune markers (monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, tumor necrosis α and interferon-γ), leptin and ghrelin were determined. Sleep duration was recorded by a questionnaire. The melatonin level at 1 h after sleep was found to be increased more than twofold in children with obesity (90.16 (57.16-129.16) pg/mL) compared to controls (29.82 (19.05-61.54) pg/mL, p < 0.001) and was related to fat mass (rho = 0.294, p < 0.001); melatonin levels at 1 h after sleep were inversely correlated with high-density lipoprotein cholesterol. Positive correlation was found with apolipoprotein B, adipokines, high sensitivity C-reactive protein, plasminogen activator inhibitor-1 and tumor necrosis factor-α. Shorter sleep duration and earlier waking times were recorded in children with obesity. In conclusion, melatonin in children with obesity appears to be involved in the global metabolic and inflammatory alteration of this condition.

Melatonin in Early Nutrition: Long-Term Effects on Cardiovascular System.

Breastfeeding protects against adverse cardiovascular outcomes in the long term. Melatonin is an active molecule that is present in the breast milk produced at night beginning in the first stages of lactation. This indoleamine appears to be a relevant contributor to the benefits of breast milk because it can affect infant health in several ways. The melatonin concentration in breast milk varies in a circadian pattern, making breast milk a chrononutrient. The consumption of melatonin can induce the first circadian stimulation in the infant's body at an age when his/her own circadian machinery is not functioning yet. This molecule is also a powerful antioxidant with the ability to act on infant cells directly as a scavenger and indirectly by lowering oxidant molecule production and enhancing the antioxidant capacity of the body. Melatonin also participates in regulating inflammation. Furthermore, melatonin can participate in shaping the gut microbiota composition, richness, and variation over time, also modulating which molecules are absorbed by the host. In all these ways, melatonin from breast milk influences weight gain in infants, limiting the development of obesity and comorbidities in the long term, and it can help shape the ideal cellular environment for the development of the infant's cardiovascular system.

Introducing sexual dysfunction in mental care.

Introduction: People with any psychiatric disorder tend to have difficulties in responding sexually. However,sexual dysfunction (SD) is usually under-recognized, even the tightly hormonal and neuronal common connexions through the brain-sex axis. Multiple sources of resistance to SD assessment and intervention persist. Areas covered: The present review aims to underline the feasibility to introduce SD evaluation in patients with any psychiatric disorders, evaluating the potential mutual benefits of their management. Expert opinion: Women and men living with mental disorders frequently display sexual difficulties; however, some of them consider sexuality as a relevant parameter of their quality of life. In fact, SD as a side effect is a frequent reason for stopping the intake of medication. What is more, a holistic approach integrating sexual function could foster a better understanding of mental pathologies due to a common origin of pathogenesis. This could improve care quality, in keeping with the global tendency toward the development of personalized medicine. Consistently, the integration of SD assessment is highly recommended in mental health, all the more so when a psychotropic drug is prescribed. An expected consequence would be a reconstruction of the healthcare professional's consideration for the sexuality of people experiencing mental disorders.

Melatonin Content of Human Milk: The Effect of Mode of Delivery.

Objective: Cesarean section rates are increasing in developed countries and could be performed as an emergency or elective procedure. Our research aim was to determine whether elective cesarean section influences the melatonin content, the main circadian hormone, in human milk. Methods: Twenty-one women after vaginal delivery and 18 women after elective cesarean section were included. Only healthy mothers with normal newborns exclusively breastfed were recruited. Two samples of human milk were collected for each woman at three stages of lactation: colostrum, transitional milk, and mature milk; at each stage, one daytime sample and another nighttime sample were obtained. In total, 228 milk samples were studied. The melatonin content was analyzed by enzyme-linked immunosorbent assay. Results: Melatonin rhythmicity with higher melatonin content at night was maintained at each of the three stages of lactation, regardless of the type of delivery. A higher melatonin content was found in daytime colostrum after cesarean section with respect to colostrum obtained from mothers after vaginal delivery (30.3 pg/mL versus 14.7 pg/mL, p = 0.020). Melatonin content decreased progressively throughout the course of lactation in both groups. This decrease was significant when comparing transitional milk to colostrum in the cesarean group, both in the daytime (p = 0.016) and nighttime samples (p = 0.048). Conclusions: Cesarean section is associated with an increase in daytime colostrum melatonin. No difference was observed in mature milk with respect to vaginal delivery. Melatonin values in human milk decrease during the first month of lactation and circadian rhythmicity was observed irrespective of the mode of delivery.

The connection of circadian rhythm to inflammatory bowel disease.

Inflammatory bowel disease (IBD) comprises a group of chronic, immune system-mediated inflammatory diseases that primarily affect the gastrointestinal tract. The pathogenesis of the intestinal lesions in IBD remains elusive, but the inflammation process could be the result of dysfunction of the innate and adaptive immune systems induced by genetic and environmental factors. In recent years, research has demonstrated a connection between environmental stressors that can influence day-night variations, also called circadian rhythms, and digestive health. In this review, we focus on alterations in the complex interactions between intestinal mucosa, microbial factors, and the immune response in the intestinal milieu. We introduce the mechanisms that establish circadian rhythms and their regulation by the circadian rhythm genes. Evidence of circadian variation in the defense mechanisms of the intestine and its implication in the maintenance of a healthy microbiota are presented. Disruption of the circadian system can increase the activity of the gut immune system and the release of inflammatory factors. The link between chronodisruption or circadian rhythm impairment and IBD demonstrated by experimental and clinical studies illustrates the potential impact of circadian rhythms on treatment of these diseases. Future studies that investigate aspects of this subject are warranted.

Circadian rhythms in the pathogenesis of gastrointestinal diseases.

The etiology of digestive pathologies such as irritable bowel syndrome (IBS), inflammatory bowel diseases (IBD) and cancer is not yet fully understood. In recent years, several studies have evidenced circadian variations in mechanisms involved in digestive health. In situations of disturbed circadian rhythms (chronodisruption) where the central clock and the peripheral clocks receive incoherent signals, the synchronicity is lost producing implications for health. This lack of coordination could alter the tissue function and cause long term damage to the organs. Life habits such as sleep, physical exercise, social interaction, and feeding times are determinants for stability and integrity of circadian rhythms. In recent years, experimental and clinical studies have consistently evidenced that the alteration of circadian rhythms is associated with the development of digestive pathologies mainly linked to dismotility or changes in microbiota composition. Likewise, it seems reasonable to deep into the importance of chronodisruption as a factor that may participate in the development of pathologies such as IBS, IBD and digestive cancers. Moreover, life habits respecting circadian rhythms should be promoted for the prevention of these diseases. Further studies will allow us a better understanding of the mechanisms acting at molecular level, and the development of new therapeutic targets.

Effects of potassium citrate or potassium chloride in patients with combined glucose intolerance: A placebo-controlled pilot study.

BACKGROUND: Experimental K(+) depletion reversibly inhibits insulin secretion, while chronic metabolic acidosis decreases insulin sensitivity. We aimed to investigate the effects of potassium supplementation and alkali supplementation in non-acidotic, normokalemic humans with combined glucose intolerance. STUDY DESIGN AND RESULTS: In this double-blind, placebo-controlled study in 11 subjects (7 male, 4 female, ages 47-63 years), 90meqs of oral KCl or Kcitrate per day for 2weeks each increased insulin production as measured by homeostasis model assessment Beta [KCl=86 (CI 81-91), Kcitrate=88 (82-94), placebo=78 (73-83)%, p<0.04], but only Kcitrate attenuated insulin resistance as assessed by HOMA-IR (insulin resistance, Kcitrate=2.8 (2.5-3.1), placebo=3.2 (2.9-3.5), p<0.03) and only Kcitrate increased quantitative insulin sensitivity check index (Quicki, Kcitrate=0.355 (0.305-0.405), placebo=0.320 (0.265-0.375) p<0.04). These results were confirmed by independent measurements, i.e. HOMA C-peptide and whole body insulin sensitivity index measured during oral glucose tolerance testing. Kcitrate significantly decreased systolic and diastolic 24-hour ambulatory blood pressures (-4.0 (-3 to -5) and -2.7 (-1.9 to -3.5), respectively as compared to placebo, p<0.02) while KCl was without a significant effect. CONCLUSIONS: K(+) supplementation in the absence of overt K(+) depletion improves beta-cell function in subjects with combined glucose intolerance. The insulin-sensitizing and hypotensive effect, however, depend on citrate as the accompanying anion.

A CETP polymorphism improves the diagnostic power of clinical examination in patients with cardiovascular disease.

AIMS: Atherosclerosis is common and myocardial infarction, stroke and peripheral arterial occlusive disease are its devastating complications. Accurate risk prediction is urgently needed. We applied molecular tests to improve early clinical identification of patients threatened by a future course of complicated active atherosclerosis. METHODS AND RESULTS: Participants were men and women seeking care in a department of general internal medicine at an academic teaching hospital in Basel, Switzerland, between September 2003 and March 2005. A maximum number of 57 patients with a medical history of proven cardiovascular events and 57 age- and gender-matched patients without cardiovascular events were selected from this cohort of 269 individuals. One of nine common single nucleotide polymorphisms (SNPs) reportedly linked to cardiovascular disease was significantly associated with cardiovascular events (p = 0.02). For CETPrs708272, the allele number per patient predisposing to cardiovascular events improved the discriminating power of clinical phenotyping for active versus inactive atherosclerosis. The area under the curve of receiver operating characteristic (ROC) for clinical examination alone was 0.627 (95% CI 0.525-0.730, p = 0.02) and increased to 0.672 (95% CI 0.571-0.772, p = 0.002) when the polymorphism was included in the assessment. CONCLUSIONS: Information about common SNPs with high impact on the individual cardiovascular risk, such as CETPrs708272, may help to predict an active, symptomatic course atherosclerosis.

Plasma electric microfield distribution with the triplet correlation contribution: High-frequency component at a neutral point.

We report on nontrivial calculations of a triplet correlation contribution to the high-frequency component of the microfield distribution at a neutral particle point by utilizing an expansion, initially proposed by Baranger and Mozer, and demonstrate that its contribution leads to a shift of the maximum in the distribution to weaker fields relative to results including the pair correlation only. The entire picture of the high-frequency microfield distribution is studied and detailed comparison with the results of Hooper is made.

Temperature-dependent pseudopotential between two pointlike electrical charges.

Pair distribution functions for particles electrically charged, at a temperature T expressed in terms of density matrices and corresponding pseudopotentials are studied, for distinguishable particles and for an electron pair. Expansions with respect to the separation distance and to a quantum parameter (approximately T(-1/2)) are carried out. Approximate expressions are derived in the limits of high and low temperatures.