bluuebunny/crossref_metadata_2025 huggingface dataset:
The Preparation and In Vitro Evaluations of a Nanoscaled Injectable Bone Repair Material
Authors: Liu Xinhui , Zhu Chao , Li Yijiong , Yan Yueling , Hou Chuanyong , Wang Hua , Yang Yelin , Guan Guoping , Feng Qingling
Published: May 2015

There are usually two forms of bone repair materials, block and granular, for common clinical use. This paper describes a novel injectable material, nano‐HA/collagen/alginate (nHAC/Alg) composite biomaterial, including its preparation and evaluations in vitro. Based on the idea of bionics and the study of collagen/calcium phosphate salt composite materials, the injectable bone repair material was developed. Then, human bone marrow stem cells (hBMSCs) were cultured on the nHAC/Alg material. The cell attachment, proliferation, and differentiation were evaluated with inverted microscope, scanning electron microscope, laser scanning confocal microscope, 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) analysis, and alkaline phosphatase (ALP) test. The results showed that nHAC/Alg not only had no negative effect on cellular functions but also promotes cell proliferation and differentiation into osteogenic cells, which suggests that the nanoscaled injectable bone repair material has good clinical application prospects for bone repair.
Evidence of Insulin Resistance and Other Metabolic Alterations in Boys with Duchenne or Becker Muscular Dystrophy
Authors: Rodríguez-Cruz Maricela , Sanchez Raúl , Escobar Rosa E. , Cruz-Guzmán Oriana del Rocío , López-Alarcón Mardia , Bernabe García Mariela , Coral-Vázquez Ramón , Matute Guadalupe , Velázquez Wong Ana Claudia
Published: May 2015

Aim. Our aim was (1) to determine the frequency of insulin resistance (IR) in patients with Duchenne/Becker muscular dystrophy (DMD/BMD), (2) to identify deleted exons of DMD gene associated with obesity and IR, and (3) to explore some likely molecular mechanisms leading to IR.Materials and Methods. In 66 patients with DMD/BMD without corticosteroids treatment, IR, obesity, and body fat mass were evaluated. Molecules involved in glucose metabolism were analyzed in muscle biopsies. Results show that 18.3%, 22.7%, and 68% were underweight, overweight, or obese, and with high adiposity, respectively; 48.5% and 36.4% presented hyperinsulinemia and IR, respectively. Underweight patients (27.3%) exhibited hyperinsulinemia and IR. Carriers of deletions in exons 45 (OR = 9.32; 95% CI = 1.16–74.69) and 50 (OR = 8.73; 95% CI = 1.17–65.10) from DMD gene presented higher risk for IR than noncarriers. We observed a greater staining of cytoplasmic aggregates for GLUT4 in muscle biopsies than healthy muscle tissue.Conclusion. Obesity, hyperinsulinemia, and IR were observed in DMD/BMD patients and are independent of corticosteroids treatment. Carriers of deletion in exons 45 or 50 from DMD gene are at risk for developing IR. It is suggested that alteration in GLUT4 in muscle fibers from DMD patients could be involved in IR.
Numerical Modeling and Mechanical Analysis of Flexible Risers
Authors: Li J. Y. , Qiu Z. X. , Ju J. S.
Published: May 2015

ABAQUS is used to create a detailed finite element model for a 10-layer unbonded flexible riser to simulate the riser’s mechanical behavior under three load conditions: tension force and internal and external pressure. It presents a technique to create detailed finite element model and to analyze flexible risers. In FEM model, all layers are modeled separately with contact interfaces; interaction between steel trips in certain layers has been considered as well. FEM model considering contact interaction, geometric nonlinearity, and friction has been employed to accurately simulate the structural behavior of riser. The model includes the main features of the riser geometry with very little simplifying assumptions. The model was solved using a fully explicit time-integration scheme implemented in a parallel environment on an eight-processor cluster and 24 G memory computer. There is a very good agreement obtained from numerical and analytical comparisons, which validates the use of numerical model here. The results from the numerical simulation show that the numerical model takes into account various details of the riser. It has been shown that the detailed finite element model can be used to predict riser’s mechanics behavior under various load cases and bound conditions.
Clinical Effects of Novel Nanoscaled Core Decompression Rods Combined with Umbilical Cord Mesenchymal Stem Cells on the Treatment of Early Osteonecrosis of the Femoral Head
Authors: Gao Hongyang , Zhang Guoping , Wang Jian , Zhao Feng , Zhang Yuchen , Wang Wei , You Yang
Published: May 2015

Osteonecrosis of the femoral head (ONFH) is one of the most common diseases in orthopedics. In this study, we investigated the clinical effects of novel nanoscaled core decompression rods combined with mesenchymal stem cells on the treatment of the ONFH. 12 adult patients with early ONFH (at the stage of Ficat II) received the treatment using the implantation of novel nanoscaled core decompression rods combined with umbilical cord mesenchymal stem cells. The grade of the patients’ hip was scored by Harris marking system before and after the surgery, and then paired t‐test was done. We assessed the curative efficiency based on the change of the patients before and after the surgery. In particular, the survival rate of femoral head was assessed at 12 months after the surgery. The results demonstrated that according to the standard of Harris Scoring, the average grade of hip joint before the surgery was 54.16  ±  4.23 points while average grade of hip joint at 12 months after the surgery was 85.28  ±  3.65 points. So, the implantation of the novel nanoscaled core decompression rods combined with mesenchymal stem cells had satisfactory clinical effects, suggesting that this implantation should be effective to treat early ONFH.
Biofilm Formation byHelicobacter pyloriand Its Involvement for Antibiotic Resistance
Authors: Yonezawa Hideo , Osaki Takako , Kamiya Shigeru
Published: May 2015

Bacterial biofilms are communities of microorganisms attached to a surface. Biofilm formation is critical not only for environmental survival but also for successful infection.Helicobacter pyloriis one of the most common causes of bacterial infection in humans. Some studies demonstrated that this microorganism has biofilm forming ability in the environment and on human gastric mucosa epithelium as well as onin vitroabiotic surfaces. In the environment,H. pyloricould be embedded in drinking water biofilms through water distribution system in developed and developing countries so that the drinking water may serve as a reservoir forH. pyloriinfection. In the human stomach,H. pyloriforms biofilms on the surface of gastric mucosa, suggesting one possible explanation for eradication therapy failure. Finally, based on the results ofin vitroanalyses,H. pyloribiofilm formation can decrease susceptibility to antibiotics andH. pyloriantibiotic resistance mutations are more frequently generated in biofilms than in planktonic cells. These observations indicated thatH. pyloribiofilm formation may play an important role in preventing and controllingH. pyloriinfections. Therefore, investigation ofH. pyloribiofilm formation could be effective in elucidating the detailed mechanisms of infection and colonization by this microorganism.
An Optimization-Based Impedance Approach for Robot Force Regulation with Prescribed Force Limits
Authors: Portillo-Vélez R. de J. , Rodriguez-Angeles A. , Cruz-Villar C. A.
Published: May 2015

An optimization based approach for the regulation of excessive or insufficient forces at the end-effector level is introduced. The objective is to minimize the interaction force error at the robot end effector, while constraining undesired interaction forces. To that end, a dynamic optimization problem (DOP) is formulated considering a dynamic robot impedance model. Penalty functions are considered in the DOP to handle the constraints on the interaction force. The optimization problem is online solved through the gradient flow approach. Convergence properties are presented and the stability is drawn when the force limits are considered in the analysis. The effectiveness of our proposal is validated via experimental results for a robotic grasping task.
Interaction ofPanax quinquefoliusSaponin and Dual Antiplatelets on Vascular Endothelial Function in Rats with Acute Myocardial Infarction
Authors: Wang Baojun , Liu Yue , Shang Qinghua , Zhang Qingxiang , Zhang Lei , Liu Jiangang , Shi Dazhuo
Published: May 2015

The objective of this study is to investigate the interaction ofPanax quinquefoliussaponin (PQS) and dual antiplatelets (aspirin and clopidogrel) on antiplatelet activity and vascular endothelial function in rats with acute myocardial infarction (AMI). Forty-eight male SD rats were randomly designed into sham group, model group, dual antiplatelet group, and PQS plus dual antiplatelet group. AMI rats were induced by ligation of left anterior descending coronary artery (LAD) and dual antiplatelet agents and additional PQS to dual antiplatelets were intragastrically administered for 28 days, respectively. The ventricular cavity area and cardiac transverse area ratio in PQS + dual antiplatelet group showed a decreased tendency. PAgT(%) decreased significantly in both dual antiplatelet group and PQS + dual antiplatelet group. TXB2concentration significantly decreased in dual antiplatelet and PQS + dual antiplatelet groups, whereas 6-keto-PGF1αconcentration significantly increased in PQS + dual antiplatelet group. Rats in PQS + dual antiplatelet group demonstrated a significant decrease in plasma ET-1 concentration and an increase in serum NO concentration compared with dual antiplatelet group. The combination therapy of PQS and dual antiplatelets showed some beneficial effects on vascular endothelial function and ventricular remodeling in rats with AMI.
Comparison of Lipoprotein-Associated Phospholipase A2 and High Sensitive C-Reactive Protein as Determinants of Metabolic Syndrome in Subjects without Coronary Heart Disease: In Search of the Best Predictor
Authors: Acevedo Mónica , Varleta Paola , Kramer Verónica , Valentino Giovanna , Quiroga Teresa , Prieto Carolina , Parada Jacqueline , Adasme Marcela , Briones Luisa , Navarrete Carlos
Published: May 2015

High sensitivity C-reactive protein (hsCRP) is a marker of metabolic syndrome (MS) and cardiovascular (CV) disease. Lipoprotein-associated phospholipase A2 (Lp-PLA2) also predicts CV disease. There are no reports comparing these markers as predictors of MS.Methods. Cross-sectional study comparing Lp-PLA2 and hsCRP as predictors of MS in asymptomatic subjects was carried out; 152 subjects without known atherosclerosis participated. Data were collected on demographics, cardiovascular risk factors, anthropometric and biochemical measurements, and hsCRP and Lp-PLA2 activity levels. A logistic regression analysis was performed with each biomarker and receiver operating characteristic (ROC) curves were constructed for MS.Results. Mean age was 46 ± 11 years, and 38% of the subjects had MS. Mean Lp-PLA2 activity was 185 ± 48 nmol/mL/min, and mean hsCRP was 2.1 ± 2.2 mg/L. Subjects with MS had significantly higher levels of Lp-PLA2 (P=0.03) and hsCRP (P<0.0001) than those without MS. ROC curves showed that both markers predicted MS.Conclusion. Lp-PLA2 and hsCRP are elevated in subjects with MS. Both biomarkers were independent and significant predictors for MS, emphasizing the role of inflammation in MS. Further research is necessary to determine if inflammation predicts a higher risk for CV events in MS subjects.
HMGB1 Promotes Systemic Lupus Erythematosus by Enhancing Macrophage Inflammatory Response
Authors: Lu Mudan , Yu Shanshan , Xu Wei , Gao Bo , Xiong Sidong
Published: May 2015

Background/Purpose. HMGB1, which may act as a proinflammatory mediator, has been proposed to contribute to the pathogenesis of multiple chronic inflammatory and autoimmune diseases including systemic lupus erythematosus (SLE); however, the precise mechanism of HMGB1 in the pathogenic process of SLE remains obscure.Method. The expression of HMGB1 was measured by ELISA and western blot. The ELISA was also applied to detect proinflammatory cytokines levels. Furthermore, nephritic pathology was evaluated by H&E staining of renal tissues.Results. In this study, we found that HMGB1 levels were significantly increased and correlated with SLE disease activity in both clinical patients and murine model. Furthermore, gain- and loss-of-function analysis showed that HMGB1 exacerbated the severity of SLE. Of note, the HMGB1 levels were found to be associated with the levels of proinflammatory cytokines such as TNF-αand IL-6 in SLE patients. Further study demonstrated that increased HMGB1 expression deteriorated the severity of SLE via enhancing macrophage inflammatory response. Moreover, we found that receptor of advanced glycation end products played a critical role in HMGB1-mediated macrophage inflammatory response.Conclusion. These findings suggested that HMGB1 might be a risk factor for SLE, and manipulation of HMGB1 signaling might provide a therapeutic strategy for SLE.
Wnt/β-Catenin Signaling Pathway in Skin Carcinogenesis and Therapy
Authors: Li Jing , Ji Ling , Chen Jieping , Zhang Wengeng , Ye Zhijia
Published: May 2015

Cooperating with other signaling pathways, Wnt signaling controls cell proliferation, morphology, motility, and embryonic development destination and maintains the homeostasis of tissues including skin, blood, intestine, and brain by regulating somatic stem cells and their niches throughout adult life. Abnormal regulation of Wnt pathways leads to neoplastic proliferation in these tissues. Recent research shows that Wnt signaling is also associated with the regulation of cancer stem cells (CSCs) through a similar mechanism to that observed in normal adult stem cells. Thus, the Wnt/β-catenin signaling pathway has been intensively studied and characterized. For this review, we will focus on the regulation of the Wnt/β-catenin signaling pathway in skin cancer. With the important role in stemness and skin CSC proliferation, the Wnt/β-catenin signaling pathway and its elements have the potential to be targets for skin cancer therapy.
Deep Venous Thrombosis with Pulmonary Embolism Related to IVIg Treatment: A Case Report and Literature Review
Authors: Flannery Michael T. , Humphrey Deborah
Published: May 2015

IVIg therapy has potentially been related to arterial and venous therapy. We performed an Ovid review focusing on IVIg and thrombotic events. While a few case reports were reviewed case series and case control studies were particularly reviewed in relation to thrombotic events. Outcomes demonstrate a correlation between underlying cardiovascular risk factors with predominately arterial events which typically occurred within 4–24 hours of infusion. While venous events occurred less commonly they were associated with traditional risk factors and occurred later, typically, 1–7 days following infusion of IVIg. Potential causation of thrombotic events was discussed.
Screening Mild and Major Neurocognitive Disorders in Parkinson’s Disease
Authors: Lucza Tivadar , Karádi Kázmér , Kállai János , Weintraut Rita , Janszky József , Makkos Attila , Komoly Sámuel , Kovács Norbert
Published: May 2015

Introduction. Among the nonmotor features of Parkinson’s disease (PD), cognitive impairment is one of the most troublesome problems. New diagnostic criteria for mild and major neurocognitive disorder (NCD) in PD were established by Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5). The aim of our study was to establish the diagnostic accuracy of widely used screening tests for NCD in PD.Methods. Within the scope of our study we evaluated the sensitivity and specificity of different neuropsychological tests (Addenbrooke’s Cognitive Examination (ACE), Mattis Dementia Rating Scale (MDRS), Mini Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA)) in 370 PD patients without depression.Results. MoCA and ACE feature the finest diagnostic accuracy for detecting mild cognitive disorder in PD (DSM-5) at the cut-off scores of 23.5 and 83.5 points, respectively. The diagnostic accuracy of these tests was 0.859 (95% CI: 0.818–0.894, MoCA) and 0.820 (95% CI: 0.774–0.859, ACE). In the detection of major NCD (DSM-5), MoCA and MDRS tests exhibited the best diagnostic accuracy at the cut-off scores of 20.5 and 132.5 points, respectively. The diagnostic accuracy of these tests was 0.863 (95% CI: 0.823–0.897, MoCA) and 0.830 (95% CI: 0.785–0.869, MDRS).Conclusion. Our study demonstrated that the MoCA may be the most suitable test for detecting mild and major NCD in PD.
Evaluation of Docetaxel-Sensitive and Docetaxel-Resistant Proteomes in PC-3 Cells
Authors: Zu Shulu , Ma Weiming , Xiao Pan , Cui Yazhou , Ma Tianjia , Zhou Chunwen , Zhang Huaiqiang
Published: May 2015

Objectives: Docetaxel was the first drug with proven survival benefit in men with castration-resistant prostate cancer. Acquired resistance to docetaxel precedes fatality in castration-resistant prostate cancer. The aims of this study were to evaluate docetaxel-sensitive and docetaxel-resistant proteomes in PC-3 cells, and to investigate the molecular mechanism of docetaxel-resistant PC-3 cells. Methods: Docetaxel-resistant PC-3 cells were developed by docetaxel dose escalation. The global profiling of the protein expression was investigated in docetaxel-sensitive and docetaxel-resistant proteomes in PC-3 cells using 2-dimensional polyacrylamide gel electrophoresis/matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results: Forty-nine differential proteins were found in docetaxel-resistant PC-3 cells in comparison with docetaxel-sensitive PC-3 cells. Expression in 29 proteins was upregulated, whereas expression in 20 proteins was downregulated. ATP synthase and galectin-1 were involved in the formation of tumor vessels; calreticulin, cathepsin D, and cofilin were involved in tumor metastasis, and GRP78 (78-kDa glucose-regulated protein) and microtubule-associated protein-6 were involved in drug resistance of tumor. Conclusion: It is suggested that a proteomic expression difference exists between docetaxel-sensitive and docetaxel-resistant PC-3 cells, which would be helpful for further understanding the molecular mechanisms of docetaxel resistance in PC-3 cells.
Patterns of Dental Macrowear in Subfossil Lemur catta from Ankilitelo Cave, Madagascar: Indications of Ecology and Habitat Use over Time
Authors: Cuozzo Frank P. , Sauther Michelle L.
Published: May 2015

The Ankilitelo cave site, Madagascar, contains a large collection of extant and recently extinct subfossil lemurs including the extant taxa Lemur catta and Eulemur rufifrons, which today are rarely found in sympatry. Dates for this assemblage range from 300 to 13,000 BP, though known dates for extinct primate specimens range between ∼500 and ∼600 BP. Data from Ankilitelo L. catta and E. rufifrons were compared to assess tooth wear in sympatric, related forms. Wear was scored using an ordinal scale from 0 to 5. For P4, M1 and M2, E. rufifrons displays significantly more wear than L. catta. Ankilitelo represents one of the most southerly samples of E. rufifrons, and wear data suggest that in the recent (i.e. Holocene) past, their diet near the edges of their geographic range included mechanically challenging foods. In contrast, sympatric L. catta was using foods in this transitional humid-dry forest with succulent woodlands that were not significantly impacted by recent human actions, and for which they were dentally adapted. Results also suggest that this non-gallery forest habitat may be the ‘adaptive home' of L. catta, given the lack of notable tooth wear when compared to populations currently living in tamarind-dominated riverine gallery forests.
Ring-Tailed Lemurs: A Species Re-Imagined
Authors: Sauther Michelle L. , Gould Lisa , Cuozzo Frank P. , Teague O’Mara M.
Published: May 2015

For over 50 years, ring-tailed lemurs have been studied continuously in the wild. As one of the most long-studied primate species, the length and breadth of their study is comparable to research on Japanese macaques, baboons and chimpanzees. They are also one of the most broadly observed of all primates, with comprehensive research conducted on their behaviour, biology, ecology, genetics, palaeobiology and life history. However, over the last decade, a new generation of lemur scholars, working in conjunction with researchers who have spent decades studying this species, have greatly enhanced our knowledge of ring-tailed lemurs. In addition, research on this species has expanded beyond traditional gallery forest habitats to now include high altitude, spiny thicket, rocky outcrop and anthropogenically disturbed coastal forest populations. The focus of this special volume is to ‘re-imagine' the ‘flagship species of Madagascar', bringing together three generations of lemur scholars.
Does the Order of Item Difficulty of the Addenbrooke's Cognitive Examination Add Anything to Subdomain Scores in the Clinical Assessment of Dementia
Authors: McGrory Sarah , Starr John M. , Shenkin Susan D. , Austin Elizabeth J. , Hodges John R.
Published: May 2015

Background: The Addenbrooke's Cognitive Examination (ACE) is used to measure cognition across a range of domains in dementia. Identifying the order in which cognitive decline occurs across items, and whether this varies between dementia aetiologies could add more information to subdomain scores. Method: ACE-Revised data from 350 patients were split into three groups: Alzheimer's type (n = 131), predominantly frontal (n = 119) and other frontotemporal lobe degenerative disorders (n = 100). Results of factor analysis and Mokken scaling analysis were compared. Results: Principal component analysis revealed one factor for each group. Confirmatory factor analysis found that the one-factor model fit two samples poorly. Mokken analyses revealed different item ordering in terms of difficulty for each group. Conclusion: The different patterns for each diagnostic group could aid in the separation of these different types of dementia.
Differential Effects of Acetylcholinesterase Inhibitors on Clinical Responses and Cerebral Blood Flow Changes in Patients with Alzheimer's Disease: A 12-Month, Randomized, and Open-Label Trial
Authors: Shimizu Soichiro , Kanetaka Hidekazu , Hirose Daisuke , Sakurai Hirohumi , Hanyu Haruo
Published: May 2015

Background/Aims: The present study evaluated the differences in treatment outcomes and brain perfusion changes among 3 types of acetylcholinesterase inhibitors (AchEIs, i.e. donepezil, rivastigmine, and galantamine). Methods: This was a prospective, longitudinal, randomized, open-label, 3-arm (donepezil, rivastigmine, or galantamine), parallel-group, 12-month clinical trial carried out in 55 patients with AD. Results: At 6 months, the results of the Mini-Mental State Examination (MMSE) and the Trail Making Test (TMT)-Part A showed an improvement versus baseline in the donepezil treatment group. All groups showed a significant increase in regional cerebral blood flow (rCBF), mainly in the frontal lobe. Significant rCBF reduction was observed in the temporal lobe and cingulate gyrus in all 3 groups. Conclusion: AchEI treatment prevents the progression of cognitive impairment and increases the relative rCBF in the frontal lobe.
Involvement of NOX in the Regulation of Renal Tubular Expression of Na/K-ATPase in Acute Unilateral Ureteral Obstruction Rats
Authors: Liu Changxuan , Song Yi , Qu Lei , Tang Jiawei , Meng Liqiang , Wang Yu
Published: May 2015

Background/Aims: Renal tubular expression of Na/K-ATPase has been reported to be rapidly reduced in kidneys after unilateral ureteral obstruction (UUO), contributing to compromised sodium regulation. In this study, apocynin was utilized to test the hypothesis that the renal nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) system is involved in the regulation of Na/K-ATPase expression in early UUO. Methods: Eighty Wistar rats underwent UUO or sham surgery, and half of each group was administered 100 mg/kg apocynin by oral gavage after surgery. Renal tissue samples were collected on day 1 and day 3 after surgery and the distribution of NOX2, NOX4 and Na/K-ATPase was assessed by immunofluorescence and immunohistochemical staining. The Heme oxygenase-1 (HO-1), NOX2, NOX4, osteopontin, Na/K-ATPase and aquaporin-1 (AQP-1) content of renal homogenates was assessed by immunoblotting, and malondialdehyde (MDA), nitric oxide (NO) content was assessed by biochemical analyses. Activity of inducible NO synthase (iNOS) and antioxidant enzymes was assessed by enzymatic assay. Results: Kidney Na/K-ATPase and AQP-1 content was decreased, and MDA and NOX4, NOX2 and HO-1 content were increased in the obstructed kidneys of UUO rats. Apocynin attenuated these changes and partially, but significantly, reversed the downregulation of Na/K-ATPase and AQP-1 in UUO rats. However, apocynin did not alter iNOS activity and NO production, osteopontin expression or the activity of antioxidant enzymes. Conclusion: Activation of the NOX system and subsequent production of ROS are likely responsible for the downregulation of renal tubular Na/K-ATPase expression in early UUO.
35-Year Follow-Up of a Case of Ring Chromosome 2: Array-CGH Analysis and Literature Review of the Ring Syndrome
Authors: Sarri Catherine , Douzgou Sofia , Kontos Haris , Anagnostopoulou Katherine , Tümer Zeynep , Grigoriadou Maria , Petersen Michael B. , Kokotas Haris , Merou Konstantina , Pandelia Efi , Giouroukou Elena , Papanikolaou Katerina , Côté Gilbert B. , Gyftodimou Yolanda
Published: May 2015

Côté et al. [1981] suggested that ring chromosomes with or without deletions share a common pattern of phenotypic anomalies, regardless of which chromosome is involved. The phenotype of this ‘general ring syndrome' consists of growth failure without malformations, few or no minor anomalies, and mild to moderate mental retardation. We reconsidered the ring chromosome 2 case previously published by Côté et al. [1981], and we characterized it by array CGH, polymorphic markers as well as subtelomere MLPA and FISH analysis. A terminal deletion (q37.3qter) of maternal origin of the long arm of the ring chromosome 2 was detected and confirmed by all the above-mentioned methods. Ring chromosome 2 cases are exceedingly rare. Only 18 cases, including the present one, have been published so far, and our patient is the longest reported survivor, with a 35-year follow-up, and the third case characterized by array-CGH analysis.
Targeted Therapies Overcoming Endocrine Resistance in Hormone Receptor-Positive Breast Cancer
Authors: Almstedt Katrin , Schmidt Marcus
Published: May 2015

Breast cancer is a heterogeneous disease with different molecular subtypes. Most tumours are hormone receptor positive (luminal subtype) with potential endocrine responsiveness. Endocrine therapy is commonly used in these patients. Disease progression caused by endocrine resistance represents a significant challenge in the treatment of breast cancer. To understand the mechanisms of resistance of long-term oestrogen-deprived breast cancer cells, it is important to focus on cross-talk between steroid receptor signalling and other growth factor receptors and intracellular pathways. (Pre-)clinical trials showed that co-targeting these pathways can restore endocrine sensitivity. The focus of the current review is on the intracellular PI3K/AKT/mTOR signalling pathway and cyclin-dependant kinases (CDKs) in oestrogen receptor (ER)-positive breast cancer. Study results clearly show that both inhibition of the PI3K/AKT/mTOR pathway and CDK4/6 are promising ways to improve the efficacy of endocrine treatment in ER-positive breast cancer patients with comparably few side effects. Further clinical trials are needed to identify the patient population who would benefit most from a dual inhibition.
Malignant Rhabdoid Tumor with Cervical Vertebra Involvement in a Teenage Child: Case Report and Review of the Literature
Authors: Tang Yu , Li Song , Qu Jintao , Zhou Yue , Xiao Jianru
Published: May 2015

Malignant rhabdoid tumor (MRT) is a highly malignant and aggressive tumor associated with the kidney that is mainly seen in children under 5 years old, resulting in a rapid fatal outcome. MRT invasion of the cervical vertebra is an extremely rare form of this malignancy. This study presents a case of MRT involving the C4 vertebra and its appendix. A 13-year-old girl was found to have vague neck pain and a mass in the left neck area of the mid-cervical spine. Percutaneous needle biopsy was performed and the histological and immunohistochemical analysis pointed towards a rhabdoid tumor. Chemotherapy and radiotherapy were performed, but the tumor mass progressively enlarged. Tumorectomy was conducted followed by another 6 courses of chemotherapy and 125I radioactive seed implantation. Unfortunately, the C4 vertebra and its appendix were found to be abnormal 3 months after the end of therapy. The patient received an additional tumorectomy, internal fixation with C4 reconstruction by a combined anterior and posterior approach, and 6 courses of consolidation chemotherapy. She is still alive 40 months since the initial diagnosis and remains asymptomatic 31 months after the surgery.
Flexible Ureteroscopy versus Retroperitoneal Laparoscopic Ureterolithotomy for the Treatment of Proximal Ureteral Stones >15 mm: A Single Surgeon Experience
Authors: Tugcu Volkan , Resorlu Berkan , Sahin Selcuk , Atar Arda , Kocakaya Ramazan , Eksi Mithat , Tasci Ali Ihsan
Published: May 2015

Objective: To compare safety and effectiveness of flexible ureteroscopy (F-URS) and laparoscopic retroperitoneal ureterolithotomy (L-RU) in treatment of proximal ureteral stones larger than 15 mm. Materials and Methods: This study included 103 patients treated with L-RU (Group I), and 80 patients treated with F-URS (Group II) due to proximal ureteral stones larger than 1.5 cm, in a single center. Patients' characteristics and procedure-related parameters including success rate, operation time, hospital stay, postoperative visual analogue scale (VAS) scores, auxiliary procedures, and complications were compared between Groups I and II. Results: It was seen that both methods were effective in the treatment of large ureteral stones; however, R-LU provided a higher stone-free rate (100 vs. 87.5%), a lower complication rate (10.6 vs. 23.7%), and a shorter operation time (65.4 vs. 75.1 min). On the other hand, patients treated with F-URS had less postoperative pain, a shorter hospital stay, a faster return to daily activities. Conclusions: For treatment of large proximal ureteral stones, L-RU provides significantly higher success and lower retreatment rate compared with F-URS. Our results also indicate that R-LU, which has been regarded as an invasive procedure is not as invasive as it is thought to be, and it must be kept in mind that F-URS may cause complications despite its noninvasive nature.
Group A Streptococcus Modulates Host Inflammation by Manipulating Polymorphonuclear Leukocyte Cell Death Responses
Authors: Tsatsaronis James A. , Ly Diane , Pupovac Aleta , Goldmann Oliver , Rohde Manfred , Taylor Jude M. , Walker Mark J. , Medina Eva , Sanderson-Smith Martina L.
Published: May 2015

Polymorphonuclear leukocyte (PMN) cell death strongly influences the resolution of inflammatory episodes, and may exacerbate adverse pathologies in response to infection. We investigated PMN cell death mechanisms following infection by virulent group A Streptococcus (GAS). Human PMNs were infected in vitro with a clinical, virulent GAS isolate and an avirulent derivative strain, and compared for phagocytosis, the production of reactive oxygen species (ROS), mitochondrial membrane depolarization and apoptotic markers. C57BL/6J mice were then infected, in order to observe the effects on murine PMNs in vivo. Human PMNs phagocytosed virulent GAS less efficiently, produced less ROS and underwent reduced mitochondrial membrane depolarization compared with phagocytosis of avirulent GAS. Morphological and biochemical analyses revealed that PMNs infected with avirulent GAS exhibited nuclear fragmentation and caspase-3 activation consistent with an anti-inflammatory apoptotic phenotype. Conversely, virulent GAS induced PMN vacuolization and plasma membrane permeabilization, leading to a necrotic form of cell death. Infection of the mice with virulent GAS engendered significantly higher systemic pro-inflammatory cytokine release and localized infiltration of murine PMNs, with cells associated with virulent GAS infection exhibiting reduced apoptotic potential. Avirulent GAS infection was associated with lower levels of proinflammatory cytokines and tissue PMN apoptosis. We propose that the differences in PMN cell death mechanisms influence the inflammatory responses to infection by GAS.
Involvement of Endoplasmic Reticulum Stress–Mediated C/EBP Homologous Protein Activation in Coxsackievirus B3–Induced Acute Viral Myocarditis
Authors: Cai Zhejun , Shen Li , Ma Hong , Yang Jin , Yang Du , Chen Han , Wei Jia , Lu Qiulun , Wang Dao Wen , Xiang Meixiang , Wang Jian’an
Published: May 2015

Background—

This study tested the hypothesis whether endoplasmic reticulum (ER) stress/C/EBP homologous protein (CHOP) signaling is linked with coxsackievirus B3 (CVB3)–induced acute viral myocarditis (AVMC) in vivo.

Methods and Results—

AVMC was induced by intraperitoneal injection of 1000 tissue culture infectious dose (TCID
50
) of CVB3 virus in mice. In AVMC mouse hearts (n=11), ER stress and CHOP were significantly activated, and were linked to the induction of proapoptotic signaling including reduction of Bcl-2, activation of Bax and caspase 3, compared with the controls (n=10), whereas these could be markedly blocked by ER stress inhibitor tauroursodeoxycholic acid administration (n=11). Moreover, chemical inhibition of ER stress significantly attenuated cardiomyocytes apoptosis, and prevented cardiac troponin I elevation, ameliorated cardiac dysfunction assessed by both hemodynamic and echocardiographic analysis, reduced viral replication, and increased survival rate after CVB3 inoculation. We further discovered that genetic ablation of CHOP (n=10) suppressed cardiac Bcl-2/Bax ratio reduction and caspase 3 activation, and prevented cardiomyotes apoptosis in vivo, compared with wild-type receiving CVB3 inoculation (n=10). Strikingly, CHOP deficiency exhibited dramatic protective effects on cardiac damage, cardiac dysfunction, viral replication, and promoted survival in CVB3-caused AVMC.

Conclusions—

Our data imply the involvement of ER stress/CHOP signaling in CVB3-induced AVMC via proapoptotic pathways, and provide a novel strategy for AVMC treatment.
Inactive Matrix Gla-Protein Is Associated With Arterial Stiffness in an Adult Population–Based Study
Authors: Pivin Edward , Ponte Belen , Pruijm Menno , Ackermann Daniel , Guessous Idris , Ehret Georg , Liu Yan-Ping , Drummen Nadja E.A. , Knapen Marjo H.J. , Pechere-Bertschi Antoinette , Paccaud Fred , Mohaupt Markus , Vermeer Cees , Staessen Jan A. , Vogt Bruno , Martin Pierre-Yves , Burnier Michel , Bochud Murielle
Published: May 2015

Increased pulse wave velocity (PWV) is a marker of aortic stiffness and an independent predictor of mortality. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular markers, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP are associated with increased PWV. We recruited participants via a multicenter family-based cross-sectional study in Switzerland. Dp-ucMGP was quantified in plasma by sandwich ELISA. Aortic PWV was determined by applanation tonometry using carotid and femoral pulse waveforms. Multiple regression analysis was performed to estimate associations between PWV and dp-ucMGP adjusting for age, renal function, and other cardiovascular risk factors. We included 1001 participants in our analyses (475 men and 526 women). Mean values were 7.87±2.10 m/s for PWV and 0.43±0.20 nmol/L for dp-ucMGP. PWV was positively associated with dp-ucMGP both before and after adjustment for sex, age, body mass index, height, systolic and diastolic blood pressure (BP), heart rate, renal function, low- and high-density lipoprotein, glucose, smoking status, diabetes mellitus, BP and cholesterol lowering drugs, and history of cardiovascular disease (
P
≤0.01). In conclusion, high levels of dp-ucMGP are independently and positively associated with arterial stiffness after adjustment for common cardiovascular risk factors, renal function, and age. Experimental studies are needed to determine whether vitamin K supplementation slows arterial stiffening by increasing MGP carboxylation.
Neutrophil Gelatinase–Associated Lipocalin, a Novel Mineralocorticoid Biotarget, Mediates Vascular Profibrotic Effects of Mineralocorticoids
Authors: Tarjus Antoine , Martínez-Martínez Ernesto , Amador Cristian , Latouche Céline , El Moghrabi Soumaya , Berger Thorsten , Mak Tak W. , Fay Renaud , Farman Nicolette , Rossignol Patrick , Zannad Faiez , López-Andrés Natalia , Jaisser Frédéric
Published: May 2015

Activation of the mineralocorticoid receptor has been shown to be deleterious in cardiovascular diseases (CVDs). We have recently shown that lipocalin 2 (Lcn2), or neutrophil gelatinase–associated lipocalin (NGAL), is a primary target of aldosterone/mineralocorticoid receptor in the cardiovascular system. Lcn2 is a circulating protein, which binds matrix metalloproteinase 9 and modulates its stability. We hypothesized that Lcn2 could be a mediator of aldosterone/mineralocorticoid receptor profibrotic effects in the cardiovascular system. Correlations between aldosterone and profibrotic markers, such as procollagen type I N-terminal peptide, were investigated in healthy subjects and subjects with abdominal obesity. The implication of Lcn2 in the mineralocorticoid pathway was studied using Lcn2 knockout mice subjected to a nephrectomy/aldosterone/salt (NAS) challenge for 4 weeks. In human subjects, NGAL/matrix metalloproteinase 9 was positively correlated with plasma aldosterone and fibrosis biomarkers. In mice, loss of Lcn2 prevented the NAS-induced increase of plasma procollagen type I N-terminal peptide, as well as the increase of collagen fibers deposition and collagen I expression in the coronary vessels and the aorta. The lack of Lcn2 also blunted the NAS-induced increase in systolic blood pressure. Ex vivo, treatment of human fibroblasts with recombinant Lcn2 induced the expression of collagen I and the profibrotic galectin-3 and cardiotrophin-1 molecules. Our results showed that Lcn2 plays a key role in aldosterone/mineralocorticoid receptor–mediated vascular fibrosis. The clinical data indicate that this may translate in human patients. Lcn2 is, therefore, a new biotarget in cardiovascular fibrosis induced by mineralocorticoid activation.
Sleeping Our Way to Consciousness: Jim Findlay’s Dream of the Red Chamber
Authors: Ferdman Bertie
Published: May 2015

At a moment when site-specific installations, urban soundwalks, immersive environments, and participatory experiences have (yet again) become popular, Jim Findlay’s Dream of the Red Chamber stands in sharp contrast, embracing what seems like the most passive state—sleep. Is it possible, via a sleep-inducing performance, to become conscious of our own letting go?
Al-Maqrīzī’s Biography of Tīmūr
Authors: Ito Takao
Published: May 2015

Durar al-ʿuqūd al-farīda fī tarāǧim aʿyān al-mufīda is an Arabic biographical dictionary by a famous historian of the Mamluk Sultanate, al-Maqrīzī, of his contemporaries. This recently published work contains a long biography of Tīmūr, or Tamerlane, the founder of the Timurid dynasty. In discussing the biography, this article presents some interesting and original details: first, it reviews the editions of Durar al-ʿuqūd that have been published to date; secondly, it gives an outline of Tīmūr’s biography; after that, it scrutinizes al-Maqrīzī’s sources for Tīmūr’s life and then the relations between his and other Arabic biographies of Tīmūr; lastly, it considers the value of the work.
Thomas Annan of Glasgow
Authors: Gossman Lionel
Published: May 2015

In the wake of Glasgow’s transformation in the nineteenth-century into an industrial powerhouse, the "Second City of the Empire,” a substantial part of the old town of Adam Smith degenerated into an overcrowded and disease-ridden slum. The Old Closes and Streets of Glasgow, Thomas Annan’s photographic record of this central section of the city prior to its demolition in accordance with the City of Glasgow Improvements Act of 1866, is widely recognized as a classic of nineteenth-century documentary photography. Annan’s achievement as a photographer of paintings and a portrait and landscape photographer is less widely known. Thomas Annan: Photographer of Victorian Scotland offers a handy, comprehensive and copiously illustrated overview of the full range of the photographer’s work. The book opens with a brief account of the immediate context of Annan’s career as a photographer: the astonishing florescence of photography in Victorian Scotland. Successive chapters deal with each of the main fields of his activity, touching along the way on issues such as the nineteenth-century debate over the status of photography — a mechanical practice or an artistic one? — and the still ongoing controversies surrounding the documentary photograph in particular. While the text itself is intended for the general reader, extensive endnotes amplify particular themes and offer guidance to readers interested in pursuing these themes further.
Projected Changes in Intense Precipitation over Europe at the Daily and Subdaily Time Scales*
Authors: Scoccimarro Enrico , Villarini Gabriele , Vichi Marcello , Zampieri Matteo , Fogli Pier Giuseppe , Bellucci Alessio , Gualdi Silvio
Published: May 2015

Heavy precipitation is a major hazard over Europe. It is well established that climate model projections indicate a tendency toward more extreme daily rainfall events. It is still uncertain, however, how this changing intensity translates at the subdaily time scales. The main goal of the present study is to examine possible differences in projected changes in intense precipitation events over Europe at the daily and subdaily (3-hourly) time scales using a state-of-the-science climate model. The focus will be on one representative concentration pathway (RCP8.5), considered as illustrative of a high rate of increase in greenhouse gas concentrations over this century. There are statistically significant differences in intense precipitation projections (up to 40%) when comparing the results at the daily and subdaily time scales. Over northeastern Europe, projected precipitation intensification at the 3-hourly scale is lower than at the daily scale. On the other hand, Spain and the western seaboard exhibit an opposite behavior, with stronger intensification at the 3-hourly scale rather than the daily scale. While the mean properties of the precipitation distributions are independent of the analyzed frequency, projected precipitation intensification exhibits regional differences. This finding has implications for the extrapolation of impacts of intense precipitation events, given the daily time scale at which the analyses are usually performed.
Strongly Coupled Data Assimilation Using Leading Averaged Coupled Covariance (LACC). Part I: Simple Model Study*
Authors: Lu Feiyu , Liu Zhengyu , Zhang Shaoqing , Liu Yun
Published: May 2015

This paper studies a new leading averaged coupled covariance (LACC) method for the strongly coupled data assimilation (SCDA). The SCDA not only uses the coupled model to generate the forecast and assimilate observations into multiple model components like the weakly coupled version (WCDA), but also applies a cross update using the coupled covariance between variables from different model components. The cross update could potentially improve the balance and quality of the analysis, but its implementation has remained a great challenge in practice because of different time scales between model components. In a typical extratropical coupled system, the ocean–atmosphere correlation shows a strong asymmetry with the maximum correlation occurring when the atmosphere leads the ocean by about the decorrelation time of the atmosphere. The LACC method utilizes such asymmetric structure by using the leading forecasts and observations of the fast atmospheric variable for cross update, therefore, increasing the coupled correlation and enhancing the signal-to-noise ratio in calculating the coupled covariance. Here it is applied to a simple coupled model with the ensemble Kalman filter (EnKF). With the LACC method, the SCDA reduces the analysis error of the oceanic variable by over 20% compared to the WCDA and 10% compared to the SCDA using simultaneous coupled covariance. The advantage of the LACC method is more notable when the system contains larger errors, such as in the cases with smaller ensemble size, bigger time-scale difference, or model biases.
Validation and Assessment of Pediatric Lead Screener Questions for Primary Prevention of Lead Exposure
Authors: Nicholson Jody S. , Cleeton Molli
Published: May 2015

Objective. Pediatric lead screener questions have previously been evaluated for their ability to identify children whose blood lead levels (BLLs) are greater than 10 µg/dL. Based on recent policy changes stressing that there is no safe BLL for children, the current study reevaluates the screener questions for their ability to identify children with BLLs less than 2 µg/dL and the validity of the questions in positively identifying those at greater risk for exposure. Method. A total of 202 parents of children enrolled in Head Start programs were administered the pediatric lead screener, questions to validate the screener questions, and children’s BLLs were collected in Summer 2013. Pediatric screener questions were validated against children’s BLL and the more comprehensive questions on lead risk. Results. In predicting BLL greater than 2 µg/dL, the pediatrician screener tool had a sensitivity of 26.3% and specificity of 72.2%. Each of the screener questions had low sensitivities for identifying children with BLLs above 2 µg/dL. The screener questions did not demonstrate adequate validity when compared against a more comprehensive battery of lead exposure risk indicators. The validation questions improved sensitivity to detect children with BLL >2 µg/dL and reduced the number of false positives. Conclusion. The pediatrician screener questions in their current format are not a useful primary prevention tool in identifying children at greater risk for lead exposure and in need of secondary prevention through the receipt of a blood lead test. A revision to the protocol for identifying children at risk could result in better primary and secondary prevention efforts.
Evaluating Guideline-Recommended Antibiotic Practices for Childhood Respiratory Infections
Authors: Wright Heather , Skinner Asheley Cockrell , Jhaveri Ravi
Published: May 2015

Objective. We sought to better understand barriers to adherence to published guidelines for respiratory infections among community providers. Methods. A case-based survey was developed and emailed to all members of the state pediatric society. Providers chose their preferred management for acute otitis media, acute bacterial sinusitis, and community-acquired pneumonia. An “answer key” and a follow-up questionnaire were distributed to assess reevaluation of current practices. Results. We received 173 completed surveys (15% response rate). While most responders followed guideline recommendations (6 of the 10 questions with ≥65% choosing recommended antibiotic), discrepancies existed in several cases. After receiving the answer key, respondents said they reviewed the guidelines (69%), adjusted their practice (26%), used cases for teaching (9%), and discussed guidelines with colleagues (21%). Conclusions. The majority of respondents followed published guidelines, but there was a tendency to overuse azithromycin in certain cases. Future guidelines including case-based discussions may enhance adherence.