Biochemical and molecular characterization of the SBiP1 chaperone from Symbiodinium microadriaticum CassKB8 and light parameters that modulate its phosphorylation.

The coding and promoter region sequences from the BiP-like protein SBiP1 from Symbiodinium microadriaticum CassKB8 were obtained by PCR, sequenced and compared with annotated sequences. The nucleotides corresponding to the full sequence were correctly annotated and the main SBiP1 features determined at the nucleotide and amino acid level. The translated protein was organized into the typical domains of the BiP/HSP70 family including a signal peptide, a substrate- and a nucleotide-binding domain, and an ER localization sequence. Conserved motifs included a highly conserved Thr513 phosphorylation site and two ADP-ribosylation sites from eukaryotic BiP's. Molecular modeling showed the corresponding domain regions and main exposed post-translational target sites in its three-dimensional structure, which also closely matched Homo sapiens BiP further indicating that it indeed corresponds to a BiP/HSP70 family protein. The gene promoter region showed at least eight light regulation-related sequences consistent with the molecule being highly phosphorylated in Thr under dark conditions and dephosphorylated upon light stimuli. We tested light parameter variations that could modulate the light mediated phosphorylation effect and found that SBiP1 Thr dephosphorylation was only significantly detected after 15-30 min light stimulation. Such light-induced dephosphorylation was observed even when dichlorophenyl dimethyl urea, a photosynthesis inhibitor, was also present in the cells during the light stimulation. Dephosphorylation occurred indistinctly under red, yellow, blue or the full visible light spectra. In additon, it was observed at a light intensity of as low as 1 µmole photon m-2 s-1. Our results indicate that: a) SBiP1 is a chaperone belonging to the BiP/HSP70 family proteins; b) its light-modulated phosphorylation/dephosphorylation most likely functions as an activity switch for the chaperone; c) this light-induced modulation occurs relatively slow but is highly sensitive to the full spectrum of visible light; and d) the light induced Thr dephosphorylation is independent of photosynthetic activity in these cells.

Anxiety, depression, perceived executive function and sugar sweetened beverages: a causal mediation analysis in Mexican young adults.

There is the notion that dysregulation of executive function (EF), which disrupts behavior and cognitive processes, may explain the emotional impairment which leads to increasing sugar sweetened beverages (SSBs) intake. We aimed to test whether anxiety and depression mediate the association between self-reported problems in EF and sugar sweetened beverage intake in Mexican adults between 18-40 years. An open survey advertised as a 'mental health and sugar sweetened beverages study' was conducted, participants were recruited through Facebook ads. Males and females, between 18-40 years, able to read and write, and currently residing in Mexico were included. We analyzed data using causal mediation analysis with latent variables using a structural equation modelling framework. Significant indirect effects were found for somatic symptoms of depression (ß = 6.601, SE = 2.657, p < .05) and anxiety (ß = .679, SE =.334, p < .05). In depression model no significant direct effects of EF were found in the depression model, however they were found in the anxiety model (ß = 1.335 SE =.566, p < .05). Somatic symptoms of depression were a total mediator, and anxiety a partial mediator. The results suggest that EF increased the probability of emotional symptoms, which led to a higher consumption of SBBs.

The Resilience of Pseudomonas aeruginosa to Antibiotics and the Designing of Antimicrobial Peptides to Overcome Microbial Resistance.

Pseudomonas aeruginosa (P. aeruginosa) is a bacterium of medical concern known for its potential to persist in diverse environments due to its metabolic capacity. Its survival ability is linked to its relatively large genome of 5.5-7 Mbp, from which several genes are employed in overcoming conventional antibiotic treatments and promoting resistance. The worldwide prevalence of antibiotic-resistant clones of P. aeruginosa necessitates novel approaches to researching their multiple resistance mechanisms, such as the use of antimicrobial peptides (AMPs). In this review, we briefly discuss the epidemiology of the resistant strains of P. aeruginosa and then describe their resistance mechanisms. Next, we explain the biology of AMPs, enlist the present database platforms that describe AMPs, and discuss their usefulness and limitations in treating P. aeruginosa strains. Finally, we present 13 AMPs with theoretical action against P. aeruginosa, all of which we evaluated in silico in this work. Our results suggest that the AMPs we evaluated have a carpet-like mode of action with a membranolytic function in Gram-positive and Gramnegative bacteria, with a clear potential of synthesis for in vitro evaluation.

Deep Learning aplicado en imágenes fotoacústicas para la Identificación del cáncer de seno / Deep Learning Applied in Photoacoustic Images for the Identification of Breast Cancer

La Imagen Fotoacústica (PAI por sus siglas en inglés), es una modalidad de imagen híbrida que fusiona la iluminación óptica y la detección por ultrasonido. Debido a que los métodos de imágenes ópticas puras no pueden mantener una alta resolución, la capacidad de lograr imágenes de contraste óptico de alta resolución en tejidos biológicos hace que la fotoacústica (PA por sus siglas en inglés) sea una técnica prometedora para varias aplicaciones de imágenes clínicas. En la actualidad el Aprendizaje Profundo (Deep Learning) tiene el enfoque más reciente en métodos basados en la PAI, donde existe una gran cantidad de aplicaciones en análisis de imágenes, en especial en el área del campo biomédico, como lo es la adquisición, segmentación y reconstrucciones de imágenes de tomografía computarizada. Esta revisión describe las últimas investigaciones en PAI y un análisis sobre las técnicas y métodos basados en Deep Learning, aplicado en diferentes modalidades para el diagnóstico de cáncer de seno(AU)

Photoacoustic Imaging (PAI) is a hybrid imaging modality that combines optical illumination and ultrasound detection. Because pure optical imaging methods cannot maintain high resolution, the ability to achieve high resolution optical contrast images in biological tissues makes Photoacoustic (PA) a promising technique for various clinical imaging applications. At present, Deep Learning has the most recent approach of methods based on PAI where there are a large number of applications in image analysis especially in the area of ​​the biomedical field, such as acquisition, segmentation and reconstructions of computed tomography imaging. This review describes the latest research in PAI and an analysis of the techniques and methods based on Deep Learning applied in different modalities for the diagnosis of breast cancer(AU)

Efficacy of a multivitamin adherence program based on cognitive dissonance for bariatric patients: A randomized controlled trial.

BACKGROUND AND OBJECTIVES: Micronutrient deficiencies are common among bariatric patients; this study aimed to determine whether a cognitive dissonance-based virtual program improved adherence to multivitamin use in bariatric patients from northern Mexico. METHODS AND STUDY DESIGN: A randomized controlled trial of the supplementation strategy was conducted over three months. The participants were randomized to an intervention or waitlisted control group and received two psycho-educative and four cognitive dissonance virtual sessions. Multiple linear regression was used to determine standardized estimates of associations between the intervention and dependent variables. Two path analyses were evaluated considering baseline and post-test measurements. RESULTS: Intervention was associated with higher concentrations of Hb (ß=0.758, p<0.001), vitamin D (ß=0.577, p<0.001), iron (ß=0.523, p<0.001), folate (ß=0.494, p<0.01), calcium (ß=0.452, p<0.01), higher adherence (ß=0.467, p<0.001), and level of knowledge (ß=0.298, p<0.05. CONCLUSIONS: The dissonance-based intervention potentiated the level of supplementation adherence. A higher level of adherence was reflected in micronutrient concentrations, thus providing confirmation of intervention. Thus, support is found for a multidisciplinary clinical practice that enhances nutrition status after bariatric surgery for obesity.

Association between Stress and Metabolic Syndrome and its Mediating Factors in University Students.

OBJECTIVES: In this study, we evaluated the association between perceived stress and indicators of metabolic syndrome and how this association is mediated by sleep problems, unhealthy eating habits, and night eating syndrome, in addition to serum levels of ghrelin and cortisol in university students. METHODS: We recruited 192 students from a public university in Mexico. Weight, height, waist circumference and blood pressure were taken in accordance with standard protocols. Validated questionnaires were used to assess perceived stress, sleep quality and eating habits. Fasting blood samples were taken to measure ghrelin, cortisol, triglycerides, glucose and HDL-C. RESULTS: Path Analysis indicated direct positive effects of stress over PSQI (ß = 0.341) and NES (ß = 0.443); PSQI over NES (ß = 0.233) and NES over glucose (ß = 0.170), triglycerides over LDL-C (ß = 0.215), waist circumference over SBP (ß = 0.259). Likewise, standardized negative regression weights of PSQI over Diet Quality Index (ß = -0.239) and ghrelin concentrations (ß = -0.132), ghrelin over Diet Quality Index (ß = -0.188) and waist circumference (ß = -0.147). Diet Quality Index over triglycerides (ß = -0.184); sleep duration over systolic blood pressure (ß = -0.242); waist circumference over HDL-C (ß = -0.256). CONCLUSION: Psychological stress leads to increased indicators of MetS via decreased sleep quality, inadequate eating habits and eating behavior in university students.

Body Image, Anxiety, and Bulimic Behavior during Confinement Due to COVID-19 in Mexico.

BACKGROUND: The potential impact of the COVID-19 pandemic on weight, shape-related appearance behaviors (body image dissatisfaction), and bulimic symptoms in nonclinical participants is poorly evaluated. This study aimed to identify the relationship between labor status, confinement degree due to COVID-19, dissatisfaction with body image, and anxiety and to discover its effect on bulimic behavior in Mexican adults. METHODS: A cross-sectional study was conducted with a non-probabilistic sample of 276 participants via an online survey. Questions addressed their anxiety, body image dissatisfaction, and bulimic behavior. RESULTS: The path analysis showed direct effects on the confinement degree (ß = -0.157); of the labor situation (ß = -0.147) and gender (ß = 0.129) on anxiety; of dissatisfaction on bulimic behavior (ß = 0.443) and anxiety about bulimic behavior (ß = 0.184); and dissatisfaction (ß = 0.085). CONCLUSIONS: The confinement, gender, and labor status are predictors of anxiety, while anxiety and body dissatisfaction directly influence bulimic behavior.

Biochemical characterization of two chitinases from Bacillus cereus sensu lato B25 with antifungal activity against Fusarium verticillioides P03.

Bacterial chitinases are a subject of intense scientific research due to their biotechnological applications, particularly their use as biological pesticides against phytopathogenic fungi as a green alternative to avoid the use of synthetic pesticides. Bacillus cereus sensu lato B25 is a rhizospheric bacterium that is a proven antagonist of Fusarium verticillioides, a major fungal pathogen of maize. This bacterium produces two chitinases that degrade the fungal cell wall and inhibit its growth. In this work, we used a heterologous expression system to purify both enzymes to investigate their biochemical traits in terms of Km, Vmax, optimal pH and temperature. ChiA and ChiB work as exochitinases, but ChiB exhibited a dual substrate activity and it is also an endochitinase. In this work, the direct addition of these chitinases inhibited fungal conidial germination and therefore they may play a major role in the antagonism against F. verticillioides.

Assessment of Alcohol Consumption and Anxiety as Predictors of Risk of Anorexia and Bulimia in Non-Clinicals Samples.

The objective of this study is to assess the effect of alcohol consumption, anxiety, and food restriction before and after consuming alcohol and body image on the risk of anorexia and bulimia in college students from Tijuana, Baja California, through predictive statistical models. A quantitative, descriptive, and cross-sectional design and a non-probabilistic sample of 526 college students from Tijuana, Baja California, México were used. Application of the scales (with acceptable psychometric properties) was conducted in classrooms. Through path analyses, four models were found with adequate indicators of goodness of fit: (1) risk of anorexia in women [Chi Square (X2) = 5.34, p = 0.376, Adjusted Determination Coefficient (R2)= 0.250]; (2) anorexia risk for men (X2 = 13.067, p = 0.192, R2 = 0.058); (3) risk of bulimia in women (X2 = 3.358, p = 0.645, R2 = 0.202); and bulimia risk for men (X2 = 14.256, p = 0.075, R2 = 0.284). The findings provide empirical evidence for the food and alcohol disturbance model.

Transformation of the rhizospheric Bacillus cereus sensu lato B25 strain using a room-temperature electrocompetent cells preparation protocol.

Bacterial transformation is a crucial step in the genetic manipulation of a bacterium. However, Gram-positive bacteria are difficult to transform and consequently many different methodologies have been developed. Here, we examined the transformation efficiencies of an electroporation protocol by varying three main factors: the composition of the electroporation buffer, the strength of the electric pulse, and the composition of the recovery media. Overall, transformation efficiency was enhanced when we prepared the electrocompetent cells at room temperature instead of an ice-cold temperature. The protocol detailed in this work was demonstrated to be applicable to another B. cereus strain and two other Bacillus species, and has the potential to be applied to other undomesticated Gram-positive and/or rhizospheric bacterial strains that are difficult to transform using current methodologies.

Specific Features of the Hypothalamic Leptin Signaling Response to Cold Exposure Are Reflected in Peripheral Blood Mononuclear Cells in Rats and Ferrets.

Objectives: Cold exposure induces hyperphagia to counteract fat loss related to lipid mobilization and thermogenic activation. The aim of this study was investigate on the molecular mechanisms involved in cold-induced compensatory hyperphagia. Methods: We analyzed the effect of cold exposure on gene expression of orexigenic and anorexigenic peptides, and of leptin signaling-related genes in the hypothalamus of rats at different ages (1, 2, 4, and 6 months), as well as in ferrets. We also evaluated the potential of peripheral blood mononuclear cells to reflect hypothalamic molecular responses. Results: As expected, cold exposure induced hypoleptinemia in rats, which could be responsible for the increased ratio of orexigenic/anorexigenic peptides gene expression in the hypothalamus, mainly due to decreased anorexigenic gene expression, especially in young animals. In ferrets, which resemble humans more closely, cold exposure induced greater changes in hypothalamic mRNA levels of orexigenic genes. Despite the key role of leptin in food intake control, the effect of cold exposure on the expression of key hypothalamic leptin signaling cascade genes is not clear. In our study, cold exposure seemed to affect leptin signaling in 4-month-old rats (increased Socs3 and Lepr expression), likely associated with the smaller-increase in food intake and decreased body weight observed at this particular age. Similarly, cold exposed ferrets showed greater hypothalamic Socs3 and Stat3 gene expression. Interestingly, peripheral blood mononuclear cells (PBMC) mimicked the hypothalamic increase in Lepr and Socs3 observed in 4-month-old rats, and the increased Socs3 mRNA expression observed in ferrets in response to cold exposure. Conclusions: The most outstanding result of our study is that PBMC reflected the specific modulation of leptin signaling observed in both animal models, rats and ferrets, which points forwards PBMC as easily obtainable biological material to be considered as a potential surrogate tissue to perform further studies on the regulation of hypothalamic leptin signaling in response to cold exposure.

A web-based clinical decision support system for gestational diabetes: Automatic diet prescription and detection of insulin needs.

BACKGROUND: The growth of diabetes prevalence is causing an increasing demand in health care services which affects the clinicians' workload as medical resources do not grow at the same rate as the diabetic population. Decision support tools can help clinicians with the inspection of monitoring data, providing a preliminary analysis to ease their interpretation and reduce the evaluation time per patient. This paper presents Sinedie, a clinical decision support system designed to manage the treatment of patients with gestational diabetes. Sinedie aims to improve access to specialized healthcare assistance, to prevent patients from unnecessary displacements, to reduce the evaluation time per patient and to avoid gestational diabetes adverse outcomes. METHODS: A web-based telemedicine platform was designed to remotely evaluate patients allowing them to upload their glycaemia data at home directly from their glucose meter, as well as report other monitoring variables like ketonuria and compliance to dietary treatment. Glycaemia values, not tagged by patients, are automatically labelled with their associated meal by a classifier based on the Expectation Maximization clustering algorithm and a C4.5 decision tree learning algorithm. Two finite automata are combined to determine the patient's metabolic condition, which is analysed by a rule-based knowledge base to generate therapy adjustment recommendations. Diet recommendations are automatically prescribed and notified to the patients, whereas recommendations about insulin requirements are notified also to the physicians, who will decide if insulin needs to be prescribed. The system provides clinicians with a view where patients are prioritized according to their metabolic condition. A randomized controlled clinical trial was designed to evaluate the effectiveness and safety of Sinedie interventions versus standard care and its impact in the professionals' workload in terms of the clinician's time required per patient; number of face-to-face visits; frequency and duration of telematics reviews; patients' compliance to self-monitoring; and patients' satisfaction. RESULTS: Sinedie was clinically evaluated at "Parc Tauli University Hospital" in Spain during 17 months with the participation of 90 patients with gestational diabetes. Sinedie detected all situations that required a therapy adjustment and all the generated recommendations were safe. The time devoted by clinicians to patients' evaluation was reduced by 27.389% and face-to-face visits per patient were reduced by 88.556%. Patients reported to be highly satisfied with the system, considering it useful and trusting in being well controlled. There was no monitoring loss and, in average, patients measured their glycaemia 3.890 times per day and sent their monitoring data every 3.477days. CONCLUSIONS: Sinedie generates safe advice about therapy adjustments, reduces the clinicians' workload and helps physicians to identify which patients need a more urgent or more exhaustive examination and those who present good metabolic control. Additionally, Sinedie saves patients unnecessary displacements which contributes to medical centres' waiting list reduction.

Cold exposure down-regulates immune response pathways in ferret aortic perivascular adipose tissue.

Perivascular adipose tissue (PVAT) surrounds blood vessels and releases paracrine factors, such as cytokines, which regulate local inflammation. The inflammatory state of PVAT has an important role in vascular disease; a pro-inflammatory state has been related with atherosclerosis development, whereas an anti-inflammatory one is protective. Cold exposure beneficially affects immune responses and, could thus impact the pathogenesis of cardiovascular diseases. In this study, we investigated the effects of one-week of cold exposure at 4°C of ferrets on aortic PVAT (aPVAT) versus subcutaneous adipose tissue. Ferrets were used because of the similarity of their adipose tissues to those of humans. A ferret-specific Agilent microarray was designed to cover the complete ferret genome and global gene expression analysis was performed. The data showed that cold exposure altered gene expression mainly in aPVAT. Most of the regulated genes were associated with cell cycle, immune response and gene expression regulation, and were mainly down-regulated. Regarding the effects on immune response, cold acclimation decreased the expression of genes involved in antigen recognition and presentation, cytokine signalling and immune system maturation and activation. This immunosuppressive gene expression pattern was depot-specific, as it was not observed in the inguinal subcutaneous depot. Interestingly, this depression in immune response related genes was also evident in peripheral blood mononuclear cells (PBMC). In conclusion, these results reveal that cold acclimation produces an inhibition of immune response-related pathways in aPVAT, reflected in PBMC, indicative of an anti-inflammatory response, which can potentially be exploited for the enhancement or maintenance of cardiovascular health.

The intake of high-fat diets induces an obesogenic-like gene expression profile in peripheral blood mononuclear cells, which is reverted by dieting.

Peripheral blood mononuclear cells (PBMC) are increasingly used for nutrigenomic studies. In this study, we aimed to identify whether these cells could reflect the development of an obesogenic profile associated with the intake of high-fat (HF) diets. We analysed, by real-time RT-PCR, the dietary response of key genes related to lipid metabolism, obesity and inflammation in PBMC of control rats, rats fed a cafeteria or a commercial HF diet and rats fed a control diet after the intake of a cafeteria diet (post-cafeteria model). Cafeteria diet intake, which resulted in important overweight and related complications, altered the expressions of most of the studied genes in PBMC, evidencing the development of an obesogenic profile. Commercial HF diet, which produced metabolic alterations but in the absence of noticeably increased body weight, also altered PBMC gene expression, inducing a similar regulatory pattern as that observed for the cafeteria diet. Regulation of carnitine palmitoyltransferase I (Cpt1a) mRNA expression was of special interest; its expression reflected metabolic alterations related to the intake of both obesogenic diets (independently of increased body weight) even at an early stage as well as metabolic recovery in post-cafeteria animals. Thus, PBMC constitute an important source of biomarkers that reflect the increased adiposity and metabolic deregulation associated with the intake of HF diets. In particular, we propose an analysis of Cpt1a expression as a good biomarker to detect the early metabolic alterations caused by the consumption of hyperlipidic diets, and also as a marker of metabolic recovery associated to weight loss.

Biotin deprivation impairs mitochondrial structure and function and has implications for inherited metabolic disorders.

Certain inborn errors of metabolism result from deficiencies in biotin containing enzymes. These disorders are mimicked by dietary absence or insufficiency of biotin, ATP deficit being a major effect,whose responsible mechanisms have not been thoroughly studied. Here we show that in rats and cultured cells it is the result of reduced TCA cycle flow, partly due to deficient anaplerotic biotin-dependent pyruvate carboxylase. This is accompanied by diminished flow through the electron transport chain, augmented by deficient cytochrome c oxidase (complex IV) activity with decreased cytochromes and reduced oxidative phosphorylation. There was also severe mitochondrial damage accompanied by decrease of mitochondria, associated with toxic levels of propionyl CoA as shown by carnitine supplementation studies, which explains the apparently paradoxical mitochondrial diminution in the face of the energy sensor AMPK activation, known to induce mitochondria biogenesis. This idea was supported by experiments on AMPK knockout mouse embryonic fibroblasts (MEFs). The multifactorial ATP deficit also provides a plausible basis for the cardiomyopathy in patients with propionic acidemia, and other diseases.Additionally, systemic inflammation concomitant to the toxic state might explain our findings of enhanced IL-6, STAT3 and HIF-1α, associated with an increase of mitophagic BNIP3 and PINK proteins, which may further increase mitophagy. Together our results imply core mechanisms of energy deficit in several inherited metabolic disorders.

Gene expression of peripheral blood mononuclear cells is affected by cold exposure.

Because of the discovery of brown adipose tissue (BAT) in humans, there is increased interest in the study of induction of this thermogenic tissue as a basis to combat obesity and related complications. Cold exposure is one of the strongest stimuli able to activate BAT and to induce the appearance of brown-like (brite) adipocytes in white fat depots (browning process). We analyzed the potential of peripheral blood mononuclear cells (PBMCs) to reflect BAT and retroperitoneal white adipose tissue (rWAT) response to 1-wk cold acclimation (4°C) at different ages of rat development (1, 2, 4, and 6 mo). As expected, cold exposure increased fatty acid ß-oxidation capacity in BAT and rWAT (increased Cpt1a expression), explaining increased circulating nonesterified free fatty acids and decreased adiposity. Cold exposure increased expression of the key thermogenic gene, Ucp1, in BAT and rWAT, but only in 1-mo-old animals. Additionally, other brown/brite markers were affected by cold during the whole developmental period studied in BAT. However, in rWAT, cold exposure increased studied markers mainly at early age. PBMCs did not express Ucp1, but expressed other brown/brite markers, which were cold regulated. Of particular interest, PBMCs reflected adipose tissue-increased Cpt1a mRNA expression in response to cold (in older animals) and browning induction occurring in rWAT of young animals (1 mo) characterized by increased Cidea expression and by the appearance of a high number of multilocular CIDE-A positive adipocytes. These results provide evidence pointing to PBMCs as an easily obtainable biological material to be considered to perform browning studies with minimum invasiveness.

Sustained exposure to diets with an unbalanced macronutrient proportion alters key genes involved in energy homeostasis and obesity-related metabolic parameters in rats.

We have investigated the effects of long term intake of two unbalanced diets (rich in fat -HF- or protein -HP-) administered under isocaloric conditions to a control balanced diet (pair-feeding) to adult rats. Isocaloric intake of a HF diet did not affect the body weight but increased adiposity, liver-fat deposition, and induced insulin resistance. Gene expression changes in the liver and adipose tissue (increased lipolytic and decreased lipogenic gene expression) could try to compensate for increased adiposity. The HP diet decreased caloric intake, the body weight, the size of subcutaneous adipocytes, and circulating cholesterol. Higher insulin levels apparently not related to insulin resistance were observed. Changes at the gene expression level reflected an adaptation to lower diet carbohydrate content and to the use of amino acids as the energy source. The kidney size increased in HP-fed animals but serum creatinine was not affected. Circulating TNF-alpha levels were higher in both dietary models. Thus, a long-term increase in dietary fat proportion produces alterations related to metabolic syndrome even in the absence of increased body weight, whereas an increase in diet protein content reduces the body weight but alters metabolic parameters and kidney size which could be linked to an increased risk of suffering from different pathologies.

Patient-oriented Computerized Clinical Guidelines for Mobile Decision Support in Gestational Diabetes.

The risks associated with gestational diabetes (GD) can be reduced with an active treatment able to improve glycemic control. Advances in mobile health can provide new patient-centric models for GD to create personalized health care services, increase patient independence and improve patients' self-management capabilities, and potentially improve their treatment compliance. In these models, decision-support functions play an essential role. The telemedicine system MobiGuide provides personalized medical decision support for GD patients that is based on computerized clinical guidelines and adapted to a mobile environment. The patient's access to the system is supported by a smartphone-based application that enhances the efficiency and ease of use of the system. We formalized the GD guideline into a computer-interpretable guideline (CIG). We identified several workflows that provide decision-support functionalities to patients and 4 types of personalized advice to be delivered through a mobile application at home, which is a preliminary step to providing decision-support tools in a telemedicine system: (1) therapy, to help patients to comply with medical prescriptions; (2) monitoring, to help patients to comply with monitoring instructions; (3) clinical assessment, to inform patients about their health conditions; and (4) upcoming events, to deal with patients' personal context or special events. The whole process to specify patient-oriented decision support functionalities ensures that it is based on the knowledge contained in the GD clinical guideline and thus follows evidence-based recommendations but at the same time is patient-oriented, which could enhance clinical outcomes and patients' acceptance of the whole system.

Reversion to a control balanced diet is able to restore body weight and to recover altered metabolic parameters in adult rats long-term fed on a cafeteria diet.

The increased intake of fat-rich foods is one of the causes of the increasing incidence of obesity. However, there are controversial data on the reversibility of diet-induced obesity and its metabolic complications when adopting a control energy-balanced diet. Our aim was to evaluate the ability to reset not only body weight but also metabolic disorders caused by a highly palatable high fat diet, cafeteria diet, administered to adult rats, when replaced by a control diet (post-cafeteria model). Four-months of cafeteria diet-feeding produced important metabolic alterations in comparison to a commercial purified high fat diet: a rapid, drastic increase in body weight, adiposity and related complications such as insulin resistance, decreased glucose tolerance and development of hepatic steatosis. At gene level, decreased lipogenic and increased lipolytic gene expression in key energy homeostatic tissues as a physiological adaptation to increased fat intake was observed. In addition, fasting response of serum parameters and of key genes in lipid metabolism was impaired in cafeteria-fed animals. Contrary to what we have previously described if cafeteria diet is administered early in life, when administered to adult animals, its replacement with a balanced diet is able to restore body weight. Cafeteria diet withdrawal also allows recovery from metabolic damage, gene expression regulation and fasting response, the degree of which is dependent on the time of exposure to the cafeteria diet. In conclusion, adherence to an ad libitum intake of a balanced standard diet can enable the recovery of healthy status in animals which were previously exposed to an unhealthy cafeteria diet in adult age.

Decreased RB1 mRNA, protein, and activity reflect obesity-induced altered adipogenic capacity in human adipose tissue.

Retinoblastoma (Rb1) has been described as an essential player in white adipocyte differentiation in mice. No studies have been reported thus far in human adipose tissue or human adipocytes. We aimed to investigate the possible role and regulation of RB1 in adipose tissue in obesity using human samples and animal and cell models. Adipose RB1 (mRNA, protein, and activity) was negatively associated with BMI and insulin resistance (HOMA-IR) while positively associated with the expression of adipogenic genes (PPARγ and IRS1) in both visceral and subcutaneous human adipose tissue. BMI increase was the main contributor to adipose RB1 downregulation. In rats, adipose Rb1 gene expression and activity decreased in parallel to dietary-induced weight gain and returned to baseline with weight loss. RB1 gene and protein expression and activity increased significantly during human adipocyte differentiation. In fully differentiated adipocytes, transient knockdown of Rb1 led to loss of the adipogenic phenotype. In conclusion, Rb1 seems to play a permissive role for human adipose tissue function, being downregulated in obesity and increased during differentiation of human adipocytes. Rb1 knockdown findings further implicate Rb1 as necessary for maintenance of adipogenic characteristics in fully differentiated adipocytes.