bluuebunny/crossref_metadata_2025 huggingface dataset:
The Inhibitory Effect ofHaloxylon salicornicumon Contraction of the Mouse Uterus
Authors: Saleem Nabila H. , Ferro Valerie A. , Simpson Ann M. , Igoli John , Gray Alexander I. , Drummond Robert M.
Published: September 2013

Haloxylon salicornicum(H. salicornicum) is a plant that is frequently taken as a tea by Bedouin women in Egypt who are experiencing difficulties during pregnancy, as well as to provide relief from dysmenorrhoea. Despite its medical use, there has been no detailed evaluation of the effect of this plant on uterine tissue. Therefore, the initial aim of this study was to determine whetherH. salicornicumaffected the contraction of the mouse uterusin vitro. The crude aqueous extract ofH. salicornicumwas found to inhibit the spontaneous contractions of the uterus, with the effect being rapid in onset and completely reversible upon washout. Subsequent purification of the plant extract resulted in the identification of synephrine and N-methyltyramine, both of which were found to have inhibitory effects on the spontaneous contractions of the uterus. The EC50for the purified constituent identified as synephrine was 0.82 ± 0.24 μg/mL. The inhibitory activity of crudeH. salicornicum, as well as the isolated constituents, could be prevented by pretreatment of the uterus with theβ-adrenoceptor antagonist propranolol. In conclusion, the use ofH. salicornicumduring preterm labour appears to be justified, and its pharmacologic effect is consistent with it acting as aβ-adrenoceptor agonist.
Altered mRNA Expression Related to the Apoptotic Effect of Three Xanthones on Human Melanoma SK-MEL-28 Cell Line
Authors: Wang Jing J. , Zhang Wei , Sanderson Barbara J. S.
Published: September 2013

We previously demonstrated thatα-mangostin,γ-mangostin, and 8-deoxygartanin have significant cytotoxic effects on human melanoma SK-MEL-28 cell line. The current study revealed the underlying mechanisms.α-Mangostin (7.5 μg/mL) activated caspase activity, with a 3-fold and 4-fold increased caspase 8 and 9 activity, respectively. The molecular mechanisms were investigated by qRT-PCR for mRNA related to cell cycle arrest in G1phase (p21WAF1and cyclin D1), apoptosis (cytochrome C, Bcl-2, and Bax), and survival pathways (Akt1, NFκB, and IκBα).α-Mangostin significantly upregulated mRNA expression of cytochrome C andp21WAF1and downregulated that of cyclin D1, Akt1, and NFκB.γ-Mangostin significantly downregulated mRNA expression of Akt1 and NFκB and upregulatedp21WAF1and IκBα. 8-Deoxygartanin significantly upregulated the mRNA expression ofp21WAF1and downregulated that of cyclin D1 and NFκB. The three xanthones significantly inhibited the mRNA expression of the BRAF V600E mutation. Moreover,α-mangostin andγ-mangostin significantly downregulated Akt phosphorylation at Ser473. In conclusion, the three xanthones induced an inhibitory effect on SK-MEL-28 cells by modulating the molecular targets involved in the apoptotic pathways.
[6]-Gingerol Prevents Disassembly of Cell Junctions and Activities of MMPs in Invasive Human Pancreas Cancer Cells through ERK/NF-κB/Snail Signal Transduction Pathway
Authors: Kim Sung Ok , Kim Mi Ryeo
Published: September 2013

To study the effects of [6]-gingerol, a ginger phytochemical, on tight junction (TJ) molecules, we investigated TJ tightening and signal transduction pathways in human pancreatic duct cell-derived cancer cell line PANC-1. The following methods were utilized: MTT assay to determine cytotoxicity; zymography to examine matrix metalloproteinase (MMP) activities; transepithelial electrical resistance (TER) and paracellular flux for TJ measurement; RT-PCR and immunoblotting for proteins related to TJ and invasion; and EMSA for NF-κB activity in PANC-1 cells. Results revealed that TER significantly increased and claudin 4 and MMP-9 decreased compared to those of the control. TJ protein levels, including zonula occludens (ZO-) 1, occludin, and E-cadherin, increased in [6]-gingerol-treated cells, which correlated with a decrease in paracellular flux and MMP activity. Furthermore, NF-κB/Snail nuclear translocation was suppressed via downregulation of the extracellular signal-regulated kinase (ERK) pathway in response to [6]-gingerol treatment. Moreover, treatment with U0126, an ERK inhibitor, completely blocked NF-κB activity. In conclusion, these findings demonstrate that [6]-gingerol regulates TJ-related proteins and suppresses invasion and metastasis through NF-κB/Snail inhibition via inhibition of the ERK pathway. Therefore, [6]-gingerol may suppress the invasive activity of PANC-1 cells.
An Optimal Control Framework for Resources Management in Agriculture
Authors: Lobo Pereira Fernando , Fontes Fernando Arménio , Ferreira Maria Margarida , Pinho Maria do Rosário , Oliveira Vilma Alves , Costa Eduardo , Silva Geraldo Nunes
Published: September 2013

An optimal control framework to support the management and
control of resources in a wide range of problems arising in agriculture is discussed. Lessons extracted from past research on the weed control problem and a survey of a vast body of pertinent literature led to the specification of key requirements to be met by a suitable optimization framework. The proposed layered control structure—including planning, coordination, and execution layers—relies on a set of nested optimization processes of
which an “infinite horizon” Model Predictive Control scheme plays a key role in planning and coordination. Some challenges and recent results on the Pontryagin Maximum Principle for infinite horizon optimal control are also discussed.
Carbonic Anhydrase: An Efficient Enzyme with Possible Global Implications
Authors: Boone Christopher D. , Gill Sonika , Habibzadegan Andrew , McKenna Robert
Published: September 2013

As the global atmospheric emissions of carbon dioxide (CO2) and other greenhouse gases continue to grow to record-setting levels, so do the demands for an efficient and inexpensive carbon sequestration system. Concurrently, the first-world dependence on crude oil and natural gas provokes concerns for long-term availability and emphasizes the need for alternative fuel sources. At the forefront of both of these research areas are a family of enzymes known as the carbonic anhydrases (CAs), which reversibly catalyze the hydration of CO2into bicarbonate. CAs are among the fastest enzymes known, which have a maximum catalytic efficiency approaching the diffusion limit of 108 M−1s−1. As such, CAs are being utilized in various industrial and research settings to help lower CO2atmospheric emissions and promote biofuel production. This review will highlight some of the recent accomplishments in these areas along with a discussion on their current limitations.
Role of Endothelial to Mesenchymal Transition in the Pathogenesis of the Vascular Alterations in Systemic Sclerosis
Authors: Jimenez Sergio A.
Published: September 2013

The pathogenesis of Systemic Sclerosis (SSc) is extremely complex, and despite extensive studies, the exact mechanisms involved are not well understood. Numerous recent studies of early events in SSc pathogenesis have suggested that unknown etiologic factors in a genetically receptive host trigger structural and functional microvascular endothelial cell abnormalities. These alterations result in the attraction, transmigration, and accumulation of immune and inflammatory cells in the perivascular tissues, which in turn induce the phenotypic conversion of endothelial cells and quiescent fibroblasts into activated myofibroblasts, a process known as endothelial to mesenchymal transition or EndoMT. The activated myofibroblasts are the effector cells responsible for the severe and frequently progressive fibrotic process and the fibroproliferative vasculopathy that are the hallmarks of SSc. Thus, according to this hypothesis the endothelial and vascular alterations, which include the phenotypic conversion of endothelial cells into activated myofibroblasts, play a crucial role in the development of the progressive fibrotic process affecting skin and multiple internal organs. The role of endothelial cell and vascular alterations, the potential contribution of endothelial to mesenchymal cell transition in the pathogenesis of the tissue fibrosis, and fibroproliferative vasculopathy in SSc will be reviewed here.
Application of D-CRDM Method in Columnar Jointed Basalts Failure Analysis
Authors: Jin Changyu , Feng Xiating , Yang Chengxiang , Fang Dan , Liu Jiangpo , Xu Shuai
Published: September 2013

Columnar jointed basalt is a type of joint rock mass formed by the combined cutting effect of original joints and aphanitic microcracks. After excavation unloading, such rock mass manifested distinct mechanical properties including discontinuity, anisotropy, and proneness of cracking. On the basis of former research findings, this paper establishes a D-CRDM method applicable to the analysis of columnar jointed basalt, which not only integrates discrete element and equivalent finite-element methods, but also takes into account the coupling effect of original joints and aphanitic microcracks. From the comparative study of field monitoring data and strain softening constitutive model calculated results, it can be found that this method may well be used for the simulation of mechanical properties of columnar jointed basalts and the determination of rock failure mechanism and failure modes, thus providing references for the selection of supporting measures for this type of rock mass.
Parasympathetic Response Profiles Related to Social Functioning in Young Children with Autistic Disorder
Authors: Sheinkopf Stephen J. , Neal-Beevers A. Rebecca , Levine Todd P. , Miller-Loncar Cynthia , Lester Barry
Published: September 2013

Psychophysiology studies of heart rate and heart rate variability can be employed to study regulatory processes in children with autism. The objective of this study was to test for differences in respiratory sinus arrhythmia (RSA; a measure of heart rate variability) and to examine the relationship between physiologic responses and measures of social behavior. Participants included 2- to 6-year-old children with Autistic Disorder and children without autism. Heart rate and RSA were derived from ECG recordings made during a baseline period and then a stranger approach paradigm. Social and adaptive behavior was assessed by parent report. Groups did not differ in mean heart rate or RSA at baseline or in response to social challenge. However, children with autism were more likely to show a physiologic response to intrusive portions of the stranger approach than to less intrusive portions of this procedure. Nonautistic children were equally likely to respond to intrusive and less intrusive social events. Within the autistic group, physiologic response to the intrusive stranger approach corresponded to higher ratings of social adaptive behaviors. These results suggest that physiologic responses to social challenge may help understand differences in social behavioral outcomes in children with autism.
Hybrid Extragradient Methods for Finding Zeros of Accretive Operators and Solving Variational Inequality and Fixed Point Problems in Banach Spaces
Authors: Ceng Lu-Chuan , Wen Ching-Feng
Published: September 2013

We introduce and analyze hybrid implicit and explicit extragradient methods for finding a zero of an accretive operator and solving a general system of variational inequalities and a fixed point problem of an infinite family of nonexpansive self-mappings in a uniformly convex Banach spaceXwhich has a uniformly Gateaux differentiable norm. We establish some strong convergence theorems for hybrid implicit and explicit extra-gradient algorithms under suitable assumptions. Furthermore, we derive the strong convergence of hybrid implicit and explicit extragradient algorithms for finding a common element of the set of zeros of an accretive operator and the common fixed point set of an infinite family of nonexpansive self-mappings and a self-mapping whose complement is strictly pseudocontractive and strongly accretive inX. The results presented in this paper improve, extend, supplement, and develop the corresponding results announced in the earlier and very recent literature.
New Guar Biopolymer Silver Nanocomposites for Wound Healing Applications
Authors: Ghosh Auddy Runa , Abdullah Md Farooque , Das Suvadra , Roy Partha , Datta Sriparna , Mukherjee Arup
Published: September 2013

Wound healing is an innate physiological response that helps restore cellular and anatomic continuity of a tissue. Selective biodegradable and biocompatible polymer materials have provided useful scaffolds for wound healing and assisted cellular messaging. In the present study, guar gum, a polymeric galactomannan, was intrinsically modified to a new cationic biopolymer guar gum alkylamine (GGAA) for wound healing applications. Biologically synthesized silver nanoparticles (Agnp) were further impregnated in GGAA for extended evaluations in punch wound models in rodents. SEM studies showed silver nanoparticles well dispersed in the new guar matrix with a particle size of ~18 nm. In wound healing experiments, faster healing and improved cosmetic appearance were observed in the new nanobiomaterial treated group compared to commercially available silver alginate cream. The total protein, DNA, and hydroxyproline contents of the wound tissues were also significantly higher in the treated group as compared with the silver alginate cream (P<0.05). Silver nanoparticles exerted positive effects because of their antimicrobial properties. The nanobiomaterial was observed to promote wound closure by inducing proliferation and migration of the keratinocytes at the wound site. The derivatized guar gum matrix additionally provided a hydrated surface necessary for cell proliferation.
Three-Dimensional Modeling of Spatial Reinforcement of Soil Nails in a Field Slope under Surcharge Loads
Authors: Zhou Yuan-de , Xu Kai , Tang Xinwei , Tham Leslie George
Published: September 2013

Soil nailing has been one of the most popular techniques for improving the stability of slopes, in which rows of nails and a structural grillage system connecting nail heads are commonly applied. In order to examine the spatial-reinforcement effect of soil nails in slopes, a three-dimensional (3D) numerical model has been developed and used to back-analyze a field test slope under surcharge loading. Incremental elastoplastic analyses have been performed to study the internal deformation within the slope and the development of nail forces during the application of top surcharge loads. Different treatments of the grillage constraints at nail heads have been studied. It is shown that the numerical predictions compare favorably with the field test measurements. Both the numerical and the field test results suggest that soil nails are capable of increasing the overall stability of a loose fill slope for the loading conditions considered in this study. The axial force mobilization in the two rows of soil nails presents a strong dependence on the relative distance with the central section. With the surcharge loads increased near the bearing capacity of the slope, a grillage system connecting all the nail heads can affect the stabilizing mechanism to a notable extent.
Faulty Sensor Node Detection Using Round Trip Time and Discrete Paths in WSNs
Authors: Duche R. N. , Sarwade N. P.
Published: September 2013

Wireless sensor networks (WSNs) with efficient and accurate design to increase the quality of service (QoS) have become a hot area of research. Implementing the efficient and accurate WSNs requires deployment of the large numbers of portable sensor nodes in the field. The quality of service of such networks is affected by lifetime and failure of sensor node. In order to improve the quality of service, the data from faulty sensor nodes has to be ignored or discarded in the decision-making process. Hence, detection of faulty sensor node is of prime importance. In the proposed method, discrete round trip paths (RTPs) are compared on the basis of round trip delay (RTD) time to detect the faulty sensor node. RTD protocol is implemented in NS2 software. WSNs with circular topology are simulated to determine the RTD time of discrete RTPs. Scalability of the proposed method is verified by simulating the WSNs with various sensor nodes.
Novel Biphasic Role of Resolvin D1 on Expression of Cyclooxygenase-2 in Lipopolysaccharide-Stimulated Lung Fibroblasts Is Partly through PI3K/AKT and ERK2 Pathways
Authors: Wu Derong , Zheng Shengxing , Li Wenjuan , Yang Li , Liu Yongjian , Zheng Xia , Yang Yi , Yang Liangmin , Wang Qian , Smith Fang Gao , Jin Shengwei
Published: September 2013

Fibroblasts, far frombeing merely bystander cells, are known to play a specific role in inflammation resolution after an acute injury. As the endogenous “braking signal,” resolvins possess potent anti-inflammatory and proresolution actions. We demonstrated that the expression of COX-2 protein was significantly peaked initially at 6 hours but then also at 48 hours after LPS stimulation in lung fibroblasts. PGE2levels also peaked at 6 hours, and PGD2levels were increased and peaked at 48 hours. However, no significant change in the protein expression of COX-1 was observed after treatment with LPS in lung fibroblasts. Exogenous resolvin D1 inhibited the first peak of COX-2 expression as well as the production of PGE2induced by LPS. In contrast, exogenous resolvin D1 increased the second peak of COX-2 expression as well as the production of PGD2induced by LPS. In addition, resolvin D1 inhibited COX-2 expression at 6 hours, which was partly through PI3K/AKT and ERK2 signalling pathways.
A Self‐Adaptive Parameter Optimization Algorithm in a Real‐Time Parallel Image Processing System
Authors: Li Ge , Zhang Xuehe , Zhao Jie , Zhang Hongli , Ye Jianwei , Zhang Weizhe
Published: September 2013

Aiming at the stalemate that precision, speed, robustness, and other parameters constrain each other in the parallel processed vision servo system, this paper proposed an adaptive load capacity balance strategy on the servo parameters optimization algorithm (ALBPO) to improve the computing precision and to achieve high detection ratio while not reducing the servo circle. We use load capacity functions (LC) to estimate the load for each processor and then make continuous self‐adaptation towards a balanced status based on the fluctuated LC results; meanwhile, we pick up a proper set of target detection and location parameters according to the results of LC. Compared with current load balance algorithm, the algorithm proposed in this paper is proceeded under an unknown informed status about the maximum load and the current load of the processors, which means it has great extensibility. Simulation results showed that the ALBPO algorithm has great merits on load balance performance, realizing the optimization of QoS for each processor, fulfilling the balance requirements of servo circle, precision, and robustness of the parallel processed vision servo system.
Cockroach Allergen Bla g 7 Promotes TIM4 Expression in Dendritic Cells Leading to Th2 Polarization
Authors: Xu Lingxiao , Zhang Miaojia , Ma Wenjing , Jin Shanshan , Song Weijuan , He Shaoheng
Published: September 2013

As one of the most common sources of indoor aeroallergens worldwide, cockroach is important in causing rhinitis and asthma while the mechanisms underlying remain obscure. Since T helper (Th) type 2 polarization plays an important role in the pathogenesis of allergic diseases, we investigated the effect of Bla g 7, a pan-allergen fromBlattella germanica(B. germanica), on Th polarization which is controlled by monocyte-derived dendritic cells (DCs). Challenged by recombinant Bla g 7 (rBla g 7), immature DCs obtained from human exhibited upregulated levels of TIM4, CD80, and CD86 and increased IL-13 secretion. Cocultured with CD4+ T cells, challenged DCs increased the ratio of IL-4+ versus IFN-γ+ of CD4+ T cells, suggesting a balance shift from Th1 to Th2. Moreover, antibodies against TIM4, CD80, and CD86 reversed the enhancement of IL-4+/IFN-γ+ ratio and alleviated the IL-13 release induced by rBla g 7, indicating that the Th2 polarization provoked by rBla g 7 challenged DCs is via TIM4-, CD80-, and CD86-dependent mechanisms. In conclusion, the present findings implied a crucial role of Bla g 7 in the development of cockroach allergy and highlighted an involvement of DCs-induced Th2 polarization in cockroach allergy.
Concurrent Use of Hypnotic Drugs and Chinese Herbal Medicine Therapies among Taiwanese Adults with Insomnia Symptoms: A Population-Based Study
Authors: Lee Kuei-Hua , Tsai Yueh-Ting , Lai Jung-Nien , Lin Shun-Ku
Published: September 2013

Background. The increased practice of traditional Chinese medicine (TCM) worldwide has raised concerns regarding herb-drug interactions. The purpose of our study is to analyze the concurrent use of Chinese herbal products (CHPs) among Taiwanese insomnia patients taking hypnotic drugs.Methods. The usage, frequency of services, and CHP prescribed among 53,949 insomnia sufferers were evaluated from a random sample of 1 million beneficiaries in the National Health Insurance Research Database. A logistic regression method was used to identify the factors that were associated with the coprescription of a CHP and a hypnotic drug. Cox proportional hazards regressions were performed to calculate the hazard ratios (HRs) of hip fracture between the two groups.Results. More than 1 of every 3 hypnotic users also used a CHP concurrently.Jia-Wei-Xiao-Yao-San(Augmented Rambling Powder) andSuan-Zao-Ren-Tang(Zizyphus Combination) were the 2 most commonly used CHPs that were coadministered with hypnotic drugs. The HR of hip fracture for hypnotic-drug users who used a CHP concurrently was 0.57-fold (95% CI = 0.47–0.69) that of hypnotic-drug users who did not use a CHP.Conclusion. Exploring potential CHP-drug interactions and integrating both healthcare approaches might be beneficial for the overall health and quality of life of insomnia sufferers.
Loss of TBK1 Induces Epithelial–Mesenchymal Transition in the Breast Cancer Cells by ERα Downregulation
Authors: Yang Kyung-Min , Jung YunShin , Lee Jeong-Mi , Kim WonJoo , Cho Jin Ki , Jeong Joon , Kim Seong-Jin
Published: September 2013

Estrogen receptor α (ERα) is the pivotal regulator of proliferation and differentiation in mammary epithelia, where it serves as a crucial prognostic marker and therapeutic target in breast cancer. In this study, we show that the loss of the kinase TANK-binding kinase 1 (TBK1) induces epithelial–mesenchymal transition in ERα-positive breast cancer cells by downregulating ERα expression. TBK1 was overexpressed in ERα-positive breast cancers, where it was associated with distant metastasis-free survival in patients, whereas it was underexpressed in ERα-negative breast cancers. TBK1 silencing decreased expression of epithelial markers and increased expression of mesenchymal markers in ERα-positive breast cancer cells, enhancing tumor growth and lung metastasis in vivo in a manner associated with downregulation of ERα expression. Mechanistically, TBK1 silencing reduced FOXO3A binding to the ERα promoter by inducing the translocation of phosphorylated FOXO3A from the nucleus to the cytoplasm. Thus, our results indicate that the loss of TBK1 expression parallels the loss of ERα expression, in turn helping drive an aggressive breast cancer phenotype. Cancer Res; 73(22); 6679–89. ©2013 AACR.
Why Your Preferred Targeted Drugs May Become Unaffordable
Authors: Piccart Martine J.
Published: September 2013

Trastuzumab, a monoclonal antibody directed at the HER2 receptor, is one of the most impressive targeted drugs developed in the last two decades. Indeed, when given in conjunction with chemotherapy, it improves the survival of women with HER2 positive breast cancer, both in advanced and in early disease. Its optimal duration, however, is poorly defined in both settings with a significant economic impact in the adjuvant setting where the drug is arbitrarily given for 1 year. This article reviews current attempts at shortening this treatment duration, emphasizing the likelihood of inconclusive results and, therefore, the need to investigate this important variable as part of the initial pivotal trials and with the support of public health systems. Failure to do so has major consequences on treatment affordability. Ongoing adjuvant trials of dual HER2 blockade, using trastuzumab in combination with a second anti-HER2 agent, and trials of the antibody–drug conjugate T-DM1 (trastuzumab–emtansine) have to all be designed with 12 months of targeted therapy. Cancer Res; 73(19); 5849–51. ©2013 AACR.
The Emerging Role of Immunosurveillance in Dictating Metastatic Spread in Breast Cancer
Authors: Slaney Clare Y. , Rautela Jai , Parker Belinda S.
Published: September 2013

It is now well known that the immune system can recognize transformed cells and control the initiation and growth of some cancers, a process termed tumor immunosurveillance. Key regulators of this process have been described in the primary tumor setting, where the balance of protumor and antitumor responses dictates tumor initiation and progression. Accumulating evidence suggests that immunosurveillance may also be critical for regulating metastatic spread, the most fatal aspect of cancer, and that mechanisms of overcoming immune control may be quite different from those at the primary site. Our recent findings support loss of type I interferon (IFN) signaling as a tumor-cell intrinsic mechanism of evading metastasis-specific immune responses in breast cancer. We revealed that type I IFN-induced innate (natural killer) and adaptive (CD8+ T cell) responses suppressed bone metastatic growth and this was associated with decreased accumulation of immune suppressor cells (myeloid-derived suppressor cells). This review summarizes recent findings that are in support of tumor-induced immunosurveillance in regulating metastatic spread, including evidence that immune regulation of primary tumors may be distinct from those dictating metastasis. Cancer Res; 73(19); 5852–7. ©2013 AACR.
Impact of Vitamin D Receptor VDR rs2228570 Polymorphism in Oldest Old
Authors: Glocke Melanie , Lang Florian , Schaeffeler Elke , Lang Thomas , Schwab Matthias , Lang Undine E.
Published: September 2013

Background: Calcitriol, a key player in the regulation of mineral metabolism, influences, directly or by increasing plasma Ca2+ and phosphate levels, a multitude of physiological functions, such as bone mineralization, cell proliferation, immune response, carbohydrate metabolism, blood pressure, platelet reactivity, gastric acid secretion, cognitive function and mood. Calcitriol is mainly effective by stimulation of the Vitamin D receptor VDR. The responsiveness of VDR may be affected by gene variants, such as the FokI polymorphism (rs2228570). The GG gene variant is expected to be more active than the GA or AA gene variant. The present study explored the impact of VDR rs2228570 on survival and health of oldest old individuals (> 90 years). Methods: 101 individuals > 90 years were examined and genotyped. As a result, the prevalence of GG, GA & AA was 36 (10 ♂, 26♀), 52 (24 ♂, 28♀) and 13 (4 ♂, 9♀), respectively, a prevalence not significantly different from the frequency in public available dbSNP and a population (n = 208) of young volunteers (average age 49 years). Results: As compared to carriers of GG, carriers of AA and/or GA displayed significantly (p<0.05) lower diastolic blood pressure (significant only in ♂), higher instrumental activity of daily life (IADL) score and more frequent hospital visits (significant only in ♂), significantly lower prevalence of depression (significant in ♀+♂), renal disease (significant only in ♀), allergy, peptic ulcer and urolithiasis (significant only in ♂), as well as significantly higher prevalence of transitoric ischemic attacks. In a younger population a German version of the NEO-FFI, allowing reliable and valid assessment of personality, revealed decreased neuroticism (significant only in ♂) and increased extraversion in AA carriers. Conclusion: The Vitamin D receptor gene variant VDR rs2228570 has only little impact on life span but may affect a variety of pathophysiologically relevant functions including mood.
Effects of Buffering Properties and Undissociated Acid Concentration on Dissolution of Dental Enamel in Relation to pH and Acid Type
Authors: Shellis R.P. , Barbour M.E. , Jesani A. , Lussi A.
Published: September 2013

To quantify the relationships between buffering properties and acid erosion and hence improve models of erosive potential of acidic drinks, a pH-stat was used to measure the rate of enamel dissolution in solutions of citric, malic and lactic acids, with pH 2.4-3.6 and with acid concentrations adjusted to give buffer capacities (β) of 2-40 (mmol·l-1)·pH-1 for each pH. The corresponding undissociated acid concentrations, [HA], and titratable acidity to pH 5.5 (TA5.5) were calculated. In relation to β, the dissolution rate and the strength of response to β varied with acid type (lactic > malic ≥ citric) and decreased as pH increased. The patterns of variation of the dissolution rate with TA5.5 were qualitatively similar to those for β, except that increasing pH above 2.8 had less effect on dissolution in citric and malic acids and none on dissolution in lactic acid. Variations of the dissolution rate with [HA] showed no systematic dependence on acid type but some dependence on pH. The results suggest that [HA], rather than buffering per se, is a major rate-controlling factor, probably owing to the importance of undissociated acid as a readily diffusible source of H+ ions in maintaining near-surface dissolution within the softened layer of enamel. TA5.5 was more closely correlated with [HA] than was β, and seems to be the preferred practical measure of buffering. The relationship between [HA] and TA5.5 differs between mono- and polybasic acids, so a separate analysis of products according to predominant acid type could improve multivariate models of erosive potential.
Oncologic Outcome after Laparoscopic Radical Cystectomy without Neoadjuvant or Adjuvant Therapy with a Median Follow-Up of 32 Months
Authors: Hermans Tom Johannes Noël , Fossion Laurent Marie Constant Leo
Published: September 2013

Introduction: We report the oncological outcome after laparoscopic radical cystectomy (LRC) and standard laparoscopic pelvic lymph node dissection (PLND) without neoadjuvant or adjuvant therapy in the treatment of bladder cancer with a median follow-up of 32 months. Materials and Methods: From September 2006 to January 2011, 40 consecutive patients underwent an LRC and standard laparoscopic PLND, and were included in this prospective observational cohort study. No patient received neoadjuvant or adjuvant therapy. Demographic, perioperative, complication, histopathologic and survival data were collected and analyzed. Results: The 2002 TNM staging for the tumors were: pT0, 4 cases; pTis, 5 cases; pT1, 4 cases; pT2, 7 cases; pT3, 13 cases; pT4, 7 cases. Positive surgical margins were reported in 3 patients (7.5%) and lymph node involvement in 9 patients (23.7%). No patient was lost to follow-up. The overall, cancer-specific and recurrence-free survival rates were 53, 73 and 70% with a median follow-up of 32 months. Eleven patients (27.5%) died of metastatic disease or local recurrence. Nonorgan-confined disease (≥pT3) and primary lymph node involvement (pN+) were significantly associated with worse overall, cancer-specific and recurrence-free survival rates. Conclusion: We report acceptable mid-term and promising long-term oncological outcome after LRC and standard laparoscopic PLND without neoadjuvant or adjuvant therapy.
Systemic Mastocytosis Accompanied by a Non-Secretory Plasma Cell Dyscrasia and Nephrotic Syndrome-Level Proteinuria in a 76-Year-Old Patient
Authors: Papadopoulou Vasiliki , Ioannou Savvas , Levidou Georgia , Variami Eleni , Kouzis Panagiotis , Siakantaris Marina
Published: September 2013

We report here the interesting case of a 76-year-old man with severe proteinuria who was diagnosed with systemic mastocytosis accompanied by a clonal non-mast-cell lineage haematological disorder (a non-secretory plasma cell dyscrasia). This is a unique report of systemic mastocytosis with a non-secretory plasma cell dyscrasia and nephrotic syndrome. The pathophysiological relevance between these entities along with the probability of occult amyloidosis is discussed.
Development of the Ciliary Body: Morphological Changes in the Distal Portion of the Optic Cup in the Human
Authors: Peces-Peña M.D. , de la Cuadra-Blanco C. , Vicente A. , Mérida-Velasco J.R.
Published: September 2013

This study seeks to determine the main events that occur in the development of the ciliary body (CB) in the 5-14th week of development. The CB develops from the distal portion of the optic cup (OC) and the neighboring mesenchyme. During the 5th week of development, 4 zones were observed in the distal portion of the OC: in zone 1, the epithelia of the outer and inner layers of the OC came into contact. This contact coincided with the appearance of mainly apical granule pigments. This zone corresponded to the anlage of the epithelial layers of the CB. In zone 2, the cells surrounded the marginal sinus and contained scarce pigment granules and nuclei in the basal position. This zone corresponded to the anlage of the iris. Zone 3 was triangular in shape and its vertex ran towards the marginal sinus and corresponded to common cell progenitors. Zone 4 corresponded to the retinal pigment epithelium anlage and the neural retina anlage. We determined the onset of the stroma and the ciliary muscle anlage at the end of the 7th week. In the 13-14th week, we observed the anlage of the orbicularis ciliaris (pars plana of the CB) and corona ciliaris (pars plicata of the CB), in addition to the anlage of the ciliary muscle. Our study, therefore, establishes a precise timetable of the development of the CB.
Clinical, Dermoscopic and Histopathological Features of Eccrine Poroid Neoplasms
Authors: Sgouros Dimitris , Piana Simonetta , Argenziano Giuseppe , Longo Caterina , Moscarella Elvira , Karaarslan Isil Kilinc , Akalin Taner , Özdemir Fezal , Zalaudek Iris
Published: September 2013

Background: Eccrine poroma (EP) belongs to the group of benign adnexal tumors, but cases of eccrine porocarcinoma (EPC) arising on long-standing and untreated EP suggest a certain risk of malignant transformation. Objectives: To describe the clinical, dermoscopic and histopathologic features associated with different extremes in the spectrum of eccrine poroid neoplasms and to review the according literature. Methods: A retrospective analysis of patient characteristics and morphologic features associated with EP, EPC in situ and invasive porocarcinoma patients who attended two skin lesion clinics in Italy and Turkey between 2010 and 2011. Results: A total of 4 cases including 1 EP, 1 EPC in situ and 2 cases of invasive EPC in 4 patients were analyzed. Recent changes including bleeding, ulceration and sudden enlargement of a pre-existing lesion were associated with malignant transformation. Dermoscopically, polymorphous vessels consisting of coiled, hairpin and linear vessels were seen at all stages of progression. Histopathological findings of EPC in situ were limited to the epidermal component and were evident only at higher magnification. Conclusions: Clinicians and pathologists should carefully evaluate EPs with a recent history of change and erosion in order to avoid overlooking the potential development of EPC.
Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration of an Intravascular Sarcoma Metastasis
Authors: Dusemund Frank , Schneider Tino , Zeisel Christoph , Rothermundt Christian , Kluckert Thomas , Schmid Sabine , Brutsche Martin H.
Published: September 2013

The role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of endovascular lesions has rarely been described. We report a case of EBUS-TBNA of a solid mass in the left pulmonary artery in a patient with synovial sarcoma of the kidney, which was performed without complications and led to the diagnosis of metastatic disease. EBUS-TBNA seems to be a rapid, minimally invasive, safe and effective diagnostic procedure in selected cases of endovascular lesions.
Allelic Interference: A Mechanism for Trans-Dominant Transmission of Loss of Function in the Neurodegeneration of Familial Alzheimer's Disease
Authors: Robakis Nikolaos K. , Georgakopoulos Anastasios
Published: September 2013

Presenilins (PSs) are catalytic components of the γ-secretase complexes that promote the ε-cleavage of cell surface proteins producing cytosolic peptides shown to function in cell signaling and gene expression. In addition, secretase cleavages at γ-sites of amyloid precursor protein substrates produce the amyloid-β (Aβ) peptides found in all people. Aggregation of Aβ peptides form the amyloid fibrils found in amyloid plaques of Alzheimer's disease (AD) patients and aged individuals. A common hypothesis suggests that AD is caused by aggregated Aβ peptides, but treatments with either inhibitors of Aβ production or anti-Aβ antibodies showed no therapeutic value. Importantly, recent evidence [Marambaud et al.: Cell 2003;114:635-645] shows that PS familial AD (FAD) mutations cause a loss of γ-secretase cleavage function at the ε-site of substrates manifested by a decreased production of cytosolic peptides and an accumulation of transmembrane γ-secretase substrates. These data support the hypothesis that PS FAD mutations promote neurotoxicity by inhibiting the γ-secretase-catalyzed ε-cleavage of substrates, thus reducing cell signaling while causing accumulation of membrane-bound cytotoxic peptides. Similar mechanisms may be involved in toxicities observed in clinical trials of γ-secretase inhibitors. A model of allelic interference may explain the dominant negative transmission of neurotoxic loss of function in FAD neurodegeneration.
Adult Height and Epigenotype in Children with Silver-Russell Syndrome Treated with GH
Authors: Binder G. , Liebl M. , Woelfle J. , Eggermann T. , Blumenstock G. , Schweizer R.
Published: September 2013

Aims: To compare adult heights of GH-treated and GH-untreated patients with Silver-Russell syndrome (SRS) who were epigenotyped. Methods: This was a nonrandomized retrospective study with matched controls at a single center. Molecular analysis of 32 out of 37 GH-treated patients (16 females) revealed IGF2-H19 epimutations in 12 and maternal uniparental disomy of chromosome 7 (matUPD7) in 5 patients; 15 were negative. At start of GH, mean age was 7.2 years and mean height -3.34 standard deviation score (SDS). Mean GH dose used was 51 µg/kg·day, mean duration of therapy was 5.6 years. Puberty was blocked by GnRH analogs in 16 patients. The untreated group comprised 13 individuals (5 females, mean age 6.8 years and mean height -3.34 SDS). End points were adult height and overall height gain. Results: GH-treated patients reached an adult height of -2.12 ± 0.98 SDS gaining 1.22 SDS in comparison to baseline. Adult height SDS of the untreated was -3.13 ± 1.37 SDS. The matched treated patients were significantly taller than their untreated counterparts. Outcome was dependent on height at start of GH and duration of therapy. Height gain was highest in the shortest patients. Conclusions: GH improved adult height in SRS to a comparable degree as reported in nonsyndromic SGA children. A trend toward a better outcome in matUPD7 needs confirmation in larger cohorts.
Aortic Intima-Media Thickness in Newborns with Congenital Hypothyroidism
Authors: Akin Mustafa Ali , Sarici Dilek , Yikilmaz Ali , Akin Leyla , Gunes Tamer , Ozturk M. Adnan , Kurtoglu Selim
Published: September 2013

Background/Aims: Congenital hypothyroidism (CH) in neonates is associated with lipid alterations that might be a risk factor for early cardiovascular disease in adult life. The aim of this study was to investigate the effect of CH on lipid metabolism and aortic intima media thickness (aIMT) as a unique finding of the increased risk of atherogenic risk in neonatal age. Methods: The study group consisted of 15 newborns with CH who were identified by neonatal mass screening (patient group), and 25 healthy newborns (control group). Serum lipid profiles and aIMT obtained from abdominal aorta were measured in all subjects. Results: The mean aIMT were higher in the patient group (0.46 ± 0.062 mm) compared with the control group (0.34 ± 0.035 mm; p = 0.006). The weight-adjusted aIMT of patients (0.13 ± 0.017 mm/kg) was also significantly greater than that of the controls (0.10 ± 0.019 mm/kg; p < 0.001). Total serum cholesterol levels were significantly higher in patients than those in healthy controls (130.80 ± 44.46 vs. 99.96 ± 18.87 mg/dl). The other lipid levels including triglyceride, low-density lipoprotein (LDL), high-density lipoprotein cholesterol and LDL cholesterol levels of the patients were slightly higher than those of the controls, without statistical significance. Conclusion: Neonates with CH have significantly higher aIMT with lipid alterations. Hypothyroidism might increase the risk of early atherosclerosis even in the neonatal period.
Can the Calcium Hypothesis Explain Synaptic Loss in Alzheimer's Disease?
Authors: Popugaeva Elena , Bezprozvanny Ilya
Published: September 2013

Alzheimer's disease (AD) is the threat of modern humankind that is provoked by increased human lifespan. Despite extensive studies on AD pathology for more than 100 years, there are no disease-preventing therapies. Growing evidence suggests the role of calcium (Ca2+) in the pathogenesis of AD. The main purpose of the article is to understand whether modern science is able to explain the synapse loss observed in early AD and discuss the role of Ca2+ hypothesis in it. Based on results obtained in our laboratory and others, we propose that familial AD-associated mutations in presenilins cause a Ca2+ overload of endoplasmic reticulum stores which leads to compensatory downregulation of the neuronal store-operated Ca2+ (nSOC) entry pathway. We propose that synaptic nSOC is necessary for the stability of mature synaptic spines and that dysfunction of this pathway may play an important role in synaptic and memory loss in AD.
Location of the Susceptibility Vessel Sign on T2*-Weighted MRI and Early Recanalization within 1 Hour after Tissue Plasminogen Activator Administration
Authors: Aoki Junya , Kimura Kazumi , Shibazaki Kensaku , Sakamoto Yuki , Saji Naoki , Uemura Junichi
Published: September 2013

Background: We have recently reported that the susceptibility vessel sign (SVS) at the proximal portion of the horizontal (M1) middle cerebral artery (MCA) on T2*-weighted MRI is a strong predictor for no early recanalization after intravenous recombinant tissue plasminogen activator (t-PA) therapy. However, it is unclear whether the presence of the SVS at other locations, such as distal M1, the vertical portion (M2) of the MCA, and distal branches (MCA distal), is a predictor for no early recanalization in acute ischemic stroke patients. Methods: The SVS was defined as a hypointense signal of the MCA on T2*-weighted MRI on admission. The locations of the SVS were classified as M1 proximal, M1 distal, and MCA distal. M1 proximal SVS was defined as an SVS at the origin of the M1. M1 distal SVS was any M1 SVS not including the origin of the M1. MCA distal SVS was an SVS further away from M1. Early recanalization was defined as a new appearance of at least one of the distal branches on MRA within 1 h after t-PA therapy. A good outcome at 3 months was defined as a modified Rankin Scale (mRS) score of 0-1. Results: Consecutive acute stroke patients admitted to our stroke center and treated with t-PA between October 2005 and October 2012 were enrolled. There were 158 patients [median age, 78 (71-84) years; 84 (53%) males; median National Institutes of Health Stroke Scale score, 16 (10-20)]. Internal carotid artery occlusion was seen in 18 (72%) of the 25 patients with M1 proximal SVS, in 3 (14%) of the 22 patients with M1 distal SVS, in 4 (9%) of the 44 patients with MCA distal SVS, and in 18 (27%) of the 67 patients with No SVS (p < 0.001). Twenty-four (96%) of the 25 patients with M1 proximal SVS had no early recanalization, while 16 (73%) of the 22 patients with M1 distal SVS, 25 (57%) of the 44 patients with MCA distal SVS, and 36 (54%) of the 67 patients with No SVS had no early recanalization (p < 0.001, 0.140, and 0.846, respectively, compared to the patients with No SVS). Multivariate analysis showed that only M1 proximal SVS was significantly associated with no early recanalization (odds ratio 16.80, 95% confidence interval 2.04-138.17, p = 0.009). Among the 95 patients with a premorbid mRS score of 0-1, none (0%) of the 16 patients with M1 proximal SVS, 5 (36%) of the 14 patients with M1 distal SVS, 12 (48%) of the 25 patients with MCA distal SVS, and 13 (33%) of the 40 patients with No SVS achieved a good outcome (p = 0.011, 1.000, and 0.295, respectively, compared to the patients with No SVS). Conclusion: M1 proximal SVS on T2*-weighted MRI is a strong predictor for no early recanalization, and all patients with it had a poor outcome. However, M1 distal SVS and MCA distal SVS were not predictors for no early recanalization, and half of the patients had a poor outcome.
Familial Progressive Supranuclear Palsy: A Literature Review
Authors: Fujioka Shinsuke , Van Gerpen Jay A. , Uitti Ryan J. , Dickson Dennis W. , Wszolek Zbigniew K.
Published: September 2013

Background: Many genes/loci associated with Parkinsonian disorders have been identified. However, the genetic causes for a number of familial forms of Parkinsonian disorders remain to be elucidated. Objective: It was the aim of this paper to review the familial progressive supranuclear palsy (PSP) cases without any known gene mutations published in the English literature. Methods: We searched the PubMed database for reports of familial PSP cases without known mutations. Results: We found 19 PSP families. The mean age at onset was approximately 60 years, and the mean disease duration was about 8 years. Parkinsonism and ophthalmoplegia were most frequently reported, and a vast majority of patients manifested with these two symptoms. Other symptoms such as falls, postural instability and pyramidal signs were also common. A small subset of patients transiently responded to L-dopa therapy. Conclusion: There is an increasing number of reported familial PSP. A recently performed genome-wide association study indicated genetic factors for this condition. Furthermore, clinical, pathological and genetic investigations will open new avenues to the discovery of causative genes and new therapeutics for PSP.