Early Life Programming of Adipose Tissue Remodeling and Browning Capacity by Micronutrients and Bioactive Compounds as a Potential Anti-Obesity Strategy.

The early stages of life, especially the period from conception to two years, are crucial for shaping metabolic health and the risk of obesity in adulthood. Adipose tissue (AT) plays a crucial role in regulating energy homeostasis and metabolism, and brown AT (BAT) and the browning of white AT (WAT) are promising targets for combating weight gain. Nutritional factors during prenatal and early postnatal stages can influence the development of AT, affecting the likelihood of obesity later on. This narrative review focuses on the nutritional programming of AT features. Research conducted across various animal models with diverse interventions has provided insights into the effects of specific compounds on AT development and function, influencing the development of crucial structures and neuroendocrine circuits responsible for energy balance. The hormone leptin has been identified as an essential nutrient during lactation for healthy metabolic programming against obesity development in adults. Studies have also highlighted that maternal supplementation with polyunsaturated fatty acids (PUFAs), vitamin A, nicotinamide riboside, and polyphenols during pregnancy and lactation, as well as offspring supplementation with myo-inositol, vitamin A, nicotinamide riboside, and resveratrol during the suckling period, can impact AT features and long-term health outcomes and help understand predisposition to obesity later in life.

Glycosaminoglycan dermatan sulfate supplementation decreases diet-induced obesity and metabolic dysfunction in mice.

Glycosaminoglycans are complex carbohydrates used as nutraceuticals for diverse applications. We studied the potential of the glycosaminoglycan dermatan sulfate (DS) to counteract the development of diet-induced obesity (DIO) using obesity-prone mice fed a high-fat diet (HFD) as a model. Oral DS supplementation protected the animals against HFD-induced increases in whole-body adiposity, visceral fat mass, adipocyte size, blood glucose levels, insulin resistance, and pro-inflammatory lipids levels in brown adipose tissue (BAT) and the liver, where it largely counteracted the HFD-induced changes in the nonpolar metabolome. Protection against DIO in the DS-supplemented mice occurred despite higher energy intake and appeared to be associated with increased energy expenditure, higher uncoupling protein 1 expression in BAT, decreased BAT "whitening," and an enhanced channeling of fuel substrates toward skeletal muscle. This work is the first preclinical study to examine the anti-obesity activity of DS tested individually in vivo. The results support possible uses of DS as an active component in functional foods/supplements to manage obesity and associated metabolic diseases.

Study protocol: Identification and validation of integrative biomarkers of physical activity level and health in children and adolescents (INTEGRActiv).

Background: Physical activity (PA) provides health benefits across the lifespan and improves many established cardiovascular risk factors that have a significant impact on overall mortality. However, discrepancies between self-reported and device-based measures of PA make it difficult to obtain consistent results regarding PA and its health effects. Moreover, PA may produce different health effects depending on the type, intensity, duration, and frequency of activities and individual factors such as age, sex, body weight, early life conditions/exposures, etc. Appropriate biomarkers relating the degree of PA level with its effects on health, especially in children and adolescents, are required and missing. The main objective of the INTEGRActiv study is to identify novel useful integrative biomarkers of PA and its effects on the body health in children and adolescents, who represent an important target population to address personalized interventions to improve future metabolic health. Methods/design: The study is structured in two phases. First, biomarkers of PA and health will be identified at baseline in a core cohort of 180 volunteers, distributed into two age groups: prepubertal (n = 90), and postpubertal adolescents (n = 90). Each group will include three subgroups (n = 30) with subjects of normal weight, overweight, and obesity, respectively. Identification of new biomarkers will be achieved by combining physical measures (PA and cardiorespiratory and muscular fitness, anthropometry) and molecular measures (cardiovascular risk factors, endocrine markers, cytokines and circulating miRNA in plasma, gene expression profile in blood cells, and metabolomics profiling in plasma). In the second phase, an educational intervention and its follow-up will be carried out in a subgroup of these subjects (60 volunteers), as a first validation step of the identified biomarkers. Discussion: The INTEGRActiv study is expected to provide the definition of PA and health-related biomarkers (PA-health biomarkers) in childhood and adolescence. It will allow us to relate biomarkers to factors such as age, sex, body weight, sleep behavior, dietary factors, and pubertal status and to identify how these factors quantitatively affect the biomarkers' responses. Taken together, the INTEGRActiv study approach is expected to help monitor the efficacy of interventions aimed to improve the quality of life of children/adolescents through physical activity. Clinical Trial Registration: ClinicalTrials.gov, Identifier NCT05907785.

Increased mRNA Levels of ADAM17, IFITM3, and IFNE in Peripheral Blood Cells Are Present in Patients with Obesity and May Predict Severe COVID-19 Evolution.

Gene expression patterns in blood cells from SARS-CoV-2 infected individuals with different clinical phenotypes and body mass index (BMI) could help to identify possible early prognosis factors for COVID-19. We recruited patients with COVID-19 admitted in Hospital Universitari Son Espases (HUSE) between March 2020 and November 2021, and control subjects. Peripheral blood cells (PBCs) and plasma samples were obtained on hospital admission. Gene expression of candidate transcriptomic biomarkers in PBCs were compared based on the patients' clinical status (mild, severe and critical) and BMI range (normal weight, overweight, and obesity). mRNA levels of ADAM17, IFITM3, IL6, CXCL10, CXCL11, IFNG and TYK2 were increased in PBCs of COVID-19 patients (n = 73) compared with controls (n = 47), independently of sex. Increased expression of IFNE was observed in the male patients only. PBC mRNA levels of ADAM17, IFITM3, CXCL11, and CCR2 were higher in those patients that experienced a more serious evolution during hospitalization. ADAM17, IFITM3, IL6 and IFNE were more highly expressed in PBCs of patients with obesity. Interestingly, the expression pattern of ADAM17, IFITM3 and IFNE in PBCs was related to both the severity of COVID-19 evolution and obesity status, especially in the male patients. In conclusion, gene expression in PBCs can be useful for the prognosis of COVID-19 evolution.

Nicotinamide Riboside Supplementation to Suckling Male Mice Improves Lipid and Energy Metabolism in Skeletal Muscle and Liver in Adulthood.

Nicotinamide riboside, an NAD+ precursor, has been attracting a lot of attention in recent years due to its potential benefits against multiple metabolic complications and age-related disorders related to NAD+ decline in tissues. The metabolic programming activity of NR supplementation in early-life stages is much less known. Here, we studied the long-term programming effects of mild NR supplementation during the suckling period on lipid and oxidative metabolism in skeletal muscle and liver tissues using an animal model. Suckling male mice received a daily oral dose of NR or vehicle (water) from day 2 to 20 of age, were weaned at day 21 onto a chow diet, and at day 90 were distributed to either a high-fat diet (HFD) or a normal-fat diet for 10 weeks. Compared to controls, NR-treated mice were protected against HFD-induced triacylglycerol accumulation in skeletal muscle and displayed lower triacylglycerol levels and steatosis degree in the liver and distinct capacities for fat oxidation and decreased lipogenesis in both tissues, paralleling signs of enhanced sirtuin 1 and AMP-dependent protein kinase signaling. These pre-clinical findings suggest that mild NR supplementation in early postnatal life beneficially impacts lipid and energy metabolism in skeletal muscle and liver in adulthood, serving as a potential preventive strategy against obesity-related disorders characterized by ectopic lipid accumulation.

Clinical algorithms for management of fetal heart rate abnormalities during labour.

OBJECTIVE: To construct algorithms with a sequential decision analysis pathway for monitoring of the fetal heart rate and managing fetal heart rate bradycardia, late decelerations and tachycardia during labour. POPULATION: Low-risk pregnant women in labour with singleton cephalic term pregnancies. SETTING: Institutional births in low- and middle-income countries. SEARCH STRATEGY: We sought relevant published clinical algorithms, guidelines and randomised trials/reviews by searching the Cochrane Library, PubMed and Google on the terms: "fetal AND heart AND rate AND algorithm AND (labour OR intrapartum)", up to March 2020. CASE SCENARIOS: The two scenarios included were fetal heart rate bradycardia or late decelerations (potentially related to uterine rupture, placental abruption, cord prolapse, maternal hypotension, uterine hyperstimulation or unexplained) and fetal heart rate tachycardia (potentially related to maternal hyperthermia, infection, dehydration or unexplained). The algorithms provide pathways for definition, assessment, diagnosis, interventions to correct the abnormalities and ongoing monitoring leading to mode of birth, and linking to other algorithms in the series. CONCLUSIONS: The algorithms provide a framework for monitoring and managing fetal heart rate bradycardia, late decelerations and tachycardia during labour. We emphasise the inherent diagnostic inaccuracy of fetal heart rate monitoring, the tendency to over-diagnose fetal compromise, the need to consider fetal heart rate information in the context of other clinical features and the need to engage in informed, shared, family-centred decision-making. We note the need for further research on methods of fetal assessment during labour including clinical fetal arousal testing and the rapid biophysical profile test. TWEETABLE ABSTRACT: Decision analysis algorithms for fetal bradycardia, late decelerations and tachycardia highlight diagnostic limitations.

Constructing evidence-based clinical intrapartum care algorithms for decision-support tools.

AIM: To describe standardised iterative methods used by a multidisciplinary group to develop evidence-based clinical intrapartum care algorithms for the management of uneventful and complicated labours. POPULATION: Singleton, term pregnancies considered to be at low risk of developing complications at admission to the birthing facility. SETTING: Health facilities in low- and middle-income countries. SEARCH STRATEGY: Literature reviews were conducted to identify standardised methods for algorithm development and examples from other fields, and evidence and guidelines for intrapartum care. Searches for different algorithm topics were last updated between January and October 2020 and included a combination of terms such as 'labour', 'intrapartum', 'algorithms' and specific topic terms, using Cochrane Library and MEDLINE/PubMED, CINAHL, National Guidelines Clearinghouse and Google. CASE SCENARIOS: Nine algorithm topics were identified for monitoring and management of uncomplicated labour and childbirth, identification and management of abnormalities of fetal heart rate, liquor, uterine contractions, labour progress, maternal pulse and blood pressure, temperature, urine and complicated third stage of labour. Each topic included between two and four case scenarios covering most common deviations, severity of related complications or critical clinical outcomes. CONCLUSIONS: Intrapartum care algorithms provide a framework for monitoring women, and identifying and managing complications during labour and childbirth. These algorithms will support implementation of WHO recommendations and facilitate the development by stakeholders of evidence-based, up to date, paper-based or digital reminders and decision-support tools. The algorithms need to be field tested and may need to be adapted to specific contexts. TWEETABLE ABSTRACT: Evidence-based intrapartum care clinical algorithms for a safe and positive childbirth experience.

Saving time in the radiotherapy procedures for COVID-19 pneumonia treatment. A single-institution experience

Background The use of low dose radiotherapy (LD-RT) for the treatment of COVID-19 pneumonia is supported by biological rationale for its immunomodulatory effect. Some institutions have started to treat these patients showing encouraging results. To shorten procedure times is crucial for the comfort of symptomatic patients receiving respiratory support and to optimize institutional facilities. Patients and methods At our institution, LD-RT is offered to hospitalized patients with COVID-19 pneumonia and signs of early cytokine-released syndrome on behalf of a multicenter study. We designed a coordinated process flow starting from the patient transfer to the simulation CT-scan (first-step), to the end of the LD-RT treatment (last step). The times spent on each step of the process flow were evaluated. Results Mean age of treated patients was 83 (72–91) years-old. The timing parameters of the first 10 consecutive patients were analyzed. Except for the first (dummy run), patients were managed from the first to the last step in a median of 38 min (25–58, SD 10.67). The most time-consuming sub-process was the contouring of the treatment volumes and dosimetry. Conclusions LD-RT is not only an encouraging option for COVID-19 pneumonia patients, but a convenient and feasible procedure if performed in a coordinated way by reducing procedure times (AU)

Protective Effects of Individual and Combined Low Dose Beta-Carotene and Metformin Treatments against High-Fat Diet-Induced Responses in Mice.

Anti-obesity activity has been reported for beta-carotene (BC) supplementation at high doses and metformin (MET). We studied whether BC treatment at a closer to dietary dose and MET treatment at a lower than therapeutic dose are effective in ameliorating unwanted effects of an obesogenic diet and whether their combination is advantageous. Obesity-prone mice were challenged with a high-fat diet (HFD, 45% energy as fat) for 4 weeks while receiving a placebo or being treated orally with BC (3 mg/kg/day), MET (100 mg/kg/day), or their combination (BC+MET); a fifth group received a placebo and was kept on a normal-fat diet (10% energy as fat). HFD-induced increases in body weight gain and inguinal white adipose tissue (WAT) adipocyte size were attenuated maximally or selectively in the BC+MET group, in which a redistribution towards smaller adipocytes was noted. Cumulative energy intake was unaffected, yet results suggested increased systemic energy expenditure and brown adipose tissue activation in the treated groups. Unwanted effects of HFD on glucose control and insulin sensitivity were attenuated in the treated groups, especially BC and BC+MET, in which hepatic lipid content was also decreased. Transcriptional analyses suggested effects on skeletal muscle and WAT metabolism could contribute to better responses to the HFD, especially in the MET and BC+MET groups. The results support the benefits of the BC+MET cotreatment.

Characterization and Outcomes of SARS-CoV-2 Infection in Patients with Sarcoidosis.

To analyze the clinical characteristics and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with sarcoidosis from a large multicenter cohort from Southern Europe and to identify the risk factors associated with a more complicated infection. We searched for patients with sarcoidosis presenting with SARS-CoV-2 infection (defined according to the European Centre for Disease Prevention and Control guidelines) among those included in the SarcoGEAS Registry, a nationwide, multicenter registry of patients fulfilling the American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and Other Granulomatous Disorders 1999 classification criteria for sarcoidosis. A 2:1 age-sex-matched subset of patients with sarcoidosis without SARS-CoV-2 infection was selected as control population. Forty-five patients with SARS-CoV-2 infection were identified (28 women, mean age 55 years). Thirty-six patients presented a symptomatic SARS-CoV-2 infection and 14 were hospitalized (12 required supplemental oxygen, 2 intensive care unit admission and 1 mechanical ventilation). Four patients died due to progressive respiratory failure. Patients who required hospital admission had an older mean age (64.9 vs. 51.0 years, p = 0.006), a higher frequency of baseline comorbidities including cardiovascular disease (64% vs. 23%, p = 0.016), diabetes mellitus (43% vs. 13%, p = 0.049) and chronic liver/kidney diseases (36% vs. 0%, p = 0.002) and presented more frequently fever (79% vs. 35%, p = 0.011) and dyspnea (50% vs. 3%, p = 0.001) in comparison with patients managed at home. Age- and sex-adjusted multivariate analysis identified the age at diagnosis of SARS-Cov-2 infection as the only independent variable associated with hospitalization (adjusted odds ratio 1.18, 95% conficence interval 1.04-1.35). A baseline moderate/severe pulmonary impairment in function tests was associated with a higher rate of hospitalization but the difference was not statistically significant (50% vs. 23%, p = 0.219). A close monitoring of SARS-CoV-2 infection in elderly patients with sarcoidosis, especially in those with baseline cardiopulmonary diseases and chronic liver or renal failure, is recommended. The low frequency of severe pulmonary involvement in patients with sarcoidosis from Southern Europe may explain the weak prognostic role of baseline lung impairment in our study, in contrast to studies from other geographical areas.

Mechanistic aspects of carotenoid health benefits - where are we now?

Dietary intake and tissue levels of carotenoids have been associated with a reduced risk of several chronic diseases, including cardiovascular diseases, type 2 diabetes, obesity, brain-related diseases and some types of cancer. However, intervention trials with isolated carotenoid supplements have mostly failed to confirm the postulated health benefits. It has thereby been speculated that dosing, matrix and synergistic effects, as well as underlying health and the individual nutritional status plus genetic background do play a role. It appears that our knowledge on carotenoid-mediated health benefits may still be incomplete, as the underlying mechanisms of action are poorly understood in relation to human relevance. Antioxidant mechanisms - direct or via transcription factors such as NRF2 and NF-κB - and activation of nuclear hormone receptor pathways such as of RAR, RXR or also PPARs, via carotenoid metabolites, are the basic principles which we try to connect with carotenoid-transmitted health benefits as exemplified with described common diseases including obesity/diabetes and cancer. Depending on the targeted diseases, single or multiple mechanisms of actions may play a role. In this review and position paper, we try to highlight our present knowledge on carotenoid metabolism and mechanisms translatable into health benefits related to several chronic diseases.

Saving time in the radiotherapy procedures for COVID-19 pneumonia treatment. A single-institution experience.

BACKGROUND: The use of low dose radiotherapy (LD-RT) for the treatment of COVID-19 pneumonia is supported by biological rationale for its immunomodulatory effect. Some institutions have started to treat these patients showing encouraging results. To shorten procedure times is crucial for the comfort of symptomatic patients receiving respiratory support and to optimize institutional facilities. PATIENTS AND METHODS: At our institution, LD-RT is offered to hospitalized patients with COVID-19 pneumonia and signs of early cytokine-released syndrome on behalf of a multicenter study. We designed a coordinated process flow starting from the patient transfer to the simulation CT-scan (first-step), to the end of the LD-RT treatment (last step). The times spent on each step of the process flow were evaluated. RESULTS: Mean age of treated patients was 83 (72-91) years-old. The timing parameters of the first 10 consecutive patients were analyzed. Except for the first (dummy run), patients were managed from the first to the last step in a median of 38 min (25-58, SD 10.67). The most time-consuming sub-process was the contouring of the treatment volumes and dosimetry. CONCLUSIONS: LD-RT is not only an encouraging option for COVID-19 pneumonia patients, but a convenient and feasible procedure if performed in a coordinated way by reducing procedure times.

Long-term programming of skeletal muscle and liver lipid and energy metabolism by resveratrol supplementation to suckling mice.

Metabolic programming by dietary chemicals consumed in early life stages is receiving increasing attention. We here studied long-term effects of mild resveratrol (RSV) supplementation during lactation on muscular and hepatic lipid metabolism in adulthood. Newborn male mice received RSV or vehicle from day 2-20 of age, were weaned onto a chow diet on day 21, and were assigned to either a high-fat diet (HFD) or a normal-fat diet on day 90 of age for 10 weeks. RSV-treated mice showed in adulthood protection against HFD-induced triacylglycerol accumulation in skeletal muscle, enhanced muscular capacities for fat oxidation and mitochondria activity, signs of enhanced sirtuin 1 and AMP-dependent protein kinase signaling in muscle, and increased fat oxidation capacities and a decreased capacity for lipogenesis in liver compared with controls. Thus, RSV supplementation in early postnatal life may help preventing later diet-related disorders linked to ectopic lipid accumulation in muscle and liver tissues.

Colaboración interprofesional en las sesiones clínicas conjuntas en una Unidad de Cuidados Intensivos: percepciones de enfermeras y médicos / Interprofessional collaboration in joint clinical sessions in an intensive care unit: Perceptions of nurses and physicians

INTRODUCCIÓN: La práctica colaborativa es un proceso interpersonal en el que interactúan diferentes disciplinas profesionales que comparten objetivos, participan en la toma de decisiones y proporcionan una atención integral y de calidad. Las sesiones clínicas conjuntas ofrecen la oportunidad de interactuar y mejorar la comunicación entre profesionales y optimizar los resultados en la práctica. OBJETIVOS: Explorar las percepciones de enfermeras y médicos sobre la práctica colaborativa en las sesiones clínicas conjuntas en Unidad de Cuidados Intensivos. MÉTODO: Estudio de análisis crítico del discurso, a través de entrevistas semiestructuradas y diarios de campo, usando como referencial teórico los conceptos de Campus, Capital y Habitus planteados por Pierre Bourdieu. PARTICIPANTES: enfermeras y médicos de una Unidad de Cuidados Intensivos, reclutados mediante muestreo intencional. Las entrevistas fueron codificadas por todos los investigadores, posteriormente se hizo una puesta en común y se interpretaron los datos en el contexto en el que fueron recogidos. RESULTADOS: Emergieron 5 categorías: 1) Concepto: integración e implicación de un equipo con aportaciones colectivas y objetivos compartidos, 2) importancia: aumenta la seguridad del paciente, mejora la satisfacción de los profesionales y la calidad de atención, 3) factores: la ausencia de cultura de organizaciones dificulta la práctica colaborativa, 4) rol: la enfermera percibió que tiene un rol pasivo (oyente) durante las sesiones clínicas y el médico un papel activo (comunicador), y 5) estrategias de mejora: establecer horario y conciliación de tareas interprofesionales. CONCLUSIONES: Existe una necesidad de empoderamiento en la participación activa por parte de las enfermeras en las sesiones clínicas conjuntas. El colectivo médico debe tener más en cuenta las percepciones humanísticas que pueden aportar otros profesionales. Fomentar la escucha activa en los médicos, mejorar la comunicación real por parte de las enfermeras y generar un espacio donde impere el respeto y la confianza, favorecerán la dinámica de trabajo interprofesional

INTRODUCTION: Collaborative practice is an interpersonal process in which different professional disciplines that share objectives interact, participate in decision-making and provide comprehensive and quality care. The joint clinical sessions offer the opportunity to interact and improve communication between professionals and optimise results in practice. AIM: To explore perceptions of nurses and physicians about collaborative practice in joint Intensive Care Unit clinical sessions. METHOD: Critical discourse analysis, through semi-structured interviews and field journals, using as theoretical reference the concepts of Campus, Capital and Habitus by Pierre Bourdieu. PARTICIPANTS: nurses and physicians of the Intensive Care Unit, who were recruited by intentional sampling. Semi-structured interviews were conducted and a discourse analysis was then performed. The interviews were coded by all the researchers, then shared and the data were interpreted in the context in which they were collected. RESULTS: Five categories emerged: 1) Concept: integration and involvement of a team with collective contributions and shared objectives, 2) importance: it increases patient safety, improves professional satisfaction and quality of care, 3) factors: the absence of culture organisations make collaborative practice difficult, 4) role: the nurse perceived that she plays a passive role (listener) during the clinical rounds and the physician an active role (communicator) and, 5) improvement strategies: to establish a schedule and balance interprofessional tasks. CONCLUSIONS: There is a need for empowerment in active participation by nursing staff in joint clinical sessions. The medical group should be more aware of the humanistic perceptions that other professionals can bring. Encouraging active listening in physicians, improving real communication by nursing staff and generating a space where respect and confidence prevail, will favour interprofessional work dynamics

Interprofessional collaboration in joint clinical sessions in an intensive care unit: Perceptions of nurses and physicians. / Colaboración interprofesional en las sesiones clínicas conjuntas en una Unidad de Cuidados Intensivos: percepciones de enfermeras y médicos.

INTRODUCTION: Collaborative practice is an interpersonal process in which different professional disciplines that share objectives interact, participate in decision-making and provide comprehensive and quality care. The joint clinical sessions offer the opportunity to interact and improve communication between professionals and optimise results in practice. AIM: To explore perceptions of nurses and physicians about collaborative practice in joint Intensive Care Unit clinical sessions. METHOD: Critical discourse analysis, through semi-structured interviews and field journals, using as theoretical reference the concepts of Campus, Capital and Habitus by Pierre Bourdieu. PARTICIPANTS: nurses and physicians of the Intensive Care Unit, who were recruited by intentional sampling. Semi-structured interviews were conducted and a discourse analysis was then performed. The interviews were coded by all the researchers, then shared and the data were interpreted in the context in which they were collected. RESULTS: Five categories emerged: 1) Concept: integration and involvement of a team with collective contributions and shared objectives, 2) importance: it increases patient safety, improves professional satisfaction and quality of care, 3) factors: the absence of culture organisations make collaborative practice difficult, 4) role: the nurse perceived that she plays a passive role (listener) during the clinical rounds and the physician an active role (communicator) and, 5) improvement strategies: to establish a schedule and balance interprofessional tasks. CONCLUSIONS: There is a need for empowerment in active participation by nursing staff in joint clinical sessions. The medical group should be more aware of the humanistic perceptions that other professionals can bring. Encouraging active listening in physicians, improving real communication by nursing staff and generating a space where respect and confidence prevail, will favour interprofessional work dynamics.

Carotenoids and carotenoid conversion products in adipose tissue biology and obesity: Pre-clinical and human studies.

Antiobesity activities of carotenoids and carotenoid conversion products (CCPs) have been demonstrated in pre-clinical studies, and mechanisms behind have begun to be unveiled, thus suggesting these compounds may help obesity prevention and management. The antiobesity action of carotenoids and CCPs can be traced to effects in multiple tissues, notably the adipose tissues. Key aspects of the biology of adipose tissues appear to be affected by carotenoid and CCPs, including adipogenesis, metabolic capacities for energy storage, release and inefficient oxidation, secretory function, and modulation of oxidative stress and inflammatory pathways. Here, we review the connections of carotenoids and CCPs with adipose tissue biology and obesity as revealed by cell and animal intervention studies, studies addressing the role of endogenous retinoid metabolism, and human epidemiological and intervention studies. We also consider human genetic variability influencing carotenoid and vitamin A metabolism, particularly in adipose tissues, as a potentially relevant aspect towards personalization of dietary recommendations to prevent or manage obesity and optimize metabolic health. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.

DNA Methylation Changes are Associated with the Programming of White Adipose Tissue Browning Features by Resveratrol and Nicotinamide Riboside Neonatal Supplementations in Mice.

Neonatal supplementation with resveratrol (RSV) or nicotinamide riboside (NR) programs in male mice brown adipocyte-like features in white adipose tissue (WAT browning) together with improved metabolism in adulthood. We tested the involvement in this programming of long-term epigenetic changes in two browning-related genes that are overexpressed in WAT of supplemented mice, Slc27a1 and Prdm16. Suckling mice received orally the vehicle, RSV or NR from postnatal days 2-to-20. After weaning (d21) onto a chow diet, male mice were habituated to a normal-fat diet (NFD) starting d75, and split on d90 into continuation on the NFD or switching to a high-fat diet (HFD) until euthanization on d164. CpG methylation by bisulfite-sequencing was analyzed on inguinal WAT. Both treatments modified methylation marks in Slc27a1 and Prdm16 and the HFD-dependent dynamics of these marks in the adult WAT, with distinct and common effects. The treatments also affected gene expression of de novo DNA methylases in WAT of young animals (euthanized at d35 in independent experiments). Studies in 3T3-L1 adipocytes indicated the direct effects of RSV and NR on the DNA methylation machinery and favoring browning features. The results support epigenetic effects being involved in WAT programming by neonatal RSV or NR supplementation in male mice.

Adjuvant therapy for true ampullary cancer: a systematic review.

BACKGROUND: Given the lack of evidence on the best adjuvant approach, this review closely examines optimal adjuvant management for resected true ampullary cancer and its histological subtypes. MATERIALS AND METHODS: A comprehensive literature search of PubMed was performed to identify studies on resected true ampullary cancers, published between January 2010 and December 2018. Data including the use of radiation, chemotherapy or chemoradiation and the outcomes were extracted. RESULTS: A total of 116 records were identified, of which 65 screened were selected. Finally, nine studies were included. Only two of the studies reported separately the outcomes of pancreatobiliary and intestinal subtypes. Patients in the selected studies were treated with a pancreaticoduodenectomy with negative margins. Patients treated with adjuvant therapy were more likely to be pT3-4 and have positive nodes; median survival ranged from 30 to 47 months. A significant benefit for adjuvant treatment was observed in four of the studies, restricted to patients at stage IIB or higher. Likewise, patients with positive nodes may have a longer median survival with adjuvant chemoradiation compared to observation. CONCLUSIONS: The present review suggests a benefit for adjuvant treatment for patients with locally advanced tumors. Randomized trials are needed to ascertain the topic, as well as studies reporting toxicity and quality of life of resected true ampullary cancer patients.