bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin Antagonizes Thrombin-Induced Microvessel Leakage
Authors: Liu Yan , Chen Xue lian , Wang Lei , Martins-Green Manuela
Published: May 2017

Sustained increase in microvessel permeability results in cell and tissue damage. To date, it has not been possible to safely and specifically block increased microvessel permeability in vivo. We showed that insulin stimulates angiogenesis and that the new microvessels are associated with more αSMA-producing cells, suggesting greater stability. In this study, we show that local injection of insulin under the skin of mice significantly inhibits thrombin-induced microvessel permeability and that insulin improves the barrier function of primary human endothelial cells under conditions that mimic endothelium in vivo. These findings indicate that insulin antagonizes thrombin-induced microvessel permeability. At the cell and molecular levels, we show that insulin interferes with thrombin-induced VE-cadherin signaling by decreasing the ability of thrombin to induce VE-cadherin translocation to the cytoskeleton/nuclear compartment, leading to microvessel leakage. Simultaneously, the rapid activation of Src by insulin followed by the activation of Rac1, a small GTPase involved in cytoskeletal reorganization, leads to the maintenance of endothelial barrier, short-circuiting the slower thrombin-induced Src-RhoA signaling that leads to endothelial permeability. This novel mechanism by which insulin inhibits thrombin-induced permeability provides support for the use of insulin treatment in pathological conditions that involve blood-barrier dysfunction, especially as resuscitation treatment methods for extensive burns, sepsis, and other severe pathological conditions.
Immunosuppressive Agents for the Treatment of Primary Sclerosing Cholangitis: A Systematic Review and Meta-Analysis
Authors: Peng Xia , Luo Xin , Hou Jing-Ying , Wu Shu-Yun , Li Liang-Zong , Zheng Ming-Hua , Wang Ling-Yun
Published: May 2017

Objectives: Currently, there are no effective therapeutic agents for patients with primary sclerosing cholangitis (PSC). This study aimed to evaluate the safety and efficiency of immunosuppressive agents (IAs) for the treatment of PSC. Methods: The literatures were searched using the following keywords singly or in combination: PSC, treatments, IAs. The primary outcome was defined as the need for liver transplantation or mortality. Results: Two hundred sixty six patients from 7 eligible studies were analyzed. IAs had no remarkable effects on the rate of mortality or liver transplantation (relative risk, RR 1.02, 95% CI 0.58-1.62, p = 0.92). Subgroup analyses showed no significant effect of IAs co-administration therapy (IAs co-administered with ursodeoxycholic acid, IA co-administered with IA; RR 1.41, 95% CI 0.40-4.95, p = 0.60). IAs caused adverse events (AEs) such as diarrhea, abdominal pain, and pruritus (RR 1.81, 95% CI 1.07-3.07, p = 0.03). IAs therapy did not significantly improve markers of liver function except for aspartate transaminase (weighted mean difference -9.76, 95% CI -12.92 to -6.6, p < 0.001). Conclusion: IAs administrated as either monotherapy or combination therapy do not reduce the risk of mortality or liver transplantation. IAs monotherapy is associated with AEs.
Analysis of Aprotinin, a Protease Inhibitor, Action on the Trafficking of Epithelial Na+ Channels (ENaC) in Renal Epithelial Cells Using a Mathematical Model
Authors: Sasamoto Kouhei , Marunaka Rie , Niisato Naomi , Sun Hongxin , Taruno Akiyuki , Pezzotti Giuseppe , Yamamoto Toshiro , Kanamura Narisato , Zhu Wenliang , Nishio Kyosuke , Inui Toshio , Eaton Douglas C. , Marunaka Yoshinori
Published: May 2017

Background/Aim: Epithelial Na+ channels (ENaC) play a crucial role in control of blood pressure by regulating renal Na+ reabsorption. Intracellular trafficking of ENaC is one of the key regulators of ENaC function, but a quantitative description of intracellular recycling of endogenously expressed ENaC is unavailable. We attempt here to provide a model for intracellular recycling after applying a protease inhibitor under hypotonic conditions. Methods: We simulated the ENaC-mediated Na+ transport in renal epithelial A6 cells measured as short-circuit currents using a four-state mathematical ENaC trafficking model. Results: We developed a four-state mathematical model of ENaC trafficking in the cytosol of renal epithelial cells that consists of: an insertion state of ENaC that can be trafficked to the apical membrane state (insertion rate); an apical membrane state of ENaC conducting Na+ across the apical membrane; a recycling state containing ENaC that are retrieved from the apical membrane state (endocytotic rate) and then to the insertion state (recycling rate) communicating with the apical membrane state or to a degradation state (degradation rate). We studied the effect of aprotinin (a protease inhibitor) blocking protease-induced cleavage of the extracellular loop of γ ENaC subunit on the rates of intracellular ENaC trafficking using the above-defined four-state mathematical model of ENaC trafficking and the recycling number relative to ENaC staying in the apical membrane. We found that aprotinin significantly reduced the insertion rate of ENaC to the apical membrane by 40%, the recycling rate of ENaC by 81%, the cumulative time of an individual ENaC staying in the apical membrane by 32%, the cumulative life-time after the first endocytosis of ENaC by 25%, and the cumulative Na+ absorption by 31%. The most interesting result of the present study is that cleavage of ENaC affects the intracellular ENaC trafficking rate and determines the residency time of ENaC, indicating that more active cleaved ENaCs stay longer at the apical membrane contributing to transcellular Na+ transport via an increase in recycling of ENaC to the apical membrane. Conclusion: The extracellular protease-induced cleavage of the extracellular loop of γ ENaC subunit increases transcellular epithelial Na+ transport by elevating the recycling rate of ENaC due to an increase in the recycling rate of ENaCs associated with increases in the insertion rate of ENaC.
Favourable Outcome in a 33-Year-Old Female with Acute Haemorrhagic Leukoencephalitis
Authors: Solis Waldo G. , Waller Sophie E. , Harris Angela K. , Sugo Ella , Hansen Mitchell A. , Lechner-Scott Jeanette
Published: May 2017

Background: Acute haemorrhagic leukoencephalitis (AHLE) is a rare and rapidly fatal disease of unknown aetiology. There is a paucity of literature on the presentation and management of this rare disease. Case Description: We report the case of a 33-year-old female presenting with headache and left-sided apraxia. Imaging revealed a right-sided white matter lesion with extensive cytotoxic oedema. Pathology was suggestive of AHLE. She underwent an open excisional biopsy and was treated with high-dose corticosteroids. Three months since symptom onset she remains clinically well with resolving apraxia and radiological appearance. Conclusion: This case may represent a milder spectrum of AHLE, which responded favourably to corticosteroids.
Nutrition, Genes, and Age-Related Macular Degeneration: What Have We Learned from the Trials?
Authors: Chew Emily Y.
Published: May 2017

The Age-Related Eye Disease Study (AREDS) and AREDS2 provided evidence for treating persons with age-related macular degeneration (AMD) with antioxidant vitamins and minerals to reduce the risk of development of late AMD. The AREDS2 data suggest that the beta-carotene in the original AREDS supplements be replaced by lutein and zeaxanthin, providing a safer drug for those who are smokers or former smokers. Even though consuming fish reduced the risk of AMD in observational studies, the AREDS2 results showed that omega-3 long-chain polyunsaturated fatty acids (docosahexaenoic acid/eicosapentaenoic acid) had no beneficial effect on AMD. Despite the major progress in the discovery of gene variants associated with AMD, the use of genetic testing to predict disease has not been clinically useful. The use of genetic testing prior to AMD therapies such as administering AREDS supplements is not recommended by the American Academy of Ophthalmology and other organizations.
Curcumin Inhibits Heat-Induced Apoptosis by Suppressing NADPH Oxidase 2 and Activating the Akt/mTOR Signaling Pathway in Bronchial Epithelial Cells
Authors: Peng Yuan , Pu Junliang , Tang Chengyong , Wu Zhongjun
Published: May 2017

Background: Heat causes bronchial epithelial cell apoptosis, which is a known factor contributing to airway damage during inhalation injury. Accumulating evidence has shown the effect of curcumin on inhibiting apoptosis. In this study, we investigated whether curcumin suppresses heat-induced apoptosis in bronchial epithelial cells and the underlying mechanism. Methods: Bronchial epithelial cell line 16HBE140 cells were incubated at either 42 °C, 47 °C, 52 °C, or 57 °C for 5 min in a cell incubator and then returned back to normal culture conditions (37 °C). An in vivo thermal inhalation injury rat model was established with a heat gun blowing hot air into the airway of rats. 16HBE140 cells and lung tissue were obtained for further study with or without curcumin treatment. Cell viability was determined by measuring the absorbance of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). 2',7'-dichlorofluorescein diacetate fluorescence was used as a measure of reactive oxygen species (ROS) production. Levels of Bcl2, Bax, α-ATP, cleaved Poly (ADP-ribose) polymerase (PARP), cleaved caspase-3, gp91phox, p47phox, p67phox, p22phox, p40phox, and Rac were determined by Western blotting. TUNEL staining was used to determine apoptosis. Results: Heat treatment triggered the apoptosis of 16HBE140 cells as shown by the increase in apoptosis molecular markers, including Bcl-2, Bax, cleaved PARP, and cleaved caspase-3. Administration of curcumin significantly inhibited apoptosis of 16HBE140 cells and suppressed the membrane translocation of NADPH oxidase 2 cytosolic components, as well as ROS production. Downregulation of Akt and mTOR phosphorylation induced by heat was also reversed by curcumin. Furthermore, we demonstrated that NADPH oxidase 2 is upstream of Akt/mTOR in heat-induced apoptosis. The protective role of curcumin on bronchial epithelia apoptosis was also confirmed in vivo by a rat inhalation injury model. Conclusion: This study demonstrates that one of the critical mechanisms underlying curcumin inhibiting heat-induced apoptosis is through suppressing NADPH Oxidase 2 and activating the Akt/mTOR signaling pathway in bronchial epithelial cells.
Relaxing Effect of TSU-68, an Antiangiogenic Agent, on Mouse Airway Smooth Muscle
Authors: Tan Honghao , Lei Jun , Xue Lu , Cai Congli , Liu Qing-hua , Shen Jinhua
Published: May 2017

Background/Aims: Recently, some small-molecule compounds that were designed for cancer therapy have acquired new roles in the treatment of pulmonary diseases. However, drug screening aimed at abnormal muscle contraction is still limited. TSU-68 is a potent, orally administered, small-molecule agent that can reduce the vascular endothelial growth factor (VEGF)-induced Ca2+ increase in endothelial cells. We questioned whether TSU-68 could also affect calcium influx and relax airway smooth muscle (ASM) cells. The current study aimed to investigate these effects and to explore the underlying mechanisms. Methods: The effects of TSU-68 on ASM cells were studied in mice using a series of biophysiological techniques, including force measurement and patch-clamp experiments. Results: TSU-68 inhibited high K+ or acetylcholine chloride (ACh)-induced pre-contracted mouse tracheal rings in a concentration-dependent manner. Further research demonstrated that the TSU-68-induced ASM relaxation was mediated by calcium, which was decreased by blocking voltage-dependent Ca2+ channels (VDCCs) and non-selective cation channels (NSCCs). Conclusion: Our data indicated that TSU-68 relaxes tense ASM by reducing the intracellular Ca2+ concentration through blocking VDCCs and NSCCs, which suggested that this small molecule might be useful in the treatment of abnormal smooth muscle.
Application of Hanging Drop Technique for Kidney Tissue Culture
Authors: Wang Shaohui , Wang Ximing , Boone Jasmine , Wie Jin , Yip Kay-Pong , Zhang Jie , Wang Lei , Liu Ruisheng
Published: May 2017

Background/Aims: The hanging drop technique is a well-established method used in culture of animal tissues. However, this method has not been used in adult kidney tissue culture yet. This study was to explore the feasibility of using this technique for culturing adult kidney cortex to study the time course of RNA viability in the tubules and vasculature, as well as the tissue structural integrity. Methods: In each Petri dish with the plate covered with sterile buffer, a section of mouse renal cortex was cultured within a drop of DMEM culture medium on the inner surface of the lip facing downward. The tissue were then harvested at each specific time points for Real-time PCR analysis and histological studies. Results: The results showed that the mRNA level of most Na+ related transporters and cotransporters were stably maintained within 6 hours in culture, and that the mRNA level of most receptors found in the vasculature and glomeruli were stably maintained for up to 9 days in culture. Paraffin sections of the cultured renal cortex indicated that the tubules began to lose tubular integrity after 6 hours, but the glomeruli and vasculatures were still recognizable up to 9 days in culture. Conclusions: We concluded that adult kidney tissue culture by hanging drop method can be used to study gene expressions in vasculature and glomeruli.
Apolipoprotein C-III Levels and Incident Coronary Artery Disease Risk
Authors: van Capelleveen Julian C. , Bernelot Moens Sophie J. , Yang Xiaohong , Kastelein John J.P. , Wareham Nicholas J. , Zwinderman Aeilko H. , Stroes Erik S.G. , Witztum Joseph L. , Hovingh G. Kees , Khaw Kay-Tee , Boekholdt S. Matthijs , Tsimikas Sotirios
Published: May 2017

Objective—

Apolipoprotein C-III (apoC-III) is a key regulator of triglyceride metabolism. Elevated triglyceride-rich lipoproteins and apoC-III levels are causally linked to coronary artery disease (CAD) risk. The mechanism(s) through which apoC-III increases CAD risk remains largely unknown. The aim was to confirm the association between apoC-III plasma levels and CAD risk and to explore which lipoprotein subfractions contribute to this relationship between apoC-III and CAD risk.

Approach and Results—

Plasma apoC-III levels were measured in baseline samples from a nested case–control study in the European Prospective Investigation of Cancer (EPIC)-Norfolk study. The study comprised 2711 apparently healthy study participants, of whom 832 subsequently developed CAD. We studied the association of baseline apoC-III levels with incident CAD risk, lipoprotein subfractions measured by nuclear magnetic resonance spectroscopy and inflammatory biomarkers. ApoC-III levels were significantly associated with CAD risk (odds ratio, 1.91; 95% confidence interval, 1.48–2.48 for highest compared with lowest quintile), retaining significance after adjustment for traditional CAD risk factors (odds ratio, 1.47; 95% confidence interval, 1.11–1.94). ApoC-III levels were positively correlated with triglyceride levels, (
r
=0.39), particle numbers of very-low-density lipoprotein (
r
=0.25), intermediate-density lipoprotein (
r
=0.23), small dense low-density lipoprotein (
r
=0.26), and high-sensitivity C-reactive protein (
r
=0.15), whereas an inverse correlation was observed with large low-density lipoprotein particle number (
r
=−0.11),
P
<0.001 for each. Mediation analysis indicated that the association between apoC-III and CAD risk could be explained by triglyceride elevation (triglyceride, very-low-density lipoprotein, and intermediate-density lipoprotein particles), small low-density lipoprotein particle size, and high-sensitivity C-reactive protein.

Conclusions—

ApoC-III levels are significantly associated with incident CAD risk. Elevated levels of remnant lipoproteins, small dense low-density lipoprotein, and low-grade inflammation may explain this association.
Implication of Inflammation and Epigenetic Readers in Coronary Artery Remodeling in Patients With Pulmonary Arterial Hypertension
Authors: Meloche Jolyane , Lampron Marie-Claude , Nadeau Valérie , Maltais Mélanie , Potus François , Lambert Caroline , Tremblay Eve , Vitry Géraldine , Breuils-Bonnet Sandra , Boucherat Olivier , Charbonneau Eric , Provencher Steeve , Paulin Roxane , Bonnet Sébastien
Published: May 2017

Objective—

Pulmonary arterial hypertension (PAH) is a vascular disease not restricted to the lungs. Many signaling pathways described in PAH are also of importance in other vascular remodeling diseases, such as coronary artery disease (CAD). Intriguingly, CAD is 4× more prevalent in PAH compared with the global population, suggesting a link between these 2 diseases. Both PAH and CAD are associated with sustained inflammation and smooth muscle cell proliferation/apoptosis imbalance and we demonstrated in PAH that this phenotype is, in part, because of the miR-223/DNA damage/Poly[ADP-ribose] polymerase 1/miR-204 axis activation and subsequent bromodomain protein 4 (BRD4) overexpression. Interestingly, BRD4 is also a trigger for calcification and remodeling processes, both of which are important in CAD. Thus, we hypothesize that BRD4 activation in PAH influences the development of CAD.

Approach and Results—

PAH was associated with significant remodeling of the coronary arteries in both human and experimental models of the disease. As observed in PAH distal pulmonary arteries, coronary arteries of patients with PAH also exhibited increased DNA damage, inflammation, and BRD4 overexpression. In vitro, using human coronary artery smooth muscle cells from PAH, CAD and non-PAH–non-CAD patients, we showed that both PAH and CAD smooth muscle cells exhibited increased proliferation and suppressed apoptosis in a BRD4-dependent manner. In vivo, improvement of PAH by BRD4 inhibitor was associated with a reduction in coronary remodeling and interleukin-6 expression.

Conclusions—

Overall, this study demonstrates that increased BRD4 expression in coronary arteries of patient with PAH contributes to vascular remodeling and comorbidity development.
Jews in the Piazza: Jewish Self-government in the Fifteenth-century Kingdom of Naples
Authors: Selleri Vincenzo
Published: May 2017

This study intends to make a contribution to the literature on Jewish autonomy in the Late Middle Ages by analyzing Jewish political life in the Kingdom of Naples in the fifteenth century. Contrary to Italian and European scholarship which has interpreted Jewry policy in the Kingdom of Naples in the fifteenth century as a direct emanation of the ‘good heart’ of the Aragonese kings, I argue that Jewish charters must be considered the product of Jewish agency. I suggest that the Jewish ruling elites, not the king nor the municipal governmets sought the administrative and juridical separation of the iudece (Jewish Communities) from the municipal governement of southern cities. Considering that Jewish political action, and the administration of the iudeca mirrored that of cities, I argue that Jewish Communities fit perfectly into the Aragonese administrative puzzle.
The restablishment of Dyckia oligantha and D. nana (Bromeliaceae, Pitcairnioideae), belonging to the D. macedoi complex
Authors: GUARÇONI ELIDIO ARMANDO EXPOSTO , AZEVEDO ARISTÉIA ALVES DE , COSTA ANDREA FERREIRA DA
Published: May 2017

The authors reestablish Dyckia oligantha and D. nana, considered synonymous of D. saxatilis and D. macedoi, respectively, on the basis of newly collected specimens from the type localities. Multivariate analysis of vegetative and reproductive characters on natural populations of the species of the D. macedoi complex were performed, allowing the recognition of D. macedoi, D. nana and D. oligantha as distinct species.
Rediscovery of Arisaema translucens (Araceae) and notes on A. tuberculatum, two strict endemics of Nilgiris, India
Authors: PRABHUKUMAR KONICKAL MAMBETTA , CHHABRA TARUN , ROBI ALOOR JOSE , JAGADEESAN RAVEENDRAN , SUNIL CHANDRASSERIL NARAYANAN , BALACHANDRAN INDIRA
Published: May 2017

Genus Arisaema Martius (1831: 449) is represented by 215 taxa worldwide (Govaerts et al. 2017), of which 61 taxa are reported so far from India including two recent discoveries from Kerala and Tamil Nadu states of Western Ghats, viz. A. peerumedense J. Mathew in Mathew & George (2017: 29), A. madhuanum Nampy & Manudev in Manudev & Nampy (2014: 269) and A. gracilentum Bruggeman (2016: 87) from Arunachal Pradesh of North-East India. During extensive surveys in the Nilgiri Biosphere Reserve, Tamil Nadu, the authors came across two fascinating Arisaema species, one from Thia Shola and the second from Pennant’s Valley forest areas. The first species is attractive by means of its translucent spathe and the latter by its long caudate limb with a filiform thread. Detailed study of relevant literature (Fischer 1933, Fischer 1934, Gusman & Gusman 2002) confirmed their identity as A. translucens Fischer (1933: 344) and A. tuberculatum Fischer (1934: 167), respectively. Arisaema translucens is described by Fischer (1933) based on the collection from Thia Shola forests by E. Barnes at an elevation of 6000 ft made in 1932. From a thorough literature survey and herbarium consultations, it became apparent that this taxon had not been collected since 1932. Hence our discovery is a recollection of this species after a lapse of 84 years from its type locality. Detailed description, colour photographs and distribution information are provided based on the recent collections.
The Role of Rough Topography in Mediating Impacts of Bottom Drag in Eddying Ocean Circulation Models
Authors: Trossman David S. , Arbic Brian K. , Straub David N. , Richman James G. , Chassignet Eric P. , Wallcraft Alan J. , Xu Xiaobiao
Published: May 2017

Motivated by the substantial sensitivity of eddies in two-layer quasigeostrophic (QG) turbulence models to the strength of bottom drag, this study explores the sensitivity of eddies in more realistic ocean general circulation model (OGCM) simulations to bottom drag strength. The OGCM results are interpreted using previous results from horizontally homogeneous, two-layer, flat-bottom, f-plane, doubly periodic QG turbulence simulations and new results from two-layer, β-plane QG turbulence simulations run in a basin geometry with both flat and rough bottoms. Baroclinicity in all of the simulations varies greatly with drag strength, with weak drag corresponding to more barotropic flow and strong drag corresponding to more baroclinic flow. The sensitivity of the baroclinicity in the QG basin simulations to bottom drag is considerably reduced, however, when rough topography is used in lieu of a flat bottom. Rough topography reduces the sensitivity of the eddy kinetic energy amplitude and horizontal length scales in the QG basin simulations to bottom drag to an even greater degree. The OGCM simulation behavior is qualitatively similar to that in the QG rough-bottom basin simulations, in that baroclinicity is more sensitive to bottom drag strength than are eddy amplitudes or horizontal length scales. Rough topography therefore appears to mediate the sensitivity of eddies in models to the strength of bottom drag. The sensitivity of eddies to parameterized topographic internal lee wave drag, which has recently been introduced into some OGCMs, is also briefly discussed. Wave drag acts like a strong bottom drag in that it increases the baroclinicity of the flow, without strongly affecting eddy horizontal length scales.
Experiencing Misgendered Pronouns: A Classroom Activity to Encourage Empathy
Authors: MacNamara Jessica , Glann Sarah , Durlak Paul
Published: May 2017

How can teachers help students understand the importance of gender pronouns for transgender and gender-nonconforming people? This article presents a gender pronoun reversal activity that simulates the experience of being verbally misgendered. Students followed up on the activity by posting reflections on an online class discussion board. The activity promoted empathy among cisgender students for transgender people and reflexivity regarding the social boundaries of gender identity. Empathy and reflexivity were common responses among students enrolled in Sociology of Diversity and Sociology of Gender at a large research university in the northeast. We present the activity, including preparation and follow-up along with an analysis of student responses.
A collaborative group study of Korean mid-career elementary teachers for professional development in music
Authors: Shin Jihae , Seog Moonjoo
Published: May 2017

Professional development for in-service teachers is necessary to meet the changing needs of students and society. This teacher collaboration study examined the experiences of mid-career elementary teachers in Korea in their music professional development. Research questions included: (1) What were the contents of discussion? (2) What was the level of participation among elementary teachers in a collaborative group? (3) How did the focus of the group change over time? The data collection included nonparticipant observation, participants’ reflective journals, researchers’ logs, and artifact collection. Findings showed that participants mainly discussed teaching strategies about music classes and reflected new knowledge that were closely related to confidence in teaching. In addition, teachers in this collaborative group played different roles throughout the group meetings depending on their expertise and interests, but there was also a need for a facilitator. Finally, teachers in the group gradually identified the importance of teacher collaboration for their professional development and attempted to be peer mentors for others outside the collaborative group.
Journeys through the Hidden City: Giving visibility to the Material Events of conflict in Belfast
Authors: Coyles David
Published: May 2017

The ‘peace-walls’ of Belfast represent a widely acknowledged architectural legacy of the Troubles, the period between 1969 and 1994 when sectarian conflict in Northern Ireland was most extreme. This paper reveals a further crucial but unacknowledged architectural legacy. It is a Hidden City of unassuming inner-city architecture where everyday pervasiveness masks a capacity to perpetuate conflict-era forces in a post-conflict city. The first half of the paper presents a Foucauldian analysis of declassified government documents revealing the knowledge created through undisclosed systems of power-relations. Here a problematisation of accepted norms reassesses the Troubles-era urban landscape and exposes the latent significance of its socio-material complexity. The second half of the paper illustrates the material consequences of related hidden policy practices on the contemporary post-conflict community. It borrows from Goffman to offer an exposition of the institutionalisation of movement and meaning at play in the Hidden City. A triangulation of interviews, photography and architectural fieldwork is used to theorise the Material Event, a construction of meaning derived from the interaction between people, architecture and the wider systems of power-relations. The paper concludes by demonstrating the complexity of the systemic challenges posed by the Material Events and how these help constrain conflict-transformation practices.
Correlations of 18F-FDG and 18F-FLT uptake on PET with Ki-67 expression in patients with lung cancer: a meta-analysis
Authors: Shen Guohua , Ma Huan , Pang Fuwen , Ren Pengwei , Kuang Anren
Published: May 2017

Background

Positron emission tomography (PET) imaging using the radiotracers 18F-fluorodeoxyglucose (FDG) or 18F-fluorothymidine (FLT) has been proposed as imaging biomarkers of cell proliferation.

Purpose

To explore the correlations of FDG and FLT uptake with the Ki-67 labeling index in patients with lung cancer.

Material and Methods

Major databases were systematically searched for all relevant literature published in English. The correlation coefficient (rho) and its 95% confidence interval (CI) of individual studies were meta-analyzed using a random-effects model. The sources of heterogeneity were explored by subgroup analyses.

Results

Twenty-seven articles involving 1213 patients were included in this meta-analysis, comprising 22 studies for FDG uptake/Ki-67 expression correlation and eight for FLT uptake/Ki-67 expression correlation. The pooled rho values for 18F-FDG/Ki-67 correlation and 18F-FLT/Ki-67 correlation were 0.45 (95% CI, 0.41–0.50) and 0.65 (95% CI, 0.56–0.73), respectively, which indicated a moderate correlation for the former and a significant one for the latter. Although the subgroup analyses based on study design, scanner, sample method, and Ki-67 labeling method did not significantly explain the heterogeneity, these factors were potential sources of heterogeneity. In lung cancer, the pooled SUVmax of FDG uptake was significantly higher than that of FLT uptake (7.59 versus 3.86, P < 0.05). In addition, compared to FDG, FLT showed higher specificity yet lower sensitivity for the diagnosis of pulmonary lesions.

Conclusion

Both 18F-FDG and 18F-FLT correlate significantly with the Ki-67 labeling index in pulmonary lesions, and the latter, with a stronger correlation, may be more reliable for assessing tumor cell proliferation in lung cancer.
Acoustic radiation force impulse imaging for detection of liver fibrosis in overweight and obese children
Authors: Berná-Serna Juan D , Sánchez-Jiménez Regina , Velázquez-Marín Francisca , Sainz de Baranda Pilar , Guzmán-Aroca Florentina , Fernández-Hernández Carmen , Doménech-Abellán Ernesto , Abellán-Rivero Dolores , Ruiz-Merino Guadalupe , Madrid-Conesa Juan , Canteras-Jordana Manuel
Published: May 2017

Background

Acoustic radiation force impulse (ARFI) is a non-invasive alternative to a liver biopsy for the evaluation of liver fibrosis (LF).

Purpose

To investigate the potential usefulness of acoustic radiation force impulse ARFI for detecting LF in overweight and obese children

Material and Methods

A cross-sectional study was conducted in 148 schoolchildren. A diagnosis of non-alcoholic fatty liver disease (NAFLD) and LF was based on ultrasound (US) and ARFI shear wave velocity (SWV).

Results

The laboratory parameters were normal in all the children. NAFLD was observed in 50 children (33.8%). The median SWV was 1.18 ± 0.28 m/s. Differences between ARFI categories and hepatic steatosis grades were observed (χ2 = 43.38, P = 0.0005). No fibrosis or insignificant fibrosis (SWV ≤ 1.60 m/s) was detected in 137 children (92.5%), and significant fibrosis (SWV > 1.60 m/s) in 11 children (7.5%), nine of whom had normal US or mild steatosis.

Conclusion

The present study is the first to evaluate the utility of the ARFI technique for detecting LF in overweight and obese children. The results of the study suggest that children with normal laboratory parameters such as normal liver ultrasound or mild steatosis may present with significant LF.
Ovarian hormones, age and pubertal development and their association with days of headache onset in girls with migraine: An observational cohort study
Authors: Martin Vincent T , Allen Janelle R , Houle Timothy T , Powers Scott W , Kabbouche Marielle A , O’Brien Hope L , Kacperski Joanne , LeCates Susan L , White Shannon , Vaughan Polly , Mandell Karen , Hershey Andrew D
Published: May 2017

Background

Fifty-three percent of adolescent girls report headaches at the onset of menses, suggesting fluctuations of ovarian hormones trigger migraine during puberty.

Aims

To determine if urinary metabolites of estrogen and progesterone are associated with days of headache onset (HO) or severity in girls with migraine.

Methods

This was a pilot study and included 34 girls with migraine balanced across three age strata (pre-pubertal (8–11), pubertal (12–15), and post-pubertal (16–17) years of age). They collected daily urine samples and recorded the occurrence and severity of headache in a daily diary. Urine samples were assayed for estrone glucuronide (E1G) and pregnandiol glucuronide (PdG) and the daily change was calculated (ΔE1G, ΔPdG). Pubertal development was assessed by age, pubertal development score (PDS), and menstrual cycle variance. The primary outcome measures were HO days and headache severity. Generalized linear mixed models were used, and included the hormonal variables and three different representations of pubertal development as covariates.

Results

Models of HO days demonstrate a significant age*PdG interaction (OR 0.85 [95% CI 0.75, 0.97]) for a 1 standard deviation increase in PdG and three-year increase in age. A separate model showed a significant PDS*PdG interaction (OR −0.85 [95% CI; 0.76, 0.95]). ΔPDG was associated with headache severity in unadjusted models ( p < 0.017).

Conclusion

Age and pubertal development could moderate the effect of ovarian hormones on days of headache onset in girls with migraine.
Idiopathic hypertrophic pachymeningitis mimicking hemicrania continua: An unusual clinical case
Authors: Russo Antonio , Silvestro Marcello , Cirillo Mario , Tessitore Alessandro , Tedeschi Gioacchino
Published: May 2017

Background

Hemicrania continua (HC) is a primary headache syndrome characterized by a unilateral, moderate, continuous headache with exacerbations marked by migrainous and cranial autonomic symptoms. However, clinical phenotypes similar to primary HC may be subtended by several disorders.

Case report

We report the case of a 62-year-old man experiencing, over the previous year, a headache completely consistent with HC and its absolute responsiveness to indomethacin therapy. Later, the patient developed diplopia caused by sixth cranial nerve palsy ipsilateral to headache. In this frame, clinical, laboratory and neuroimaging characteristics supported the diagnosis of idiopathic hypertrophic pachymeningitis (IHP).

Conclusions

IHP is a rare fibrosing inflammatory disorder leading to a localized or diffuse dura mater thickening. IHP clinical manifestations are a progressively worsening headache and signs related to cranial nerves involvement and venous sinus thrombosis. Here, we report, for the first time, a HC phenotype subtended by IHP.
Reliability and Relationship to Retention of Assessing an Acquisition Rate for Sight Words With Kindergarten Students
Authors: Taylor Crystal N. , Aguilar Lisa , Burns Matthew K. , Preast June L. , Warmbold-Brann Kristy
Published: May 2017

Teaching children too many words during a lesson reduces retention. The amount of new information a student can successfully rehearse and recall later is called acquisition rate (AR), which has been reliably measured with students in first, third, and fifth grades. The purpose of this study was to examine the reliability of assessing AR for sight words with kindergarten students. A total of 32 kindergarten students from five classrooms across two elementary schools participated in the study. AR was measured twice over a 2-week period, and 1-day retention was measured for the first AR. The AR data resulted in a 2-week delayed alternate form reliability of r = .83, and there was also a strong correlation between AR and number of words retained 1 day later. The limitations, implications, and considerations for the name of the construct being assessed are discussed.
Growth factor functionalized biomaterial for drug delivery and tissue regeneration
Authors: Leonard Alex , Koria Piyush
Published: May 2017

Elastin-like polypeptides are a class of naturally derived and non-immunogenic biomaterials that are widely used in drug delivery and tissue engineering. Elastin-like polypeptides undergo temperature-mediated inverse phase transitioning, which allows them to be purified in a relatively simple manner from bacterial expression hosts. Being able to genetically encode elastin-like polypeptides allows for the incorporation of bioactive peptides, thereby functionalizing them. Here, we report the synthesis of a biologically active epidermal growth factor–elastin-like polypeptide fusion protein that could aid in wound healing. Epidermal growth factor plays a crucial role in wound healing by inducing cell proliferation and migration. The use of exogenous epidermal growth factor has seen success in the treatment of acute wounds, but has seen relatively minimal success in chronic wounds because the method of delivery does not prevent it from diffusing away from the application site. Our data show that epidermal growth factor–elastin-like polypeptide retained the biological activity of epidermal growth factor and the phase transitioning property of elastin-like polypeptide. Furthermore, the ability of the epidermal growth factor–elastin-like polypeptide to self-assemble near physiological temperatures could allow for the formation of drug depots at the wound site and minimize diffusion, increasing the bioavailability of epidermal growth factor and enhancing tissue regeneration.
Estimator-based multiobjective robust control strategy for an active pantograph in high-speed railways
Authors: Lu Xiaobing , Liu Zhigang , Song Yang , Wang Hongrui , Zhang Jing , Wang Yanbo
Published: May 2017

Active control of the pantograph is one of the promising measures for decreasing fluctuation in the contact force between the pantograph and the catenary. In this paper, an estimator-based multiobjective robust control strategy is proposed for an active pantograph, which consists of a state estimator and a robust H∞ controller. The former serves as an essential tool for obtaining the states of the pantograph considering randomly missing measurements, and the latter is employed for decreasing the contact force fluctuation considering the limitation of the control force and collector uplift. Control performance is evaluated by implementing the control strategy with a nonlinear pantograph–catenary system model, in which the catenary is modeled based on nonlinear cable and truss elements. The robustness of the proposed control strategy is investigated under parameter perturbations and environmental disturbance, respectively. Furthermore, its advantage is verified by comparing it with an existing controller. Simulation results show that the control strategy can decrease the fluctuation in the contact force and reject parametric uncertainties and stochastic wind field.
Ellagic acid protects against arsenic trioxide–induced cardiotoxicity in rat
Authors: Hemmati AA , Olapour S , Varzi H Najafzadeh , Khodayar MJ , Dianat M , Mohammadian B , Yaghooti H
Published: May 2017

Arsenic trioxide (As2O3) is utilized for treating patients suffering from hematological malignancies particularly acute promyelocytic leukemia. Unfortunately, the extensive application of this chemotherapeutic agent has been limited due to its adverse effects such as cardiotoxicity. Ellagic acid, as a phenolic compound, has shown to exert antioxidant, anti-inflammatory, antifibrotic, and antiatherogenic properties. It is also capable of protecting against drug toxicity. In this study, we evaluated whether ellagic acid can protect against As2O3-induced heart injury in rats. Thirty-two male Wistar rats were randomly divided into four treatment groups, that is, control (0.2 mL of normal saline, intraperitoneally (ip)), As2O3 (5 mg/kg, ip), As2O3 plus ellagic acid, and ellagic acid (30 mg/kg, orally) groups. The drugs were administered daily for 10 days and pretreatment with ellagic acid was performed 1 h prior to As2O3 injection. Cardiotoxicity was characterized by electrocardiological, biochemical, and histopathological evaluations. Our results showed that ellagic acid pretreatment significantly ameliorated As2O3-induced increase in glutathione peroxidase activity and malondialdehyde concentration ( p < 0.05 and p < 0.001, respectively) and also diminished QTc prolongation ( p < 0.0001) and cardiac tissue damages. Pretreatment with ellagic acid also lowered the increased troponin I ( p < 0.0001) and creatine kinase isoenzyme MB ( p < 0.01) levels in response to As2O3. In conclusion, results of this study demonstrated that ellagic acid has beneficial cardioprotective effects against As2O3 toxicity. It is suggested that the protective effects were mediated by antioxidant properties of ellagic acid.
Urine peptidomic biomarkers for diagnosis of patients with systematic lupus erythematosus
Authors: Pejchinovski M , Siwy J , Mullen W , Mischak H , Petri M A , Burkly L C , Wei R
Published: May 2017

Background

Systematic lupus erythematosus (SLE) is characterized with various complications which can cause serious organ damage in the human body. Despite the significant improvements in disease management of SLE patients, the non-invasive diagnosis is entirely missing. In this study, we used urinary peptidomic biomarkers for early diagnosis of disease onset to improve patient risk stratification, vital for effective drug treatment.

Methods

Urine samples from patients with SLE, lupus nephritis (LN) and healthy controls (HCs) were analyzed using capillary electrophoresis coupled to mass spectrometry (CE-MS) for state-of-the-art biomarker discovery.

Results

A biomarker panel made up of 65 urinary peptides was developed that accurately discriminated SLE without renal involvement from HC patients. The performance of the SLE-specific panel was validated in a multicentric independent cohort consisting of patients without SLE but with different renal disease and LN. This resulted in an area under the receiver operating characteristic (ROC) curve (AUC) of 0.80 ( p < 0.0001, 95% confidence interval (CI) 0.65–0.90) corresponding to a sensitivity and a specificity of 83% and 73%, respectively. Based on the end terminal amino acid sequences of the biomarker peptides, an in silico methodology was used to identify the proteases that were up or down-regulated. This identified matrix metalloproteinases (MMPs) as being mainly responsible for the peptides fragmentation.

Conclusions

A laboratory-based urine test was successfully established for early diagnosis of SLE patients. Our approach determined the activity of several proteases and provided novel molecular information that could potentially influence treatment efficacy.
Impact of the immune cell population in peripheral blood on response and survival in patients receiving neoadjuvant chemotherapy for advanced gastric cancer
Authors: He Qi , Li Guoli , Ji Xiang , Ma Long , Wang Xulin , Li Yang , Fan Chaogang
Published: May 2017

We aimed to investigate the prognostic value of the immune cells population in peripheral blood from patients with advanced gastric cancer treated with neoadjuvant chemotherapy. A total of 105 patients with advanced gastric cancer were evaluated in this study. Blood samples were collected before and 1 week after the last dose of chemotherapy. The percentage of CD3+, CD3+CD4+, CD3+CD8+, and CD4+CD25+Foxp3+ T cells was assessed using flow cytometry analysis. The relationship between T cell subsets and clinical outcome was evaluated. The percentage of CD3+CD8+ lymphocytes was significantly increased after chemotherapy and CD4+CD25+Foxp3+ regulatory T cells (Tregs) decreased ( p = 0.003 and p < 0.001, respectively). The percentage of CD3+CD8+ lymphocytes and Tregs was strongly associated with response to chemotherapy ( p = 0.017 and p < 0.030, respectively). Patients with high CD3+CD8+ T cells and low CD4+CD25+Foxp3+ Tregs had significantly increased overall survival ( p = 0.012 and p = 0.048, respectively). Neither CD3+ nor CD3+CD4+ T cells showed significant changes after chemotherapy or correlations with the clinical outcome. The positive correlation between a high CD3+CD8+ T cells or low CD4+CD25+Foxp3+ Tregs and clinical outcome indicates its key role in the prognosis of gastric cancer patients and may serve as a biomarker to identify patients likely to benefit from neoadjuvant chemotherapy.
The CNGRCLLII(KLAKLAK)2 peptide shows cytotoxicity against HUVECs by inducing apoptosis: An in vitro and in vivo study
Authors: Wang Guanying , Yuan Na , Huang Shangke , Feng Lu , Han Rui , Zhang Yujiao , Ren Juan , Meng Min , Zhao Xinhan
Published: May 2017

Fibrinogen Asn-Gly-Arg motif can specifically recognize and bind to Aminopeptidase N (CD13) on vascular endothelial cells in newly formed tumor vessels. Adipose-derived stem cells can serve as ideal vectors for gene therapy because of their ability of migrating to tumor tissues. First, this study was aimed to design a new peptide (CNGRCLLII(KLAKLAK)2) named CNAK which contains cyclic Asn-Gly-Arg motif and test its biological activity against human umbilical vein endothelial cells. Second, we aimed to construct stably transfected adipose-derived stem cells which express the CNAK peptide and investigate their anti-angiogenic activity in vivo. Adipose-derived stem cells were employed to localize CNAK on vascular endothelial cells in tumors based on their homing property. First of all, the new peptide was synthesized, which effectively entered into CD13+ human umbilical vein endothelial cells and showed cytotoxicity against human umbilical vein endothelial cells. The peptide induced apoptosis of human umbilical vein endothelial cells in a time- and dose-dependent manner, inhibited the expression of Bcl-2, and promoted the expression of Caspase-3 in human umbilical vein endothelial cells. Furthermore, the migration and tube formation of human umbilical vein endothelial cells were inhibited by CNAK. Primary adipose-derived stem cells were then isolated and identified. Stably transfected adipose-derived stem cells which express CNAK peptide (CNAK-ASCs) were successfully established, and the migration of CNAK-ASCs was assessed. In vivo, CNAK-ASCs were found to inhibit the growth and angiogenesis of breast cancer xenografts. This effect may be through inhibiting the secretion of matrix metalloproteinase-2 and membrane type 1-matrix metalloproteinase in vivo. It was also found that CNAK-ASCs reduced the quantity of breast cancer stem cells in tumor tissues. Our data suggested that the new peptide CNAK containing Asn-Gly-Arg motif had anti-angiogenic activity in vitro and in vivo.