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Psychosocial status and lifestyle are key risk factors of non-communicable diseases (NCDs), which, in turn, are main drivers of healthcare costs and morbimortality worldwide, including Chile. Mediterranean diet (MedDiet) is one of the healthiest dietary patterns under study. However, its impact on high-risk conditions, such as metabolic syndrome (MetS), and NCDs outside the Mediterranean Basin remains mostly unexplored. Even though Central Chile has an environment, food production, and culinary traditions comparable to those present in Mediterranean countries, few studies -some with significant methodological limitations- have evaluated the effect of MedDiet on health and/or disease in Chilean subjects. Importantly, a Mediterranean lifestyle is a modus vivendi that integrates physical health with mental and social well-being. Psychological well-being (PWB) is associated with healthy behaviors, positive health outcomes, and longevity, thereby emerging as a novel healthcare goal. We report here an ongoing randomized controlled clinical trial in Chilean patients with MetS seeking to test whether (1) a PWB theory-based intervention facilitates induction to and increases long-term adherence to a locally adapted MedDiet, and (2) a MedDiet intervention -implemented alone or combined with well-being promotion- is more effective at reversing MetS compared to individuals following a low-fat diet without psychological support. The CHILEan MEDiterranean (CHILEMED) diet intervention study is a 1-year trial including patients with MetS living in Chile. Participants will be assigned randomly by a computer-generated random number sequence to one of the three intervention arms: a) low-fat diet as control group, b) MedDiet alone, and c) MedDiet plus well-being support. Patients will be followed-up by individual and/or group online nutritional sessions or phone cal as well as 6- and 12-month in-person re-assessment of medical history, medication use, food intake, PWB, anthropometrics/physical exam, and blood collection for laboratory analysis. The primary outcome of the trial will be the effect of the MedDiet -with or without PWB intervention- on overall reversal of MetS compared to low-fat diet alone. Based on a statistical superiority trial, expected impact, and patient loss, the estimated study sample is 339 subjects (113 individuals per arm in 3 equal-sized groups). Currently, we have enrolled 179 patients, predominantly women, evenly distributed by age (group means ranging from 45.7 to 48,9 years-old), 3/4 are obese with almost all of them showing abdominal obesity, 70% are hypertensive, whereas

Abstract Background High-density lipoprotein (HDL) plays a critical role in protection against atherosclerosic and cardiovascular disease (ASCVD). In addition to contributing to clearing excess vascular cholesterol, HDL particles exhibit antioxidative functions, helping to attenuate adverse effects of oxidized low-density lipoproteins. However, these beneficial properties can be undermined by oxidative stress, inflammation, and unhealthy lifestyles and diet, as well as influenced by race and sex. Thus, when assessing cardiovascular risk, it is important to consider multifactorial aspects of HDL, including antioxidant activity rather than just total amount and type of HDL-cholesterol (HDL-C) particles. Because prior research showed HDL peroxide content (HDLperox) can be inversely associated with normal anti-oxidant HDL activity, elevated HDLperox may serve as a bioindicator of HDL dysfunction. Methods In this study, data from a large national cohort of Americans was utilized to determine the impact of sex, race, and diabetes status on HDLperox in middle-aged and older adults. A previously developed cell-free fluorometric method was utilized to quantify HDLperox in serum depleted of apo-B containing lipoproteins. Results In keeping with predictions, white men and diabetics exhibited HDLperox in the atypical upper range, suggestive of less functional HDL. White men had higher HDLperox levels than African American males (13.46 ± 6.10 vs. 10.88 ± 5.81, p

BackgroundSphingolipids are components of cell membrane structure, but also circulate in serum and are essential mediators of many cellular functions. While ceramides have been proposed previously as a useful biomarker for cardiometabolic disease, the involvement of other sphingolipids is still controversial. The aim of this study was to investigate the cross-sectional association between blood sphingolipidomic profiles and metabolic syndrome (MetS) as well as other atherosclerotic risk factors in a large population-based study in the U.S.MethodsClinical data and serum sphingolipidomic profiling from 2,063 subjects who participated in the biomarker project of the Midlife in the United States (MIDUS) study were used.ResultsConsistent with previous reports, we found a positive association between most ceramide levels and obesity, atherogenic dyslipidemia, impaired glucose metabolism, and MetS prevalence. In contrast, most simple β-glycosphingolipids (i.e., hexosylceramides and lactosylceramides) were inversely associated with dysmetabolic biomarkers. However, this latter sphingolipid class showed a positive link with inflammatory and vascular damage-associated biomarkers in subjects with MetS. Through metabolic network analysis, we found that the relationship between ceramides and simple β-glycosphingolipids differed significantly not only according to MetS status, but also with respect to the participants' C-reactive protein levels.ConclusionOur findings suggest that a comprehensive sphingolipid profile is more informative about MetS than ceramides alone, and it may reveal new insights into the pathophysiology and further diabetic vs. cardiovascular risk in patients with MetS.

Abstract Emerging research has linked psychological well-being with many physiological markers as well as morbidity and mortality. In this analysis, the relationship between components of eudaimonic well-being and serum sphingolipids levels was investigated using data from a large national survey of middle-aged American adults (Midlife in the United States). Health behaviors (i.e., diet, exercise, and sleep) were also examined as potential mediators of these relationships. Serum levels of total ceramides—the main molecular class of sphingolipids previously associated with several disease conditions—were inversely linked with environmental mastery. In addition, significant correlations were found between specific ceramide, dihydroceramide, and hexosylceramides species with environmental mastery, purpose in life, and self-acceptance. Using hierarchical regression and mediation analyses, health behaviors appeared to mediate these associations. However, the link between ceramides and environmental mastery was partially independent of health behaviors, suggesting the role of additional mediating factors. These findings point to sphingolipid metabolism as a novel pathway of health benefits associated with psychological well-being. In particular, having a sense of environmental mastery may promote restorative behaviors and benefit health via improved blood sphingolipid profiles.

Metabolic syndrome (MetS) is a multicomponent risk condition that reflects the clustering of individual cardiometabolic risk factors related to abdominal obesity and insulin resistance. MetS increases the risk for cardiovascular diseases (CVD) and type 2 diabetes mellitus (T2DM). However, there still is not total clinical consensus about the definition of MetS, and its pathophysiology seems to be heterogeneous. Moreover, it remains unclear whether MetS is a single syndrome or a set of diverse clinical conditions conferring different metabolic and cardiovascular risks. Indeed, traditional biomarkers alone do not explain well such heterogeneity or the risk of associated diseases. There is thus a need to identify additional biomarkers that may contribute to a better understanding of MetS, along with more accurate prognosis of its various chronic disease risks. To fulfill this need, omics technologies may offer new insights into associations between sphingolipids and cardiometabolic diseases. Particularly, ceramides –the most widely studied sphingolipid class– have been shown to play a causative role in both T2DM and CVD. However, the involvement of simple glycosphingolipids remains controversial. This review focuses on the current understanding of MetS heterogeneity and discuss recent findings to address how sphingolipid profiling can be applied to better characterize MetS-associated risks.

El impacto del consumo de cigarrillo a nivel respiratorio y cardiovascular ha sido extensamente investigado, sin embargo, aún queda mucho por estudiar sobre su impacto en el tracto gastrointestinal. Está demostrado que el tabaquismo es un importante factor de riesgo para desórdenes gastrointestinales, incluyendo úlceras pépticas, Enfermedad de Crohn y distintos tipos de cáncer. Los mecanismos propuestos incluyen daños a nivel de la mucosa, alteraciones en la irrigación del tejido y cambios en la respuesta inmune. Paradojalmente, el consumo de cigarrillo constituye un factor protector para el desarrollo y la progresión de la Colitis Ulcerosa. Esta patología, junto a la Enfermedad de Crohn, conforman las dos entidades más importantes dentro de las Enfermedades Inflamatorias Intestinales y comparten diversas características. El impacto diferencial del consumo de cigarrillo entre ambas ha sido un tema de gran interés en los últimos treinta años, y aún no ha logrado ser esclarecido. En esta revisión describiremos los efectos conocidos del tabaquismo sobre el tracto gastrointestinal, y particularmente en la inflamación intestinal, profundizando en los estudios disponibles que intentan explicar el efecto opuesto del cigarrillo en la Enfermedad de Crohn y la Colitis Ulcerosa

The main environmental risk factor associated with the development of Crohn's disease (CD) is cigarette smoking. Although the mechanism is still unknown, some studies have shown that cigarette exposure affects the intestinal barrier of the small bowel. Among the factors that may be involved in this process are Paneth cells. These specialized epithelial cells are located into the small intestine, and they are able to secrete antimicrobial peptides, having an essential role in the control of the growth of microorganisms. Alterations in its function are associated with inflammatory processes, such as CD. To study how cigarette components impact ileum homeostasis and Paneth cells integrity, we used intragastric administration of cigarette smoke condensate (CSC) in mice. Our results showed that inflammation was triggered after mucosal exposure of CSC, which induced particular alterations in Paneth cells granules, antimicrobial peptide production, and a reduction of bactericidal capacity. In fact, exposure to CSC generated an imbalance in the fecal bacterial population and increased the susceptibility of mice to develop ileal damage in response to bacterial infection. Moreover, our results obtained in mice unable to produce interleukin 10 (IL-10−/− mice) suggest that CSC treatment can induce a symptomatic enterocolitis with a pathological inflammation in genetically susceptible individuals.

Paneth cells (PCs) are specialized epithelial cells of the small bowel that contain multiple secretory granules filled with antimicrobial peptides and trophic factors, which are essential for the control of the microorganisms growth and maintaining intestinal integrity. Alterations in their function are associated with an imbalance of the normal microbiota, gastrointestinal infections and inflammatory processes, such as Crohn's disease (CD). One of the most common murine models for studying CD is IL-10-/- mouse. IL-10-/- mice when housed in conventional conditions and take contact with commensal microorganisms develop an acute enterocolitis mediated by a Th1 immune response. Even though, alterations in PCs function are related to CD, they had not been characterized yet in this mouse model. Here we show that in specific pathogen free conditions IL-10-/- mice have aberrant granules and a large number of immature PCs at the bottom of the crypt in the ileum of IL-10-/- mice before developing intestinal inflammation, along with a reduced expression of Indian Hedgehog. In addition, IL-10-/- Paneth cells presented a reduced expression of cryptidin-4, and a heterogeneous distribution of lysozyme+ granules. The alterations in the maturation of the PCs at the bottom of the crypt were not modified after the colonization by the conventional microbiota. On the other hand, depletion of microbiota altered the phenotype, but did not normalize PCs. Our results suggest that IL-10 could be necessary for the integrity of PCs. Moreover, our results help to explain why IL-10-/- mice develop enterocolitis in response to microorganisms.

Heme Oxygenase 1 (HMOX1) is an enzyme that catalyzes the reaction that degrades the heme group contained in several important proteins, such as hemoglobin, myoglobin, and cytochrome p450. The enzymatic reaction catalyzed by HMOX1 generates Fe2+, biliverdin and CO. It has been shown that HMOX1 activity and the by-product CO can downmodulate the damaging immune response in several models of intestinal inflammation as a result of pharmacological induction of HMOX1 expression and the administration of non-toxic amounts of CO. Inflammatory Bowel Diseases, which includes Crohn's Disease (CD) and Ulcerative Colitis (UC), are one of the most studied ailments associated to HMOX1 effects. However, microbiota imbalances and infections are also important factors influencing the occurrence of acute and chronic intestinal inflammation, where HMOX1 activity may play a major role. As part of this article we discuss the immune modulatory capacity of HMOX1 during IBD, as well during the infections and interactions with the microbiota that contribute to this inflammatory disease.

Infectious diarrhea can be caused by a large number of microorganisms including bacteria virus and parasites. The clinical syndromic approach has been traditionally used to guide therapy. The aim of this study was to characterize the etiology of acute diarrhea by the FilmArray GI panel and to correlate it with its clinical presentation in an adult population presenting to the emergency room in a developing country. MATERIAL AND METHODS:Adult patients attending the ER due to acute diarrhea were selected. All patients included had a FilmArray GI panel performed and the clinical characteristics were recorded. RESULTS:One hundred and ninety-nine patients were included. One hundred and eighteen (59.3%) were females. The mean age was 43 years old. Thirty three percent of the patients presented dysentery, 36.7% fever, 54.8% referred nauseas and 35.7% vomiting. Sixty three percent of the patients presented some degree of dehydration. In total, 221 microorganisms were detected of which 71.5% corresponded to bacteria (158/221), 19.9% to virus (44/221) and 8.6% to parasites (19/221). In 133 (67.0%) of 199 patients at least one microorganism was identified. Infections with more than one microorganism were detected in 27.1% of the patients. Polimicrobial infections were associated with a higher frequency of nausea (50.0% vs 32.0%, p 0.046), abdominal pain (87.0% vs 44.0%, p

Cigarette smoking is a major risk factor for gastrointestinal disorders, such as peptic ulcer, Crohn’s disease (CD), and several cancers. The mechanisms proposed to explain the role of smoking in these disorders include mucosal damage, changes in gut irrigation, and impaired mucosal immune response. Paradoxically, cigarette smoking is a protective factor for the development and progression of ulcerative colitis (UC). UC and CD represent the two most important conditions of inflammatory bowel diseases, and share several clinical features. The opposite effects of smoking on these two conditions have been a topic of great interest in the last 30 years, and has not yet been clarified. In this review, we summarize the most important and well-understood effects of smoking in the gastrointestinal tract; and particularly, in intestinal inflammation, discussing available studies that have addressed the causes that would explain the opposite effects of smoking in CD and UC.