716 research outputs found

    Transient inactivation of the infralimbic cortex induces antidepressant-like effects in the rat

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    Affective disorders are among the main causes of disability worldwide, yet the underlying pathophysiology remains poorly understood. Recently, landmark neuroimaging studies have shown increased metabolic activity in Brodmann Area 25 (BA25) in depressed patients. Moreover, functional inactivation of this region using deep brain stimulation alleviated depressive symptoms in severely depressed patients. Thus, we examined the effect of a similar manipulation, pharmacological inactivation of the infralimbic cortex, the rodent correlate of BA25, in an animal model of antidepressant activity: the modified rat forced swim test. Transient inactivation of the infralimbic cortex using muscimol reduced immobility, an antidepressant-like effect in the test. Importantly, this activity was not the result of a general increase in locomotor activity. Activation of the infralimbic cortex using bicuculline did not alter behaviour. Finally, we examined the effect of muscimol in animals bred for high anxiety-related behaviour, which also display elevated depression-related behaviour. Transient inactivation of the infralimbic cortex decreased the high inborn depression-like behaviour of these rats. These results show that it is possible to replicate findings from a clinical trial in a rodent model. Further, they support the use of the forced swim test to gain greater understanding of the neurocircuitry involved in depression and antidepressant-action

    The role of primary healthcare professionals in oral cancer prevention and detection

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    AIM: To investigate current knowledge, examination habits and preventive practices of primary healthcare professionals in Scotland, with respect to oral cancer, and to determine any relevant training needs. SETTING: Primary care. METHOD: Questionnaires were sent to a random sample of 357 general medical practitioners (GMPs) and 331 dental practitioners throughout Scotland. Additionally, focus group research and interviews were conducted amongst primary healthcare team members. RESULTS: Whilst 58% of dental respondents reported examining regularly for signs of oral cancer, GMPs examined patients' mouths usually in response to a complaint of soreness. The majority of GMPs (85%) and dentists (63%) indicated that they felt less than confident in detecting oral cancer, with over 70% of GMPs identifying lack of training as an important barrier. Many practitioners were unclear concerning the relative importance of the presence of potentially malignant lesions in the oral cavity. A high proportion of the GMPs indicated that they should have a major role to play in oral cancer detection (66%) but many felt strongly that this should be primarily the remit of the dental team. CONCLUSION: The study revealed a need for continuing education programmes for primary care practitioners in oral cancer-related activities. This should aim to improve diagnostic skills and seek to increase practitioners' participation in preventive activities

    Insulin and GH Signaling in Human Skeletal Muscle In Vivo following Exogenous GH Exposure: Impact of an Oral Glucose Load

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    GH induces acute insulin resistance in skeletal muscle in vivo, which in rodent models has been attributed to crosstalk between GH and insulin signaling pathways. Our objective was to characterize time course changes in signaling pathways for GH and insulin in human skeletal muscle in vivo following GH exposure in the presence and absence of an oral glucose load.Eight young men were studied in a single-blinded randomized crossover design on 3 occasions: 1) after an intravenous GH bolus 2) after an intravenous GH bolus plus an oral glucose load (OGTT), and 3) after intravenous saline plus OGTT. Muscle biopsies were taken at t = 0, 30, 60, and 120. Blood was sampled at frequent intervals for assessment of GH, insulin, glucose, and free fatty acids (FFA).GH increased AUC(glucose) after an OGTT (p<0.05) without significant changes in serum insulin levels. GH induced phosphorylation of STAT5 independently of the OGTT. Conversely, the OGTT induced acute phosphorylation of the insulin signaling proteins Akt (ser(473) and thr(308)), and AS160.The combination of OGTT and GH suppressed Akt activation, whereas the downstream expression of AS160 was amplified by GH. WE CONCLUDED THE FOLLOWING: 1) A physiological GH bolus activates STAT5 signaling pathways in skeletal muscle irrespective of ambient glucose and insulin levels 2) Insulin resistance induced by GH occurs without a distinct suppression of insulin signaling proteins 3) The accentuation of the glucose-stimulated activation of AS 160 by GH does however indicate a potential crosstalk between insulin and GH.ClinicalTrials.gov NCT00477997

    The Cost of Sex: Quantifying Energetic Investment in Gamete Production by Males and Females

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    The relative energetic investment in reproduction between the sexes forms the basis of sexual selection and life history theories in evolutionary biology. It is often assumed that males invest considerably less in gametes than females, but quantifying the energetic cost of gamete production in both sexes has remained a difficult challenge. For a broad diversity of species (invertebrates, reptiles, amphibians, fishes, birds, and mammals), we compared the cost of gamete production between the sexes in terms of the investment in gonad tissue and the rate of gamete biomass production. Investment in gonad biomass was nearly proportional to body mass in both sexes, but gamete biomass production rate was approximately two to four orders of magnitude higher in females. In both males and females, gamete biomass production rate increased with organism mass as a power law, much like individual metabolic rate. This suggests that whole-organism energetics may act as a primary constraint on gamete production among species. Residual variation in sperm production rate was positively correlated with relative testes size. Together, these results suggest that understanding the heterogeneity in rates of gamete production among species requires joint consideration of the effects of gonad mass and metabolism

    Progress in Understanding and Treating SCN2A-Mediated Disorders

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    Advances in gene discovery for neurodevelopmental disorders have identified SCN2A dysfunction as a leading cause of infantile seizures, autism spectrum disorder, and intellectual disability. SCN2A encodes the neuronal sodium channel NaV1.2. Functional assays demonstrate strong correlation between genotype and phenotype. This insight can help guide therapeutic decisions and raises the possibility that ligands that selectively enhance or diminish channel function may improve symptoms. The well-defined function of sodium channels makes SCN2A an important test case for investigating the neurobiology of neurodevelopmental disorders more generally. Here, we discuss the progress made, through the concerted efforts of a diverse group of academic and industry scientists as well as policy advocates, in understanding and treating SCN2A-related disorders

    A double blind randomized trial of wound infiltration with ropivacaine after breast cancer surgery with axillary nodes dissection

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    <p>Abstract</p> <p>Background</p> <p>The effect of local infiltration after breast surgery is controversial. This prospective double blind randomized study sought to document the analgesic effect of local anaesthetic infiltration after breast cancer surgery.</p> <p>Methods</p> <p>Patients scheduled for mastectomy or tumorectomy and axillary nodes dissection had immediate postoperative infiltration of the surgical wound with 20 ml of ropivacaine 7.5 mg.ml<sup>-1 </sup>or isotonic saline. Pain was assessed on a visual analogue scale at H2, H4, H6, H12, H24, H72, and at 2 month, at rest and on mobilization of the arm. Patient'comfort was evaluated with numerical 0-3 scales for fatigue, quality of sleep, state of mood, social function and activity.</p> <p>Results</p> <p>Twenty-two and 24 patients were included in the ropivacaine and saline groups respectively. Postoperative pain was lower at rest and on mobilization at 2, 4 and 6 hour after surgery in the ropivacaine group. No other difference in pain intensity and patient 'comfort scoring was documented during the first 3 postoperative days. Patients did not differ at 2 month for pain and comfort scores.</p> <p>Conclusion</p> <p>Single shot infiltration with ropivacaine transiently improves postoperative pain control after breast cancer surgery.</p> <p>Trial registration number</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01404377">NCT01404377</a></p

    Quantitative imaging of concentrated suspensions under flow

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    We review recent advances in imaging the flow of concentrated suspensions, focussing on the use of confocal microscopy to obtain time-resolved information on the single-particle level in these systems. After motivating the need for quantitative (confocal) imaging in suspension rheology, we briefly describe the particles, sample environments, microscopy tools and analysis algorithms needed to perform this kind of experiments. The second part of the review focusses on microscopic aspects of the flow of concentrated model hard-sphere-like suspensions, and the relation to non-linear rheological phenomena such as yielding, shear localization, wall slip and shear-induced ordering. Both Brownian and non-Brownian systems will be described. We show how quantitative imaging can improve our understanding of the connection between microscopic dynamics and bulk flow.Comment: Review on imaging hard-sphere suspensions, incl summary of methodology. Submitted for special volume 'High Solid Dispersions' ed. M. Cloitre, Vol. xx of 'Advances and Polymer Science' (Springer, Berlin, 2009); 22 pages, 16 fig

    Gallstones, cholecystectomy and risk of cancers of the liver, biliary tract and pancreas

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    To examine the association between gallstones and cholecystectomy, we conducted a nationwide population-based cohort study in Denmark. Patients with a discharge diagnosis of gallstones from 1977 to 1989 were identified from the Danish National Registry of Patients and followed up for cancer occurrence until death or the end of 1993 by record linkage to the Danish Cancer Registry. Included in the cohort were 60 176 patients, with 471 450 person–years of follow-up. Cancer risks were estimated by standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) stratified by years of follow-up and by cholecystectomy status. Among patients without cholecystectomy, the risks at 5 or more years of follow-up were significantly elevated for cancers of liver (SIR = 2.0, CI = 1.2–3.1) and gallbladder (SIR = 2.7, CI = 1.5–4.4) and near unity for cancers of extrahepatic bile duct (SIR = 1.1), ampulla of Vater (SIR = 1.0) and pancreas (SIR = 1.1). The excess risk of liver cancer was seen only among patients with a history of hepatic disease. Among cholecystectomy patients, the risks at 5 or more years of follow-up declined for cancers of liver (SIR = 1.1) and extrahepatic bile duct (SIR = 0.7), but were elevated for cancers of ampulla of Vater (SIR = 2.0, CI = 1.0–3.7) and pancreas (SIR = 1.3, CI = 1.1–1.6). These findings confirm that gallstone disease increases the risk of gallbladder cancer, whereas cholecystectomy appears to increase the risk of cancers of ampulla of Vater and pancreas. Further research is needed to clarify the carcinogenic risks associated with gallstones and cholecystectomy and to define the mechanisms involved. © 1999 Cancer Research Campaig

    Combination antiretroviral therapy and the risk of myocardial infarction

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