bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug Resistance Reversal Potential of Ursolic Acid Derivatives against Nalidixic Acid‐ and Multidrug‐resistant Escherichia coli
Authors: Dwivedi Gaurav Raj , Maurya Anupam , Yadav Dharmendra Kumar , Khan Feroz , Darokar Mahendra P. , Srivastava Santosh Kumar 
Published: December 2014

As a part of our drug discovery program, ursolic acid was chemically transformed into six semi‐synthetic derivatives, which were evaluated for their antibacterial and drug resistance reversal potential in combination with conventional antibiotic nalidixic acid against the nalidixic acid‐sensitive and nalidixic acid‐resistant strains of Escherichia coli. Although ursolic acid and its all semi‐synthetic derivatives did not show antibacterial activity of their own, but in combination, they significantly reduced the minimum inhibitory concentration of nalidixic acid up to eightfold. The 3‐O‐acetyl‐urs‐12‐en‐28‐isopropyl ester (UA‐4) and 3‐O‐acetyl‐urs‐12‐en‐28‐n‐butyl ester (UA‐5) derivatives of ursolic acid reduced the minimum inhibitory concentration of nalidixic acid by eightfold against nalidixic acid‐resistant and four and eightfold against nalidixic acid‐sensitive, respectively. The UA‐4 and UA‐5 were further evaluated for their synergy potential with another antibiotic tetracycline against the multidrug‐resistant clinical isolate of Escherichia coli‐KG4. The results showed that both these derivatives in combination with tetracycline reduced the cell viability in concentration‐dependent manner by significantly inhibiting efflux pump. This was further supported by the in silico binding affinity of UA‐4 and UA‐5 with efflux pump proteins. These ursolic acid derivatives may find their potential use as synergistic agents in the treatment of multidrug‐resistant Gram‐negative infections.
3‐Keto‐1,5‐bisphosphonates Alleviate Serum‐Oxidative Stress in the High‐fat Diet Induced Obesity in Rats
Authors: Lahbib Karima , Aouani Iyadh , Cavalier Jean‐François , Touil Soufiane 
Published: December 2014

Obesity has become a leading global health problem owing to its strong association with a high incidence of oxidative stress. Many epidemiologic studies showed that an antioxidant supplementation decreases the state of oxidative stress. In the present work, a HFD‐induced rat obesity and oxidative stress were used to investigate the link between fat deposition and serum‐oxidative stress markers. We also studied the effect of a chronic administration of 3‐keto‐1,5‐bisphosphonates 1 (a & b) (40 μg/kg/8 weeks/i.p.). Exposure of rats to HFD during 16 weeks induced fat deposition, weight gain and metabolic disruption characterized by an increase in cholesterol, triglyceride and glycemia levels, and a decrease in ionizable calcium and free iron concentrations. HFD also induced serum‐oxidative stress status vocalized by an increase in ROS (H2O2), MDA and PC levels, with a decrease in antioxidant enzyme activity (CAT, GPx, SOD). Importantly, 3‐keto‐1,5‐bisphosphonates corrected all the deleterious effects of HFD treatment in vivo, but it failed to inhibit lipases in vitro and in vivo. These studies suggest that 3‐keto‐1,5‐bisphosphonates 1 could be considered as safe antioxidant agents that should also find other potential biological applications.
A 2013 European survey of clinical practice patterns in the management of Graves' disease
Authors: Bartalena L. , Burch H.B. , Burman K.D. , Kahaly G.J. 
Published: December 2014

SummaryObjectiveManagement of Graves' disease (GD) in Europe was published in 1987. Aim of this survey was to provide an update on clinical practice in Europe, and to compare it with a 2011 American survey.DesignMembers of the European Thyroid Association (ETA) were asked to participate in a survey on management of GD, using the same questionnaire of a recent American survey.ResultsA total of 147 ETA members participated. In addition to serum TSH and free T4 assays, most respondents would request TSH‐receptor autoantibody (TRAb) measurement (85·6%) and thyroid ultrasound (70·6%) to confirm aetiology, while isotopic studies were selected by 37·7%. Antithyroid drug (ATD) therapy was the preferred first‐line treatment (83·8%). Compared to the previous European survey, Europeans currently more frequently use TRAb measurement and thyroid ultrasound for diagnosis and evaluation, but first‐line treatment remains ATDs in a similar percentage of respondents. Current clinical practice patterns differ from those in North America, where isotopic studies are more frequently used, and radioiodine (RAI) still is first‐line treatment. When RAI treatment is selected in the presence of mild Graves' orbitopathy and/or associated risk factors for its occurrence/exacerbation, steroid prophylaxis is frequently used. The preferred ATD in pregnancy is propylthiouracil in the first trimester and methimazole in the second and third trimesters, similar to North America.ConclusionsSignificant changes in clinical practice patterns in Europe were noted compared to the previous European survey, as well as persisting differences in diagnosis and therapy between Europe and North America.
Leuprolide acetate‐stimulated androgen response during female puberty
Authors: Hernandez María Isabel , Martinez‐Aguayo Alejandro , Cavada Gabriel , Avila Alejandra , Iñiguez German , Mericq Veronica 
Published: December 2014

SummaryBackgroundA physiological increase in androgen levels occurs during adolescence. Measuring androgen concentrations is the best method to distinguish normal evolution processes from hyperandrogenic disorders.HypothesisThe increase in circulating androgens during puberty is inversely associated with insulin sensitivity in normal weight girls.ObjectiveTo assess circulating levels of ovarian androgens and anti‐Müllerian hormone (AMH) at baseline and after GnRH analogue (GnRH‐a) stimulation in normal pubertal girls across different Tanner stages. We also studied the association between this response and insulin sensitivity.DesignProspective study of healthy girls (6–12 years) from the local community (n = 63).MethodsTanner I (n = 23) subjects were assessed cross‐sectionally, and Tanner II girls (n = 40) were evaluated every 6 months until they reached Tanner V. Early morning dehydroepiandrosterone sulphate (DHEA‐S), AMH, sex hormone‐binding globulin (SHBG), androstenedione, glucose and insulin levels were measured. A GnRH‐a test (500 μg/m2; sc) and oral glucose intolerance test (OGTT) were performed. Differences throughout puberty were evaluated.ResultsBasal and/or stimulated Testosterone DHEA‐S and 17‐hydroxyprogesterone (17OHP) were inversely associated with insulin sensitivity (WIBSI) from the beginning of puberty, whereas androstenedione was directly associated with gonadotrophins. AMH was inversely associated with basal and stimulated gonadotrophins and directly with insulin area under the curve (AUC) only in the early stages of puberty. 17OHP and testosterone responsiveness increased significantly during puberty in all subjects, whereas testosterone levels changed less consistently. This pattern of ovarian‐steroidogenic response was most evident during mid‐ and late puberty. Moreover, during late puberty only, basal 17OHP, testosterone and DHEA‐S were positively associated with gonadotrophins.ConclusionIn normal nonobese girls born appropriate for gestational age, androgen synthesis was associated with insulin sensitivity in early puberty and with LH only in late puberty.
Understanding the effects of one's actions upon hidden objects and the development of search behaviour in 7‐month‐old infants
Authors: O'Connor Richard J. , Russell James 
Published: December 2014

AbstractInfants' understanding of how their actions affect the visibility of hidden objects may be a crucial aspect of the development of search behaviour. To investigate this possibility, 7‐month‐old infants took part in a two‐day training study. At the start of the first session, and at the end of the second, all infants performed a search task with a hiding‐well. On both days, infants had an additional training experience. The ‘Agency group’ learnt to spin a turntable to reveal a hidden toy, whilst the ‘Means‐End’ group learnt the same means‐end motor action, but the toy was always visible. The Agency group showed greater improvement on the hiding‐well search task following their training experience. We suggest that the Agency group's turntable experience was effective because it provided the experience of bringing objects back into visibility by one's actions. Further, the performance of the Agency group demonstrates generalized transfer of learning across situations with both different motor actions and stimuli in infants as young as 7 months.
Infant's action skill dynamically modulates parental action demonstration in the dyadic interaction
Authors: Fukuyama Hiroshi , Qin Shibo , Kanakogi Yasuhiro , Nagai Yukie , Asada Minoru , Myowa‐Yamakoshi Masako 
Published: December 2014

AbstractWhen interacting with infants, human adults modify their behaviours in an exaggerated manner. Previous studies have demonstrated that infant‐directed modification affects the infant's behaviour. However, little is known about how infant‐directed modification is elicited during infant–parent interaction. We investigated whether and how the infant's behaviour affects the mother's action during an interaction. We recorded three‐dimensional information of cup movements while mothers demonstrated a cup‐nesting task during interaction with their infants aged 11 to 13 months. Analyses revealed that spatial characteristics of the mother's task demonstration clearly changed depending on the infant's object manipulation. In particular, the variance in the distance that the cup was moved decreased after the infant's cup nesting and increased after the infant's task‐irrelevant manipulation (e.g. cup banging). This pattern was not observed for mothers with 6‐ to 8‐month‐olds, who do not have the fine motor skill to perform the action. These results indicate that the infant's action skill dynamically affects the infant‐directed action and suggest that the mother is sensitive to the infant's potential to learn a novel action.A video abstract of this article can be viewed at: https://www.youtube.com/watch?v=VNS2IHwLIhg&feature=youtu.be
Health‐economic analysis of real‐time continuous glucose monitoring in people with Type 1 diabetes
Authors: Roze S. , Saunders R. , Brandt A.‐S. , de Portu S. , Papo N. L. , Jendle J. 
Published: December 2014

AbstractAimTo evaluate the clinical benefits and cost‐effectiveness of the sensor‐augmented pump compared with self–monitoring of plasma glucose plus continuous subcutaneous insulin infusion in people with Type 1 diabetes.MethodsThe CORE Diabetes Model was used to simulate disease progression in a cohort of people with baseline characteristics taken from a published meta‐analysis. Direct and indirect costs for 2010–2011 were calculated from a societal payer perspective, with cost‐effectiveness calculated over the patient's lifetime. Discount rates of 3% per annum were applied to the costs and the clinical outcomes.ResultsUse of the sensor‐augmented pump was associated with an increase in mean discounted, quality–adjusted life expectancy of 0.76 quality–adjusted life years compared with continuous subcutaneous insulin infusion (13.05 ± 0.12 quality–adjusted life years vs 12.29 ± 0.12 quality–adjusted life years, respectively). Undiscounted life expectancy increased by 1.03 years for the sensor‐augmented pump compared with continuous subcutaneous insulin infusion. In addition, the onset of complications was delayed (by a mean of 1.15 years) with use of the sensor‐augmented pump. This analysis resulted in an incremental cost–effectiveness ratio of 367,571 SEK per quality–adjusted life year gained with the sensor‐augmented pump. The additional treatment costs related to the use of the sensor‐augmented pump were partially offset by the savings attributable to the reduction in diabetes‐related complications and the lower frequency of self‐monitoring of plasma glucose.ConclusionsAnalysis using the CORE Diabetes Model showed that improvements in glycaemic control associated with sensor‐augmented pump use led to a reduced incidence of diabetes‐related complications and a longer life expectancy. Use of the sensor‐augmented pump was associated with an incremental cost–effectiveness ratio of 367,571 SEK per quality–adjusted life year gained, which is likely to represent good value for money in the treatment of Type 1 diabetes in Sweden.
The effect of muraglitazar on adiponectin signalling, mitochondrial function and fat oxidation genes in human skeletal muscle in vivo
Authors: Coletta D. K. , Fernandez M. , Cersosimo E. , Gastaldelli A. , Musi N. , DeFronzo R. A. 
Published: December 2014

AbstractAimsThe molecular mechanisms by which muraglitazar (peroxisome proliferator‐activated receptor γ/α agonist) improves insulin sensitivity in Type 2 diabetes mellitus are not fully understood. We hypothesized that muraglitazar would increase expression of 5′‐monophosphate‐activated protein kinase and genes involved in adiponectin signalling, free fatty acid oxidation and mitochondrial function in skeletal muscle.MethodsSixteen participants with Type 2 diabetes received muraglitazar, 5 mg/day (n = 12) or placebo (n = 4). Before and after 16 weeks, participants had vastus lateralis muscle biopsy followed by 180 min euglycaemic hyperinsulinaemic clamp.ResultsMuraglitazar increased plasma adiponectin (9.0 ± 1.1 to 17.8 ± 1.5 μg/ml, P < 0.05), while no significant change was observed with placebo. After 16 weeks with muraglitazar, fasting plasma glucose declined by 31%, fasting plasma insulin decreased by 44%, insulin‐stimulated glucose disposal increased by 81%, HbA1c decreased by 21% and plasma triglyceride decreased by 39% (all P < 0.05). Muraglitazar increased mRNA levels of 5′‐monophosphate‐activated protein kinase, adiponectin receptor 1, adiponectin receptor 2, peroxisome proliferator‐activated receptor gamma coactivator–1 alpha and multiple genes involved in mitochondrial function and fat oxidation. In the placebo group, there were no significant changes in expression of these genes.ConclusionsMuraglitazar increases plasma adiponectin, stimulates muscle 5′‐monophosphate‐activated protein kinase expression and increases expression of genes involved in adiponectin signalling, mitochondrial function and fat oxidation. These changes represent important cellular mechanisms by which dual peroxisome proliferator‐activated receptor agonists improve skeletal muscle insulin sensitivity.
Effects of metformin on energy intake and satiety in obese children
Authors: Adeyemo M. A. , McDuffie J. R. , Kozlosky M. , Krakoff J. , Calis K. A. , Brady S. M. , Yanovski J. A. 
Published: December 2014

AimsTo investigate the effects of metformin on appetite and energy intake in obese children with hyperinsulinaemia.MethodsWe conducted a 6‐month randomized, double‐blind, placebo‐controlled trial to evaluate the effects of metformin 1000 mg twice daily on body weight and energy balance in 100 obese children with hyperinsulinaemia aged 6–12 years. The children ate ad libitum from standardized food arrays on two separate occasions before and after 6 months of study medication. The first test meal was consumed after an overnight fast. The second was preceded by a pre‐meal load. For each test meal, energy intake was recorded, and the children completed scales of hunger, fullness and desire to eat.ResultsData from the meal studies at baseline and after treatment with study medication were available for 84 children (metformin‐treated, n = 45; placebo‐treated, n = 39). Compared with placebo, metformin treatment elicited significant reductions from baseline in adjusted mean ± standard error of the mean energy intake after the pre‐meal load (metformin: −104.7 ± 83.8 kcal vs. placebo: +144.2 ± 96.9 kcal; p = 0.034) independently of changes in body composition. Metformin also significantly decreased ratings of hunger (−1.5 ± 5.6 vs. +18.6 ± 6.3; p = 0.013) and increased ratings of fullness (+10.1 ± 6.2 vs. −12.8 ± 7.0; p = 0.01) after the pre‐meal load.ConclusionsThese data suggest that decreased perceived hunger resulting in diminished food intake are among the mechanisms by which metformin treatment reduces body weight in overweight children with hyperinsulinaemia.
Right Ventricular Myocardial Motion and Deformation in Adolescents and Young Adults after Repair of Coarctation of the Aorta
Authors: Li Vivian W. Y. , Cheung Yiu‐fai 
Published: December 2014

BackgroundAlteration of right ventricular (RV) function has been found in patients with pressure‐loaded left ventricles due to systemic hypertension and aortic stenosis. We tested the hypothesis that RV mechanics are altered in adolescents and adults with repaired coarctation of the aorta (CoA).MethodsTwenty‐eight (15 male) patients, aged 23.7 ± 6.5 years, and 28 (14 male) controls were studied. M‐mode, tissue Doppler imaging, and speckle tracking echocardiography were performed to assess, respectively, LV mass and RV wall thickness, RV myocardial tissue velocities, and deformation. Systolic (P = 0.14) and diastolic (P = 0.32) blood pressures were similar between patients and controls.ResultsCompared with controls, patients had significantly greater LV mass (P = 0.016) and RV anterior wall thickness (P = 0.012). Tricuspid annular systolic (P < 0.001) and early diastolic (P < 0.001) velocities, isovolumic acceleration (P = 0.004), global RV systolic longitudinal strain (P = 0.03), systolic strain rate (P = 0.012), and early (P = 0.021) and late (P = 0.012) diastolic strain rates were significantly lower in patients than controls. Patients with an associated ventricular septal defect (n = 6) requiring closure compared to those without had even lower tricuspid annular systolic (P = 0.01) and early diastolic (P = 0.041) velocities. Left ventricular mass correlated negatively with RV systolic strain rate (r = −0.27, P = 0.045) and tricuspid annular early diastolic velocity (r = −0.40, P = 0.002), while RV anterior wall thickness correlated negatively with tricuspid annular systolic (r = −0.42, P = 0.002) and late diastolic (r = −0.40, P = 0.003) velocities, and positively with e/a ratio (r = 0.31, P = 0.024).ConclusionRV systolic and diastolic mechanics are impaired in patients late after repair of CoA and related to increased LV mass and RV thickness.
Synaptic vesicle glycoprotein 2A modulates vesicular release and calcium channel function at peripheral sympathetic synapses
Authors: Vogl Christian , Tanifuji Shota , Danis Benedicte , Daniels Veronique , Foerch Patrik , Wolff Christian , Whalley Benjamin J. , Mochida Sumiko , Stephens Gary J. 
Published: December 2014

AbstractSynaptic vesicle glycoprotein (SV)2A is a transmembrane protein found in secretory vesicles and is critical for Ca2+‐dependent exocytosis in central neurons, although its mechanism of action remains uncertain. Previous studies have proposed, variously, a role of SV2 in the maintenance and formation of the readily releasable pool (RRP) or in the regulation of Ca2+ responsiveness of primed vesicles. Such previous studies have typically used genetic approaches to ablate SV2 levels; here, we used a strategy involving small interference RNA (siRNA) injection to knockdown solely presynaptic SV2A levels in rat superior cervical ganglion (SCG) neuron synapses. Moreover, we investigated the effects of SV2A knockdown on voltage‐dependent Ca2+ channel (VDCC) function in SCG neurons. Thus, we extended the studies of SV2A mechanisms by investigating the effects on vesicular transmitter release and VDCC function in peripheral sympathetic neurons. We first demonstrated an siRNA‐mediated SV2A knockdown. We showed that this SV2A knockdown markedly affected presynaptic function, causing an attenuated RRP size, increased paired‐pulse depression and delayed RRP recovery after stimulus‐dependent depletion. We further demonstrated that the SV2A–siRNA‐mediated effects on vesicular release were accompanied by a reduction in VDCC current density in isolated SCG neurons. Together, our data showed that SV2A is required for correct transmitter release at sympathetic neurons. Mechanistically, we demonstrated that presynaptic SV2A: (i) acted to direct normal synaptic transmission by maintaining RRP size, (ii) had a facilitatory role in recovery from synaptic depression, and that (iii) SV2A deficits were associated with aberrant Ca2+ current density, which may contribute to the secretory phenotype in sympathetic peripheral neurons.
Parallel pathways from motor and somatosensory cortex for controlling whisker movements in mice
Authors: Sreenivasan Varun , Karmakar Kajari , Rijli Filippo M. , Petersen Carl C. H. 
Published: December 2014

AbstractMice can gather tactile sensory information by actively moving their whiskers to palpate objects in their immediate surroundings. Whisker sensory perception therefore requires integration of sensory and motor information, which occurs prominently in the neocortex. The signalling pathways from the neocortex for controlling whisker movements are currently poorly understood in mice. Here, we delineate two pathways, one originating from primary whisker somatosensory cortex (wS1) and the other from whisker motor cortex (wM1), that control qualitatively distinct movements of contralateral whiskers. Optogenetic stimulation of wS1 drove retraction of contralateral whiskers while stimulation of wM1 drove rhythmic whisker protraction. To map brainstem pathways connecting these cortical areas to whisker motor neurons, we used a combination of anterograde tracing using adenoassociated virus injected into neocortex and retrograde tracing using monosynaptic rabies virus injected into whisker muscles. Our data are consistent with wS1 driving whisker retraction by exciting glutamatergic premotor neurons in the rostral spinal trigeminal interpolaris nucleus, which in turn activate the motor neurons innervating the extrinsic retractor muscle nasolabialis. The rhythmic whisker protraction evoked by wM1 stimulation might be driven by excitation of excitatory and inhibitory premotor neurons in the brainstem reticular formation innervating both intrinsic and extrinsic muscles. Our data therefore begin to unravel the neuronal circuits linking the neocortex to whisker motor neurons.
Factors controlling labile soil organic matter vulnerability to loss following disturbance as assessed by measurement of soil‐respired δ13CO2
Authors: Zakharova A. , Beare M. H. , Cieraad E. , Curtin D. , Turnbull M. H. , Millard P. 
Published: December 2014

SummaryLabile soil organic matter (SOM) is often stabilized in soil, but is vulnerable to loss after soil disturbance. We used measurements of the 13carbon (13C) signature of soil‐respired CO2 (δ13CO2) immediately after the disturbance caused by coring and sampling the soil, to assess labile SOM availability and potential vulnerability to loss. We incubated a range of pasture soils over 300 minutes and periodically measured δ13CO2. Strong temporal trends in δ13CO2 suggest that labile SOM became vulnerable to loss within minutes of soil disturbance. Equilibrium soil‐respired δ13CO2 values were a function of the amount of labile SOM (measured as hot‐water extractable C, HWEC), total soil C and soil protection capacity (measured as specific soil surface area, SSA). An independent experimental approach that immobilized labile SOM on to allophane (a clay mineral with a large active surface area) was used to assess the effect of SSA on equilibrium soil‐respired δ13CO2. In this experiment δ13CO2 shifted progressively to more enriched values during the first six days of soil incubations after allophane addition, suggesting that labile SOM became less available after stabilization by allophane. At the same time there was a large reduction in HWEC when compared with the control treatments, also indicating limited availability of labile SOM. Further studies coupling the isotopic measurements with CO2 evolution rates are needed to test directly whether equilibrium δ13CO2 can reflect labile SOM vulnerability to loss.