bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficiency of Base Excision Repair of Oxidative DNA Damage and Its Impact on the Risk of Colorectal Cancer in the Polish Population
Authors: Kabzinski J. , Mucha B. , Cuchra M. , Markiewicz L. , Przybylowska K. , Dziki A. , Dziki L. , Majsterek I.
Published: November 2015

DNA oxidative lesions are widely considered as a potential risk factor for colorectal cancer development. The aim of this work was to determine the role of the efficiency of base excision repair, both in lymphocytes and in epithelial tissue, in patients with CRC and healthy subjects. SNPs were identified within genes responsible for steps following glycosylase action in BER, and patients and healthy subjects were genotyped. A radioisotopic BER assay was used for assessing repair efficiency and TaqMan for genotyping. Decreased BER activity was observed in lymphocyte extract from CRC patients and in cancer tissue extract, compared to healthy subjects. In addition, polymorphisms of EXO1, LIG3, and PolB may modulate the risk of colorectal cancer by decreasing (PolB) or increasing (LIG3 and EXO1) the chance of malignant transformation.
Bone Marrow‐Derived Cells as a Therapeutic Approach to Optic Nerve Diseases
Authors: Mesentier-Louro Louise A. , Zaverucha-do-Valle Camila , Rosado-de-Castro Paulo H. , Silva-Junior Almir J. , Pimentel-Coelho Pedro M. , Mendez-Otero Rosalia , Santiago Marcelo F.
Published: November 2015

Following optic nerve injury associated with acute or progressive diseases, retinal ganglion cells (RGCs) of adult mammals degenerate and undergo apoptosis. These diseases have limited therapeutic options, due to the low inherent capacity of RGCs to regenerate and due to the inhibitory milieu of the central nervous system. Among the numerous treatment approaches investigated to stimulate neuronal survival and axonal extension, cell transplantation emerges as a promising option. This review focuses on cell therapies with bone marrow mononuclear cells and bone marrow‐derived mesenchymal stem cells, which have shown positive therapeutic effects in animal models of optic neuropathies. Different aspects of available preclinical studies are analyzed, including cell distribution, potential doses, routes of administration, and mechanisms of action. Finally, published and ongoing clinical trials are summarized.
Ciprofloxacin Improves the Stemness of Human Dermal Papilla Cells
Authors: Kiratipaiboon Chayanin , Tengamnuay Parkpoom , Chanvorachote Pithi
Published: November 2015

Improvement in the expansion method of adult stem cells may augment their use in regenerative therapy. Using human dermal papilla cell line as well as primary dermal papilla cells as model systems, the present study demonstrated that ciprofloxacin treatment could prevent the loss of stemness during culture. Clonogenicity and stem cell markers of dermal papilla cells were shown to gradually decrease in the culture in a time‐dependent manner. Treatment of the cells with nontoxic concentrations of ciprofloxacin could maintain both stem cell morphology and clonogenicity, as well as all stem cells markers. We found that ciprofloxacin exerted its effect through ATP‐dependent tyrosine kinase/glycogen synthase kinase3β dependent mechanism which in turn upregulated β‐catenin. Besides, ciprofloxacin was shown to induce epithelial‐mesenchymal transition in DPCs as the transcription factors ZEB1 and Snail were significantly increased. Furthermore, the self‐renewal proteins of Wnt/β‐catenin pathway, namely, Nanog and Oct‐4 were significantly upregulated in the ciprofloxacin‐treated cells. The effects of ciprofloxacin in preserving stem cell features were confirmed in the primary dermal papilla cells directly obtained from human hair follicles. Together, these results revealed a novel application of ciprofloxacin for stem cell maintenance and provided the underlying mechanisms that are responsible for the stemness in dermal papilla cells.
Polyphenols as Modulator of Oxidative Stress in Cancer Disease: New Therapeutic Strategies
Authors: Mileo Anna Maria , Miccadei Stefania
Published: November 2015

Cancer onset and progression have been linked to oxidative stress by increasing DNA mutations or inducing DNA damage, genome instability, and cell proliferation and therefore antioxidant agents could interfere with carcinogenesis. It is well known that conventional radio‐/chemotherapies influence tumour outcome through ROS modulation. Since these antitumour treatments have important side effects, the challenge is to develop new anticancer therapeutic strategies more effective and less toxic for patients. To this purpose, many natural polyphenols have emerged as very promising anticancer bioactive compounds. Beside their well‐known antioxidant activities, several polyphenols target epigenetic processes involved in cancer development through the modulation of oxidative stress. An alternative strategy to the cytotoxic treatment is an approach leading to cytostasis through the induction of therapy‐induced senescence. Many anticancer polyphenols cause cellular growth arrest through the induction of a ROS‐dependent premature senescence and are considered promising antitumour therapeutic tools. Furthermore, one of the most innovative and interesting topics is the evaluation of efficacy of prooxidant therapies on cancer stem cells (CSCs). Several ROS inducers‐polyphenols can impact CSCs metabolisms and self‐renewal related pathways. Natural polyphenol roles, mainly in chemoprevention and cancer therapies, are described and discussed in the light of the current literature data.
Gearbox Fault Diagnosis in a Wind Turbine Using Single Sensor Based Blind Source Separation
Authors: Qian Yuning , Yan Ruqiang
Published: November 2015

This paper presents a single sensor based blind source separation approach, namely, the wavelet-assisted stationary subspace analysis (WSSA), for gearbox fault diagnosis in a wind turbine. Continuous wavelet transform (CWT) is used as a preprocessing tool to decompose a single sensor measurement data into a set of wavelet coefficients to meet the multidimensional requirement of the stationary subspace analysis (SSA). The SSA is a blind source separation technique that can separate the multidimensional signals into stationary and nonstationary source components without the need for independency and prior information of the source signals. After that, the separated nonstationary source component with the maximum kurtosis value is analyzed by the enveloping spectral analysis to identify potential fault-related characteristic frequencies. Case studies performed on a wind turbine gearbox test system verify the effectiveness of the WSSA approach and indicate that it outperforms independent component analysis (ICA) and empirical mode decomposition (EMD), as well as the spectral-kurtosis-based enveloping, for wind turbine gearbox fault diagnosis.
Three‐Dimensional Aggregates Enhance the Therapeutic Effects of Adipose Mesenchymal Stem Cells for Ischemia‐Reperfusion Induced Kidney Injury in Rats
Authors: Zhao Xiaozhi , Qiu Xuefeng , Zhang Yanting , Zhang Shiwei , Gu Xiaoping , Guo Hongqian
Published: November 2015

It has been shown that administration of adipose derived mesenchymal stem cells (AdMSCs) enhanced structural and functional recovery of renal ischemia‐reperfusion (IR) injury. Low engraftment of stem cells, however, limits the therapeutic effects of AdMSCs. The present study was designed to enhance the therapeutic effects of AdMSCs by delivering AdMSCs in a three‐dimensional (3D) aggregates form. Microwell was used to produce 3D AdMSCs aggregates. In vitro data indicated that AdMSCs in 3D aggregates were less susceptible to oxidative and hypoxia stress induced by 200 μM peroxide and hypoxia/reoxygenation, respectively, compared with those cultured in two‐dimensional (2D) monolayer. Furthermore, AdMSCs in 3D aggregates secreted more proangiogenic factors than those cultured in 2D monolayer. 2D AdMSCs or 3D AdMSCs aggregates were injected into renal cortex immediately after induction of renal IR injury. In vivo data revealed that 3D aggregates enhanced the effects of AdMSCs in recovering function and structure after renal IR injury. Improved grafted AdMSCs were observed in kidney injected with 3D aggregates compared with AdMSCs cultured in 2D monolayer. Our results demonstrated that 3D AdMSCs aggregated produced by microwell enhanced the retention and therapeutic effects of AdMSCs for renal IR injury.
Spheroid Culture of Mesenchymal Stem Cells
Authors: Cesarz Zoe , Tamama Kenichi
Published: November 2015

Compared with traditional 2D adherent cell culture, 3D spheroidal cell aggregates, or spheroids, are regarded as more physiological, and this technique has been exploited in the field of oncology, stem cell biology, and tissue engineering. Mesenchymal stem cells (MSCs) cultured in spheroids have enhanced anti‐inflammatory, angiogenic, and tissue reparative/regenerative effects with improved cell survival after transplantation. Cytoskeletal reorganization and drastic changes in cell morphology in MSC spheroids indicate a major difference in mechanophysical properties compared with 2D culture. Enhanced multidifferentiation potential, upregulated expression of pluripotency marker genes, and delayed replicative senescence indicate enhanced stemness in MSC spheroids. Furthermore, spheroid formation causes drastic changes in the gene expression profile of MSC in microarray analyses. In spite of these significant changes, underlying molecular mechanisms and signaling pathways triggering and sustaining these changes are largely unknown.
Nr2e1 Deficiency Augments Palmitate‐Induced Oxidative Stress in Beta Cells
Authors: Shi Xiaoli , Deng Haohua , Dai Zhe , Xu Yancheng , Xiong Xiaokan , Ma Pei , Cheng Jing
Published: November 2015

Nuclear receptor subfamily 2 group E member 1 (Nr2e1) has been regarded as an essential regulator of the growth of neural stem cells. However, its function elsewhere is unknown. In the present study, we generated Nr2e1 knockdown MIN6 cells and studied whether Nr2e1 knockdown affected basal beta cell functions such as proliferation, cell death, and insulin secretion. We showed that knockdown of Nr2e1 in MIN6 cells resulted in increased sensitivity to lipotoxicity, decreased proliferation, a partial G0/G1 cell‐cycle arrest, and higher rates of apoptosis. Moreover, Nr2e1 deficiency exaggerates palmitate‐induced impairment in insulin secretion. At the molecular level, Nr2e1 deficiency augments palmitate‐induced oxidative stress. Nr2e1 deficiency also resulted in decreases in antioxidant enzymes and expression level of Nrf2. Together, this study indicated a potential protective effect of Nr2e1 on beta cells, which may serve as a target for the development of novel therapies for diabetes.
Design of an Active Multispectral SWIR Camera System for Skin Detection and Face Verification
Authors: Steiner Holger , Sporrer Sebastian , Kolb Andreas , Jung Norbert
Published: November 2015

Biometric face recognition is becoming more frequently used in different application scenarios. However, spoofing attacks with facial disguises are still a serious problem for state of the art face recognition algorithms. This work proposes an approach to face verification based on spectral signatures of material surfaces in the short wave infrared (SWIR) range. They allow distinguishing authentic human skin reliably from other materials, independent of the skin type. We present the design of an active SWIR imaging system that acquires four-band multispectral image stacks in real-time. The system uses pulsed small band illumination, which allows for fast image acquisition and high spectral resolution and renders it widely independent of ambient light. After extracting the spectral signatures from the acquired images, detected faces can be verified or rejected by classifying the material as “skin” or “no-skin.” The approach is extensively evaluated with respect to both acquisition and classification performance. In addition, we present a database containing RGB and multispectral SWIR face images, as well as spectrometer measurements of a variety of subjects, which is used to evaluate our approach and will be made available to the research community by the time this work is published.
RS485 Image Sensor for Digital Cinema System
Authors: Kim Eunju , Kang Seokhoon , Lee Sangsoon
Published: November 2015

To activate various devices using RS485, a repeater is generally used. In current digital cinema systems, each device is controlled with RS485 by mixing RS485 and DMX512. However, as today’s cinema equips hundreds of 4D chairs and the environmental directors, it is nearly infeasible for the legacy system to control. To this end, this paper designs and implements a new system which makes hundreds of 4D chairs and the environmental directors be controlled simultaneously exploiting RS485 network topology and its repeaters. The proposed approach is tested in a real-time system for assessing the performance by Paessler Router Traffic Grapher (PRTG) in Windows environment. Simulation results show that the tested system supports 4D chairs and their motions are well operated simultaneously with RS485.
Heightening Energetic Stress Selectively Targets LKB1-Deficient Non–Small Cell Lung Cancers
Authors: Momcilovic Milica , McMickle Robert , Abt Evan , Seki Atsuko , Simko Sarah A. , Magyar Clara , Stout David B. , Fishbein Michael C. , Walser Tonya C. , Dubinett Steven M. , Shackelford David B.
Published: November 2015

Inactivation of the LKB1 tumor suppressor is a frequent event in non–small cell lung carcinoma (NSCLC) leading to the activation of mTOR complex 1 (mTORC1) and sensitivity to the metabolic stress inducer phenformin. In this study, we explored the combinatorial use of phenformin with the mTOR catalytic kinase inhibitor MLN0128 as a treatment strategy for NSCLC bearing comutations in the LKB1 and KRAS genes. NSCLC is a genetically and pathologically heterogeneous disease, giving rise to lung tumors of varying histologies that include adenocarcinomas and squamous cell carcinomas (SCC). We demonstrate that phenformin in combination with MLN0128 induced a significant therapeutic response in KRAS/LKB1–mutant human cell lines and genetically engineered mouse models of NSCLC that develop both adenocarcinomas and SCCs. Specifically, we found that KRAS/LKB1–mutant lung adenocarcinomas responded strongly to phenformin + MLN0128 treatment, but the response of SCCs to single or combined treatment with MLN0128 was more attenuated due to acquired resistance to mTOR inhibition through modulation of the AKT-GSK signaling axis. Combinatorial use of the mTOR inhibitor and AKT inhibitor MK2206 robustly inhibited the growth and viability of squamous lung tumors, thus providing an effective strategy to overcome resistance. Taken together, our findings define new personalized therapeutic strategies that may be rapidly translated into clinical use for the treatment of KRAS/LKB1–mutant adenocarcinomas and squamous cell tumors. Cancer Res; 75(22); 4910–22. ©2015 AACR.
Attenuating Hypoxia-Induced Apoptosis and Autophagy of Mesenchymal Stem Cells: the Potential of Sitagliptin in Stem Cell-Based Therapy
Authors: Wang Xi-Mei , Yang Yue-Jin , Wu Yong-Jian , Zhang Qian , Qian Hai-Yan
Published: November 2015

Background/Aims: Dipeptidyl peptidase-4 (DPP-4) inhibitors have pleiotropic effects on cardiovascular protection beyond the antidiabetic property. However, it remains unknown that the impact of one DPP-4 inhibitor sitagliptin on the survival of mesenchymal stem cells (MSCs) in hypoxia and serum deprivation (H/SD) environment. Methods: The apoptosis and autophagy of MSCs were analyzed in different concentrations of sitagliptin under H/SD condition. For later studies, we tested the relationship between anti-apoptotic and anti-autophagic effects of sitagliptin. The level of cell apoptosis was analyzed by Annexin V-FITC/PI staining, western blot of Bcl-2 and Bax proteins. Autophagy flux was assessed by multiple autophagy related proteins and substrates. Cell autophagy was identified by acridine orange staining, western blot of Beclin 1 and light chain 3 protein, and transmission electron microscopy. Results: We demonstrated that sitagliptin attenuated hypoxia-induced apoptosis and autophagy of MSCs. Furthermore, sitagliptin regulated cell autophagy by Bcl-2/ Beclin 1 pathway in H/SD condition. Conclusions: This study provides insight into the utility of the DPP-4 inhibitor sitagliptin for MSCs transplantation in the ischemic microenvironment that extends its antidiabetic property.
The Effects of Adjuvant Endocrine Treatment on Serum Leptin, Serum Adiponectin and Body Composition in Patients with Breast Cancer: The Izmir Oncology Group (IZOG) Study
Authors: Akyol Murat , Demir Leyla , Alacacioglu Ahmet , Ellidokuz Hülya , Kucukzeybek Yuksel , Yildiz Yasar , Gumus Zehra , Bayoglu Vedat , Yildiz Ibrahim , Salman Tarık , Varol Umut , Kucukzeybek Betul , Demir Lutfiye , Dirican Ahmet , Sutcu Recep , Tarhan Mustafa Oktay
Published: November 2015

Background: A limited number of studies have been conducted on the effects of hormonal therapy with tamoxifen (TMX) or aromatase inhibitors (AIs) on plasma levels of leptin and adiponectin, as well as body composition in breast cancer (BC) patients. Therefore, we aimed to analyze the relationship between adipocytokines and body composition as well as the effects of TMX and AIs on plasma adiponectin, leptin, leptin/adiponectin ratio (LAR) and body composition. Methods: Patients were treated with either TMX or AI according to their menopausal status after adjuvant radiotherapy. Changes in body composition and serum leptin and adiponectin levels were evaluated. We recorded the type of hormonal therapy, BMI, waist/hip ratio (WHR), leptin and adiponectin levels at study entry, and after 6 and 12 months. Results: From baseline to the 6- and 12-month follow-ups, there were statistically significant increases in WHR (p = 0.003), fat mass (p = 0.041), and serum leptin (p < 0.001) and adiponectin levels (p < 0.001). The changes in body composition and serum leptin and adiponectin levels were similar in TMX and AI groups. A statistically significant decrease was found in total body water and LAR (p < 0.001). Although weight and body fat percentage increased, such increases were not statistically significant. A positive correlation was found between baseline BMI and serum leptin levels. This correlation was maintained at 6 and 12 months. The negative correlation found between serum adiponectin levels at baseline and baseline BMI did not last throughout the study. Conclusion: In this study, increased leptin and adiponectin levels and a decreased LAR were found in both AI and TMX groups. These changes might have occurred through both mechanisms of hormonal therapy and body composition changes. Therefore, AIs and TMX may exert their protective effects for BC patients by decreasing LAR rather than affecting leptin or adiponectin alone.
Demineralized Dentin Matrix Induces Odontoblastic Differentiation of Dental Pulp Stem Cells
Authors: Liu Guolin , Xu Guoquan , Gao Zhenhua , Liu Zhenhai , Xu Junji , Wang Jinsong , Zhang Chunmei , Wang Songlin
Published: November 2015

The aim of this study was to investigate the effect of demineralized dentin matrix (DDM) on dental pulp stem cells (DPSCs) and the potential of complexes with DPSCs and DDM for mineralized tissue formation. Stem cells derived from the dental pulp of healthy pigs aged 18 months were isolated and cultured. DPSCs were incubated with alpha-minimum essential medium treated with DDM extract at 1 mg/ml (DDM1) or 10 mg/ml (DDM10). The concentrations of 3 growth factors in DDM extract was measured by enzyme-linked immunosorbent assay. Adhesion of DPSCs on DDM and hydroxyapatite-tricalcium phosphate (HA-TCP) surfaces was observed using scanning electron microscopy. Cell proliferation was evaluated with cell counting kit-8 and migration by Transwell migration assays. Odontoblastic differentiation was assessed by alkaline phosphatase (ALP) and alizarin red staining, ALP activity and real-time polymerase chain reaction analysis of markers of ALP, runt-related transcription factor 2, type I collagen, dentin matrix acidic phosphoprotein-1, osteonectin and dentin sialophosphoprotein (DSPP). Finally, DPSCs were combined with DDM and placed subcutaneously in nude mice for 12 weeks; DPSCs combined with HA-TCP and DDM alone served as controls. DDM could promote DPSC adhesion, migration and odontoblastic differentiation. Mineralized tissue formation was observed with the DPSC and DDM combination and the DPSC and HA-TCP combination. The mineralized tissue of the DPSC + DDM combination stained positive for DSPP, similar to the dentin tissue. These results indicate that DDM induces DPSC odontoblastic differentiation, suggesting applications for dentin regeneration.
Vestibular Schwannoma: The Evolution of Hearing and Tumor Size in Natural Course and after Treatment by LINAC Stereotactic Radiosurgery
Authors: Ikonomidis Christos , Pica Alessia , Bloch Jocelyne , Maire Raphael
Published: November 2015

Objective: To review the natural course of tumor size and hearing during conservative management of 151 patients with unilateral vestibular schwannoma (VS), and to evaluate the same parameters for the part of the group (n = 84) who were treated by LINAC stereotactic radiosurgery (SRS). Methods: In prospectively collected data, patients underwent MRI and complete audiovestibular tests at inclusion, during the conservative management period and after SRS. Hearing was graded according to the Gardner-Robertson (GR) scale and tumor size according to Koos. Statistics were performed using Kaplan-Meier survival analysis and multivariate analyses including linear and logistic regression. Specific insight was given to patients with serviceable hearing. Results: During the conservative management period (mean follow-up time: 24 months, range: 6-96), the annual risk of GR class degradation was 6% for GRI and 15% for GR II patients. Hearing loss as an initial symptom was highly predictive of further hearing loss (p = 0.003). Tumor growth reached 25%. For SRS patients, functional hearing preservation was 51% at 1 year and 36% at 3 years. Tumor control was 94 and 91%, respectively. Conclusion: In VS patients, hearing loss at the time of diagnosis is a predictor of poorer hearing outcome. LINAC SRS is efficient for tumor control. Patients who preserved their pretreatment hearing presented less hearing loss per year after SRS than before treatment, suggesting a protective effect of SRS when cochlear function can be preserved.
The Effect of Apatinib on the Metabolism of Carvedilol Both in vitro and in vivo
Authors: Lin Dan , Wang Zhe , Li Junwei , Wang Li , Wang Shuanghu , Hu Guo-Xin , Liu Xinshe
Published: November 2015

Background: In light of the growing number of cancer survivors, the incidence of cardiovascular complications in these patients had also increased, while the effect of apatinib on the pharmacokinetic of cardioprotective drug (carvedilol) in rats or human is still unknown. The present work was to study the impact of apatinib on the metabolism of carvedilol both in vitro and vivo. Methods: A specific and sensitive ultra-performance liquid-chromatography tandem mass spectrometry method was applied to determine the concentration of carvedilol and its metabolites (4′-hydroxyphenyl carvedilol [4′-HPC], 5′-hydroxyphenyl carvedilol [5′-HPC] and o-desmethyl carvedilol [o-DMC]). Results: The inhibition ratios in human liver microsomes were 10.28, 10.89 and 5.94% for 4′-HPC, 5′-HPC and o-DMC, respectively, while in rat liver microsomes, they were 3.22, 1.58 and 1.81%, respectively. The data in vitro of rat microsomes were consistent with the data in vivo that the inhibition of 4′-HPC and 5′-HPC formation was higher than the control group. Conclusion: Our study showed that apatinib could significantly inhibit the formation of carvedilol metabolites both in human and rat liver microsomes. It is recommended that the effect of apatinib on the metabolism of carvedilol should be noted and carvedilol plasma concentration should be monitored.
Establishing the Evidence Bar for Molecular Diagnostics in Personalised Cancer Care
Authors: Schneider Daniel , Bianchini Giampaolo , Horgan Denis , Michiels Stefan , Witjes Wim , Hills Robert , Plun-Favreau Juliette , Brand Angela , Lawler Mark ,   on behalf of EAPM Working Group for Oncology Clinical Research
Published: November 2015

While personalised cancer medicine holds great promise, targeting therapies to the biological characteristics of patients is limited by the number of validated biomarkers currently available. The implementation of biomarkers has undergone many challenges with few biomarkers reaching cancer patients in the clinic. There have been many biomarkers that have been published and claimed to be therapeutically useful, but few become part of the clinical decision-making process due to technical, validation and market access issues. To reduce this attrition rate, there is a significant need for policy makers and reimbursement agencies to define specific evidence requirements for the introduction of biomarkers into clinical practice. Once these requirements are more clearly defined, in an analogous manner to pharmaceuticals, researchers and diagnostic companies can better focus their biomarker research and development on meeting these specific requirements, which should lead to the more rapid introduction of new molecular oncology tests for patient benefit.
Evaluation of the Biocompatibility of Dialysis Membranes
Authors: Kokubo Kenichi , Kurihara Yoshitaka , Kobayashi Kozue , Tsukao Hiroshi , Kobayashi Hirosuke
Published: November 2015

Background: Improvements in the biocompatibility of dialysis membranes have reduced biological responses elicited by blood-membrane interactions. In this article, recent technological developments in dialysis membranes with regard to biocompatibility and recent progress in the evaluation of the biocompatibility of dialysis membranes are reviewed. Summary: The focus of investigation into dialysis membranes in recent years has focused on not only membrane materials, but also their surface textures, which have been changed, for example, by coating with vitamin E or by changing the amount and type of hydrophilizing agents used. Research and development is directed at altering the chemical and physical properties of membrane surfaces to suppress biological responses that are particularly elicited as a result of platelet activation. To develop membranes with excellent biocompatibility, biocompatibility should be evaluated on a like-for-like basis under conditions that are similar to those in clinical settings. Evaluation using actual dialyzers can be performed using porcine blood, platelet-rich plasma isolated from porcine blood (and platelet-rich plasma with leukocytes), or suspension of neutrophils isolated from porcine blood or cultured human monocytes. Key Messages: Highly biocompatible dialysis membranes can be developed when the overall correlations among biological reactions are examined by integrating all data on biological responses elicited by blood-membrane interactions or mutual interactions among blood cells.
Uremic Solutes Produced by Colon Microbes
Authors: Tanaka Hisae , Sirich Tammy L. , Meyer Timothy W.
Published: November 2015

Background: Colon microbes produce a large number of organic compounds that are foreign to mammalian cell metabolism. Summary: Some of the compounds made by microbes are absorbed in the colon and then normally excreted by the kidneys. Accumulation of these compounds in the plasma as uremic solutes may contribute to illness in patients whose kidneys have failed. Mass spectrometry is expanding our knowledge of the chemical identity of the colon-derived uremic solutes, and DNA sequencing technologies are providing new knowledge of the microbes and metabolic pathways by which they are made. Because they are made in an isolated compartment by microbes, their production may prove simpler to suppress than the production of other uremic solutes. Key Messages: To the extent that they are toxic, suppressing their production could improve the health of renal failure patients without the need for more intensive or prolonged dialysis.
Effectiveness and Tolerability of THC/CBD Oromucosal Spray for Multiple Sclerosis Spasticity in Italy: First Data from a Large Observational Study
Authors: Trojano Maria , Vila Carlos
Published: November 2015

Background: The prospective, non-interventional Mobility Improvement (MOVE) 2 study was designed to provide real life data on clinical outcomes of patients with treatment-resistant multiple sclerosis (MS) spasticity receiving routine treatment with tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (Sativex®), subsequent to its approval in European countries. Methods: This interim analysis reports on MOVE 2 patients from Italy. Results: Interim data from 322 patients (58.3% female; mean age 51.1 ± 10.2 years) were analyzed. From baseline to month 3 of treatment (Visit 3), the mean 0-10 Numerical Rating Scale (NRS) score decreased by -19.1% (-1.6 points, p < 0.0001) and the mean modified Ashworth score decreased from 2.6 to 2.3 points (p < 0.0001). At Visit 3, 24.6% of 203 patients with available data were clinically relevant responders (≥30% improvement from baseline NRS score; p < 0.001 vs. baseline). The mean reported dose of THC:CBD oromucosal spray was 6.1 ± 2.5 sprays/day at Visit 1 (1 month) and 5.1 ± 2.6 sprays/day at Visit 3 (range 1-12 sprays/day at both timepoints). Forty-one (13.1%) patients reported at least one adverse event (AE), which included 3 serious AEs (1 unrelated). AEs with an incidence ≥1% were dizziness (5.6%), confusion (2.5%), nausea (1.25%) and somnolence (1.25%). Conclusion: In everyday clinical practice in Italy, THC:CBD oromucosal spray provided symptomatic relief of MS spasticity with good tolerability in a relevant number of previously resistant patients.
Oxidative Balance Score and Chronic Kidney Disease
Authors: Ilori Titilayo O. , Sun Ro Young , Kong So Yeon , Gutierrez Orlando M. , Ojo Akinlolu O. , Judd Suzanne E. , Narayan K.M. Venkat , Goodman Michael , Plantinga Laura , McClellan William
Published: November 2015

Background: The oxidative balance score (OBS) is a composite estimate of the overall pro- and antioxidant exposure status in an individual. The aim of this study was to determine the association between OBS and renal disease. Methods: Using the Reasons for Geographic and Racial Differences in Stroke cohort study, OBS was calculated by combining 13 a priori-defined pro- and antioxidant factors by using baseline dietary and lifestyle assessment. OBS was divided into quartiles (Q1-Q4) with the lowest quartile, Q1 (predominance of pro-oxidants), as the reference. Multivariable logistic regression and Cox proportional hazards models were used to estimate adjusted ORs for albuminuria defined as urine albumin/creatinine ratio (ACR) >30 mg/g, macroalbuminuria defined as ACR >300 mg/g and chronic kidney disease (CKD) defined as estimated glomerular filtration rate <60 ml/min/1.73 m2 according to the Chronic Kidney Disease Epidemiology Collaboration and hazards ratios for end-stage renal disease (ESRD), respectively. Results: Of the 19,461 participants analyzed, 12.9% had albuminuria and 10.1% had CKD at baseline; over a median follow-up of 3.5 years (range 2.14-4.32 years), 0.46% developed ESRD. Higher OBS quartiles were associated with lower prevalence of CKD (OR vs. Q1: Q2 = 0.93 [95% CI 0.80-1.08]; Q3 = 0.90 [95% CI 0.77-1.04] and Q4 = 0.79 [95% CI 0.67-0.92], p for trend <0.01). The associations between OBS and albuminuria (p for trend 0.31) and incident ESRD (p for trend 0.56) were not significant in the fully adjusted models. Conclusions: These findings suggest that higher OBS is associated with lower prevalence of CKD. Lack of association with ESRD incidence in the multivariable analyses indicates that temporal relation between OBS and renal damage remains unclear.
A Randomised Crossover Trial: The Effect of Inulin on Glucose Homeostasis in Subtypes of Prediabetes
Authors: Guess Nicola D. , Dornhorst Anne , Oliver Nick , Frost Gary S.
Published: November 2015

Background: Fermentable carbohydrates (FCHO) have been shown to improve insulin sensitivity in normoglycaemic and insulin-resistant subjects. However, there are no data on subjects with prediabetes. We aimed to investigate the effect of the FCHO inulin, on glucose homeostasis in subjects with prediabetes. Methods: In a double-blind and placebo-controlled crossover study, 40 volunteers with prediabetes were randomly allocated to take 30 g/day of inulin or cellulose for 2 weeks in a crossover trial, following a 4-week dose-escalation run-in. Fasting insulin and glucose were measured for all subjects. Fifteen of the 40 subjects also underwent a meal tolerance test to assess insulin sensitivity, free fatty acids and glucagon-like peptide-1 concentrations. A subanalysis was carried out to examine any differences between the prediabetes subtypes. Results: Inulin was associated with a significant increase in (0-30 min)incremental AUC (iAUC) for insulin (treatment: p < 0.04) and (0-60 min)iAUC for insulin (treatment: p < 0.04) compared to control. There was a significant reduction in insulin resistance measured by the homeostatic model assessment in the isolated-impaired fasting glucose (p < 0.05) but not in the isolated-impaired glucose tolerance groups (p = 0.59). Conclusion: The FCHO, inulin, may have unique metabolic effects that are of particular benefit to people at risk of diabetes, which warrant further investigation.
Function of grunts, girneys and coo calls of Japanese macaques (Macaca fuscata) in relation to call usage, age and dominance relationships
Authors: Katsu Noriko , Yamada Kazunori , Nakamichi Masayuki
Published: November 2015

We investigated how the context of the production of vocalizations used in social interactions among Japanese macaques (Macaca fuscata) affects their outcome. We focused on a variety of soft vocalizations, including three acoustically distinct call types: grunts, girneys, and coo calls. We predicted that call outcomes would be influenced by call combinations and exchanges, and by the relationship between the caller and the recipient. We observed social interactions among female Japanese macaques, and found that individuals were less likely to initiate agonistic behaviour when they emitted calls. Call exchanges and call combinations increased the occurrence of affiliative interactions. The probability of affiliative interaction following a given type of call differed according to the relationship between the caller and the recipient. These findings suggest that recipients interpret these calls within a social context; they also demonstrate the existence of complex communicative abilities that integrate vocalizations and context in these monkeys.
Jiang Baili: Frustrated Military Intellectual in Republican China
Authors: Setzekorn Eric
Published: November 2015

The 1911-1927 period represented a window of opportunity for the creation of a Chinese military structure with a professional officer corps. After the fall of the Qing dynasty, Jiang Baili emerged as a rare military theorist who had intellectual status, a nuanced understanding of civil-military affairs, and both domestic and foreign military training. The failure of Jiang Baili to influence China’s military development was mainly due to his individual difficulties in focusing his intellectual talents on real-world issues. After producing two seminal works in the 1910s, Jiang lived for another twenty years as a marginalized, increasingly eccentric military analyst.
Catalogue of the Iranian Microgastrinae (Hymenoptera: Braconidae)
Authors: GADALLAH NEVEEN S. , GHAHARI HASSAN , PERIS-FELIPO FRANCISCO JAVIER
Published: November 2015

In the present study, the Iranian Microgastrinae (Hymenoptera: Braconidae) fauna is summarized. It is based on a detailed study of all available published data and new material collected. In total 99 species belonging to 8 genera are from Iran: Apanteles Förster, 1862 (36 species), Cotesia Cameron, 1891 (34 species), Deuterixys Mason, 1981 (1 species), Diolcogaster Ashmead, 1900 (4 species), Microgaster Latreille, 1804 (4 species), Microplitis Förster, 1862 (11 species), Pholesetor Mason, 1981 (4 species) and Protapanteles Ashmead, 1898 (5 species) in 4 tribes (Apantilini, Cotesiini, Microgastrini and Microplitini). A faunistic list with distribution data, and host records are given. Four species are new records for the fauna of Iran: Apanteles brunnistigma Abdinbekova, 1969, A. ingenuoides Papp, 1971, Microplitis decipiens Prell, 1925 and M. marshallii Kokujev, 1898.
An annotated checklist of the Cladocera (Crustacea: Branchiopoda) of Colombia
Authors: KOTOV ALEXEY A. , FUENTES-REINÉS JUAN M.
Published: November 2015

Based on the revision of available literature on the Colombian Cladocera (Crustacea: Branchiopoda), we present an annotated checklist, with taxonomical comments for all taxa recorded since the start of research on this group in the country in 1913. We have listed 101 valid taxa, of which most records belong to the Caribbean region of Colombia. The situation in Colombian Cladocera taxonomy is, at present, unfavorable for any realistic conclusions on biodiversity, ecology and biogeography.
Bees of the Lasioglossum series (Hymenoptera: Halictidae) in South Korea, with an illustrated keys to species
Authors: MURAO RYUKI , LEE HEUNG-SIK , TADAUCHI OSAMU
Published: November 2015

The South Korean fauna of the bee genus Lasioglossum Curtis (Halictidae: Halictini) belonging to the Lasioglossum series (i.e., those with the second submarginal crossvein strong) are reviewed. A total of 12 species are recognized for the country. Lasioglossum circularum Fan & Ebmer is recorded for the first time from the Korean Peninsula and the following species are newly recorded from South Korea: L. denticolle (Morawitz), L. formosae (Strand), L. kansuense (Blüthgen), L. occidens (Smith), L. sutshanicum Pesenko, and L. upinense (Morawitz). Bionomical data as well as illustrated keys to females and males of South Korean species are provided. DNA sequences including a part of barcode region are given for L. kansuense and L. occidens.
Six new species of Triomicrus Sharp from southern China (Coleoptera: Staphylinidae: Pselaphinae)
Authors: SHEN JIA-WEI , YIN ZI-WEI , LI LI-ZHEN
Published: November 2015

Seven species of the genus Triomicrus Sharp are recognized in southern China, six of them are described as new: T. acutus  and T. nanlingensis Shen & Yin, sp. n. (Guangdong), T. pinnatus Shen & Yin, sp. n. (Guangdong and Hunan), T. cochlis Shen & Yin, sp. n. (Guangdong, Hunan and Guangxi), and T. cavus Shen & Yin, sp. n. and T. longus Shen & Yin, sp. n. (Guangxi). A key for the identification of Triomicrus in southern China is presented.
Sales Compensation Strategy
Authors: Madhani Pankaj M.
Published: November 2015

Sales compensation is of primary concern to both sales employees and sales organization as it is central to their working relationship. Compensation strategy decision regarding pay level (total earnings generated) and pay mix (relative proportion of fixed pay and variable pay) are both vital in sales compensation plan. This research explains major attributes of pay level and pay mix design of sales organization and identifies various factors influencing it. Advantages and disadvantages of fixed as well as variable pay are presented in the article. It also provides analytical frameworks and models for calculating optimal pay level and pay mix. An effective compensation plan through optimal design of pay level and pay mix successfully balances the needs of salespeople, sales organization and customers simultaneously to maximize value of the organization. Finally, research concludes with an illustration to provide methodology for calculating optimal value of pay level and pay mix in a sales organization.
Epistemological issues in the history of Italian psychiatry: the contribution of Gaetano Perusini (1879–1915)
Authors: Passione Roberta
Published: November 2015

In the late nineteenth and early twentieth centuries, Italian psychiatry was characterized by its emphasis on an organic explanation of mental illness. ‘Cerebral mythology’ was a major influence in Italy, at least until the second half of the twentieth century, often at the expense of the development of psychology. In this context, a few psychiatrists adopted a different epistemological perspective, based on a more ‘integrative’ view of their discipline. In particular, Gaetano Perusini stands out. He promoted the concept of psychiatry as a science which embraced many different fields, thus emphasizing the theme of pluralism, which is still debated today in the philosophy of science and psychiatric practice.
The creator of the term ‘anancasm’ was Hungarian: Guyla Donáth (1849–1944)
Authors: Steinberg Holger
Published: November 2015

There is considerable confusion in the field of research on the history of psychiatry as to who created the term anancasm. This article seeks to clarify that the term was coined by the Hungarian psychiatrist Gyula Donáth, who was born in Baja, on the Danube, and worked mainly in Budapest. Donáth’s publications reveal that his predominant sphere of interest and research was neurology and psychiatry. A number of his publications deal with epilepsy and obsessive-compulsive disorders. After a period of intensive research, during which he spent some time in Berlin at the clinic of neuroscientist Carl Westphal, Donáth proposed the term ‘anancasm’ in 1895 to describe compulsive mental processes.
The ‘Preliminary Discourse’ to Methodical Nosology, by François Boissier de Sauvages (1772)
Authors: Starkstein SE , Berrios GE
Published: November 2015

The eighteenth century witnessed an intense drive to classify diseases as natural kinds. Together with Linné, Macbride, Cullen, Sagar and Vogel, François Boissier de Sauvages, Professor of Medicine at Montpellier, was an important player in this process. In his monumental Nosologie Méthodique, Sauvages based his nosological system on the more botanico view proposed by Thomas Sydenham, namely, that human diseases (including mental ailments) should be classified in the same way as were plants. Classic Text No. 104 is an abridged translation of the Preliminary Discourse to the Nosologie Méthodique.
‘A Berlin psychiatrist with an American passport’: Lothar Kalinowsky, electroconvulsive therapy and international exchange in the mid-twentieth century
Authors: Rzesnitzek Lara
Published: November 2015

The emigration of Lothar Kalinowsky (1899–1992) might, at first glance, seem to be a history of coincidence and twists of fate, but it is shown to be a truly entangled and intertwined history and story. The international introduction of electroconvulsive therapy was not only closely involved with the political, scientific and economic conditions during World War II, but the story of Kalinowsky’s relevance to it emerges from competing stories, told differently in Europe and the USA – and by Kalinowsky himself. Tracing these stories up to the end of the 1960s reveals Kalinowsky as an influential inheritor and patron of Berlin Biological Psychiatry, rather than telling the history of an émigré innovator of international neuropsychiatric research.
Bilobate leaves of Bauhinia (Leguminosae, Caesalpinioideae, Cercideae) from the middle Miocene of Fujian Province, southeastern China and their biogeographic implications
Authors: Lin Yanxiang , Wong William Oki , Shi Gongle , Shen Si , Li Zhenyu
Published: November 2015

Background

Morphological and molecular phylogenetic studies suggest that the pantropical genusBauhiniaL. s.l. (Bauhiniinae, Cercideae, Leguminosae) is paraphyletic and may as well be subdivided into nine genera, includingBauhiniaL. s.s. and its allies. Their leaves are usually characteristic bilobate and are thus easily recognized in the fossil record. This provides the opportunity to understand the early evolution, diversification, and biogeographic history of orchid trees from an historical perspective under the framework of morphological and molecular studies.

Results

The taxonomy, distribution, and leaf architecture ofBauhiniaand its allies across the world are summarized in detail, which formed the basis for classifying the bilobate leaf fossils and evaluating the fossil record and biogeography ofBauhinia. Two species ofBauhiniaare described from the middle Miocene Fotan Group of Fujian Province, southeastern China.Bauhinia ungulatoidessp. nov. is characterized by shallowly to moderately bilobate, pulvinate leaves with shallowly cordate bases and acute apices on each lobe, as well as paracytic stomatal complexes.Bauhinia fotanaF.M.B. Jacques et al. emend. possesses moderately bilobate, pulvinate leaves with moderately to deeply cordate bases and acute or slightly obtuse apices on each lobe.

Conclusions

Bilobate leaf fossilsBauhinia ungulatoidesandB. fotanatogether with other late Paleogene – early Neogene Chinese record of the genus suggest thatBauhiniahad been diverse in South China by the late Paleogene. Their great similarities to some species from South America and South Asia respectively imply thatBauhiniamight have undergone extensive dispersals and diversification during or before the Miocene. The fossil record, extant species diversity, as well as molecular phylogenetic analyses demonstrate that the Bauhiniinae might have originated in the Paleogene of low-latitudes along the eastern Tethys Seaway. They dispersed southwards into Africa, migrated from Eurasia to North America via the North Atlantic Land Bridge or floating islands during the Oligocene. Then the genus spread into South America probably via the Isthmus of Panama since the Miocene onward, and underwent regional extinctions in the Boreotropics of mid-high-latitudes during the Neogene climatic cooling. Hence,Bauhiniapresently exhibits a pantropical intercontinental disjunct distribution.
Hippocampal atrophy but not white-matter changes predicts the long-term cognitive response to cholinesterase inhibitors in Alzheimer’s disease
Authors: Cheng Yu-Wen , Chen Ta-Fu , Cheng Ting-Wen , Lai Ya-Mei , Hua Mau-Sun , Chen Ya-Fang , Chiu Ming-Jang
Published: November 2015

Introduction

This study aimed to investigate the feasibility of predicting the long–term effects of cholinesterase inhibitors (ChEI) with common clinical neuroimaging parameters of Alzheimer’s disease, including medial temporal lobe atrophy (MTA) and white matter hyperintensity (WMH).

Method

A cohort of 353 patients with very mild to moderate Alzheimer’s disease received cholinesterase inhibitors and were followed for a median of 46.6 months. Baseline clinical data, including age, educational level, Clinical Dementia Rating (CDR), Taiwanese Mental State Examination (TMSE), and visual scoring for MTA and WMH were tested as possible predictive factors that influence the survival from a TMSE decline of at least 3 points.

Results

During the follow-up period, 162(46 %) patients had a significant TMSE decline. Patients with age-adjusted prominent MTA had a significantly shorter TMSE-decline free interval than those without (43.4 ± 4.5 months vs. 68.2 ± 9.5 months, log rank test p-value =0.001). However, the severity of WMH does not significantly influence cognitive outcomes. Cox regression analysis identified that younger age at the time of starting ChEI (p < 0.0005) and higher total MTA scores (p = 0.002) predict a more rapid TMSE decline under ChEI therapy.

Conclusions

Younger age at the time of starting ChEI and higher visual scoring of MTA may imply a more advanced Alzheimer’s pathology. WMH load is not a prognostic indicator of treatment response to ChEI.