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Glioblastomas exhibit remarkable heterogeneity at various levels, including motility modes and mechanoproperties that contribute to tumor resistance and recurrence. In a recent study using gridded micropatterns mimicking the brain vasculature, glioblastoma cell motility modes, mechanical properties, formin content, and substrate chemistry are linked. Now is presented, SP2G (SPheroid SPreading on Grids), an analytic platform designed to identify the migratory modes of patient‐derived glioblastoma cells and rapidly pinpoint the most invasive sub‐populations. Tumorspheres are imaged as they spread on gridded micropatterns and analyzed by this semi‐automated, open‐source, Fiji macro suite that characterizes migration modes accurately. SP2G can reveal intra‐patient motility heterogeneity with molecular correlations to specific integrins and EMT markers. This system presents a versatile and potentially pan‐cancer workflow to detect diverse invasive tumor sub‐populations in patient‐derived specimens and offers a valuable tool for therapeutic evaluations at the individual patient level. [ABSTRACT FROM AUTHOR]

Objectives: To assess perioperative outcomes, complications, and rate of uretero–ileal anastomotic stricture (UAS) in patients undergoing retrosigmoid ileal conduit after radical cystectomy (RC). Patients and Methods: Clinical records of consecutive patients receiving retrosigmoid ileal conduit after open RC for bladder cancer between March 2016 and June 2020 at two academic centres were prospectively collected. Two expert surgeons performed all cases. Operating room (OR) time, estimated blood loss (EBL), transfusion rate, and 90‐day postoperative complications classified according to the Clavien–Dindo system, were assessed. In particular, rate of UAS, defined as upper urinary tract dilatation requiring endourological or surgical management, was evaluated. Results: A total of 97 patients were analysed. The median (interquartile range [IQR]) OR time was 245 (215–290) min, median (IQR) EBL was 350 (300–500) mL, and blood transfusions were given to 15 (15.5%) cases. There were no intraoperative complications. There were 90‐day postoperative complications in 33 patients (34%), being major (Grade III–V) in 19 (19.6%). Two patients died from early postoperative complications. At a median (IQR) follow‐up of 25 (14–40) months, there was only one case (1%) of UAS, involving the right ureter and requiring an open uretero–ileal re‐implantation. Conclusion: The retrosigmoid ileal conduit is a safe and valid option for non‐continent urinary diversion after RC, ensuring a very low risk of UAS at an intermediate‐term follow‐up. [ABSTRACT FROM AUTHOR]

In the Neotropical region, euphonias (Euphonia spp., Fringillidae) are the quintessential example of specialized bird frugivores, making the bulk of feeding visits to certain mistletoes (Phoradendron spp., Santalaceae) and epiphytes in the genus Rhipsalis (Cactaceae), whose fruits have high water and low sugar and protein concentrations. Surprisingly, a mechanistic explanation for such specialized, otherwise rare, relationships is lacking. Using captive birds and artificial diets, we contrasted euphonias with frugivorous tanagers in the genus Thraupis (Thraupidae), which rarely eats Rhipsalis fruits, to test the hypothesis that the digestive capacity of euphonias entails them to exploit such low‐energy fruits. We expected that compensatory feeding in response to decreasing energy density would occur only in euphonias, whose higher reliance on fruits would entail a lower nitrogen requirement than the tanagers. Euphonias and tanagers were both able to compensate energy intake as sugar density decreased, and both species had the same mass‐corrected energy intake at any given sugar concentration. Similarly, euphonias and tanagers did not differ in mass‐corrected maintenance nitrogen requirement. Therefore, the physiological traits we investigated do not explain euphonias' specialization on Rhipsalis fruits. The fast rates of fruit passage typical of specialized avian frugivores as euphonias that entail the processing of a large volume of fruits and the putative better abilities of such birds to deal with secondary compounds likely present in Rhipsalis fruits are other possible mechanisms that should be considered in future studies to unveil the mechanisms underlying the intriguing specialized relationships between euphonias and certain fruits. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease of unknown etiology with minimal treatment options. Repetitive alveolar epithelial injury has been suggested as one of the causative mechanisms of this disease. Type 2 alveolar epithelial cells (AEC2) play a crucial role during fibrosis by functioning as stem cells able to repair epithelial damage. The DNA demethylase Tet methylcytosine dioxygenase 2 (TET2) regulates the stemness of multiple types of stem cells, but whether it also affects the stemness of AEC2 during fibrosis remains elusive. To study the role of TET2 in AEC2 during fibrosis, we first determined TET2 protein levels in the lungs of IPF patients and compared TET2 expression in AEC2 of IPF patients and controls using publicly available data sets. Subsequently, pulmonary fibrosis was induced by the intranasal administration of bleomycin to wild‐type and AEC2‐specific TET2 knockout mice to determine the role of TET2 in vivo. Fibrosis was assessed by hydroxyproline analysis and fibrotic gene expression. Additionally, macrophage recruitment and activation, and epithelial injury were analyzed. TET2 protein levels and gene expression were downregulated in IPF lungs and AEC2, respectively. Bleomycin inoculation induced a robust fibrotic response as indicated by increased hydroxyproline levels and increased expression of pro‐fibrotic genes. Additionally, increased macrophage recruitment and both M1 and M2 activation were observed. None of these parameters were, however, affected by AEC2‐specific TET2 deficiency. TET2 expression is reduced in IPF, but the absence of TET2 in AEC2 cells does not affect the development of bleomycin‐induced pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the ability of original tumour contact surface area (CSA) to predict postoperative complications and renal function impairment in a series of patients who underwent elective partial nephrectomy (PN) for renal masses. Materials and Methods: We analysed the clinical records of 531 consecutive patients who underwent elective PN because of a suspicion of kidney cancer at five academic, high‐volume centres between January 2014 and December 2016. Each participating centre evaluated prospectively the radiological images to evaluate the CSA and to assign a PADUA score. Several expert surgeons performed the surgical procedures in each participating centre. Binary logistic regression was used to perform both univariable and multivariable analyses to identify predictors of postoperative complications. Linear regression analysis was used to identify independent predictors of absolute change in estimated glomerular filtration rate (eGFR; ACE). Results: The median (interquartile range) CSA value was 14.2 (7.4–25.1) cm2. A total of 349 tumours (65.7%) had a CSA ≤ 20 cm2 and the remaining 182 (34.3%) had a CSA > 20 cm2. PNs were performed using an open approach in 237 (44.6%) cases, a pure laparoscopic approach in 152 cases (28.6%), and a robot‐assisted approach in the remaining 142 cases (26.7%). Multivariable analyses found that only age (odds ratio [OR] 1.037, 95% confidence interval [CI] 1.018–1.057) and PADUA score (OR 1.289, 95%CI 1.132–1.469) were independent predictors of postoperative complications. Tumour CSA (OR 1.020, 95%CI 1.010–1.030) was found to be an independent predictor of postoperative complications only when PADUA score was removed from the model. Age (from −0.639 to −0.306; P < 0.001); body mass index (from 0.267 to 1.076; P = 0.001), age‐adjusted Charlson score (from −3.193 to −0.259; P = 0.02), preoperative eGFR value (from −0.939 to −0.862; P < 0.001) and tumour CSA (from −0.260 to −0.048; P = 0.005) were found to be independent predictors of ACE. Conclusions: Tumour CSA is an independent predictor of postoperative renal function. Conversely, at multivariable analysis, PADUA score outperformed tumour CSA to predict postoperative complications after PN. The complexity of The Leslie et al. formula for calculating tumour CSA is a potential limitation with regard to its diffusion and application in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Optimal procedure for storage of feline blood is needed. Open-collection systems have been employed in feline medicine, thus limiting the possibility for storage. Objectives: To evaluate indicators of quality of feline blood stored for 35 days at +4°C in a closed-collection system specifically designed for cats. Animals: Eight healthy adult European domestic shorthair cats with a weight of 5-6.8 kg. Methods: This is a case series study. A bacteriological test, CBC, blood smear, pH, osmotic fragility, 2,3-diphosphoglycerate (2,3-DPG), and adenosine triphosphate (ATP) measurement were performed weekly on whole blood (WB) units from day 1 to day 35 after donation. The hemolysis index, lactate and potassium concentrations, prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen were measured on plasma aliquots. Results: One out of eight blood units (BUs) had bacterial growth (Serratia marcescens) at day 35. No significant differences were found regarding CBC, morphology, pH, and osmotic fragility. Despite high inter-individual variability and low starting levels, significant decreases in the mean concentrations of 2,3-DPG (T0 1.99 mmol/g Hb, SD 0.52, T35 1.25 mmol/g Hb, SD 1.43; P5.003) and ATP (T0 1.45 mmol/g Hb, SD 0.71, T35 0.62 mmol/g Hb, SD 0.51; P<.001) were detected during the study, as opposed to an increase in hemolysis (T0 0.11 mmol/L, SD 0.07, T35 0.84 mmol/L, SD 0.19; P<.001), lactate (T0 3.30 mmol/L, SD 0.86, T35 13.36 mmol/L, SD 2.90; P<.001), and potassium (T0 3.10 mmol/L, SD 0.21, T35 4.12 mmol/L, SD 0.35; P<.001) concentrations. Conclusions and Clinical Importance: The commercial BU kit is appropriate for blood collection and conservation of WB in cats. The maintenance of WB quality indicators during storage is essential for future improvements of feline transfusion medicine [ABSTRACT FROM AUTHOR]

Objectives To validate Graves' classification of the intrarenal arteries and to verify the absence of collateral arterial blood supply between different renal segments, in order to maximize peri-operative and functional outcomes of partial nephrectomy. Materials and Methods The study was performed on 15 normal kidneys sampled from eight unembalmed cadavers. Kidneys with the surrounding perirenal fat tissue were removed en bloc with the abdominal segment of the aorta. The renal artery was injected with acrylic and radiopaque resins, with the specimen suspended in water. CT examination of the injected kidneys was performed to analyse the branches located deeply. After imaging acquisition, the specimens were treated with sodium hydroxide for removal of the parenchyma to obtain vascular casts. Results Ten casts (66.6%) showed the classic subdivision of the main artery into single posterior and anterior branches. With regard to the distribution of the segmental or second-order arteries, only two casts (13%) showed a pattern similar to that described by Graves, characterized by four segmental (second-order) branches coming from the anterior renal artery (apical, superior, middle and inferior). In the remaining 13 kidneys (87%) a different arterial vascular network was detected. In 10 casts (80%) a single renal segment was vascularized by two or more different branches coming from an artery leading to another segment (multiple vascularization). Multiple vascularization was observed in three (20%) apical segments, five (33%) superior segments, six (40%) middle segments, seven (47%) inferior segments and two (13%) posterior segments. Conclusions This study shows that in the human kidneys the arterial vasculature is frequently different from that described by Graves. Moreover, in a significant percentage of cases, a single renal segment receives two or more branches that originate from an artery leading to another segment. [ABSTRACT FROM AUTHOR]

Objectives To describe step-by-step an original urethrovesical anastomosis technique (urethral fixation) in patients undergoing retropubic radical prostatectomy ( RRP), to compare their early urinary continence recovery with those in a control group receiving a standard anastomosis technique and to identify the predictors of early urinary continence recovery. Patients and methods We compared 70 patients who underwent RRP with the urethral-fixation technique with a contemporary control group of 51 patients who received RRP with a standard urethrovesical anastomosis. In the urethral-fixation group, the urethrovesical anastomosis was made using eight single sutures. Specifically, to avoid retraction and/or deviations, we fixed the urethral stump laterally to the medial portion of levator ani muscle. Also, to maintain the normal position in the context of the pelvic floor, we fixed the urethral sphincter deeper to the medial dorsal raphe using a 3-0 polydioxanone suture at the 6 o'clock position before completing the incision of the urethral wall. Urinary continence recovery was evaluated at 1, 4, 8 and 12 weeks after catheter removal. Patients self-reporting no urine leak were considered continent. Uni- and multivariable analyses were used to identify predictors of urinary incontinence at the different follow-up time-points. Results The evaluated groups had comparable preoperative variables. At 1 week after catheter removal, 32 (45.7%) patients in the urethral-fixation group and 10 (19.6%) in the control group were continent ( P = 0.01). At 4 weeks after catheter removal, 46 (65.7%) patients in the urethral-fixation group and 16 (31.4%) in the control group were continent ( P = 0.001). At 8 weeks after catheter removal, 59 (84.3%) patients in the urethral-fixation group and 21 (41.2%) in the control group were continent ( P < 0.001). Finally, at 12 weeks after catheter removal, 63 (90%) patients in the urethral-fixation group and 32 (62.7%) in the control group were continent ( P = 0.001). The urethral-fixation technique was an independent predictor of urinary continence recovery at 1 week [odds ratio ( OR) 4.305; P = 0.002); 4 weeks ( OR 4.784; P < 0.001); 8 weeks ( OR 7.678; P < 0.001) and 12 weeks ( OR 5.152; P = 0.001) after catheter removal. Conclusions The urethral-fixation technique significantly improves early urinary continence recovery in comparison with the standard technique. Moreover, our study confirmed that this surgical technique is an independent predictor of urinary continence recovery at 1, 4, 8 and 12 weeks after catheter removal. [ABSTRACT FROM AUTHOR]

In the last 10 years, it was possible to state that CAVM was diagnosed I in utero i few times, due to the lack of understanding of the condition and because the difficult to visualise, but with the advent of high-resolution ultrasound, imaging exam has improved and elevated the diagnosis of CAVM in the last years. Results Using the colour Doppler ultrasound, one case of CAVM was diagnosed prenatally at 33 weeks of gestation, at another time, combined with magnetic resonance imaging (MRI) it diagnosed five cases of CAVM. Cerebral arteriovenous malformations (CAVM) of the fetus are rare and are considered congenital in nature. [Extracted from the article]

R2176 --> 891.1 --> The insular cortex (IC) has been described as part of the central network implicated in the behavioral and physiological responses to emotional stress. Besides, it has been reported a site‐specific control of physiological functions along the rostrocaudal axis of the IC. Nevertheless, evaluation of a functional topography of the IC in the regulation of the responses to stressful stimuli has never been documented. Therefore, this study aimed to investigate the impact of acute restraint stress in neuronal activation at different sites along the rostrocaudal axis of the IC in rats. Furthermore, we evaluated the involvement of IC rostrocaudal subregions in the cardiovascular responses to acute restraint stress. For this, male Wistar rats (60‐days‐old) were used. The restraint stress was performed by placing the animals in a cylindrical plastic tube for 60 minutes. For the cardiovascular study, different set of animals had cannula‐guide bilaterally implanted into the anterior, rostral posterior of caudal posterior subregions of the IC; and the non‐selective synaptic inhibitor CoCl2(1mM/100nL) was microinjected 10 min before the restraint onset. We observed that acute restraint stress increased the number of Fos‐immunoreactive cells in the rostral posterior region of the IC (t=2.95, df=14, P=0.0106), while fewer activated cells were identified in the anterior (t=2.44, df=14, P= 0.0276) and caudal posterior (t=2.27, df=14, P=0.0388) regions. Treatment of the anterior region of the IC with CoCl2 did not affect the blood pressure (F(1,15)=0.90, P>0.05) and heart rate (F(1,15)=0.3, P>0.05) increases and the sympathetically‐mediated cutaneous vasoconstriction (F(1,15)=2.23, P>0.05) evoked by restraint stress. However, synaptic ablation of the rostral posterior IC decreased the restraint‐evoked arterial pressure increase (F(1,21)=5.3, P=0.0313), but without affecting the tachycardia (F(1,21)=4.1, P=0.0561) and the reduction in tail skin temperature (F(1,21)=0.05, P>0.05). Besides, bilateral microinjection of CoCl2 into the caudal posterior IC decreased the tachycardia to restraint stress (F(1,17)=11.3, P=0.0036), but without affecting the blood pressure (F(1,17)= 0.2, P>0.05) and tail skin temperature (F(1,17)= 1.4, P>0.05) responses. Taken together, these findings indicate a site‐specific regulation of stress response along the rostrocaudal axis of the IC. [ABSTRACT FROM AUTHOR]

Objective To describe Ebola cases in the district Ebola management centre of in Kailahun, a remote rural district of Sierra Leone, in terms of geographic origin, patient and hospitalisation characteristics, treatment outcomes and time from symptom onset to admission. Methods Data of all Ebola cases from June 23rd to October 5th 2014 were reviewed. Ebola was confirmed by reverse-transcriptase-polymerase-chain-reaction assay. Results Of 489 confirmed cases (51% male, median age 28 years), 166 (34%) originated outside Kailahun district. Twenty-eight (6%) were health workers: 2 doctors, 11 nurses, 2 laboratory technicians, 7 community health workers and 6 other cadres. More than 50% of patients had fever, headache, abdominal pain, diarrhoea/vomiting. An unusual feature was cough in 40%. Unexplained bleeding was reported in 5%. Outcomes for the 489 confirmed cases were 227 (47%) discharges, 259 (53%) deaths and 3 transfers. Case fatality in health workers (68%) was higher than other occupations (52%, P = 0.05). The median community infectivity time was 6.5 days for both general population and health workers ( P = 0.4). Conclusions One in three admitted cases originated outside Kailahun district due to limited national access to Ebola management centres - complicating contact tracing, safe burial and disinfection measures. The comparatively high case fatality among health workers requires attention. The community infectivity time needs to be reduced to prevent continued transmission. [ABSTRACT FROM AUTHOR]

The goal in blog search is to rank blogs according to their recurrent relevance to the topic of the query. State-of-the-art approaches view it as an expert search or resource selection problem. We investigate the effect of content-based similarity between posts on the performance of the retrieval system. We test two different approaches for smoothing (regularizing) relevance scores of posts based on their dependencies. In the first approach, we smooth term distributions describing posts by performing a random walk over a document-term graph in which similar posts are highly connected. In the second, we directly smooth scores for posts using a regularization framework that aims to minimize the discrepancy between scores for similar documents. We then extend these approaches to consider the time interval between the posts in smoothing the scores. The idea is that if two posts are temporally close, then they are good sources for smoothing each other's relevance scores. We compare these methods with the state-of-the-art approaches in blog search that employ Language Modeling-based resource selection algorithms and fusion-based methods for aggregating post relevance scores. We show performance gains over the baseline techniques which do not take advantage of the relation between posts for smoothing relevance estimates. [ABSTRACT FROM AUTHOR]

Dynamic exercise evokes sustained cardiovascular changes, which are characterized by blood pressure and heart rate (HR) increases. Although it is well accepted that there is a central nervous system (CNS) mediation of cardiovascular adjustments during dynamic exercise, information on the role of specific CNS structures is limited. The bed nucleus of the stria terminalis (BST) is a forebrain structure known to be involved in central cardiovascular control. Based on this, we tested the hypothesis that BST modulates HR and mean arterial pressure (MAP) responses evoked when rats are submitted to dynamic exercise. Male Wistar rats were tested at three levels of exercise (0.4, 0.8 and 1 km h−1) on a rodent treadmill before and after BST treatment with CoCl2, a non-selective neurotransmission blocker. Bilateral microinjection of CoCl2 (1 nmol in 100 nl artificial cerebrospinal fluid) into the BST reduced the pressor response to exercise at 0.4 km h−1 as well as the tachycardic responses evoked by exercise at 0.4, 0.8 and 1 km h−1. The BST treatment with CoCl2 did not affect baseline MAP or HR, suggesting a lack of tonic BST influence on cardiovascular parameters at rest. Moreover, BST treatment with CoCl2 did not affect motor performance in the open-field test, which indicates that effects of BST inhibition on cardiovascular responses to dynamic exercise are not due to changes in motor activity. The present results suggest that local neurotransmission in the BST modulates exercise-related cardiovascular adjustments. Data indicate that BST facilitates pressor and tachycardic responses evoked by dynamic exercise in rats. [ABSTRACT FROM AUTHOR]

1. In the present study, we investigated the effects of inhibition of the lateral hypothalamus (LH) neurotransmission with bilateral microinjection of CoCl2, a non-selective blocker of neurotransmission, on modulation of cardiac baroreflex responses in conscious rats as well as the involvement of LH glutamatergic neurotransmission in this modulation. 2. Reflex bradycardiac and tachycardiac responses to blood pressure increases (following i.v. infusion of phenylephrine) or decreases (following i.v. infusion of sodium nitroprusside) were investigated in conscious male Wistar rats. Responses were evaluated before and after microinjection of 1 nmol/100 nL CoCl2, 2 nmol/100 nL 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzoquinoxaline-7-sulphonamide (NBQX; a selective non- N-methyl-d-aspartate (NMDA) glutamate receptor antagonist) or different doses (2, 4 or 8 nmol/100 nL) of the selective NMDA glutamate receptor antagonist LY235959. 3. Microinjection of CoCl2 into the LH had no effect on the tachycardiac baroreflex response, but did evoke a decrease in the reflex bradycardia caused by increases in blood pressure. Microinjection of NBQX into the LH had a similar effect on reflex bradycardia as CoCl2, but had no effect on the tachycardiac response. Microinjection of increasing doses of LY235959 into the LH had no effect on the cardiac baroreflex response. 4. In conclusion, the data suggest that the LH has a tonic facilitatory influence on the parasympathetic component of the baroreflex. The results also indicate that this facilitatory influence is mediated by local LH glutamatergic neurotransmission through non-NMDA glutamatergic receptors. [ABSTRACT FROM AUTHOR]

Microinjection of noradrenaline into the bed nucleus of the stria terminalis (BST) has been reported to cause a pressor response in unanesthetized rats, which was shown to be mediated by acute vasopressin release into the systemic circulation. In the present study we verified the involvement of magnocellular neurons of the hypothalamic paraventricular (PVN) or supraoptic (SON) nuclei and the local neurotransmitter involved in the pressor response to noradrenaline microinjection into the BST. The PVN pretreatment with the non-selective neurotransmission blocker CoCl2 (1 nmol/100 nL) inhibited the noradrenaline-evoked pressor response. However, responses were not affected by SON treatment with CoCl2. Further experiments were carried out to test if glutamatergic neurotransmission in the PVN mediates the pressor response evoked by noradrenaline microinjection into the BST. Pretreatment of the PVN with the selective N-methyl-d-aspartate (NMDA) receptor antagonist LY235959 (2 nmol/100 nL) did not affect the noradrenaline-evoked pressor response. However, PVN pretreatment with the selective non-NMDA receptor antagonist NBQX (2 nmol/100 nL) significantly reduced the pressor response to noradrenaline microinjection into the BST. In conclusion, our results suggest that pressor responses to noradrenaline microinjection into the BST are mediated by PVN magnocellular neurons without involvement of SON neurons. They also suggest that a glutamatergic neurotransmission through non-NMDA glutamate receptors in the PVN mediates the response. [ABSTRACT FROM AUTHOR]

Background and Purpose: We have previously shown that noradrenaline microinjected into the bed nucleus of stria terminalis (BST) elicited pressor and bradycardiac responses in unanaesthetized rats. In the present study, we investigated the subtype of adrenoceptors that mediates the cardiovascular response to noradrenaline microinjection into the BST.Experimental Approach: Cardiovascular responses following noradrenaline microinjection into the BST of male Wistar rats were studied before and after BST pretreatment with different doses of the selective alpha(1)-adrenoceptor antagonist WB4101, the alpha(2)-adrenoceptor antagonist RX821002, the combination of WB4101 and RX821002, the non-selective beta-adrenoceptor antagonist propranolol, the selective beta(1)-adrenoceptor antagonist CGP20712 or the selective beta(2)-adrenoceptor antagonist ICI118,551.Key Results: Noradrenaline microinjected into the BST of unanaesthetized rats caused pressor and bradycardiac responses. Pretreatment of the BST with different doses of either WB4101 or RX821002 only partially reduced the response to noradrenaline. However, the response to noradrenaline was blocked when WB4101 and RX821002 were combined. Pretreatment with this combination also shifted the resulting dose-effect curve to the left, clearly showing a potentiating effect of this antagonist combination. Pretreatment with different doses of either propranolol or CGP20712 increased the cardiovascular responses to noradrenaline microinjected into the BST. Pretreatment with ICI118,551 did not affect cardiovascular responses to noradrenaline.Conclusion and Implications: The present results indicate that alpha(1) and alpha(2)-adrenoceptors mediate the cardiovascular responses to noradrenaline microinjected into the BST. In addition, they point to an inhibitory role played by the activation of local beta(1)-adrenoceptors in the cardiovascular response to noradrenaline microinjected into the BST. [ABSTRACT FROM AUTHOR]

Background and purpose:We have previously shown that noradrenaline microinjected into the bed nucleus of stria terminalis (BST) elicited pressor and bradycardiac responses in unanaesthetized rats. In the present study, we investigated the subtype of adrenoceptors that mediates the cardiovascular response to noradrenaline microinjection into the BST.Experimental approach:Cardiovascular responses following noradrenaline microinjection into the BST of male Wistar rats were studied before and after BST pretreatment with different doses of the selective α1-adrenoceptor antagonist WB4101, the α2-adrenoceptor antagonist RX821002, the combination of WB4101 and RX821002, the non-selective β-adrenoceptor antagonist propranolol, the selective β1-adrenoceptor antagonist CGP20712 or the selective β2-adrenoceptor antagonist ICI118,551.Key results:Noradrenaline microinjected into the BST of unanaesthetized rats caused pressor and bradycardiac responses. Pretreatment of the BST with different doses of either WB4101 or RX821002 only partially reduced the response to noradrenaline. However, the response to noradrenaline was blocked when WB4101 and RX821002 were combined. Pretreatment with this combination also shifted the resulting dose-effect curve to the left, clearly showing a potentiating effect of this antagonist combination. Pretreatment with different doses of either propranolol or CGP20712 increased the cardiovascular responses to noradrenaline microinjected into the BST. Pretreatment with ICI118,551 did not affect cardiovascular responses to noradrenaline.Conclusion and implications:The present results indicate that α1 and α2-adrenoceptors mediate the cardiovascular responses to noradrenaline microinjected into the BST. In addition, they point to an inhibitory role played by the activation of local β1-adrenoceptors in the cardiovascular response to noradrenaline microinjected into the BST.British Journal of Pharmacology (2008) 153, 583–590; doi:10.1038/sj.bjp.0707591; published online 26 November 2007 [ABSTRACT FROM AUTHOR]

The authors report on an experimental study on the differences between spoken and written queries. A set of written and spontaneous spoken queries are generated by users from written topics. These two sets of queries are compared in qualitative terms and in terms of their retrieval effectiveness. Written and spoken queries are compared in terms of length, duration, and part of speech. In addition, assuming perfect transcription of the spoken queries, written and spoken queries are compared in terms of their aptitude to describe relevant documents. The retrieval effectiveness of spoken and written queries is compared using three different information retrieval models. The results show that using speech to formulate one's information need provides a way to express it more naturally and encourages the formulation of longer queries. Despite that, longer spoken queries do not seem to significantly improve retrieval effectiveness compared with written queries. [ABSTRACT FROM AUTHOR]

The connective tissue disorders (also called collagen vascular diseases) represent an heterogeneous group of immunologically mediated inflammatory disorders with a large variety of affected organs besides the lungs. The respiratory system may be involved in all its components: airways, vessels, parenchyma, pleura, respiratory muscles, etc. The frequency, clinical presentation, prognosis and response to therapy vary, depending on the pattern of involvement as well as on the underlying connective tissue disorders. The subject of this review is to describe the most frequent type of lung disorders observed in patients with connective tissue disease (CTD). We will focus on the most frequent CTD: systemic lupus erythematosus, rheumatoid arthritis, scleroderma, Sjogren's syndrome, dermatopolymyositis and mixed CTD. [ABSTRACT FROM AUTHOR]

Detecting and correctly identifying haemoglobin (Hb) variants is typically achieved by a two-levels laboratory approach. We report our experience in dealing with 91 Hb variants, including a number of frequent and a few rare variants. Screening included akaline agarose gel electrophoresis (AGE), ion-exchange automated high-performance liquid chromatography (HPLC) and a test for deoxyhaemoglobin solubility. Identification was based on electrospray ionization–mass spectrometry (ESI–MS). Our results confirmed the advantages of HPLC over AGE for screening, because of the occurrence of some electrophoretically‘silent’ variants. ESI–MS permitted the definitive identification of 90 of the 91 variants included in the study, in some cases (e.g. HbS) through the application of a simple protocol (direct injection of the sample), in other cases requiring the application of more demanding procedures (purification of the variant chain and peptide analysis after enzymatic or chemical cleavage). In an additional case (Hb J-Oxford), ESI–MS assay did not lead to definitive identification, but gave indications for designing the appropriate primers to focus DNA sequence analysis on the specific region of the gene. Deoxyhaemoglobin solubility test was positive only in the presence of HbS. We conclude that HPLC and ESI–MS are advantageously integrated into a two-level analytical system for the detection and confirmation of variant Hbs. [ABSTRACT FROM AUTHOR]

Asthma control and prevention of exacerbations are primary objectives for asthma care. However there is a lack of universal definition of these notions which may therefore have a different meaning according to the physician's practice. In the present survey, 1805 general practitioners, 551 pulmonologists, 176 allergologists and 470 resuscitation/emergency care physicians were randomly selected in fall 2001 and asked to answer one question on asthma control and three questions on asthma exacerbation. Regarding asthma control, the presence of minimum symptoms was the primary criterion for asthma specialists (pulmonologists and allergologists), while a normal respiratory function was first considered by nonspecialist physicians (general practitioners and emergency care physicians). The first criterion of mild exacerbation for asthma specialists was the occurrence during at least 2 days of an increase in the frequency of dyspnoea and/or the use of short-acting bronchodilators. For nonspecialist physicians, dyspnoea affecting daily activities and/or sleeping was the preferred notion. Hospitalization was unanimously recognized as the first criterion for severe exacerbations. A decrease in peak expiratory flow of more than 30% below the baseline value on two consecutive days and an episode requiring systemic corticosteroids were the next criteria. This survey emphasizes the complexity of the notions of asthma control and exacerbation and provides novel informations to orient continuing education programmes. [ABSTRACT FROM AUTHOR]

Research on the use of mathematical, logical, and forreal methods, has been central to Information Retrieval research for a long time. Research in this area is important not only because it helps enhancing retrieval effectiveness, but also because it helps clarifying the underlying concepts of Information Retrieval. in this article we outline some of the major aspects of the subject, and summarize the papers of this special issue with respect to how they relate to these aspects. We conclude by highlighting some directions of future research, which are needed to better understand the formal characteristics of Information Retrieval. [ABSTRACT FROM AUTHOR]

Focuses on a study of a user's perception of the relevance of documents. How users' perception varies depending on the form that retrieved documents are presented; Effectiveness of advanced multimedia information retrieval applications; Low levels of users' perception of relevance of retrieved documents; Prevalent interest in ubiquitous computing.

Background and objective: Genetic analysis is emerging for interstitial lung diseases (ILDs); however, ILD practices are not yet standardized. We surveyed patients', relatives' and pulmonologists' experiences and needs on genetic testing in ILD to evaluate the current situation and identify future needs. Methods: A clinical epidemiologist (MT) together with members of the ERS taskforce and representatives of the European Idiopathic Pulmonary Fibrosis and related disorders Federation (EU‐IPFF) patient organisation developed a survey for patients, relatives and pulmonologists. Online surveys consisted of questions on five main topics: awareness of hereditary ILD, the provision of information, genetic testing, screening of asymptomatic relatives and clinical impact of genetic analysis in ILD. Results: Survey respondents consisted of 458 patients with ILD, 181 patients' relatives and 352 pulmonologists. Most respondents think genetic testing can be useful, particularly for explaining the cause of disease, predicting its course, determining risk for developing disease and the need to test relatives. Informing patients and relatives on genetic analysis is primarily performed by the pulmonologist, but 88% (218) of pulmonologists identify a need for more information and 96% (240) ask for guidelines on genetic testing in ILD. A third of the pulmonologists who would offer genetic testing currently do not offer a genetic test, primarily because they have limited access to genetic tests. Following genetic testing, 72% (171) of pulmonologists may change the diagnostic work‐up and 57% (137) may change the therapeutic approach. Conclusion: This survey shows that there is wide support for implementation of genetic testing in ILD and a high need for information, guidelines and access to testing among patients, their relatives and pulmonologists. [ABSTRACT FROM AUTHOR]

Background and objective: Data regarding interstitial lung disease (ILD) in the setting of systemic lupus erythematosus (SLE) are limited. We used a nationwide database to determine the incidence and the prevalence of ILD in SLE. Methods: Characteristics of all SLE inpatients admitted between 2011 and 2012 in France were analysed through the French medico‐administrative database. Features associated with the presence of ILD were studied. Cox hazard model was used to measure the impact of ILD on survival from the first stay to 2020. The incidence of ILD in SLE was estimated by analysing the onset of ILD from 2013 to 2020 in SLE patients who had no evidence of ILD in 2013. Results: Between 2011 and 2012, 10,460 SLE patients had at least one hospital stay and could be traced until 2020. Among them, 134 (1.2%) had an ILD diagnosed at baseline. The frequency of ILD in SLE was higher in patients who had an associated autoimmune disease such as Sjögren's syndrome or systemic sclerosis (29.9% vs. 5.9%, p < 0.0001). ILD was associated with an increased risk of death in SLE in the multivariable analysis (hazard ratio [95% CI] 1.992 [1.420–2.794]; p < 0.0001). Among the 31,029 SLE patients with no evidence of ILD at baseline, ILD occurred in 795 (2.6%) between 2013 and 2020. The incidence rate of ILD in SLE was 10.26 for 1000 patient‐years [95% CI: 10.24–10.28]. Conclusion: In SLE, ILD is exceedingly rare, often associated with another systemic autoimmune disorder and appears as a major risk factor for death. [ABSTRACT FROM AUTHOR]

The article discusses a case of a 14-year-old adolescent female who was presented for evaluation of hypersensitivity to glatiramer acetate. After several tests, she was found to have an immunoglobulin E (IgE)-mediated allergy to glatiramer acetate. A desensitization protocol was formulated with a gradual dose of escalation period to address the problem.

The article discusses the surgical margin (SM) after a radical prostatectomy which is more complex. It cites on the clinical significance of close surgical margin (CSMs) with tumour approaching but a far less investigated field of research. The article also discusses the principles to ascertain the significance of CSMs which include uniform definition, accurate pathology examination and correct prognostic assessment.

Introduction: Launois-Bensaude syndrome (LBS) is a rare disease, characterized by the accumulation of fatty tissue predominantly in the neck, shoulders and thorax, whose diagnostic is clinical. Objectives: We describe a new case in a 73 year-old man. As the patient was obese, complained of snoring and was treated for hypertension, we looked for a morbid association with an obstructive sleep apnea syndrome (OSAS). Methods: A polysomnography (PSG) and a cervical magnetic resonance imaging (MRI) were performed. Results: PSG demonstrated OSAS with an apnea-hypopnea index of 43/h. Cervical MRI showed fatty infiltration resulting in airway narrowing at the pharyngeal but not at the tracheal level. Only, 3 cases of such a morbid association have already been published; in 2 of these patients was a tracheal compression. More over a metabolic syndrome was present. Conclusions: This observation draws attention to the need for seeking OSAS among patients affected by LBS, even in a moderate form, and emphasises the roles of the upper airway narrowing by the fat infiltration as well as the role of the metabolic syndrome in the genesis of OSAS. Please cite this paper as: Jalladeau E, Crestani B, Laissy J-P and Vecchierini MF. A case of obstructive sleep apnea syndrome: unusual comorbidity. The Clinical Respiratory Journal 2008; 2: 239–241. [ABSTRACT FROM AUTHOR]

We included women addressed for the exploration of an undetermined or suspicious mass, excluded all patients that did not undergo ultrasound or MR imaging. Moreover, MUFI may help at improving diagnostic performances of the combination of simple ultrasound and MR imaging. [Extracted from the article]

Background and Objective Methods Results Conclusion Chronic interstitial lung disease (ILD) occurs rarely with systemic lupus erythematosus (SLE) as compared with other connective tissue diseases. This multicentric retrospective study of patients with SLE‐ILD from the OrphaLung and French SLE networks during 2005–2020 aimed to describe the characteristics of patients with SLE‐ILD and analyse factors associated with prognosis.We analysed data for 89 patients with SLE‐ILD (82 women, 92.1%) (median age at SLE diagnosis: 35 years [interquartile range 27–47]). All patients met the 2019 EULAR/ACR criteria for the diagnosis of SLE.Forty two (47.2%) patients were positive for anti‐ribonuclear protein antibodies and 45 (50.6%) for anti SSA/Ro antibodies. A total of 58 (65.2%) patients had another connective tissue disease: Sjögren's syndrome (n = 33, 37.1%), systemic sclerosis (n = 14, 15.7%), inflammatory myopathy (n = 6, 6.7%), or rheumatoid arthritis (n = 6, 6.7%). ILD was diagnosed along with SLE in 25 (28.1%) patients and at a median of 6 (0–14) years after the SLE diagnosis. The most frequent CT pattern was suggestive of non‐specific interstitial pneumonia (n = 41, 46.0%) with or without superimposed organizing pneumonia. After a median follow‐up of 86.5 [39.5–161.2] months, 18 (20.2%) patients had died and 6 (6.7%) underwent lung transplantation. The median 5‐year and 10‐year transplantation‐free survival were 96% (92–100) and 87% (78–97). In total, 44 (49.4%) patients showed ILD progression. Cutaneous manifestations and Raynaud's phenomenon were associated with better survival. Only forced vital capacity was significantly associated with survival and ILD progression.ILD is a rare manifestation of SLE with good overall prognosis but with possible risk of ILD progression. Patients with SLE‐ILD frequently have another connective tissue disease. [ABSTRACT FROM AUTHOR]

Fake news is considered one of the main threats of our society. The aim of fake news is usually to confuse readers and trigger intense emotions to them in an attempt to be spread through social networks. Even though recent studies have explored the effectiveness of different linguistic patterns for fake news detection, the role of emotional signals has not yet been explored. In this paper, we focus on extracting emotional signals from claims and evaluating their effectiveness on credibility assessment. First, we explore different methodologies for extracting the emotional signals that can be triggered to the users when they read a claim. Then, we present emoCred, a model that is based on a long‐short term memory model that incorporates emotional signals extracted from the text of the claims to differentiate between credible and non‐credible ones. In addition, we perform an analysis to understand which emotional signals and which terms are the most useful for the different credibility classes. We conduct extensive experiments and a thorough analysis on real‐world datasets. Our results indicate the importance of incorporating emotional signals in the credibility assessment problem. [ABSTRACT FROM AUTHOR]

To maintain the health and well‐being of all mammals, numerous aspects of physiology are controlled by neuroendocrine mechanisms. These mechanisms ultimately enable communication between neurones and glands throughout the body and are centrally mediated by neuropeptides and/or steroid hormones. A recent session at the International Workshop in Neuroendocrinology highlighted the essential roles of some of these neuropeptide and steroid hormone mediators in the neuroendocrine regulation of stress‐, reproduction‐ and behaviour‐related processes. Accordingly, the present review highlights topics presented in this session, including the role of the neuropeptides corticotrophin‐releasing factor and gonadotrophin‐releasing hormone in stress and reproductive physiology, respectively. Additionally, it details an important role for gonadal sex steroids in the development of behavioural sex preference. [ABSTRACT FROM AUTHOR]

This study investigated the role of AT1, AT2 and Mas angiotensinergic receptors within the MeA in autonomic, cardiovascular and baroreflex changes evoked by a 10‐day (1 hr daily) repeated restraint stress (RRS) protocol. Analysis of cardiovascular function after the end of the RRS protocol indicated increased values of arterial pressure, without heart rate changes. Arterial pressure increase was not affected by acute MeA treatment after the RRS with either the selective AT1 receptor antagonist losartan, the selective AT2 receptor antagonist PD123319 or the selective Mas receptor antagonist A‐779. Analysis of heart rate variability indicated that RRS increased the sympathetic tone to the heart, which was inhibited by MeA treatment with either losartan, PD123319 or A‐779. Baroreflex function assessed using the pharmacological approach via intravenous infusion of vasoactive agents revealed a facilitation of tachycardia evoked by blood pressure decrease in chronically stressed animals, which was inhibited by MeA treatment with losartan. Conversely, baroreflex responses during spontaneous fluctuations of blood pressure were impaired by RRS, and this effect was not affected by injection of the angiotensinergic receptor antagonists into the MeA. Altogether, the data reported in the present study suggest an involvement of both angiotensinergic receptors present in the MeA in autonomic imbalance evoked by RRS, as well as an involvement of MeA AT1 receptor in the enhanced baroreflex responses during full range of blood pressure changes. Results also indicate that RRS‐evoked increase in arterial pressure and impairment of baroreflex responses during spontaneous variations of arterial pressure are independent of MeA angiotensinergic receptors. [ABSTRACT FROM AUTHOR]

• Malnutrition prevention is mandatory for gestational caloric restriction. • Gestational caloric restriction increases mitochondrial function in pups' adulthood. • Pups go through adaptation during development. • Gestational caloric restriction acts on METS complexes, especially in the cerebellum. • Gestational caloric restriction directly affects litter brain. Developmental origins of health and disease (DOHaD) is a field of biological science dedicated to investigating how different interventions during development affect an individual's life. Diet is an essential way to interact with the environment, and during pregnancy affects not only the mother but also can impact the next generations. One of these interventions is caloric restriction (CR), which has shown positive redox modulation in rats' offspring when malnutrition is responsibly controlled. Considering that mitochondrial metabolism is determinant for redox status, we investigated parameters related to mitochondrial functionality and reactive species levels in offspring's brain from rats delivered to pregnant caloric restricted dams. Therefore, pregnant rats were divided between control (ad libitum food) and CR (20% food restriction plus micronutrients supplementation) groups, and offspring's brain was analyzed on post-natal days (PND) 0, 7, 21, and 60. Mitochondrial function, as well as superoxide content, were decreased in most brain areas on PND0 and went through adaptation, showing increased mass and membrane potential in adulthood. Concerning mitochondrial electron transport system (METS), the most affected area was the cerebellum, which was impaired at birth and activated at adulthood. In conclusion, our results show that gestational CR promotes adaptation from impaired mitochondrial parameters at birth, improving mitochondrial function when compared to control, without increasing superoxide generation, at adult age. More studies are necessary in order to support the use of CR as a clinical approach. [ABSTRACT FROM AUTHOR]

The metabolic transition from anaerobic glycolysis and fatty acid β‐oxidation to glycolysis coupled to oxidative phosphorylation is a key process for the transition of quiescent neural stem cells to proliferative neural progenitor cells. However, a full characterization of the metabolic shift and the involvement of mitochondria during the last step of neurogenesis, from neuroblasts to neuron maturation, is still elusive. Here, we describe a model of neuroblasts, Neuro2a cells, with impaired differentiation capacity due to mitochondrial dysfunction. Using a detailed biochemical characterization consisting of steady‐state metabolomics and metabolic flux analysis, we find increased fatty acid β‐oxidation as a peculiar feature of neuroblasts with altered mitochondria. The consequent metabolic switch favors neuroblast proliferation at the expense of neuron maturation. [ABSTRACT FROM AUTHOR]

Objective: To simplify the original Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) classification of renal tumours, generating a new system able to predict equally or better the risk of overall complications in patients undergoing partial nephrectomy (PN); and to test if the addition of the contact surface area (CSA) parameter improves the accuracy of the original PADUA and new Simplified PADUA REnal (SPARE) nephrometry classification systems. Patients and Methods: We analysed the clinical records of 531 patients who underwent PN (open, laparoscopic and robot‐assisted) for renal tumours at five tertiary academic referral centres from January 2014 to December 2016. The ability of each variable included in the PADUA classification to predict overall complications was tested using binary logistic regression analysis. The variables that were not statistically significant were excluded from the SPARE classification. In addition to the original PADUA and SPARE systems, another two models were generated adding tumour CSA. Receiver operating characteristic curve analysis was used to compare the ability of the four different models to predict overall complications. Binary logistic regression was used to perform both univariable and multivariable analyses looking for predictors of postoperative complications. Linear regression analysis was used to identify independent predictors of absolute change in estimated glomerular filtration rate (eGFR; ACE). Results: The SPARE nephrometry score system including: (i) rim location, (ii) renal sinus involvement, (iii) exophytic rate, and (iv) tumour dimension; showed equal performance in comparison with the original PADUA score (area under the curve [AUC] 0.657 vs 0.664). Adding tumour CSA to the original PADUA (AUC 0.661) or to the SPARE (AUC 0.658) scores did not increase the accuracy of either system to predict overall complications. The SPARE system (odds ratio 1.2, 95% confidence interval 1.1–1.3) was an independent predictor of postoperative overall complications. Age (P < 0.001), body mass index (P < 0.001), Charlson Comorbidity Index (P = 0.02), preoperative eGFR (P < 0.001), and tumour CSA (P = 0.005) were independent predictors of ACE. Limitations include the retrospective design and the lack of central imaging review. Conclusions: The new SPARE score is comprised of only four variables instead of the original six and its accuracy to predict overall complications is similar to that of the original PADUA score. Addition of tumour CSA was not associated with an increase in prognostic accuracy. The SPARE system could replace the original PADUA score to evaluate the complexity of tumours suitable for PN. [ABSTRACT FROM AUTHOR]

Background: Jabuticaba is a tasty Brazilian fruit that can be used in vinegar production. This study aimed to determine the phenolic, volatile, and sensory profiles; antioxidant activity; and chemical characteristics of vinegars produced with fruits, with and without the peel, of Myrciaria cauliflora (Mart.) O.Berg and Myrciaria jaboticaba (Vell.) Berg. Results: Fourteen phenolic compounds were identified and quantified, classified between phenolic acids and flavonoids, with emphasis on 3,4‐dihydroxybenzoic acid, chlorogenic acid, and sinapic acid. The highest antioxidant activity was found in M. jaboticaba vinegar, made with unpeeled fruits. For volatile compounds, 21 esters, 7 alcohols, 5 terpenes, 1 ketone, and 1 vinylarene were identified. Sensory analysis showed similarities in terms of taste and differences in terms of odor between Jabuticaba vinegars and commercial vinegars. The mineral content demonstrates the nutritional potential of vinegars in terms of macro and micronutrients, with a predominance of potassium and calcium. Phenolic compounds, acetic acid, and esters were the main chemical groups identified. Vinegars, in general, showed differences concerning the presence and absence of peels. Conclusion: Vinegars produced with different varieties of Jabuticabas can be a promising alternative for obtaining beverages with important compounds for human health, promoting local production, and adding value to regional products. [ABSTRACT FROM AUTHOR]

The article focuses on outcomes of patients with small renal tumours who are treated with robot-assisted or open partial nephrectomy. Topics discussed include comparison of transperitoneal robot assisted partial nephrectomy (RAPN) and retroperitoneal open partial nephrectomy (OPN), multivariable analysis of body mass index (BMI) and Charlson comorbidity index to predict complications and complications of RAPN and OPN such as estimated blood loss (EBL) or genitourinary complications.

Background and Objective: The minor T‐allele of the MUC5B promoter polymorphism rs35705950 is strongly associated with idiopathic pulmonary fibrosis (IPF). However, conflicting results have been reported on the relationship between the MUC5B minor allele and survival and it is unknown whether a specific subgroup of IPF patients might benefit from MUC5B minor allele carriage. We investigated the association between MUC5B rs35705950, survival and patient characteristics in a real‐world population of European IPF patients. Methods: In this retrospective study, 1751 patients with IPF from 8 European centres were included. MUC5B rs35705950 genotype, demographics, clinical characteristics at diagnosis and survival data were analysed. Results: In a multi‐variate Cox proportional hazard model the MUC5B minor allele was a significant independent predictor of survival when adjusted for age, sex, high resolution computed tomography pattern, smoking behaviour and pulmonary function tests in IPF. MUC5B minor allele carriers were significantly older at diagnosis (p = 0.001). The percentage of MUC5B minor allele carriers increased significantly with age from 44% in patients aged <56 year, to 63% in patients aged >75. In IPF patients aged <56, the MUC5B minor allele was not associated with survival. In IPF patients aged ≥56, survival was significantly better for MUC5B minor allele carriers (45 months [CI: 42–49]) compared to non‐carriers (29 months [CI: 26–33]; p = 4 × 10−12). Conclusion: MUC5B minor allele carriage associates with a better median transplant‐free survival of 16 months in the European IPF population aged over 56 years. MUC5B genotype status might aid disease prognostication in clinical management of IPF patients. In idiopathic pulmonary fibrosis (IPF), the proportion of MUC5B rs35705950 minor allele carriers increases significantly with age. In IPF patients diagnosed at ≥56 years, transplant free survival is significantly better for MUC5B minor allele carriers compared to non‐carriers. These findings support implementation of MUC5B genotyping for clinical prognostication in IPF. [ABSTRACT FROM AUTHOR]

ABSTRACT Systems consolidation has been described as a time-dependent reorganization process involving the neocortical and hippocampal networks underlying memory storage and retrieval. Previous studies of our lab were able to demonstrate that systems consolidation is a dynamic process, rather than a merely passive, time-dependent phenomenon. Here, we studied the influence of sequential learning in contextual fear conditioning (CFC) with different training intensities in the time-course of hippocampal dependency and contextual specificity. We found that sequential learning with high-intensity shocks during CFC induces generalization of the first learning (context A) and maintains contextual specificity of the second learning (context B) 15 days after acquisition. Moreover, subsequent experiences reorganize brain structures involved in retrieval, accelerating the involvement of cortical structures and diminishing the hippocampal participation. Exposure to original context before novelty seems to only induce context specificity in hippocampal-dependent memories. We propose that systems consolidation could be considered a potential biological mechanism for reducing possible interferences between similar memory traces. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Opinion mining refers to the use of natural language processing, text analysis, and computational linguistics to identify and extract subjective information in textual material. Opinion mining, also known as sentiment analysis, has received a lot of attention in recent times, as it provides a number of tools to analyze public opinion on a number of different topics. Comparative opinion mining is a subfield of opinion mining which deals with identifying and extracting information that is expressed in a comparative form (e.g., 'paper X is better than the Y'). Comparative opinion mining plays a very important role when one tries to evaluate something because it provides a reference point for the comparison. This paper provides a review of the area of comparative opinion mining. It is the first review that cover specifically this topic as all previous reviews dealt mostly with general opinion mining. This survey covers comparative opinion mining from two different angles. One from the perspective of techniques and the other from the perspective of comparative opinion elements. It also incorporates preprocessing tools as well as data set that were used by past researchers that can be useful to future researchers in the field of comparative opinion mining. [ABSTRACT FROM AUTHOR]

Background: The mechanisms by which genetic and environmental factors interact to promote asthma remain unclear. Both the IL‐4 receptor alpha chain R576 (IL‐4RαR576) variant and Notch4 license asthmatic lung inflammation by allergens and ambient pollutant particles by subverting lung regulatory T (Treg) cells in an IL‐6‐dependent manner. Objective: We examined the interaction between IL‐4RαR576 and Notch4 in promoting asthmatic inflammation. Methods: Peripheral blood mononuclear cells (PBMCs) of asthmatics were analyzed for T helper type 2 cytokine production and Notch4 expression on Treg cells as a function of IL4RR576 allele. The capacity of IL‐4RαR576 to upregulate Notch4 expression on Treg cells to promote severe allergic airway inflammation was further analyzed in genetic mouse models. Results: Asthmatics carrying the IL4RR576 allele had increased Notch4 expression on their circulating Treg cells as a function of disease severity and serum IL‐6. Mice harboring the Il4raR576 allele exhibited increased Notch4‐dependent allergic airway inflammation that was inhibited upon Treg cell‐specific Notch4 deletion or treatment with an anti‐Notch4 antibody. Signaling via IL‐4RαR576 upregulated the expression in lung Treg cells of Notch4 and its downstream mediators Yap1 and beta‐catenin, leading to exacerbated lung inflammation. This upregulation was dependent on growth factor receptor‐bound protein 2 (GRB2) and IL‐6 receptor. Conclusion: These results identify an IL‐4RαR576‐regulated GRB2‐IL‐6‐Notch4 circuit that promotes asthma severity by subverting lung Treg cell function. [ABSTRACT FROM AUTHOR]

Many transition-metal complexes and some metal-free compounds are able to bind carbon monoxide, a molecule which has the strongest chemical bond in nature. However, very few of them have been shown to induce the cleavage of its C−O bond and even fewer are those that are able to transform CO into organic reagents with potential in organic synthesis. This work shows that bis(pinacolato)diboron, B2pin2, reacts with ruthenium carbonyl to give metallic complexes containing borylmethylidyne (CBpin) and diborylethyne (pinBC≡CBpin) ligands and also metal-free perborylated C1 and C2 products, such as C(Bpin)4 and C2(Bpin)6, respectively, which have great potential as building blocks for Suzuki-Miyaura cross-coupling and other reactions. The use of 13CO-enriched ruthenium carbonyl has demonstrated that the boron-bound carbon atoms of all of these reaction products arise from CO ligands. [ABSTRACT FROM AUTHOR]

Many transition-metal complexes and some metal-free compounds are able to bind carbon monoxide, a molecule which has the strongest chemical bond in nature. However, very few of them have been shown to induce the cleavage of its C−O bond and even fewer are those that are able to transform CO into organic reagents with potential in organic synthesis. This work shows that bis(pinacolato)diboron, B2pin2, reacts with ruthenium carbonyl to give metallic complexes containing borylmethylidyne (CBpin) and diborylethyne (pinBC≡CBpin) ligands and also metal-free perborylated C1 and C2 products, such as C(Bpin)4 and C2(Bpin)6, respectively, which have great potential as building blocks for Suzuki-Miyaura cross-coupling and other reactions. The use of 13CO-enriched ruthenium carbonyl has demonstrated that the boron-bound carbon atoms of all of these reaction products arise from CO ligands. [ABSTRACT FROM AUTHOR]

Cocaine and anabolic–androgenic steroids are substances commonly co-abused. The use of anabolic steroids and cocaine has increased among adolescents. However, few studies investigated the consequences of the interaction between anabolic–androgenic steroids in animals’ model of adolescence. We examined the effects of acute and repeated testosterone administration on cocaine-induced locomotor activity in adult and adolescent rats. Rats received ten once-daily subcutaneous (s.c.) injections of testosterone (10 mg/kg) or vehicle. Three days after the last testosterone or vehicle injections rats received an intraperitoneal (i.p.) challenge injection of either saline or cocaine (10 mg/kg). A different subset of rats was treated with a single injection of testosterone (10 mg/kg) or vehicle and three days later was challenged with cocaine (10 mg/kg, i.p.) or saline. Immediately after cocaine or saline injections the locomotor activity was recorded during forty minutes. Our results demonstrated that repeated testosterone induced locomotor sensitization to cocaine in adolescent but not adult rats. [ABSTRACT FROM AUTHOR]

R3361 --> 534.9 --> The lateral hypothalamus (LH) is an important hypothalamic area that has been implicated in the integration of behavioral and physiological responses to stress. The corticotropin‐releasing factor (CRF) system has been shown to be an important neurochemical mechanism in the central nervous system involved in the etiology of the behavioral changes evoked by exposure to aversive situations. The exposure to chronic stress affects the expression of CRF neurotransmission components in brain regions controlling stress responses. However, the role of CRF neurotransmission within the LH in the anxiogenic responses evoked by acute and repeated restraint stress (RS) has not been investigated. Here, was investigated the effect of bilateral microinjection into the LH of the selective CRF1 receptor antagonist CP376395 or the selective CRF2 receptor antagonist antisauvagine‐30 (ASV‐30) in the anxiogenic responses following the first and the 10th session of restraint stress (RS) in male rats. For this, male Wistar rats (250g) had cannula‐guide bilaterally implanted within the LH. The RS was realized by placing the animals in a plastic cylindrical tube for 60 minutes. Independent sets of animals received CP376395 (0.01 mol/100nL), ASV‐30 (0.01 mol/100nL) or vehicle into the LH 10 minutes before the onset of the first or 10th session of RS. Immediately after the end of the stress session, the animals were individually placed in the elevated plus maze (EPM) for 5 minutes to assess anxiety‐related behaviors. The behavioral analysis revealed that an acute RS session decreased the % of entries and time in the open arms of the EPM in vehicle‐treated animals, when compared to animals that were not submitted to restraint stress (i.e., naïve group) (P<0.05). Bilateral microinjection of either CP376395 or ASV‐30 into the LH inhibited the decreased open‐arms exploration caused by acute restraint stress (P<0.05). We did not identify behavioral changes in the EPM in animals repeatedly subjected to restraint stress, and pharmacological treatments also had no behavioral effect when administered before the 10th RS session (P>0.05). Taken together, the results indicates that the CRFergic neurotransmission in the LH, acting through activation of both CRF1 and CRF2 receptors, is involved in the generation of anxiety‐like behaviors induced by acute restraint stress, and the previous repeated exposure to this stressor affect this control. [ABSTRACT FROM AUTHOR]

Adolescence has been proposed as an ontogenic period of vulnerability to stress. Nevertheless, the impact of stressful events during adolescence in cardiovascular activity is poorly understood. Therefore, the purpose of this study was to investigate the immediate and long-lasting effects of exposure to stressful events during adolescence in cardiovascular function of rats. To this end, we compared the impact of 10-days exposure to two chronic stress protocols: the repeated restraint stress (RRS, homotypic) and chronic variable stress (CVS, heterotypic). Independent groups of animals were tested 24 h (immediate) or three weeks (long-lasting) following completion of stress period. Exposure to CVS, but not RRS, during adolescence increased basal HR values without affecting arterial pressure, which was followed by augmented power of oscillatory component at low frequency (sympathetic-related) of the pulse interval (PI). RRS enhanced variance of the PI with an increase in the power of both low and high (parasympathetic-related) frequency components. RRS also increased the baroreflex gain. Neither RRS nor CVS affected systolic arterial pressure variability. The RRS-evoked changes in PI variability were long-lasting and persisted into adulthood while all alterations evoked by the CVS were reversed in adulthood. These findings indicate a stress type-specific influence in immediate and long-term effects of stress during adolescence in cardiovascular function. While immediate changes in cardiovascular function were mainly observed following CVS, long-lasting autonomic consequences in adulthood were observed only in animals exposed to RRS during adolescence. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the role of the lateral hypothalamus ( LH) and its local glutamatergic neurotransmission in the cardiovascular adjustments observed when rats are submitted to acute restraint stress. Bilateral microinjection of the nonspecific synaptic inhibitor Co Cl2 (0.1 nmol in 100 nL) into the LH enhanced the heart rate ( HR) increase evoked by restraint stress without affecting the blood pressure increase. Local microinjection of the selective N-methyl- d-aspartate ( NMDA) glutamate receptor antagonist LY235959 (2 nmol in 100 nL) into the LH caused effects that were similar to those of Co Cl2. No changes were observed in the restraint-related cardiovascular response after a local microinjection of the selective non- NMDA glutamatergic receptor antagonist NBQX (2 nmol in 100 nL) into the LH. Intravenous administration of the muscarinic cholinergic receptor antagonist homatropine methyl bromide (0.2 mg/kg), a quaternary ammonium drug that does not cross the blood-brain barrier, abolished the changes in cardiovascular responses to restraint stress following LH treatment with LY235959. In summary, our findings show that the LH plays an inhibitory role on the HR increase evoked by restraint stress. Present results also indicate that local NMDA glutamate receptors, through facilitation of cardiac parasympathetic activity, mediate the LH inhibitory influence on the cardiac response to acute restraint stress. [ABSTRACT FROM AUTHOR]

Background and Purpose: The Arp2/3 multiprotein complex regulates branched polymerisation of the actin cytoskeleton and may contribute to collagen synthesis and fibrogenesis in the lung. Experimental Approach Expression of Arp2/3 components was assessed in human lung fibroblasts and in the bleomycin‐induced pulmonary fibrosis model in mice. The Arp2/3 complex was repressed with the allosteric inhibitor CK666 and with interfering RNAs targeting the ARP2, ARP3 and ARPC2 subunits (siARP2, siARP3 and siARPC2) in CCD‐16Lu human lung fibroblasts in vitro. Mice received daily intraperitoneal injections of CK666 from the 7th to the 14th day after tracheal bleomycin instillation. Key Results: Expression of Arp2/3 complex subunits mRNAs was increased in fibroblasts treated with TGF‐β1 and in the lungs of bleomycin‐treated mice compared with controls. In vitro, CK666 and siARPC2 inhibited cell growth and TGF‐β1‐induced α‐smooth muscle actin (ACTA2) and collagen‐1 (COL1) expression. CK666 also decreased ACTA2 and COL1 expression in unstimulated cells. CK666 reduced Akt phosphorylation and repressed phospho‐GSK3β, β‐catenin and MRTF‐A levels in unstimulated fibroblasts. In vivo, CK666 reduced levels of both procollagen‐1 and insoluble collagen in bleomycin‐treated mice. Conclusion and Implications: Expression of the Arp2/3 complex was increased in profibrotic environments in vitro and in vivo. Inhibition of the Arp2/3 complex repressed ACTA2 and COL1 expression and repressed an Akt/phospho‐GSK3β/β‐catenin/MRTF‐A pathway in lung fibroblasts. CK666 exerted antifibrotic properties in the lung in vivo. Inhibition of the Arp2/3 complex could represent an interesting new therapy for idiopathic pulmonary fibrosis and other fibrotic interstitial lung diseases. [ABSTRACT FROM AUTHOR]