First report of eprinomectin-resistant isolates of Haemonchus contortus in 5 dairy sheep farms from the Pyrénées Atlantiques département in France.

Infection of sheep by gastrointestinal nematodes (GIN) in pastoral systems such as those found in the South Western area of France, the Pyrénées Atlantiques, is one of the main reasons for economic loss and degradation of their welfare. In the present study, the efficacy of eprinomectin (EPN) was monitored on farms from this area following suspicion of lack of anthelmintic efficacy. Suspicions were raised by veterinarians, based on clinical signs ranging from milk and body condition loss, to anaemia, and mortality. Resistance was evaluated according to the World Association for the Advancement for Veterinary Parasitology (WAAVP) guidelines using fecal egg count reduction tests reinforced by individual analysis of drug concentration in the serum of all treated ewes by high-performance liquid chromatography (HPLC). EPN was administered by subcutaneous (SC) and topical (T) route according to manufacturer's requirements, as well as by the oral route (O) with the topical solution according to off-labelled practices in the field. For the first time in France, the presence of resistant isolates of Haemonchus contortus to EPN was observed in 5 dairy sheep farms. The HPLC dosages showed exposure of worms to concentrations compatible with anthelmintic activity for animals treated by the SC and O routes. By contrast, they showed under exposure to the drug of most individuals treated by the T route. EPN is the only null milk withdrawal anthelmintic molecule currently available. The presence of resistant isolates of the pathogenic H. contortus to EPN in this important dairy region requires an urgent change in grazing, and sometimes production, systems.

Assessing the potential outcomes of achieving the World Health Organization global non-communicable diseases targets for risk factors by 2025: is there also an economic dividend?

OBJECTIVES: This study assesses the change in premature mortality and in morbidity under the scenario of meeting the World Health Organization (WHO) global targets for non-communicable disease (NCD) risk factors (RFs) by 2025 in France. It also estimates medical expenditure savings because of the reduction of NCD burden. STUDY DESIGN: A microsimulation model is used to predict the future health and economic outcomes in France. METHODS: A 'RF targets' scenario, assuming the achievement of the six targets on RFs by 2025, is compared to a counterfactual scenario with respect to disability-adjusted life years and healthcare costs differences. RESULTS: The achievement of the RFs targets by 2025 would save about 25,300 (and 75,500) life years in good health in the population aged 25-64 (respectively 65+) years on average every year and would help to reduce healthcare costs by about €660 million on average per year, which represents 0.35% of the current annual healthcare spending in France. Such a reduction in RFs (net of the natural decreasing trend in mortality) would contribute to achieving about half of the 2030 NCD premature mortality target in France. CONCLUSIONS: The achievement of the RF targets would lead France to save life years and life years in good health in both working-age and retired people and would modestly reduce healthcare expenditures. To achieve RFs targets and to curb the growing burden of NCDs, France has to strengthen existing and implement new policy interventions.

Promoting sport and physical activity in Italy: a cost-effectiveness analysis of seven innovative public health policies.

BACKGROUND: Inactive lifestyles are a key risk factor underpinning the development of many chronic diseases, yet more than half of the Italian population does not meet WHO thresholds for at least moderate physical activity. This study aims to make the economic case to upscale investments in policy actions to promote exercise and physical activity. STUDY DESIGN: Modelling-based cost-effectiveness analysis in Italy. METHODS: The study assesses the impact on health and healthcare expenditure of seven public health policies to promote exercise and physical activity against a business as usual scenario. Assessed policies include: promotion of active transport, workplace sedentarily interventions, investments in sports and recreation, mass media campaigns, prescription of physical activity in primary care, school-based interventions and mobile apps. RESULTS: Public policies to promote exercise have the potential to improve population health and produce savings in healthcare expenditure. Assessed policies can avoid hundreds of cases of cardiovascular diseases and diabetes per year and tens of cases of cancer resulting in gains in DALYs in the order of thousands per year. In the medium-term, the vast majority of policies show excellent cost-effectiveness ratio, below internationally recognized thresholds. CONCLUSIONS: Investing in policies to promote active lifestyles is a good investment for Italy.

Cartography of cell morphology in tomato pericarp at the fruit scale.

In fleshy fruits, the variability of cell morphology at the fruit scale is largely unknown. It presents both a huge variability and a high level of organization. Better knowledge of cell morphology heterogeneity within the fruit is necessary to understand fruit development, to model fruit mechanical behaviour, or to investigate variations of physico-chemical measurements. A generic approach is proposed to build cartographies of cell morphology at the fruit scale, which depict regions corresponding to different cell morphologies. The approach is based on: (1) sampling the whole fruit at known positions; (2) imaging and quantifying local cell morphology; (3) pooling measurements to take biological variability into account and (4) projecting results in a morphology model of the whole fruit. The result is a synthetic representation of cell morphology variations within the whole fruit. The method was applied to the characterization of cell morphology in tomato pericarp. Two different imaging scales that provided complementary descriptions were used: 3D confocal microscopy and macroscopy. The approach is generic and can be adapted to other fruits or other products.

Host-specific differentiation among populations of Venturia inaequalis causing scab on apple, pyracantha and loquat.

Patterns of multilocus DNA sequence variation within and between closely related taxa can provide insights into the history of divergence. Here, we report on DNA polymorphism and divergence at six nuclear loci in globally distributed samples of the ascomycete Venturia inaequalis, responsible for scab on apple, loquat, and pyracantha. Isolates from different hosts were differentiated but did not form diagnosable distinct phylogenetic species. Parameters of an Isolation-with-Migration model estimated from the data suggested that the large amount of variation shared among groups more likely resulted from recent splitting than from extensive genetic exchanges. Inferred levels of gene flow among groups were low and more concentrated toward recent times, and we identified two potentially recent one-off shifters from apple and pyracantha to loquat. These findings support a scenario of recent divergence in allopatry followed by introgression through secondary contact, with groups from loquat and pyracantha being the most recently differentiated.

Carbohydrase Complexes Rich in Xylanases and Arabinofuranosidases Affect the Autofluorescence Signal and Liberate Phenolic Acids from the Cell Wall Matrix in Wheat, Maize, and Rice Bran: An In Vitro Digestion Study.

The high fiber content of cereal coproducts used in animal feed reduces the digestibility and nutrient availability. Therefore, the aim of this study was to elucidate the ability of two carbohydrase complexes to degrade the cell wall of wheat, maize, and rice during in vitro digestion. One complex was rich in cell-wall-degrading enzymes (NSPase 1), and the other was similar but additionally enriched with xylanases and arabinofuranosidases (NSPase 2). Degradation of arabinoxylan, the main cereal cell wall polysaccharide, was followed directly by gas-liquid chromatography (GLC) and indirectly through phenolic acid liberation as quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The effect was additionally visualized using a unique multispectral autofluorescence approach. Wheat fractions, in particular aleurone, were susceptible to degradation as judged from the redistribution of arabinoxylan (25% reduction in insoluble arabinoxylan), whereas the highest relative liberation of ferulic acid was observed in rice bran (6%). All cereal fractions, except for maize, had a higher release of ferulic acid with NSPase 2 than NSPase 1 (38% in rice and wheat bran, 30% in wheat whole grain, and 28% in wheat aleurone). Thus, the carbohydrase complexes were able to degrade important cell wall components during in vitro digestion but apparently through different mechanisms in wheat, maize, and rice.

Stereological estimation for layered structures based on slabs perpendicular to a surface.

This paper deals with the characterization of layered structures sampled with respect to a reference surface. A scheme where thick slabs are sampled perpendicular to a curved surface is considered, resulting in a non-uniform sampling of the structure. We present an estimation procedure based on the Horvitz-Thompson principle. An approximation of the sampling probability is proposed, which depends on the local surface curvatures, on the slab dimensions and on the intensity function of slab anchors. The practical determination of local parameters is detailed for the case of a revolution surface. The procedure is applied to the estimation of surface area density of cell walls in tomato pericarp.

[Does breast density have an impact on the indications for MRI?]. / La densité mammaire change-t-elle les indications d'IRM du sein?

MRI indications in breast imaging in breast imaging are now well codified. In diagnostic and screening, MRI in recommended in patients with likely metastatic lymph nodes and in metastasis of unknown cause, and in women with high risk family. In characterisation MRI is recommend in non-calcified subtle findings, non suitable for biopsy. In the staging of a diagnosed breast cancer, MRI has a great impact both for the diagnosis and for the treatment, event if group of women for whom MRI is recommended is still discussed. In follow-up of patients with an history of breast cancer, MRI permits to differentiate recurrence from scarr and to monitor the response to a neo-adjuvant chemotherapy. Dense breast don't constitute a MRI indication by itself, but strengthen recognized MRI indications. Fatty breast easily readable on mammogram don't justify not to perform MRI in the screening of women with high risk family. Conservely in the staging of a breast cancer in an woman or in the monitoring of a neo-adjuvant chemotherapy fatty breast may make US sufficient.

Effect of flour minor components on bubble growth in bread dough during proofing assessed by magnetic resonance imaging.

Fermentation of dough made from standard flour for French breadmaking was followed by nuclear magnetic resonance imaging at 9.4 T. The growth of bubbles (size > 117 microm) was observed for dough density between 0.8 and 0.22 g cm(-3). Cellular structure was assessed by digital image analysis, leading to the definition of fineness and rate of bubble growth. Influence of composition was studied through fractionation by extraction of soluble fractions (6% db), by defatting (< 1% db) and by puroindolines (Pin) addition (< or = 0.1%). Addition of the soluble fraction increased the dough specific volume and bubble growth rate but decreased fineness, whereas defatting and Pin addition only increased fineness. The role of molecular components of each fraction could be related to dough elongational properties. A final comparison with baking results confirmed that the crumb cellular structure was largely defined after fermentation.

Action of dopamine on the exocrine pancreatic secretion of the intact dog.

The effects of dopamine and domperidone, a dopamine antagonist, have been studied on the exocrine secretion of the dog pancreas. The purpose of this study was to see if dopamine acted on enzyme secretion and if its action was merely 'pharmacological' or had a physiological role. Conscious Beagle dogs, fitted with Thomas cannulae were studied following infusions of dopamine 125-1000 micrograms kg-1 h-1. During dopamine infusion, a secretory peak lasting 10 min was observed. This was followed by a stable plateau which was approximately 1/3 of the peak. The pattern of water, bicarbonate and protein secretion was similar. The maximum effect was obtained with 500 micrograms kg-1 h-1 dopamine. The stimulatory action of dopamine was blocked by domperidone, without any detected effect on the central nervous system, but not by propranolol or phenoxybenzamine. Domperidone 10 micrograms kg-1 almost completely suppressed the secretory response to the maximally effective dose of dopamine. This inhibition was not competitive. Atropine decreased the secretory response to dopamine. The protein response was not observed when dopamine was infused against a background infusion of secretin. This suggests that the effect of dopamine on protein secretion could be due to a wash-out phenomenon. The maximally effective dose of domperidone, 10 micrograms kg-1, did not modify the pancreatic response to a solid meal. Thus, in the non-anaesthetized dog, the effect of dopamine on water and bicarbonate secretion has been confirmed. It is concluded that dopamine had no detectable action on protein secretion and that the physiological role of dopamine with respect to pancreatic secretion is still questionable.

The role of nicotinic receptors in dog pancreatic exocrine secretion.

1 The effects of pentamethonium, an autonomic ganglion blocker, were studied on the exocrine pancreatic secretion of six conscious dogs given intravenous infusions of urecholine, caerulein or pentagastrin on a background of submaximal doses of secretin. 2 Urecholine-induced protein secretion was not affected but both caerulein- and to a smaller extent, pentagastrin-induced protein secretions were depressed by pentamethonium. 3 These results indicate that intravenous caerulein and pentagastrin, but not urecholine, act at least partially via nicotinic receptors. 4 Volume and bicarbonate output were depressed by pentamethonium when stimulated by intravenous caerulein with a background of secretin, but not when stimulated by pentagastrin on a background of secretin. 5 From these data it is suggested that caerulein and pentagastrin may potentiate secretin-stimulated hydrelatic secretion by different mechanisms.

The effect of oxyntomodulin (glucagon-37) and glucagon on exocrine pancreatic secretion in the conscious rat.

The inhibitory effect of glucagon on exocrine pancreas has been the subject of controversial reports. On the other hand, oxyntomodulin (bioactive enteroglucagon or glucagon-37), a 37 amino acid peptide isolated from porcine lower intestine, has been shown to be 10-20 times more potent than glucagon in inhibiting gastric acid secretion in the rat. In view of this, the effect of glucagon and oxyntomodulin on basal and caerulein-stimulated pancreatic secretion has been studied, during re-introduction of pancreatic juice into duodenum, in the conscious rat provided with pancreatic and duodenal fistulas. A depression of pancreatic function was observed with both peptides on the three parameters studied: (volume of juice secreted, bicarbonate and protein output), either under basal conditions or during stimulation by caerulein. In all the experimental conditions used, oxyntomodulin was ca. ten times more potent than glucagon in its inhibitory effect. The fact that oxyntomodulin, as what is observed in the stomach, is one order of magnitude more potent than glucagon in inhibiting pancreatic secretion suggests that the biological mechanisms by which the peptides of the glucagon-family act on exocrine pancreas are similar, or related to that present at the gastric level.

Response of the exocrine pancreas to graded doses of secretin in calcium-treated and normal dogs.

Persisting modifications induced by repeated intravenous calcium infusion (acute hypercalcaemia) were investigated in 6 Thomas fistula dogs: 4 controls and 4 calcium-treated dogs, two of which were studied as controls. (a) The pancreatic response to graded doses of synthetic secretin (water and bicarbonate outputs) was significantly reduced in calcium-treated dogs when compared with controls. As both the D50 for secretin-induced response increased, and the maximal secretory response decreased, if may be concluded that calcium treatment decreased the sensitivity of duct cells to secretin and reduced their secretory capacity. (b) A similar dose-response relationship was observed between secretin and pancreatic calcium outputs in controls and calcium-treated dogs. The secretin induced pancreatic calcium secretion was independent of protein secretion and latter not being modified by secretin. Thus it may be assumed that the secretory fluid calcium originated form a protein independent pool and had a dose-dependent relationship to secretin. (c) These results help to illuminate the aetiology of chronic pancreatitis induced by acute hypercalcaemia and by hyperparathyroidism.

Action of gastrointestinal hormones on the myoelectric activity of the sphincter of Oddi in living rabbit.

The aim of this work was to compare the action of gastrointestinal (GI) hormones on the myoelectrical activity of the sphincter of Oddi. Using an experimental design previously described, we studied the electrical activity of the sphincter of Oddi and compared the percentage variation in the number of spikes before and after injection of hormones. Increasing doses of the following hormones were injected i.v. at random: CCK, OP-CCK, caerulein, bombesin, gastrin, secretin and glucagon. CCK and caerulein (as previously found), and also bombesin, OP-CCK and gastrin increased the spikes activity of the sphincter of Oddi. Secretin had no effect and glucagon decreased this activity. There was no tachyphylaxis, but a good dose-effect relationship for each hormone. Compared on a molar basis caerulein is 8 times more effective than CCK and OP-CCK which in turn are more potent than bombesin. Gastrin acts only at pharmacological doses.

Pancreatic responses to endogenous and exogenous gastrin in the dog.

Serum gastrin and pancreatic secretion were measured in conscious Thomas fistula dogs during infusion of increasing doses of porcine gastrin, against a background of secretin. Dose-response relationships were calculated for the effects of gastrin on pancreatic secretion. Gastrin release was also measured after a test meal and after vagal stimulation with 2-deoxyglucose. Peak serum gastrin levels after these stimuli were less than the serum gastrin level associated with the minimal effective dose of gastrin. From the dose-response relationship of serum gastrin and pancreatic protein output, it was possible to calculate the protein output corresponding to the peak gastrin levels after 2-deoxyglucose or a meal. These were equivalent to 20-30% of the observed protein response to these stimuli. We conclude that gastrin plays at most a small part in the stimulation of pancreatic secretion after a meal and in response to 2-deoxyglucose. We also found that truncal vagotomy reduces pancreatic sensitivity to gastrin.

The cephalogastric phase of the pancreatic response to food in the dog.

We studied post-meal pancreatic secretion and gastrin release in conscious dogs with duodenal Thomas cannulas. Normal dogs were tested in physiological conditions and with an i.v. infusion of atropine 20 micrograms/kg/h or secretin 0.5 CU/kg/h. The responses were also studied after antral and truncal vagotomy. In the early phase (0-20 min) of the response, before gastric emptying started, antral vagotomy reduced fluid and protein outputs, and truncal vagotomy reduced them still more. Atropine reduced only the protein response. Gastrin release reached a peak after 20-25 min. After antral and truncal vagotomy, gastrin release was reduced within 10 min after the meal. Late-phase (greater than 20 min) pancreatic secretion depended on the presence of chyme in the duodenum. The effects of atropine and antral vagotomy in the cephalogastric phase could be explained by antropancreatic reflexes stimulating fluid secretion (atropine-resistant pathway) and protein output (atropine-sensitive pathway).

Structural and functional effects of long-term alcohol administration on the dog exocrine pancreas submitted to two different diets.

Our purpose was to study the influence of two different levels of dietary protein and fat on the action of chronic alcohol feeding on the exocrine pancreatic secretion and the pancreatic morphology of conscious dogs. Ten animals were provided with gastric and duodenal cannulas. Five of them (group H) received a high-protein (39% of calories), high-fat (34%) diet, and the five others (group L) a moderately low-protein (15%), low-fat (20%) diet. Animals were housed in closed kennels lightened with artificial light and did not have free access to sunlight. Five series of experiments were performed just before and 5 and 12 months after daily alcohol administration through the gastric cannula (2 g/kg/day). Volume, bicarbonate, and protein were measured under basal conditions after intragastric ethanol infusion (1.5 g/kg), under hormonal stimulation with 1 clinical unit (CU)/kg/h secretin or 1 CU/kg/h secretin plus 3 Crick Harper Rate (CHR) U/kg/h cholecystokinin (CCK), before and after intravenous ethanol 1.3 g/kg for 20 min, and after intragastric ethanol (1 g/kg) given with a meal. Group H was the most sensitive to the action of chronic alcohol feeding. At the end of 1 year of alcohol administration, volume and bicarbonate were not affected, but protein secretion was significantly increased in basal conditions and under secretin infusion, but not under CCK infusion or in response to a meal. The secretory pattern of these dogs was different from the response of dogs studied in previous experiments having the same diet but housed in an open kennel and having free access to outside and sunlight. In group L, protein was less affected, but volume and bicarbonate were significantly decreased 1 year under secretin stimulation. Histological damages were seen in the two groups characterized by a slight periacinar fibrosis and alterations of ductal cells. Acinar and ductal luminae were dilated and filled with protein plugs also present in pancreatic juice and able to stop the flow of juice. At the difference from human beings, these plugs were built up of all secretory protein but not of an insoluble fibrillar molecular form of pancreatic stone protein. This study confirms the role of chronic alcoholism on the formation of protein plugs and shows the influence of nutritional and environmental conditions.

Repeated I. V. injections of calcium salts give rise to increased exocrine pancreatic cell sensitivity to caerulein and urecholine in the dog.

The persisting modifications induced by repeated intravenous infusion of calcium salts were investigated in five dogs with Thomas fistulae. Five control dogs were also tested. In calcium treated dogs the pancreatic secretion stimulated by graded doses of either caerulein or urecholine showed: a) an increase in the sensitivity of acinar cells to caerulein and urecholine and potentiation by caerulein of the water and bicarbonate response to secretin, in contrast to the decreased sensitivity to secretin alone reported previously. b) an inhibition of water and bicarbonate secretion with urecholine stimulation, c) an inhibition of calcium secretion which was significant with caerulein. These findings could explain the data previously observed on basal pancreatic secretion of calcium treated dogs such as protein hypersecretion with protein precipitates and reduced bicarbonate secretion which are similar to modifications observed in chronic alcoholic dogs and men. These results have a clinical relevance to the understanding of the pathology of chronic pancreatitis.

Specific Polymerase Chain Reaction Identification of Venturia nashicola Using Internally Transcribed Spacer Region in the Ribosomal DNA.

ABSTRACT A technique based on the polymerase chain reaction (PCR) was developed for the identification of Venturia nashicola using nucleotide sequence information of the ribosomal DNA region. The complete internal transcribed spacer (ITS) region of V. nashicola strains and phylo-genetically related species was amplified with the two universal ITS1 and ITS4 primers, sequenced, and digested with five restriction enzymes. The alignment of nucleotide sequences and analyses of digestion patterns indicated constant polymorphisms between V. nashicola and related species at nucleotides 126 and 127, which overlapped a TaqI restriction site. An oligonucleotide primer named A126 was designed for identifying this variable region. A primer set (A126 and ITS4) that allowed the amplification of a 391-bp DNA fragment within the ITS region by PCR was specific to V. nashicola when it was checked against fungal genomic DNAs of related fungi. This primer set was a good candidate for a species-specific reagent in a procedure for identification of V. nashicola by PCR.