A Neural Circuit Arbitrates between Persistence and Withdrawal in Hungry Drosophila

In pursuit of food, hungry animals mobilize significant energy resources and overcome exhaustion and fear. How need and motivation control the decision to continue or change behavior is not understood. Using a single fly treadmill, we show that hungry flies persistently track a food odor and increase their effort over repeated trials in the absence of reward suggesting that need dominates negative experience. We further show that odor tracking is regulated by two mushroom body output neurons (MBONs) connecting the MB to the lateral horn. These MBONs, together with dopaminergic neurons and Dop1R2 signaling, control behavioral persistence. Conversely, an octopaminergic neuron, VPM4, which directly innervates one of the MBONs, acts as a brake on odor tracking by connecting feeding and olfaction. Together, our data suggest a function for the MB in internal state-dependent expression of behavior that can be suppressed by external inputs conveying a competing behavioral drive

Pathogenesis and management of Buerger's disease

Buerger’s disease or thromboangiitis obliterans causes pain, ulceration, or gangrene in the lower or upper extremity. It is associated with chronic cigarette smoking and is believed to be an immune mediated vasculitis. The pathogenesis is still unknown but recent postulate of its association with odontal bacteria has generated much renewed interest. Despite its recognition more than a century ago, little progress has been made in its treatment. Until the pathogenesis is elucidated, abstinence from cigarette is the only effective therapy

Assessment of perinatal outcome after sustained tocolysis in early labour (APOSTEL-II trial)

Contains fulltext : 80242.pdf (publisher's version ) (Open Access)BACKGROUND: Preterm labour is the main cause of perinatal morbidity and mortality in the Western world. At present, there is evidence that tocolysis for 48 hours is useful in women with threatened preterm labour at least before 32 weeks. This allows transfer of the patient to a perinatal centre, and maximizes the effect of corticosteroids for improved neonatal survival. It is questionable whether treatment with tocolytics should be maintained after 48 hours. METHODS/DESIGN: The APOSTEL II trial is a multicentre placebo-controlled study. Pregnant women admitted for threatened preterm labour who have been treated with 48 hours corticosteroids and tocolysis will be eligible to participate in the trial between 26+0 and 32+2 weeks gestational age. They will be randomly allocated to nifedipine (intervention) or placebo (control) for twelve days or until delivery, whatever comes first.Primary outcome is a composite of perinatal death, and severe neonatal morbidity up to evaluation at 6 months after birth. Secondary outcomes are gestational age at delivery, number of days in neonatal intensive care and total days of the first 6 months out of hospital. In addition a cost-effectiveness analysis will be performed. Analysis will be by intention to treat. The power calculation is based on an expected 11% difference in adverse neonatal outcome. This implies that 406 women have to be randomised (two sided test, beta 0.2 at alpha 0.05). DISCUSSION: This trial will provide evidence as to whether maintenance tocolysis reduces severe perinatal morbidity and mortality in women with threatened preterm labour before 32 weeks. TRIAL REGISTRATION: Clinical trial registration: http://www.trialregister.nl, NTR 1336, date of registration: June 3rd 2008

Computational investigation of diesel nozzle internal flow during the complete injection event

[EN] Currently, diesel engines are calibrated using more and more complex multiple injection strategies. Under these conditions, the characteristics of the flow exiting the fuel injector are strongly affected by the transient interaction between the needle, the sac volume and the orifices, which are not yet clear. In the current paper, a methodology combining a 1D injector model and 3D-CFD simulations is proposed. First, the characteristics of the nozzle flow have been experimentally assessed in transient conditions by means of injection rate and momentum flux measurements. Later, the 3D-CFD modeling approach has been validated at steady-state fixed lift conditions. Finally, a previously developed 1D injector model has been used to extract the needle lift profiles and transient pressure boundary conditions used for the full-transient 3D-CFD simulations, using adaptive mesh refinement (AMR) strategies to be able to simulate the complete injection rate starting from 1 mu m lift.This work was partly sponsored by "Ministerio de Economia y Competitividad'', of the Spanish Government, in the frame of the Project "Estudio de la interaccion chorro-pared en condiciones realistas de motor'', Reference TRA2015-67679-c2-1-R. The authors would like also to thank the computer resources, technical expertise and assistance provided by Universidad de Valencia in the use of the supercomputer "Tirant''. Mr. Jaramillo's Thesis is funded by "Conselleria d'Educacio, Cultura i Esports'' of Generalitat Valenciana in the frame of the program "Programa VALI + D para investigadores en formacion, Reference ACIF/2015/040.Salvador, FJ.; De La Morena, J.; Bracho Leon, G.; Jaramillo-Císcar, D. (2018). Computational investigation of diesel nozzle internal flow during the complete injection event. Journal of the Brazilian Society of Mechanical Sciences and Engineering. 40(3):153-167. https://doi.org/10.1007/s40430-018-1074-zS153167403Hall CAS, Lambert JG, Balogh SB (2014) EROI of different fuels and the implications for society. Energy Policy 64:141–152. https://doi.org/10.1016/j.enpol.2013.05.049Lujan JM, Tormos B, Salvador FJ, Gargar K (2009) Comparative analysis of a DI diesel engine fuelled with biodiesel blends during the European MVEG-A cycle: preliminary study (I). 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Nutrition and lung cancer: a case control study in Iran

Background: Despite many prospective and retrospective studies about the association of dietary habit and lung cancer, the topic still remains controversial. So, this study aims to investigate the association of lung cancer with dietary factors. Method: In this study 242 lung cancer patients and their 484 matched controls on age, sex, and place of residence were enrolled between October 2002 to 2005. Trained physicians interviewed all participants with standardized questionnaires. The middle and upper third consumer groups were compared to the lower third according to the distribution in controls unless the linear trend was significant across exposure groups. Result: Conditional logistic regression was used to evaluate the association with lung cancer. In a multivariate analysis fruit (Ptrend < 0.0001), vegetable (P = 0.001) and sunflower oil (P = 0.006) remained as protective factors and rice (P = 0.008), bread (Ptrend = 0.04), liver (P = 0.004), butter (Ptrend = 0.04), white cheese (Ptrend < 0.0001), beef (Ptrend = 0.005), vegetable ghee (P < 0.0001) and, animal ghee (P = 0.015) remained as risk factors of lung cancer. Generally, we found positive trend between consumption of beef (P = 0.002), bread (P < 0.0001), and dairy products (P < 0.0001) with lung cancer. In contrast, only fruits were inversely related to lung cancer (P < 0.0001). Conclusion: It seems that vegetables, fruits, and sunflower oil could be protective factors and bread, rice, beef, liver, dairy products, vegetable ghee, and animal ghee found to be possible risk factors for the development of lung cancer in Iran

The relationship of systemic markers of renal function and vascular function with retinal blood vessel responses

Purpose: To test the hypothesis of a significant relationship between systemic markers of renal and vascular function (processes linked to cardiovascular disease and its development) and retinal microvascular function in diabetes and/or cardiovascular disease.Methods: Ocular microcirculatory function was measured in 116 patients with diabetes and/or cardiovascular disease using static and continuous retinal vessel responses to three cycles of flickering light. Endothelial function was evaluated by von Willebrand factor (vWf), endothelial microparticles and soluble E selectin, renal function by serum creatinine, creatinine clearance and estimated glomerular filtration rate (eGFR). HbA1c was used as a control index.Results: Central retinal vein equivalence and venous maximum dilation to flicker were linked to HbA1c (both p<0.05). Arterial reaction time was linked to serum creatinine (p=0.036) and eGFR (p=0.039), venous reaction time was linked to creatinine clearance (p=0.018). Creatinine clearance and eGFR were linked to arterial maximum dilatation (p<0.001 and p=0.003 respectively) and the dilatation amplitude (p=0.038 and p=0.048 respectively) responses in the third flicker cycle. Of venous responses to the first flicker cycle, HbA1c was linked to the maximum dilation response (p=0.004) and dilatation amplitude (p=0.017), vWf was linked to the maximum constriction response (p=0.016), and creatinine clearance to the baseline diameter fluctuation (p=0.029). In the second flicker cycle, dilatation amplitude was linked to serum creatinine (p=0.022). Conclusions: Several retinal blood vessel responses to flickering light are linked to glycaemia and renal function, but only one index is linked to endothelial function. Renal function must be considered when interpreting retinal vessel responses

Complementary intestinal mucosa and microbiota responses to caloric restriction

The intestine is key for nutrient absorption and for interactions between the microbiota and its host. Therefore, the intestinal response to caloric restriction (CR) is thought to be more complex than that of any other organ. Submitting mice to 25% CR during 14 days induced a polarization of duodenum mucosa cell gene expression characterised by upregulation, and downregulation of the metabolic and immune/inflammatory pathways, respectively. The HNF, PPAR, STAT, and IRF families of transcription factors, particularly the Pparα and Isgf3 genes, were identified as potentially critical players in these processes. The impact of CR on metabolic genes in intestinal mucosa was mimicked by inhibition of the mTOR pathway. Furthermore, multiple duodenum and faecal metabolites were altered in CR mice. These changes were dependent on microbiota and their magnitude corresponded to microbial density. Further experiments using mice with depleted gut bacteria and CR-specific microbiota transfer showed that the gene expression polarization observed in the mucosa of CR mice is independent of the microbiota and its metabolites. The holistic interdisciplinary approach that we applied allowed us to characterize various regulatory aspects of the host and microbiota response to CR

Fecal microbiota and bile acid interactions with systemic and adipose tissue metabolism in diet-induced weight loss of obese postmenopausal women

Microbiota and bile acids in the gastrointestinal tract profoundly alter systemic metabolic processes. In obese subjects, gradual weight loss ameliorates adipose tissue inflammation and related systemic changes. We assessed how rapid weight loss due to a very low calorie diet (VLCD) affects the fecal microbiome and fecal bile acid composition, and their interactions with the plasma metabolome and subcutaneous adipose tissue inflammation in obesity. We performed a prospective cohort study of VLCD-induced weight loss of 10% in ten grades 2-3 obese postmenopausal women in a metabolic unit. Baseline and post weight loss evaluation included fasting plasma analyzed by mass spectrometry, adipose tissue transcription by RNA sequencing, stool 16S rRNA sequencing for fecal microbiota, fecal bile acids by mass spectrometry, and urinary metabolic phenotyping by H-NMR spectroscopy. Outcome measures included mixed model correlations between changes in fecal microbiota and bile acid composition with changes in plasma metabolite and adipose tissue gene expression pathways. Alterations in the urinary metabolic phenotype following VLCD-induced weight loss were consistent with starvation ketosis, protein sparing, and disruptions to the functional status of the gut microbiota. We show that the core microbiome was preserved during VLCD-induced weight loss, but with changes in several groups of bacterial taxa with functional implications. UniFrac analysis showed overall parallel shifts in community structure, corresponding to reduced abundance of the genus Roseburia and increased Christensenellaceae;g__ (unknown genus). Imputed microbial functions showed changes in fat and carbohydrate metabolism. A significant fall in fecal total bile acid concentration and reduced deconjugation and 7-α-dihydroxylation were accompanied by significant changes in several bacterial taxa. Individual bile acids in feces correlated with amino acid, purine, and lipid metabolic pathways in plasma. Furthermore, several fecal bile acids and bacterial species correlated with altered gene expression pathways in adipose tissue. VLCD dietary intervention in obese women changed the composition of several fecal microbial populations while preserving the core fecal microbiome. Changes in individual microbial taxa and their functions correlated with variations in the plasma metabolome, fecal bile acid composition, and adipose tissue transcriptome