bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain processing of consonance/dissonance in musicians and controls: a hemispheric asymmetry revisited
Authors: Proverbio Alice Mado , Orlandi Andrea , Pisanu Francesca
Published: July 2016

It was investigated to what extent musical expertise influences the auditory processing of harmonicity by recording event‐related potentials. Thirty‐four participants (18 musicians and 16 controls) were asked to listen to hundreds of chords, differing in their degree of consonance, their complexity (from two to six composing sounds) and their range (distance of two adjacent pitches, from quartertones to more than 18 semitone steps). The task consisted of detecting rare targets. An early auditory N1 was observed that was modulated by chord dissonance in both groups. The response was generated in the right medial temporal gyrus (MTG) for consonant chords but in the left MTG for dissonant chords according to swLORETA reconstruction performed. An anterior negativity (N2) was enhanced only in musicians in response to chords featuring quartertones, thus suggesting a greater pitch sensitivity for simultaneous pure tones in the skilled brain. The P300 was affected by the frequency range only in musicians, who also showed a greater sensitivity to sound complexity. A strong left hemispheric specialization for processing quartertones in the left temporal cortex of musicians was observed at N2 level (250–350 ms), which was observed on the right side in controls. Additionally, in controls, widespread activity of the right limbic area was associated with listening to close frequencies causing disturbing beats, possibly suggesting a negative aesthetic appreciation for these stimuli. Overall, the data show a finer and more tuned neural representation of pitch intervals in musicians, linked to a marked specialization of their left temporal cortex (BA21/38).
The active zone protein CAST regulates synaptic vesicle recycling and quantal size in the mouse hippocampus
Authors: Kobayashi Shizuka , Hida Yamato , Ishizaki Hiroyoshi , Inoue Eiji , Tanaka‐Okamoto Miki , Yamasaki Miwako , Miyazaki Taisuke , Fukaya Masahiro , Kitajima Isao , Takai Yoshimi , Watanabe Masahiko , Ohtsuka Toshihisa , Manabe Toshiya
Published: July 2016

Synaptic efficacy is determined by various factors, including the quantal size, which is dependent on the amount of neurotransmitters in synaptic vesicles at the presynaptic terminal. It is essential for stable synaptic transmission that the quantal size is kept within a constant range and that synaptic efficacy during and after repetitive synaptic activation is maintained by replenishing release sites with synaptic vesicles. However, the mechanisms for these fundamental properties have still been undetermined. We found that the active zone protein CAST (cytomatrix at the active zone structural protein) played pivotal roles in both presynaptic regulation of quantal size and recycling of endocytosed synaptic vesicles. In the CA1 region of hippocampal slices of the CAST knockout mice, miniature excitatory synaptic responses were increased in size, and synaptic depression after prolonged synaptic activation was larger, which was attributable to selective impairment of synaptic vesicle trafficking via the endosome in the presynaptic terminal likely mediated by Rab6. Therefore, CAST serves as a key molecule that regulates dynamics and neurotransmitter contents of synaptic vesicles in the excitatory presynaptic terminal in the central nervous system.
Chronic D2/3 agonist ropinirole treatment increases preference for uncertainty in rats regardless of baseline choice patterns
Authors: Tremblay Melanie , Silveira Mason M. , Kaur Sukhbir , Hosking Jay G. , Adams Wendy K. , Baunez Christelle , Winstanley Catharine A.
Published: July 2016

D2/3 receptor agonists are effective treatments for Parkinson's disease (PD), but can precipitate impulse control disorders (ICDs) including gambling disorder (GD). The neurobiological mechanisms underlying this devastating side‐effect of dopamine agonist replacement therapy (DRT), and any dependence on the dopamine depletion caused by PD, are unclear. It is also unclear whether previous biases towards risk or uncertainty are a risk factor for developing these ICDs. We investigated whether chronic D2/3 agonist administration (5 mg/kg/day ropinirole for 28 days) altered performance of a rat model of gambling‐like behaviour, the rodent betting task (rBT), and examined if baseline behaviour predicted this behavioural change. The rBT captures individual differences in subjective preference for uncertain outcomes: animals choose between guaranteed or probabilistic reinforcement of equal expected value. Chronic ropinirole dramatically increased selection of the uncertain option in two‐thirds of animals, regardless of baseline preferences. The effect on choice in the rBT was replicated in a dorsolateral striatal 6‐hydroxydopamine (6‐OHDA) rat model of early PD. These studies are the first to look at individual differences in response to chronic, rather than pulsatile, dosing of DRT in a rodent model of gambling behaviour. These findings suggest that DRT‐induced PG may stem from increases in subjective valuation of uncertainty. Such symptoms likely arise because of changes in dopaminergic striatal signalling caused by DRT rather than from an interaction between pre‐morbid behaviours or PD itself.
Progressive tauopathy in P301S tau transgenic mice is associated with a functional deficit of the olfactory system
Authors: Yang Sujeong , Kuan Wei‐Li , Spillantini Maria Grazia
Published: July 2016

Multiple neurodegenerative disorders with tau pathology are characterised by the loss of memory and cognitive decline that can be associated with other symptoms including olfactory alterations that are often regarded as an early symptom of the diseases. Here, we have investigated whether olfactory dysfunction is present in the P301S human tau transgenic mice and if it is associated to tau pathology. Progressive tauopathy and neurodegeneration were noticeable in the olfactory bulb and piriform cortex at early age in the P301S human tau transgenic mice and olfactory sensitivity for social or non‐social odours was significantly impaired at 3 months of age, when the piriform cortex‐dependent odour‐cross habituation was also disrupted. The olfactory alterations in the P301S tau transgenic mouse line provide an in vivo system where to test the mechanism‐based therapies for the common and yet untreatable tauopathies.
Perceived state of self during motion can differentially modulate numerical magnitude allocation
Authors: Arshad Q. , Nigmatullina Y. , Roberts R. E. , Goga U. , Pikovsky M. , Khan S. , Lobo R. , Flury A.‐S. , Pettorossi V. E. , Cohen‐Kadosh R. , Malhotra P. A. , Bronstein A. M.
Published: July 2016

Although a direct relationship between numerical allocation and spatial attention has been proposed, recent research suggests that these processes are not directly coupled. In keeping with this, spatial attention shifts induced either via visual or vestibular motion can modulate numerical allocation in some circumstances but not in others. In addition to shifting spatial attention, visual or vestibular motion paradigms also (i) elicit compensatory eye movements which themselves can influence numerical processing and (ii) alter the perceptual state of ‘self’, inducing changes in bodily self‐consciousness impacting upon cognitive mechanisms. Thus, the precise mechanism by which motion modulates numerical allocation remains unknown. We sought to investigate the influence that different perceptual experiences of motion have upon numerical magnitude allocation while controlling for both eye movements and task‐related effects. We first used optokinetic visual motion stimulation (OKS) to elicit the perceptual experience of either ‘visual world’ or ‘self’‐motion during which eye movements were identical. In a second experiment, we used a vestibular protocol examining the effects of perceived and subliminal angular rotations in darkness, which also provoked identical eye movements. We observed that during the perceptual experience of ‘visual world’ motion, rightward OKS‐biased judgments towards smaller numbers, whereas leftward OKS‐biased judgments towards larger numbers. During the perceptual experience of ‘self‐motion’, judgments were biased towards larger numbers irrespective of the OKS direction. Contrastingly, vestibular motion perception was found not to modulate numerical magnitude allocation, nor was there any differential modulation when comparing ‘perceived’ vs. ‘subliminal’ rotations. We provide a novel demonstration that numerical magnitude allocation can be differentially modulated by the perceptual state of self during visual but not vestibular mediated motion.
Phosphorylation of NMDA receptor GluN2B subunit at Tyr1472 is important for trigeminal processing of itch
Authors: Inoue Akitoshi , Uchida Hitoshi , Nakazawa Takanobu , Yamamoto Tadashi , Ito Seiji
Published: July 2016

Itch and pain are intimately related and may share similar peripheral and central mechanisms and pathways. However, it has been believed that synaptic glutamate release from a group of peripheral nociceptors is required to sense pain and suppress itch. Although we previously demonstrated that phosphorylation of GluN2B subunits of the NMDA receptor at Tyr1472 is important for central sensitization in a neuropathic pain model of mice with a knock‐in mutation of the Tyr1472 site to phenylalanine of GluN2B (Y1472F‐KI), the role of NMDA receptors in itch transmission remains unknown. Here, we demonstrated that the scratching behaviors elicited by various pruritogens applied to the cheek and c‐fos expression in the region innervated by the trigeminal nerve were markedly attenuated in the Y1472F‐KI mice. The c‐fos immunoreactivity was co‐localized with the receptor of gastrin‐releasing peptide (GRP). Scratching behaviors evoked by chloroquine were inhibited by the NMDA receptor antagonists D‐AP5 and CP101,606 and by the Src kinase inhibitor PP2. Direct activation of the trigeminal region by intracisternal administration of NMDA and GRP induced robust scratching behaviors, both of which were reduced by the GRP receptor antagonist RC‐3095. Taken together, the data obtained in this present study are the first to demonstrate that phosphorylation of GluN2B subunit at Tyr1472 is important for trigeminal transmission of itch and suggest that the NMDA receptor activation occurs upstream of the GRP‐GRP receptor pathway.
Is electrical coupling involved in the generation of posterior hypothalamic theta rhythm?
Authors: Bocian Renata , Caban Bartosz , Kłos‐Wojtczak Paulina , Konopacki Jan , Kowalczyk Tomasz
Published: July 2016

Data obtained inin vitroexperiments and urethane anaesthetized animals have revealed that the mechanisms responsible for the generation of hippocampal cholinergic theta rhythm are specifically affected by the administration of broad spectrum gap junctions (GJs) blocker – carbenoxolone (CBX). The aim of this study was to examine the effect ofGJs modulation on the production of posterior hypothalamic theta. Specifically, we were interested in evaluating whetherCBXcould attenuate the theta rhythm recorded from the supramammillary nucleus and posterior hypothalamic nuclei, in bothin vitroandin vivopreparations. The data we obtained fromin vitroandin vivopreparations demonstrated that the administration ofCBXdid not suppress cholinergically induced theta in posterior hypothalamic area (PHa) slices nor the theta rhythm observed in thePHa of urethane anaesthetized rats. Moreover, the application of trimethylamine, while very effective in the enhancement of hippocampal theta rhythm, did not produce any changes in theta oscillations observed in eitherin vitroorin vivoposterior hypothalamic area preparations. These data show that electrical coupling viaGJs is not involved in theta rhythm generation in thePHa. Surprisingly, we observed a significant enhancement of theta activity in response to the carbenoxolone administration in bothin vitroandin vivoPHa preparations. The theta rhythm enhancement detected in those experiments was attenuated by the application of spironolactone (mineralocorticoid receptors antagonist). We suggest that the observed excitatory effects ofCBXon posterior hypothalamic oscillatory activity in the theta band could be mediated by mineralocorticoid receptors.
Hemispheric asymmetries in subcortical visual and auditory relay structures in congenital deafness
Authors: Amaral L. , Ganho‐Ávila A. , Osório A. , Soares M. J. , He D. , Chen Q. , Mahon B. Z. , Gonçalves O. F. , Sampaio A. , Fang F. , Bi Y. , Almeida J.
Published: July 2016

Neuroplasticity – the capacity of the brain to change as a response to internal and external pressures – has been studied from a number of different perspectives. Perhaps one of the most powerful models is the study of populations that have been congenitally deprived of a sense. It has been shown that the right Auditory Cortex (AC) of congenitally deaf humans is neuroplastically modified in order to represent visual properties of a stimulus. One unresolved question is how this visual information is routed to the AC of congenitally deaf individuals. Here, we performed volumetric analysis of subcortical auditory and visual brains regions – namely the thalamus (along with three thalamic nuclei: the pulvinar, the lateral geniculate nucleus and the medial geniculate nucleus), and the inferior and superior colliculi – in deaf and hearing participants in order to identify which structures may be responsible for relaying visual information toward the altered AC. Because there is a hemispheric asymmetry in the neuroplastic changes observed in the AC of the congenitally deaf, we reasoned that subcortical structures that also showed a similar asymmetry in their total volume could have been enlisted in the effort of relaying visual information to the neuroplastically altered right AC. We show that for deaf, but not for hearing individuals, the right thalamus, right lateral geniculate nucleus and right inferior colliculus are larger than their left counterparts. These results suggest that these subcortical structures may be responsible for rerouting visual information to the AC in congenital deafness.
Deep brain stimulation in the central nucleus of the amygdala decreases ‘wanting’ and ‘liking’ of food rewards
Authors: Ross Shani E. , Lehmann Levin Emily , Itoga Christy A. , Schoen Chelsea B. , Selmane Romeissa , Aldridge J. Wayne
Published: July 2016

We investigated the potential of deep brain stimulation (DBS) in the central nucleus of the amygdala (CeA) in rats to modulate functional reward mechanisms. The CeA is the major output of the amygdala with direct connections to the hypothalamus and gustatory brainstem, and indirect connections with the nucleus accumbens. Further, the CeA has been shown to be involved in learning, emotional integration, reward processing, and regulation of feeding. We hypothesized that DBS, which is used to treat movement disorders and other brain dysfunctions, might block reward motivation. In rats performing a lever‐pressing task to obtain sugar pellet rewards, we stimulated the CeA and control structures, and compared stimulation parameters. During CeA stimulation, animals stopped working for rewards and rejected freely available rewards. Taste reactivity testing during DBS exposed aversive reactions to normally liked sucrose tastes and even more aversive taste reactions to normally disliked quinine tastes. Interestingly, given the opportunity, animals implanted in the CeA would self‐stimulate with 500 ms trains of stimulation at the same frequency and current parameters as continuous stimulation that would stop reward acquisition. Neural recordings during DBS showed that CeA neurons were still active and uncovered inhibitory‐excitatory patterns after each stimulus pulse indicating possible entrainment of the neural firing with DBS. In summary, DBS modulation of CeA may effectively usurp normal neural activity patterns to create an ‘information lesion’ that not only decreased motivational ‘wanting’ of food rewards, but also blocked ‘liking’ of rewards.
Buffering of protons released by mineral formation during amelogenesis in mice
Authors: Bronckers Antonius L. J. J. , Lyaruu Don M. , Jalali Rozita , DenBesten Pamela K.
Published: July 2016

Regulation of pH by ameloblasts during amelogenesis is critical for enamel mineralization. We examined the effects of reduced bicarbonate secretion and the presence or absence of amelogenins on ameloblast modulation and enamel mineralization. To that end, the composition of fluorotic and non‐fluorotic enamel of several different mouse mutants, including enamel of cystic fibrosis transmembrane conductance regulator‐deficient (Cftr null), anion exchanger‐2‐deficient (Ae2a,b null), and amelogenin‐deficient (Amelx null) mice, was determined by quantitative X‐ray microanalysis. Correlation analysis was carried out to compare the effects of changes in the levels of sulfated‐matrix (S) and chlorine (Cl; for bicarbonate secretion) on mineralization and modulation. The chloride (Cl−) levels in forming enamel determined the ability of ameloblasts to modulate, remove matrix, and mineralize enamel. In general, the lower the Cl− content, the stronger the negative effects. In Amelx‐null mice, modulation was essentially normal and the calcium content was reduced least. Retention of amelogenins in enamel of kallikrein‐4‐deficient (Klk4‐null) mice resulted in decreased mineralization and reduced the length of the first acid modulation band without changing the total length of all acidic bands. These data suggest that buffering by bicarbonates is critical for modulation, matrix removal and enamel mineralization. Amelogenins also act as a buffer but are not critical for modulation.
An epidemiological survey on the prevalence of equine peripheral dental caries in the United Kingdom and possible risk factors for its development
Authors: Borkent D. , Reardon R. J. M. , McLachlan G. , Smith S. , Dixon P. M.
Published: July 2016

Background

Equine peripheral caries (PC) is an increasingly recognised disorder that causes premature wear of teeth and dental fractures and thus has major welfare implications. Little information is available on its prevalence or severity in UK horses and there are no proven associations with any risk factors.

Objectives

To document the prevalence of PC over a wide area of the UK, assess its intraoral distribution and severity in affected horses and examine for potential risk factors for its development.

Study design

Cross sectional study.

Methods

Experienced personnel were recruited for a UK wide dental survey on their patients during dental examinations. Established guidelines were used for grading PC. Frequency of PC occurrence was compared between teeth and dental arcades using McNemar's tests. Potential risk factors for PC were screened using univariable logistic regression prior to building a multivariable model.

Results

A total of 706 horses were examined by 25 participants, showing a 51.7% prevalence of PC (365/706). Some regional differences in prevalence were found. The PC primarily affected the cheek teeth with the 12 caudal being significantly more commonly affected than the 12 rostral cheek teeth. Most of the hypothesised risk factors including age, breed, sex, time at pasture and feeding of silage (haylage) were unproven. A limited association with moderate levels of concentrate feeding was observed. The presence of concurrent dental abnormalities were significantly associated with the likelihood of having PC.

Main limitations

Not all regions in UK were included and there may be inconsistencies between examiners.

Conclusions

Peripheral caries is common in British horses, primarily affecting the caudal cheek teeth. There was limited evidence of an association between feeding and PC. The association between PC and concurrent dental disorders indicates that these should be addressed in affected horses.
Effect of subacute agomelatine treatment on painful diabetic neuropathy: involvement of catecholaminergic mechanisms
Authors: Aydın Taliha H. , Can Özgür D. , Demir Özkay Ümide , Turan Nazlı
Published: July 2016

In this study, we investigated the effects of subacute agomelatine (40 and 80 mg/kg) administration on chronic hyperglycemia, metabolic parameters, and pain perception in streptozotocin‐induced diabetic rats. Fasting blood glucose measurements and oral glucose tolerance tests were performed to evaluate the effect of agomelatine on glycemia, while metabolic parameters were monitored using metabolic cages. Potential effect of agomelatine on diabetes‐induced mechanical and thermal allodynia was evaluated using dynamic plantar aesthesiometer and warm plate (38 °C) tests, respectively. Additionally, influence of agomelatine on hyperalgesia occurring in connection with diabetic neuropathy was examined using the Randall–Selitto (mechanical nociceptive stimulus), Hargreaves (thermal nociceptive stimulus), and cold plate (4 °C, thermal nociceptive stimulus) tests. Obtained data indicated that, in diabetic rats, agomelatine significantly improved hyperalgesia and allodynia responses, without no effect on hyperglycemia or the associated polydipsia, polyuria, and hyperphagia. Therapeutic potential of agomelatine on neuropathic pain was suppressed with α‐methyl‐para‐tyrosine methyl ester (an inhibitor of catecholamine synthesis), phentolamine (a nonselective α‐adrenoceptor antagonist), and propranolol (a nonselective β‐adrenoceptor antagonist) administrations. However, p‐chlorophenylalanine methyl ester (an inhibitor of serotonin synthesis) pretreatment could not be achieved to reverse these antihyperalgesic and antiallodynic effects. These results suggest that the curative effect of agomelatine on neuropathic pain is mediated through rising synaptic catecholamine levels as well as through interactions with both α‐ and β‐adrenoceptors. To our knowledge, this is the first study to show findings that indicate catecholaminergic system mediated antihyperalgesic and antiallodynic effects of agomelatine.
Realized climate niche breadth varies with population trend and distribution in North American birds
Authors: Ralston Joel , DeLuca William V. , Feldman Richard E. , King David I.
Published: July 2016

Aim

Ecological niche theory states that realized niche breadth should increase with population growth. This relationship has been studied extensively in the context of density‐dependent habitat selection, and there is evidence that animal populations at higher density occupy a wider range of vegetation types. To our knowledge, no previous studies have investigated the relationship between population growth and climate niche breadth (i.e. the range of climatic conditions occupied). Here we aim to estimate the influence of population trend, as well as changes in distribution, on realized climate niche breadth.

Location

North America.

Methods

We estimated changes in realized climate niche breadth and distribution between 1980 and 2012 for 46 bird species using data from the North American Breeding Bird Survey (BBS) and standard ecological niche modelling techniques. We analysed changes in niche breadth in relation to population trends and distributional changes from the BBS for these same species.

Results

Changes in realized climate niche breadth were significantly and positively associated with population growth, as reflected by BBS population trends, and with changes in distributional extent. Using variance partitioning, we showed that 44.2% of the variation in change in niche breadth can be explained by population trend, and that roughly half of this was independent of changes in distribution.

Conclusions

Realized climate niche breadth is variable on an ecological time‐scale as a function of population trend. Mechanisms associated with changes in distribution and those acting within current species range limits appear to be equally important in driving this relationship. Observed changes in niche breadth may violate distribution modelling assumptions of niche conservatism. Studying how population growth influences realized climate niche breadth is therefore important for understanding dynamic species distributions, responses to climate change and our ability to model future species distributions.
Combination of neutrophil‐to‐lymphocyte ratio and early des‐γ‐carboxyprothrombin change ratio as a useful predictor of treatment response for hepatic arterial infusion chemotherapy against advanced hepatocellular carcinoma
Authors: Tsunematsu Seiji , Suda Goki , Yamasaki Kazushi , Kimura Megumi , Takaaki Izumi , Umemura Machiko , Ito Jun , Sato Fumiyuki , Nakai Masato , Sho Takuya , Morikawa Kenichi , Ogawa Koji , Kamiyama Toshiya , Taketomi Akinobu , Sakamoto Naoya
Published: July 2016

Aim

Hepatic arterial infusion chemotherapy (HAIC) is a potent therapeutic option for advanced hepatocellular carcinoma (HCC). However, there are few known predictive factors of treatment response to HAIC. We clarified the most accurate predictive factors early on in treatment.

Methods

Study subjects were 70 patients with advanced HCC who had been treated with HAIC. We assessed the relationships between patient characteristics, change ratios of early tumor markers, tumor response, progression‐free survival (PFS), and overall survival.

Results

After two courses of HAIC, 1 (1.4%), 16 (22.9%), 30 (42.8%), and 23 (32.9%) of the 70 patients showed complete response, partial response, stable disease, and progressive disease, respectively. Overall survival was related to Child–Turcotte–Pugh score, extrahepatic metastasis, and the des‐γ‐carboxyprothrombin (DCP) response. Univariate and multivariate analyses identified the neutrophil‐to‐lymphocyte ratio (NLR) and DCP response as significant determinants of treatment response and PFS. Progression‐free survival with a low NLR (<2.87) was significantly longer than with a high NLR (median, 8.4 months vs. 2.8 months, respectively). Progression‐free survival was 7.2 months for patients with a responsive DCP (<0.7) and 2.3 months for an unresponsive DCP (≥0.7). Additionally, even with baseline high NLR, patients with responsive DCP achieved better PFS.

Conclusion

Baseline NLR and early DCP response were significant predictors of treatment response and PFS after HAIC for patients with advanced HCC. The combination of baseline NLR and early DCP response could be accurate and useful predictive factors of response to HAIC and could help optimize treatments for patients with advanced HCC.
MicroRNA‐135b inhibits odontoblast‐like differentiation of human dental pulp cells by regulating Smad5 and Smad4
Authors: Song Z. , Chen L. L. , Wang R. F. , Qin W. , Huang S. H. , Guo J. , Lin Z. M. , Tian Y. G.
Published: July 2016

Aim

To investigate the function of miRNAs in odontoblast‐like differentiation of human dental pulp cells (hDPCs).

Methodology

Integrated comparative miRNA microarray profiling was used to determine the differential miRNAs expression in odontoblast‐like differentiation of hDPCs. The abundance of microRNA‐135b (miR‐135b) was measured by quantitative real‐time reverse transcriptase polymerase chain reaction (qRT‐PCR) and in situ hybridization (ISH). Bioinformatic analyses combined with luciferase assays were utilized to identify the targets interacting with miR‐135b. Overexpression of miR‐135b was performed to investigate the role and mechanism in odontoblast‐like differentiation of hDPCs. Statistical analysis was performed by one‐way analysis of variance (anova) or Student's t‐test.

Results

Thirty‐six differentially expressed microRNAs in odontoblast‐like differentiation of hDPCs were identified. MiR‐135b expression was significantly downregulated during hDPCs differentiation (P < 0.05). In addition, miR‐135b was able to bind to the 3′‐UTR of the Smad5 and Smad4 and repressed these two genes expression (P < 0.05). Furthermore, overexpression of miR‐135b suppressed odontoblast‐like differentiation of hDPCs and attenuated the expression of Smad5 and Smad4 (P < 0.05).

Conclusions

These observations indicated a potential role of miR‐135b in mediating odontoblast‐like differentiation of hDPCs and inhibition of miR‐135b might be a promising therapeutic way to facilitate dentine tissue engineering.
Antioxidant and hypoglycaemic effects of tilapia skin collagen peptide in mice
Authors: Zhang Ruilin , Chen Jian , Jiang Xiongwu , Yin Lasheng , Zhang Xuewu
Published: July 2016

In this study, tilapia collagen peptide (TCP) was prepared by alcalase hydrolysis of tilapia skin, and the antioxidant and hypoglycaemic effects of TCP were investigated. The results showed that TCP possessed DPPH and ABTS+ free radicals‐scavenging activities. In diabetic mice in which diabetes was induced by injection of alloxan (50 mg kg−1 bw), high‐dose TCP (1.7 g kg−1 bw) and the drug metformin (1.0 g kg−1 bw) were found to reduce 31.8% and 30.3% of blood glucose levels in 25 days, respectively. Moreover, in diabetic mice receiving high‐dose TCP, antioxidant enzymes SOD and CAT were increased by 23% and 59.2%, respectively, and MDA was decreased by 39.1%. Comparing the treated high‐dose TCP group with the metformin group, there were similar SOD (61.5 U mg−1 vs. 60.2 U mg−1) and MDA (1.4 nmol mg−1 vs. 1.3 nmol mg−1), but more (~7%) CAT (359.8 U g−1 vs. 336.1 U g−1). Together, the present data, for the first time, demonstrated that TCP possessed hypoglycaemic effects in mice.
Interatrial Conduction Time Can Predict New‐Onset Atrial Fibrillation After Radiofrequency Ablation of Isolated, Typical Atrial Flutter
Authors: HENMI RYUTA , EJIMA KOICHIRO , SHODA MORIO , YAGISHITA DAIGO , HAGIWARA NOBUHISA
Published: July 2016

Interatrial Conduction Time

Introduction

Many patients with successful atrial flutter (AFL) ablation will develop atrial fibrillation (AF) during follow‐up. This study aimed to determine whether prolonged interatrial conduction time (IACT) is associated with risk for new‐onset AF after ablation of isolated, typical AFL.

Methods

Participants were 80 consecutive patients who underwent successful radiofrequency ablation of isolated, typical AFL from 2004 to 2012. Patients with any history of AF prior to AFL ablation were excluded. IACT was defined as the interval from the earliest onset of the P‐wave on the ECG to the latest activation in the coronary sinus catheter during sinus rhythm measured after AFL ablation. New‐onset AF was identified from 12‐lead ECGs, 24‐hour ambulatory monitoring, and device interrogations.

Results

During a mean follow‐up of 4.1 ± 2.5 years after successful AFL ablation, 22 patients (27.5%) developed new‐onset AF. Cox regression multivariate analysis demonstrated that IACT was the independent predictor of new‐onset AF after AFL ablation (hazard ratio: 1.03; 95% confidence interval: 1.00–1.06; P = 0.02). IACT was accurate in predicting new‐onset AF (AUC = 0.70). The optimal cut‐off point of IACT for predicting new‐onset AF was 120 milliseconds (sensitivity 47.6%, specificity 89.8%). Kaplan–Meier curves showed that new‐onset AF after AFL ablation was significantly higher in patients with IACT ≥120 milliseconds than in patients with IACT< 120 milliseconds (P = 0.0016).

Conclusion

Prolonged IACT predicted new‐onset AF after ablation of isolated AFL. This finding may contribute to guiding decisions regarding the maintenance of anticoagulation after AFL ablation.
Catheter Ablation for Atrial Arrhythmias in Patients With Cardiac Amyloidosis
Authors: TAN NICHOLAS Y. , MOHSIN YOUSEF , HODGE DAVID O. , LACY MARTHA Q. , PACKER DOUGLAS L. , DISPENZIERI ANGELA , GROGAN MARTHA , ASIRVATHAM SAMUEL J. , MADHAVAN MALINI , McLEOD CHRISTOPHER J.
Published: July 2016

Catheter Ablation for Atrial Arrhythmias in Patients With CA

Background

Cardiac amyloidosis (CA) is associated with increased atrial arrhythmias risk. The efficacy/safety of catheter‐based ablation therapy in patients with CA has not been adequately assessed.

Methods and Results

All diagnosed CA patients who underwent atrial arrhythmia ablation therapy from 1995 to 2015 were reviewed. Arrhythmia recurrence, NYHA symptoms, and mortality were recorded. A total of 26 patients with CA and atrial arrhythmias were included; there were 7 light‐chain (AL), 17 wild‐type transthyretin (ATTRwt), and 2 mutated transthyretin (ATTRm) amyloidosis patients in total. Of which 13 underwent atrial arrhythmia ablation (CA‐A) and 13 underwent AV nodal ablation (CA‐AVN). In the CA‐A group, there were: 3 with atrial fibrillation (AF); 6 with atrial flutter (AFL); 2 with AF/AFL; and 2 with atrial tachycardia (AT). One‐year and 3‐year recurrence‐free survival were 75% and 60%, respectively. NYHA symptom improvement 6 months postablation was observed in both CA‐A and CA‐AVN groups: 7/10 (70%) and 4/8 (50%), respectively. Eleven patients with CA died (8 in CA‐AVN group vs. 3 in CA‐A group).

Conclusions

Catheter‐based ablation for patients with CA appears to provide important symptomatic relief. However, mortality from the underlying disease remains a significant issue for the amyloid light‐chain subtype.
Cryoballoon versus Radiofrequency Catheter Ablation in Atrial Fibrillation: A Meta‐Analysis
Authors: CARDOSO RHANDERSON , MENDIRICHAGA RODRIGO , FERNANDES GILSON , HEALY CHRIS , LAMBRAKOS LITSA K. , VILES‐GONZALEZ JUAN F. , GOLDBERGER JEFFREY J. , MITRANI RAUL D.
Published: July 2016

Cryoballoon vs. Radiofrequency AF Ablation

Introduction

Radiofrequency (RF) and cryoballoon (CB) catheter ablation are effective for pulmonary vein isolation (PVI) in atrial fibrillation (AF). This report presents an updated meta‐analysis comparing the efficacy and safety of CB versus RF ablations in AF.

Methods

Databases and conference abstracts were systematically searched for studies that directly compared CB and RF PVI, and reported safety or efficacy outcomes in follow‐up ≥12 months. Recurrent atrial tachyarrhythmias (AT) were defined as AF, atrial flutter, or atrial tachycardia.

Results

Twenty‐two studies and 8,668 patients were included. Freedom from AT was not significantly different between CB and RF ablations in the pooled population (OR 1.12; 95%CI 0.97–1.29; P = 0.13) and in randomized trials (OR 1.0; 95%CI 0.65–1.56; P = 0.99). Second‐generation CB (CB2; 78.1%) and contact‐force (CF) sensing RF (78.2%) have improved procedure success rate as compared to first‐generation technology (57.9% CB, 58.1% RF). As compared to CF‐RF, CB2 demonstrated similar freedom from recurrent AT (OR 1.04; 95%CI 0.71–1.51; P = 0.84). The incidence of pericardial effusions (OR 0.44; 95%CI 0.28–0.69; P < 0.01), tamponade (OR 0.31; 95%CI 0.15–0.64; P < 0.01), and non‐AF AT (OR 0.46; 95%CI 0.26–0.83; P < 0.01) were significantly lower with CB ablation, whereas transient phrenic nerve palsy was more incident after CB (OR 7.40; 95%CI 2.56–21.34; P < 0.01).

Conclusion

There was comparable freedom from AT between CB and RF in patients with AF undergoing PVI. Additionally, freedom from AT was similar between CB2 and CF‐RF. However, CB was associated with a lower incidence of pericardial effusions or tamponade, albeit with a higher rate of transient phrenic nerve palsies.
Azilsartan in Patients With Mild to Moderate Hypertension Using Clinic and Ambulatory Blood Pressure Measurements
Authors: Perez Alfonso , Cao Charlie
Published: July 2016

This was a phase 2, multicenter, randomized, parallel‐group, double‐blind dose‐ranging study. Hypertensive adults (n=555) received one of five doses of azilsartan (AZL; 2.5, 5, 10, 20, 40 mg), olmesartan medoxomil (OLM) 20 mg, or placebo once daily. The primary endpoint was change in trough clinic diastolic blood pressure (DBP) at week 8. Compared with placebo, all AZL doses (except 2.5 mg) provided statistically and clinically significant reductions in DBP and systolic blood pressure (SBP) based on both clinic blood pressure (BP) and 24‐hour ambulatory BP monitoring (ABPM). AZL 40 mg was statistically superior vs OLM. Clinic BP was associated with a pronounced placebo effect (−6 mm Hg), whereas this was negligible with ABPM (±0.5 mm Hg). Adverse event frequency was similar in the AZL and placebo groups. Based on these and other findings, subsequent trials investigated the commercial AZL medoxomil tablet at doses 20 to 80 mg/d using 24‐hour ABPM.
Mutations in the mevalonate pathway genes in Chinese patients with porokeratosis
Authors: Li M. , Li Z. , Wang J. , Ni C. , Sun Z. , Wilson N.J. , Zhang J. , Chen F. , Li X. , Du X. , Yu H. , Zhang L. , Smith F.J.D. , Zhang G. , Yao Z.
Published: July 2016

Background

Porokeratosis (PK, MIM 175800) is a chronic autosomal dominant cutaneous keratinization disorder, which has a wide variety of clinical manifestations.

Objectives

We analysed the molecular basis of 10 families and 12 sporadic cases with different subtypes of porokeratosis in the Chinese population.

Methods

Genomic DNA was extracted from peripheral blood samples. Mutation screening was performed by direct sequencing of exons and flanking intron–exon boundaries for the entire coding region of four mevalonate pathway genes and SLC17A9 gene.

Results

We detected three novel mutations and seven previously described mutations by direct sequence analysis of the PCR products. Mutations p.Phe249Ser and p.Asn292Ser in mevalonate decarboxylase (MVD) were the most common mutations in this PK cohort; their presence was 27.3% and 13.6% respectively.

Conclusions

This study extended the mutation spectrum of PK in the Chinese Han population and provided further evidence for the genetic basis of PK. We first identified MVD simultaneously responsible for porokeratosis palmaris et plantaris disseminate development and confirmed the genotype–phenotype correlations.
Comparative histological analysis of drug‐induced maculopapular exanthema and DRESS
Authors: Skowron F. , Bensaid B. , Balme B. , Depaepe L. , Kanitakis J. , Nosbaum A. , Maucort‐Boulch D. , Bérard F. , D'Incan M. , Kardaun S.H. , Nicolas J.‐F.
Published: July 2016

Background

Cutaneous adverse drug reactions frequently present as a benign maculopapular exanthema (MPE) with a rapid healing. Sometimes systemic signs are present, which could represent a more severe or systemic MPE (sMPE) or even be the initial phase of a drug reaction with eosinophilia and systemic symptoms (DRESS). Histopathology associated with MPE, sMPE and DRESS has not been well characterized.

Objectives

To study the cutaneous histopathological changes associated with MPE, sMPE and DRESS.

Methods

A retrospective clinicopathological analysis of 13 cases of MPE, 13 of sMPE and 45 of DRESS, collected in one centre from 2005 to 2013.

Results

The number of histopathological changes per section increased gradually from MPE to sMPE and DRESS. Prevalence of spongiosis, dermal lymphocytes, eosinophils and neutrophils did not differ between MPE, sMPE and DRESS. Keratinocyte damage, rare in MPE, was regularly found in sMPE and frequent in DRESS. The density of the inflammatory infiltrate increased progressively from MPE to sMPE and DRESS. Atypical lymphocytes were absent in MPE, present in sMPE and more frequent in DRESS. Deep dermal involvement and leukocytoclastic vasculitis were only observed in DRESS.

Limitations

This was a retrospective study.

Conclusions

Numerous histopathological changes per section in drug‐induced exanthema should alert for a more severe form of cutaneous adverse drug reactions, i.e. DRESS.
Acne and dairy products in adolescence: results from a Norwegian longitudinal study
Authors: Ulvestad M. , Bjertness E. , Dalgard F. , Halvorsen J.A.
Published: July 2016

Background

Acne is a very common skin condition, and it is of great interest to elucidate lifestyle factors that may contribute to its occurrence. In the last decade, the acne‐diet connection has been brought back to credibility.

Objective

To examine whether high intakes of dairy products in early adolescence is associated with moderate to severe acne in later adolescence.

Methods

The study is a longitudinal, questionnaire‐based population study of Norwegian adolescents. Students attending the 10th grade (15–16 years old) of compulsory schooling in Oslo in 2000–2001 and the 13th grade (18–19 years old) 3 years later, in 2004, were invited. Dairy product consumption was self‐reported at age 15–16 and acne severity was self‐assessed and reported at age 18–19.

Results

The overall prevalence of moderate to severe acne was 13.9%. High intakes (≥2 glasses per day) of full‐fat dairy products were associated with moderate to severe acne. In boys with exclusively high intakes of full‐fat dairy products, the odds ratio for acne was 4.81 (1.59–14.56). A high total intake of dairy products was associated with acne in girls (OR 1.80, 1.02–3.16). No significant associations were found between acne and intake of semi‐skimmed or skimmed dairy products, and not with moderate intakes of any fat variety of dairy products.

Conclusion

This study shows association between high intakes of dairy products and acne in adolescence. Our findings support a hypothesis suggesting that dairy consumption may be a factor contributing to acne. The study is based on multiple hypothesis testing, and the methodological limitations must be considered when interpreting the results.
Prognostic clinical factors associated with remission and relapse in bullous pemphigoid
Authors: Lee J.H. , Kim T.H. , Park S.H. , Han K. , Kim S.‐C.
Published: July 2016

Background

Prognostic factors for remission and relapse of bullous pemphigoid (BP) remain uncertain.

Objective

To evaluate clinical factors associated with remission and relapse in Korean patients with BP.

Methods

A retrospective analysis was conducted of 174 patients diagnosed with BP between 1993 and 2014 at Gangnam Severance Hospital in Seoul, Korea.

Results

Of the 174 identified patients, 131 (75.29%) achieved remission after a mean treatment duration of 393.69 days. Prognostic factors for remission were older age (≥70 years) and the absence of an admission history. Of 131 patients who achieved remission, 40 patients (30.53%) experienced relapse after a mean duration of 335.65 days. However, no statistically significant factors were predictive of relapse by multivariate analysis.

Conclusions

This study suggests BP patients who are older and have no admission history tend to achieve remission.
Both short‐term and long‐term dermoscopy monitoring is useful in detecting melanoma in patients with multiple atypical nevi
Authors: Moscarella E. , Tion I. , Zalaudek I. , Lallas A. , Kyrgidis A. , Longo C. , Lombardi M. , Raucci M. , Satta R. , Alfano R. , Argenziano G.
Published: July 2016

Background

Digital dermoscopy monitoring (DDM) is an effective strategy for melanoma detection. Two methods are currently employed. Short‐term follow‐up (STFU) for the evaluation of single, atypical lesions to detect subtle changes over a short period of time (3–6 months). Long‐term follow‐up (LTFU) is recommended for patients with multiple nevi. Although a study demonstrated that STFU improves the patients’ compliance for DDM, little remains known about the impact and reliability of STFU in this setting.

Objectives

The aim of this retrospective, observational study was to evaluate the impact and reliability of a schedule combining STFU and LTFU in patients with multiple atypical nevi.

Methods

We searched our database for all cases of patients with multiple atypical nevi occurring between 2006 and 2014.

Results

A total of 3823 lesions in 541 patients were dermoscopically monitored (mean number = 7 lesions per patient; median = 6 lesions; range, 2–51). In all, 264 (6.9%) lesions in 184 (34.4%) patients were excised (mean of 0.5 lesions per patient). In total, 197 (74.6%) lesions were excised at follow‐up, with melanomas representing 30.5% of lesions excised after follow‐up. A total of 30 (33.3%) melanomas were excised at baseline, 23 (25.6%) after STFU and 37 (41.1%) after LTFU. There was no difference in the number of in situ melanomas detected at baseline with those detected after follow‐up. The mean Breslow thickness of melanomas detected at baseline was higher than those detected after STFU (P = 0.038) and LTFU (P = 0.055).

Conclusions

Our study confirm that digital dermoscopy follow‐up is a valid management strategy for patients with multiple atypical nevi, with short‐term monitoring playing an effective role also in this setting of patients.
Occasional recombination of a selfish X‐chromosome may permit its persistence at high frequencies in the wild
Authors: Pieper K. E. , Dyer K. A.
Published: July 2016

The sex‐ratio X‐chromosome (SR) is a selfish chromosome that promotes its own transmission to the next generation by destroying Y‐bearing sperm in the testes of carrier males. In some natural populations of the fly Drosophila neotestacea, up to 30% of the X‐chromosomes are SR chromosomes. To investigate the molecular evolutionary history and consequences of SR, we sequenced SR and standard (ST) males at 11 X‐linked loci that span the ST X‐chromosome and at seven arbitrarily chosen autosomal loci from a sample of D. neotestacea males from throughout the species range. We found that the evolutionary relationship between ST and SR varies among individual markers, but genetic differentiation between SR and ST is chromosome‐wide and likely due to large chromosomal inversions that suppress recombination. However, SR does not consist of a single multilocus haplotype: we find evidence for gene flow between ST and SR at every locus assayed. Furthermore, we do not find long‐distance linkage disequilibrium within SR chromosomes, suggesting that recombination occurs in females homozygous for SR. Finally, polymorphism on SR is reduced compared to that on ST, and loci displaying signatures of selection on ST do not show similar patterns on SR. Thus, even if selection is less effective on SR, our results suggest that gene flow with ST and recombination between SR chromosomes may prevent the accumulation of deleterious mutations and allow its long‐term persistence at relatively high frequencies.
Physiological limit of the daily endogenous cholecalciferol synthesis from UV light in cattle
Authors: Hymøller L. , Jensen S. K. , Kaas P. , Jakobsen J.
Published: July 2016

The link between UV light (sunlight) and endogenous cholecalciferol (vitamin D3) synthesis in the skin of humans has been known for more than a 100 years, since doctors for the first time successfully used UV light to cure rickets in children. Years later, it was shown that UV light also had a significant effect on the cholecalciferol status in the body of cattle. The cholecalciferol status in the body is measured as the plasma concentration of 25‐hydroxycholecalciferol, which in cattle and humans is the major circulating metabolite of cholecalciferol. Very little is, however, known about the quantitative efficiency of UV light as a source of cholecalciferol in cattle nutrition and physiology. Hence, the aim of this study was to determine the efficiency of using UV light for increasing the plasma 25‐hydroxycholecalciferol concentration in cholecalciferol‐deprived cattle. Twelve cows deprived of cholecalciferol for 6 months were divided into three treatment groups and exposed to UV light for 30, 90 or 120 min/day during 28 days. UV‐light wavelengths ranged from 280 to 415 nm and 30‐min exposure to the UV light was equivalent to 60‐min average summer‐sunlight exposure at 56 °N. Blood samples were collected every 3–4 days and analysed for 25‐hydroxycholecalciferol and cholecalciferol. Results showed that increasing the exposure time from 90–120 min/day did not change the slope of the daily increase in plasma 25‐hydroxycholecalciferol. Hence, it appears that cholecalciferol‐deprived dairy cattle are able to increase their plasma 25‐hydroxycholecalciferol concentration by a maximum of 1 ng/ml/day from UV‐light exposure.