bluuebunny/crossref_metadata_2025_split huggingface dataset:
Posttranscriptional regulation ofFOXOexpression: microRNAs and beyond
Authors: Urbánek P , Klotz L‐O 
Published: February 2016

Forkhead box, class O (FOXO) transcription factors are major regulators of diverse cellular processes, including fuel metabolism, oxidative stress response and redox signalling, cell cycle progression and apoptosis. Their activities are controlled by multiple posttranslational modifications and nuclear‐cytoplasmic shuttling. Recently, post‐transcriptional regulation of FOXO synthesis has emerged as a new regulatory level of their functions. Accumulating evidence suggests that this post‐transcriptional mode of regulation of FOXO activity operates in response to stressful stimuli, including oxidative stress. Here, we give a brief overview on post‐transcriptional regulation of FOXO synthesis by microRNAs (miRNAs) and by RNA‐binding regulatory proteins, human antigen R (HuR) and quaking (QKI). Aberrant post‐transcriptional regulation of FOXOs is frequently connected with various disease states. We therefore discuss characteristic examples ofFOXOregulation at the post‐transcriptional level under various physiological and pathophysiological conditions, including oxidative stress and cancer. The picture emerging from this summary points to a diversity of interactions between miRNAs/miRNA‐induced silencing complexes and RNA‐binding regulatory proteins. Better insight into these complexities of post‐transcriptional regulatory interactions will add to our understanding of the mechanisms of pathological processes and the role of FOXO proteins.Linked ArticlesThis article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visithttp://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc
Translational mixed‐effects PKPD modelling of recombinant human growth hormone – from hypophysectomized rat to patients
Authors: Thorsted A , Thygesen P , Agersø H , Laursen T , Kreilgaard M 
Published: February 2016

Background and PurposeWe aimed to develop a mechanistic mixed‐effects pharmacokinetic (PK)–pharmacodynamic (PD) (PKPD) model for recombinant human growth hormone (rhGH) in hypophysectomized rats and to predict the human PKPD relationship.Experimental ApproachA non‐linear mixed‐effects model was developed from experimental PKPD studies of rhGH and effects of long‐term treatment as measured by insulin‐like growth factor 1 (IGF‐1) and bodyweight gain in rats. Modelled parameter values were scaled to human values using the allometric approach with fixed exponents for PKs and unscaled for PDs and validated through simulations relative to patient data.Key ResultsThe final model described rhGH PK as a two compartmental model with parallel linear and non‐linear elimination terms, parallel first‐order absorption with a total s.c. bioavailability of 87% in rats. Induction of IGF‐1 was described by an indirect response model with stimulation of kin and related to rhGH exposure through an Emax relationship. Increase in bodyweight was directly linked to individual concentrations of IGF‐1 by a linear relation. The scaled model provided robust predictions of human systemic PK of rhGH, but exposure following s.c. administration was over predicted. After correction of the human s.c. absorption model, the induction model for IGF‐1 well described the human PKPD data.ConclusionsA translational mechanistic PKPD model for rhGH was successfully developed from experimental rat data. The model links a clinically relevant biomarker, IGF‐1, to a primary clinical end‐point, growth/bodyweight gain. Scaling of the model parameters provided robust predictions of the human PKPD in growth hormone‐deficient patients including variability.
The Privileged Status of Category Representations in Early Development
Authors: Cimpian Andrei 
Published: February 2016

AbstractThe ability to carve the world into broad categories (e.g., DOG) made up of distinct individuals (e.g., Lassie and Toto) is essential for adaptive behavior and has been the focus of extensive research in cognitive and developmental psychology. Classic work on the development of category representations has revealed that they emerge early: Even infants can conceive of distinct objects as equivalent members of the same category. However, more recently, research on conceptual development has begun to suggest a stronger conclusion, namely that mental representations of categories are privileged by our cognitive systems relative to representations of similar, but noncategorical, entities. According to this research, which I review in this article, our minds may be structured to facilitate the acquisition, retention, and manipulation of category‐level information. This conclusion goes beyond current theories of conceptual development.
Weight gain in Turner Syndrome: association to puberty induction? – longitudinal analysis of KIGS data
Authors: Reinehr Thomas , Lindberg Anders , Toschke Christina , Cara Jose , Chrysis Dionisis , Camacho‐Hübner Cecilia 
Published: February 2016

SummaryContextGirls with Turner Syndrome (TS) treated or not treated with growth hormone (GH) are prone to overweight. Therefore, we hypothesize that puberty induction inTSis associated with weight gain.MethodsWe analyzed weight changes (BMI‐SDS) between onset ofGHtreatment and near adult height (NAH) in 887 girls withTSenrolled inKIGS(Pfizer International Growth Database). Puberty was induced with estrogens in 646 (72·8%) girls withTS.ResultsWeight status did not change significantly betweenGHtreatment start and 1 year later (mean difference −0·02BMI‐SDS), but increased significantly (P< 0·001) untilNAH(+0·40BMI‐SDS). TheBMI‐SDSincreased +0·21 until start of puberty (P< 0·001). Girls with spontaneous and induced puberty showed similarBMI‐SDSchanges. Puberty induction at ≥12 years was associated with a significant (P< 0·001) less increase ofBMI‐SDS(+0·7BMI‐SDS) between baseline andNAHcompared to puberty induction at <12 year (+1·0BMI‐SDS). In multiple linear regression analyses changes ofBMI‐SDSbetween baseline andNAHwere negatively associated with baselineBMI‐SDS(P< 0·001),GHdoses (P= 0·015), and age at puberty induction (P< 0·001), positively with years onGHtreatment (P= 0·004), while duration and dose of estrogens, its route of administration (transdermal/oral), changes of height‐SDS, thyroxin and oxandrolone treatment, and karyotype did not correlate significantly to changes ofBMI‐SDSin this time period.ConclusionsPuberty does not seem to play a major role in weight gain in girls withTSsince the majority of the increases inBMI‐SDSoccurred before puberty. However, late puberty induction seems to decrease the risk of weight gain.
Prevalence and correlates of vitamin D deficiency in adults after traumatic brain injury
Authors: Jamall Omer A. , Feeney Claire , Zaw‐Linn Joanna , Malik Aysha , Niemi Mari E.K. , Tenorio‐Jimenez Carmen , Ham Timothy E. , Jilka Sagar R. , Jenkins Peter O. , Scott Gregory , Li Lucia M. , Gorgoraptis Nikolaos , Baxter David , Sharp David J. , Goldstone Anthony P. 
Published: February 2016

SummaryObjectivesTraumatic brain injury (TBI) is a major cause of long‐term disability with variable recovery. Preclinical studies suggest that vitamin D status influences the recovery after TBI. However, there is no published clinical data on links between vitamin D status and TBI outcomes. The aim was to determine the (i) prevalence of vitamin D deficiency/insufficiency, and associations of vitamin D status with (ii) demographic factors and TBI severity, and with (iii) cognitive function, symptoms and quality of life, in adults after TBI.DesignRetrospective audit of patients seen between July 2009 and March 2015. Serum vitamin D (25‐hydroxy‐cholecalciferol) was categorized as deficient (<40 nmol/l), insufficient (40–70 nmol/l) or replete (>70 nmol/l).PatientsA total of 353 adults seen in tertiary hospital clinic (75·4% lighter skinned, 74·8% male, age median 35·1 year, range 26·6–48·3 year), 0·3–56·5 months after TBI (74·5% moderate–severe).MeasurementsSerum vitamin D concentrations; Addenbrooke's Cognitive Examination (ACE‐R), Beck Depression Inventory‐II (BDI‐II), SF‐36 Quality of Life, Pittsburgh Sleep Quality Index.ResultsIn total, 46·5% of patients after TBI had vitamin D deficiency and 80·2% insufficiency/deficiency. Patients with vitamin D deficiency had lower ACE‐R scores than those of vitamin D replete (mean effect size ± SEM 4·5 ± 2·1, P = 0·034), and higher BDI‐II scores than those of vitamin D insufficient (4·5 ± 1·6, P = 0·003), correcting for age, gender, time since TBI and TBI severity. There was no association between vitamin D status and markers of TBI severity, sleep or quality of life.ConclusionVitamin D deficiency is common in patients after TBI and associated with impaired cognitive function and more severe depressive symptoms.
The influence of thiazide intake on calcium and parathyroid hormone levels in patients with primary hyperparathyroidism
Authors: Riss Philipp , Kammer Michael , Selberherr Andreas , Bichler Christoph , Kaderli Reto , Scheuba Christian , Niederle Bruno 
Published: February 2016

SummaryObjectiveThe effects of thiazide medication in patients with primary hyperparathyroidism (PHPT) have so far not been elucidated. The aim of this study was to analyse the extent to which the administration of thiazides may influence biochemical parameters and therefore the diagnosis of PHPT in a large cohort of patients.Design and patientsThe biochemical parameters of 1066 patients with PHPT were analysed, and drug history was documented. Calcium (Ca)/creatinine clearance ratio (CCCR) was calculated. The results of patients given thiazides (n = 170) and those not given thiazides (n = 896) were analysed and compared.MeasurementsTwenty‐four‐hour urinary calcium excretion (24hU), albumin‐corrected serum calcium, PTH, creatinine, 1,25OH‐ and 25OH‐vitamin D were measured, and CCCR was calculated.Results24hUCa and CCCR were significantly lower in patients on thiazides (P = 0·02 and P = 0·0068, resp.), and serum creatinine was significantly higher in those subjects (P < 0·0001). Serum Ca levels only proved different in an analysis of covariance among patients younger than 60 years (P = 0·003). Nevertheless, PTH was not different in both groups (P = 0·917).ConclusionsAccording to recently published guidelines, 24hUCa measurement is necessary to give indication for surgery in asymptomatic patients and to distinguish between PHPT and familial hypocalciuric hypercalcaemia [FHH]. Thiazides significantly decrease 24hUCa, yet neither increase serum Ca nor influence PTH levels in patients with PHPT. However, discontinuing thiazides is crucial for a correct CCCR calculation to pre‐operatively rule out FHH. As a consequence, the withdrawal of thiazide medication must be recommended for the diagnosis of PHPT prior to surgery.
α‐ketoglutarate is associated with delayed wound healing in diabetes
Authors: Tan Qin , Wang Wei , Yang Chuan , Zhang Jinglu , Sun Kan , Luo Heng cong , Mai Li fang , Lao Yu , Yan Li , Ren Meng 
Published: February 2016

SummaryAimA high level of matrix metalloproteinase 9 (MMP‐9) is a predictor of poor wound healing in diabetic foot ulcers. In skin keratinocytes, site‐specific DNA demethylation plays an important role in MMP‐9 expression. Ten‐eleven translocation enzyme 2 (TET2) protein, one member of TET family, could rely on α‐ketoglutarate (α‐KG) as cosubstrate to exhibit catalytic activity of DNA demethylation. Here, we aimed to explore the changes of α‐KG and its relationship with MMP‐9 and TET2 during diabetic wound healing.MethodsSeventy‐one cases of patients with diabetic foot ulcers and 53 cases of nondiabetic ulcers were enrolled. Serum, urine and wound fluids were collected for measurement of α‐KG levels and MMP‐9 expression. Skin tissues were collected for the measurement of TET2 and MMP‐9 expression. Clinical parameters were collected, and transcutaneous oxygen pressure (TcPO2) levels of feet were detected.ResultsThe levels of α‐KG, TET2 and MMP‐9 were significantly increased in diabetic wound compared with nondiabetic wound (P = 0·010, 0·016 and 0·025). There was a significant correlation between a low TcPO2 and a high α‐KG level of wound fluids (r = −0·395, P = 0·002). Further analysis showed that α‐KG concentration had a positive correlation with both haemoglobin A1c (HbA1C) and 2 h postprandial blood glucose (PBG) (r = 0·393, P = 0·005; r = 0·320, P = 0·025, respectively).ConclusionsThe levels of α‐KG, TET2 and MMP‐9 were significantly increased in diabetic wound compared with nondiabetic wound. Elevated α‐KG was related to local hypoxia ischaemia status and systematic poor glycaemic control.
Ribonucleic acid sequencing data mining: A new tool for understanding neuroimmunological conditions
Authors: Sato Wakiro , Yamamura Takashi 
Published: February 2016

AbstractRNA sequencing is a next‐generation sequencing‐based approach for comprehensive gene expression analysis. The “big data’’ of RNA sequencing have been deposited in public databases. Two recent studies attempted to use such data to answer clinically relevant questions pertaining to neuroimmunology.
Astrocyte‐intrinsic regulation of central nervous system inflammation and neurodegeneration
Authors: Rothhammer Veit , Quintana Francisco J. 
Published: February 2016

AbstractAstrocytes constitute the majority of cells in the mammalian brain, where they carry out fine‐tuned tasks that include, for example, the formation of the blood–brain barrier, the provision of structural support, the regulation of ion homeostasis and neurotransmitter recycling, and the modulation of neuronal function. In the context of autoimmune inflammation in the central nervous system during multiple sclerosis, these and other functions are challenged, while astrocytes modulate the local inflammatory response not only by regulating the blood–brain barrier permeability, but also by controlling the recruitment and activation of inflammatory cells and neurotoxicity. In the present review, we discuss astrocyte‐intrinsic mechanisms that affect multiple sclerosis pathology and might provide potential targets for therapeutic intervention.
Economic Analysis and Species at Risk: Lessons Learned and Future Challenges
Authors: Adamowicz Wiktor L. (Vic) 
Published: February 2016

The Canadian Species at Risk Act (SARA) has been in existence for 13 years. It was, and in many ways continues to be, controversial. The U.S. Endangered Species Act (ESA) originated in 1973 and has also been controversial. In the 1990s, concerns were raised by economists in Canada and the United States on the design of endangered species (ES) policy. Their concerns surrounded the reconsideration of the ESA and the establishment of SARA. What have we learned since the implementation of SARA over this time? How has the U.S. experience with the ESA informed SARA and its approach? How has the role of economic analysis in ES policy evolved? What continue to be the challenges and what are the opportunities? This paper reviews the concerns raised in the past, and evaluates the lessons learned regarding economics and ES. The unique aspects of the economic analysis of ES problems relative to other environmental concerns are outlined. The paper concludes with a discussion of ways to lessen the tension in debate about the role of economics in ES policy, and embrace the potential for more effective policy analysis and design through integration of economic analysis into conservation policy.Au Canada, la Loi sur les espèces en péril (LEP) est entrée en vigueur il y a 13 ans. Elle avait soulevé la controverse et, à certains égards, c'est encore le cas. Aux États‐Unis, l'Endangered Species Act (ESA – loi sur les espèces en voie de disparition) a vu le jour en 1973 et a aussi fait l'objet de controverse. Au cours des années 1990, des économistes canadiens et américains ont exprimé des préoccupations au sujet de la conception des politiques visant à protéger les espèces en voie de disparition. Leurs préoccupations ont mené à un réexamen de l'ESA et à la mise en œuvre de la LEP. Quelles leçons avons‐nous apprises depuis la mise en œuvre de la LEP? De quelle façon l'expérience des États‐Unis avec l'ESA a‐t‐elle influencé l’élaboration de la LEP et sa stratégie? De quelle façon le rôle de l'analyse économique des politiques visant à protéger les espèces en voie de disparition a‐t‐il évolué? Quels sont, encore aujourd'hui, les défis à relever et les occasions à saisir? Le présent article passe en revue les préoccupations passées et examine les leçons apprises concernant l’économie et les espèces en voie de disparition. Il met en lumière les caractéristiques uniques de l'analyse économique des problèmes liés aux espèces en voie de disparition comparativement à d'autres préoccupations environnementales. Il inclut une discussion sur les façons d'atténuer les tensions dans le débat sur le rôle de l’économie dans l’élaboration des politiques visant à protéger les espèces en voie de disparition et accueille la possibilité de procéder à l'analyse et à la conception efficaces de politiques grâce à l'intégration de l'analyse économique dans l’élaboration des politiques de la conservation.—
Competition in Canada's Agricultural Value Chains: The Case of Grain
Authors: Brewin Derek G. 
Published: February 2016

To open this address, I would like to advocate for membership in the Canadian Agricultural Economics Society (CAES). The fact that applied economics offers theory and methods that help us address topics as diverse as the Canadian grain value chain and the economics of species at risk speaks well for the future of our discipline. There is a vast array of work for us to do. Membership in the CAES offers an excellent link to the most up‐to‐date research in this area through our journal and conferences. Every society I attend inspires me to examine my own research and look at problems in new ways using new tools I learned from presentations made by the members of CAES. The main message of my address is to promote the application of Game Theory strategies as a way to understand behavior in the grain value chain. These tools are already being applied in areas as different as optimizing tradable systems of environmental goods and assessing competitive behavior in beef packing.Tout d'abord, je tiens à mentionner que j'appuie l'adhésion à la Société canadienne d'agroéconomie (SCAE). Le fait que l’économie appliquée offre la théorie et les méthodes qui nous aident à examiner des sujets aussi variés que la chaîne de valeur des grains du Canada et l’économie des espèces en péril augure bien pour l'avenir de notre discipline. La diversité du travail à accomplir est immense. Être membre de la SCAE procure un lien privilégié à la recherche de pointe grâce à notre Revue et à nos conférences. Aujourd'hui, mon message vise principalement à promouvoir l'application des stratégies de la théorie des jeux pour comprendre le comportement au sein de la chaîne de valeur des grains. Certains domaines, tels que l'optimisation des systèmes d’échange des biens environnementaux et l’évaluation du comportement concurrentiel dans le secteur du conditionnement du bœuf, utilisent déjà ces outils. La panoplie d'outils à notre disposition est mise en valeur dans notre Revue et lors de nos congrès. Tous les congrès auxquels j'assiste me motivent à examiner ma propre recherche et à analyser les problèmes sous un angle différent grâce aux nouveaux outils mis au point et présentés par les membres de la SCAE.
Treatment of perianal fistula in Crohn's disease: a systematic review and meta‐analysis comparing seton drainage and anti‐tumour necrosis factor treatment
Authors: de Groof E. J. , Sahami S. , Lucas C. , Ponsioen C. Y. , Bemelman W. A. , Buskens C. J. 
Published: February 2016

AbstractAimThe introduction of anti‐tumour necrosis factor (anti‐TNF; infliximab and adalimumab) has changed the management of Crohn's perianal fistula from almost exclusively surgical treatment to one with a much larger emphasis on medical therapy. The aim of this systematic review was to provide an overview of the success rates of setons and anti‐TNF for Crohn's perianal fistula.MethodStudies evaluating the effect of setons and anti‐TNF on Crohn's perianal fistula were included. Studies assessing perianal fistula in children, rectovaginal and rectourinary fistulae were excluded. The primary end‐point was the fistula closure rate. Partial closure and recurrence rates were secondary end‐points.ResultsTen studies on seton drainage were included (n = 305). Complete closure varied from 13.6% to 100% and recurrence from 0% to 83.3%. In 34 anti‐TNF studies (n = 1449), complete closure varied from 16.7% and 93% (partial closure 8.0–91.2%) and recurrence from 8.0% to 40.9%. Four randomized controlled trials (n = 1028) comparing anti‐TNF with placebo showed no significant difference in complete or partial closure in meta‐analysis (risk difference 0.12, 95% CI −0.06 to 0.30 and 0.09, 95% CI −0.23 to 0.41, respectively). Subgroup analysis (n = 241) showed a significant advantage for complete fistula closure with anti‐TNF in two trials with follow‐up > 4 weeks (46% vs 13%, P = 0.003 and 30% vs 13%, P = 0.03). Of four included cohort studies, two revealed a significant difference in response in favour of combined treatment (P = 0.001 and P = 0.014).ConclusionClosure and recurrence rates after seton drainage as well as anti‐TNF vary widely. Despite a large number of studies, no conclusions can be drawn regarding the preferred strategy. However, combination therapy with (temporary) seton drainage, immunomodulators and anti‐TNF may be beneficial in achieving perianal fistula closure.
Function and clinical implications of short‐chain fatty acids in patients with mixed refractory constipation
Authors: Shi Y. , Chen Q. , Huang Y. , Ni L. , Liu J. , Jiang J. , Li N. 
Published: February 2016

AbstractAimThe present study was designed to investigate the function and clinical implications of stool short‐chain fatty acids (SCFAs) in patients with mixed refractory constipation.MethodAscending colon specimens obtained from 30 patients with ascending colon cancer were regarded as the control group. Ascending colon specimens obtained from patients with mixed refractory constipation were regarded as the experimental group and were divided into three subgroups, according to Wexner scores [A constipation scoring system to simplify evaluation and management of constipated patients. Dis Colon Rectum 1996; 39: 681–5] of 16–20, 21–25 and 26–30, with 30 patients in each group. The stool SCFAs were extracted and quantitatively analysed using gas chromatography‐mass spectrometry (GC‐MS). The expression of G protein‐coupled receptor 43 (GPR43) and of choline acetyltransferase (ChAT) were detected by immunofluorescence, reverse transcription‐polymerase chain reaction (RT‐PCR) and western blotting of colon samples.ResultsThe levels of acetate, propionate and butyrate were significantly lower in the experimental group than in the control group (P < 0.05). Compared with the control group, the densitometric quantification and mean density of GPR43 and ChAT proteins, and expression of GPR43 and CHAT genes, were significantly decreased in the patients with mixed refractory constipation (P < 0.05).ConclusionIn the patients with mixed refractory constipation, the levels of stool SCFAs, including acetate, propionate and butyrate, as well as the levels of GPR43 and ChAT expressed in the colon, which were all negatively correlated with the Wexner score, were decreased and may be associated with the pathogenesis of mixed refractory constipation.