bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oestrogen‐dependent satellite cell activation and proliferation following a running exercise occurs via the PI3K signalling pathway and not IGF‐1
Authors: Mangan G. , Bombardier E. , Mitchell A. S. , Quadrilatero J. , Tiidus P. M. 
Published: May 2014

AbstractAimThe purpose of this study was to determine whether 17β‐estradiol (E2) enhances the activation, proliferation and differentiation of muscle satellite cells (SC) following eccentric exercise either via insulin‐like growth factor‐1 (IGF‐1) or through phosphatidylinositol 3‐kinase (PI3K) signalling.MethodsThis study used 64, 9‐week‐old, ovariectomized Sprague–Dawley rats that were divided into eight treatments groups based on oestrogen status (0.25 mg oestrogen pellet or sham), exercise status (90 min run @ 17 m min−1, −13.5° or unexercised) and PI3K signalling inhibition (0.7 mg wortmannin kg−1 body weight or DMSO control).ResultsSignificant increases in total SCs were found in both soleus and white gastrocnemius muscles (immunofluorescent co‐localization of Pax7+ nuclei) 72 h following eccentric exercise (P < 0.05). Oestrogen supplementation caused a further enhancement in total SCs in exercised rats (P < 0.05). In animals where the PI3K pathway was inhibited, regardless of oestrogen or exercise status, there was no significant enhancement of SC number in both the soleus or white gastrocnemius muscles. Interestingly, oestrogen supplementation lowered muscle levels of IGF‐1 with this effect being most prominent in the soleus muscle. While IGF‐1 was increased following exercise (P < 0.05), oestrogen supplementation abrogated this increase back to sedentary levels.ConclusionThese data suggest that the increase in SC population following exercise in oestrogen‐supplemented females may be mediated via PI3K pathway signalling and not IGF‐1.
Clinical impact of c‐MET expression and genetic mutational status in colorectal cancer patients after liver resection
Authors: Shoji Hirokazu , Yamada Yasuhide , Taniguchi Hirokazu , Nagashima Kengo , Okita Natsuko , Takashima Atsuo , Honma Yoshitaka , Iwasa Satoru , Kato Ken , Hamaguchi Tetsuya , Shimada Yasuhiro 
Published: May 2014

c‐MET is implicated in the pathogenesis and growth of a wide variety of human malignancies, including colorectal cancer (CRC). The aim of the present study was to clarify the association between c‐MET expression and tumor recurrence in CRC patients after curative liver resection, and to evaluate concordance in c‐MET expression and various mutations of KRAS, BRAF and PIK3CA between primary CRC and paired liver metastases. A cohort of patients was tested for c‐MET immunoreactivity (i.e. immunohistochemistry [IHC]) and KRAS, BRAF and PIK3CA mutations. Analyses were performed both on primary tumors and paired liver metastases, and the association between IHC and mutations results were assessed. A total of 108 patients were eligible. A total of 53% of patients underwent simultaneous resection of primary tumors and metastases, and the others underwent metachronous resection. Levels of concordance between primary tumors and metastases were 65.7%, 87.7%, 100% and 95.2% for c‐MET, KRAS, BRAF and PIK3CA, respectively. High levels of c‐MET expression (c‐MET‐high) in the primary tumors were observed in 52% of patients. Relapse‐free survival was significantly shorter for patients with c‐MET‐high primary tumors (9.7 months) than for those with c‐MET‐low primary tumors (21.1 months) (P = 0.013). These results suggest that a high level of genetic concordance in KRAS, BRAF and PIK3CA between primary tumors and liver metastases, and c‐MET‐high in the primary tumors were associated with shorter relapse‐free survival after hepatic metastasectomy.
Routine prophylactic central neck dissection for low‐risk papillary thyroid cancer is not cost‐effective
Authors: Garcia Arturo , Palmer Barnard J.A. , Parks Nancy A. , Liu Terrence H. 
Published: May 2014

SummaryBackgroundThe role of routine prophylactic central neck dissection (CND) in papillary thyroid cancer (PTC) remains controversial. The aim of this study was to evaluate the cost utility of the addition of routine CND in patients with low‐risk PTC compared with total thyroidectomy (TT) alone.MethodsA Markov model for low‐risk PTC was constructed with a treatment algorithm based on the American Thyroid Association guidelines for well‐differentiated thyroid carcinoma. Utilities and outcome probabilities were derived from published medical literature. US 2010 costs were examined from a society perspective using Medicare reimbursement rates and opportunity loss based on published US government data. Monte Carlo simulation and sensitivity analysis were used to examine the uncertainty of probability, cost and utility estimates.ResultsInitial TT alone is more cost‐effective than TT with CND, resulting in a cost savings of US $5763 per patient with slightly higher effectiveness per patient (0·03 QALY) for a cost savings of $285 per QALY. Sensitivity analysis shows that TT alone offers no advantage when radioactive iodine (RAI) becomes more detrimental to a patient's state of health, when the incidence of non‐neck recurrence increases above 5% in patients undergoing TT alone or decreases below 3·9% in patients undergoing TT with CND or when the rate of permanent hypocalcaemia rises above 4%.ConclusionsTT with CND is not a cost‐effective strategy in low‐risk PTC. Initial TT alone is favourable because of the low complication rates and low recurrence rates associated with the initial surgery. Alternative strategies such as unilateral prophylactic neck dissection require additional study to assess their cost‐effectiveness.
Cortical bone mineral density in patients with congenital adrenal hyperplasia due to 21‐hydroxylase deficiency
Authors: El‐Maouche Diala , Collier Suzanne , Prasad Mala , Reynolds James C. , Merke Deborah P. 
Published: May 2014

SummaryBackgroundPrior studies reveal that bone mineral density (BMD) in congenital adrenal hyperplasia (CAH) is mostly in the osteopaenic range and is associated with lifetime glucocorticoid dose. The forearm, a measure of cortical bone density, has not been evaluated.ObjectiveWe aimed to evaluate BMD at various sites, including the forearm, and the factors associated with low BMD in CAH patients.MethodsEighty CAH adults (47 classic, 33 nonclassic) underwent dual‐energy‐x‐ray absorptiometry and laboratory and clinical evaluation. BMD Z‐scores at the AP spine, total hip, femoral neck, forearm and whole body were examined in relation to phenotype, body mass index, current glucocorticoid dose, average 5‐year glucocorticoid dose, vitamin D, 17‐hydroxyprogesterone, androstenedione, testosterone, dehydroepiandrosterone and dehydroepiandrosterone sulphate (DHEAS).ResultsReduced BMD (T‐score <−1 at hip, spine, or forearm) was present in 52% and was more common in classic than nonclassic patients (P = 0·005), with the greatest difference observed at the forearm (P = 0·01). Patients with classic compared to nonclassic CAH, had higher 17‐hydroxyprogesterone (P = 0·005), lower DHEAS (P = 0·0002) and higher non‐traumatic fracture rate (P = 0·0005). In a multivariate analysis after adjusting for age, gender, height standard deviation, phenotype and cumulative glucocorticoid exposure, higher DHEAS was independently associated with higher BMD at the spine, radius and whole body.ConclusionClassic CAH patients have lower BMD than nonclassic patients, with the most affected area being the forearm. This first study of forearm BMD in CAH patients suggests that low DHEAS may be associated with weak cortical bone independent of glucocorticoid exposure.
Does omega‐3 fatty acids supplementation affect circulating leptin levels? A systematic review and meta‐analysis on randomized controlled clinical trials
Authors: Hariri Mitra , Ghiasvand Reza , Shiranian Afshin , Askari Gholamreza , Iraj Bijan , Salehi‐Abargouei Amin 
Published: May 2014

SummaryBackgroundOmega‐3 fatty acids have attracted researchers for their effect on circulatory hormone‐like peptides affecting weight control.ObjectiveOur objective was to conduct a systematic review and meta‐analysis on randomized controlled trials (RCTs) assessed the effects of omega‐3 supplementation on serum leptin concentration and to find the possible sources of heterogeneity in their results.MethodsWe searched PubMed/Medline, Google Scholar, Ovid, SCOPUS and ISI web of science up to April 2014. RCTs conducted among human adults, examined the effect of omega‐3 fatty acid supplements on serum leptin concentrations as an outcome variable were included. The mean difference and standard deviation (SD) of changes in serum leptin levels were used as effect size for the meta‐analysis. Summary mean estimates with their corresponding SDs were derived using random effects model.ResultsTotally 14 RCTs were eligible to be included in the systematic review, and the meta‐analysis was performed on 13 articles. Our analysis showed that omega‐3 supplementation significantly reduces leptin levels (mean difference (MD) = −1·71 ng/ml 95% confidence interval (CI): −3·17 to −0·24, P = 0·022). Subgroup analysis based on BMI status showed that the omega‐3 supplementation reduces leptin when used for nonobese subjects (MD = −3·60 ng/ml; 95% CI −6·23 to −0·90; P = 0·011); however, this was not true for obese participants (MD = −0·86 ng/ml; 95% CI: −2·63 to −0·90; P = 0·296). Subgroup analysis based on omega‐3 source also showed that omega‐3 from marine sources may significantly reduce leptin levels (MD = −1·73 ng/ml; 95% CI −3·25 to −0·2; P = 0·026), but plant sources do not significantly affect serum leptin levels (MD = −1·48 ng/ml; 95% CI −6·78 to 3·23; P = 0·585). Our results were highly sensitive to one study.ConclusionsOmega‐3 supplementation might moderately decrease circulatory leptin levels only among nonobese adults. RCTs with longer follow‐up period, using higher doses for obese adults and exploring the effect in different genders, are needed to replicate our results.
Acute and chronic effects of kisspeptin‐54 administration on GH, prolactin and TSH secretion in healthy women
Authors: Jayasena Channa N. , Comninos Alexander N. , Narayanaswamy Shakunthala , Bhalla Sanjana , Abbara Ali , Ganiyu‐Dada Zainab , Busbridge Mark , Ghatei Mohammad A. , Bloom Stephen R. , Dhillo Waljit S. 
Published: May 2014

SummaryBackgroundThe peptide hormone kisspeptin is essential for human reproduction, acting on the hypothalamus to stimulate gonadotrophin‐releasing hormone (GnRH) secretion. Kisspeptin is currently being evaluated as a novel therapeutic for women with infertility. However, some animal studies suggest that kisspeptin may also stimulate growth hormone (GH), prolactin and thyroid‐stimulating hormone (TSH) secretion, with implications for its safety; no previous study has investigated whether kisspeptin stimulates these pituitary hormones in humans.AimTo determine whether kisspeptin‐54 modulates GH, prolactin and TSH secretion in healthy women.Design and participantsProspective, single‐blinded, placebo‐controlled, one‐way crossover study. Five healthy women received 7 days of twice‐daily subcutaneous bolus vehicle (month 1) or 6·4 nmol/kg kisspeptin‐54 (month 2).MeasurementsSerum samples were analysed post hoc for GH, prolactin and TSH.ResultsMean serum GH, PRL and TSH did not change during the first 4 h following kisspeptin‐54 injection when compared with vehicle. The mean frequency or amplitude of GH pulses (which influence GH function) did not change acutely following kisspeptin‐54 injection when compared with vehicle. No chronic changes in serum GH, PRL or TSH were observed over the 7‐day period of twice‐daily kisspeptin‐54 injections when compared with vehicle.ConclusionWhile we cannot exclude any effect of kisspeptin‐54 on GH, prolactin or TSH secretion, we observed no significant changes in these hormones at a dose of kisspeptin‐54 administration known to stimulate gonadotrophin secretion in a small study of healthy women. These data have important implications for the potential of kisspeptin to treat patients with infertility.
Impact of unilateral vocal fold mobility impairment on laryngopulmonary physiology
Authors: Nouraei S.A.R. , Whitcroft K. , Patel A. , Chatrath P. , Sandhu G.S. , Kaddour H. 
Published: May 2014

ObjectiveTo examine the impact of unilateral vocal fold mobility impairment (UVFMI) on airway physiology.Study designCross‐sectional observational study.ParticipantsThere were 21 patients with UVFMI and 53 controls.Main outcome measuresAll patients and patient controls underwent a maximum‐effort flow‐volume loop examination. Forced expiratory flow in one second (FEV1), forced expiratory volume (FVC), peak inspiratory flow rate and peak expiratory flow rate (PIFR and PEFR, respectively) and area under the inspiratory and expiratory flow‐volume loops (AUCInspiratory and AUCExpiratory, respectively) were measured. The ratio of PEFR to PIFR and AUCExpiratory to AUCInspiratory was derived.ResultsThere were 48 males and 26 females. Mean age at measurement was 39 ± 11 years. Patients and controls were matched for age, sex, height and weight. None of the expiratory variables were significantly different between the groups. PIFR was significantly lower in UVFMI patients compared with controls (3.4 ± 1.2 versus 5.3 ± 1.8; P < 0.0001), as was AUCInspiratory (11.5 ± 6.3 versus 17.5 ± 8.5; P = 0.0002). PEFR/PIFR provided the best differentiation between patients with UVFMI and controls with an area under the Receiver Operating Characteristic (ROC) curve of 0.96 and at a threshold of 1.9, and PEFR/PIFR had sensitivity and specificity of 95.2% and 90.6%, respectively.ConclusionsFlow‐volume loops are a non‐invasive method of studying vocal abduction and could compliment voice assessment and laryngoscopy in UVFMI. With further research, they could provide an outcome measure for laryngeal rehabilitative procedures, and a shared physiological language for screening and surgical quality assurance.
Cell proliferation in in vivo‐like three‐dimensional cell culture is regulated by sequestration of ERK1/2 to lipid rafts
Authors: Skrobanska R. , Evangelatov A. , Stefanova N. , Topouzova‐Hristova T. , Momchilova A. , Pankov R. 
Published: May 2014

AbstractObjectivesRegulatory mechanisms of cell proliferation have been extensively studied as they represent major challenges when dealing with pathologies such as fibrosis, tumourigenesis or tissue regeneration. Numerous in vitro studies still exploit conventional, two‐dimensional cell cultures where cells are forced to adhere to unnaturally stiff and flat surfaces of culture dishes. In the living organism, however, each cell is in contact with components of the extracellular matrix and/or neighbouring cells, thus creating a complex three‐dimensional (3D) tissue structure. The current paper describes a native 3D culture of cells, based on the GD25β1 fibroblast cell line, and its use for investigating cell proliferation in in vivo‐like conditions.Materials and methodsFour‐day post‐confluent culture of GD25β1 fibroblasts resulted in formation of a 3D system of cells embedded in naturally synthesized extracellular matrix. Morphological characterization of the culture was performed by histochemistry, immunohistochemistry and immunofluorescence. Viability/proliferation was assayed by MTT testing, FACS analysis and Western blotting for determination of expression levels and activation status of the relevant signalling molecules.ResultsGD25b1 fibroblasts, grown as 3D culture, gave rise to tissue‐like structures characterized by low level of apoptosis, low senescence and development of 3D matrix adhesions, typical of living tissues. Transition to three‐dimensionality led to a switch from exponential to linear culture growth, accompanied by accumulation of activated ERK1/2 into caveolin‐containing raft domains. Disruption of raft domains as well as reverse transition from 3D back to monolayer culture led to release of phosphorylated ERK1/2 from rafts, activation of cyclin D1 expression and increase in proliferation levels.ConclusionsThese results imply that under in vivo‐like conditions, cells might achieve reduction of their proliferation level by sequestering activated ERK1/2 to lipid rafts.
Research in practice: Substance P antagonism in chronic pruritus
Authors: Lotts Tobias , Ständer Sonja 
Published: May 2014

SummaryPruritus is an unpleasant sensation of the skin, which triggers a desire to scratch or rub. The chronic form (≥6 weeks’ duration) often occurs as a side effect of many diseases and is usually accompanied by a high loss in quality of life for patients, especially in cases in which the symptom is chronic without adequate treatment options. In recent years, the situation improved continuously, guidelines for chronic pruritus have been defined and standard medications have been proposed. For many reasons, there are still patients who are unable to obtain relief. New therapeutic approaches are therefore urgently needed. Blocking the neuropeptide substance P is a promising strategy; substance P mediates clinically relevant pro‐inflammatory effects by binding to the neurokinin 1 receptor (NK‐1R). This led us to hypothesize that NK‐1R antagonists are promising therapeutic options for chronic pruritus. Several international case series have meanwhile proven the antipruritic effect of the NK‐1R antagonist aprepitant for various forms of chronic pruritus. Initiation of clinical trials with new NK‐1R‐antagonists as a new therapeutic option continues this trend.
Modelling the genetic contribution to mental illness: a timely end for the psychiatric rodent?
Authors: Davis Brittany A. , Isles Anthony R. 
Published: May 2014

AbstractRodent models are a key factor in the process of translating psychiatric genetics and genomics findings, allowing us to shed light on how risk‐genes confer changes in neurobiology by merging different types of data across fields, from behavioural neuroscience to the burgeoning omics (e.g. genomics, epigenomics, proteomics, etc.). Moreover, they also provide an indispensable first step for drug discovery. However, recent evidence from both clinical and genetic studies highlights possible limitations in the current methods for classifying psychiatric illness, as both symptomology and underlying genetic risk are found to increasingly overlap across disorder diagnoses. Meanwhile, integration of data from animal models across disorders is currently limited. Here, we argue that behavioural neuroscience is in danger of missing informative data because of the practice of trying to ‘diagnose’ an animal model with a psychiatric illness. What is needed is a shift in emphasis, from seeking to ally an animal model to a specific disorder, to one focused on a more systematic assessment of the neurobiological and behavioural outcomes of any given genetic or environmental manipulation.
Estradiol regulates responsiveness of the dorsal premammillary nucleus of the hypothalamus and affects fear‐ and anxiety‐like behaviors in female rats
Authors: Litvin Yoav , Cataldo Giuseppe , Pfaff Donald W. , Kow Lee‐Ming 
Published: May 2014

AbstractResearch suggests a causal link between estrogens and mood. Here, we began by examining the effects of estradiol (E2) on rat innate and conditioned defensive behaviors in response to cat odor. Second, we utilized whole‐cell patch clamp electrophysiological techniques to assess noradrenergic effects on neurons within the dorsal premammillary nucleus of the hypothalamus (PMd), a nucleus implicated in fear reactivity, and their regulation by E2. Our results show that E2 increased general arousal and modified innate defensive reactivity to cat odor. When ovariectomized females treated with E2 as opposed to oil were exposed to cat odor, they showed elevations in risk assessment and reductions in freezing, indicating a shift from passive to active coping. In addition, animals previously exposed to cat odor showed clear cue + context conditioning 24 h later. However, although E2 persisted in its effects on general arousal in the conditioning task, its effects on fear disappeared. In the patch clamp experiments noradrenergic compounds that typically induce fear clearly excited PMd neurons, producing depolarizations and action potentials. E2 treatment shifted some excitatory effects of noradrenergic agonists to inhibitory, possibly by differentially affecting α‐ and β‐adrenoreceptors. In summary, our results implicate E2 in general arousal and fear reactivity, and suggest these may be governed by changes in noradrenergic responsivity in the PMd. These effects of E2 may have ethological relevance, serving to promote mate seeking even in contexts of ambiguous threat and shed light on the involvement of estrogen in mood and its associated disorders.
Distinguishing informational from value‐related encoding of rewarding and punishing outcomes in the human brain
Authors: Jessup Ryan K. , O'Doherty John P. 
Published: May 2014

AbstractThere is accumulating evidence implicating a set of key brain regions in encoding rewarding and punishing outcomes, including the orbitofrontal cortex, medial prefrontal cortex, ventral striatum, anterior insula, and anterior cingulate. However, it has proved challenging to reach consensus concerning the extent to which different brain areas are involved in differentially encoding rewarding and punishing outcomes. Here, we show that many of the brain areas involved in outcome processing represent multiple outcome components: encoding the value of outcomes (whether rewarding or punishing) and informational coding, i.e. signaling whether a given outcome is rewarding or punishing, ignoring magnitude or experienced utility. In particular, we report informational signals in the lateral orbitofrontal cortex and anterior insular cortex that respond to both rewarding and punishing feedback, even though value‐related signals in these areas appear to be selectively driven by punishing feedback. These findings highlight the importance of taking into account features of outcomes other than value when characterising the contributions of different brain regions in outcome processing.
Asymmetric Assortative Mating Behaviour Reflects Incomplete Pre‐zygotic Isolation in the Nasonia Species Complex
Authors: Buellesbach Jan , Greim Christopher , Raychoudhury Rhitoban , Schmitt Thomas 
Published: May 2014

AbstractPreference of con‐ over heterospecific mates leading to assortative mating can substantially contribute to pre‐zygotic reproductive isolation and prevent fitness losses if post‐zygotic hybridization barriers already exist. The jewel wasp genus Nasonia displays quite strong and well‐studied post‐zygotic reproductive isolation due to a ubiquitous Wolbachia infection causing cytoplasmic incompatibility between different species. Pre‐zygotic isolation, however, has received far less research attention in this model organism, especially concerning the mechanisms and criteria of mate choice. In the present study, we analysed mate rejection and mate acceptance rates in cross‐comparisons between all four Nasonia species. We put emphasis on observing which sex is more likely to interrupt interspecific matings and how discriminatory behaviour varies across the different species in all possible combinations. We found an asymmetric distribution of assortative mating among the four Nasonia species that appears to be highly influenced by the respective combinations of sex and species. Females appeared to be the main discriminators against heterospecific mating partners, but interestingly, we could also detect mate discrimination and rejection behaviour in males, a widely neglected factor in research on mating behaviour in general and on Nasonia in particular. Moreover, the asymmetry in the assortative mating behaviour was partially reflective of sym‐ or allopatric distributions of natural Nasonia populations.