Protein Ingredient Quality within Infant Formulas Impacts Plasma Amino Acid Concentrations in Neonatal Minipiglets.

BACKGROUND: Infant formulas (IFs), the only adequate substitute to human milk, are complex matrices that require numerous ingredients and processing steps that may impact protein digestion and subsequent amino acid (AA) absorption. OBJECTIVES: The objective was to understand the impact of the protein ingredient quality within IFs on postprandial plasma AA profiles. METHODS: Four isonitrogenous and isocaloric IFs were produced at a semi-industrial scale using whey proteins from different origins (cheese compared with ideal whey) and denaturation levels (IF-A, -B, -C), and caseins with different supramolecular organizations (IF-C, -D). Ten Yucatan minipiglets (12- to 27-d-old) were used as a human infant model and received each IF for 3 d according to a Williams Latin square followed by a 2-d wash-out period. Jugular plasma was regularly sampled from 10 min preprandial to 4 h postprandial on the third day to measure free AAs, urea, insulin, and glucose concentrations. Data were statistically analyzed using a mixed linear model with diet (IFs), time, and sex as fixed factors and piglet as random factor. RESULTS: IFs made with cheese whey (IF-A and -B) elicited significantly higher plasma total and essential AA concentrations than IFs made with ideal whey (IF-C and -D), regardless of the pre- and postprandial times. Most of the differences observed postprandially were explained by AA homeostasis modifications. IFs based on cheese whey induced an increased plasma concentration of Thr due to both a higher Thr content in these IFs and a Thr-limiting degrading capability in piglets. The use of a nonmicellar casein ingredient led to reduced plasma content of AA catabolism markers (IF-D compared with IF-C). CONCLUSIONS: Overall, our results highlight the importance of the protein ingredient quality (composition and structure) within IFs on neonatal plasma AA profiles, which may further impact infant protein metabolism.

The Yucatan minipig model: A new preclinical model of malnutrition in obese patients with acute or chronic diseases.

BACKGROUND & AIMS: Malnutrition can develop in patients with obesity suffering from acute or chronic illness or after obesity surgery, promoting sarcopenic obesity. A better understanding of this pathophysiology and the development of new therapeutics for chronic diseases, that are often complicated with malnutrition and obesity, justify the development of new animal experimental models close to the human physiology. This study aims to characterize the effects of obesity and underfeeding on Yucatan obese minipigs, assessing its validity as a preclinical model for obesity-related malnutrition. METHODS: Sixteen 30-month-old Yucatan minipigs were divided into two groups for 8 weeks: a standard diet group (ST, n = 5) and an obesogenic diet group (OB, n = 11). After 8 weeks, the OB group was further divided into two sub-groups: a standard diet group (OB-ST, n = 5) and a low-calorie/low-protein diet group (OB-LC/LP, n = 6) for 8 weeks. Body composition by CT-Scan and blood parameters were monitored, and trapezius muscle biopsies were collected to analyse signaling pathways involved in protein turnover and energy metabolism. RESULTS: At W8, OB-ST animals exhibited significantly higher body weight (+37.7%, p = 0.03), muscle mass (+24.9%, p = 0.02), and visceral fat (+192.0%, p = 0.03) compared to ST. Trapezius cross sectional area (CSA) normalized to body weight was lower in OB-ST animals (-15.02%, p = 0.017). At W16, no significant changes were observed in protein turnover markers, although REDD1 increased in OB-ST (96.4%, p = 0.02). After 8 weeks of low-caloric/low protein diet, OB-LC/LP showed decreased body weight (-9.8%, p = 0.03), muscle mass (-6.5%, p = 0.03), and visceral fat (-41.5%, p = 0.03) compared to OB-ST animals. Trapezius fiber CSA significantly decreased in OB-LC/LP (-36.1%, p < 0.0001) and normalized to body weight (-25.4%, p < 0.0001), combined to higher ubiquitinated protein content (+38.3%, p = 0.02). CONCLUSION: Our data support that the Yucatan minipig model mimics nutritional and skeletal muscle phenotypes observed in obese patients, with or without protein-energy malnutrition. It also reproduces muscle atrophy observed in chronic diseases or post-obesity surgery, making it a promising preclinical model for obesity-related malnutrition.

Casein structures differently affect postprandial amino acid delivery through their intra-gastric clotting properties.

We aimed to assess if casein structure affects its digestion and its subsequent amino acid delivery kinetic. Higher nitrogen levels were recovered in dialysates after in vitro digestions of sodium caseinate (SC, formed of small aggregates) compared to micellar casein (MC, native form of casein) and calcium caseinate (CC, intermediate structure). Likewise, plasma indispensable amino-acid concentration peak was higher after SC compared to MC or CC ingestion in healthy volunteers in a randomized, double blind, cross-over study. In pigs, gamma-scintigraphy using labelled meals revealed that SC was mainly localized in the proximal part of the stomach whereas MC was distributed in the whole gastric cavity. Caseins were found in both solid and liquid phases and partly hydrolyzed casein in the solid phase shortly after SC drink ingestion. These data support the concept of slow (MC) and rapid (SC) casein depending of casein structure, likely due to their intra-gastric clotting properties.

Exploration of fMRI brain responses to oral sucrose after Roux-en-Y gastric bypass in obese yucatan minipigs in relationship with microbiota and metabolomics profiles.

BACKGROUND & AIMS: In most cases, Roux-en-Y gastric bypass (RYGBP) is an efficient intervention to lose weight, change eating behavior and improve metabolic outcomes in obese patients. We hypothesized that weight loss induced by RYGBP in obese Yucatan minipigs would induce specific modifications of the gut-brain axis and neurocognitive responses to oral sucrose stimulation in relationship with food intake control. METHODS: An integrative study was performed after SHAM (n = 8) or RYGBP (n = 8) surgery to disentangle the physiological, metabolic and neurocognitive mechanisms of RYGBP. BOLD fMRI responses to sucrose stimulations at different concentrations, brain mRNA expression, cecal microbiota, and plasma metabolomics were explored 4 months after surgery and integrated with WGCNA analysis. RESULTS: We showed that weight loss induced by RYGBP or SHAM modulated differently the frontostriatal responses to oral sucrose stimulation, suggesting a different hedonic treatment and inhibitory control related to palatable food after RYGBP. The expression of brain genes involved in the serotoninergic and cannabinoid systems were impacted by RYGBP. Cecal microbiota was deeply modified and many metabolite features were differentially increased in RYGBP. Data integration with WGCNA identified interactions between key drivers of OTUs and metabolites features linked to RYGBP. CONCLUSION: This longitudinal study in the obese minipig model illustrates with a systemic and integrative analysis the mid-term consequences of RYGBP on brain mRNA expression, cecal microbiota and plasma metabolites. We confirmed the impact of RYGBP on functional brain responses related to food reward, hedonic evaluation and inhibitory control, which are key factors for the success of anti-obesity therapy and weight loss maintenance.

Acute Effects of Different Electroacupuncture Point Combinations to Modulate the Gut-Brain Axis in the Minipig Model.

This study aimed to compare the gut-brain axis responses to acute electroacupuncture (EA) at different acupoint combinations in the minipig model. Four adult Yucatan minipigs were subjected twice to four acute EA treatments (25-minute acute sessions) including sham (false acupoints) and control (no EA), during anesthesia and according to a Latin-square design paradigm. Acupoint combinations (4 loci each) are head-abdomen (#70 Dafengmen, #35 Sanwan), back (bilateral #27 Pishu, #28 Weishu), leg (bilateral #79 Hangou, #63 Housanli), and sham (2 bilateral points that are not acupoints). Electrocardiograms were performed to explore heart rate variability (HRV). Infrared thermography was used to measure skin temperature at the stimulation points. Saliva (cortisol) and blood samples (leptin, total/active ghrelin, insulin, and glucose) were collected for further analyses before and after acute EA. All animals were also subjected to BOLD fMRI to investigate the brain responses to EA. Acute EA significantly modulated several physiological and metabolic parameters compared to basal, sham, and/or control conditions, with contrasting effects in terms of BOLD responses in brain regions involved in the hedonic and cognitive control of food intake. The head-abdomen combination appeared to be the most promising combination in terms of brain modulation of the corticostriatal circuit, with upregulation of the dorsolateral prefrontal cortex, dorsal striatum, and anterior cingulate cortex. It also induced significantly lower plasma ghrelin levels compared to sham, suggesting anorectic effects, as well as no temperature drop at the stimulation site. This study opens the way to a further preclinical trial aimed at investigating chronic EA in obese minipigs.

The Yucatan minipig model: A new preclinical model of malnutrition induced by a low-calorie/low-protein diet.

BACKGROUND & AIMS: Severe malnutrition exposes patients to adverse outcomes and a higher mortality risk. The Yucatan minipig, closer to human physiology than murine models could be a pertinent and innovative experimental model for studying the physiopathology and consequences of severe malnutrition. The present study aimed to determine whether a low calorie/low protein diet (LC/LP) can reproduce marasmus malnutrition in minipigs, and to characterize body composition, gut microbiota, malnutrition-related blood parameters, and histological and molecular skeletal muscle patterns. METHODS: Eleven Yucatan minipigs were subjected to two different diets: a standard control diet (ST) (n = 5) and a LC/LP diet (n = 6). LC/LP animals daily received 50% of an isocaloric low-protein diet (10.37 MJ/kg, 8.6% protein). Body composition was measured by computed tomography (CT-scan) before (T0) and after 8 weeks of diet (T8). Trapezius and biceps femoris muscles were sampled at the end of protocol to perform histological and molecular analyses. Gut microbiota composition were was also analyzed at T0 and T8 in fecal samples. RESULTS: Eight weeks of LC/LP diet significantly reduced body weight (-12.3 ± 9.5%, P = 0.03) and gut microbiota richness (i.e. number of observed species) (-10.4 ± 8.3%, P = 0.014) compared to baseline. After 8 weeks, LC/LP animals exhibited a significant reduction of retroperitoneal fat and skeletal muscle surface areas (P = 0.03 and P = 0.047, respectively), whereas these parameters remained unchanged in ST animals. These reductions were associated with lower muscle fiber cross-sectional area (CSA) in trapezius (P < 0.001) and biceps femoris (P = 0.003) in LC/LP animals compared to ST. LC/LP diet promoted an increase of AMP kinase phosphorylation in trapezius and biceps femoris (P = 0.05), but did not affect cytochrome c and COX IV protein content, markers of mitochondrial content. Gene and proteins involved in ubiquitin-proteasome system and apoptosis remained unchanged after 8 weeks of LC/LP diet both in trapezius and biceps femoris. CONCLUSION: All these findings support that this experimental minipig model of severe malnutrition is valid to mimic pathophysiological changes occurring in human protein-energy marasmus malnutrition and muscle atrophy associated with malnutrition, as observed in patients with secondary sarcopenia.

A maternal Western diet during gestation and lactation modifies offspring's microglial cell density and morphology in the hippocampus and prefrontal cortex in Yucatan minipigs.

Changes in microglial development and morphology can be induced by inflammatory conditions and associated with eating or mood disorders, such as hyperphagia or depression. In a previous paper in the minipig model, we showed that maternal Western diet during gestation and lactation decreased hippocampus neurogenesis and food-rewarded cognitive abilities in the progeny. Whether these alterations are concomitant with a central inflammatory process in brain structures involved in learning and memory (hippocampus, HPC), cognitive (prefrontal cortex, PFC), or hedonic (orbitofrontal cortex, OFC) control of food intake is still unknown. In the present study, Yucatan minipigs (Sus scrofa) sows were exposed to two different diets during gestation and lactation (standard, SD N = 7 vs. Western diet, WD N = 9). Iba1 is a calcium-binding protein specifically expressed in microglia in the brain, which plays an important role in the regulation of the microglia function. Iba1 expression was examined by immunohistochemical analyses in the PFC, OFC and HPC of piglets. The density of microglial cells, as well as their morphology, were assessed in order to have an indirect insight of microglial cell activation state possibly in relationship with neuroinflammation. The density of Iba1-positive cells was higher in the PFC but not in the HPC of WD compared to SD piglets (p < 0.001). In the HPC, anterior and dorsolateral PFC, WD piglets had more unipolar cells, contrary to SD that had more multipolar cells (P < 0.0001). Opposite effects were observed in the OFC, with SD presenting more unipolar (P < 0.001) microglial cells compared to WD. We showed here that maternal diet during pregnancy and lactation had significant effects on morphological changes of microglial cells in the offspring, and that these effects differed between the HPC and PFC, suggesting different response mechanisms to the early nutritional environment.

Validation of a Psychosocial Chronic Stress Model in the Pig Using a Multidisciplinary Approach at the Gut-Brain and Behavior Levels.

Psychological chronic stress is an important risk factor for major depressive disorder, of which consequences have been widely studied in rodent models. This work aimed at describing a pig model of chronic stress based on social isolation, environmental impoverishment and unpredictability. Three groups of animals of both sexes were constituted. Two were exposed to the psychosocial stressors while receiving (SF, n = 12) or not (SC, n = 22) the antidepressant fluoxetine, and a third group (NSC, n = 22) remained unstressed. Animals were observed in home pens and during dedicated tests to assess resignation and anxiety-like behaviors. Brain structure and function were evaluated via proton MRS and fMRI. Hippocampal molecular biology and immunodetection of cellular proliferation (Ki67+) and neuron maturation (DCX+) in the dentate gyrus were also performed. Salivary cortisol, fecal short-chain fatty acids (SCFAs), and various plasmatic and intestinal biomarkers were analyzed. Compared to NSC, SC animals showed more resignation (p = 0.019) and had a higher level of salivary cortisol (p = 0.020). SC brain responses to stimulation by a novel odor were lower, similarly to their hippocampal neuronal density (p = 0.015), cellular proliferation (p = 0.030), and hippocampal levels of BDNF and 5-HT1AR (p = 0.056 and p = 0.007, respectively). However, the number of DCX+ cells was higher in the ventral dentate gyrus in this group (p = 0.025). In addition, HOMA-IR was also higher (p < 0.001) and microbiota fermentation activity was lower (SCFAs, SC/NSC: p < 0.01) in SC animals. Fluoxetine partially or totally reversed several of these effects. Exposure to psychosocial stressors in the pig model induced effects consistent with the human and rodent literature, including resignation behavior and alterations of the HPA axis and hippocampus. This model opens the way to innovative translational research exploring the mechanisms of chronic stress and testing intervention strategies with good face validity related to human.

Gastric Emptying and Dynamic In Vitro Digestion of Drinkable Yogurts: Effect of Viscosity and Composition.

Gastric emptying of food is mainly driven by the caloric concentration, the rheological properties of the chyme, and the physical state (liquid/solid) of food once in the stomach. The present work investigated: (1) The effect of the composition and the viscosity of drinkable yogurts on gastric emptying in pigs, and (2) the behavior of yogurts during dynamic in vitro digestion. Three isocaloric liquid yogurts were manufactured: Two enriched in protein and fiber showing either a low (LV) or high (HV) viscosity, one control enriched in sugar and starch (CT). They were labelled with 99mTc-sulfur colloid and given to pigs (n = 11) to determine gastric emptying pattern by gamma scintigraphy. Then dynamic in vitro digestion of the yogurts was done using the parameters of gastric emptying determined in vivo. Gastric emptying half-times were significantly longer for LV than CT, whereas HV exhibited an intermediate behavior. In vitro gastric digestion showed a quick hydrolysis of caseins, whereas whey proteins were more resistant in the stomach particularly for LV and HV. During the intestinal phase, both whey proteins and caseins were almost fully hydrolyzed. Viscosity was shown to affect the behavior of yogurt in the small intestine.

Maternal Western diet during gestation and lactation modifies adult offspring's cognitive and hedonic brain processes, behavior, and metabolism in Yucatan minipigs.

This study explores the long-term effects of exposure to a maternal Western diet (WD) vs. standard diet (SD) in the Yucatan minipig, on the adult progeny at lean status ( n = 32), and then overweight status. We investigated eating behavior, cognitive abilities, brain basal glucose metabolism, dopamine transporter availability, microbiota activity, blood lipids, and glucose tolerance. Although both groups demonstrated similar cognitive abilities in a holeboard test, WD pigs expressed a higher stress level than did SD pigs (immobility, P < 0.05) and lower performance in an alley maze ( P = 0.06). WD pigs demonstrated lower dopamine transporter binding potential in the hippocampus and parahippocampal cortex ( P < 0.05 for both), as well as a trend in putamen ( P = 0.07), associated with lower basal brain activity in the prefrontal cortex and nucleus accumbens ( P < 0.05) compared with lean SD pigs. Lean WD pigs demonstrated a lower glucose tolerance than did SD animals (higher glucose peak, P < 0.05) and a tendency to a higher incremental area under the curve of insulin from 0 to 30 minutes after intravenous glucose injection ( P < 0.1). Both groups developed glucose intolerance with overweight, but WD animals were less impacted than SD animals. These results demonstrate that maternal diet shaped the offspring's brain functions and cognitive responses long term, even after being fed a balanced diet from weaning, but behavioral effects were only revealed in WD pigs under anxiogenic situation; however, WD animals seemed to cope better with the obesogenic diet from a metabolic standpoint.-Gautier, Y., Luneau, I., Coquery, N., Meurice, P., Malbert, C.-H., Guerin, S., Kemp, B., Bolhuis, J. E., Clouard, C., Le Huërou-Luron, I., Blat, S., Val-Laillet, D. Maternal Western diet during gestation and lactation modifies adult offspring's cognitive and hedonic brain processes, behavior, and metabolism in Yucatan minipigs.

Oral sodium butyrate impacts brain metabolism and hippocampal neurogenesis, with limited effects on gut anatomy and function in pigs.

Butyrate can improve gut functions, whereas histone deacetylase inhibitors might alleviate neurocognitive alterations. Our aim was to assess whether oral butyrate could modulate brain metabolism and plasticity and if this would relate to gut function. Sixteen pigs were subjected to sodium butyrate (SB) supplementation via beverage water or water only [control (C)]. All pigs had blood sampled after 2 and 3 wk of treatment, and were subjected to a brain positron emission tomography after 3 wk. Animals were euthanized after 4 wk to sample pancreas, intestine, and brain for gut physiology and anatomy measurements, as well as hippocampal histology, Ki67, and doublecortin (DCX) immunohistochemistry. SB compared with C treatment triggered basal brain glucose metabolism changes in the nucleus accumbens and hippocampus ( P = 0.003), increased hippocampal granular cell layer volume ( P = 0.006), and neurogenesis (Ki67: P = 0.026; DCX: P = 0.029). After 2 wk of treatment, plasma levels of glucose, insulin, lactate, glucagon-like peptide 1, and peptide tyrosine tyrosine remained unchanged. After 3 wk, plasma levels of lactate were lower in SB compared with C animals ( P = 0.028), with no difference for glucose and insulin. Butyrate intake impacted very little gut anatomy and function. These results demonstrate that oral SB impacted brain functions with little effects on the gut.-Val-Laillet, D., Guérin, S., Coquery, N., Nogret, I., Formal, M., Romé, V., Le Normand, L., Meurice, P., Randuineau, G., Guilloteau, P., Malbert, C.-H., Parnet, P., Lallès, J.-P., Segain, J.-P. Oral sodium butyrate impacts brain metabolism and hippocampal neurogenesis, with limited effects on gut anatomy and function in pigs.

A maternal Western diet during gestation and lactation modifies offspring's microbiota activity, blood lipid levels, cognitive responses, and hippocampal neurogenesis in Yucatan pigs.

A suboptimal early nutritional environment (i.e., excess of energy, sugar, and fat intake) can increase susceptibility to diseases and neurocognitive disorders. The purpose of this study was to investigate in nonobese Yucatan minipigs (Sus scrofa) the impact of maternal diet [standard diet (SD) vs. Western diet (WD)] during gestation and 25 d of lactation on milk composition, blood metabolism, and microbiota activity of sows (n = 17) and their piglets (n = 65), and on spatial cognition (n = 51), hippocampal plasticity (n = 17), and food preferences/motivation (n = 51) in the progeny. Milk dry matter and lipid content, as well as plasma total cholesterol and free fatty acid (FFA) concentrations (P < 0.05) were higher in WD than in SD sows. Microbiota activity decreased in both WD sows and 100-d-old piglets (P < 0.05 or P < 0.10, depending on short-chain FAs [SCFAs]). At weaning [postnatal day (PND) 25], WD piglets had increased blood triglyceride and FFA levels (P < 0.01). Both SD and WD piglets consumed more of a known SD than an unknown high-fat and -sucrose (HFS) diet (P < 0.0001), but were quicker to obtain HFS rewards compared with SD rewards (P < 0.01). WD piglets had higher working memory (P = 0.015) and reference memory (P < 0.001) scores, which may reflect better cognitive abilities in the task context and a higher motivation for the food rewards. WD piglets had a smaller hippocampal granular cell layer (P = 0.03) and decreased neurogenesis (P < 0.005), but increased cell proliferation (P < 0.001). A maternal WD during gestation and lactation, even in the absence of obesity, has significant consequences for piglets' blood lipid levels, microbiota activity, gut-brain axis, and neurocognitive abilities after weaning.-Val-Laillet, D., Besson, M., Guérin, S., Coquery, N., Randuineau, G., Kanzari, A., Quesnel, H., Bonhomme, N., Bolhuis, J. E., Kemp, B., Blat, S., Le Huërou-Luron, I., Clouard, C. A maternal Western diet during gestation and lactation modifies offspring's microbiota activity, blood lipid levels, cognitive responses, and hippocampal neurogenesis in Yucatan pigs.

Alcohol-attributable mortality in France.

BACKGROUND: Alcohol consumption is high in France. AIM: Estimation of alcohol-attributable mortality in France by sex, age and dose, for year 2009. METHOD: We combined survey and sales data to estimate the prevalence of alcohol consumption by age, sex and dose category. For each cause of death, the relative risk of death as a function of dose was obtained from a meta-analysis and combined with prevalence data to obtain the attributable fraction; this fraction multiplied by the number of deaths gave the alcohol-attributable mortality. RESULTS: A total of 36,500 deaths in men are attributable to alcohol in France in 2009 (13% of total mortality) versus 12,500 in women (5% of total mortality). Overall, this includes 15,000 deaths from cancer, 12,000 from circulatory disease, 8000 from digestive system disease, 8000 from external causes and 3000 from mental and behavioural disorder. The alcohol-attributable fractions are 22% and 18% in the population aged 15 to 34 and 35 to 64, respectively, versus 7% among individuals aged 65 or more. Alcohol is detrimental even at a low dose of 13 g per day, causing 1100 deaths. CONCLUSION: With 49 000 deaths in France for the year 2009, the alcohol toll is high, and the effect of alcohol is detrimental even at low dose. Alcohol consumption is responsible for a large proportion of premature deaths. These results stress the importance of public health policies aimed at reducing alcohol consumption in France.

Copeptin for rapid rule out of acute myocardial infarction in emergency department.

BACKGROUND: Copeptin, in combination with conventional troponin (cTn), has been suggested as a means of rapid rule out of the diagnosis of acute myocardial infarction (AMI). This study aims to assess the value of copeptin for rule out of AMI, according to the pre-test probability (PTP). METHODS: In a prospective multicentric study, we enrolled patients presenting into emergency departments with chest pain <6h, copeptin was measured, and PTP was quoted. The discharge diagnosis was adjudicated by 2 independent experts using all available data, including cTnI. RESULTS: 317 patients were included: 148 (46%) had low, 110 (35%) moderate and 59 (19%) high PTP. Final diagnosis was AMI in 45 patients (14%). Median copeptin level was higher in AMI patients compared with that in patients having other diagnoses (23.2 vs. 9.9 pmol/L, p=0.01). A copeptin level ≥10.7 pmol/L in combination with cTnI detected AMI with higher sensitivity than for cTnI alone (98 [87-100] vs. 71 [55-83] %, p=0.001), whatever the PTP. The negative predictive value of the combination copeptin+cTnI was increased, compared to that of cTnI alone (99 [97-100] vs. 95 [92-97] %, p<0.05). CONCLUSIONS: In triage of chest pain patients, the additional use of copeptin with conventional cTnI might allow a rapid and reliable rule out of the diagnosis of AMI regardless of the PTP.

Decisional procalcitonin thresholds are not adapted to elderly patients admitted to the emergency room.

CONTEXT: Diagnosis of sepsis in elderly is challenging. OBJECTIVES: We investigated whether procalcitonin concentrations in elderly differed from values for the general population. METHODS: Procalcitonin measurement was assessed prospectively in 307 apyretic patients ≥75 years visiting the emergency department. RESULTS: Median age was 86 years [IQR81-90] and 222 (72%) were female. Procalcitonin concentration was 0.057 µg/L [0.040-0.092]; 99th percentile was 0.661 µg/L. Patients with procalcitonin concentrations above decisional thresholds had lower glomerular filtration rate and higher C-reactive protein concentrations. CONCLUSIONS: Baseline procalcitonin levels are increased in elderly. Elevated values are common and associated to low-grade inflammation and lower eGFR.

[Cancer before age 40 in France]. / Les cancers avant 40 ans en France.

Cancer is a rare pathology before the age of 40: a total of 14,000 new cases have been diagnosed in patients under age 40 in 2005, 1,700 under age 15 and 12,500 in the age-group of 15 to 39, this represents 4% of the cancers diagnosed in 2005. The number of deaths is small: in 2008, 2,235 patients died before age 40 in France, 246 under age 15 and 1,989 between age 15 and 39; this corresponds to 1% of the cancer deaths in 2008. The incidence increased between 1980 and 2005, both in the population aged 0 to 14 and in the population aged 15 to 39. Overall, cancer mortality has been decreasing for more than 25 years. The only increase in mortality is observed for brain tumours in children. The overall incidence increase is mostly due to the extension of screening coverage and to improvements in diagnostic procedures. The decrease observed for cervix cancer and lung cancer in men demonstrates the efficacy of screening and of tobacco smoking prevention. The mortality decrease is explained both by improved treatments and by the decreased incidence of some types of cancer. The increasing brain tumours mortality in children is worrying.

Mid-regional pro atrial natriuretic peptide allows the accurate identification of patients with atrial fibrillation of short time of onset: a pilot study.

OBJECTIVES: Atrial fibrillation (AF) is a common arrhythmia; its most prevalent and devastating complication is stroke. A delay of AF onset >48 h is believed to be clinically significant. Mid-regional pro A-type natriuretic peptide (MR-proANP) could be of interest in the identification of the time from onset of AF to presentation. DESIGN AND METHODS: We measured MR-proANP plasma concentration at presentation in consecutive patients in whom onset of AF was determined, without evidence of concomitant acute heart failure. RESULTS: Forty-seven patients were included. Patients with an AF onset <48 h (n=19) had decreased MR-proANP concentrations versus patients with onset >48 h (144.0 [129.2-213.7] versus 321.7 [236.4-425.6] pmol/L, p<0.001); MR-proANP was the only independent variable associated with AF <48 h according to multivariate analysis. Area under the ROC curve for identify AF onset <48 h was 0.878 [95%CI 0.778-0.978]. CONCLUSIONS: MR-proANP concentration may reliably identify the time from onset of AF to presentation.

Is mid-regional pro-atrial natriuretic peptide (MRproANP) an accurate marker of bacteremia in pyelonephritis?

INTRODUCTION: Mid-regional pro-atrial natriuretic peptide (MRproANP) increases during systemic infections and could possibly correlate with bacteremia. METHODS: We determined the characteristics of MRproANP for accuracy to detect positive blood culture. RESULTS: Bacteremia was positive in 58 (15%) of 347 patients. MRproANP levels increased in patients with bacteremia (98.4 pmol/L [interquartile range (IQR) 68.2-153.1] vs. 66.4 pmol/L [IQR 51.0-90.3], p <0.01). Performance of MRproANP to predict bacteremia [AUC = 0.69, 95%CI: 0.61-0.77] was equivalent to C-reactive protein (0.66 [95%CI: 0.59-0.74], p = 0.53) but less accurate than procalcitonin (0.78 [95%CI: 0.72-0.84], p <0.001). CONCLUSION: Although MRproANP increased in bacteremic patients with acute pyelonephritis, results of likelihood ratios discarded its use at bedside to predict bacteremia.

Changes in brain activity after a diet-induced obesity.

Compared to lean subjects, obese men have less activation in the dorsolateral prefrontal cortex, a brain area implicated in the inhibition of inappropriate behavior, satiety, and meal termination. Whether this deficit precedes weight gain or is an acquired feature of obesity remains unknown. An adult animal model of obesity may provide insight to this question since brain imaging can be performed in lean vs. obese conditions in a controlled study. Seven diet-induced obese adult minipigs were compared to nine lean adult minipigs housed in the same conditions. Brain activation after an overnight fasting was mapped in lean and obese subjects by single photon emission computed tomography. Cerebral blood flow, a marker of brain activity, was measured in isoflurane-anesthetized animals after the intravenous injection of 99mTc-HMPAO (750 MBq). Statistical analysis was performed using statistical parametric mapping (SPM) software and cerebral blood flow differences were determined using co-registered T1 magnetic resonance imaging (MRI) and histological atlases. Deactivations were observed in the dorsolateral and anterior prefrontal cortices in obese compared to lean subjects. They were also observed in several other structures, including the ventral tegmental area, the nucleus accumbens, and nucleus pontis. On the contrary, activations were found in four different regions, including the ventral posterior nucleus of the thalamus and middle temporal gyrus. Moreover, the anterior and dorsolateral prefrontal cortices as well as the insular cortex activity was negatively associated with the body weight. We suggested that the reduced activation of prefrontal cortex observed in obese humans is probably an acquired feature of obesity since it is also found in minipigs with a diet-induced obesity.