bluuebunny/crossref_metadata_2025 huggingface dataset:
Ex VivoEquine Medial Tibial Plateau Contact Pressure With an Intact Medial Femoral Condyle, With a Medial Femoral Condylar Defect, and After Placement of a Transcondylar Screw Through the Condylar Defect
Authors: Bonilla Alvaro G. , Williams Jarred M. , Litsky Alan S. , Santschi Elizabeth M.
Published: August 2014

Objective

To determineex vivocontact data on the equine medial tibial plateau loaded by an intact medial femoral condyle (MFC), by an MFC with an osteochondral defect, and with a screw inserted in lag fashion through the MFC defect.

Study Design

Ex vivoexperiment.

Animals

Stifles (n = 6). Horses (n = 4).

Methods

Stifle joints were axially loaded to 1800 N at 155°, 145°, and 130°, under 3 conditions: Intact, MFC with a 15 mm circular osteochondral defect, and with a transcondylar screw inserted in lag fashion through the defect. An electronic pressure sensor (Tekscan®) on the medial tibial plateau recorded contact area, force, peak pressure, and contact maps. Stress load (N/cm2) was calculated for the entire medial plateau and in 3 sub‐regions; cranial, caudal, and central. Significance was set atP ≤ .05.

Results

Flexion increased force, contact area, and stress load for all conditions. An MFC defect significantly reduced force at both flexion angles and contact area at 145°. The transcondylar screw returned force to intact values at 130° and reduced contact area in extension. Intact MFC contact maps revealed pressure peaks on the central cartilage at all angles and contact pressure and area expansion and caudal movement with flexion. Contact maps with an MFC defect amplified the caudal and abaxial pressure movement during flexion, and the screw did not further change them.

Conclusions

Stifle flexion increases force, contact area, and stress load on the medial tibial plateau and is most pronounced caudally. An MFC defect alters load on the medial tibial plateau, and a transcondylar screw may reverse some of those changes.
A randomized controlled trial of fentanyl in the pre‐emptive treatment of pain associated with turning in patients under mechanical ventilation: research protocol
Authors: Robleda Gemma , Roche‐Campo Ferran , Urrútia Gerard , Navarro Marta , Sendra Maria‐Àngels , Castillo Ana , Rodríguez‐Arias Ainhoa , Juanes‐Borrejo Elena , Gich Ignasi , Mancebo Jordi , Baños Josep‐E.
Published: August 2014

Aim

To compare the effectiveness and safety of fentanyl with placebo as pre‐emptive treatment for pain associated with turning in patients in intensive care units.

Background

Turning is frequently a painful procedure in this setting. Pre‐emptive administration of supplementary analgesia may help decrease this pain. However, medical literature on pre‐emptive analgesia in these patients is scarce.

Design

A randomized, double‐blind, controlled clinical trial.

Methods

This study will assess the benefits and risks of pre‐emptive analgesia with fentanyl compared with placebo on turning‐associated pain. Eighty patients will be recruited from among those older than 18 years and needing mechanical ventilation for at least 24 hours. Pain intensity will be assessed using the Behavioral Pain Scale. Primary outcome will be pain intensity between the baseline and 30 minutes after turning, measured by the area under the curve of the pain scale scores. Secondary outcomes will be the usefulness of physiological parameters and the Bispectral Index to measure pain and the safety of pre‐emptive fentanyl in turning. The study protocol was approved in February 2011.

Discussion

If pre‐emptive fentanyl is more effective than placebo and reasonably safe, the results of the current study may change nursing attitude in managing turning in critically ill patients. As a consequence, pain may be decreased during this nursing procedure.
Decreased expression of microRNA‐21 correlates with the imbalance of Th17 and Treg cells in patients with rheumatoid arthritis
Authors: Dong Liyang , Wang Xuefeng , Tan Jun , Li Hao , Qian Wei , Chen Jianguo , Chen Qiaoyun , Wang Jun , Xu Wenlin , Tao Caihua , Wang Shengjun
Published: August 2014

The imbalance of Th17/Treg cell populations has been suggested to be involved in the regulation of rheumatoid arthritis (RA) pathogenesis; however, the mechanism behind this phenomenon remains unclear. Recent studies have shown how microRNAs (miRNAs) are important regulators of immune responses and are involved in the development of a variety of inflammatory diseases, including RA. In this study, we demonstrated that the frequencies of CD3+CD4+IL‐17+Th17 cells were significantly higher, and CD4+CD25+FOXP3+ Treg cells significantly lower in peripheral blood mononuclear cells from RA patients. Detection of cytokines from RA patients revealed an elevated panel of pro‐inflammatory cytokines, including IL‐17, IL‐6, IL‐1β, TNF‐α and IL‐22, which carry the inflammatory signature of RA and are crucial in the differentiation and maintenance of pathogenic Th17 cells and dysfunction of Treg cells. However, the level of miR‐21 was significantly lower in RA patients, accompanied by the increase in STAT3 expression and activation, and decrease in STAT5/pSTAT5 protein and Foxp3 mRNA levels. Furthermore, lipopolysaccharide stimulation up‐regulated miR‐21 expression from healthy controls, but down‐regulated miR‐21 expression from RA patients. Therefore, we speculate that miR‐21 may be part of a negative feedback loop in the normal setting. However, miR‐21 levels decrease significantly in RA patients, suggesting that this feedback loop is dysregulated and may contribute to the imbalance of Th17 and Treg cells. MiR‐21 may thus serve as a novel regulator in T‐cell differentiation and homoeostasis, and provides a new therapeutic target for the treatment of RA.
Detection of Invalid Test Scores: The Usefulness of Simple Nonparametric Statistics
Authors: Tendeiro Jorge N. , Meijer Rob R.
Published: August 2014

In recent guidelines for fair educational testing it is advised to check the validity of individual test scores through the use of person‐fit statistics. For practitioners it is unclear on the basis of the existing literature which statistic to use. An overview of relatively simple existing nonparametric approaches to identify atypical response patterns is provided. A simulation study was conducted to compare the different approaches and on the basis of the literature review and the simulation study guidelines for the use of person‐fit approaches are given.
A common variant in the glucokinase regulatory gene rs780094 and risk of nonalcoholic fatty liver disease: A meta‐analysis
Authors: Zain Shamsul Mohd , Mohamed Zahurin , Mohamed Rosmawati
Published: August 2014

Background and Aim

Although studies have suggested that rs780094, a common variant in the glucokinase regulatory (GCKR) gene to be associated with type 2 diabetes, obesity, and their related traits, the genetic basis of the association between GCKR rs780094 and nonalcoholic fatty liver disease (NAFLD) is still being examined. This meta‐analysis was performed to evaluate the effect strength caused by GCKR rs780094 on NAFLD.

Methods

We searched Medline, PubMed, Scopus, and Embase for relevant articles published up to April 2014. Data were extracted, and summary estimates of the association between GCKR rs780094 and NAFLD were examined. Heterogeneity and publication bias were also examined.

Results

This meta‐analysis incorporated a total of 2091 NAFLD cases and 3003 controls from five studies. Overall, the pooled result indicated that the GCKR rs780094 was significantly associated with increased risk of NAFLD (additive: odds ratio (OR) 1.25, 95% confidence interval (CI) 1.14–1.36, P < 0.00001). Analysis also revealed significant associations with different alternative genetic models for the inheritance: dominant, recessive, and homozygote (OR 1.40, 95%CI 1.23–1.61, P < 0.00001; OR 0.79, 95% CI 0.68–0.91, P = 0.001, and; (OR 1.27, 95% CI 1.10–1.47, P = 0.001, respectively), but not the heterozygote model. Population subgroup analysis demonstrated similar effect size in both Asians and non‐Asians (OR 1.27, 95%CI 1.12–1.45, P = 0.0003 and OR 1.22, 95%CI 1.10–1.37, P = 0.0003, respectively).

Conclusions

Our meta‐analysis provides evidence of significant association between GCKR rs780094 and risk of NAFLD. Similar effect size was demonstrated in both Asian and non‐Asian populations.
Long‐term lamivudine treatment achieves regression of advanced liver fibrosis/cirrhosis in patients with chronic hepatitis B
Authors: Xu Bei , Lin Lanyi , Xu Guoguang , Zhuang Yan , Guo Qing , Liu Yunye , Wang Hui , Zhou Xiaqiu , Wu Shanming , Bao Shisan , Cai Wei , Xie Qing
Published: August 2014

Background and Aim

Antiviral therapy is important in advanced liver fibrosis/cirrhosis with chronic hepatitis B (AdLF‐CHB) patients, but complete regression of cirrhosis remains to be the challenge. We aimed to investigate whether up to 10 years lamivudine treatment achieves liver fibrosis/cirrhosis regression in AdLF‐CHB patients.

Methods

Improvement of hepatic fibrosis/cirrhosis, virological response and disease progression were evaluated in 28 AdLF‐CHB patients with up to 10 years lamivudine treatment. Liver biopsy was performed in all of the 28 patients at baseline, but only 19 patients had second biopsy at year 10.

Results

There were 24 hepatitis B e antigen (HBeAg)‐positive and 4 HBeAg‐negative patients within the original 28 AdLF‐CHB patients. At the end of 10 years lamivudine treatment, 20 of the 24 HBeAg‐positive patients had HBeAg loss. HBeAg seroconversion was detected in 10 of these 20 HBeAg loss patients. HBsAg loss was observed in 4 of the original 28 patients. Among these four HBsAg loss patients, three had HBsAg seroconversion. All patients achieved hepatitis B virus DNA (HBV DNA) undetectable. Histopathology was evaluated between paired original and final liver biopsies among 19 patients as follows: 4/19 achieved complete liver fibrosis/cirrhosis regression; 9/19 improved in Ishak fibrosis score; whereas 6/19 showed no fibrosis improvement. About 75% patients achieved inflammatory/fibrotic improvement. No significant disease progression was observed in 24/28 patients. Furthermore, no significant difference in histopathology improvement, cirrhosis regression, disease progression between non‐resistance and rescue for resistance was observed.

Conclusion

Long‐term lamivudine therapy achieves regression of fibrosis/cirrhosis and improvement of histological and disease progression in AdLF‐CHB patients.
Inconsistent hepatic antifibrotic effects with the iron chelator deferasirox
Authors: Sobbe Amy , Bridle Kim R , Jaskowski Lesley , de Guzman C Erika , Santrampurwala Nishreen , Clouston Andrew D , Campbell Catherine M , Subramaniam V Nathan , Crawford Darrell H G
Published: August 2014

Background and Aim

Development of effective antifibrotic treatments that can be translated to clinical practice is an important challenge in contemporary hepatology. A recent report on β‐thalassemia patients demonstrated that deferasirox treatment reversed or stabilized liver fibrosis independent of its iron‐chelating properties. In this study, we investigated deferasirox in cell and animal models to better understand its potential antifibrotic effects.

Methods

The LX‐2 stellate cell line was treated with 5 μM or 50 μM deferasirox (Exjade, Novartis Pharmaceuticals Australia, North Ryde, NSW, Australia) for up to 120 h. Three‐week‐old multidrug resistance 2 null (Mdr2–/–) mice received oral deferasirox or vehicle for 4 weeks (30 mg/kg/day). Cells and liver tissue were collected for assessment of fibrosis and fibrogenic gene expression.

Results

In LX‐2 cells treated with 50 μM deferasirox for 12 h, α1(I)procollagen expression was decreased by 25%, with maximal reductions (10‐fold) seen following 24–120 h of treatment. Similarly, α‐smooth muscle actin (αSMA) expression was significantly lower. Alterations in matrix remodeling genes, specifically decreased expression of matrix metalloproteinase‐2 and tissue inhibitor of metalloproteinase‐2, were observed. There was no significant difference in hepatic hydroxyproline content in Mdr2–/– mice following deferasirox administration (vehicle: 395 ± 27 μg/g vs deferasirox: 421 ± 33 μg/g). Similarly, no changes in the expression of fibrogenic genes were observed.

Conclusion

Despite reductions in α1(I)procollagen and αSMA expression and alterations in matrix degradation genes in LX‐2 cells, deferasirox did not exhibit antifibrotic activity in Mdr2–/– mice. Given the positive outcomes seen in human trials, it may be appropriate to study deferasirox in other animal models of fibrosis and/or for a longer duration of therapy.
Association of downregulation of WWOX with poor prognosis in patients with intrahepatic cholangiocarcinoma after curative resection
Authors: Huang Changjun , Tian Yuan , Peng Rui , Zhang Changhe , Wang Dong , Han Sheng , Jiao Chenyu , Wang Xing , Zhang Hai , Wang Yun , Li Xiangcheng
Published: August 2014

Background and Aim

Downregulation of the WW domain containing oxidoreductase (WWOX) has been reported to be involved in tumorigenesis in several neoplasms. This study sought to investigate the expression and role of WWOX in intrahepatic cholangiocarcinoma (ICC).

Methods

WWOX expression was measured by quantitative real‐time polymerase chain reaction (PCR), immunoblot, immunofluorescence, and immunohistochemistry. The prognostic significance was assessed by Kaplan–Meier and Cox regression analyses. The role of WWOX in proliferation, anchorage‐independent growth, gene expression regulation, and tumorigenesis was assessed by WWOX re‐expression using lentivirus. Methylation‐specific PCR was performed to evaluate the methylation status of the WWOX gene regulatory region. A DNA methyltransferase inhibitor, 5‐aza‐2′‐deoxycytidine (AZA), was used to activate the endogenous WWOX gene in ICC cells both in vitro and in vivo.

Results

The expression of WWOX in ICC tissues was much lower than that in nontumorous samples and showed reverse correlation with proliferative status. Restoration of WWOX expression resulted in suppression of the growth of WWOX‐deficient ICC cells through activation of the intrinsic apoptotic signaling pathway, but did not affect growth of WWOX‐sufficient human intrahepatic biliary epithelial derived non‐cancer cells. Multivariate analyses revealed that downregulation of WWOX was an unfavorable predictor for overall survival and cumulative recurrence rates. The WWOX gene regulatory region was frequently methylated in ICC tissues and cell lines, and intratumoral WWOX restoration, through AZA injection, suppressed tumor growth in nude mice.

Conclusion

Downregulation of WWOX may occur as a result of hypermethylation and implies a poor prognosis in ICC; WWOX re‐expression may be a potential molecular therapeutic target for ICC.
Small intestinal contrast ultrasonography for the detection of small bowel complications in Crohn's disease: Correlation with intraoperative findings and magnetic resonance enterography
Authors: Kumar Shankar , Hakim Aishah , Alexakis Christopher , Chhaya Vivek , Tzias Demitrios , Pilcher James , Vlahos Johnny , Pollok Richard
Published: August 2014

Background and Aims

In evaluating small bowel Crohn's disease (CD), small intestine contrast‐enhanced ultrasonography (SICUS) is emerging as an alternative to magnetic resonance enterography (MRE). This retrospective study compared the diagnostic accuracy of SICUS and MRE with surgical findings, and their level of agreement.

Methods

We identified a cohort of CD patients investigated by either SICUS and/or MRE that subsequently required resective bowel surgery within 6 months. The accuracy and agreement of SICUS and MRE to detect small bowel complications were compared with intraoperative findings using kappa coefficient (κ). Agreement between SICUS and MRE in those undergoing both modalities was also assessed.

Results

A total of 67 patients were evaluated; 25 underwent SICUS and 17 underwent MRE prior to surgery. Another 25 patients underwent both SICUS and MRE. When compared with intraoperative findings, the sensitivity of SICUS and MRE was 87.5% and 100%, respectively, in detecting strictures, 87.7% and 66.7% for fistulae, 100% for both in identifying abscesses, 100% and 66.7% for bowel dilatation, and 94.7% and 81.8% in defining bowel wall thickening. When correlating SICUS and MRE with surgery, there was a high level of agreement in localizing strictures (κ = 0.75, 0.88, respectively), fistulae (κ = 0.82, 0.79) and abscesses (κ = 0.87, 0.77). Concordance between SICUS and MRE was substantial or almost complete in identifying stricturing disease (κ = 0.84), their number and location (κ = 0.85), fistulae (κ = 0.65), and mucosal thickening (κ = 0.61).

Conclusion

SICUS accurately identified small bowel complications and correlated well with MRE and intraoperative findings. SICUS offers an alternative in the preoperative assessment of CD.
Long‐term clinical outcome of patients with cirrhosis and refractory ascites treated with transjugular intrahepatic portosystemic shunt insertion
Authors: Tan Hiang Keat , James Paul Damien , Sniderman Kenneth Wilfred , Wong Florence
Published: August 2014

Background and Aim

Transjugular intrahepatic portosystemic shunt (TIPS) is indicated for the treatment of refractory ascites in cirrhosis. The long‐term outcome of TIPS for refractory ascites is unknown. The aim of this study is to describe the natural history of patients with refractory ascites post‐TIPS, and compare between polytetrafluoroethylene (PTFE)‐covered versus bare stents.

Methods

A retrospective chart review of patients who had TIPS for refractory ascites was conducted. Prospectively collected data include demographics, angiographic data, blood work, and urinary sodium excretion.

Results

There were 136 patients who received TIPS (bare = 104, covered = 32) for over 22 years. Patients with PTFE stents had lower international normalized ratio and model for end‐stage liver disease score. More patients with bare stents developed shunt dysfunction (74.0% vs 24.1%, P < 0.0001) and required more TIPS revisions (1.6 ± 0.2/patient vs 0.2 ± 0.1, P < 0.0001). Urinary sodium excretion increased significantly from first month and progressed to 98 ± 9 mmol/day at 12th month post‐TIPS (P < 0.001 vs baseline), concurrent with improved renal function. Most patients (77.6%) completely cleared the ascites without diuretics, but many achieved this beyond 2 years. Number of TIPS revision was predictive of complete response at 12 months (odds ratio [OR] 0.7, 95% confidence interval [CI] 0.5–0.9, P < 0.05). Age (hazard ratio [HR] = 1.05 [95% CI 1.02–1.08], P < 0.01), complete response (HR = 0.22 [95% CI 0.12–0.40], P < 0.0001) and polytetrafluoroethylene stents (HR = 0.23 [95% CI 0.05–0.97], P < 0.05) were predictive of survival.

Conclusion

TIPS is an effective treatment for cirrhotic refractory ascites. Ascites clearance is dependent on number of TIPS revision, whereas survival is predicted by younger age, complete response, and covered stent use, although era effect likely contributed to improved survival with covered stent use.
Use of non‐invasive serum glycan markers to distinguish non‐alcoholic steatohepatitis from simple steatosis
Authors: Yamasaki Yasushi , Nouso Kazuhiro , Miyahara Koji , Wada Nozomu , Dohi Chihiro , Morimoto Yuki , Kinugasa Hideaki , Takeuchi Yasuto , Yasunaka Tetsuya , Kuwaki Kenji , Onishi Hideki , Ikeda Fusao , Miyake Yasuhiro , Nakamura Shinichiro , Shiraha Hidenori , Takaki Akinobu , Iwasaki Yoshiaki , Amano Maho , Nishimura Shin‐Ichiro , Yamamoto Kazuhide
Published: August 2014

Background and Aims

Serum glycans have been reported to be promising diagnostic markers for many inflammatory diseases and cancers. The aims of this study were to investigate whole glycan expression in patients with non‐alcoholic fatty liver diseases and to evaluate the potential use of glycan profiles as new clinical biomarkers to distinguish non‐alcoholic steatohepatitis (NASH) from simple steatosis (SS).

Methods

We collected sera from 42 histologically proven NASH and 15 SS patients prior to treatment. Serum glycan profiles were measured by comprehensive, quantitative, high‐throughput glycome analysis, and diagnostic values of serum glycans for NASH prediction were examined.

Results

Among the 41 serum glycans examined, the expression levels of 8 glycans in NASH were significantly higher than those of SS. Out of these eight glycans, three glycans (m/z 1955, 2032, and 2584) showed high areas under the receiver operating characteristic curve (0.833, 0.863, and 0.866, respectively) for distinguishing NASH from SS. In multivariate analyses with clinical parameters and serum glycans, these three glycans were significant predictive factors for distinguishing NASH from SS. The odds ratio of m/z 1955, 2032, and 2584 were 48.5, 6.46, and 11.8, respectively. These glycans also correlated significantly with lobular inflammation, ballooning, and fibrosis, but not with steatosis.

Conclusion

We clearly demonstrated whole‐serum glycan profiles in NASH patients, and the feasibility of serum glycans (m/z 1955, 2032, and 2584) as new noninvasive biomarkers for distinguishing NASH from SS.
Safety and efficacy of entecavir in adefovir‐experienced patients
Authors: Nguyen Nghia H , Trinh Huy N , Nguyen Thuan T , Do Son T , Tran Phuong , Nguyen Huy A , Nguyen Khanh K , Garcia Ruel T , Lutchman Glen A , Nguyen Mindie H
Published: August 2014

Background and Aim

Suboptimal viral suppression with adefovir (ADV) poses a challenge in managing chronic hepatitis B. Few studies have evaluated the efficacy of entecavir (ETV) in ADV‐experienced patients. Our aim is to assess treatment effectiveness of ETV in ADV‐experienced patients.

Methods

ADV‐experienced patients switched to ETV were enrolled from six US clinics. Patients completed a median of 24 months of ETV after switch. Patients were categorized into partial responders (detectable HBV‐DNA at switch) or complete responders (undetectable HBV‐DNA at switch) to ADV. Primary and secondary outcome measurements were complete viral suppression (CVS, HBV‐DNA < 60 IU/mL) and biochemical response (BR, alanine aminotransferase [ALT] < 40 U/L), respectively.

Results

A total of 120 patients were included in the analysis (80 ADV partial responders; 40 ADV complete responders). In partial responders, CVS rate was 84% after 24 months of ETV. BR rate was 58% at switch to ETV and increased to 90% after 24 months. All complete responders continued to experience CVS after switch. On multivariate analysis inclusive of age, male gender, ALT level at switch, and history of lamivudine (LAM) exposure, we identified positive, hepatitis B e antigen status before ADV and higher HBV‐DNA level at time of switch as significant independent negative predictors of CVS. In eight patients with ADV resistance, seven achieved CVS after 24 months of ETV, and all achieved BR.

Conclusion

In ADV‐experienced patients, high rates of CVS and BR can be achieved/sustained after switching to ETV, including those with ADV resistance or with prior exposure to LAM.
Congenital toxoplasmosis from a mother with type 2 diabetes mellitus: A case report
Authors: Sato Shimpei , Nishida Masakazu , Nasu Kaei , Narahara Hisashi , Norose Kazumi , Aosai Fumie
Published: August 2014

A 33‐year‐old woman with type 2 diabetes mellitus (DM) was suspected of being primarily infected with Toxoplasma gondii at 12 weeks of gestation (GW). Although acetylspiramycin was started at 17 GW, the T. gondii DNA gene was detected in the amniotic fluid at 18 GW. Chemotherapy was changed to pyrimethamine plus sulfadiazine from 20 GW, but was changed back to acetylspiramycin after 2 weeks because of vomiting. Acetylspiramycin was continued until her delivery. DM was controlled well during the pregnancy. An asymptomatic male baby was born by cesarean section at 37 GW, and was treated with acetylspiramycin for 4 weeks because the polymerase chain reaction results of umbilical cord blood were positive. He has developed normally until the present, that is, 6 months of age. Herein, we describe a case report in which symptomatic congenital toxoplasmosis was avoided in a pregnant woman with an immunosuppressive risk due to prompt chemotherapy.
Fatal case of multiple recurrences of endometrial stromal sarcoma after fertility‐sparing management
Authors: Morimoto Atsushi , Tsubamoto Hiroshi , Inoue Kayo , Ikeda Yuuki , Hirota Seiichi
Published: August 2014

Several cases of the uterus being preserved after diagnosis of endometrial stromal sarcoma (ESS) have been reported. Most of these patients were alive and did not experience relapse, but this might have reflected the short follow‐up period, given the indolent recurrence of ESS. We report the first fatal case of ESS 10 years after fertility‐sparing management. A specimen obtained from the last operation showed loss of estrogen receptor status and expression of c‐kit without c‐kit or PDGFR‐α gene mutations.
Days of Labour: Topographies of Power in Modern Peripheral Capitalism. The Case of The Industrial City ofŁódź
Authors: Marzec Wiktor , Zysiak Agata
Published: August 2014

The article investigates the city ofŁódź as an exceptional case of a settlement constitutive of different kinds and techniques of power typical of nineteenth century industrial capitalism. We considerFoucault's disciplinary power/biopower through the convergence of the paternalistic gaze of the factory owner, and theTsarist rule in theScheibler andGrohman industrial establishment and the nearby workers housing estate. The aim of this article is to investigate a specificlocusof peripheral capitalism and the relations accompanying it through theFoucauldian analysis of power. We argue that unique and unstable patterns of correlation of power techniques emerged here. Power is no longer strictly related to the temporal matrix or the functional demands of capitalist production, and only temporarily ossified in contingent configurations. WhileFoucault's canonical theoretical premises and concepts are of explanatory value, the very relations between them become problematic when confronted with the particular entanglement inŁódź. Therefore we opt for the new paradigm of power analysis throughS.J.Collier's “topological analysis”.
Elevation in 5‐FU‐induced apoptosis in Head and Neck Cancer Stem Cells by a combination of CDHP and GSK3β inhibitors
Authors: Shigeishi Hideo , Biddle Adrian , Gammon Luke , Rodini Camila O. , Yamasaki Miho , Seino Sayaka , Sugiyama Masaru , Takechi Masaaki , Mackenzie Ian C.
Published: August 2014

Background

Cancer stem cells (CSCs) are involved in both tumourigenesis and in tumour recurrence after therapy. In head and neck squamous cell carcinoma (HNSCC), there are two biologically different CSC phenotypes both of which express high levels of CD44 but differ in their expression levels of epithelial‐specific antigen (ESA). One phenotype is CD44high/ESAhigh and has epithelial features (Epi‐CSCs), while the other is CD44high/ESAlow, has undergone epithelial to mesenchymal transition (EMT‐CSCs), has mesenchymal features and is migratory (Biddle et al., 2011). CSCs are resistant to therapeutically induced apoptosis but the molecular mechanisms by which they develop apoptotic resistance remains unclear. However, glycogen synthase kinase 3β (GSK3β) contributes to regulation of both the self‐renewal and switching of these two CSC phenotypes (Shigeishi et al., 2013).

Methods

CD44high/ESAlow, CD44high/ESAhigh and CD44low cells were FACS sorted from the HNSCC cell line LUC4, and 5‐FU‐induced apoptosis was analysed by Annexin V staining followed by flow cytometry analysis.

Results

CD44high/ESAlow cells exhibited marked resistance to 5‐FU‐induced apoptosis and had high expression of dihydropyrimidine dehydrogenase (DPD). The DPD inhibitor, 5‐chloro‐2, 4‐dihydroxypyridine (CDHP) significantly enhanced 5‐FU‐induced apoptosis of CD44high/ESAlow cells. Inhibition of GSK3β induced CD44high/ESAlow cells to undergo mesenchymal‐to‐epithelial transition (MET) to CD44high/ESAhigh cells and pre‐existing CD44high/ESAhigh cells to differentiate. Apoptosis induced by 5‐FU was thus facilitated. Combination of both CDHP and GSK3β inhibitors markedly enhanced 5‐FU‐induced apoptosis of CD44high/ESAlow cells.

Conclusions

Our results suggest potentially new approaches for the elimination of the therapy resistant HNSCC CSC population.
Gene–environment interaction and susceptibility in head and neck cancer patients and in their first‐degree relatives: a study of Northeast Indian population
Authors: Choudhury Javed Hussain , Ghosh Sankar Kumar
Published: August 2014

Background

The environmental and genetic factors are known to be associated with head and neck squamous cell carcinoma (HNSCC). Here, we investigated the GSTM1 and GSTT1 polymorphisms and tobacco uses in patients and in their first‐degree relatives to evaluate susceptibility toward HNSCC. Further, we explored high‐risk interaction between genetic and environmental risk factors.

Subjects and methods

Genotyping of GSTM1 and GSTT1 was performed in 170 patients, 300 first‐degree relatives of patients and 300 controls using multiplex PCR. Multifactor dimensionality reduction (MDR) and logistic regression approach were applied for statistical analysis.

Results

Analysis revealed that GSTM1 and GSTT1 null genotype frequencies were significantly higher in patients (adjusted odds ratio (OR) = 2.18; P < 0.001 and OR = 1.61; P = 0.031, respectively). Also, the GSTM1 and GSTT1 null genotype frequencies were significantly higher in first‐degree relatives of patients compared with controls (P = 0.004 and P = 0.041, respectively). In MDR analysis, the best model for HNSCC risk was four‐factors model of tobacco, betel quid chewing, smoking and GSTM1 null genotypes (cross‐validation consistency = 10/10 and P < 0.0001), whereas in interaction entropy graphs, tobacco chewing and GSTM1 null genotype further showed strongest synergistic interaction.

Conclusion

GSTM1 and GSTT1 null genotypes may act as markers to determine the genetic susceptibility in HNSCC patients and in their first‐degree relatives. Furthermore, tobacco chewing and GSTM1 null genotype interaction identified as the strongest gene‐environment model to predict HNSCC.
A Meta‐Analytic Test of Redundancy and Relative Importance of the Dark Triad and Five‐Factor Model of Personality
Authors: O'Boyle Ernest H. , Forsyth Donelson R. , Banks George C. , Story Paul A. , White Charles D.
Published: August 2014

We examined the relationships between Machiavellianism, narcissism, and psychopathy—the three traits of the Dark Triad (DT)—and the Five‐Factor Model (FFM) of personality. The review identified 310 independent samples drawn from 215 sources and yielded information pertaining to global trait relationships and facet‐level relationships. We used meta‐analysis to examine (a) the bivariate relations between the DT and the five global traits and 30 facets of the FFM, (b) the relative importance of each of the FFM global traits in predicting DT, and (c) the relationship between the DT and FFM facets identified in translational models of narcissism and psychopathy. These analyses identified consistent and theoretically meaningful associations between the DT traits and the facets of the FFM. The five traits of the FFM, in a relative importance analysis, accounted for much of the variance in Machiavellianism, narcissism, and psychopathy, respectively, and facet‐level analyses identified specific facets of each FFM trait that were consistently associated with narcissism (e.g., angry/hostility, modesty) and psychopathy (e.g., straightforwardness, deliberation). The FFM explained nearly all of the variance in psychopathy (R2c = .88) and a substantial portion of the variance in narcissism (R2c = .42).
Specific and Sensitive Detection of Phytophthora nicotianae by Nested PCR and Loop‐mediated Isothermal Amplification Assays
Authors: Li Benjin , Liu Peiqing , Xie Shiyong , Yin Rongmei , Weng Qiyong , Chen Qinghe
Published: August 2014

Phytophthora nicotianae is an important soilborne plant pathogen. It causes black shank in tobacco and other commercially important crop diseases. Early and accurate detection of P. nicotianae is essential for controlling these diseases. In this study, primers based on the Ras‐related protein gene (Ypt1) of P. nicotianae were tested for their specific detection of the pathogen using nested PCR and LAMP assays. For specificity testing, DNA extracts from 47 P. nicotianae isolates, 45 isolates of 16 different oomycetes and 25 isolates of other fungal species were used; no cross‐reaction with other pathogens was observed. The sensitivity assay showed that the nested PCR and LAMP assays had detection limits of 100 fg and 10 fg genomic DNA per 25‐μl reaction, respectively. Furthermore, the nested PCR and LAMP assays were used for the detection of DNA from naturally P. nicotianae‐infected tobacco tissues and soil. Our results suggest that the LAMP assay has the greatest potential for the specific detection of P. nicotianae in regions that are at risk of contracting tobacco black shank disease and that the Ypt1 gene is a novel and effective target of P. nicotianae LAMP visual detection.
Phylogenetic trait conservation in the partner choice of a group of ectomycorrhizal trees
Authors: Hayward Jeremy , Horton Thomas R.
Published: August 2014

Ecological interactions are frequently conserved across evolutionary time. In the case of mutualisms, these conserved interactions may play a large role in structuring mutualist communities. We hypothesized that phylogenetic trait conservation could play a key role in determining patterns of association in the ectomycorrhizal symbiosis, a globally important trophic mutualism. We used the association between members of the pantropical plant tribe Pisonieae and its fungal mutualist partners as a model system to test the prediction that Pisonieae‐associating ectomycorrhizal fungi will be more closely related than expected by chance, reflecting a conserved trait. We tested this prediction using previously published and newly generated sequences in a Bayesian framework incorporating phylogenetic uncertainty. We report that phylogenetic trait conservation does exist in this association. We generated a five‐marker phylogeny of members of the Pisonieae and used this phylogeny in a Bayesian relaxed molecular clock analysis. We established that the most recent common ancestors of Pisonieae species and Pisonieae‐associating fungi sharing phylogenetic conservation of their patterns of ectomycorrhizal association occurred no more recently than 14.2 Ma. We therefore suggest that phylogenetic trait conservation in the Pisonieae ectomycorrhizal mutualism association represents an inherited syndrome which has existed for at least 14 Myr.
Clausena agasthyamalayana sp. nov. (Rutaceae) from Kerala, India
Authors: Kumar E. S. Santhosh , Shareef S. M. , Roy P. E. , Veldkamp J. F.
Published: August 2014

A new species of Clausena, C. agasthyamalayana is described and illustrated from the southern Western Ghats, Kerala, India. It is similar to C. indica but differs from it being of dwarf habit, and having greenish–black bark, smaller and fewer leaflets, obovate and coriaceous leaves with obtuse or emarginated apex, elliptic and obtuse petals, oblong‐cordate anthers, consistently 4‐locular ovary with 2 ovules in each chamber and ellipsoid fruits.
Advances in epilepsy treatment: lacosamide pharmacokinetic profile
Authors: Cawello Willi , Stockis Armel , Andreas Jens‐Otto , Dimova Svetlana
Published: August 2014

Lacosamide (LCM) is a functionalized amino acid specifically developed for use as an antiepileptic drug (AED) and is currently indicated as adjunctive treatment for partial‐onset seizures in adults with focal epilepsy (maximum approved dose 400 mg/day). Characterization of the pharmacokinetic profile is an important aspect in the development of LCM. Studies in healthy subjects and in patients with focal epilepsy have established that LCM has several favorable pharmacokinetic characteristics, including rapid absorption and high oral bioavailability not affected by food, linear and dose‐proportional pharmacokinetics, low inter‐ and intraindividual variability, low plasma protein binding, renal elimination, and a low potential for clinically relevant pharmacokinetic drug–drug interactions both with AEDs and other common medications. Studies have demonstrated bioequivalence among the three LCM formulations (oral tablets, oral solution, and solution for intravenous (IV) infusion), allowing direct conversion to or from oral and IV administration without titration. Thus, the favorable and predictable pharmacokinetic profile and bioequivalence of LCM formulations, coupled with the low potential for clinically relevant pharmacokinetic drug–drug interactions, make LCM an easy‐to‐use adjunctive treatment for the management of patients with focal epilepsy.
The effects of plant traits on species' responses to present and historical patch configurations and patch age
Authors: Hemrová Lucie , Münzbergová Zuzana
Published: August 2014

Patch configuration is viewed as an important factor affecting the distributions of plant species. Although a number of studies have explored the relationship between plant life‐history traits and species’ distributions in fragmented landscapes, the effect of individual traits on the dependence of species on historical versus current landscape configurations remains unclear.

We identified the extent to which present (2000s) and historical (1843, 1954, 1980s) patch configurations (area and connectivity) and patch age affected the distributions of 99 species inhabiting dry calcareous grasslands. We used traits related to dispersal, survival, growth and habitat preferences to explain the dependence of 60 of these species on present and historical configurations, and the age of grassland patches.

We found that most of the species had an affinity to currently or historically large, older and more isolated patches. This suggests that many dry grassland species are not in equilibrium with the current landscape, as their distributions still reflect past landscape structures. Rapidly growing species with higher seed bank longevity and nutrient requirements primarily occur in young, large grassland patches whereas species with the opposite traits occur in older, historically large and currently more isolated smaller patches. We hypothesise that patch quality is the reason why different species occupy patches of different age. Species occupying young, large patches commonly disperse by endozoochory. By contrast, no dispersal trait is associated with species occupying old, usually isolated patches. Our results suggest that species occupying old patches are exposed to higher potential risk of extinction, as their distributions are probably limited by the low number and connectivity of available suitable patches and poor dispersal ability. We thus suggest that the dynamics of these species can effectively be supported by improving the quality of young grassland patches.
Robustness of mutualistic networks under phenological change and habitat destruction
Authors: Revilla Tomás A. , Encinas‐Viso Francisco , Loreau Michel
Published: August 2014

Climate change can alter species phenologies and therefore disrupt species interactions. Habitat destruction can damage biodiversity and population viability. However, we still know very little about the potential effects of these two factors on the diversity and structure of interaction networks when both act simultaneously. Here we developed a mutualistic metacommunity model to explore the effects of habitat destruction and phenological changes on the diversity and structure of plant–pollinator networks. Using an empirical data set of plant and pollinator interactions and their duration in days, we simulated increasing levels of habitat destruction, under projected scenarios of phenological shifts as well for historically recorded changes in phenologies. On one hand, we found that habitat destruction causes catastrophic collapse in global diversity, as well as inducing alternative states. On the other hand, phenological shifts tend to make interactions weaker, increasing local extinction rates. Together, habitat destruction and phenological changes act synergistically, making metacommunities even more vulnerable to global collapse. Metacommunities are also more vulnerable to collapses under scenarios of historical change, in which phenologies are shortened, not just shifted. Furthermore, connectance and nestedness tends to decrease gradually with habitat destruction before the global collapse. Small phenological shifts can raise connectance slightly, due novel interactions appearing in a few generalist species, but larger shifts always reduce connectance. We conclude that the robustness of mutualistic metacommunities against habitat destruction can be greatly impaired by the weakening of positive interactions that results from the loss of phenological overlap.
Relative roles of resource stimulus and vegetation architecture on the paths of flies foraging for fruit
Authors: Verdeny‐Vilalta Oriol , Aluja Martín , Casas Jérôme
Published: August 2014

Many animals use their perceptual abilities to orient and locate resources in architecturally complex environments. However, it is not well known how the strength of a stimulus source affects the geometry of animal movement in architecturally complex environments. We mapped the 3D vegetation architecture of four apple trees of varying morphology and age and recorded the paths of apple maggot fliesRhagoletis pomonellaforaging for artificial fruit. We compared the observed movement with the one obtained from a random walk model on a graph to estimate both 1) the attraction radius and strength of a fruit and 2) the relative roles of the architecture of vegetation and of the strength of attraction of a fruit on the movement of flies. The attraction radius is the maximal distance at which a stimulus source biases the movement of individuals and the attraction strength measures how strong this bias is. Plant architectural complexity is defined according to both foliage density and its 3D distribution within the canopy. A single fruit induces a bias in the path orientation of an insect that is at a large distance, relative to a tree volume, but it has no effect on the step length of moves. The plant complexity makes a minor contribution to defining the radius of the sphere of attraction, but a large contribution to the attraction strength. Conditional on visiting the location, the plant architecture plays a minor role compared to that of the presence of the fruit. Our findings show that the complexity of the environment can alter the use of sensory information, which has important implications for animal movements in complex environments. The importance of our results in animal dispersal and foraging is considered.
Comparison of actual oxygen delivery kinetics to those predicted by mathematical modeling following stage 1 palliation just prior to superior cavopulmonary anastomosis
Authors: Yuki Koichi , DiNardo James A.
Published: August 2014

Background

Optimizing systemic oxygen delivery (DO2) and hemodynamics in children with hypoplastic left heart syndrome (HLHS) is a clinical challenge. Mathematical modeling of the HLHS circulation has been used to determine the relationship between oxygen kinetic parameters and DO2 and to determine how DO2 might be optimized. The model demonstrates that neither arterial oxygen saturation (SaO2) nor mixed venous oxygen saturation (SvO2) alone accurately predicts DO2.

Objectives

Oxygen delivery kinetics predicted by previously described mathematical modeling were compared with actual patients' hemodynamic data. We sought to determine which patient derived parameters correlated best with DO2.

Methods

Patients with HLHS who underwent cardiac catheterization prior to surgery to create a superior cavopulmonary anastomosis from 2007 to 2011 were identified. Hemodynamic data obtained were compared with the data derived from the mathematical model. Correlations between SaO2, SvO2, SaO2‐SvO2, SaO2/(SaO2‐SvO2), pulmonary‐to‐systemic blood flow ratio (Qp/Qs), and DO2 were evaluated using both linear and nonlinear analyses, and R2 was calculated.

Results/Conclusions

Patients' data fit most aspects of the mathematical model. DO2 had the best correlation with SaO2/(SaO2‐SvO2; R2 = 0.8755) followed by SaO2‐SvO2 (R2 = 0.8063), while SaO2 or SvO2 alone did not demonstrate a significant correlation as predicated by the mathematical model (R2 = 0.09564 and 0.4831, respectively). SaO2/(SaO2‐SvO2) would be useful clinically to track changes in DO2 that occur with changes in patient condition or with interventions.
Neural Markers of Neuropathic Pain Associated with Maladaptive Plasticity in Spinal Cord Injury
Authors: Pascoal‐Faria Paula , Yalcin Nilufer , Fregni Felipe
Published: August 2014

Objectives

Given the potential use of neural markers for the development of novel treatments in spinal cord pain, we aimed to characterize the most effective neural markers of neuropathic pain following spinal cord injury (SCI).

Methods

A systematic PubMed review was conducted, compiling studies that were published prior to April, 2014 that examined neural markers associated with neuropathic pain after SCI using electrophysiological and neuroimaging techniques.

Results

We identified 6 studies: Four using electroencephalogram (EEG); 1 using magnetic resonance imaging (MRI) and FDG‐PET (positron emission tomography); and 1 using MR spectroscopy. The EEG recordings suggested a reduction in alpha EEG peak frequency activity in the frontal regions of SCI patients with neuropathic pain. The MRI scans showed volume loss, primarily in the gray matter of the left dorsolateral prefrontal cortex, and by FDG‐PET, hypometabolism in the medial prefrontal cortex was observed in SCI patients with neuropathic pain compared with healthy subjects. In the MR spectroscopy findings, the presence of pain was associated with changes in the prefrontal cortex and anterior cingulate cortex.

Conclusions

When analyzed together, the results of these studies seem to point out to a common marker of pain in SCI characterized by decreased cortical activity in frontal areas and possibly increased subcortical activity. These results may contribute to planning further mechanistic studies as to better understand the mechanisms by which neuropathic pain is modulated in patients with SCI as well as clinical studies investigating best responders of treatment.
Fisetin Inhibits UVB‐induced Cutaneous Inflammation and Activation of PI3K/AKT/NFκB Signaling Pathways in SKH‐1 Hairless Mice
Authors: Pal Harish Chandra , Athar Mohammad , Elmets Craig A. , Afaq Farrukh
Published: August 2014

Solar ultraviolet B (UVB) radiation has been shown to induce inflammation, DNA damage, p53 mutations and alterations in signaling pathways eventually leading to skin cancer. In this study, we investigated whether fisetin reduces inflammatory responses and modulates PI3K/AKT/NFκB cell survival signaling pathways in UVB‐exposed SKH‐1 hairless mouse skin. Mice were exposed to 180 mJ cm−2 of UVB radiation on alternate days for a total of seven exposures, and fisetin (250 and 500 nmol) was applied topically after 15 min of each UVB exposure. Fisetin treatment to UVB‐exposed mice resulted in decreased hyperplasia and reduced infiltration of inflammatory cells. Fisetin treatment also reduced inflammatory mediators such as COX‐2, PGE2 as well as its receptors (EP1–EP4) and MPO activity. Furthermore, fisetin reduced the level of inflammatory cytokines TNFα, IL‐1β and IL‐6 in UVB‐exposed skin. Fisetin treatment also reduced cell proliferation markers as well as DNA damage as evidenced by increased expression of p53 and p21 proteins. Further studies revealed that fisetin inhibited UVB‐induced expression of PI3K, phosphorylation of AKT and activation of the NFκB signaling pathway in mouse skin. Overall, these data suggest that fisetin may be useful against UVB‐induced cutaneous inflammation and DNA damage.
Both Random and Guided
Authors: van Woudenberg R. , Rothuizen‐van der Steen J.
Published: August 2014

This paper argues, first, that biological evolution can be both random and divinely guided at the same time. Next it discusses the idea that the claim that evolution is unguided is not part of the science of evolution, and defends it against a number of objections.