bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti‐Inflammatory Activity of Saponins from Quinoa (Chenopodium quinoa Willd.) Seeds in Lipopolysaccharide‐Stimulated RAW 264.7 Macrophages Cells
Authors: Yao Yang , Yang Xiushi , Shi Zhenxing , Ren Guixing
Published: April 2014

Quinoa (Chenopodium quinoa Willd.) is a pseudocereal from South Americas that has received increased interest around the world because it is a good source of different nutrients and rich in saponins. However, the saponins in quinoa seeds planted in China were poorly known. We obtained 4 quinoa saponin fractions, Q30, Q50, Q70, and Q90, and 11 saponins were determined by HPLC‐MS. Q50 possessed 8 individual saponins and had the highest content of saponins. We further evaluated the anti‐inflammatory activity on RAW 264.7 murine macrophage cells of the 4 fractions. The 4 fractions not only dose‐dependently decreased the production of inflammatory mediators NO but also inhibited the release of inflammatory cytokines including tumor necrosis factor‐α and interleukin‐6 in lipopolysaccharide‐induced RAW264.7 cells. These results suggest that quinoa saponins may be used as functional food components for prevention and treatment of inflammation.

Practical Application

Our findings demonstrate that saponins from the quinoa have the potential to anti‐inflammation by suppressing the release of inflammatory cytokines.
Viscoelastic Properties of Soft Materials on a Basis of Starch Mixtures
Authors: Orczykowska Magdalena , Dziubiński Marek
Published: April 2014

The effect of concentration of carbohydrates on viscoelastic properties of corn and rice starch is discussed in this paper. The texture of starch pastes was estimated using a fractional rheological linear standard solid model. Rheological parameters of the model were identified and their changes for different values of sugar concentrations in the 2 tested starches were discussed.

Practical Application

The fractional rheological models can be very useful to control the biomaterial texture for the needs of final product, which is particularly significant from the point of view of materials engineering. The proposed method for interpretation of the results of rheological measurements of these pastes allows for a comprehensive estimation of the analyzed biomaterial texture.
Identification and evaluation of models of antenatal care in Australia – A review of the evidence
Authors: Brock Erin , Charlton Karen E. , Yeatman Heather
Published: April 2014

Background

Antenatal care has been routine practice throughout the world since early in the 20th century, and in most developed countries, antenatal care consists of a scheduled program of individual consultations with a healthcare practitioner, using a doctor or midwife. Women seek antenatal care that provides a physical review of the health and development of their unborn baby, the reassurance and ability to be listened to and the opportunity for their partner to be involved in their care.

Aims

To identify the types of antenatal care services that are available to Australian women and investigate the views and opinions of Australian women related to these services.

Materials and Methods

A systematic literature review using Scopus and Medline databases was used to find appropriate journal articles in January 2013. Articles were restricted to those in the Australian setting from the past 10 years with a focus on different models of antenatal care and the views and experiences of women during their antenatal care.

Results

Eighteen relevant peer‐reviewed journal articles were included. Emerging forms of antenatal care that are showing increasing levels of satisfaction from Australian women include continuity of carer, the midwifery‐led care and group‐ or community‐led care. These approaches are proving to be safe and successful.

Conclusion

Newer models of antenatal care in Australia may offer benefits over standard practice.
Radical nephrectomy and vena caval thrombectomy with the use of cardiopulmonary bypass
Authors: Raman Avi , Jawale Atul , Grant Alexander
Published: April 2014

Background

This study aimed to report on the experience of a single surgeon in a regional Australian centre with radical nephrectomy and vena caval thrombectomy with the use of cardiopulmonary bypass.

Methods

Fifteen consecutive patients undergoing radical nephrectomy and vena caval thrombectomy with cardiopulmonary bypass over a 13‐year period were identified. Retrospective analysis of prospectively collected data was used. Data were collected on intra‐operative and pathological findings as well as post‐operative complications. Oncological outcomes and long‐term follow‐up were analysed retrospectively in this study.

Results

All patients had a radical nephrectomy and vena caval thrombectomy with cardiopulmonary bypass. The median operating time was 336 min (mean 326.1 min), and median transfusion of packed red blood cells was 8 units (mean 6.9). The median bypass time was 107 min (mean 112.3 min), and the median circulation arrest time was 25 min (mean 25.3 min). Median length of hospital stay was 11 days (mean 14.5 days). Minor complications were seen in two patients and major complications seen in six, with one intra‐operative death. Disease recurrence was seen in 1 of 14 patients who were considered completely resected at the time of operation. The overall 5‐year survival rate was 84%. Median follow‐up was 32 months (range 0–158). Median survival time was 135 months.

Conclusions

Radical nephrectomy with caval thrombectomy with cardiopulmonary bypass can be performed in a regional centre with acceptable post‐operative morbidity and mortality. Long‐term survival is possible in some patients.
Outcome for children and young people with Early T‐cell precursor acute lymphoblastic leukaemia treated on a contemporary protocol, UKALL 2003
Authors: Patrick Katharine , Wade Rachel , Goulden Nick , Mitchell Chris , Moorman Anthony V. , Rowntree Clare , Jenkinson Sarah , Hough Rachael , Vora Ajay
Published: April 2014

We investigated the outcome for children and young people with Early T‐precursor acute lymphoblastic leukaemia (ETP‐ALL), a recently described poor prognosis sub‐group of T‐ALL, treated on a contemporary protocol, UKALL 2003. After a median follow‐up of 4 years and 10 months, the ETP sub‐group, representing 16% of T‐ALL patients, had non‐significantly inferior 5‐year event‐free survival (76·7% vs. 84·6%, P = 0·2) and overall survival (82·4% vs. 90·9%, P = 0·1), and a higher relapse rate (18·6% vs. 9·6%, P = 0·1) compared to typical T‐ALL. ETP‐ALL has an intermediate risk outcome, which does not warrant experimental treatment or first remission allogeneic transplant for the group universally.
Investigating G protein signalling bias at the glucagon‐like peptide‐1 receptor in yeast
Authors: Weston C , Poyner D , Patel V , Dowell S , Ladds G
Published: April 2014

Background and Purpose

The glucagon‐like peptide 1 (GLP‐1) receptor performs an important role in glycaemic control, stimulating the release of insulin. It is an attractive target for treating type 2 diabetes. Recently, several reports of adverse side effects following prolonged use of GLP‐1 receptor therapies have emerged: most likely due to an incomplete understanding of signalling complexities.

Experimental Approach

We describe the expression of the GLP‐1 receptor in a panel of modified yeast strains that couple receptor activation to cell growth via single Gα/yeast chimeras. This assay enables the study of individual ligand–receptor G protein coupling preferences and the quantification of the effect of GLP‐1 receptor ligands on G protein selectivity.

Key Results

The GLP‐1 receptor functionally coupled to the chimeras representing the human Gαs, Gαi and Gαq subunits. Calculation of the dissociation constant for a receptor antagonist, exendin‐3 revealed no significant difference between the two systems. We obtained previously unobserved differences in G protein signalling bias for clinically relevant therapeutic agents, liraglutide and exenatide; the latter displaying significant bias for the Gαi pathway. We extended the use of the system to investigate small‐molecule allosteric compounds and the closely related glucagon receptor.

Conclusions and Implications

These results provide a better understanding of the molecular events involved in GLP‐1 receptor pleiotropic signalling and establish the yeast platform as a robust tool to screen for more selective, efficacious compounds acting at this important class of receptors in the future.
Adrenocortical adenomas with regression and myelolipomatous changes: urinary steroid profiling supports a distinctive benign neoplasm
Authors: Perna Victoria , Taylor Norman F. , Dworakowska Dorota , Schulte Klaus‐Martin , Aylwin Simon , Al‐Hashimi Fatima , Diaz‐Cano Salvador J.
Published: April 2014

Background

Adrenocortical neoplasms are classically divided into adenomas (ACA) and carcinomas (ACC). Heterogeneous appearance and greater size are criteria to suggest malignancy, along with the urinary steroid profile (USP). The presence of regression and myelolipomatous changes in adenomas (ACA‐RML) can contribute to confusion with ACC and its USP remains unknown.

Objective

To evaluate the features of ACA‐RML in comparison with other adrenocortical neoplasms.

Methods

We selected consecutive ACA (11), ACA‐RML (7) and ACC (13) cases for which USP analysis was performed before surgery and tissue was available for histological evaluation (King's College Hospital, 2005–2012). Cases were classified according to WHO and Armed Forces Institute of Pathology criteria. USPs were obtained by gas chromatography/mass spectrometry. Total excretion of individual steroids and indices (sums and ratios chosen to reflect steroid metabolic activity) were compared between ACA‐RML, ACA and ACC.

Results

In comparison with ACA, tumours in ACA‐RML were significantly larger (8·5 ± 2·4 vs 3·5 ± 1·0, P = 0·002), presented in older patients and showed relatively higher incidence in males. Mitotic figure counts were significantly lower (0·39 ± 0·04 vs 0·93 ± 0·11 in ACA, P = 0·001) and revealed higher frequency of apoptotic cells (100% vs 9% in ACA, P = 0·001). The USP of ACA‐RML showed no diagnostic features of ACC. No differences from ACA were significant, but there was a tendency towards lower dehydroepiandrosterone DHA and DHA metabolites.

Conclusions

ACA‐RML reveals distinctive histological features and lack of USP markers of malignancy. More cases of this rare tumour may confirm differences from ACA in steroid excretion. It is important to recognize ACA‐RML because its size and heterogeneous appearance raise the possibility of ACC.
In Vivo Two‐photon Fluorescence Microscopy Reveals Disturbed Cerebral Capillary Blood Flow and Increased Susceptibility to Ischemic Insults in Diabetic Mice
Authors: Huang Ji‐Yun , Li Li‐Tao , Wang Huan , Liu Shuang‐Shuang , Lu Ying‐Mei , Liao Mei‐Hua , Tao Rong‐Rong , Hong Ling‐Juan , Fukunaga Kohji , Chen Zhong , Wilcox Christopher S. , Lai En Yin , Han Feng
Published: April 2014

Aims

Diabetes mellitus increases the risk of stroke, but the mechanisms are unclear. The present study tested the hypothesis that diabetes mellitus disturbs the brain microcirculation and increases the susceptibility to cerebral damage in a middle cerebral artery occlusion (MCAO) model of ischemia.

Methods

Diabetes was induced by streptozocin in mice expressing green fluorescent protein in endothelial cells (Tie2‐GFP mice). Four weeks later, they were subjected to transient (20 min) MCAO. In vivo blood flow was measured by two‐photon laser‐scanning microscopy (TPLSM) in cerebral arteries, veins, and capillaries.

Results

There was a significant decrease in red blood cell (RBC) velocity in capillaries in diabetic mice as assessed by TPLSM, yet the regional cerebral blood flow, as assessed by laser Doppler flowmetry, was maintained. Brain capillary flow developed turbulence after MCAO only in diabetic mice. These mice sustained increased neurological deficits after MCAO which were accompanied by an exaggerated degradation of tight junction proteins and blunted CaMKII phosphorylation in cerebral tissues indicating disruption of the blood–brain barrier and disturbed cognitive potential.

Conclusion

Diabetic mice are more susceptible to disturbances of cerebral capillary blood flow which may predispose them to neurovascular defects following ischemia.
Telaprevir with peginterferon/ribavirin for retreatment of null responders with advanced fibrosis post‐orthotopic liver transplant
Authors: Kwo Paul Y. , Ghabril Marwan , Lacerda Marco A. , Joseph Tector Alfred , Fridell Jonathan A. , Vianna Rodrigo
Published: April 2014

Introduction

Aggressive recurrence of hepatitis C remains problematic post‐orthotopic liver transplant (OLT). There are limited data on treatment of HCV infection with telaprevir/boceprevir therapy with peginterferon/ribavirin (PR) post‐OLT.

Aim

To review our experience with telaprevir addition to peginterferon/ribavirin in treatment of aggressive hepatitis C in null responders to PR post‐OLT.

Methods

Adult patients with recurrent HCV infection post‐OLT with null response to peginterferon/ribavirin for 12 wk (<2 log reduction) received four‐wk lead‐in PEG‐IFN alfa‐2b (1.0 μg/kg/wk) plus RBV (600–1000 mg/d) followed by addition of telaprevir 750 q8. All patients were converted to cyclosporine from tacrolimus (TAC).

Results

Seven patients (3 M, 4 F), mean age 56 yr, were treated. Three were <1 yr post‐OLT, six had cirrhosis and one bridging fibrosis. Three of seven achieved sustained virologic response. All patients required RBV dose reduction, 6/7 required erythropoietin, 5/7 required filgrastim, and 2/7 required eltrombopag for platelets <20 000 μL. There were no supratherapeutic/subtherapeutic CYA levels encountered, no episodes of renal insufficiency.

Conclusions

Conversion to CYA followed by four‐wk peginterferon/ribavirin lead‐in with addition of telaprevir can lead to significant clearance rates at week 24 in null responders with advanced fibrosis although high rates of anemia/RBV dose reduction, growth factor, and transfusion requirements were noted.
Three‐dimensional tumor volume and serum alpha‐fetoprotein are predictors of hepatocellular carcinoma recurrence after liver transplantation: refined selection criteria
Authors: Kashkoush Samy , El Moghazy Walid , Kawahara Toshiyasu , Gala‐Lopez Boris , Toso Christian , Kneteman Norman M.
Published: April 2014

Total tumor volume (TTV), as a better predictor of hepatocellular carcinoma (HCC) recurrence after liver transplant, has been explored by our center. Some tumors are not typically spherical but rather ellipsoid or spheroid, and calculating their TTV based on one dimension only may overestimate their volume and exclude them from candidacy for transplantation. Our aim was to study the actual tumor volume (ATV) calculated using the ellipsoid formula and assess its impact on recurrence. HCC patients transplanted between 1990 and 2010 at University of Alberta Hospital were analyzed. Tumor volumes were calculated using both formulas: [(4/3) πr3] (r = max. radius) and [(4/3) πabc] (a, b, c = the 3 radiuses). A total of 115 patients were included with a mean follow‐up of 4.99 ± 4.23 yr. Five‐yr recurrence‐free survival was 79.8%. Univariate analysis for predictors of recurrence included: maximum tumor diameter, ATV, TTV, and alpha‐fetoprotein (AFP) ≥ 400 ng/mL. Multivariate analysis showed that ATV and AFP ≥ 400 ng/mL were the only predictors of recurrence. Combining both variables provides better predication of recurrence with accuracy that exceeds 80%. Three‐dimensional calculation of tumor volume is of critical importance for the group of patients with ellipsoid tumors where volumes are overestimated with the spherical formula and could lead to inappropriate exclusion from transplant.
Distinct local circuit properties of the superficial and intermediate layers of the rodent superior colliculus
Authors: Phongphanphanee Penphimon , Marino Robert A. , Kaneda Katsuyuki , Yanagawa Yuchio , Munoz Douglas P. , Isa Tadashi
Published: April 2014

The superior colliculus (SC) is critical in localizing salient visual stimuli and making decisions on the location of the next saccade. Lateral interactions across the spatial map of the SC are hypothesized to help mediate these processes. Here, we investigate lateral interactions within the SC by applying whole‐cell recordings in horizontal slices of mouse SC, which maintained the local structure of the superficial (SCs) visual layer, which is hypothesized to participate in localizing salient stimuli, and the intermediate (SCi) layer, which is supposed to participate in saccade decision‐making. When effects of either electrical or chemical (uncaging of free glutamate) stimuli were applied to multiple sites with various distances from the recorded cell, a pattern of center excitation‐surround inhibition was found to be prominent in SCs. When the interactions of synaptic effects induced by simultaneous stimulation of two sites were tested, non‐linear facilitatory or inhibitory interactions were observed. In contrast, in the SCi, stimulation induced mainly excitation, which masked underlying inhibition. The excitatory synaptic effects of stimulation applied at remote sites were summed in a near linear manner. The result suggested that SCs lateral interactions appear suitable for localizing salient stimuli, while the lateral interactions within SCi are more suitable for faithfully accumulating subthreshold signals for saccadic decision‐making. Implementation of this laminar‐specific organization makes the SC a unique structure for serially processing signals for saliency localization and saccadic decision‐making.
Periodontal disease and stroke: a meta‐analysis of cohort studies
Authors: Lafon A. , Pereira B. , Dufour T. , Rigouby V. , Giroud M. , Béjot Y. , Tubert‐Jeannin S.
Published: April 2014

This review aimed to determine the association between periodontal disease and stroke incidence by a meta‐analysis of cohort studies. Cohort studies that evaluated the incidence of stroke (fatal or non‐fatal, ischaemic or haemorrhagic) and baseline periodontal status and calculated relative risk values were included. The quality of the included studies was assessed using an evaluation grid. The analyses were conducted separately for three outcomes: periodontitis, gingivitis and loss of teeth. Adjusted values of relative risk or of hazard ratio were used to assess risk values in each study. Random effects meta‐analyses were conducted when data could be pooled. From the 743 references retrieved, only nine cohort studies were suitable for inclusion in this review. Quality scores of the studies varied greatly. Three prospective studies, which used reliable indicators of periodontal disease, obtained the highest scores. Conversely, three studies that used a subjective evaluation of stroke incidence or diagnosed stroke without imaging obtained the lowest score. The results of the meta‐analyses varied depending on the outcome considered and the type of stroke. The risk of stroke was significantly increased by the presence of periodontitis [relative risk 1.63 (1.25, 2.00)]. Tooth loss was also a risk factor for stroke [relative risk 1.39 (1.13, 1.65)]. The risk of stroke did not vary significantly with the presence of gingivitis. This review shows that periodontitis and tooth loss are associated with the occurrence of stroke.
Congenital triple oesophageal stricture and megaoesophagus in a neonatal colt
Authors: Bezdekova B. , Skoric M. , Pekarkova M.
Published: April 2014

Congenital oesophageal stenosis is rarely described in horses. This case report describes a neonatal colt with signs of a milky nasal discharge and cervical swelling present from birth. The diagnostic evaluation revealed a triple oesophageal stricture, identified as congenital fibromuscular oesophageal stenosis. A megaoesophagus was seen cranial to the strictures, but its aetiology remains unexplained. To the authors’ knowledge, multiple oesophageal stenosis together with megaoesophagus has not previously been described in the horse.
Bottom‐up effects of lake sediment on pelagic food‐web compartments: a mesocosm study
Authors: Harrault Loïc , Allard Béatrice , Mériguet Jacques , Carmignac David , Huon Sylvain , Gauzens Benoit , Lacroix Gérard
Published: April 2014

Sediment plays a key role in organic matter (OM) and internal nutrient cycling in lakes. The role of sediment as a source of OM and its potential bottom‐up effects on the pelagic food web have rarely been studied. Particularly, the influence of the biochemical composition of sediment OM on pelagic compartments remains largely unknown.

During a 5‐month experiment, we studied the influence of two different sediments added at the bottom of large replicated mesocosms on the biomass of seston and zooplankton, and their elemental and lipid compositions. The influence of sediment treatments on sedimentation rates, elemental and biochemical compositions and potential biodegradability of recently sedimented OM (c. 1 week) was also examined.

The two added sediments (S1 and S2) presented contrasting elemental and biochemical compositions and potential biodegradabilities. According to their contents of organic carbon, nitrogen, proteins, sugars and polyunsaturated fatty acids, S2 appeared to be much more biodegradable than S1. Therefore, the S2 sediment was expected to release more nutrients and OM to the water column than S1, leading to changes in communities, stoichiometry and lipid compositions of pelagic compartments.

Probably due to its very poor content of labile compounds, the presence of S1 at the bottom of the mesocosms did not induce changes in the biomass of seston and zooplankton. Only few changes in the stoichiometry of these compartments were observed. In contrast, S2 sediment released more phosphorus and dissolved OM into the water column than S1. As a result, the S2 treatment induced an increase in seston biomass and therefore in zooplankton biomass via herbivory.

None of the sediment treatments affected the lipid composition of seston and zooplankton. Moreover, neither S1 nor S2 induced changes in the sedimentation rates, elemental and lipid compositions, and potential biodegradability of recent sediments. Our mesocosm experiment suggests that differences in the quality of lake sediments lead to moderate changes in the pelagic communities in the absence of planktivorous or omnivorous fish.

Our results could partly explain the efficiency of biomanipulation for improving water quality of eutrophic lakes despite potential nutrient release from sediment.
Germline de novo mutations and linkage markers vs. DNA sequencing for carrier detection in von Willebrand disease
Authors: Ahmad F. , Oyen F. , Jan R. , Budde U. , Schneppenheim R. , Saxena R.
Published: April 2014

Linkage analysis in autosomal inherited von Willebrand disease (VWD) is important to diagnose the carriers and reduce the burden of severe type VWD. The study was designed to identify the carriers and estimate the frequency of variable number of tandem repeats (VNTR) instability in VWD families. Carrier detection was performed in eight recessive type 3 VWD (VWD3) families using VNTRs VWF1 and VWF2, RsaI (789Thr/Ala) linkage markers, multimer analysis and DNA sequencing. Moreover, five dominant VWD families were studied through DNA sequencing and multimer analysis. Frequency of VWF VNTR instability was investigated in 20 VWD families. In VWD3 families, a total of 22 (81.5%) carriers were identified using VWF1 and VWF2 markers. However, only 13(48.1%) carriers were identified through RsaI markers. Mutation screening revealed 22(81.5%) carriers in VWD3 and 4 (33.3%) carriers in VWD2 families. In comparison to DNA sequencing, the accuracy of VWF1 and VWF2 markers in VWD3 was 85.7% while RsaI could identify 68.2% carriers accurately. Mutations p.R1205H and p.C1272R were identified as de novo in families. Multimer analysis confirmed the identified carriers in VWD2 families. Three VWD families were found to be carrying VNTR instability for VWF1 and VWF2 locus. VNTRs could be an effective linkage markers for carrier detection in VWD3 families. However, in the event of germline de novo mutations and VNTR instability, it may confound risk of misdiagnosis of carriers. Multimer analysis could be an alternative way of carrier detection in dominant type 2A and type 2B VWD families.
A minimally painful, comfortable, and safe technique for hemodialysis catheter placement in children: Superficial cervical plexus block
Authors: Çiftci Taner , Daskaya Hayrettin , Yıldırım Mehmet B. , Söylemez Haluk
Published: April 2014

The superficial cervical plexus block (SCPB) is utilized in pediatric patients to perform certain surgical procedures, but there is no evidence supporting its use in hemodialysis catheter placement. We evaluated the analgesic effectiveness, intraoperative complications, and patient satisfaction associated with SCPB for pediatric patients in renal failure undergoing emergent dialysis catheterization. A total of 52 patients ranging from 1 to 17 years old that required emergent dialysis catheter placement and received SCPB were included in this study. During the catheterization, intraoperative pain scores, requirement for additional analgesia, catheterization access site, and intraoperative complications were recorded. The Children's Hospital of Eastern Ontario Pain Scale (mCHEOPS) was used to determine pain ratings during skin puncture with the needle, skin dilatation, and securing the catheter with stitches. The patients had an average age of 8.46 ± 5.3 years. The preferred catheterization entry site was through right internal jugular vein, which was achieved in 80.7% of patients. However, 19.3% of patients required access through the right subclavian vein. The average mCHEOPS score during skin puncture was 1.4 ± 0.5, and the mean mCHEOPS score was 2.3 ± 0.6 for skin dilatation. Finally, the average mCHEOPS score while securing the catheter with stitches was 1.3 ± 0.4. No patient required fentanyl for additional analgesia. No intraoperative complications occurred. The benefits gained from using SCPB performed by an experienced anesthesiologist for hemodialysis catheter placement include providing sufficient analgesia and optimal surgical conditions while avoiding the complications associated with general anesthesia for pediatric patients with renal failure.
Pulsatile exposure to simulated reflux leads to changes in gene expression in a 3D model of oesophageal mucosa
Authors: Green Nicola H. , Nicholls Zoe , Heath Paul R. , Cooper‐Knock Jonathan , Corfe Bernard M. , MacNeil Sheila , Bury Jonathan P.
Published: April 2014

Oesophageal exposure to duodenogastroesophageal refluxate is implicated in the development of Barrett's metaplasia (BM), with increased risk of progression to oesophageal adenocarcinoma. The literature proposes that reflux exposure activates NF‐κB, driving the aberrant expression of intestine‐specific caudal‐related homeobox (CDX) genes. However, early events in the pathogenesis of BM from normal epithelium are poorly understood. To investigate this, our study subjected a 3D model of the normal human oesophageal mucosa to repeated, pulsatile exposure to specific bile components and examined changes in gene expression. Initial 2D experiments with a range of bile salts observed that taurochenodeoxycholate (TCDC) impacted upon NF‐κB activation without causing cell death. Informed by this, the 3D oesophageal model was repeatedly exposed to TCDC in the presence and absence of acid, and the epithelial cells underwent gene expression profiling. We identified ~300 differentially expressed genes following each treatment, with a large and significant overlap between treatments. Enrichment analysis (Broad GSEA, DAVID and Metacore™; GeneGo Inc) identified multiple gene sets related to cell signalling, inflammation, proliferation, differentiation and cell adhesion. Specifically NF‐κB activation, Wnt signalling, cell adhesion and targets for the transcription factors PTF1A and HNF4α were highlighted. Our data suggest that HNF4α isoform switching may be an early event in Barrett's pathogenesis. CDX1/2 targets were, however, not enriched, suggesting that although CDX1/2 activation reportedly plays a role in BM development, it may not be an initial event. Our findings highlight new areas for investigation in the earliest stages of BM pathogenesis of oesophageal diseases and new potential therapeutic targets.
Through Thickness Mechanical Properties of Chemical Vapor Infiltration and Nano‐Infiltration and Transient Eutectic‐Phase Processed SiC/SiC Composites
Authors: Shih Chunghao , Katoh Yutai , Ozawa Kazumi , Lara‐Curzio Edgar , Snead Lance
Published: April 2014

The through thickness (interlaminar) shear strength and trans‐thickness tensile strength of three different nuclear‐grade SiC/SiC composites were evaluated at room temperature by the double‐notched shear and diametral compression tests, respectively. With increasing densification of the interlaminar matrix region, a transition in failure locations from interlayer to intrafiber bundle was observed, along with significant increases in the value of the interlaminar shear strength. Under trans‐thickness tensile loading, cracks were found to propagate easily in the unidirectional composite. The 2D woven composite had a higher trans‐thickness tensile strength (38 MPa) because the failure mode involved debonding, fiber pull‐out and fiber failure.
A de novo transcriptome of European pollen beetle populations and its analysis, with special reference to insecticide action and resistance
Authors: Zimmer C. T. , Maiwald F. , Schorn C. , Bass C. , Ott M.‐C. , Nauen R.
Published: April 2014

The pollen beetle Meligethes aeneus is the most important coleopteran pest in European oilseed rape cultivation, annually infesting millions of hectares and responsible for substantial yield losses if not kept under economic damage thresholds. This species is primarily controlled with insecticides but has recently developed high levels of resistance to the pyrethroid class. The aim of the present study was to provide a transcriptomic resource to investigate mechanisms of resistance. cDNA was sequenced on both Roche (Indianapolis, IN, USA) and Illumina (LGC Genomics, Berlin, Germany) platforms, resulting in a total of ∼53 m reads which assembled into 43 396 expressed sequence tags (ESTs). Manual annotation revealed good coverage of genes encoding insecticide target sites and detoxification enzymes. A total of 77 nonredundant cytochrome P450 genes were identified. Mapping of Illumina RNAseq sequences (from susceptible and pyrethroid‐resistant strains) against the reference transcriptome identified a cytochrome P450 (CYP6BQ23) as highly overexpressed in pyrethroid resistance strains. Single‐nucleotide polymorphism analysis confirmed the presence of a target‐site resistance mutation (L1014F) in the voltage‐gated sodium channel of one resistant strain. Our results provide new insights into the important genes associated with pyrethroid resistance in M. aeneus. Furthermore, a comprehensive EST resource is provided for future studies on insecticide modes of action and resistance mechanisms in pollen beetle.
Spinal cord stimulation to achieve wound healing in a primary lower limb critical ischaemia referral centre
Authors: De Caridi Giovanni , Massara Mafalda , David Antonio , Giardina Massimiliano , La Spada Michele , Stilo Francesco , Spinelli Francesco , Grande Raffaele , Butrico Lucia , de Franciscis Stefano , Serra Raffaele
Published: April 2014

Critical lower limb ischaemia is a diffuse pathology that could cause claudication, severe ischaemic pain and tissue loss. The common treatment includes modification of risk factors, pharmacological therapy and endovascular or surgical revascularisation of the lower limb to restore a pulsatile flow distally. Spinal cord stimulator is seen as a valid alternative in patients unsuitable for revascularisation after endovascular or surgical revascularisation failure and as adjuvant therapy in the presence of a functioning bypass in patients with extensive tissue loss and gangrene presenting a slow and difficult wound healing. We report our experience on spinal cord stimulation (SCS) indication and implantation in patients with critical lower limb ischaemia, at a high‐volume centre for the treatment of peripheral arterial disease.
Inching Toward Accountability: The Evolution of Brazil's Anticorruption Institutions, 1985–2010
Authors: Praça Sérgio , Taylor Matthew M.
Published: April 2014

This article analyzes the evolution of the network of Brazilian federal accountability institutions over the course of the past generation, between the transition to democracy and the end of President Luiz Inácio Lula da Silva’s second term. Substantively, the article charts the significant gains that have been made in accountability institutions. Theoretically, it evaluates the evolution of these institutions as a consequence of the distribution of rules, routines, roles, and resources across a larger institutional network, demonstrating that changes in the various bureaucratic agencies have mutually reinforced each other and generated autocatalytic processes of reform.
Adrenomedullin increases the short‐circuit current in the rat prostate: Receptors, chloride channels, the effects of cAMP and calcium ions and implications on fluid secretion
Authors: Liao S. B. , Cheung K. H. , Cheung M. P. L. , Wong P. F. , O W. S. , Tang F.
Published: April 2014

In this study, we have investigated the effects of adrenomedullin on chloride and fluid secretion in the rat prostate. The presence of adrenomedullin (ADM) in rat prostate was confirmed using immunostaining, and the molecular species was determined using gel filtration chromatography coupled with an enzyme‐linked assay for ADM. The effects of ADM on fluid secretion were studied by short‐circuit current technique in a whole mount preparation of the prostate in an Ussing chamber. The results indicated that the ADM level was higher in the ventral than the dorso‐lateral prostate and the major molecular species was the active peptide. ADM increased the short‐circuit current through both the cAMP‐ and calcium‐activated chloride channels in the ventral lobe, but only through the calcium‐activated channels in the dorso‐lateral lobe. These stimulatory effects were blocked by the calcitonin gene‐related peptide (CGRP) receptor antagonist, hCGRP8‐37. We conclude that ADM may regulate prostatic fluid secretion through the chloride channels, which may affect the composition of the seminal plasma bathing the spermatozoa and hence fertility.
White matter microstructural changes in psychogenic erectile dysfunction patients
Authors: Zhang P. , Liu J. , Li G. , Pan J. , Li Z. , Liu Q. , Qin W. , Dong M. , Sun J. , Huang X. , Wu T. , Chang D.
Published: April 2014

Brain dysfunction in erectile dysfunction (ED) has been identified by multiple neuroimaging studies. A recent MRI study indicated grey matter alterations in ED patients. This study aims to investigate the microstructural changes of cerebral white matter (WM) in psychological ED patients and their possible correlations with clinical variables. Twenty‐seven psychological ED patients and 27 healthy subjects (HS) were included and underwent a magnetic resonance (MR) diffusion tensor imaging (DTI) scan. The tract‐based spatial statistics were employed to identify the WM structure alterations in psychological ED patients. The multiple DTI‐derived indices′ [fractional anisotropy (FA), axial diffusivity (AD) and mean diffusivity (MD)] correlations with the symptoms and their durations, respectively, were analysed. The IIEF‐5, quality of erection questionnaire (QEQ) and the self‐esteem and relationship (SEAR) questionnaire were used to assess the symptoms of psychological ED patients. Compared with HS, the psychological ED patients showed increased FA values, reduced MD values and reduced AD values in multiple WM tracts including the corpus callosum (genu, body and splenium), corticospinal tract, internal capsule, corona radiata, external capsule and superior longitudinal fasciculus (p < 0.05, threshold‐free cluster enhancement corrected). Both of the IIEF scores and QEQ scores of ED patients showed a significantly negative correlation with the average FA values, and positive correlation with average AD values and MD values in the splenium of the corpus callosum (p < 0.05). The results provided preliminary evidence of WM microstructural changes in patients with psychological ED. The morphological alterations in the splenium of the corpus callosum were related to the symptom severity.
Protamine mRNA ratio in stallion spermatozoa correlates with mare fecundity
Authors: Paradowska‐Dogan A. , Fernandez A. , Bergmann M. , Kretzer K. , Mallidis C. , Vieweg M. , Waliszewski P. , Zitzmann M. , Weidner W. , Steger K. , Kliesch S.
Published: April 2014

Highly compacted sperm DNA in protamine toroids and a minor fraction of nucleohistones are prerequisites for the efficient transmission of the paternal genome into the oocyte at fertilization. The objective of this study was to evaluate whether protamines might serve as a prognostic factor for stallion fertility. In situ hybridization detected specific expression of P1mRNAin the cytoplasm of stage I to VII spermatids, whereas comparable immunohistochemical stainings showed that protein expression was delayed till elongating spermatids in differentiation stages III to VIII. No staining was detectable in cryptorchid testis because of the lack of spermatids in the seminiferous tubules. Using quantitative real‐time polymerase chain reaction, we identifiedmRNAtranscripts of P1 and 2 variants of protamine‐ 2 (P2, P3) in ejaculated spermatozoa from 45 thoroughbred stallions. According to the mare fertility descriptor (i.e. the ‘none‐return‐rate 28 percentage’ or NRR28%), stallions were divided into three groups (i.e. high, reduced and low fertility). The P2/P1mRNAratio was found to be significantly reduced in the group with lower fertility (p = 0.016) and was slightly correlated with sperm concentration (correlation coefficientr = 0.263). Furthermore, morphologically abnormal sperm count negatively correlated with P2/P1mRNAratio, indicating that spermatozoa carrying head defects display a diminished protamine ratio (r = −0.348). Conversely, the P2/P1 ratio was positively correlated with mare fertility or NRR28% (r = 0.274). Interestingly, P3/P1mRNAratio remained unaltered in the investigated groups indicating that this variant plays a minor role in equine sperm chromatin compaction. Aberrant protamine transcripts content in equine spermatozoa was not associated with DNA defragmentation rate as measured by flow cytometric acridine orange test. On the basis of these results, we suggest that, similar to human, equine protamine expression constitutes a checkpoint of spermatogenesis and as a corollary the level of protaminemRNAmay reflect the quality of spermatogenesis and spermatozoa's fertilizing capacity.
Visit‐to‐Visit Variability of Blood Pressure and Renal Function Decline in Patients With Diabetic Chronic Kidney Disease
Authors: Yokota Kei , Fukuda Masamichi , Matsui Yoshio , Kario Kazuomi , Kimura Kenjiro
Published: April 2014

The authors previously reported that the visit‐to‐visit variability of blood pressure is correlated with renal function decline in nondiabetic chronic kidney disease. Little is known about the association between visit‐to‐visit variability and renal function decline in patients with diabetic chronic kidney disease. The authors retrospectively studied 69 patients with diabetic chronic kidney disease stage 3a, 3b, or 4. The standard deviation and coefficient of variation of blood pressure in 12 consecutive visits were defined as visit‐to‐visit variability of blood pressure. The median observation period was 32 months. In univariate correlation, the standard deviation and coefficient of variation of blood pressure were not significantly associated with the slope of estimated glomerular filtration rate. There was no significant association between the visit‐to‐visit variability of blood pressure and renal function decline in patients with diabetic chronic kidney disease, in contrast with our previous study of nondiabetic patients with chronic kidney disease.
Proteasome inhibitors – molecular basis and current perspectives in multiple myeloma
Authors: Kubiczkova Lenka , Pour Ludek , Sedlarikova Lenka , Hajek Roman , Sevcikova Sabina
Published: April 2014

Inhibition of proteasome, a proteolytic complex responsible for the degradation of ubiquitinated proteins, has emerged as a powerful strategy for treatment of multiple myeloma (MM), a plasma cell malignancy. First‐in‐class agent, bortezomib, has demonstrated great positive therapeutic efficacy in MM, both in pre‐clinical and in clinical studies. However, despite its high efficiency, a large proportion of patients do not achieve sufficient clinical response. Therefore, the development of a second‐generation of proteasome inhibitors (PIs) with improved pharmacological properties was needed. Recently, several of these new agents have been introduced into clinics including carfilzomib, marizomib and ixazomib. Further, new orally administered second‐generation PI oprozomib is being investigated. This review provides an overview of main mechanisms of action of PIs in MM, focusing on the ongoing development and progress of novel anti‐proteasome therapeutics.
Does the dimension of the graft influence patient morbidity and root coverage outcomes? A randomized controlled clinical trial
Authors: Zucchelli Giovanni , Mounssif Ilham , Mazzotti Claudio , Montebugnoli Lucio , Sangiorgi Matteo , Mele Monica , Stefanini Martina
Published: April 2014

Aim

Primary aim of this study was to evaluate if patient morbidity was improved by diminishing graft thickness and height; secondary objective was to evaluate if such graft modifications influence root coverage and aesthetic outcomes.

Methods

60 Miller class I and II gingival recessions (GR) (≥3 mm in depth) were treated with the coronally advanced flap plus extraoral de‐epithelialized free gingival graft (FGG). In 30 randomly selected control GRs (“big graft group”), the FGG thickness was ≥2 mm and the height was equal to bone dehiscence (BD); in the other 30 test defects (“small graft group”), the thickness of the FGG was <2 mm and the height was 4 mm. The post‐operative patient morbidity was assessed 1 week after the surgery. The clinical and aesthetic evaluations were performed 1 year after the surgery.

Results

Lower analgesic assumption, better post‐operative course evaluations, better patient colour match scores and better periodontist aesthetic assessments were reported in the “small graft” group. No statistically significant differences were demonstrated between the two groups in terms of recession reduction, CRC and increase in KTH. Greater GT increase was obtained in the control‐treated sites.

Conclusions

Coronally advanced flap plus CTG of reduced thickness and height was associated with less patient morbidity, better aesthetic evaluations with no difference in RC outcomes.
An RCT comparing patient‐centred outcome variables of guided surgery (bone or mucosa supported) with conventional implant placement
Authors: Vercruyssen Marjolein , De Laat Antoon , Coucke Wim , Quirynen Marc
Published: April 2014

Aim

To assess in a randomized study the patient‐centred outcome of two guided surgery systems (mucosa or bone supported) compared to conventional implant placement, in fully edentulous patients.

Material and Methods

Fifty‐nine patients (72 jaws) with edentulous maxillas and/ or mandibles, were consecutively recruited and randomly assigned to one of the treatment groups. Outcome measures were the Dutch version of the McGill Pain Questionnaire (MPQ‐DLV), the Health‐related quality of life instrument (HRQOL), visual analogue scales (VAS), the duration of the procedure, and the analgesic doses taken each day.

Results

Three hundred and fourteen implants were placed successfully. No statistical differences could be shown between treatment groups on pain response (MPQ‐DLV), treatment perception (VAS) or number or kind of pain killers. For the HRQOLI‐instrument, a significant difference was found between the Materialise Mucosa and Materialise Bone group at day 1 (p = 0.02) and day 2 (p = 0.01). For the duration of the surgery, a statistical difference (p = 0.005) was found between the Materialise mucosa and the Mental group, in favour of the first.

Conclusion

In this study little difference could be found in the patient outcome variables of the different treatment groups. However there was a tendency for patients treated with conventional flapped implant placement to experience the pain for a longer period of time.
Periodontal infection, impaired fasting glucose and impaired glucose tolerance: results from the Continuous National Health and Nutrition Examination Survey 2009–2010
Authors: Arora Nidhi , Papapanou Panos N. , Rosenbaum Michael , Jacobs David R. , Desvarieux Moïse , Demmer Ryan T.
Published: April 2014

Aim

We investigated the relationship between periodontal disease, a clinical manifestation of periodontal infection, and pre‐diabetes.

Methods

The National Health and Nutrition Examination Survey, 2009–2010 enrolled 1165 diabetes‐free adults (51% female) aged 30–80 years (mean ± SD=50 ± 14) who received a full‐mouth periodontal examination and an oral glucose tolerance test. Participants were classified as having none/mild, moderate or severe periodontitis and also according to mean probing depth ≥2.19 mm or attachment loss ≥1.78 mm, (respective 75th percentiles). Pre‐diabetes was defined according to ADA criteria as either: (i) impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). In multivariable logistic regression models, the odds of IFG and IGT were regressed on levels of periodontitis category.

Results

The odds ratios and 95% confidence intervals for having IGT among participants with moderate or severe periodontitis, relative to participants with none/mild periodontitis were 1.07 [0.50, 2.25] and 1.93 [1.18, 3.17], p = 0.02. The ORs for having IFG were 1.14 [0.74, 1.77] and 1.12 [0.58, 2.18], p = 0.84. PD ≥75th percentile was related to a 105% increase in the odds of IGT: OR [95% CI] = 2.05 [1.24, 3.39], p = 0.005.

Conclusions

Periodontal infection was positively associated with prevalent impaired glucose tolerance in a cross‐sectional study among a nationally representative sample.
Editorial: The power of treatment studies to explore causal processes in childhood disorders
Authors: Norbury Courtenay Frazier
Published: April 2014

We all have a tendency to be easily seduced by Occam's razor, or the desire to accept the simplest hypothesis to explain a given phenomenon. If we observe that children with ADHD come from more impoverished backgrounds or have diets that contain more additives than their peers, then a parsimonious theory would be that poverty and/or diet are causal factors in the development of ADHD. Such theories are all the more attractive because they suggest potential targets for intervention: improve family circumstances and child diet and symptoms of ADHD should diminish. Of course in reality untangling causal relationships is much more complicated. We now accept that many common disorders reflect the confluence of genetic and environmental risk factors, but that any given risk factor is likely to account for only a tiny amount of explained variance in symptom profile. What's more, in order to fulfil the promise of intervention, we must begin to unravel the precise mechanisms by which identified risk factors affect the developing system. This issue showcases two key methodologies for understanding causal influences on developmental disorders: longitudinal designs and well‐controlled intervention studies. Both may employ statistical techniques that can identify the mediators of observed associations, elucidating potential mechanistic processes.