bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetics as the mediator of fetal programming of adult onset disease: what is the evidence?
Authors: Saffery Richard , Novakovic Boris 
Published: May 2014

AbstractThe Developmental Origins of Health and Disease hypothesis describes how early life environmental factors influence development in a way that impacts later health and disease risk. The hypothesis is supported by a large number of animal studies and a smaller number of observational studies in humans. Epigenetic variation induced in early life has emerged as a prime candidate to be the mediator of such effects, but little direct evidence of this relation exists in humans, primarily due to the inherent problems associated with unraveling the relative contributions of genetic and environmental variables to phenotypic diversity. There are several prerequisites for establishing a causal link that include demonstrating interindividual epigenetic variability in early life in response to specific environmental exposures. Further, compelling evidence linking epigenetic change to disease, prior to onset is required. Finally, the functional relevance of specific epigenetic change must be demonstrated. Evidence is emerging in all of these areas but, ultimately, only large longitudinal life‐course studies, commencing prior to birth, can provide direct evidence in support of a role of epigenetic processes as a driver of Developmental Origins of Health and Disease in humans.
Severity‐dependent association between ganglion cell inner plexiform layer thickness and macular mean sensitivity in open‐angle glaucoma
Authors: Kim Ko Eun , Park Ki Ho , Jeoung Jin Wook , Kim Seok Hwan , Kim Dong Myung 
Published: May 2014

AbstractPurposeTo evaluate the structure–function relationship between macular mean sensitivity (mMS) and ganglion cell inner plexiform layer thickness (GCIPLT) according to glaucoma severity and to compare it with that between mMS and peripapillary retinal nerve fibre layer thickness (pRNFLT), using spectral‐domain (Cirrus) optical coherence tomography (OCT).MethodsThree hundred and sixty‐two eyes of 362 patients with open‐angle glaucoma of differing severity (preperimetric, early, moderate, and advanced) together with 130 eyes of 130 healthy controls, all of whom underwent Cirrus OCT imaging and 30‐2 standard automated perimetry (SAP), were included in the study. The mMS was assessed by calculating the average of sensitivities at 12 central SAP points. The relationships between mMS and the various GCIPLT (average, minimum, superior, and inferior) parameters obtained by Cirrus OCT were evaluated according to disease severity using a linear regression model and were then compared with those between pRNFLT parameters and mMS.ResultsThe mMS and GCIPLT showed stronger relationships with the increase in glaucoma severity, but this was not the case with the pRNFLT parameters. In preperimetric glaucoma, the associations between mMS and both GCIPLT and pRNFLT were not significant. In moderate and advanced glaucoma, all GCIPLT parameters showed a statistically significant relationship with mMS. However, pRNFLT showed a moderate association in early and moderate glaucoma and none at all in advanced glaucoma.ConclusionsGCIPLT showed a stronger structure–function relationship with mMS in more advanced stages of glaucoma compared to pRNFLT. GCIPLT reflected macular functional damage better than pRNFLT in advanced glaucoma.
Riccardin D, a Macrocyclic Bisbibenzy, Inhibits Human Breast Cancer Growth through the Suppression of Telomerase Activity
Authors: Sun Cui‐Cui , Xu Hui‐Min , Yuan Yi , Gao Zu‐Hua , Lou Hong‐Xiang , Qu Xian‐Jun 
Published: May 2014

AbstractRiccardin D, a liverwort‐derived naturally occurring macrocyclic bisbibenzyl, has been found to exert anticancer effects in multiple cancer cell types. In this study, we investigated the effect and mechanism of Riccardin D on human breast cancer. Experiments were performed on human breast cancer MCF‐7 and MDA‐MB‐231 cells. The antitumour effects of Riccardin D were assessed by the 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide (MTT) assay and human breast cancer xenografts mice model. TRAPeze® XL Telomerase Detection assay was used for the detection of telomerase activity. γ‐H2AX foci formation was tested for the induction of DNA damage response. Cell cycle distribution was analysed by flow cytometry, and cell apoptosis was determined by annexin V‐FITC/PI staining, terminal deoxynucleotidyl transferase‐mediated dUTP nick end labelling (TUNEL) assay and Western blotting. Riccardin D effectively inhibited the growth of MCF‐7 and MDA‐MB‐231 cells in vitro. And Riccardin D also effectively delayed the growth of MCF‐7 and MDA‐MB‐231‐luc‐D3H2LN xenografts without significant loss of body‐weight. Further analysis suggested that Riccardin D's effects may arise from its suppression of telomerase activity, which led to telomere dysfunction. Telomerase inhibition and telomere dysfunction could activate the canonical ataxia telangiectasia‐mutated (ATM) kinase‐mediated DNA damage response, as shown by elevated expression of γ‐H2AX, p‐ATM and p‐Chk2. This is finally followed by the induction of cell cycle arrest and apoptosis, as shown by the increase of TUNEL‐stained cells, caspase activation, PARP cleavage and the increase of bax/bcl‐2 ratio. Moreover, Riccardin D induced p53‐proficient MCF‐7 cells to arrest in G1 phase and p53‐deficient MDA‐MB‐231 cells to arrest in G2/M phase. Overall, these results demonstrate that Riccardin D may inhibit human breast cancer growth through suppression of telomerase activity.
Saquinavir‐NO Inhibits IL‐6 Production in Macrophages
Authors: Momčilović Miljana , Mangano Katia , Jevtić Bojan , Mammana Santa , Stošić‐Grujičić Stanislava , Nicoletti Ferdinando , Miljković Djordje 
Published: May 2014

AbstractCovalent attachment of the nitric oxide (NO) moiety to the HIV protease inhibitor Saquinavir (Saq) produced a new chemical entity, named Saquinavir‐NO, (Saq‐NO) with reduced toxicity and potent immunoregulatory influence on T lymphocytes. In this study, we have compared head‐to‐head the effects of Saq‐NO and Saq on mouse and rat peritoneal macrophage cytokine secretion and NO production upon in vitro, ex vivo and in vivo conditions. The results demonstrate that Saq‐NO, but not Saq, potently decreased interleukin (IL)‐10, IL‐6 and nitrite accumulation and increased the levels of IL‐1β and tumour necrosis factor (TNF) in supernatants of mouse and rat macrophage cultures in vitro. Treatment of mice with Saq‐NO, but not Saq, inhibited ex vivo secretion of IL‐6 from macrophages. Consistent with these findings, Saq‐NO also reduced blood levels of IL‐6 in lipopolysaccharide‐treated mice. The observed inhibitory influence of Saq‐NO on IL‐6 generation in macrophages may be involved in the observed antitumour and immunomodulatory effects of the drug.
Sexual function and health‐related quality of life in women with classic bladder exstrophy
Authors: Deans Rebecca , Liao Lih‐Mei , Wood Dan , Woodhouse Christopher , Creighton Sarah M. 
Published: May 2014

ObjectiveTo investigate sexual function and quality of life in adolescent and adult women with classic bladder exstrophy (BE).Materials and MethodsA two‐part observational cross‐sectional study with a questionnaire arm and a retrospective case review arm was performed. The study was undertaken in a centre providing a tertiary referral gynaecology and urology service. Outcomes were sexual function and quality‐of‐life scores.ResultsA total of 44 patients with BE were identified from departmental databases and included in the study, of whom 28 (64%) completed postal questionnaires. Sexual function scores and quality‐of‐life visual analogue scales were significantly poorer compared with normative data.ConclusionsBladder exstrophy has a detrimental psychological impact on women. In future, methodical multidisciplinary paediatric follow‐up research will help to identify predictors of better and worse adolescent and adult outcomes. Development and evaluation of cost‐effective psychological interventions to target specific problems is also warranted.
Robot‐assisted laparoscopic ureteric reimplantation: extravesical technique
Authors: Dangle Pankaj P. , Shah Anup , Gundeti Mohan S. 
Published: May 2014

ObjectivesTo describe our standardised approach to performing robot‐assisted extravesical ureteric reimplantation.Patients and MethodsA total of 29 children, with high grade (III–V) vesico‐ureteric reflux (VUR) underwent robot‐assisted extravesical ureteric reimplantation between September 2010 and September 2013. Follow‐up renal ultrasonography was performed at 1 month and 3 months and a voiding cysto‐urethrogram (VCUG) was obtained at 4 months to assess VUR resolution.ResultsThe mean (range) patient age at the time of surgery was 5.38 (3.0–10.0) years. Postoperative VCUG showed complete resolution of VUR in 32/40 ureters (80%). Of the remaining refluxing ureters, downgrading of VUR on VCUG was shown in 7/8 ureters (87.5%). The mean (range) length of hospital stay was 1.8 (1–3) days.ConclusionsIn conclusion, robot‐assisted extravesical ureteric reimplantation is technically feasible with acceptable resolution of VUR.
Determination of optimal drug dose and light dose index to achieve minimally invasive focal ablation of localised prostate cancer using WST11‐vascular‐targeted photodynamic (VTP) therapy
Authors: Moore Caroline M. , Azzouzi Abel‐Rahmene , Barret Eric , Villers Arnauld , Muir Gordon H. , Barber Neil J. , Bott Simon , Trachtenberg John , Arumainayagam Nimalan , Gaillac Bertrand , Allen Clare , Schertz Avigdor , Emberton Mark 
Published: May 2014

ObjectiveTo determine the optimal drug and light dose for prostate ablation using WST11 (TOOKAD® Soluble) for vascular‐targeted photodynamic (VTP) therapy in men with low‐risk prostate cancer.Patients and MethodsIn all, 42 men with low‐risk prostate cancer were enrolled in the study but two who underwent anaesthesia for the procedure did not receive the drug or light dose. Thus, 40 men received a single dose of 2, 4 or 6 mg/kg WST11 activated by 200 J/cm light at 753 nm. WST11 was given as a 10‐min intravenous infusion. The light dose was delivered using cylindrical diffusing fibres within hollow plastic needles positioned in the prostate using transrectal ultrasonography (TRUS) guidance and a brachytherapy template. Magnetic resonance imaging (MRI) was used to assess treatment effect at 7 days, with assessment of urinary function (International Prostate Symptom Score [IPSS]), sexual function (International Index of Erectile Function [IIEF]) and adverse events at 7 days, 1, 3 and 6 months after VTP. TRUS‐guided biopsies were taken at 6 months.ResultsIn all, 39 of the 40 treated men completed the follow‐up. The Day‐7 MRI showed maximal treatment effect (95% of the planned treatment volume) in men who had a WST11 dose of 4 mg/kg, light dose of 200 J/cm and light density index (LDI) of >1. In the 12 men treated with these parameters, the negative biopsy rate was 10/12 (83%) at 6 months, compared with 10/26 (45%) for the men who had either a different drug dose (10 men) or an LDI of <1 (16). Transient urinary symptoms were seen in most of the men, with no significant difference in IPSS score between baseline and 6 months after VTP. IIEF scores were not significantly different between baseline and 6 months after VTP.ConclusionTreatment with 4 mg/kg TOOKAD Soluble activated by 753 nm light at a dose of 200 J/cm and an LDI of >1 resulted in treatment effect in 95% of the planned treatment volume and a negative biopsy rate at 6 months of 10/12 men (83%).
Of mice and men: modelling post‐stroke depression experimentally
Authors: Kronenberg G , Gertz K , Heinz A , Endres M 
Published: May 2014

At least one‐third of stroke survivors suffer from depression. The development of comorbid depression after stroke is clinically highly significant because post‐stroke depression is associated with increased mortality, slows recovery and leads to worse functional outcomes. Here, we review the evidence that post‐stroke depression can be effectively modelled in experimental rodents via a variety of approaches. This opens an exciting new window onto the neurobiology of depression and permits probing potential underlying mechanisms such as disturbed cellular plasticity, neuroendocrine dysregulation, neuroinflammation, and neurodegeneration in a novel context. From the point of view of translational stroke research, extending the scope of experimental investigations beyond the study of short‐term end points and, in particular, acute lesion size, may help improve the relevance of preclinical results to human disease. Furthermore, accumulating evidence from both clinical and experimental studies offers the tantalizing prospect of 5‐hydroxytryptaminergic antidepressants as the first pharmacological therapy for stroke that would be available during the subacute and chronic phases of recovery. Interdisciplinary neuropsychiatric research will be called on to dissect the mechanisms underpinning the beneficial effects of antidepressants on stroke recovery.Linked ArticlesThis article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20
Overexpression of oxytocin receptors in the hypothalamic PVN increases baroreceptor reflex sensitivity and buffers BP variability in conscious rats
Authors: Lozić Maja , Greenwood Michael , Šarenac Olivera , Martin Andrew , Hindmarch Charles , Tasić Tatjana , Paton Julian , Murphy David , Japundžić‐Žigon Nina 
Published: May 2014

Background and PurposeThe paraventricular nucleus (PVN) of the hypothalamus is an important integrative site for neuroendocrine control of the circulation. We investigated the role of oxytocin receptors (OT receptors) in PVN in cardiovascular homeostasis.Experimental ApproachExperiments were performed in conscious male Wistar rats equipped with a radiotelemetric device. The PVN was unilaterally co‐transfected with an adenoviral vector (Ad), engineered to overexpress OT receptors, and an enhanced green fluorescent protein (eGFP) tag. Control groups: PVN was transfected with an Ad expressing eGFP alone or untransfected, sham rats (Wt). Recordings were obtained without and with selective blockade of OT receptors (OTX), during both baseline and stressful conditions. Baroreceptor reflex sensitivity (BRS) and cardiovascular short‐term variability were evaluated using the sequence method and spectral methodology respectively.Key ResultsUnder baseline conditions, rats overexpressing OT receptors (OTR) exhibited enhanced BRS and reduced BP variability compared to control groups. Exposure to stress increased BP, BP variability and HR in all rats. In control groups, but not in OTR rats, BRS decreased during stress. Pretreatment of OTR rats with OTX reduced BRS and enhanced BP and HR variability under baseline and stressful conditions. Pretreatment of Wt rats with OTX, reduced BRS and increased BP variability under baseline and stressful conditions, but only increased HR variability during stress.Conclusions and ImplicationsOT receptors in PVN are involved in tonic neural control of BRS and cardiovascular short‐term variability. The failure of this mechanism could critically contribute to the loss of autonomic control in cardiovascular disease.
Calorie restriction and Roux‐en‐Y gastric bypass have opposing effects on circulating FGF21 in morbidly obese subjects
Authors: Lips Mirjam A. , de Groot Gerrit H. , Berends Frits J. , Wiezer Renee , van Wagensveld Bart A. , Swank Dingeman J. , Luijten Arijan , van Dijk Ko Willems , Pijl Hanno , Jansen Peter L.M. , Schaap Frank G. 
Published: May 2014

SummaryObjectiveTo study the effect of different weight loss strategies on levels of the metabolic regulator FGF21 in morbidly obese females with normal glucose tolerance (NGT) or type 2 diabetes mellitus (T2DM).DesignObservational intervention trial.Patients and measurementsWeight reduction was achieved by Gastric Banding (GB, n = 11) or Roux‐en‐Y Gastric Bypass (RYGB, n = 16) in subjects with NGT, and by RYGB (n = 15) or a very‐low‐calorie diet (VLCD, n = 12) in type 2 diabetics. Fasted and/or postprandial levels of FGF21, FGF19 (an FGF21‐related postprandial hormone) and bile salts (implicated in regulation of FGF21 and FGF19 expression) were measured before, and 3 and 12 weeks after intervention.ResultsFasted FGF21 levels were elevated in T2DM subjects. Calorie restriction by either GB or VLCD lowered bile salt and FGF21 levels. In contrast, RYGB surgery was associated with elevated bile salt and FGF21 levels.ConclusionsCalorie restriction and RYGB have opposite effects on serum bile salt and FGF21 levels. Calorie restriction results in FGF21 approaching nonobese control levels, suggesting that this intervention is effective in reducing the “nutritional crisis” that appears to underly FGF21 elevation in obesity. FGF21 elevation after RYGB may contribute to the beneficial effect of this procedure.
Evaluation of a confocal Raman probe for pathological diagnosis during colonoscopy
Authors: Wood J. J. , Kendall C. , Hutchings J. , Lloyd G. R. , Stone N. , Shepherd N. , Day J. , Cook T. A. 
Published: May 2014

AbstractAimRaman spectroscopy of human tissue can provide a unique biochemical ‘fingerprint’ that alters with disease progression. Light incident on tissue is scattered and may be altered in wavelength, which can be represented as a Raman spectrum. A confocal fibreoptic Raman probe designed to fit down the accessory channel of a colonoscope has been constructed. This in‐vitro study evaluated the accuracy of pathological diagnosis in the colon using probe‐based Raman spectroscopy.MethodBiopsy samples were collected at colonoscopy, snap frozen and stored at −80°C. Raman spectra with 10‐s and 1‐s acquisition periods were measured with the probe tip in contact with the mucosal surface of thawed specimens. Mathematical modelling using principal component analysis followed by linear discriminant analysis was used to correlate Raman spectra with histopathological diagnoses.ResultsThree‐hundred and seventy‐five Raman spectra were measured from a total of 356 colon biopsies (81 of normal colon mucosa, 79 of hyperplastic polyps, 92 of adenomatous polyps, 64 of adenocarcinoma and 40 of ulcerative colitis) from 177 patients. Spectral classification accuracies comparing pathology pairs ranged from 72.1 to 95.9% for 10‐s acquisitions and from 61.5 to 95.1% for 1‐s acquisitions. For a three‐group model of normal, adenomatous and adenocarcinoma tissue, accuracies were 74.1% for 10‐s acquisitions and 63.5% for 1‐s acquisitions.ConclusionThe confocal Raman probe system can distinguish between different colorectal pathologies. The probe has potential to establish Raman spectroscopy as a clinical tool for instant diagnosis at colonoscopy.
Women with pre‐gestational diabetes have a higher risk of stillbirth at all gestations after 32 weeks
Authors: Holman N. , Bell R. , Murphy H. , Maresh M. 
Published: May 2014

AbstractAimTo explore the additional risk of stillbirths and to quantify that risk according to gestational age among women with diabetes.MethodsData on pregnancies ending in 2007 and 2008 in women with pre‐gestational diabetes in three English regional audits were identified. A prospective audit collected data on all pregnancies delivering between June 2010 and May 2011 in one region and in 13 other units across England. The data on all singleton pregnancies from these two cohorts were combined. Comparisons were made to all births in England and Wales for the same time period using data from the Office for National Statistics.ResultsIn the cohort of women with pre‐gestational diabetes there were a total of 2085 singleton pregnancies, of which 29 resulted in a stillbirth (overall stillbirth rate 13.9 per 1000, 95% CI 9.7–19.9, relative risk compared with all pregnancies in England and Wales 2.73, 95% CI 2.61–2.84). The relative risk of stillbirth between 32 and 34 weeks' gestation was 4.95 (95% CI 4.24–5.78), 3.77 (95% CI 3.42–4.16) at 35 to 36 weeks, 5.75 (95% CI 5.43–6.09) for deliveries at 37 or 38 weeks and 7.34 (95% CI 6.52–8.25) for those born at 39 weeks or more.ConclusionWomen with diabetes have a significantly higher risk of stillbirth at all gestations after 32 weeks and this additional risk is not just confined to pregnancies at 37 weeks or more.
Urbanisation tolerance and the loss of avian diversity
Authors: Sol Daniel , González‐Lagos Cesar , Moreira Darío , Maspons Joan , Lapiedra Oriol 
Published: May 2014

AbstractUrbanisation is considered an important driver of current biodiversity loss, but the underlying causes are not fully understood. It is generally assumed that this loss reflects the fact that most organisms do not tolerate well the environmental alterations associated with urbanisation. Nevertheless, current evidence is inconclusive and the alternative that the biodiversity loss is the result of random mechanisms has never been evaluated. Analysing changes in abundance between urbanised environments and their non‐urbanised surroundings of > 800 avian species from five continents, we show here that although random processes account for part of the species loss associated with urbanisation, much of the loss is associated with a lack of appropriate adaptations of most species for exploiting resources and avoiding risks of the urban environments. These findings have important conservation implications because the extinction of species with particular features should have higher impact on biodiversity and ecosystem function than a random loss.
Visual Discrimination Learning in the Small Octopus Octopus ocellatus
Authors: Tomita Mitsuru , Aoki Setsuyuki 
Published: May 2014

AbstractOctopus ocellatus is a small benthic species of octopus that is easy to rear and spawns large eggs during a short life cycle. These and other features of O. ocellatus may make it an advantageous subject for a broad range of behavioral studies, including those involving various types of learning. However, no type of learning has been studied in O. ocellatus. In a successive visual discrimination task, in which a ‘positive’ or ‘negative’ stimulus (white or black rectangle) was presented to a subject octopus and appropriate rewards or punishments were given to the subject, the rate of ‘correct’ responses (i.e., touches to the positive stimulus or refraining from the negative stimulus) gradually increased. Moreover, ‘observer’ octopuses that observed another octopus performing a visual discrimination task in which reward was also given to the ‘incorrect’ responses (touches to the negative stimulus) showed a higher ratio of incorrect responses in their test sessions. These results, coupled with the physical characteristics of O. ocellatus, indicate that this species is potentially suitable for neurogenetic and neuroembryological studies of learning.
Defining dermal adipose tissue
Authors: Driskell Ryan R. , Jahoda Colin A. B. , Chuong Cheng‐Ming , Watt Fiona M. , Horsley Valerie 
Published: May 2014

AbstractHere, we explore the evolution and development of skin‐associated adipose tissue with the goal of establishing nomenclature for this tissue. Underlying the reticular dermis, a thick layer of adipocytes exists that encases mature hair follicles in rodents and humans. The association of lipid‐filled cells with the skin is found in many invertebrate and vertebrate species. Historically, this layer of adipocytes has been termed subcutaneous adipose, hypodermis and subcutis. Recent data have revealed a common precursor for dermal fibroblasts and intradermal adipocytes during development. Furthermore, the development of adipocytes in the skin is independent from that of subcutaneous adipose tissue development. Finally, the role of adipocytes has been shown to be relevant for epidermal homoeostasis during hair follicle regeneration and wound healing. Thus, we propose a refined nomenclature for the cells and adipose tissue underlying the reticular dermis as intradermal adipocytes and dermal white adipose tissue, respectively.