bluuebunny/crossref_metadata_2025 huggingface dataset:
Bakers' cyst and tibiofemoral abnormalities are more distinctive MRI features of symptomatic osteoarthritis than patellofemoral abnormalities
Authors: Visser A W , Mertens B , Reijnierse M , Bloem J L , de Mutsert R , le Cessie S , Rosendaal F R , Kloppenburg M
Published: May 2016

Objective

To investigate which structural MR abnormalities discriminate symptomatic knee osteoarthritis (OA), taking co-occurrence of abnormalities in all compartments into account.

Methods

The Netherlands Epidemiology of Obesity (NEO) study is a population-based cohort aged 45–65 years. In 1285 participants (median age 56 years, 55% women, median body mass index (BMI) 30 kg/m2), MRI of the right knee were obtained. Structural abnormalities (osteophytes, cartilage loss, bone marrow lesions (BMLs), subchondral cysts, meniscal abnormalities, effusion, Baker's cyst) at 9 patellofemoral and tibiofemoral locations were scored following the knee OA scoring system. Symptomatic OA in the imaged knee was defined following the American College of Rheumatology criteria. Logistic ridge regression analyses were used to investigate which structural abnormalities discriminate best between individuals with and without symptomatic OA, crude and adjusted for age, sex and BMI.

Results

Symptomatic knee OA was present in 177 individuals. Structural MR abnormalities were highly frequent both in individuals with OA and in those without. Baker's cysts showed the highest adjusted regression coefficient (0.293) for presence of symptomatic OA, followed by osteophytes and BMLs in the medial tibiofemoral compartment (0.185–0.279), osteophytes in the medial trochlear facet (0.262) and effusion (0.197).

Conclusions

Baker's cysts discriminate best between individuals with and without symptomatic knee OA. Structural MR abnormalities, especially in the medial side of the tibiofemoral joint and effusion, add further in discriminating symptomatic OA. Baker's cysts may present as a target for treatment.
Age‐associated and breed‐associated variations in haematological and biochemical variables in young labrador retriever and miniature schnauzer dogs
Authors: Brenten Thomas , Morris Penelope J. , Salt Carina , Raila Jens , Kohn Barbara , Schweigert Florian J. , Zentek Jürgen
Published: May 2016

Breed, sex and age effects on haematological and biochemical variables were investigated in 24 labrador retriever and 25 miniature schnauzer dogs during the first year of life. Blood samples were taken regularly between weeks 8 and 52. White blood cell and red blood cell counts, haemoglobin concentration, haematocrit, mean cell volume, mean cell haemoglobin, mean cell haemoglobin concentration, platelet count as well as total protein, albumin, calcium, phosphate, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase, total cholesterol, triglycerides, creatine and urea were evaluated. For all haematological and biochemical parameters, there were significant effects of age on test results. Statistically significant effects for breed and the breed×age interaction on test results were observed for most of the parameters with the exception of haemoglobin. Variations in test results illustrate growth related alterations in body tissue and metabolism leading to dynamic and marked changes in haematological and biochemical parameters, which have to be considered for the interpretation of clinical data obtained from dogs in the first year of life.
Conjunctival flora of healthy and diseased eyes of grey seals (Halichoerus grypus): implications for treatment
Authors: Fleming M. , Bexton S.
Published: May 2016

Ocular pathology is relatively common in stranded seals admitted to wildlife rehabilitation hospitals. Some have pre‐existing problems, while others develop eye problems in captivity, and in particular ulcerative keratitis, due to factors such as large prominent eyes, suboptimal water quality, trauma and infighting. Despite treatment, corneal ulcerations can rapidly progress to ‘melting’ ulcers with subsequent rupture of the globe. In this case series, 32 grey seals (Halichoerus grypus) had conjunctival swabs taken on admission to a UK wildlife hospital to identify ocular bacterial flora and nine had subsequent swabs taken after four weeks to see if this changed in captivity. Additionally, nine seals with ocular pathology were also swabbed. Although a wide range of bacteria were cultured on admission, the most common isolates were Gemella haemolysans, Escherichia coli and Clostridium perfringens. All ‘melting’ ulcers were associated with Pseudomonas aeruginosa, which suggests this bacterial species may be significant in the pathogenesis of progressive stromal ulceration in grey seals.
The antioxidant edaravone prevents cardiac dysfunction by suppressing oxidative stress in type 1 diabetic rats and in high-glucose-induced injured H9c2 cardiomyoblasts
Authors: Ji Lei , Liu Yingying , Zhang Ying , Chang Wenguang , Gong Junli , Wei Shengnan , Li Xudong , Qin Ling
Published: May 2016

Edaravone, a radical scavenger, has been recognized as a potential protective agent for cardiovascular diseases. However, little is known about the effect of edaravone in cardiac complications associated with diabetes. Here, we have demonstrated that edaravone prevents cardiac dysfunction and apoptosis in the streptozotocin-induced type 1 diabetic rat heart. Mechanistic studies revealed that edaravone treatment improved cardiac function and restored superoxide dismutase levels. In addition, treatment of diabetic animals by edaravone increased protein expressions of sirtuin-1 (SIRT-1), peroxisome proliferator activated receptor γ coactivator α (PGC-1α), nuclear factor like-2 (NRF-2), and B cell lymphoma 2 (Bcl-2), and reduced protein expressions of Bax and Caspase-3 compared to the control group. High glucose incubation resulted in the production of reactive oxygen species (ROS) and cell death. Treatment of high-glucose-incubated H9c2 cells by edaravone reduced ROS production and cell death. In addition, the treatment of high-glucose-incubated H9c2 cells by edaravone increased the activity of antioxidative stress by increasing SIRT-1, PGC-1α, and NRF-2, and this treatment also reduced apoptosis by increasing Bcl-2 expression and reducing Bax and Caspase-3 expressions. Knockdown SIRT-1 with small interferer RNA abolished the effects of edaravone. Overall, our data demonstrated that edaravone may be an effective agent against the development of diabetic cardiomyopathy.
Guided Learning of Control Graphs for Physics-Based Characters
Authors: Liu Libin , Panne Michiel Van De , Yin Kangkang
Published: May 2016

The difficulty of developing control strategies has been a primary bottleneck in the adoption of physics-based simulations of human motion. We present a method for learning robust feedback strategies around given motion capture clips as well as the transition paths between clips. The output is a control graph that supports real-time physics-based simulation of multiple characters, each capable of a diverse range of robust movement skills, such as walking, running, sharp turns, cartwheels, spin-kicks, and flips. The control fragments that compose the control graph are developed using guided learning. This leverages the results of open-loop sampling-based reconstruction in order to produce state-action pairs that are then transformed into a linear feedback policy for each control fragment using linear regression. Our synthesis framework allows for the development of robust controllers with a minimal amount of prior knowledge.
Perilipin 5 is dispensable for normal substrate metabolism and in the adaptation of skeletal muscle to exercise training
Authors: Mohktar Ruzaidi A. M. , Montgomery Magda K. , Murphy Robyn M. , Watt Matthew J.
Published: May 2016

Cytoplasmic lipid droplets provide a reservoir for triglyceride storage and are a central hub for fatty acid trafficking in cells. The protein perilipin 5 (PLIN5) is highly expressed in oxidative tissues such as skeletal muscle and regulates lipid metabolism by coordinating the trafficking and the reversible interactions of effector proteins at the lipid droplet. PLIN5 may also regulate mitochondrial function, although this remains unsubstantiated. Hence, the aims of this study were to examine the role of PLIN5 in the regulation of skeletal muscle substrate metabolism during acute exercise and to determine whether PLIN5 is required for the metabolic adaptations and enhancement in exercise tolerance following endurance exercise training. Using muscle-specific Plin5 knockout mice ( Plin5MKO), we show that PLIN5 is dispensable for normal substrate metabolism during exercise, as reflected by levels of blood metabolites and rates of glycogen and triglyceride depletion that were indistinguishable from control (lox/lox) mice. Plin5MKOmice exhibited a functional impairment in their response to endurance exercise training, as reflected by reduced maximal running capacity (20%) and reduced time to fatigue during prolonged submaximal exercise (15%). The reduction in exercise performance was not accompanied by alterations in carbohydrate and fatty acid metabolism during submaximal exercise. Similarly, mitochondrial capacity (mtDNA, respiratory complex proteins, citrate synthase activity) and mitochondrial function (oxygen consumption rate in muscle fiber bundles) were not different between lox/lox and Plin5MKOmice. Thus, PLIN5 is dispensable for normal substrate metabolism during exercise and is not required to promote mitochondrial biogenesis or enhance the cellular adaptations to endurance exercise training.
Cellular response of mucociliary differentiated primary bronchial epithelial cells to diesel exhaust
Authors: Zarcone Maria C. , Duistermaat Evert , van Schadewijk Annemarie , Jedynska Aleksandra , Hiemstra Pieter S. , Kooter Ingeborg M.
Published: May 2016

Diesel emissions are the main source of air pollution in urban areas, and diesel exposure is linked with substantial adverse health effects. In vitro diesel exposure models are considered a suitable tool for understanding these effects. Here we aimed to use a controlled in vitro exposure system to whole diesel exhaust to study the effect of whole diesel exhaust concentration and exposure duration on mucociliary differentiated human primary bronchial epithelial cells (PBEC). PBEC cultured at the air-liquid interface were exposed for 60 to 375 min to three different dilutions of diesel exhaust (DE). The DE mixture was generated by an engine at 47% load, and characterized for particulate matter size and distribution and chemical and gas composition. Cytotoxicity and epithelial barrier function was assessed, as well as mRNA expression and protein release analysis. DE caused a significant dose-dependent increase in expression of oxidative stress markers ( HMOX1 and NQO1; n = 4) at 6 h after 150 min exposure. Furthermore, DE significantly increased the expression of the markers of the integrated stress response CHOP and GADD34 and of the proinflammatory chemokine CXCL8, as well as release of CXCL8 protein. Cytotoxic effects or effects on epithelial barrier function were observed only after prolonged exposures to the highest DE dose. These results demonstrate the suitability of our model and that exposure dose and duration and time of analysis postexposure are main determinants for the effects of DE on differentiated primary human airway epithelial cells.
Reduced force of diaphragm muscle fibers in patients with chronic thromboembolic pulmonary hypertension
Authors: Manders Emmy , Bonta Peter I. , Kloek Jaap J. , Symersky Petr , Bogaard Harm-Jan , Hooijman Pleuni E. , Jasper Jeff R. , Malik Fady I. , Stienen Ger J. M. , Vonk-Noordegraaf Anton , de Man Frances S. , Ottenheijm Coen A. C.
Published: May 2016

Patients with pulmonary hypertension (PH) suffer from inspiratory muscle weakness. However, the pathophysiology of inspiratory muscle dysfunction in PH is unknown. We hypothesized that weakness of the diaphragm, the main inspiratory muscle, is an important contributor to inspiratory muscle dysfunction in PH patients. Our objective was to combine ex vivo diaphragm muscle fiber contractility measurements with measures of in vivo inspiratory muscle function in chronic thromboembolic pulmonary hypertension (CTEPH) patients. To assess diaphragm muscle contractility, function was studied in vivo by maximum inspiratory pressure (MIP) and ex vivo in diaphragm biopsies of the same CTEPH patients ( N = 13) obtained during pulmonary endarterectomy. Patients undergoing elective lung surgery served as controls ( N = 15). Muscle fiber cross-sectional area (CSA) was determined in cryosections and contractility in permeabilized muscle fibers. Diaphragm muscle fiber CSA was not significantly different between control and CTEPH patients in both slow-twitch and fast-twitch fibers. Maximal force-generating capacity was significantly lower in slow-twitch muscle fibers of CTEPH patients, whereas no difference was observed in fast-twitch muscle fibers. The maximal force of diaphragm muscle fibers correlated significantly with MIP. The calcium sensitivity of force generation was significantly reduced in fast-twitch muscle fibers of CTEPH patients, resulting in a ∼40% reduction of submaximal force generation. The fast skeletal troponin activator CK-2066260 (5 μM) restored submaximal force generation to levels exceeding those observed in control subjects. In conclusion, diaphragm muscle fiber contractility is hampered in CTEPH patients and contributes to the reduced function of the inspiratory muscles in CTEPH patients.
The pathophysiology of chronic constipation
Authors: Andrews Christopher N , Storr Martin
Published: May 2016

Constipation is broadly defined as an unsatisfactory defecation characterized by infrequent stools, difficult stool passage or both. The common approach to the pathophysiology of constipation groups the disorder into primary and secondary causes. Primary causes are intrinsic problems of colonic or anorectal function, whereas secondary causes are related to organic disease, systemic disease or medications. The normal process of colonic transit and defecation is discussed, and the etiology of constipation is reviewed.
Novel Strategies for the Improvement of Stem Cells’ Transplantation in Degenerative Retinal Diseases
Authors: Nicoară Simona Delia , Șușman Sergiu , Tudoran Oana , Bărbos Otilia , Cherecheș Gabriela , Aștilean Simion , Potara Monica , Sorițău Olga
Published: May 2016

Currently, there is no cure for the permanent vision loss caused by degenerative retinal diseases. One of the novel therapeutic strategies aims at the development of stem cells (SCs) based neuroprotective and regenerative medicine. The main sources of SCs for the treatment of retinal diseases are the embryo, the bone marrow, the region of neuronal genesis, and the eye. The success of transplantation depends on the origin of cells, the route of administration, the local microenvironment, and the proper combinative formula of growth factors. The feasibility of SCs based therapies for degenerative retinal diseases was proved in the preclinical setting. However, their translation into the clinical realm is limited by various factors: the immunogenicity of the cells, the stability of the cell phenotype, the predilection of SCs to form tumors in situ, the abnormality of the microenvironment, and the association of a synaptic rewiring. To improve SCs based therapies, nanotechnology offers a smart delivery system for biomolecules, such as growth factors for SCs implantation and differentiation into retinal progenitors. This review explores the main advances in the field of retinal transplantology and applications of nanotechnology in the treatment of retinal diseases, discusses the challenges, and suggests new therapeutic approaches in retinal transplantation.
Carbofuran Modulating Functions of Acetylcholinesterase from Rat BrainIn Vitro
Authors: Gupta Vivek Kumar , Pathak Ashutosh , Siddiqi Nikhat Jamal , Sharma Bechan
Published: May 2016

Carbofuran, a potential environmental xenobiotic, has the ability to cross blood brain barrier and to adversely influence brain functions. In the present study, the impact of carbofuran on the biophysical and biochemical properties of rat brain AChE has been evaluatedin vitro. This enzyme was membrane-bound which could be solubilised using Triton-X100 (0.2%, v/v), a nonionic detergent, in the extraction buffer (50 mM phosphate, pH 7.4). The enzyme was highly stable up to one month when stored at-20°C and exhibited optimum activity at pH 7.4 and 37°C. AChE displayed a direct relationship between activity and varying substrate concentrations (acetylthiocholine iodide (ATI)) by following Michaelis-Menten curve. TheKmandVmaxvalues as computed from the Lineweaver-Burk double reciprocal plot of the data were found to be 0.07 mM and 0.066 µmole/mL/min, respectively. The enzyme exhibited IC50value for carbofuran equal to 6.0 nM. The steady-state kinetic studies to determine mode of action of carbofuran on rat brain AChE displayed it to be noncompetitive in nature withKivalue equal to 5 nm. These experiments suggested that rat brain AChE was very sensitive to carbofuran and this enzyme might serve as a significant biomarker of carbofuran induced neurotoxicity.
Guizhi Fuling Wan, a Traditional Chinese Herbal Formula, Sensitizes Cisplatin‐Resistant Human Ovarian Cancer Cells through Inactivation of the PI3K/AKT/mTOR Pathway
Authors: Han Li , Guo Xiaojuan , Bian Hua , Yang Lei , Chen Zhong , Zang Wenhua , Yang Jingke
Published: May 2016

The aim of the study was to explore the possible mechanisms that Guizhi Fuling Wan (GFW) enhances the sensitivity of the SKOV3/DDP ovarian cancer cells and the resistant xenograft tumours to cisplatin. Rat medicated sera containing GFW were prepared by administering GFW to rats, and the primary bioactive constituents of the sera were gallic acid, paeonol, and paeoniflorin analysed by HPLC/QqQ MS. Cell counting kit‐8 analysis was shown that coincubation of the sera with cisplatin/paclitaxel enhanced significantly the cytotoxic effect of cisplatin or paclitaxel in SKOV3/DDP cells. The presence of the rat medicated sera containing GFW resulted in an increase in rhodamine 123 accumulation by flow cytometric assays and a decrease in the protein levels of P‐gp, phosphorylation of AKT at Ser473, and mTOR in a dose‐dependent manner in SKOV3/DDP cells by western blot analysis, but the sera had no effect on the protein levels of PI3K p110α and total AKT. The low dose of GFW enhanced the anticancer efficacy of cisplatin and paclitaxel treatment in resistant SKOV3/DDP xenograft tumours. GFW could sensitize cisplatin‐resistant SKOV3/DDP cells by inhibiting the protein level and function of P‐gp, which may be medicated through inactivation of the PI3K/AKT/mTOR pathway.
Financial Time Series Prediction Using Elman Recurrent Random Neural Networks
Authors: Wang Jie , Wang Jun , Fang Wen , Niu Hongli
Published: May 2016

In recent years, financial market dynamics forecasting has been a focus of economic research. To predict the price indices of stock markets, we developed an architecture which combined Elman recurrent neural networks with stochastic time effective function. By analyzing the proposed model with the linear regression, complexity invariant distance (CID), and multiscale CID (MCID) analysis methods and taking the model compared with different models such as the backpropagation neural network (BPNN), the stochastic time effective neural network (STNN), and the Elman recurrent neural network (ERNN), the empirical results show that the proposed neural network displays the best performance among these neural networks in financial time series forecasting. Further, the empirical research is performed in testing the predictive effects of SSE, TWSE, KOSPI, and Nikkei225 with the established model, and the corresponding statistical comparisons of the above market indices are also exhibited. The experimental results show that this approach gives good performance in predicting the values from the stock market indices.
A Novel Clustering Method Combining ART with Yu’s Norm for Fault Diagnosis of Bearings
Authors: Xu Zengbing , Li Youyong , Wang Zhigang , Xuan Jianping
Published: May 2016

Clustering methods have been widely applied to the fault diagnosis of mechanical system, but the characteristic that the number of cluster needs to be determined in advance limits the application range of the method. In this paper, a novel clustering method combining the adaptive resonance theory (ART) with the similarity measure based on the Yu’s norm is presented and applied to the fault diagnosis of rolling element bearings, which can be adaptive to generate the number of cluster by the vigilance parameter test. Time-domain features, frequency-domain features, and time series model parameters are extracted to demonstrate the fault-related information about the bearings, and then considering the irrelevance or redundancy of some features many salient features are selected by an improved distance discriminant technique and input into the proposed clustering method to diagnose the faults of bearings. The experiment results confirmed that the proposed clustering method can diagnose the fault categories accurately and has better diagnosis performance compared with fuzzy ART and Self-Organizing Feature Map (SOFM).
An Azimuth-Based Dead-End Avoiding Routing Mechanism for Providing Reliable IP Connectivity in Multihop Wireless Networks
Authors: Yu Hyun , Ahn Sanghyun
Published: May 2016

In a multihop wireless network, such as a wireless sensor network (WSN), with nodes being aware of their locations, the geographic routing scheme is an effective way of delivering packets to their destinations because of its 1-hop beacon broadcasting based routing related information exchange operation. The routing information obtained via 1-hop beaconing is local in the sense that it is just 1-hop compared to the multihop end-to-end routing. Hence, at some point, packets may experience no more place to be forwarded to (i.e., dead-ends). In this paper, we propose a geographical routing mechanism adopting the concept of the azimuth to reduce the possibility of packets confronting dead-ends. In other words, the node with a packet to be forwarded to the final destination figures out the next-hop node by utilizing the azimuth of the destination as a routing metric. Besides, we propose additional routing metrics for stable next-hop node selection to provide reliable IP connectivity. In order to validate the performance of the proposed routing mechanism, we evaluate its performance through the NS-2 based simulations and show that our mechanism outperforms the other schemes in terms of the packet delivery success rate, the end-to-end delay, and the number of dead-end encounters.
Neuroendocrine Cancer of Rectum Metastasizing to Ovary
Authors: Amin Sapna Vinit , Kumaran Aswathy , Bharatnur Sunanda , Vasudeva Akhila , Udupa Kartik , Venkateshiah Dinesh Bangalore , Bhat Shaila T.
Published: May 2016

Neuroendocrine carcinomas (NECs) are rare malignancies that originate from the hormone-producing cells of the body’s neuroendocrine system. Rectal high grade NEC (HG-NEC) constituting less than 1% of colorectal cancers can cause large ovarian metastasis that may be the initial presenting complaint. Ovarian Krukenberg tumor from a primary rectal HG-NEC is a very unusual and exceedingly uncommon differential diagnosis for secondary ovarian malignancy. This case report describes one such extremely rare case of a woman who had presented to the gynecology department with features suggestive of ovarian malignancy and was ultimately diagnosed to have Krukenberg tumor originating from neuroendocrine cancer of rectum. We felt this is a good opportunity to spread more light on neuroendocrine neoplasms that are very rare in gynecological practice.
Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade
Authors: Lotem Michal , Merims Sharon , Frank Stephen , Hamburger Tamar , Nissan Aviram , Kadouri Luna , Cohen Jonathan , Straussman Ravid , Eisenberg Galit , Frankenburg Shoshana , Carmon Einat , Alaiyan Bilal , Shneibaum Shlomo , Ozge Ayyildiz Zeynep , Isbilen Murat , Mert Senses Kerem , Ron Ilan , Steinberg Hanna , Smith Yoav , Shiloni Eitan , Gure Ali Osmay , Peretz Tamar
Published: May 2016

Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence.Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH) response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival.Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p=0.0001) 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2), MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p=0.007).Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity.
Garlic Attenuates Plasma and Kidney ACE‐1 and AngII Modulations in Early Streptozotocin‐Induced Diabetic Rats: Renal Clearance and Blood Pressure Implications
Authors: Al-Qattan Khaled K. , Thomson Martha , Jayasree Divya , Ali Muslim
Published: May 2016

Raw garlic aqueous extract (GE) has ameliorative actions on the renin‐angiotensin system in type‐1 diabetes mellitus (DM); however its effects on plasma and kidney angiotensin I converting enzyme type‐1 (ACE‐1) and angiotensin II (AngII) require further elucidation. This study investigated the effect of GE on plasma and kidney ACE‐1 and AngII concentrations and in relation to systemic and renal clearance indicators significant to blood pressure (BP) homeostasis in early streptozotocin‐ (STZ‐) induced type‐1 DM. Normal rats (n = 10) received 0.5 mL normal saline (NR/NS), diabetic rats (n = 10) received 0.5 mL NS (DR/NS), and treated diabetic rats (n = 10) received 50 mg/0.1 mL/100 g body weight GE (DR/GE) as daily intraperitoneal injections for 8 weeks. Compared to NR/NS, DR/NS showed a significant increase in plasma ACE‐1 and AngII and conversely a decrease in kidney ACE‐1 and AngII. These changes were associated with an increase in BP and clearance functions. Alternatively and compared to DR/NS, DR/GE showed normalization or attenuation in plasma and kidney ACE‐1 and AngII. These GE induced rectifications were associated with moderation in BP elevation and renal clearance functions. Garlic attenuates modulations in plasma and kidney ACE‐1 and AngII, in addition to BP and renal clearance function in type‐1 DM.
Influence of Environmental Factors and Relationships between Vanadium, Chromium, and Calcium in Human Bone
Authors: Lanocha-Arendarczyk Natalia , Kosik-Bogacka Danuta I. , Kalisinska Elzbieta , Sokolowski Sebastian , Kolodziej Lukasz , Budis Halina , Safranow Krzysztof , Kot Karolina , Ciosek Zaneta , Tomska Natalia , Galant Katarzyna
Published: May 2016

The aim of this study was to investigate the impact of environmental factors on the concentrations of vanadium (V), chromium (Cr), and calcium (Ca) and to examine the synergistic or antagonistic relationships between these metals, in cartilage (C), cortical bone (CB), and spongy bone (SB) samples obtained following hip joint surgery on patients with osteoarthritis in NW Poland. We found significantly higher concentrations of V and Cr in spongy bone in patients who consumed game meat and also those with prosthetic implants. Chromium levels were significantly lower in patients with kidney diseases. The greatest positive correlations were found between spongy bone V and (i) the amount of consumed beer and (ii) seafood diet. Correlation analysis also showed a significant correlation between Cr levels and seafood diet. To a certain extent these results indicate that the concentrations of V, Cr, and Ca in the human hip joint tissues are connected with occupational exposure, kidney diseases, diet containing game meat, sea food, beer, and the presence of implants. Furthermore, we noted new types of interactions in specific parts of the femoral head. Vanadium may contribute to the lower bone Ca levels, especially in the external parts (cartilage and cortical bone).
Performance Analysis of M2M Sensor Networks
Authors: Wang Jingjing , Xu Lingwei , Dong Xinli , Shi Wei , Niu Qiuna
Published: May 2016

The average symbol error probability (ASEP) and outage probability (OP) performance of mobile-to-mobile (M2M) senor networks employing transmit antenna selection (TAS) and selection combining (SC) over N-Nakagami fading channels are investigated in this paper. Based on the moment generating function (MGF) approach, the exact ASEP expressions are derived for several modulation schemes. The exact closed-form OP expressions are also presented. Then, the ASEP and OP performance under different conditions are evaluated through numerical simulations to confirm the accuracy of the analysis. The simulation results show that the number of antennas, the fading coefficient, and the number of cascaded components have an important influence on the ASEP and OP performance.
Acupuncture Decreases NF‐κB p65, miR‐155, and miR‐21 and Increases miR‐146a Expression in Chronic Atrophic Gastritis Rats
Authors: Zhang Jialing , Huang Kangbai , Zhong Guoxin , Huang Yong , Li Suhe , Qu Shanshan , Zhang Jiping
Published: May 2016

Acupuncture has been used to treat chronic atrophic gastritis (CAG) in traditional Chinese medicine (TCM) for centuries. In this study, we evaluated the effect of acupuncture at Zusanli (ST36), Zhongwan (CV12), and Pishu (BL20) acupoints on weight changes of rats, histological changes of gastric glands, and expressions changes of nuclear factor‐kappa B (NF‐κB) p65, microRNA‐ (miR‐) 155, miR‐21, and miR‐146a in CAG rats induced by N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG) combined with irregular diet. Consequently, we found that acupuncture treatment elevated body weight of rats significantly when compared to the model group. By observing histological changes, we found that the acupuncture group showed better improvement of gastric mucosa injury than the model group. Our results also demonstrated upregulation of NF‐κB p65, miR‐155, and miR‐21 in gastric tissue of CAG rats and a positive correlation between miR‐155 and miR‐21. Relatively, expression of miR‐146a was downregulated and negative correlation relationships between miR‐146a and miR‐155/miR‐21 in CAG rats were observed. Additionally, expressions of NF‐κB p65, miR‐155, and miR‐21 were downregulated and miR‐146a was upregulated after acupuncture treatment. Taken together, our data imply that acupuncture can downregulate NF‐κB p65, miR‐155, and miR‐21 and upregulate miR‐146a expression in CAG rats. NF‐κB p65, miR‐155, miR‐21, and miR‐146a may play important roles in therapeutic effect of acupuncture in treating CAG.
Mouse Models in Prostate Cancer Translational Research: From Xenograft to PDX
Authors: Rea Domenica , del Vecchio Vitale , Palma Giuseppe , Barbieri Antonio , Falco Michela , Luciano Antonio , De Biase Davide , Perdonà Sisto , Facchini Gaetano , Arra Claudio
Published: May 2016

Despite the advancement of clinical and preclinical research on PCa, which resulted in the last five years in a decrement of disease incidence by 3-4%, it remains the most frequent cancer in men and the second for mortality rate. Based on this evidence we present a brief dissertation on numerous preclinical models, comparing their advantages and disadvantages; among this we report the PDX mouse models that show greater fidelity to the disease, in terms of histopathologic features of implanted tumor, gene and miRNA expression, and metastatic pattern, well describing all tumor progression stages; this characteristic encourages the translation of preclinical results. These models become particularly useful in meeting the need of new treatments identification that eradicate PCa bone metastases growing, clarifying pathway of angiogenesis, identifying castration-resistant stem-like cells, and studying the antiandrogen therapies. Also of considerable interest are the studies of 3D cell cultures derived from PDX, which have the ability to maintain PDX cell viability with continued native androgen receptor expression, also showing a differential sensitivity to drugs. 3D PDX PCa may represent a diagnostic platform for the rapid assessment of drugs and push personalized medicine. Today the development of preclinical models in vitro and in vivo is necessary in order to obtain increasingly reliable answers before reaching phase III of the drug discovery.
Rapalogs Efficacy Relies on the Modulation of Antitumor T-cell Immunity
Authors: Beziaud Laurent , Mansi Laura , Ravel Patrice , Marie-Joseph Elodie Lauret , Laheurte Caroline , Rangan Laurie , Bonnefoy Francis , Pallandre Jean-René , Boullerot Laura , Gamonet Clémentine , Vrecko Sindy , Queiroz Lise , Maurina Tristan , Mouillet Guillaume , Hon Thierry Nguyen Tan , Curtit Elsa , Royer Bernard , Gaugler Béatrice , Bayry Jagadeesh , Tartour Eric , Thiery-Vuillemin Antoine , Pivot Xavier , Borg Christophe , Godet Yann , Adotévi Olivier
Published: May 2016

The rapalogs everolimus and temsirolimus that inhibit mTOR signaling are used as antiproliferative drugs in several cancers. Here we investigated the influence of rapalogs-mediated immune modulation on their antitumor efficacy. Studies in metastatic renal cell carcinoma patients showed that everolimus promoted high expansion of FoxP3+Helios+Ki67+ regulatory CD4 T cells (Tregs). In these patients, rapalogs strongly enhanced the suppressive functions of Tregs, mainly in a contact-dependent manner. Paradoxically, a concurrent activation of spontaneous tumor-specific Th1 immunity also occurred. Furthermore, a high rate of Eomes+CD8+ T cells was detected in patients after a long-term mTOR inhibition. We found that early changes in the Tregs/antitumor Th1 balance can differentially shape the treatment efficacy. Patients presenting a shift toward decreased Tregs levels and high expansion of antitumor Th1 cells showed better clinical responses. Studies conducted in tumor-bearing mice confirmed the deleterious effect of rapalogs-induced Tregs via a mechanism involving the inhibition of antitumor T-cell immunity. Consequently, the combination of temsirolimus plus CCR4 antagonist, a receptor highly expressed on rapalogs-exposed Tregs, was more effective than monotherapy. Altogether, our results describe for the first time a dual impact of host adaptive antitumor T-cell immunity on the clinical effectiveness of rapalogs and prompt their association with immunotherapies. Cancer Res; 76(14); 4100–12. ©2016 AACR.
All Things in Moderation: Prevention of Intestinal Adenomas by DNA Hypomethylation
Authors: Lee Kwang-Ho , Laird Peter W.
Published: May 2016

DNA hypomethylation can prevent intestinal tumorigenesis, presumably by reducing epigenetic silencing of tumor-suppressor genes. A study in this issue by Sheaffer and colleagues challenges this notion by showing that severe DNA hypomethylation by tissue-specific Dnmt1 knockout can actually promote intestinal adenoma formation. Cancer Prev Res; 9(7); 509–11. ©2016 AACR.

See related article by Sheaffer, et al., p. 534
Report of an Early Stopped Randomized Trial Comparing Cisplatin vs. Cisplatin/Ifosfamide/ 5-Fluorouracil in Recurrent Cervical Cancer
Authors: Cadron Isabelle , Jakobsen Anders , Vergote Ignace
Published: May 2016

This paper reports on an early stopped prospective randomized phase III trial comparing cisplatin, ifosfamide and 5-fluorouracil (PIF) with cisplatin monotherapy in the treatment of recurrent cervical cancer. The aim of the study was to compare response rates, survival, side effects and quality of life. Cisplatin monotherapy was given in a dose of 37.5 mg/m2 on days 1 + 2 of 4-week schedules. In the PIF regimen, cisplatin was given in the same manner, ifosfamide in a dose of 2 g/m2 on days 1 + 2 together with mesna 0.5 g/m2, 5-fluorouracil 500 mg/m2 on days 1 + 2, and folinic acid 30 mg/m2 also on days 1 + 2. This regimen was also given in 4-week schedules. The intention had been to include 200 patients in the trial but because of poor accrual the trial was stopped prematurely. Twenty-four patients were included, 3 of which not eligible, and of the remaining 21 patients, 11 were randomized to the cisplatin group and 10 to the PIF group. Median survival for the cisplatin group amounted to 13 months and for the PIF regimen to 12.3 months. The most important side effects were hematologic, with more thrombocytopenia and leukopenia in the PIF regimen. The response rate for the PIF regimen was 40% (4 partial remissions) and 9% for the cisplatin group (1 complete remission). No firm conclusions can be drawn from this trial due to the low number of participants. Still, we believe that the response and survival rates observed with PIF are interesting and that it is important to report all trials, even if they are stopped earlier than intended.
Characterization of Kidney and Skeleton Phenotypes of Mice Double Heterozygous for Foxc1 and Foxc2
Authors: Motojima Masaru , Tanimoto Sho , Ohtsuka Masato , Matsusaka Taiji , Kume Tsutomu , Abe Koichiro
Published: May 2016

Foxc1 and Foxc2 play key roles in mouse development. Foxc1 mutant mice develop duplex kidneys with double ureters, and lack calvarial and sternal bones. Foxc2 null mice have been reported to have glomerular abnormalities in the kidney and axial skeletal anomalies. Expression patterns of Foxc1 and Foxc2 overlap extensively and are believed to have interactive roles. However, cooperative roles of these factors in glomerular and skeletal development are unknown. Therefore, we examined the kidneys and skeleton of mice that were double heterozygous for Foxc1 and Foxc2. Double heterozygotes were generated by mating single heterozygotes for Foxc1 and Foxc2. Newborn double heterozygous mice showed many anomalies in the kidney and urinary tract resembling Foxc1 phenotypes, including duplex kidneys, double ureters, hydronephrosis and mega-ureter. Some mice had hydronephrosis alone. In addition to these macroscopic anomalies, some mice had abnormal glomeruli and disorganized glomerular capillaries observed in Foxc2 phenotypes. Interestingly, these mice also showed glomerular cysts not observed in the single-gene knockout of either Foxc1 or Foxc2 but observed in conditional knockout of Foxc2 in the kidney. Serial section analysis revealed that all cystic glomeruli were connected to proximal tubules, precluding the possibility of atubular glomeruli resulting in cyst formation. Dorsally opened vertebral arches and malformations of sternal bones in the double heterozygotes were phenotypes similar to Foxc1 null mice. Absent or split vertebral bodies in the double heterozygotes were phenotypes similar to Foxc2 null mice, whilst hydrocephalus noted in the Foxc1 phenotype was not observed. Thus, Foxc1 and Foxc2 have a role in kidney and axial skeleton development. These transcription factors might interact in the regulation of the embryogenesis of these organs.
Taurine Reduced Epidural Fibrosis in Rat Models after Laminectomy via Downregulating EGR1
Authors: Yang Lei , Tang Jian , Chen Hongtao , Ge Dawei , Sui Tao , Que Jun , Cao Xiaojian , Ge Yingbin
Published: May 2016

Background/Aims: Epidural fibrosis, a common complication after laminectomy, has been demonstrated to be closely associated with poor surgical outcomes. Previous studies showed that taurine had remarkable anti-fibrotic effects on lung and liver fibrosis. We performed this study to investigate the effects of taurine in rat models of epidural fibrosis after laminectomy and to explore the potential molecular mechanism. Methods: Laminectomy was performed on each rat to establish epidural fibrosis model. After taurine treatment, Masson's trichrome and immunohistochemistry staining were used to examine epidural fibrosis. Cell viability was determined using the Cell Counting Kit-8 assay. Annexin V/Propidium Iodide double staining was performed to detect fibroblasts apoptosis. Microarray was adopted to identify significantly changed mRNAs. mRNA expression was measured by qRT-PCR. Lentivirus infection was performed to establish stable knockdown and overexpression cell lines. The expression of fibrosis-related proteins was determined via Western blot. Results: Taurine treatment markedly reduced laminectomy-induced epidural fibrosis in rat models. However, this effect of taurine was independent on TGF-β/Smad pathway, evidenced by no change in the expression of TGF-β and its receptors. Besides, taurine had almost no effect on cell apoptosis. Interestingly, taurine treatment significantly decreased expression of EGR1 (Early growth response protein 1), an enhancer of fibrosis, both in vivo and in vitro. Furthermore, overexpression of EGR1 increased activation of fibroblasts, while EGR1 knockdown achieved an opposite effect, indicating that EGR1 plays a key role in the inhibitory effect of taurine on TGF-β-induced fibrosis. Conclusions: Reduced epidural fibrosis in vivo and decreased activation of fibroblasts in vitro after taurine treatment was mediated by EGR1. Taurine promises to be a potential prevention for epidural fibrosis after laminectomy.
Controlled Penetration of a Novel Dimeric Ceramide into and across the Stratum Corneum Using Microemulsions and Various Types of Semisolid Formulations
Authors: Neubert Reinhard H.H. , Sonnenberger Stefan , Dobner Bodo , Gray Jr. Charles W. , Barger K. Natalie , Sevi-Maxwell Kara , Sommer Elfi , Wohlrab Johannes
Published: May 2016

Ceramides (CERs) are integral parts of the intercellular lipid lamellae of the stratum corneum (SC), which is responsible for the barrier function of the skin. Many skin diseases such as atopic dermatitis and psoriasis are associated with the depletion or disturbance of the level of CERs in the SC. Administration of an exogenous novel dimeric ceramide (dCER) deep into the SC may help to stabilize the SC barrier substantially and to treat some skin disease conditions. Consequently, with the help of the existing technology, it might be possible to formulate various pharmaceutical dosage forms that can facilitate penetration of dCER into the SC. Therefore, the penetration of dCER was studied using a high-performance liquid chromatography/atmospheric-pressure ionization/mass spectrometry method for the detection and quantification of exogenous dCER in the SC as well as other skin layers. Penetration studies were carried out in the Franz diffusion cell using excised human skin ex vivo. Penetration of dCER was studied with 3 model formulations: a colloidal formulation (microemulsion), a cream formulation with ethoxydiglycol as penetration enhancer and a nanoformulation. The highest concentrations of dCER in the different skin layers were found after application of the cream with penetration enhancer. Surprisingly, the lowest concentrations of dCER in the different skin layers were found after application of the microemulsion.
Retroclival Pneumocephalus Associated with Bilateral Abducens Palsy in a Child
Authors: Paiva Aline Lariessy Campos , de Aguiar Guilherme Brasileiro , Ferraz Vinicius Riccieri , Araújo João Luiz Vitorino , Toita Milton Hikaro , Veiga José Carlos Esteves
Published: May 2016

Traumatic brain injury (TBI) is less common in children than in adults. Posterior fossa lesions are even more uncommon, but, when present, are usually epidural hematomas. These lesions, even when small, may have a bad outcome because of the possibility of compression of the important structures that the infratentorial compartment contains, such as the brainstem and cranial nerves, and the constriction of the fourth ventricle, causing acute hydrocephalus. Although unusual, posterior fossa lesions are increasingly being diagnosed because of the better quality of and easier access to cranial tomography. In this paper, we report a case of a 12-year-old male patient who had suffered a TBI and presented with several pneumocephali, one of them in the retroclival region, causing a mass effect and then compression of the sixth cranial nerve which is the most susceptible to these injuries. We discuss these traumatic posterior fossa lesions, with an emphasis on retroclival pneumocephalus, not yet described in the literature in association with bilateral abducens palsy. In addition, we discuss associated lesions and the trauma mechanism.
Feasibility of Exercise Training in Cancer Patients Scheduled for Elective Gastrointestinal Surgery
Authors: Valkenet Karin , Trappenburg Jaap C.A. , Schippers Carlo C. , Wanders Lisa , Lemmens Lidwien , Backx Frank J.G. , van Hillegersberg Richard
Published: May 2016

Background/Aims: This study examines the feasibility of a preoperative exercise program to improve the physical fitness of a patient before gastrointestinal surgery. Methods: An outpatient exercise program was developed to increase preoperative aerobic capacity, peripheral muscle endurance and respiratory muscle function in patients with pancreatic, liver, intestinal, gastric or esophageal cancer. During a consult at the outpatient clinic, patients were invited to participate in the exercise program when their surgery was not scheduled within 2 weeks. Results: The 115 participants followed on average 5.7 (3.5) training sessions. Adherence to the exercise program was high: 82% of the planned training sessions were attended, and no adverse events occurred. Mixed model analyses showed a significant increase of maximal inspiratory muscle strength (84.1-104.7 cm H2O; p = 0.00) and inspiratory muscle endurance (35.0-39.5 cm H2O; p = 0.00). No significant changes were found in aerobic capacity and peripheral muscle strength. Conclusion: This exercise program in patients awaiting oncological surgery is feasible in terms of participation and adherence. Inspiratory muscle function improved significantly as a result of inspiratory muscle training. The exercise program however failed to result in improved aerobic capacity and peripheral muscle strength, probably due to the limited number of training sessions as a result of the restricted time interval between screening and surgery.
Strategic Matching of Teachers and Schools with (and without) Accountability Pressure
Authors: Ahn Tom
Published: May 2016

Accountability systems are designed to introduce market pressures to increase efficiency in education. One potential channel by which this can occur is to match with effective teachers in the transfer market. I use a smooth maximum score estimator model, North Carolina data, and the state's bonus system to analyze how teachers and schools change matching behavior in response to accountability pressure. Schools under a high degree of accountability pressure match with teachers who are better at raising test scores. Estimation with a control year sample (when pressure was absent) bolsters these findings. Accountability pressure seems to motivate schools to compete for effective teachers.