bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of girls with pituitary hyperplasia and sexual precocity secondary to primary hypothyroidism
Authors: Hu Yan‐Yan , Li Gui‐Mei , Hu Wen‐Wen , Wang Yi 
Published: October 2013

AbstractAimTo investigate the different characteristics of girls with pituitary hyperplasia secondary to primary hypothyroidism (PPH), with and without sexual precocity.MethodsPituitary hyperplasia secondary to primary hypothyroidism girls were divided into two groups: group A, with sexual precocity (n = 8), and group B, without sexual precocity (n = 14). The following values were measured before and after 3 months levothyroxine therapy: free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), follicle‐stimulating hormone (FSH), luteinising hormone (LH), prolactin (PRL), estradiol (E2), testosterone (T), pituitary height, uterine volume (UV), ovarian volume (OV) and follicular diameter (FD).ResultsThyrotropin, FSH, PRL, E2, T, pituitary height, UV, OV and FD were higher in group A than group B (all p < 0.05); FT3, FT4 and LH levels were not different (all p > 0.05). In all of the PPH girls, pituitary height was correlated with FT3, FT4 and PRL (r = −0.545, p = 0.009, r = −0.567, p = 0.006 and r = 0.666, p = 0.001, respectively). PRL was positively correlated with UV, FD and FSH (r = 0.581, p = 0.005, r = 0.482, p = 0.031 and r = 0.667, p = 0.001, respectively), and FSH was positively correlated with OV (r = 0.522, p = 0.013). These abnormalities regressed after therapy.ConclusionPituitary hyperplasia secondary to primary hypothyroidism girls with sexual precocity have increased plasma TSH, FSH, PRL, E2 and T levels, pituitary height and uterine, ovarian and follicular size.
Aortic intima‐media thickness measured by trans‐abdominal ultrasound as an early life marker of subclinical atherosclerosis
Authors: McCloskey Kate , Vuillermin Peter , Ponsonby Anne‐Louise , Cheung Michael , Skilton Michael R , Burgner David 
Published: October 2013

AbstractAtherosclerosis is a chronic inflammatory process that begins in early life. Improved identification of markers of early atherosclerosis via neonatal aortic intima‐media thickness (aIMT) measurement may allow the development of interventions to prevent or reduce later cardiovascular disease.ConclusionUsing aIMT, studies have shown that antenatal factors such as intra‐uterine growth retardation, prematurity, maternal factors and inflammation are associated with early cardiovascular changes.
Distinguishing the impact of dexlansoprazole on heartburn vs. regurgitation in patients with gastro‐oesophageal reflux disease
Authors: Peura D. A. , Pilmer B. , Hunt B. , Mody R. , Perez M. C. 
Published: October 2013

SummaryBackgroundGastro‐oesophageal reflux disease (GERD) is characterised by symptomatic heartburn and regurgitation. Treatment with proton pump inhibitors (PPI) effectively decreases heartburn symptoms, but their effects on symptomatic regurgitation are less clear.AimTo determine the impact of PPI therapy on heartburn and regurgitation severity in patients with either non‐erosive GERD (NERD) or erosive oesophagitis (EE).MethodsEndoscopically‐confirmed NERD patients received dexlansoprazole 30 or 60 mg or placebo in a randomised, blinded, 4‐week study. Endoscopically‐confirmed EE patients received dexlansoprazole 60 mg or lansoprazole 30 mg in two 8‐week, randomised, blinded healing studies. The Patient Assessment of Upper Gastrointestinal Symptom Severity questionnaire, which includes a heartburn/regurgitation subscale, was administered to assess symptom severity at baseline, and at weeks 2 and 4 of the NERD study and at weeks 4 and 8 during the EE trials. We defined separate subscales for heartburn and regurgitation for this post‐hoc analysis. Among patients with both symptoms at baseline, improvements in individual heartburn and regurgitation subscales along with the original combined heartburn/regurgitation subscale were determined.ResultsIn the NERD and EE studies, 661 and 1909 patients, respectively, had both heartburn and regurgitation at baseline. NERD patients receiving dexlansoprazole 30 and 60 mg experienced significantly greater improvements in symptom severity for both heartburn and regurgitation compared with placebo. EE patients receiving dexlansoprazole 60 mg had significantly greater improvements in heartburn/regurgitation and heartburn‐only subscales at week 4 compared with those receiving lansoprazole.ConclusionsDexlansoprazole appears to be effective in improving both heartburn and regurgitation, and this improvement is maintained for the duration of treatment.
Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non‐alcoholic fatty liver disease
Authors: Schwimmer J. B. , Newton K. P. , Awai H. I. , Choi L. J. , Garcia M. A. , Ellis L. L. , Vanderwall K. , Fontanesi J. 
Published: October 2013

SummaryBackgroundScreening overweight and obese children for non‐alcoholic fatty liver disease (NAFLD) is recommended by paediatric and endocrinology societies. However, gastroenterology societies have called for more data before making a formal recommendation.AimTo determine whether the detection of suspected NAFLD in overweight and obese children through screening in primary care and referral to paediatric gastroenterology resulted in a correct diagnosis of NAFLD.MethodsInformation generated in the clinical evaluation of 347 children identified with suspected NAFLD through screening in primary care and referral to paediatric gastroenterology was captured prospectively. Diagnostic outcomes were reported. The diagnostic performance of two times the upper limit of normal (ULN) for alanine aminotransferase (ALT) was assessed.ResultsNon‐alcoholic fatty liver disease was diagnosed in 55% of children identified by screening and referral. Liver disease other than NAFLD was present in 18% of those referred. Autoimmune hepatitis was the most common alternative diagnosis. Children with NAFLD had significantly (P < 0.05) higher screening ALT (98 ± 95) than children with liver disease other than NAFLD (86 ± 74). Advanced fibrosis was present in 11% of children. For the diagnosis of NAFLD, screening ALT two times the clinical ULN had a sensitivity of 57% and a specificity of 71%.ConclusionsScreening of overweight and obese children in primary care for NAFLD with referral to paediatric gastroenterology has the potential to identify clinically relevant liver pathology. Consensus is needed on how to value the risk and rewards of screening and referral, to identify children with liver disease in the most appropriate manner.
Ex vivo bupivacaine treatment results in increased adipogenesis of skeletal muscle cells in the rat
Authors: Yamanouchi Keitaro , Nakamura Katsuyuki , Takegahara Yuki , Nakano Shin‐ichi , Nishihara Masugi 
Published: October 2013

AbstractIntramuscular adipose tissue (IMAT) is observed in some skeletal muscle pathologies. IMAT is implicated not only in the disorders of muscle contraction, but also of metabolism and insulin sensitivity due to its nature as a secretary organ. Several studies indicate the presence of cells with adipogenic potential in skeletal muscle. However, the mechanism of fate specification that triggers these cells to enter an adipogenic program in vivo remains to be solved. In the present study, we examined whether activation of the adipogenic program of muscle‐resident cells precedes their proliferation upon muscle injury. For this purpose, muscle injury was induced by injecting bupivacaine (BPVC) to excised skeletal muscle ex vivo. Cells isolated from ex vivo BPVC‐treated muscle exhibited higher adipogenic potential than those from saline‐treated muscle. Pre‐plating exposure of skeletal muscle cells to basic fibroblast growth factor (bFGF) mimicked the effect of ex vivo BPVC‐treatment, suggesting that bFGF released from extracellular matrix in response to muscle injury activates their adipogenic program. Interestingly, the number of myotubes were significantly reduced in the culture from BPVC‐treated muscle, suggesting that adipocytes negatively regulate myogenesis.
Vegetation succession in restoration of disturbed sites in Central Europe: the direction of succession and species richness across 19 seres
Authors: Prach Karel , Řehounková Klára , Lencová Kamila , Jírová Alena , Konvalinková Petra , Mudrák Ondřej , Študent Vojtěch , Vaněček Zdeněk , Tichý Lubomír , Petřík Petr , Šmilauer Petr , Pyšek Petr 
Published: October 2013

AbstractQuestions(1) How do seres differ with respect to vegetation changes? (2) What are the directions of succession? (3) How do species numbers change? (4) How do target species, i.e. those typical of natural and semi‐natural vegetation, participate in succession? (5) Are spontaneously developed successional stages acceptable from the point of view of ecosystem restoration?LocationExtracted peatlands, bulldozed sites in forests destroyed by air pollution, an emerged bottom of a water reservoir, corridors of former Iron Curtain, artificial fishpond islands and barriers, sedimentary basins, spoil heaps from mining, stone quarries, forest clearings, road verges, sand and gravel‐sand pits, ruderal urban sites, river gravel bars and abandoned arable fields, located in various parts of the Czech Republic in Central Europe.MethodsPhytosociological relevés were recorded in 10–25 m2 plots located in the centre of representative successional stages defined by their age, ranging from 1 to 100 yrs. In total, we obtained 2392 vegetation samples containing 951 species. We performed DCA ordination to compare 19 seres. Desirable target species were considered as those representing (semi)‐natural vegetation and all Red List species.ResultsThe seres studied are more similar in their species composition in the initial and early stages, in which synathropic species prevail, than in the later stages when the vegetation differentiates. This divergence is driven mainly by local moisture conditions. In most cases, succession led to woodland, which usually established after ca. 20 yrs. In very dry or wet places (with limited presence of woody species) open vegetation developed, often highly valuable from the restoration and conservation point of view. The total number of species and the number of target species increased in the majority of seres with successional age.ConclusionsThe vegetation in the sites studied formed a continuum along a moisture gradient and by successional age. The individual seres largely overlapped in their species composition; the sere identity was not significant. Spontaneous succession usually proceeded towards woodland, except at very dry or wet sites, and generally appeared to be an ecologically suitable way of ecosystem restoration of disturbed sites because target species became dominant over time.
Role of Pre‐Junctional CB1, But not CB2, TRPV1 or GPR55 Receptors in Anandamide‐Induced Inhibition of the Vasodepressor Sensory CGRPergic Outflow in Pithed Rats
Authors: Marichal‐Cancino Bruno A. , Altamirano‐Espinoza Alain H. , Manrique‐Maldonado Guadalupe , MaassenVanDenBrink Antoinette , Villalón Carlos M. 
Published: October 2013

AbstractStimulation of the perivascular sensory outflow in pithed rats produces vasodepressor responses mediated by CGRP release. Interestingly, endocannabinoids such as anandamide (which interacts with CB1, CB2, TRPV1 and GPR55 receptors) can regulate the activity of perivascular sensory nerves in dural blood vessels by modulating CGRP release. Yet, as no publication has reported whether this mechanism is operative in the healthy systemic vasculature, this study has specifically analysed the receptors mediating the potential inhibitory effects of the cannabinoid (CB) receptor agonists anandamide (non‐selective), JWH‐015 (CB2) and lysophosphatidylinositol (GPR55) on the rat vasodepressor sensory CGRPergic outflow (an index of systemic vasodilatation). Healthy pithed rats were pre‐treated with consecutive i.v. continuous infusions of hexamethonium, methoxamine and the above agonists. Electrical spinal (T9–T12) stimulation of the vasodepressor sensory CGRPergic outflow or i.v. injections of α–CGRP produced frequency‐dependent or dose‐dependent vasodepressor responses. The infusions of anandamide in a dose‐dependent manner inhibited the vasodepressor responses by electrical stimulation (remaining unaffected by JWH‐015 or lysophosphatidylinositol), but not those by α–CGRP. After i.v. administration of antagonists, the inhibition by 3.1 μg/kg min anandamide was: (i) potently blocked by 31–100 μg/kg NIDA41020 (CB1), (ii) unaffected by 180 μg/kg AM630 (CB2), 31 μg/kg cannabidiol (GPR55) or 31–100 μg/kg capsazepine (TRPV1) and (iii) slightly blocked by 310 μg/kg AM630. The above doses of antagonists were enough to block their respective receptors. These results suggest that anandamide‐induced inhibition of the vasodepressor sensory CGRPergic outflow is mainly mediated by pre‐junctional activation of CB1 receptors, with no pharmacological evidence for the role of CB2, TRPV1 or GPR55 receptors.
Bone marrow stroma‐mediated resistance to FLT3 inhibitors in FLT3‐ITD AML is mediated by persistent activation of extracellular regulated kinase
Authors: Yang Xiaochuan , Sexauer Amy , Levis Mark 
Published: October 2013

SummaryA consistent pattern of response has been observed when FMS‐like tyrosine kinase 3 (FLT3) tyrosine kinase inhibitors (TKIs) have been used as monotherapy to treat patients with relapsed or refractory FLT3‐ internal tandem duplication (ITD) acute myeloid leukaemia (AML). Circulating blasts are cleared from the peripheral blood, while bone marrow blasts are either unaffected or are cleared from the marrow at a much slower rate. We used an in vitro model of FLT3‐ITD AML blasts co‐cultured with normal human bone marrow stromal cells to investigate the basis for this dichotomous response pattern to FLT3 inhibitors. We have found that in blasts on stroma, potent FLT3 inhibition predominantly results in cell cycle arrest rather than apoptosis. The anti‐apoptotic effect is mediated through a combination of direct cell‐cell contact and soluble factors. The addition of exogenous FLT3 ligand (FL) augments the protection, primarily by shifting the 50% inhibitory concentration for FLT3 inhibition upwards. Cytokine‐activated extracellular regulated kinase (ERK), rather than STAT5, appears to be the most important downstream signalling protein mediating the protective effect, and inhibition of MEK significantly abrogates stromal‐mediated resistance. These findings explain the phenomenon of peripheral blood versus bone marrow blast responses and suggest that the combination of potent FLT3 inhibition and MEK inhibition is a promising strategy for the treatment of FLT3‐ITD AML.
Financial Participation: Does the Risk Transfer Story Hold in France?
Authors: Baghdadi Leila , Bellakhal Rihab , Diaye Marc‐Arthur 
Published: October 2013

AbstractSeveral articles report a positive effect of financial participation (profit sharing (PS) and employee share ownership) on firms' economic performance. This increase can be obtained in two main ways: by increasing the effort (extrinsic, intrinsic or commitment) of workers, directly or indirectly through worker selection; or by transferring more risk to the workers. The question is, of course, not neutral. Indeed, if the risk transfer story is true then it means that the increase of economic performance is obtained at the expense of workers, who take on the burden of more risks. The question is especially important in France where financial participation is associated with tax exemption for firms and where it is forbidden by law to substitute base wage and PS. The purpose of our article is to use an employer–employee dataset to answer the question of whether financial participation schemes are mainly designed as a risk transfer (from firms to workers) device.
External validation of preoperative and postoperative nomograms for prediction of cancer‐specific survival, overall survival and recurrence after robot‐assisted radical cystectomy for urothelial carcinoma of the bladder
Authors: Al‐Daghmin Ali , English Stephen , Kauffman Eric C. , Din Rakeeba , Khan Aabroo , Syed Johar R. , Sztorc Jenna , Mehedint Diana , Sharif Mohammad , Shi Yi , Wilding Gregory , Guru Khurshid A. 
Published: October 2013

Objective
To externally validate currently available bladder cancer nomograms for prediction of all‐cause survival (ACS), cancer‐specific survival (CSS), other‐cause mortality (OCM) and progression‐free survival (PFS).
Patients and Methods
Retrospective analysis of a prospectively maintained database of 282 patients who underwent robot‐assisted radical cystectomy (RARC) at a single institution was performed.
The Bladder Cancer Research Consortium (BCRC), International Bladder Cancer Nomogram Consortium (IBCNC) and Lughezzani nomograms were used for external validation, and evaluation for accuracy at predicting oncological outcomes.
The 2‐ and 5‐year oncological outcomes were compared, and nomogram performance was evaluated through measurement of the concordance (c‐index) between nomogram‐derived predicted oncological outcomes and observed oncological outcomes.
Results
The median (range) patient age was 70 (36–90) years. At a mean follow‐up of 20 months, local or distant disease recurrence developed in 30% of patients. With an overall mortality rate of 33%, 17% died from bladder cancer.
The actuarial 2‐ and 5‐year PFS after RARC was 62% (95% confidence interval [CI] 54–68) and 55% (95% CI 46–63), respectively.
The actuarial 2‐ and 5‐year ACS was 66% (95% CI 59–72) and 47% (95% CI 37–55), respectively, and the 2‐ and 5‐year CSS was 81% (95% CI 74–86) and 67% (95% CI 57–76), respectively.
The PFS c‐index for IBCNC was 0.70 at 5 years, and for BCRC was 0.77 at both the 2 and 5 years. The accuracy of ACS and CSS prediction was evaluated using the BCRC and Lughezzani nomograms. Using the BCRC nomogram, c‐indices of for 2‐ and 5‐year ACS were each 0.73 and c‐indices for 2‐ and 5‐year CSS were 0.70 each. The performance of Lughezzani nomogram for 5‐year ACS, cancer‐specific mortality and OCM were 0.73, 0.72 and 0.40, respectively.
The BCRC nomogram prediction of advanced pathological stage and lymph node metastasis was modest, with c‐indices of 0.66 and 0.61, respectively.
Conclusions
Bladder cancer nomograms available from the current open RC literature adequately predict ACS, CSS and PFS after RARC.
However, prediction of advanced tumour stage and lymph node metastasis was modest and the Lughezzani nomogram failed to predict OCM.
Midkine in nephrogenesis, hypertension and kidney diseases
Authors: Sato Waichi , Sato Yuka 
Published: October 2013

Midkine (MK; K; gene abbreviation, Mdk: mus musculus, MDK: homo sapiens) is a multifunctional heparin‐binding growth factor that regulates cell growth, survival and migration as well as anti‐apoptotic activity in nephrogenesis and development. Proximal tubular epithelial cells are the main sites of MK expression in the kidneys. The pathophysiological roles of MK are diverse, ranging from the development of acute kidney injury (AKI) to the progression of chronic kidney disease, often accompanied by hypertension, renal ischaemia and diabetic nephropathy. The obvious hypertension that develops in Mdk+/+ mouse models of renal ablation compared with Mdk−/− mice eventually leads to progressive renal failure, such as glomerular sclerosis and tubulointerstitial damage associated with elevated plasma angiotensin (Ang) II levels. MK is also induced in the lung endothelium by oxidative stress and subsequently up‐regulated by ACE, which hydrolyzes Ang II to induce further oxidative stress, thus accelerating MK generation; this leads to a vicious cycle of positive feedback in the MK‐Ang II pathway. Kidney–lung interactions involving positive feedback between the renin‐angiotensin system and MK might partly account for the pathogenesis of hypertension and kidney damage. MK is also involved in the pathogenesis of AKI and diabetic nephropathy through the recruitment of inflammatory cells. In contrast, MK plays a protective role against crescentic glomerulonephritis, by down‐regulating plasminogen activator inhibitor‐1. These diverse actions of MK might open up new avenues for targeted approaches to treating hypertension and various renal diseases.Linked ArticlesThis article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐4
Melatonin modulates microsomal PGE synthase 1 and NF‐E2‐related factor‐2‐regulated antioxidant enzyme expression in LPS‐induced murine peritoneal macrophages
Authors: Aparicio‐Soto M , Alarcón‐de‐la‐Lastra C , Cárdeno A , Sánchez‐Fidalgo S , Sanchez‐Hidalgo M 
Published: October 2013

Background and PurposeIncreasing evidence demonstrates that melatonin regulates inflammatory and immune processes acting as both an activator and inhibitor of these responses. Nevertheless, the molecular mechanisms of its anti‐inflammatory action remain unclear. Here we have characterized the cellular mechanisms underlying the redox modulation of LPS‐stimulated inflammatory responses in murine peritoneal macrophages by melatonin to provide insight into its anti‐inflammatory effects.Experimental ApproachMurine peritoneal macrophages were isolated and treated with melatonin in the presence or absence of LPS (5 μg·mL−1) for 18 h. Cell viability was determined using sulforhodamine B assay and NO production was measured using the Griess reaction. Pro‐inflammatory enzymes and transcription factors were detected by Western blotting.Key ResultsWithout affecting cell viability, melatonin (12.5, 25, 50 and 100 μM) reduced the level of nitrites, inducible NOS (iNOS), COX‐2 and microsomal PGE synthase‐1 (mPGES1) protein, and p38 MAPK phosphorylation, and prevented NF‐κB translocation. Furthermore, melatonin treatment significantly increased NF‐E2‐related factor 2 (Nrf2) and haem oxygenase 1 (HO1) protein levels in murine macrophages exposed to LPS.Conclusions and ImplicationsMelatonin reduced pro‐inflammatory mediators and enhanced the expression of HO1 via NF‐κB, p38 MAPK and Nrf2 cascade signalling pathways in murine macrophages. Thus, melatonin might be a promising target for diseases associated with overactivation of macrophages.
Cell death and the mitochondria: therapeutic targeting of the BCL‐2 family‐driven pathway
Authors: Roy M J , Vom A , Czabotar P E , Lessene G 
Published: October 2013

The principal biological role of mitochondria is to supply energy to cells; although intriguingly, evolution has bestowed another essential function upon these cellular organelles: under physiological stress, mitochondria become the cornerstone of apoptotic cell death. Specifically, mitochondrial outer membrane permeabilization (MOMP) allows cell death factors such as cytochrome c to be released into the cytoplasm, thus inducing caspase activation and the eventual destruction of essential cellular components. Proteins of the B‐cell lymphoma 2 (BCL‐2) family control the tightly regulated pathway that causes MOMP. The equilibrium between pro‐survival and pro‐apoptotic members of the BCL‐2 family dictates the fate of cells, the homeostasis of organs and, by extension, the health of whole organisms. Dysregulation of this equilibrium is involved in a large number of diseases such as cancer, autoimmunity and neurodegenerative conditions. Modulating the activity of the BCL‐2 family of proteins with small molecules or peptides is an attractive but challenging therapeutic goal. This review highlights the latest developments in this field and provides evidence that this strategy is likely to have a positive effect on the treatment of still poorly addressed medical conditions.Linked ArticlesThis article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue‐8