bluuebunny/crossref_metadata_2025 huggingface dataset:
The tumor suppressor p53 guides GluA1 homeostasis through Nedd4‐2 during chronic elevation of neuronal activity
Authors: Jewett Kathryn A. , Zhu Jiuhe , Tsai Nien‐Pei
Published: August 2015

Chronic activity perturbation in neurons can trigger homeostatic mechanisms to restore the baseline function. Although the importance and dysregulation of neuronal activity homeostasis has been implicated in neurological disorders such as epilepsy, the complete signaling by which chronic changes in neuronal activity initiate the homeostatic mechanisms is unclear. We report here that the tumor suppressor p53 and its signaling are involved in neuronal activity homeostasis. Upon chronic elevation of neuronal activity in primary cortical neuron cultures, the ubiquitin E3 ligase, murine double minute‐ 2 (Mdm2), is phosphorylated by the kinase Akt. Phosphorylated Mdm2 triggers the degradation of p53 and subsequent induction of a p53 target gene, neural precursor cell expressed developmentally down‐regulated gene 4‐like (Nedd4‐2). Nedd4‐2 encodes another ubiquitin E3 ligase. We identified glutamate receptor subunit 1 (GluA1), subunit of alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors as a novel substrate of Nedd4‐2. The regulation of GluA1 level is known to be crucial for neuronal activity homeostasis. We confirmed that, by pharmacologically inhibiting Mdm2‐mediated p53 degradation or genetically reducing Nedd4‐2 in a mouse model, the GluA1 ubiquitination and down‐regulation induced by chronically elevated neuronal activity are both attenuated. Our findings demonstrate the first direct function of p53 in neuronal homeostasis and elucidate a new mechanism by which cortical neurons respond to chronic activity perturbation.

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Chronic neuronal activity perturbation triggers homeostatic mechanisms at the synapses. We reported that the tumor suppressor p53 and its modulator Mdm2 guide the ubiquitination and down‐regulation of the GluA1 subunit of AMPA receptor during activity stimulation. Nedd4‐2, a direct target of p53, is identified as a new ubiquitin E3 ligase for GluA1, providing a novel mechanism to fine‐tune post‐synaptic homeostasis.
miR‐144‐3p exerts anti‐tumor effects in glioblastoma by targeting c‐Met
Authors: Lan Fengming , Yu Huiming , Hu Man , Xia Tingyi , Yue Xiao
Published: August 2015

The study aimed to explore the specific function and mechanism of miR‐144‐3p in glioblastoma (GBM) cells with different phosphatase and tensin homolog (PTEN) phenotypes. We demonstrated that the miR‐144‐3p level was significantly down‐regulated in glioma compared with the non‐neoplastic brain tissues, and decreased with ascending grades. The loss of miR‐144‐3p effectively predicted the decreased overall survival in glioma patients. Interestingly, the expression of MET was up‐regulated and inversely associated with miR‐144‐3p level in glioma tissues. Next, we certified that miR‐144‐3p specifically bound to MET 3′‐untranslated region (3′ UTR) and inhibited its expression. miR‐144‐3p potently repressed GBM cell proliferation and invasion via suppressing MET in vitro and in vivo. In addition, our results showed no difference in malignancy inhibition induced by miR‐144‐3p in GBM cells with different PTEN phenotypes. miR‐144‐3p inhibited several survival signaling pathways by targeting MET independent of PTEN status in GBM cells. Over‐expression of miR‐144‐3p inhibited survival capability and increased apoptosis, resulting in enhancement of radiation and temozolomide sensitivity. Our data provide new insights into the potential application of miR‐144‐3p in GBM therapy by targeting MET and then inhibiting the downstream signaling.

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We propose that the microRNA miR‐144‐3p plays an essential anti‐tumor role in glioblastoma. A newly identified miR‐144‐3p/MET signaling axis could represent a novel target for cellular resistance to cancer therapeutic drugs and radiation in glioblastoma patients. Jak, janus kinase; Grb2, Growth factor receptor‐bound protein 2; HGF; miR, microRNA; PI3K, phosphoinositol‐3‐kinase; Raf, rapidly accelerated fibrosarcoma; STAT, Signal Transducers and Activators of Transcription.
Reduction in NPY‐positive neurons and dysregulation of excitability in young senescence‐accelerated mouse prone 8 (SAMP8) hippocampus precede the onset of cognitive impairment
Authors: Sawano Erika , Iwatani Kanako , Tominaga‐Yoshino Keiko , Ogura Akihiko , Tashiro Tomoko
Published: August 2015

The senescence‐accelerated mouse prone 8 (SAMP8) strain is considered a neurodegeneration model showing age‐related cognitive deficits with little physical impairment. Young SAMP8 mice, however, exhibit signs of disturbances in development such as marked hyperactivity and reduced anxiety well before the onset of cognitive impairment. As the key enzyme in local regulation of thyroid hormone (TH) signaling, type 2 deiodinase, was significantly reduced in the SAMP8 hippocampus relative to that of the normally aging SAM‐resistant 1 (SAMR1), we used these two strains to compare the development of the hippocampal GABAergic system, which is known to be strongly affected by hypothyroidism. Among GABAergic components, neuronal K+/Cl− co‐transporter 2 was down‐regulated in SAMP8 transiently at 2 weeks. Although distribution of total GABAergic neurons was similar in both strains, 22–30% reduction was observed in the neuropeptide Y (NPY)‐positive subpopulation of GABAergic neurons in SAMP8. Electrophysiological studies on hippocampal slices obtained at 4 weeks revealed that epileptiform activity, induced by high‐frequency stimulation, lasted four times longer in SAMP8 compared with SAMR1, indicating a dysregulation of excitability that may be linked to the behavioral abnormalities of young SAMP8 and to neurodegeneration later on in life. Local attenuation of TH signaling may thus impact the normal development of the GABAergic system.

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Senescence‐accelerated mouse prone 8 (SAMP8) shows marked hyperactivity and reduced anxiety before the onset of cognitive impairment. Compared with the normally aging SAM‐resistant 1 (SAMR1), NPY‐positive subpopulation of GABAergic neurons was reduced by 22–30% in the young SAMP8 hippocampus, leading to longer lasting epileptiform activity after high frequency stimulation. Reduction in the TH‐activating type 2 deiodinase is suggested as a cause of this GABAergic impairment.
Eyebrow restoration: the approach, considerations, and technique in follicular unit transplantation
Authors: Tomc Christa M , Malouf Peter J
Published: August 2015

Background

Eyebrows serve a key role in eye protection, communication, and self‐expression. Trends in eyebrow grooming are constantly evolving, often requiring plucking, waxing, or laser hair removal to style. When combined with the natural thinning of the brow with aging, the result can be a sparse or even absent eyebrow hair over time. Follicular unit transplantation provides a means of restoring eyebrow fullness and architecture. With careful attention and augmentation of follicle transfer techniques, a natural end result is possible.
Looking for Someone to Blame: Delegation, Cognitive Dissonance, and the Disposition Effect
Authors: CHANG TOM Y. , SOLOMON DAVID H. , WESTERFIELD MARK M.
Published: August 2015

We analyze brokerage data and an experiment to test a cognitive dissonance based theory of trading: investors avoid realizing losses because they dislike admitting that past purchases were mistakes, but delegation reverses this effect by allowing the investor to blame the manager instead. Using individual trading data, we show that the disposition effect—the propensity to realize past gains more than past losses—applies only to nondelegated assets like individual stocks; delegated assets, like mutual funds, exhibit a robust reverse‐disposition effect. In an experiment, we show that increasing investors' cognitive dissonance results in both a larger disposition effect in stocks and a larger reverse‐disposition effect in funds. Additionally, increasing the salience of delegation increases the reverse‐disposition effect in funds. Cognitive dissonance provides a unified explanation for apparently contradictory investor behavior across asset classes and has implications for personal investment decisions, mutual fund management, and intermediation.
Incidence of temporomandibular joint clicking in adolescents with and without unilateral posterior cross‐bite: a 10‐year follow‐up study
Authors: Michelotti A. , Iodice G. , Piergentili M. , Farella M. , Martina R.
Published: August 2015

Among different malocclusions, posterior cross‐bite is thought to have a strong impact on the correct functioning of the masticatory system. The association between unilateral posterior cross‐bite (UPCB) and temporomandibular joint (TMJ) clicking, however, remains still controversial. The aim of this study was to investigate whether the presence of UCPB during early adolescence increases the risk of reporting TMJ clicking after a long‐term follow‐up. A longitudinal survey design was carried out in a group of 12‐year‐old young adolescents, who were examined at baseline for TMJ clicking sounds and unilateral posterior cross‐bite. After 10 years, 519 subjects could be reached by a telephone survey. Standardised questions were used to collect self‐reported TMJ sounds and to determine whether participants had received an orthodontic treatment. Logistic regression analysis revealed a significant association between unilateral posterior cross‐bite and subjectively reported TMJ clicking (odds ratio = 6·0; 95% confidence limits = 3·4–10·8; P < 0·0001). The incidence of TMJ clicking was 12%. At a ten‐year follow‐up, self‐reports of TMJ clicking were significantly associated with the presence of UPCB at baseline, but not with the report of having received an orthodontic treatment. Within the limitation of this study, the presence of unilateral posterior cross‐bite in young adolescents may increase the risk of reporting TMJ sounds at a 10‐year follow‐up. The provision of an orthodontic treatment, however, does not appear to reduce the risk of reporting TMJ sounds.
What Triggers Anger in Everyday Life? Links to the Intensity, Control, and Regulation of These Emotions, and Personality Traits
Authors: Kashdan Todd B. , Goodman Fallon R. , Mallard Travis T. , DeWall C. Nathan
Published: August 2015

Why do people experience anger? Most of our knowledge on anger‐triggering events is based on the study of reactions at a single time point in a person's life. Little research has examined how people experience anger in their daily life over time. In this study, we conducted a comprehensive examination of the situational determinants of anger over the course of 3 weeks. Using daily diary methodology, people (N = 173; 2,342 anger episodes) reported their most intense daily anger and, with an open‐ended format, described the trigger. Participants also answered questions on anger intensity, control, and regulatory strategies, along with baseline personality trait measures. Using an iterative coding system, five anger trigger categories emerged: other people, psychological and physical distress, intrapersonal demands, environment, and diffuse/undifferentiated/unknown. Compared with other triggers, when anger was provoked by other people or when the source was unknown, there was a stronger positive association with anger intensity and lack of control. Personality traits (i.e., anger, mindfulness, psychological need satisfaction, the Big Five) showed few links to the experience and regulation of daily anger. Although aversive events often spur anger, the correlates and consequences of anger differ depending on the source of aversion; personality traits offer minimal value in predicting anger in daily life.
Phytochemical analysis of Passiflora loefgrenii Vitta, a rich source of luteolin-derived flavonoids with antioxidant properties
Authors: Argentieri Maria Pia , Levi Marisa , Guzzo Flavia , Avato Pinarosa
Published: August 2015

Objectives

The paper describes the flavonoid composition of the aerial parts (young leaves, YL; adult leaves, AL; stems, ST) of Passiflora loefgrenii Vitta, a rare species native to Brazil, where it is traditionally used as food. Antioxidant potential has also been evaluated. To the best of our knowledge, no phytochemical and biological study on this species has been reported previously.

Methods

Compositional data have been acquired combining HPLC-diode array detector (DAD) and Electrospary ionization-tandem mass spectrometry (ESI-MS/MS) analyses. Antioxidant activity has been evaluated by the 2,2′-di-phenyl-1-picrylhydrazyl method.

Key findings

Glycosylated flavones, with luteolin as the main aglycone, can be regarded as biomarkers for this drug. Qualitative composition of the extracts from YL, AL and ST was similar. The bulk of the constituents was made up by 8-C-ß-glucosyl luteolin (orientin), 7-O-α-rhamnosyl-6-C-ß-glucosyl luteolin and 6-C-α-rhamnosyl luteolin, which totally amounted to 16.57 (73%), 10.77 (74%) and 5.07 (77%) μg/mg in YL, AL and ST, respectively. P. loefgrenii showed a good antioxidant activity (IC50 of 350 μg/ml), higher than generally reported for other passifloras.

Conclusions

P. loefgrenii, rich in luteolin glycosides, can be regarded as a good candidate to be explored for therapeutic properties other than the sedative one since it represents a rich source of valuable flavonoids with antioxidant potential.
Topical application of the hexane fraction of Lacistema pubescens reduces skin inflammation and cytokine production in animal model
Authors: da Silva Josiane Mello , Conegundes Jéssica Leiras Mota , Mendes Renata de Freitas , Pinto Nícolas de Castro Campos , Gualberto Ana Cristina Moura , Ribeiro Antônia , Gameiro Jacy , de Aguiar Jair Adriano Kopke , Castañon Maria Christina Marques Nogueira , Scio Elita
Published: August 2015

Objectives

The aim of this study was to investigate the acute topical anti-inflammatory effect of the hexane fraction (HLP) of Lacistema pubescens in mice.

Methods

Ear oedema models induced by croton oil, arachidonic acid, phenol, histamine, ethyl phenyl propiolate and capsaicin. Histopathological analyses of ear tissue samples sensitized with croton oil were performed. Myeloperoxidase activity (MPO), the pro-inflammatory cytokine-inhibitory effect and dermatoxicity were also evaluated.

Key findings

HLP (1, 0.5 and 0.1 mg/ear) resulted in a substantial reduction in skin thickness or tissue weight on all models tested, except for capsaicin-induced ear oedema, similar to dexamethasone (0.1 mg/ear) and/or indomethacin (0.5 mg/ear). Histopathological analyses and neutrophil-mediated MPO activity confirmed the topical anti-inflammatory effect of HLP. In addition, HLP reduced IL-1β, IL-6 and tumour necrosis factor-α cytokine levels. Sitosterol-rich fraction (SRF), obtained from HLP fractionation, reduced ear oedema on croton oil and phenol models at the same dose of dexamethasone (0.1 mg/ear). No dermotoxicity was observed.

Conclusions

The mechanism of action of HLP was associated with the inhibition of several pro-inflammatory mediators, including cytokines, arachidonic acid metabolites and histamine, which suggested a glucocorticoid-like effect, reinforced by the presence of the steroid sitosterol. This is the first report on anti-inflammatory activity of L. pubescens leaves.
Tolerance evaluation of overdosed dietary levels of 25‐hydroxyvitamin D3 in growing piglets
Authors: von Rosenberg S. J. , Weber G. M. , Erhardt A. , Höller U. , Wehr U. A. , Rambeck W. A.
Published: August 2015

Forty‐eight, cross‐bred (GL × LW × P) piglets were used in a 42‐day tolerance trial to assess the effects of feeding diets supplemented with vitamin D or increasing levels of 25‐hydroxyvitamin D3 (25‐OH‐D3). Six‐week‐old piglets (24 castrate males, 24 females) were used. Two replicate groups of 6 piglets were randomized by weight and allocated to four dietary treatments. The control group (T1) was supplemented with 50 μg vitamin D3/kg feed. The experimental groups received 25‐OH‐D3 at the recommended dose (T2: 50 μg/kg = 1x), at 250 μg/kg (T3: 5x) or at 500 μg/kg (T4: 10x) respectively. Feed intake and daily weight gain were measured weekly, and the animals were examined by a veterinarian daily. After 42 days, body mass, blood, urine, bone and tissue samples were analysed and a pathology examination conducted. Dietary treatments had no significant effect on final body mass or daily weight gain. The 25‐OH‐D3 plasma concentration in T1 was 17 ± 3 ng/ml (mean ± SD) while the respective values of the experimental groups were significantly increased in T2, T3 and T4. Tissue concentrations of 25‐OH‐D3 were higher in liver and muscle for T3 and T4 and in skin for T4 than in T1. However, neither gross pathology nor histology, nor blood and urine characteristics, nor bone parameters were affected by dietary treatments. Weight of organs as well as dry matter, ash and calcium content of kidneys remained unaffected by dietary 25‐OH‐D3 intake. Furthermore, no changes were observed for general indicators of health. The results of this study demonstrated that feeding piglets with 25‐OH‐D3 at 5 or 10 times the recommended level had no adverse effects on any of the biological parameters measured. It was concluded that 25‐OH‐D3 can be regarded as a supplement with a very high safety margin when used at the recommended level.
The influences of ambient temperature and crude protein levels on performance and serum biochemical parameters in broilers
Authors: Liu Q. W. , Feng J. H. , Chao Z. , Chen Y. , Wei L. M. , Wang F. , Sun R. P. , Zhang M. H.
Published: August 2015

This study was undertaken to investigate the effects of ambient temperature, crude protein levels and their interaction on performance and serum biochemical parameters of broiler chickens. A total of 216 Arbor Acre broiler chickens (108 males and 108 females) were used in a 2 × 3 factorial arrangement and randomly reared at two temperatures (normal temperature: 23 °C; daily cyclic high temperature: 28–32 °C) and fed on three diets with different crude protein levels (153.3, 183.3 or 213.3 g/kg, with constant essential amino acids) from 28 to 42 days of age. Daily cyclic high ambient temperature decreased final body weight, average daily weight gain, average daily feed intake and serum total protein contents (p < 0.001, p < 0.001, p < 0.001, p = 0.008 respectively), but increased feed/gain, mortality, respiratory rate, rectal temperature, serum uric acid contents and serum creatine kinase activity (p = 0.008, p = 0.003, p < 0.0001, p < 0.0001, p < 0.0001, p = 0.003 respectively), irrespective of crude protein levels. At the ambient temperature, reducing crude protein levels resulted in an increase in feed/gain (p < 0.001), but a decrease in serum total protein and uric acid contents. Only serum creatine kinase activity in broiler chickens was interacted by daily cyclic high ambient temperature and dietary crude protein levels (p = 0.003). These results indicated that daily cyclic high ambient temperature had a great effect on performance and serum biochemical parameters in broiler chickens, whereas dietary crude protein levels affected them partially.
Rapamycin, a specific inhibitor of the target of rapamycin complex 1, disrupts intestinal barrier integrity in broiler chicks
Authors: Liu S. Q. , Zhao J. P. , Fan X. X. , Liu G. H. , Jiao H. C. , Wang X. J. , Sun S. H. , Lin H.
Published: August 2015

To uncover the molecular mechanisms underlying the intestinal barrier integrity, this study determined whether the rapamycin (RAPA)‐sensitive target of rapamycin complex 1 (TORC1) pathway was involved in this process. Three groups of 4‐day‐old male chicks were randomly subjected to one of the following treatments for 6 days: high‐dose RAPA [a specific inhibitor of TORC1; an intraperitoneal injection of 1.0 mg/kg body weight (BW), once daily at 09:00 hours], low‐dose RAPA (0.4 mg/kg BW) and RAPA vehicle (control). Results showed that the RAPA treatment increased mortality, while decreasing villus height (p < 0.01), claudin 1 expression, content of immunoglobulin A (IgA), extent of TORC1 phosphorylation (p < 0.05), ratio of villus height to crypt depth (p < 0.01), and population of IgA‐positive B cells in intestinal mucosa, particularly for the jejunum. Some aspects of these responses were dose dependent and appeared to result from weight loss. Together, RAPA exerts the expected inhibition of small intestinal development and IgA production in birds, suggesting the important role of TORC1 in gut barrier integrity.
The effect of 48‐hour fasting on taurine status in healthy adult dogs
Authors: Gray K. , Alexander L. G. , Staunton R. , Colyer A. , Watson A. , Fascetti A. J.
Published: August 2015

Low circulating taurine concentrations may be a risk factor for dilated cardiomyopathy (DCM) in dogs. Circulating taurine is typically measured in the clinic 4–5 h after feeding, largely because the impact of later sampling is not known. The objective of this study was to measure taurine in the blood during a 48‐h fast in 12 healthy adult Labrador Retrievers to refine sampling methodology for determination of taurine status. Plasma and whole blood (WB) taurine concentrations did not fall to levels indicative of clinical deficiency throughout fasting; WB was the more reliable indicator of taurine status. This study shows that blood samples can be taken for assessment of taurine status any time up to 48 h after ingestion of a meal in healthy adult dogs.
New species of Clade B Symbiodinium (Dinophyceae) from the greater Caribbean belong to different functional guilds: S. aenigmaticum sp. nov., S. antillogorgium sp. nov., S. endomadracis sp. nov., and S. pseudominutum sp. nov.
Authors: Parkinson John Everett , Coffroth Mary Alice , LaJeunesse Todd C.
Published: August 2015

Molecular approaches have begun to supersede traditional morphometrics in the species delineation of micro‐eukaryotes. In addition to fixed differences in DNA sequences, recent genetics‐based descriptions within the dinoflagellate genus Symbiodinium have incorporated confirmatory morphological, physiological, and ecological evidence when possible. However, morphological and physiological data are difficult to collect from species that have not been cultured, while the natural ecologies of many cultured species remain unknown. Here, we rely on genetic evidence—the only data consistently available among all taxa investigated—to describe four new Clade B Symbiodinium species. The ‘host‐specialized’ species (S. antillogorgium sp. nov. and S. endomadracis sp. nov.) engage in mutualisms with specific cnidarian hosts, but exhibit differences in our ability to culture them in vitro. The ecologically ‘cryptic’ species (S. aenigmaticum sp. nov. and S. pseudominutum sp. nov.) thrive in culture, but their roles or functions in the ecosystem (i.e., niches) are yet to be documented. These new species call further attention to the spectrum of ecological guilds among Symbiodinium.
Low‐Field Magnetic Resonance Imaging and Multislice Computed Tomography for the Detection of Cervical Syringomyelia in Dogs
Authors: Kromhout K. , van Bree H. , Broeckx B.J.G. , Bhatti S. , De Decker S. , Polis I. , Gielen I.
Published: August 2015

Background

Syringomyelia (SM) is defined as the presence of fluid‐containing cavities within the parenchyma of the spinal cord. Sagittal magnetic resonance (MR) images have been described as the preferred technique for visualizing SM in dogs and humans.

Objective

To investigate whether computed tomography (CT) can be used to diagnose SM.

Animals

Thirty‐two client‐owned dogs referred for investigation of the cervical spine on magnetic resonance imaging (MRI) and CT.

Methods

Two reviewers retrospectively analyzed sagittal and transverse T1‐weighted spin echo (T1WSE) MR images and CT images from each dog for the presence of SM and, if SM was present, the width (mm, syrinx width [SW]) was measured. The results were analyzed statistically.

Results

For the presence of SM there was a moderate interobserver agreement for MR (81%, κ = 0.54) and almost perfect agreement for CT (94%, κ = 0.87). There was a moderate intramodality agreement for both observers (observer 1 81%, κ = 0.59; observer 2 81%, κ = 0.57). For measurement of SW the repeatability was the best on the midsagittal T1WSE images (95% repeatability coefficient <0.52 mm) and the reproducibility was the best on midsagittal images in both modalities (95% limits of agreement −0.55–0.45; P = 0.002).

Conclusion and Clinical Importance

Both techniques can be used to detect SM. Midsagittal MR and CT images are best used for measuring SW. Computed tomography can be used as a diagnostic tool for SM when MRI is not available, but CT cannot replace MRI as the standard screening technique for the detection of SM in Cavalier King Charles Spaniel for breeding purposes.
Evaluation of the Cortisol‐to‐ACTHRatio in Dogs with Hypoadrenocorticism, Dogs with Diseases Mimicking Hypoadrenocorticism and in Healthy Dogs
Authors: Boretti F.S. , Meyer F. , Burkhardt W.A. , Riond B. , Hofmann‐Lehmann R. , Reusch C.E. , Sieber‐Ruckstuhl N.S.
Published: August 2015

Background

The adrenocorticotropic hormone (ACTH) stimulation test is the gold standard for diagnosing hypoadrenocorticism (HA) in dogs. However, problems with the availability of syntheticACTH(tetracosactrin/cosyntropin) and increased costs have prompted the need for alternative methods.

Objectives

To prospectively evaluate the cortisol‐to‐ACTHratio (CAR) as a screening test for diagnosing canineHA.

Animals

Twenty three dogs with newly diagnosedHA; 79 dogs with diseases mimickingHA; 30 healthy dogs.

Methods

PlasmaACTHand baseline cortisol concentrations were measured beforeIVadministration of 5 μg/kgACTHin all dogs.CARwas calculated and the diagnostic performance ofACTH, baseline cortisol,CARand sodium‐to‐potassium ratios (SPRs) was assessed based on receiver operating characteristics (ROC) curves calculating the area under theROCcurve.

Results

TheCARwas significantly lower in dogs withHAcompared to that in healthy dogs and in those with diseases mimickingHA(P < .0001). There was an overlap betweenHAdogs and those withHAmimicking diseases, butCARstill was the best parameter for diagnosingHA(ROC AUC0.998), followed by theACTHconcentration (ROC AUC0.97), baseline cortisol concentration (ROC AUC0.96), and SPR (ROC AUC0.86). With aCARof >0.01 the diagnostic sensitivity and specificity were 100% and 99%, respectively.

Conclusion and Clinical Importance

Calculation of theCARis a useful screening test for diagnosing primaryHA. As a consequence of the observed overlap between the groups, however, misdiagnosis cannot be completely excluded. Moreover, additional studies are needed to evaluate the diagnostic reliability ofCARin more dogs with secondaryHA.
Angiogenesis Revisited: An Overlooked Role of Endothelial Cell Metabolism in Vessel Sprouting
Authors: Vandekeere Saar , Dewerchin Mieke , Carmeliet Peter
Published: August 2015

During vessel sprouting, endothelial “tip” cells migrate at the forefront, while the endothelial “stalk” cells elongate the sprout; endothelial “phalanx” cells line quiescent vessels. Tip and stalk cells can dynamically switch phenotypes under the control of VEGF and Notch signaling. Novel findings now show that in addition to signaling cascades, metabolism coregulates the formation of the new vasculature. Recent studies demonstrated that ECs rely primarily on glycolysis for ATP production, that glycolysis is further enhanced in angiogenic ECs, and that the key glycolytic regulator PFKFB3 codetermines angiogenesis by controlling the balance of tip versus stalk cells and promoting a migratory tip cell phenotype. On the other hand, FAO regulates endothelial stalk cell proliferation by providing carbon sources for biosynthetic processes, more particularly for de novo nucleotide synthesis for DNA replication. Here, we overview the current understanding of the various metabolic pathways in ECs and their impact on vessel formation in health and disease.
Reparixin attenuates neuronal injury in experimental Klebsiella pneumoniae meningoencephalitis through dual effects on neuroprotection and neuroinflammation
Authors: Chiu Chien‐Tsai , Wen Li‐Li , Pao Hsin‐Ping , Yang Ling‐Yu , Huang Ya‐Ni , Wang Jia‐Yi
Published: August 2015

Aims

Bacterial meningitis causes high mortality and brain damage. The host immune response is associated with brain injury. Chemokine (C‐X‐C motif) (CXC) chemokines are neutrophil chemoattractants. This study focused on the beneficial effects of intracerebroventricular administration of reparixin, an inhibitor of chemokine (C‐X‐C motif) receptor (CXCR)1/2, to rats at 2 h following experimental Klebsiella pneumoniae meningoencephalitis.

Methods

We used a previously established meningoencephalitis animal model in which Sprague‐Dawley rats were infected by K. pneumoniae. Sham and infected animals were treated with vehicle or reparixin and sacrificed at various time points. Leukocyte infiltration into cerebrospinal fluid (CSF) and brain as well as gene and protein expression of chemokines and receptors, and neuronal apoptosis were examined. Primary cultures of neuron/glia were infected with K. pneumoniae as an in vitro model of meningoencephalitis.

Results

Levels of chemokine (C‐X‐C motif) ligand (CXCL)2 in CSF time‐dependently increased markedly as early as 2 h, and peaked at 8 h following infection and were much higher than those in serum collected simultaneously. Reparixin significantly reduced leukocyte infiltration into CSF and brain tissues, clinical illness, and brain cell apoptosis at 24 h. Reparixin reduced the elevated CSF concentrations of chemokines [CXCL1, CXCL2, chemokine (C‐C motif) ligand (CCL)2 and CCL5] and proinflammatory cytokines. Reparixin also reduced the expression of mRNA of various chemokines, chemokine receptors and proinflammatory cytokines in infected brain tissues. Using primary cultures that are devoid of leukocytes, we further observed that reparixin attenuated the neuronal, but not microglial cell death after infection.

Conclusions

Reparixin not only reduces amplified inflammation, but also provides direct neuroprotective effects in K. pneumoniae meningoencephalitis.
The journey into fatherhood: A grounded theory study
Authors: Sansiriphun Nantaporn , Kantaruksa Kannika , Klunklin Areewan , Baosuang Chavee , Liamtrirat Saowanee
Published: August 2015

The objective of this study was to explore the process of transition into fatherhood for Thai men from childbirth to the postpartum period. Forty‐one first‐time Thai fathers were voluntarily recruited from two hospitals in Chiang Mai, Thailand, from December 2012 to June 2013. In‐depth interviews were used to collect the data, which were analyzed based on grounded theory methodology. The basic social process that emerged as the core category was termed: “the journey into fatherhood.” This process was divided into three phases: labor, delivery, and family beginning. Within this process, there were various situations, challenges, and pressures, which caused many changes of mood and feelings for the first‐time fathers. Throughout this process, they applied various strategies to manage their concerns and needs, in order to develop into masterly fathers. Identifying the process of the journey into fatherhood provides nurses and midwives insight into the new fathers' experiences, which will enable them to be more sensitive, respectful, and effective caregivers.
The impact of surgical excisions on human gastric slow wave conduction, defined by high‐resolution electrical mapping and in silico modeling
Authors: Du P. , Hameed A. , Angeli T. R. , Lahr C. , Abell T. L. , Cheng L. K. , O'Grady G.
Published: August 2015

Background

Gastric contractions are coordinated by slow waves, generated by interstitial cells of Cajal (ICC). Gastric surgery affects slow wave conduction, potentially contributing to postoperative gastric dysfunction. However, the impact of gastric cuts on slow waves has not been comprehensively evaluated. This study aimed to define consequences of surgical excisions on gastric slow waves by applying high‐resolution (HR) electrical mapping and in silico modeling.

Methods

Patients undergoing gastric stimulator implantation (n = 10) underwent full‐thickness stapled excisions (25 × 15 mm, distal corpus) for histological evaluation, enabling HR mapping (256 electrodes; 36 cm2) over and adjacent to excisions. A biophysically based in silico model of bidirectionally coupled ICC networks was developed and applied to investigate the underlying conduction mechanisms and importance of excision orientation.

Key Results

Normal gastric slow waves propagated aborally (3.0 ± 0.2 cpm). Excisions induced complete conduction block and wavelets that rotated around blocks, then propagated rapidly circumferentially distal to the blocks (8.5 ± 1.2 vs normal 3.6 ± 0.4 mm/s; p < 0.01). This ‘conduction anisotropy' homeostatically restored antegrade propagating gastric wavefronts distal to excisions. Excisions were associated with complex dysrhythmias in five patients: retrograde propagation (3/10), ectopics (3/10), functional blocks (2/10), and collisions (1/10). Simulations demonstrated conduction anisotropy emerged from bidirectional coupling within ICC layers and showed transverse incision length and orientation correlated with the degree of conduction distortion.

Conclusions & Inferences

Orienting incisions in the longitudinal gastric axis causes least disruption to electrical conduction and motility. However, if transverse incisions are made, a homeostatic mechanism of gastric conduction anisotropy compensates by restoring aborally propagating wavefronts. Complex dysrhythmias accompanying excisions could modify postoperative recovery in susceptible patients.
Neuromechanical factors involved in the formation and propulsion of fecal pellets in the guinea‐pig colon
Authors: Costa M. , Wiklendt L. , Simpson P. , Spencer N. J. , Brookes S. J. , Dinning P. G.
Published: August 2015

Background

The neuromechanical processes involved in the formation and propulsion of fecal pellets remain incompletely understood.

Methods

We analyzed motor patterns in isolated segments of the guinea‐pig proximal and distal colon, using video imaging, during oral infusion of liquid, viscous material, or solid pellets.

Key Results

Colonic migrating motor complexes (CMMCs) in the proximal colon divided liquid or natural semisolid contents into elongated shallow boluses. At the colonic flexure these boluses were formed into shorter, pellet‐shaped boluses. In the non‐distended distal colon, spontaneous CMMCs produced small dilations. Both high‐ and low‐viscosity infusions evoked a distinct motor pattern that produced pellet‐shaped boluses. These were propelled at speeds proportional to their surface area. Solid pellets were propelled at a speed that increased with diameter, to a maximum that matched the diameter of natural pellets. Pellet speed was reduced by increasing resistive load. Tetrodotoxin blocked all propulsion. Hexamethonium blocked normal motor patterns, leaving irregular propagating contractions, indicating the existence of neural pathways that did not require nicotinic transmission.

Conclusions & Inferences

Colonic migrating motor complexes are responsible for the slow propulsion of the soft fecal content in the proximal colon, while the formation of pellets at the colonic flexure involves a content‐dependent mechanism in combination with content‐independent spontaneous CMMCs. Bolus size and consistency affects propulsion speed suggesting that propulsion is not a simple reflex but rather a more complex process involving an adaptable neuromechanical loop.
Synthesis and pharmacological evaluation of glycosides of resveratrol, pterostilbene, and piceatannol
Authors: Shimoda Kei , Kubota Naoji , Uesugi Daisuke , Hamada Hatsuyuki , Tanigawa Masato , Hamada Hiroki
Published: August 2015

To enhance their water solubility and pharmacological activities, the stilbenes resveratrol, pterostilbene, and piceatannol were glycosylated to their monoglucosides (β‐glucosides) and diglycosides (β‐maltosides) by cultured cells and cyclodextrin glucanotransferase (CGTase). Cultured cells of Phytolacca americana and glucosyltransferase (PaGT) were capable of glucosylation of resveratrol to its 3‐ and 4′‐β‐glucosides. Pterostilbene was slightly transformed into its 4′‐β‐glucoside by P. americana cells. Piceatannol was readily converted into piceatannol 4′‐β‐glucoside, with the highest yield among the three substrates. The 3‐ and 4′‐β‐glucosides of resveratrol were subjected to further glycosylation by CGTase to give 3‐ and 4′‐β‐maltoside derivatives. The inhibitory action of resveratrol and pterostilbene toward histamine release induced with compound 48/80 from rat peritoneal mast cells was improved by β‐glucosylation and/or β‐maltosylation (i.e., the inhibitory activity for histamine release of the 3‐ and 4′‐β‐glucosides of resveratrol, the 3‐ and 4′‐β‐maltosides of resveratrol, and the 4′‐β‐glucoside of pterostilbene was higher than that of the corresponding aglycones, resveratrol and pterostilbene, respectively). In addition, the phosphodiesterase (PDE) inhibitory activity of resveratrol and pterostilbene was enhanced by β‐glucosylation and/or β‐maltosylation (i.e., the PDE inhibitory activities of the 3‐ and 4′‐β‐glucosides of resveratrol, the 4′‐β‐maltoside of resveratrol, and the 4′‐β‐glucoside of pterostilbene were higher than those of the corresponding aglycones, resveratrol and pterostilbene, respectively).
Resveratrol metabolite profiling in clinical nutrition research—from diet to uncovering disease risk biomarkers: epidemiological evidence
Authors: Rabassa Montserrat , Zamora‐Ros Raul , Urpi‐Sarda Mireia , Andres‐Lacueva Cristina
Published: August 2015

Resveratrol is a bioactive plant compound that has drawn scientific and media attention owing to its protective effects against a wide variety of illnesses, including cardiovascular diseases and cancer. In the last two decades, a plethora of preclinical studies have shown these beneficial effects, and some of them have been supported by clinical trials. However, there are few epidemiological studies assessing these relationships, showing mostly inconsistent results among them. This could be partially due to the difficulty of accurately estimating dietary resveratrol exposure. The development of Phenol‐Explorer, a database containing resveratrol food‐composition data, will facilitate the estimation of resveratrol intake. Moreover, the discovery and validation of a nutritional biomarker of this exposure, urinary resveratrol metabolite profile, will allow a more accurate assessment of dietary resveratrol exposure. Few epidemiological studies have assessed the potential health effects of resveratrol. Resveratrol was not associated with total mortality, cancer, or cardiovascular events, but it was associated with an improvement of serum glucose and triglyceride levels and a decrease in heart rate. Together, these findings suggest a potential cardioprotective effect of resveratrol in epidemiological studies, although the evidence is still scarce.
The complex contribution of chemokines to neuroinflammation: switching from beneficial to detrimental effects
Authors: Le Thuc Ophélia , Blondeau Nicolas , Nahon Jean‐Louis , Rovère Carole
Published: August 2015

Inflammation is an innate mechanism that defends organisms against harmful stimuli. Inflammation leads to the production and secretion of proinflammatory mediators that activate and recruit immune cells to damaged tissues, including the brain, to resolve the cause of inflammation. In the central nervous system, inflammation is referred to as neuroinflammation, which occurs in various pathological conditions of the brain. The primary role of neuroinflammation is to protect the brain. However, prolonged and/or inappropriate inflammation can be harmful for the brain, from individual cells to the whole tissue. This review focuses on a particular type of inflammatory mediator, chemokines, and describes their complex effects both under physiological and pathophysiological conditions of the brain. The clinical relevance of the multiple characters of chemokines is highlighted with respect to acute and chronic inflammation of the brain, including their actions in stroke and Alzheimer's disease, respectively.
Comparison of central venous catheterization techniques in pediatric patients: needle vs angiocath
Authors: Song In‐Kyung , Lee Ji‐Hyun , Kang Joo‐Eun , Oh Hye‐Won , Kim Hee‐Soo , Park Hee‐Pyoung , Kim Jin‐Tae
Published: August 2015

Background

A needle or an angiocath has been generally used as a route for inserting a guide wire during central venous catheterization. We compared the needle with the angiocath for ultrasound‐guided central venous catheterization in pediatric patients concerning accuracy and easiness.

Methods

One hundred and thirty‐two patients aged between 1 day and 5 years were randomized into the needle and the angiocath groups. The study was separately carried out in two age groups: newborns vs infants and children. The primary outcome was time to successful insertion of the guide wire. Secondary outcomes including other time variables (time to 1st successful puncture of the vein, time between 1st successful puncture of the vein and successful insertion of the guide wire, total time to successful central venous catheterization), frequency variables (number of the puncture attempts, number of the guide wire insertion attempts), success rates (1st successful puncture rate, 1st successful guide wire insertion rate), and complications.

Results

There were no statistically significant differences in time and frequency variables, success rates, and complications between both the age groups. Time to 1st successful puncture of the vein (36.8 ± 31.7 vs 19.8 ± 27.1 s; 95% CI of mean difference 2.2–31.8; P = 0.03) and number of puncture attempts (1.6 ± 0.7 vs 1.3 ± 0.8; P = 0.02) were significantly greater in newborns with the needle, whereas with the angiocath, the number of puncture attempts was larger in newborns than in infants and children (1.7 ± 1.2 vs 1.2 ± 0.7; P = 0.02).

Conclusion

The angiocath showed no superiority over the needle for ultrasound‐guided central venous catheterization in pediatric patients. Regardless of the needle or the angiocath, puncture of the vein was more difficult in newborns than in infants and children.
Autism spectrum disorder (ASD) and its perioperative management
Authors: Taghizadeh Neda , Davidson Andrew , Williams Katrina , Story David
Published: August 2015

Autism spectrum disorder (ASD) is now diagnosed in more than 1 in 100 children, so it is not surprising that anesthetists are increasingly providing care for children with this diagnosis. The diagnostic classification for ASD has recently changed and our understanding of the causes and management of ASD are also changing rapidly. This review provides a timely update to increase understanding and awareness of the problems that children with ASD experience, and to minimize perioperative problems. Current literature on premedication and the increasing use of alpha‐2 agonists such as clonidine and dexmedetomidine as well as the use of old favorites midazolam and ketamine is reviewed. Some simple strategies that will improve care and decrease anxiety, like social stories, the use of tablet computers, other comfort items or games for distraction, and using favorite drinks to disguise the bitter taste of medications, are described. Remember, the parents are their child's expert and will know what agitates and settles them. Talking to them prior to the day of the procedure is ideal. The importance of staff training and having a clinical practice guideline available at every institution cannot be overstated.
Sources of resistance to Indian pathotypes of Puccinia graminis tritici and P. triticina in durum wheat
Authors: Mishra Akhilesh N. , Shirsekar Gautam S. , Yadav Sitaram , Kaushal Kamini , Dubey Vijay G. , Sai Prasad Sakuru V.
Published: August 2015

Stem rust and leaf rust are important diseases affecting durum wheat production in India. Inheritance and extent of diversity in resistance were studied in five durum genotypes, viz. ʽB 662', ʽED 2398‐A', ʽHG 110', ʽIWP 5019' and ʽLine 1172ʼ using Pgt pathotypes 40A and 117‐6, and Pt pathotypes 12‐2 and 104‐2. F2 and F3 analyses showed that resistance was conferred by one or two genes in each line. In all, four genes for resistance to 40A, and eight each for pathotypes 117‐6 and 12‐2 were identified among the five genotypes, and three for resistance to 104‐2 among B 662, ED 2398‐A and IWP 5019 were indicated by tests of allelism. Although the gene identities are not known, at least some of them should be different from Sr2, Sr7b, Sr8a, Sr8b, Sr9e, Sr9g, Sr11, Sr12, Sr13, Sr14, Sr17, Sr23 and Sr28; and from Lr3, Lr14a, Lr23 and Lr27 + Lr31. These genotypes enrich the diversity of resistance to stem rust and leaf rust for durum wheat improvement.
Photoisomerization of Trans Ortho‐, Meta‐, Para‐Nitro Diarylbutadienes: A Case of Regioselectivity
Authors: Agnihotri Harsha , Paramasivam Mahalingavelar , Palakollu Veerabhadraiah , Kanvah Sriram
Published: August 2015

A series of ortho‐, meta‐ and para‐substituted trans‐nitro aryl (phenyl and pyridyl) butadienes have been synthesized and characterized. The effect of substitution and positional selectivity on their fluorescence and photoisomerization were systematically investigated. Among all dienes, meta‐ and para‐nitro phenyl‐substituted derivatives exhibit remarkable solvatochromic emission shifts due to intramolecular charge transfer. On the other hand, ortho derivatives undergo regioselective isomerization upon photoexcitation in contrast to inefficient isomerization of para and meta nitro‐substituted dienes. Single crystal X‐ray analysis revealed existence of intramolecular hydrogen bonding between the nitro group and the hydrogen of the proximal double bond. This restricts the rotation of the proximal double bond thereby allowing regioselective isomerization. The observations were also supported by NMR spectroscopic studies.
Coronary Heart Disease and Stroke in Adults Born Preterm – The Helsinki Birth Cohort Study
Authors: Kajantie Eero , Osmond Clive , Eriksson Johan G.
Published: August 2015

Background

Adults born preterm have increased risk factors for cardiovascular disease. We studied the cumulative incidence of manifest coronary heart disease (CHD) and stroke in adults born preterm.

Methods

We studied 19 015 people born in Helsinki, Finland, during 1924–44. Of them, 137 (0.7%) were born early (<34 weeks) and 1006 (5.3%) late preterm (34 to <37 weeks). We ascertained CHD and stroke from the National Hospital Discharge and Death Registers and estimated hazard ratios (HRs) by Cox regression.

Results

A total of 3027 subjects (15.9%) had CHD and 1805 (9.5%) stroke. HRs for CHD were 1.17 (95% confidence interval 0.83, 1.65) for early and 0.99 (0.85, 1.14) for late preterm. For stroke, they were 0.84 (0.50, 1.39) and 0.86 (0.71, 1.06). HRs were little changed when adjusted for childhood and adult socio‐economic position and birthweight for gestation standard deviation score. They were similar for first‐ever events before or after 65 years, for haemorrhagic and thrombotic stroke, and for men and women, except that the HR for CHD for women born early preterm was 1.98 (1.18, 3.30).

Conclusions

We found no increased risk of CHD or stroke up to old age in people born preterm, although women born early preterm had a higher rate of CHD. There is a discrepancy between increased risk factors in younger generations born preterm and little or no increase in manifest disease in older age. Uncovering reasons underlying this discrepancy may give important insights into the prevention of cardiovascular disease.