bluuebunny/crossref_metadata_2025 huggingface dataset:
Frozen section during partial nephrectomy: does it predict positive margins?
Authors: Gordetsky Jennifer , Gorin Michael A. , Canner Joe , Ball Mark W. , Pierorazio Phillip M. , Allaf Mohamad E. , Epstein Jonathan I.
Published: December 2014

Objective

To investigate the clinical utility of frozen section (FS) analysis performed during partial nephrectomy (PN) and its influence on intra‐operative management.

Patients and Methods

We performed a retrospective analysis of consecutive PN cases from 2010 to 2013. We evaluated the concordance between the intra‐operative FS diagnosis and the FS control diagnosis, a postoperative quality assurance measure performed on all FS diagnoses after formalin fixation of the tissue. We also evaluated the concordance between the intra‐operative FS diagnosis and the final specimen margin. Operating reports were reviewed for change in intra‐operative management for cases with a positive or atypia FS diagnosis, or if the mass was sent for FS.

Results

A total of 576 intra‐operative FSs were performed in 351 cases to assess the PN tumour bed margin, 19 (5.4%) of which also had a mass sent for FS to assess the tumour type. The concordance rate between the FS diagnosis and the FS control diagnosis was 98.3%. There were 30 (8.5%) final positive specimen margins, of which four (13.3%) were classified as atypia, 17 (56.7%) as negative and nine (30%) as positive on FS diagnosis. Intra‐operative management was influenced in six of nine cases with a positive FS diagnosis and in one of nine cases with an FS diagnosis of atypia.

Conclusions

The relatively high false‐negative rate, controversy over the prognosis of a positive margin, and inconsistency in influencing intra‐operative management are arguments against the routine use of FS in PN cases.
Clinical and genomic analysis of metastatic prostate cancer progression with a background of postoperative biochemical recurrence
Authors: Alshalalfa Mohammed , Crisan Anamaria , Vergara Ismael A. , Ghadessi Mercedeh , Buerki Christine , Erho Nicholas , Yousefi Kasra , Sierocinski Thomas , Haddad Zaid , Black Peter C. , Karnes R. Jeffrey , Jenkins Robert B. , Davicioni Elai
Published: December 2014

Objective

To better characterize the genomics of patients with biochemical recurrence (BCR) who have metastatic disease progression in order to improve treatment decisions for prostate cancer.

Methods

The expression profiles of three clinical outcome groups after radical prostatectomy (RP) were compared: those with no evidence of disease (NED; n = 108); those with BCR (rise in prostate‐specific antigen [PSA] level without metastasis; n = 163); and those with metastasis (n = 192). The patients were profiled using Human Exon 1.0 ST microarrays, and outcomes were supported by a median 18 years of follow‐up. A metastasis signature was defined and verified in an independent RP cohort to ensure the robustness of the signature. Furthermore, bioinformatics characterization of the signature was conducted to decipher its biology.

Results

Minimal gene expression differences were observed between adjuvant treatment‐naïve patients in the NED group and patients without metastasis in the BCR group. More than 95% of the differentially expressed genes (metastasis signature) were found in comparisons between primary tumours of metastasis patients and the two other outcome groups. The metastasis signature was validated in an independent cohort and was significantly associated with cell cycle genes, ubiquitin‐mediated proteolysis, DNA repair, androgen, G‐protein coupled and NOTCH signal transduction pathways.

Conclusion

This study shows that metastasis development after BCR is associated with a distinct transcriptional programme that can be detected in the primary tumour. Patients with NED and BCR have highly similar transcriptional profiles, suggesting that measurement of PSA on its own is a poor surrogate for lethal disease. Use of genomic testing in patients undergoing RP with an initial rise in PSA level may be useful to improve secondary therapy decision‐making.
Basal expression of insulin‐like growth factor 1 receptor determines intrinsic resistance of cancer cells to a phosphatidylinositol 3‐kinase inhibitor ZSTK474
Authors: Isoyama Sho , Kajiwara Gensei , Tamaki Naomi , Okamura Mutsumi , Yoshimi Hisashi , Nakamura Naoki , Kawamura Kento , Nishimura Yumiko , Namatame Nachi , Yamori Takao , Dan Shingo
Published: December 2014

Drug resistance often critically limits the efficacy of molecular targeted drugs. Although pharmacological inhibition of phosphatidylinositol 3‐kinase (PI3K) is an attractive therapeutic strategy for cancer therapy, molecular determinants for efficacy of PI3K inhibitors (PI3Kis) remain unclear. We previously identified that overexpression of insulin‐like growth factor 1 receptor (IGF1R) contributed to the development of drug resistance after long‐term exposure to PI3Kis. In this study, we examined the involvement of basal IGF1R expression in intrinsic resistance of drug‐naïve cancer cells to PI3Kis and whether inhibition of IGF1R overcomes the resistance. We found that cancer cells highly expressing IGF1R showed resistance to dephosphorylation of Akt and subsequent antitumor effect by ZSTK474 treatment. Knockdown of IGF1R by siRNAs facilitated the dephosphorylation and enhanced the drug efficacy. These cells expressed tyrosine‐phosphorylated insulin receptor substrate 1 at high levels, which was dependent on basal IGF1R expression. In these cells, the efficacy of ZSTK474 in vitro and in vivo was improved by its combination with the IGF1R inhibitor OSI‐906. Finally, we found a significant correlation between the basal expression level of IGF1R and the inefficacy of ZSTK474 in an in vivo human cancer panel, as well as in vitro. These results suggest that basal IGF1R expression affects intrinsic resistance of cancer cells to ZSTK474, and IGF1R is a promising target to improve the therapeutic efficacy. The current results provide evidence of combination therapy of PI3Kis with IGF1R inhibitors for treating IGF1R‐positive human cancers.
Radiation signatures in childhood thyroid cancers after the Chernobyl accident: Possible roles of radiation in carcinogenesis
Authors: Suzuki Keiji , Mitsutake Norisato , Saenko Vladimir , Yamashita Shunichi
Published: December 2014

After the Tokyo Electric Power Company Fukushima Daiichi nuclear power plant accident, cancer risk from low‐dose radiation exposure has been deeply concerning. The linear no‐threshold model is applied for the purpose of radiation protection, but it is a model based on the concept that ionizing radiation induces stochastic oncogenic alterations in the target cells. As the elucidation of the mechanism of radiation‐induced carcinogenesis is indispensable to justify the concept, studies aimed at the determination of molecular changes associated with thyroid cancers among children who suffered effects from the Chernobyl nuclear accident will be overviewed. We intend to discuss whether any radiation signatures are associated with radiation‐induced childhood thyroid cancers.
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

Objective

Management 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.

Design

Members 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.

Results

A 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.

Conclusions

Significant 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

Background

A physiological increase in androgen levels occurs during adolescence. Measuring androgen concentrations is the best method to distinguish normal evolution processes from hyperandrogenic disorders.

Hypothesis

The increase in circulating androgens during puberty is inversely associated with insulin sensitivity in normal weight girls.

Objective

To 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.

Design

Prospective study of healthy girls (6–12 years) from the local community (n = 63).

Methods

Tanner 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.

Results

Basal 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.

Conclusion

In 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

Infants' 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

When 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

Aim

To 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.

Methods

The 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.

Results

Use 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.

Conclusions

Analysis 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

Aims

The 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.

Methods

Sixteen 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.

Results

Muraglitazar 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.

Conclusions

Muraglitazar 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

Aims

To investigate the effects of metformin on appetite and energy intake in obese children with hyperinsulinaemia.

Methods

We 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.

Results

Data 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.

Conclusions

These 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

Background

Alteration 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).

Methods

Twenty‐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.

Results

Compared 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).

Conclusion

RV 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

Synaptic 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

Mice 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

Labile 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.
A positive diagnosis of functional (psychogenic) tics
Authors: Demartini B. , Ricciardi L. , Parees I. , Ganos C. , Bhatia K. P. , Edwards M. J.
Published: December 2014

Background and purpose

Functional tics, also called psychogenic tics or pseudo‐tics, are difficult to diagnose because of the lack of diagnostic criteria and their clinical similarities to organic tics. The aim of the present study was to report a case series of patients with documented functional tics and to describe their clinical characteristics, risk factors and psychiatric comorbidity. Also clinical tips are suggested which might help the differential diagnosis in clinical practice.

Methods and results

Eleven patients (mean age at onset 37.2, SD 13.5; three females) were included with a documented or clinically established diagnosis of functional tics, according to consultant neurologists who have specific expertise in functional movement disorders or in tic disorders. Adult onset, absent family history of tics, inability to suppress the movements, lack of premonitory sensations, absence of pali‐, echo‐ and copro‐phenomena, presence of blocking tics, the lack of the typical rostrocaudal tic distribution and the coexistence of other functional movement disorders were common in our patients.

Conclusions

Our data suggest that functional tics can be differentiated from organic tics on clinical grounds, although it is also accepted that this distinction can be difficult in certain cases. Clinical clues from history and examination described here might help to identify patients with functional tics.
Surviving 10 years with deep brain stimulation for Parkinson's disease – a follow‐up of 79 patients
Authors: Bang Henriksen M. , Johnsen E. L. , Sunde N. , Vase A. , Gjelstrup M. C. , Østergaard K.
Published: December 2014

Background and purpose

Deep brain stimulation (DBS) for severe Parkinson's disease (PD) outperforms the best medical treatment in controlling motor symptoms and improving quality of life. Nevertheless disease progression cannot be controlled, and the development of dementia over time is nearly inevitable, often resulting in nursing home placement. Ten‐year survival, development of hallucinations, dementia and nursing home placement were examined and adverse events were assessed.

Method

Patient files were scrutinized from baseline up to 10 years of treatment or death on all 79 PD patients treated with DBS of the subthalamic nucleus from 1998 to 2003 at Aarhus University Hospital.

Results

Twenty‐four patients died during the follow‐up period of 10 years. Age above 60 years at surgery increased mortality 2.3‐fold (P = 0.04). Of the 55 surviving patients 29 (53%) were demented and 19 (35%) were in nurs‐ing homes. Average time from operation to dementia was 5.6 ± 2.9 years. Hallucinations and nursing home placement were associated with increased mortality.

Conclusion

Survival of 70% after a mean of 25 years of PD including 10 years with DBS illustrates that this is a selected group of PD patients. The prevalence of dementia steadily increased after surgery as expected from disease progression and can be an early event. Compared with the few similar long‐term studies, the present study presents a larger cohort followed at the same DBS center for a longer period of time and none was lost to follow‐up, making conclusions more valid. The present findings are of significant prognostic help for the patient, caregiver and physician when treatment with DBS has to be decided.
Better object recognition and naming outcome withMRI‐guided stereotactic laser amygdalohippocampotomy for temporal lobe epilepsy
Authors: Drane Daniel L. , Loring David W. , Voets Natalie L. , Price Michele , Ojemann Jeffrey G. , Willie Jon T. , Saindane Amit M. , Phatak Vaishali , Ivanisevic Mirjana , Millis Scott , Helmers Sandra L. , Miller John W. , Meador Kimford J. , Gross Robert E.
Published: December 2014

Objectives

Patients with temporal lobe epilepsy (TLE) experience significant deficits in category‐related object recognition and naming following standard surgical approaches. These deficits may result from a decoupling of core processing modules (e.g., language, visual processing, and semantic memory), due to “collateral damage” to temporal regions outside the hippocampus following open surgical approaches. We predicted that stereotactic laser amygdalohippocampotomy (SLAH) would minimize such deficits because it preserves white matter pathways and neocortical regions that are critical for these cognitive processes.

Methods

Tests of naming and recognition of common nouns (Boston Naming Test) and famous persons were compared with nonparametric analyses using exact tests between a group of 19 patients with medically intractable mesialTLEundergoingSLAH(10 dominant, 9 nondominant), and a comparable series ofTLEpatients undergoing standard surgical approaches (n = 39) using a prospective, nonrandomized, nonblinded, parallel‐group design.

Results

Performance declines were significantly greater for the patients with dominantTLEwho were undergoing open resection versusSLAHfor naming famous faces and common nouns (F = 24.3, p < 0.0001, η2 = 0.57, and F = 11.2, p < 0.001, η2 = 0.39, respectively), and for the patients with nondominantTLEundergoing open resection versusSLAHfor recognizing famous faces (F = 3.9, p < 0.02,η2 = 0.19). When examined on an individual subject basis, noSLAHpatients experienced any performance declines on these measures. In contrast, 32 of the 39 patients undergoing standard surgical approaches declined on one or more measures for both object types (p < 0.001, Fisher's exact test). Twenty‐one of 22 left (dominant)TLEpatients declined on one or both naming tasks after open resection, while 11 of 17 right (nondominant)TLEpatients declined on face recognition.

Significance

Preliminary results suggest (1) naming and recognition functions can be spared inTLEpatients undergoingSLAH, and (2) the hippocampus does not appear to be an essential component of neural networks underlying name retrieval or recognition of common objects or famous faces.
Oxcarbazepine and its active metabolite, (S)‐licarbazepine, exacerbate seizures in a mouse model of genetic generalized epilepsy
Authors: Kim Tae Hwan , Reid Christopher A. , Petrou Steven
Published: December 2014

Oxcarbazepine (OXC), widely used to treat focal epilepsy, is reported to exacerbate seizures in patients with generalized epilepsy. OXC is metabolized to monohydroxy derivatives in two enantiomeric forms: (R)‐licarbazepine and (S)‐licarbazepine. Eslicarbazepine acetate is a recently approved antiepileptic drug that is rapidly metabolized to (S)‐licarbazepine. It is not known whether (S)‐licarbazepine exacerbates seizures. Here, we test whether OXC or either of its enantiomers exacerbates the number of spike‐and‐wave discharges (SWDs) in mice harboring the human γ‐aminobutyric acid A receptor (GABAA)γ2(R43Q) mutation. OXC (20 mg/kg), (S)‐licarbazepine (20 mg/kg), and (R)‐licarbazepine (20 mg/kg) all significantly increased the number of SWDs, while their duration was unaffected. The potential for (S)‐licarbazepine to exacerbate SWDs suggests that eslicarbazepine acetate should be used with caution in generalized epilepsy. Furthermore, generalized seizure exacerbation for first‐, second‐, and third‐generation carbamazepine‐based compounds is likely to occur through a common mechanism.
Should consciousness describe seizures and what terms should be applied? Epilepsia's survey results
Authors: Mathern Gary W. , Beninsig Laurie , Nehlig Astrid
Published: December 2014

Objective

From May to September 2014, Epilepsia conducted an online survey seeking opinions on whether consciousness should be used in describing focal and generalized seizures, and what terms should be applied to describe focal seizures with loss of awareness and amnesia. This study reports the findings of that survey.

Methods

Two questions asked if consciousness should be used to classify seizures and what terms should be applied. Another four questions addressed demographic information.

Results

Of 209 individuals that started the poll, 147 (70.3%) completing it, and most that completed it were epileptologists (66%) from Europe (41%) and North America (27%). A majority (64%) indicated that the presence or absence of consciousness should be used to describe focal and generalized seizures, whereas 23% said it should not be used. When asked what term should be used to describe focal seizures with altered awareness and amnesia, 36% said focal impaired consciousness seizures (FICS), 30% selected complex partial seizures (CPS), and 16% answered focal dyscognitive seizures.

Significance

This survey indicates that most responders prefer that consciousness be considered in the description of focal and generalized seizures, despite the difficulty in determining awareness clinically. Furthermore, responders could not agree on a single term that could be used to define focal seizures with loss of awareness and amnesia.
Choosing between a Student–Run and Professionally Managed Venture Accelerator
Authors: Adomdza Gordon K.
Published: December 2014

This case presents challenges facing a student–run venture accelerator at a major university in the United States. The student–run model has attracted much media attention for its uniqueness, but it has also raised questions about its sustainability. Signals from a new dean, not invested in the student model, are putting much pressure on the student–chief executive officer to change course—to tweak the student–run model and fight for its future or cave in to pressures to “professionalize” it and let students take a backseat in management. The case highlights challenges in entrepreneurial leadership of a student–run accelerator at the point of initial growth.
The Impact of Sovereign Rating News on European Banks
Authors: Caselli Stefano , Gandolfi Gino , Soana Maria Gaia
Published: December 2014

This paper examines the spillover effect of Eurozone sovereign rating changes announced by Standard and Poor's, Moody's, and Fitch on domestic bank share prices in the period 2002–2012. This spillover effect appears negative in the case of downgrades, but insignificant for upgrades. Surprisingly, announcement of sovereign negative credit watches results in increased bank stock returns. Bank share price losses following sovereign downgrades increase as bank leverage, efficiency, and equity performance increase, and they decrease as bank systematic risk and payout ratio increase. On the contrary, bank share prices rise following sovereign negative credit watches, as leverage and bank size decrease and as bank systematic risk increases.
Evapotranspiration of annual and perennial biofuel crops in a variable climate
Authors: Abraha Michael , Chen Jiquan , Chu Housen , Zenone Terenzio , John Ranjeet , Su Yahn‐Jauh , Hamilton Stephen K. , Robertson G. Philip
Published: December 2014

Eddy covariance measurements were made in seven fields in the Midwest USA over 4 years (including the 2012 drought year) to estimate evapotranspiration (ET) of newly established rain‐fed cellulosic and grain biofuel crops. Four of the converted fields had been managed as grasslands under the USDA's Conservation Reserve Program (CRP) for 22 years, and three had been in conventional agriculture (AGR) soybean/corn rotation prior to conversion. In 2009, all sites were planted to no‐till soybean except one CRP grassland that was left unchanged as a reference site; in 2010, three of the former CRP sites and the three former AGR sites were planted to annual (corn) and perennial (switchgrass and mixed‐prairie) grasslands. The annual ET over the 4 years ranged from 45% to 77% (mean = 60%) of the annual precipitation (848–1063 mm; November–October), with the unconverted CRP grassland having the highest ET (622–706 mm). In the fields converted to annual and perennial crops, the annual ET ranged between 480 and 639 mm despite the large variations in growing‐season precipitation and in soil water contents, which had strong effects on regional crop yields. Results suggest that in this humid temperate climate, which represents the US Corn Belt, water use by annual and perennial crops is not greatly different across years with highly variable precipitation and soil water availability. Therefore, large‐scale conversion of row crops to perennial biofuel cropping systems may not strongly alter terrestrial water balances.
Are soil‐adjusted vegetation indices better than soil‐unadjusted vegetation indices for above‐ground green biomass estimation in arid and semi‐arid grasslands?
Authors: Ren H. , Feng G.
Published: December 2014

Accurate estimation of grassland biomass has been a central focus due to its importance in ecosystem processes and carbon cycles. This study aimed to examine whether the performance of soil‐adjusted vegetation indices for estimating above‐ground green biomass was better than that of soil‐unadjusted vegetation indices in arid and semi‐arid grasslands. Above‐ground green biomass in desert steppe of Inner Mongolia and corresponding moderate‐resolution imaging spectroradiometer (MODIS) surface reflectance 8‐day composite MOD09Q1 data were collected during late September of 2013. Results showed that soil‐adjusted SAVI (soil‐adjusted vegetation index), MSAVI (modified soil‐adjusted vegetation index), OSAVI (optimized soil‐adjusted vegetation index), TSAVI (transformed soil‐adjusted vegetation index), ATSAVI (adjusted transformed soil‐adjusted vegetation index) and PVI (perpendicular vegetation index) did not improve estimation accuracy over soil‐unadjusted simple ratio (SR) and normalized difference vegetation index (NDVI), due to low green vegetation cover (<30%) in the study area. Our results suggest that these soil‐adjusted vegetation indices may be not suitable for describing green vegetation information in arid and semi‐arid grasslands with low green vegetation cover (<30%).
Human mediator MED17 subunit plays essential roles in gene regulation by associating with the transcription and DNA repair machineries
Authors: Kikuchi Yuko , Umemura Hiroyasu , Nishitani Saori , Iida Satoshi , Fukasawa Rikiya , Hayashi Hiroto , Hirose Yutaka , Tanaka Aki , Sugasawa Kaoru , Ohkuma Yoshiaki
Published: December 2014

In eukaryotes, holo‐Mediator consists of four modules: head, middle, tail, and CDK/Cyclin. The head module performs an essential function involved in regulation of RNA polymerase II (Pol II). We studied the human head module subunit MED17 (hMED17). Recent structural studies showed that yeast MED17 may function as a hinge connecting the neck and movable jaw regions of the head module to the fixed jaw region. Luciferase assays in hMED17‐knockdown cells showed that hMED17 supports transcriptional activation, and pulldown assays showed that hMED17 interacted with Pol II and the general transcription factors TFIIB, TBP, TFIIE, and TFIIH. In addition, hMED17 bound to a DNA helicase subunit of TFIIH, XPB, which is essential for both transcription and nucleotide excision repair (NER). Because hMED17 associates with p53 upon UV‐C irradiation, we treated human MCF‐7 cells with either UV‐C or the MDM2 inhibitor Nutlin‐3. Both treatments resulted in accumulation of p53 in the nucleus, but hMED17 remained concentrated in the nucleus in response to UV‐C. hMED17 colocalized with the NER factors XPB and XPG following UV‐C irradiation, and XPG and XPB bound to hMED17 in vitro. These findings suggest that hMED17 may play essential roles in switching between transcription and NER.
Construction and validation of a scale of assessment of self‐care behaviors with arteriovenous fistula in hemodialysis
Authors: Sousa Clemente Neves , Apóstolo João Luís Alves , Figueiredo Maria Henriqueta Jesus Silva , Dias Vanessa Filipa Ferreira , Teles Paulo , Martins Maria Manuela
Published: December 2014

Several guidelines recommend the importance of educating the patient about the care of vascular access. Nurses have a key role in promoting the development of self‐care behaviors by providing the necessary knowledge to patients, so that they develop the necessary skills to take care of the arteriovenous fistula (AVF). This article describes the process of building a scale of assessment of self‐care behaviors with arteriovenous fistula in hemodialysis (ASBHD‐AVF). This is a cross‐sectional study in which the development, construction, and validation process followed the directions of the authors Streiner and Norman. This is a convenience sample, sequential, and nonprobabilistic constituted by 218 patients. The study was conducted in two stages during 2012–2014. The first phase corresponds to the scale construction process, 64 patients participated, while the second corresponds to the evaluation of metric properties and 154 patients participated. The principal component analysis revealed a two‐factor structure, with factorial weights between 0.805 and 0.511 and between 0.700 and 0.369, respectively, explaining 39.12% of the total variance of the responses. The Cronbach's alpha of the subscale management of signs and symptoms is 0.797 and from the subscale prevention of complications is 0.722. The ASBHD‐AVF revealed properties that allow its use to assess the self‐care behaviors in the maintenance and conservation of the AVF.