BioMed Research International The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Breast Stimulation in Low-Risk Primigravidas at Term: Does It Aid in Spontaneous Onset of Labour and Vaginal Delivery? A Pilot Study Thu, 27 Nov 2014 06:44:39 +0000 Aims. The aim of the study was to elicit the safety and efficacy of breast stimulation as an intervention to prevent postdatism and as an aid in spontaneous onset of labour. Methods. Primigravidas with cephalic presentation, without any high-risk factor, were recruited between 36 to 38 weeks of gestation. 200 patients were recruited and randomized into two groups (n = 100). Breast stimulation was advised to one group but not to the other group. Bishop’s scoring was done at 38 weeks and repeated at 39 weeks of gestation. Maternal and fetal outcomes were compared in two groups. Result. Bishop’s score changed from 3.12 (±1.01) to 3.9 (±1.08) in control group and from 3.02 (±0.82) to 6.08 (±1.29) in breast stimulation group after one week ( value < 0.0001). The period of gestation at delivery was 39.5 (±2.3) weeks in control group and 39.2 (±2.8) weeks in intervention group ( value: 0.044). There were increased chances of vaginal delivery in intervention group (P value: 0.046). Duration of labor, hyperstimulation, presence of meconium stained liquor, postpartum hemorrhage, and neonatal outcomes were similar in both groups. Conclusion. Breast stimulation in low-risk primigravidas helps in cervical ripening and increases chances of vaginal delivery. Nilanchali Singh, Reva Tripathi, Yedla Manikya Mala, and Niharika Yedla Copyright © 2014 Nilanchali Singh et al. All rights reserved. Are There Differences in the Health Outcomes of Mothers in Europe and East-Asia? A Cross-Cultural Health Survey Thu, 27 Nov 2014 06:21:48 +0000 The aim of the current study was to investigate differences in quality of life outcomes and depression of mothers in East-Asia and Central Europe. 170 women in Japan and 226 women in Austria with children between 3 and 5 answered the same cross-culturally validated questionnaires. The Quality of Life Questionnaire from the WHO (WHOQOL-Bref), the Patient Health Questionnaire (PHQ-2), the Sense of Coherence Scale (SOC-13), a Social Support Scale (MSPSS), and questions on gender orientation were used. In all dimensions of QOL (physical, psychological, social, and environmental) Japanese women had lower QOL scores compared to Austrian mothers (). Seven percent of women in both countries experienced major depression. In both countries sense of coherence, experienced stress level, satisfaction with income, social support, and gender roles had an influence on QOL and depressive symptoms. Mothers in Japan consider life events less comprehensible, manageable, and meaningful and experience less support. Consequently, creating an environment where fathers could be more involved in child rearing and mothers have more opportunities to choose between life styles and working and social environments would improve QOL not only in Japanese mothers but also in other countries all over the world. Eva Mautner, Chie Ashida, Elfriede Greimel, Uwe Lang, Christina Kolman, Daniela Alton, and Wataru Inoue Copyright © 2014 Eva Mautner et al. All rights reserved. Perineal Ultrasound as a Complement to POP-Q in the Assessment of Cystoceles Thu, 27 Nov 2014 00:10:16 +0000 Purpose. In the present study we want to propose a classification system to quantify cystoceles by perineal ultrasound (PUS). Materials and Methods. 120 PUS data were analyzed measuring the distance between the lowest point of the bladder and the midpubic line (MPL) during rest and Valsalva. Results were classified into groups and compared to POP-Q using the -coefficient. Results for exact bladder position were checked for interrater reliability using ICC and Pearson’s coefficient and results for classification were checked using the κ-coefficient. Bladder positions at rest and Valsalva were correlated with the distance between these points. Results. Highly significant differences concerning the position at rest and the distance between rest and Valsalva were found between the groups. For the interrater agreement, the Pearson correlation coefficient was , the ICC (A-1) = 0.98, and . Comparing the classification results for POP-Q and PUS, the kappa-coefficient was . Conclusion. PUS using the MPL and the classification system is a highly reliable tool for the evaluation of cystoceles. PUS shows good correlation with POP-Q. Furthermore, PUS offers a doubtless identification of the descending organ. Further studies are needed to evaluate the clinical use of the classification system proposed here. Laila Najjari, Julia Hennemann, Pia Larscheid, Thomas Papathemelis, and Nicolai Maass Copyright © 2014 Laila Najjari et al. All rights reserved. Resveratrol as a Therapeutic Agent for Alzheimer’s Disease Wed, 26 Nov 2014 09:06:01 +0000 Alzheimer’s disease (AD) is the most common cause of dementia, but there is no effective therapy till now. The pathogenic mechanisms of AD are considerably complex, including Aβ accumulation, tau protein phosphorylation, oxidative stress, and inflammation. Exactly, resveratrol, a polyphenol in red wine and many plants, is indicated to show the neuroprotective effect on mechanisms mostly above. Recent years, there are numerous researches about resveratrol acting on AD in many models, both in vitro and in vivo. However, the effects of resveratrol are limited by its pool bioavailability; therefore researchers have been trying a variety of methods to improve the efficiency. This review summarizes the recent studies in cell cultures and animal models, mainly discusses the molecular mechanisms of the neuroprotective effects of resveratrol, and thus investigates the therapeutic potential in AD. Teng Ma, Meng-Shan Tan, Jin-Tai Yu, and Lan Tan Copyright © 2014 Teng Ma et al. All rights reserved. Bone Tissue Engineering for Dentistry and Orthopaedics Wed, 26 Nov 2014 08:24:13 +0000 Yin Xiao Copyright © 2014 Yin Xiao. All rights reserved. Complex Network-Driven View of Genomic Mechanisms Underlying Parkinson’s Disease: Analyses in Dorsal Motor Vagal Nucleus, Locus Coeruleus, and Substantia Nigra Wed, 26 Nov 2014 07:51:54 +0000 Parkinson’s disease (PD)—classically characterized by severe loss of dopaminergic neurons in the substantia nigra pars compacta—has a caudal-rostral progression, beginning in the dorsal motor vagal nucleus and, in a less extent, in the olfactory system, progressing to the midbrain and eventually to the basal forebrain and the neocortex. About 90% of the cases are idiopathic. To study the molecular mechanisms involved in idiopathic PD we conducted a comparative study of transcriptional interaction networks in the dorsal motor vagal nucleus (VA), locus coeruleus (LC), and substantia nigra (SN) of idiopathic PD in Braak stages 4-5 (PD) and disease-free controls (CT) using postmortem samples. Gene coexpression networks (GCNs) for each brain region (patients and controls) were obtained to identify highly connected relevant genes (hubs) and densely interconnected gene sets (modules). GCN analyses showed differences in topology and module composition between CT and PD networks for each anatomic region. In CT networks, VA, LC, and SN hub modules are predominantly associated with neuroprotection and homeostasis in the ageing brain, whereas in the patient’s group, for the three brain regions, hub modules are mostly related to stress response and neuron survival/degeneration mechanisms. Beatriz Raposo Corradini, Priscila Iamashita, Edilaine Tampellini, José Marcelo Farfel, Lea Tenenholz Grinberg, and Carlos Alberto Moreira-Filho Copyright © 2014 Beatriz Raposo Corradini et al. All rights reserved. The Significance of Body Mass Index in Calculating the Cut-Off Points for Low Muscle Mass in the Elderly: Methodological Issues Tue, 25 Nov 2014 09:53:05 +0000 Objectives. Cut-off points (COPs) for appendicular lean mass (ALM) index, essential to define low muscle mass (LMM) in the elderly, have never been officially defined for Poland. The aim of the study was to establish them. Additionally, the significance of body mass index (BMI) for correctly defining the COPs in a young, healthy reference group was assessed. Methods. The study was composed of reference group () and the elderly group (). In all subjects, body composition was assessed by bioimpedance analysis, and ALM index was calculated. Next, COPs (kg/m2) were set up for the whole reference group and for particular subgroups with different BMIs separately. They were used to diagnose sarcopenia in the elderly. Results. COP for all young females was 5.37 (COP-F), while it was equal to 5.52 (COP-F2) when only those with a recommended BMI (18.50–24.99 kg/m2) were taken into consideration. For males, it was 7.32 and 7.29, respectively. Only 7% of elderly females had LMM based on COP-F and 15% had LMM based on COP-F2 ; for males, the percentages were 18% and 16%, respectively. Conclusions. COPs for LMM for Poland are 5.52 kg/m2 (females) and 7.29 kg/m2 (males). The reference group BMI is an important factor in establishing COPs for low muscle mass. Roma Krzymińska-Siemaszko, Natasza Czepulis, Aleksandra Suwalska, Lechoslaw B. Dworak, Anna Fryzowicz, Beata Madej-Dziechciarow, and Katarzyna Wieczorowska-Tobis Copyright © 2014 Roma Krzymińska-Siemaszko et al. All rights reserved. Contribution of Crk Adaptor Proteins to Host Cell and Bacteria Interactions Tue, 25 Nov 2014 00:00:00 +0000 The Crk adaptor family of proteins comprises the alternatively spliced CrkI and CrkII isoforms, as well as the paralog Crk-like (CrkL) protein, which is encoded by a different gene. Initially thought to be involved in signaling during apoptosis and cell adhesion, this ubiquitously expressed family of proteins is now known to play essential roles in integrating signals from a wide range of stimuli. In this review, we describe the structure and function of the different Crk proteins. We then focus on the emerging roles of Crk adaptors during Enterobacteriaceae pathogenesis, with special emphasis on the important human pathogens Salmonella, Shigella, Yersinia, and enteropathogenic Escherichia coli. Throughout, we remark on opportunities for future research into this intriguing family of proteins. Narcisa Martinez-Quiles, Leigh Ann Feuerbacher, María Benito-León, and Philip R. Hardwidge Copyright © 2014 Narcisa Martinez-Quiles et al. All rights reserved. Coapplication of Lidocaine and Membrane-Impermeable Lidocaine Derivative QX-222 Produces Divergent Effects on Evoked and Spontaneous Nociceptive Behaviors in Mice Mon, 24 Nov 2014 12:36:54 +0000 The present study was aimed at investigating the analgesic properties of a combination of lidocaine and QX-222 and its effects on evoked pain behavior (complete Freund’s adjuvant-induced allodynia and hyperalgesia in inflammatory condition) and spontaneous pain behavior (formalin-induced acute pain) in mice. Drugs were injected adjacent to sciatic nerve or into plantar. Motor function, thermal withdrawal latency, mechanical withdrawal threshold, and licking/biting were evaluated by behavioral tests. A combination of lidocaine and QX-222 adjacent sciatic nerve injection produced the long-lasting sensory-specific nerve block, and intraplantar injection inhibited spontaneous pain in the formalin-treated mice but did not detectably attenuated hyperalgesia and allodynia in the complete Freund’s adjuvant- (CFA-) treated mice. Our results suggest that a combination of lidocaine and QX-222 achieves a long-lasting differential block (sensory selective) and produces divergent effects on evoked and spontaneous pain behaviors in mice. Si-Ping Hu, Jing-Jing Zhao, Wei-Xing Wang, Yang Liu, He-Fen Wu, Chao Chen, Liang Yu, and Jing-Bing Gui Copyright © 2014 Si-Ping Hu et al. All rights reserved. 3D Dynamic Culture of Rabbit Articular Chondrocytes Encapsulated in Alginate Gel Beads Using Spinner Flasks for Cartilage Tissue Regeneration Mon, 24 Nov 2014 11:36:22 +0000 Cell-based therapy using chondrocytes for cartilage repair suffers from chondrocyte dedifferentiation. In the present study, the effects of an integrated three-dimensional and dynamic culture on rabbit articular chondrocytes were investigated. Cells (passages 1 and 4) were encapsulated in alginate gel beads and cultured in spinner flasks in chondrogenic and chondrocyte growth media. Subcutaneous implantation of the cell-laden beads was performed to evaluate the ectopic chondrogenesis. It was found that cells remained viable after 35 days in the three-dimensional dynamic culture. Passage 1 cells demonstrated a proliferative growth in both media. Passage 4 cells showed a gradual reduction in DNA content in growth medium, which was attenuated in chondrogenic medium. Deposition of glycosaminoglycans (GAG) was found in all cultures. While passage 1 cells generally produced higher amounts of GAG than passage 4 cells, GAG/DNA became similar on day 35 for both cells in growth media. Interestingly, GAG/DNA in growth medium was greater than that in chondrogenic medium for both cells. Based on GAG quantification and gene expression analysis, encapsulated passage 1 cells cultured in growth medium displayed the best ectopic chondrogenesis. Taken together, the three-dimensional and dynamic culture for chondrocytes holds great potential in cartilage regeneration. Feiyue Xu, Lei Xu, Qi Wang, Zhaoyang Ye, Yan Zhou, and Wen-Song Tan Copyright © 2014 Feiyue Xu et al. All rights reserved. Erratum to “A De Novo Genome Assembly Algorithm for Repeats and Nonrepeats” Mon, 24 Nov 2014 00:00:00 +0000 Shuaibin Lian, Qingyan Li, Zhiming Dai, Qian Xiang, and Xianhua Dai Copyright © 2014 Shuaibin Lian et al. All rights reserved. Expression of Phosphocitrate-Targeted Genes in Osteoarthritis Menisci Sun, 23 Nov 2014 07:42:13 +0000 Phosphocitrate (PC) inhibited calcium crystal-associated osteoarthritis (OA) in Hartley guinea pigs. However, the molecular mechanisms remain elusive. This study sought to determine PC targeted genes and the expression of select PC targeted genes in OA menisci to test hypothesis that PC exerts its disease modifying activity in part by reversing abnormal expressions of genes involved in OA. We found that PC downregulated the expression of numerous genes classified in immune response, inflammatory response, and angiogenesis, including chemokine (C-C motif) ligand 5, Fc fragment of IgG, low affinity IIIb receptor (FCGR3B), and leukocyte immunoglobulin-like receptor, subfamily B member 3 (LILRB3). In contrast, PC upregulated the expression of many genes classified in skeletal development, including collagen type II alpha1, fibroblast growth factor receptor 3 (FGFR3), and SRY- (sex determining region Y-) box 9 (SOX-9). Immunohistochemical examinations revealed higher levels of FCGR3B and LILRB3 and lower level of SOX-9 in OA menisci. These findings indicate that OA is a disease associated with immune system activation and decreased expression of SOX-9 gene in OA menisci. PC exerts its disease modifying activity on OA, at least in part, by targeting immune system activation and the production of extracellular matrix and selecting chondroprotective proteins. Yubo Sun, David R. Mauerhan, Nury M. Steuerwald, Jane Ingram, Jeffrey S. Kneisl, and Edward N. Hanley Jr. Copyright © 2014 Yubo Sun et al. All rights reserved. Kinematic Analysis of Healthy Hips during Weight-Bearing Activities by 3D-to-2D Model-to-Image Registration Technique Sun, 23 Nov 2014 00:00:00 +0000 Dynamic hip kinematics during weight-bearing activities were analyzed for six healthy subjects. Continuous X-ray images of gait, chair-rising, squatting, and twisting were taken using a flat panel X-ray detector. Digitally reconstructed radiographic images were used for 3D-to-2D model-to-image registration technique. The root-mean-square errors associated with tracking the pelvis and femur were less than 0.3 mm and 0.3° for translations and rotations. For gait, chair-rising, and squatting, the maximum hip flexion angles averaged 29.6°, 81.3°, and 102.4°, respectively. The pelvis was tilted anteriorly around 4.4° on average during full gait cycle. For chair-rising and squatting, the maximum absolute value of anterior/posterior pelvic tilt averaged 12.4°/11.7° and 10.7°/10.8°, respectively. Hip flexion peaked on the way of movement due to further anterior pelvic tilt during both chair-rising and squatting. For twisting, the maximum absolute value of hip internal/external rotation averaged 29.2°/30.7°. This study revealed activity dependent kinematics of healthy hip joints with coordinated pelvic and femoral dynamic movements. Kinematics’ data during activities of daily living may provide important insight as to the evaluating kinematics of pathological and reconstructed hips. Daisuke Hara, Yasuharu Nakashima, Satoshi Hamai, Hidehiko Higaki, Satoru Ikebe, Takeshi Shimoto, Masanobu Hirata, Masayuki Kanazawa, Yusuke Kohno, and Yukihide Iwamoto Copyright © 2014 Daisuke Hara et al. All rights reserved. CR TKA UHMWPE Wear Tested after Artificial Aging of the Vitamin E Treated Gliding Component by Simulating Daily Patient Activities Thu, 20 Nov 2014 10:06:53 +0000 The wear behaviour of total knee arthroplasty (TKA) is dominated by two wear mechanisms: the abrasive wear and the delamination of the gliding components, where the second is strongly linked to aging processes and stress concentration in the material. The addition of vitamin E to the bulk material is a potential way to reduce the aging processes. This study evaluates the wear behaviour and delamination susceptibility of the gliding components of a vitamin E blended, ultra-high molecular weight polyethylene (UHMWPE) cruciate retaining (CR) total knee arthroplasty. Daily activities such as level walking, ascending and descending stairs, bending of the knee, and sitting and rising from a chair were simulated with a data set received from an instrumented knee prosthesis. After 5 million test cycles no structural failure of the gliding components was observed. The wear rate was with  mg/million cycles falling within the limit of previous reports for established wear test methods. Jens Schwiesau, Bernhard Fritz, Ines Kutzner, Georg Bergmann, and Thomas M. Grupp Copyright © 2014 Jens Schwiesau et al. All rights reserved. Differences in Anatomy and Kinematics in Asian and Caucasian TKA Patients: Influence on Implant Positioning and Subsequent Loading Conditions in Mobile Bearing Knees Thu, 20 Nov 2014 09:58:28 +0000 The objective of our study was to determine the mechanical stress conditions under tibiofemoral loading with an overlay of knee kinematics in deep flexion on two different mobile bearing designs in comparison to in vivo failure modes. This study investigates the seldom but severe complication of fatigue failure of polyethylene components at mobile bearing total knee arthroplasty designs. Assuming a combination of a floor-based lifestyle and tibial malrotation as a possible reason for a higher failure rate in Asian countries we developed a simplified finite element model considering a tibiofemoral roll-back angle of 22° and the range of rotational motion of a clinically established floating platform design (e.motion FP) at a knee flexion angle of 120° in order to compare our results to failure modes found in retrieved implants. Compared to the failure mode observed in the clinical retrievals the locations of the occurring stress maxima as well as the tensile stress distribution show analogies. From our observations, we conclude that the newly introduced finite element model with an overlay of deep knee flexion (lateral roll-back) and considerable internally rotated tibia implant positioning is an appropriate analysis for knee design optimizations and a suitable method to predict clinical failure modes. Allan Maas, Tae Kyun Kim, Rolf K. Miehlke, Thomas Hagen, and Thomas M. Grupp Copyright © 2014 Allan Maas et al. All rights reserved. Chronic Kidney Disease Requiring Healthcare Services: A New Approach to Evaluate Epidemiology of Renal Disease Thu, 20 Nov 2014 07:11:32 +0000 Background. Screening-based CKD estimates may not provide a sufficient insight into the impact of CKD on the use of healthcare resources in clinical practice. The aim of this study was to evaluate the epidemiology of “medicalized” CKD, that is, CKD requiring healthcare services, in an outpatient setting. Design, Setting, Participants, and Measurements. This is a retrospective, longitudinal population-based study conducted in a large general practice setting in Southern Italy (Caserta) using a healthcare database. Over 2006–2011, all patients with a CKD diagnosis, either through CKD-related indications of use associated with drug prescriptions or through CKD-related hospital discharge diagnoses/procedures, were identified using this database. The prevalence of “medicalized” CKD in the general population of Caserta was estimated by age, gender, and calendar year. Results. Overall, 1,989 (1.3%) patients with a diagnosis of CKD were identified from 2006–2011 in the Caserta general population. The one year prevalence increased from 0.9% in 2006 to 1.6% in 2011, which is much lower compared to previous screening-based studies. The prevalence was slightly higher in males and increased significantly with advancing age (in 2011, 0.2% in ≤44 years old versus 9.2% in >80 years old). Conclusions. The findings of this study suggest that, in the general population, the prevalence of “medicalized” CKD is lower compared to the screening-based CKD prevalence. Gianluca Trifirò, Janet Sultana, Francesco Giorgianni, Ylenia Ingrasciotta, Michele Buemi, Marco Muscianisi, Daniele Ugo Tari, Margherita Perrotta, Valeria Canale, Vincenzo Arcoraci, and Domenico Santoro Copyright © 2014 Gianluca Trifirò et al. All rights reserved. Different Resting-State Functional Connectivity Alterations in Smokers and Nonsmokers with Internet Gaming Addiction Tue, 18 Nov 2014 13:42:02 +0000 This study investigated changes in resting-state functional connectivity (rsFC) of posterior cingulate cortex (PCC) in smokers and nonsmokers with Internet gaming addiction (IGA). Twenty-nine smokers with IGA, 22 nonsmokers with IGA, and 30 healthy controls (HC group) underwent a resting-state fMRI scan. PCC connectivity was determined in all subjects by investigating synchronized low-frequency fMRI signal fluctuations using a temporal correlation method. Compared with the nonsmokers with IGA, the smokers with IGA exhibited decreased rsFC with PCC in the right rectus gyrus. Left middle frontal gyrus exhibited increased rsFC. The PCC connectivity with the right rectus gyrus was found to be negatively correlated with the CIAS scores in the smokers with IGA before correction. Our results suggested that smokers with IGA had functional changes in brain areas related to motivation and executive function compared with the nonsmokers with IGA. Xue Chen, Yao Wang, Yan Zhou, Yawen Sun, Weina Ding, Zhiguo Zhuang, Jianrong Xu, and Yasong Du Copyright © 2014 Xue Chen et al. All rights reserved. Neuroprotective Effects of Geniposide in SH-SY5Y Cells and Primary Hippocampal Neurons Exposed to Aβ42 Tue, 18 Nov 2014 09:37:50 +0000 Our former studies have suggested that TongLuoJiuNao (TLJN) is clinically efficacious in the treatment of dementia and improving learning and memory in AD models. When Aβ aggregated with oligomer, it is known to be able to induce cellular toxicity as well as cognitive impairment. We tested the possibility that TLJN affects the formation of Aβ oligomers. In our experiment, TLJN improved cell viability, inhibited LDH release, and promoted the outgrowth of neurites of neurons treated with Aβ. Geniposide, the main component of TLJN, could increase the cell viability of SY5Y-APP695sw cells. The cytotoxicity of pretreated Aβ with geniposide was decreased in a dose-dependent manner. SDS-PAGE and Western blotting showed that geniposide and TLJN stimulated Aβ oligomer assembly. Compared with the control, more and longer fibrils of Aβ in the presence of geniposide were observed under electron microscope though the fibrils became less sensitive to thioflavin T staining. In sum, geniposide is able to protect neurons from Aβ-induced damage by remodeling Aβ. Ping Sun, Haimin Ding, Mi Liang, Xiaojing Li, Weichuan Mo, Xu Wang, Ying Liu, Rongqiao He, and Qian Hua Copyright © 2014 Ping Sun et al. All rights reserved. Therapeutic Efficacy of pH-Dependent Release Formulation of Mesalazine on Active Ulcerative Colitis Resistant to Time-Dependent Release Formulation: Analysis of Fecal Calprotectin Concentration Tue, 18 Nov 2014 07:43:14 +0000 Purpose. Few reports have compared the clinical efficacy of a pH-dependent release formulation of mesalazine (pH-5-ASA) with a time-dependent release formulation (time-5-ASA). We examined whether pH-5-ASA is effective for active ulcerative colitis (UC) in patients resistant to time-5-ASA. Methods. We retrospectively and prospectively analyzed the efficacy of pH-5-ASA in mildly to moderately active UC patients in whom time-5-ASA did not successfully induce or maintain remission. The clinical efficacy of pH-5-ASA was assessed by clinical activity index (CAI) before and after switching from time-5-ASA. In addition, the efficacy of pH-5-ASA on mucosal healing (MH) was evaluated in a prospective manner by measuring fecal calprotectin concentration. Results. Thirty patients were analyzed in a retrospective manner. CAI was significantly reduced at both 4 and 8 weeks after switching to pH-5-ASA. In the prospective study (), administration of pH-5-ASA also significantly reduced CAI scores at 4 and 8 weeks in these patients who were resistant to time-5-ASA. In addition, fecal calprotectin concentration was significantly decreased along with improvement in CAI after switching to pH-5-ASA. Conclusions. Our results suggest that pH-5-ASA has clinical efficacy for mildly to moderately active patients with UC in whom time-5-ASA did not successfully induce or maintain remission. Kousaku Kawashima, Shunji Ishihara, Takafumi Yuki, Koji Onishi, Yoshinori Kushiyama, Hirofumi Fujishiro, Youichi Miyaoka, Mika Yuki, Yoshinori Komazawa, Takashi Tanimura, Hiroki Sonoyama, Yasumasa Tada, Ryusaku Kusunoki, Akihiko Oka, Nobuhiko Fukuba, Naoki Oshima, Ichiro Moriyama, and Yoshikazu Kinoshita Copyright © 2014 Kousaku Kawashima et al. All rights reserved. Nek2 Is a Novel Regulator of B Cell Development and Immunological Response Mon, 17 Nov 2014 09:36:31 +0000 The serine/threonine kinase Nek2 is commonly found upregulated in a wide variety of neoplasms including diffuse large B cell lymphoma and multiple myeloma. High expression of Nek2 is implicated in the induction of chromosomal instability, promotion of cell proliferation, and drug resistance in tumor cells as well as a marker for poor clinical outcomes. Despite its well recorded involvement in chromosomal instability and neoplastic growth, little is known about the involvement of Nek2 in B cell development. Here we report the development of a transgenic mouse line with conditional expression of Nek2 in the B cell lineage and the effects it has on the development of B cells. Interestingly, we found that the overexpression of Nek2 does not induce spontaneous tumor formation within the transgenic mice up to 24 months after induction. Instead, overexpression of Nek2 in the B cell lineage affects the development of B cells by increasing the proportion of immature B cells in the bone marrow and decreasing B-1 B cells in peritoneal cavity. Furthermore, Nek2 transgenic mice develop spontaneous germinal centers and exhibit an enhanced T cell dependent immune response. Altogether, our data demonstrates a novel role for Nek2 in regulating B cell development and the immune response. Zhimin Gu, Wen Zhou, Junwei Huang, Ye Yang, Erik Wendlandt, Hongwei Xu, Xiao He, Guido Tricot, and Fenghuang Zhan Copyright © 2014 Zhimin Gu et al. All rights reserved. A Proposed Methodology to Control Body Temperature in Patients at Risk of Hypothermia by means of Active Rewarming Systems Mon, 17 Nov 2014 08:27:32 +0000 Hypothermia is a common complication in patients undergoing surgery under general anesthesia. It has been noted that, during the first hour of surgery, the patient’s internal temperature () decreases by 0.5–1.5°C due to the vasodilatory effect of anesthetic gases, which affect the body’s thermoregulatory system by inhibiting vasoconstriction. Thus a continuous check on patient temperature must be carried out. The currently most used methods to avoid hypothermia are based on passive systems (such as blankets reducing body heat loss) and on active ones (thermal blankets, electric or hot-water mattresses, forced hot air, warming lamps, etc.). Within a broader research upon the environmental conditions, pollution, heat stress, and hypothermia risk in operating theatres, the authors set up an experimental investigation by using a warming blanket chosen from several types on sale. Their aim was to identify times and ways the human body reacts to the heat flowing from the blanket and the blanket’s effect on the average temperature and, as a consequence, on temperature of the patient. The here proposed methodology could allow surgeons to fix in advance the thermal power to supply through a warming blanket for reaching, in a prescribed time, the desired body temperature starting from a given state of hypothermia. Silvia Costanzo, Alessia Cusumano, Carlo Giaconia, and Sante Mazzacane Copyright © 2014 Silvia Costanzo et al. All rights reserved. Rapid and Sensitive PCR-Dipstick DNA Chromatography for Multiplex Analysis of the Oral Microbiota Mon, 17 Nov 2014 07:11:31 +0000 A complex of species has been associated with dental caries under the ecological hypothesis. This study aimed to develop a rapid, sensitive PCR-dipstick DNA chromatography assay that could be read by eye for multiplex and semiquantitative analysis of plaque bacteria. Parallel oligonucleotides were immobilized on a dipstick strip for multiplex analysis of target DNA sequences of the caries-associated bacteria, Streptococcus mutans, Streptococcus sobrinus, Scardovia wiggsiae, Actinomyces species, and Veillonella parvula. Streptavidin-coated blue-colored latex microspheres were to generate signal. Target DNA amplicons with an oligonucleotide-tagged terminus and a biotinylated terminus were coupled with latex beads through a streptavidin-biotin interaction and then hybridized with complementary oligonucleotides on the strip. The accumulation of captured latex beads on the test and control lines produced blue bands, enabling visual detection with the naked eye. The PCR-dipstick DNA chromatography detected quantities as low as 100 pg of DNA amplicons and demonstrated 10- to 1000-fold higher sensitivity than PCR-agarose gel electrophoresis, depending on the target bacterial species. Semiquantification of bacteria was performed by obtaining a series of chromatograms using serial 10-fold dilution of PCR-amplified DNA extracted from dental plaque samples. The assay time was less than 3 h. The semiquantification procedure revealed the relative amounts of each test species in dental plaque samples, indicating that this disposable device has great potential in analysis of microbial composition in the oral cavity and intestinal tract, as well as in point-of-care diagnosis of microbiota-associated diseases. Lingyang Tian, Takuichi Sato, Kousuke Niwa, Mitsuo Kawase, Anne C. R. Tanner, and Nobuhiro Takahashi Copyright © 2014 Lingyang Tian et al. All rights reserved. A Comprehensive Review of Contemporary Role of Local Treatment of the Primary Tumor and/or the Metastases in Metastatic Prostate Cancer Mon, 17 Nov 2014 06:46:22 +0000 To provide an overview of the currently available literature regarding local control of primary tumor and oligometastases in metastatic prostate cancer and salvage lymph node dissection of clinical lymph node relapse after curative treatment of prostate cancer. Evidence Acquisition. A systematic literature search was conducted in 2014 to identify abstracts, original articles, review articles, research articles, and editorials relevant to the local control in metastatic prostate cancer. Evidence Synthesis. Local control of primary tumor in metastatic prostate cancer remains experimental with low level of evidence. The concept is supported by a growing body of genetic and molecular research as well as analogy with other cancers. There is only one retrospective observational population based study showing prolonged survival. To eradicate oligometastases, several options exist with excellent local control rates. Stereotactic body radiotherapy is safe, well tolerated, and efficacious treatment for lymph node and bone lesions. Both biochemical and clinical progression are slowed down with a median time to initiate ADT of 2 years. Salvage lymph node dissection is feasible in patients with clinical lymph node relapse after local curable treatment. Conclusion. Despite encouraging oncologic midterm results, a complete cure remains elusive in metastatic prostate cancer patients. Further advances in imaging are crucial in order to rapidly evolve beyond the proof of concept. Fouad Aoun, Alexandre Peltier, and Roland van Velthoven Copyright © 2014 Fouad Aoun et al. All rights reserved. Cross-Comparison of Leaching Strains Isolated from Two Different Regions: Chambishi and Dexing Copper Mines Sun, 16 Nov 2014 09:41:30 +0000 A cross-comparison of six strains isolated from two different regions, Chambishi copper mine (Zambia, Africa) and Dexing copper mine (China, Asia), was conducted to study the leaching efficiency of low grade copper ores. The strains belong to the three major species often encountered in bioleaching of copper sulfide ores under mesophilic conditions: Acidithiobacillus ferrooxidans, Acidithiobacillus thiooxidans, and Leptospirillum ferriphilum. Prior to their study in bioleaching, the different strains were characterized and compared at physiological level. The results revealed that, except for copper tolerance, strains within species presented almost similar physiological traits with slight advantages of Chambishi strains. However, in terms of leaching efficiency, native strains always achieved higher cell density and greater iron and copper extraction rates than the foreign microorganisms. In addition, microbial community analysis revealed that the different mixed cultures shared almost the same profile, and At. ferrooxidans strains always outcompeted the other strains. Baba Ngom, Yili Liang, and Xueduan Liu Copyright © 2014 Baba Ngom et al. All rights reserved. Cellular Levels of Oxidative Stress Affect the Response of Cervical Cancer Cells to Chemotherapeutic Agents Sun, 16 Nov 2014 08:26:03 +0000 Treatment of advanced and relapsed cervical cancer is frequently ineffective, due in large part to chemoresistance. To examine the pathways responsible, we employed the cervical carcinoma-derived SiHa and CaSki cells as cellular models of resistance and sensitivity, respectively, to treatment with chemotherapeutic agents, doxorubicin, and cisplatin. We compared the proteomic profiles of SiHa and CaSki cells and identified pathways with the potential to contribute to the differential response. We then extended these findings by comparing the expression level of genes involved in reactive oxygen species (ROS) metabolism through the use of a RT-PCR array. The analyses demonstrated that the resistant SiHa cells expressed higher levels of antioxidant enzymes. Decreasing or increasing oxidative stress led to protection or sensitization, respectively, in both cell lines, supporting the idea that cellular levels of oxidative stress affect responsiveness to treatment. Interestingly, doxorubicin and cisplatin induced different profiles of ROS, and these differences appear to contribute to the sensitivity to treatment displayed by cervical cancer cells. Overall, our findings demonstrate that cervical cancer cells display variable profiles with respect to their redox-generating and -adaptive systems, and that these different profiles have the potential to contribute to their responses to treatments with chemotherapy. Maria Filippova, Valery Filippov, Vonetta M. Williams, Kangling Zhang, Anatolii Kokoza, Svetlana Bashkirova, and Penelope Duerksen-Hughes Copyright © 2014 Maria Filippova et al. All rights reserved. Differentiation of Benign Angiomatous and Microcystic Meningiomas with Extensive Peritumoral Edema from High Grade Meningiomas with Aid of Diffusion Weighted MRI Sun, 16 Nov 2014 07:51:57 +0000 Objective. To determine whether angiomatous and microcystic meningiomas which mimic high grade meningiomas based on extent of peritumoral edema can be reliably differentiated as low grade tumors using normalized apparent diffusion coefficient (ADC) values. Methods. Preoperative magnetic resonance imaging (MRI) of seventy patients with meningiomas was reviewed. Morphologically, the tumors were divided into 3 groups. Group 1 contained 12 pure microcystic, 3 pure angiomatoid and 7 mixed angiomatoid and microcystic tumors. Group 2 included World Health Organization (WHO) grade II and WHO grade III tumors, of which 28 were atypical and 9 were anaplastic meningiomas. Group 3 included WHO grade I tumors of morphology different than angiomatoid and microcystic. Peritumoral edema, normalized ADC, and cerebral blood volume (CBV) were obtained for all meningiomas. Results. Edema index of tumors in group 1 and group 2 was significantly higher than in group 3. Normalized ADC value in group 1 was higher than in group 2, but not statistically significant between groups 1 and 3. CBV values showed no significant group differences. Conclusion. A combination of peritumoral edema index and normalized ADC value is a novel approach to preoperative differentiation between true aggressive meningiomas and mimickers such as angiomatous and microcystic meningiomas. Avetis Azizyan, Paula Eboli, Doniel Drazin, James Mirocha, Marcel M. Maya, and Serguei Bannykh Copyright © 2014 Avetis Azizyan et al. All rights reserved. Inhibition of Brain Swelling after Ischemia-Reperfusion by β-Adrenergic Antagonists: Correlation with Increased K+ and Decreased Ca2+ Concentrations in Extracellular Fluid Thu, 13 Nov 2014 12:18:28 +0000 Infarct size and brain edema following ischemia/reperfusion are reduced by inhibitors of the Na+, K+, 2Cl−, and water cotransporter NKCC1 and by β1-adrenoceptor antagonists. NKCC1 is a secondary active transporter, mainly localized in astrocytes, driven by transmembrane Na+/K+ gradients generated by the Na+,K+-ATPase. The astrocytic Na+,K+-ATPase is stimulated by small increases in extracellular K+ concentration and by the β-adrenergic agonist isoproterenol. Larger K+ increases, as occurring during ischemia, also stimulate NKCC1, creating cell swelling. This study showed no edema after 3 hr medial cerebral artery occlusion but pronounced edema after 8 hr reperfusion. The edema was abolished by inhibitors of specifically β1-adrenergic pathways, indicating failure of K+-mediated, but not β1-adrenoceptor-mediated, stimulation of Na+,K+-ATPase/NKCC1 transport during reoxygenation. Ninety percent reduction of extracellular Ca2+ concentration occurs in ischemia. Ca2+ omission abolished K+ uptake in normoxic cultures of astrocytes after addition of 5 mM KCl. A large decrease in ouabain potency on K+ uptake in cultured astrocytes was also demonstrated in Ca2+-depleted media, and endogenous ouabains are needed for astrocytic K+ uptake. Thus, among the ionic changes induced by ischemia, the decrease in extracellular Ca2+ causes failure of the high-K+-stimulated Na+,K+-ATPase/NKCC1 ion/water uptake, making β1-adrenergic activation the only stimulus and its inhibition effective against edema. Dan Song, Junnan Xu, Ting Du, Enzhi Yan, Leif Hertz, Wolfgang Walz, and Liang Peng Copyright © 2014 Dan Song et al. All rights reserved. Increased DJ-1 in Urine Exosome of Korean Males with Parkinson’s Disease Thu, 13 Nov 2014 10:08:52 +0000 Parkinson’s disease (PD) is a difficult disease to diagnose although it is the second most common neurodegenerative disease. Recent studies show that exosome isolated from urine contains LRRK2 or DJ-1, proteins whose mutations cause PD. To investigate a potential use for urine exosomes as a tool for PD diagnosis, we compared levels of LRRK2, α-synuclein, and DJ-1 in urine exosomes isolated from Korean PD patients and non-PD controls. LRRK2 and DJ-1, but not α-synuclein, were detected in the urine exosome samples, as reported previously. We initially could not detect any significant difference in these protein levels between the patient and the control groups. However, when age, disease duration, L-dopa daily dose, and gender were considered as analytical parameters, LRRK2 and DJ-1 protein levels showed clear gender-dependent differences. In addition, DJ-1 level was significantly higher (1.7-fold) in male patients with PD than that in male non-PD controls and increased in an age-dependent manner in male patients with PD. Our observation might provide a clue to lead to a novel biomarker for PD diagnosis, at least in males. Dong Hwan Ho, Sanghak Yi, Hyemyung Seo, Ilhong Son, and Wongi Seol Copyright © 2014 Dong Hwan Ho et al. All rights reserved. Comparative Hair Restorer Efficacy of Medicinal Herb on Nude (Foxn) Mice Thu, 13 Nov 2014 05:52:28 +0000 Eclipta alba (L.) Hassk, Asiasarum sieboldii (Miq.) F. Maek (Asiasari radix), and Panax ginseng C. A. Mey (red ginseng) are traditionally acclaimed for therapeutic properties of various human ailments. Synergistic effect of each standardized plant extract was investigated for hair growth potential on nude mice, as these mutant mice genetically lack hair due to abnormal keratinization. Dried plant samples were ground and extracted by methanol. Topical application was performed on the back of nude mice daily up to completion of two hair growth generations. The hair density and length of Eclipta alba treated mice were increased significantly than control mice. Hair growth area was also distinctly visible in Eclipta alba treated mice. On the other hand, Asiasari radix and Panax ginseng treated mice developing hair loss were recognized from the abortive boundaries of hair coverage. Histomorphometric observation of nude mice skin samples revealed an increase in number of hair follicles (HFs). The presence of follicular keratinocytes was confirmed by BrdU labeling, S-phase cells in HFs. Therefore, Eclipta alba extract and/or phytochemicals strongly displayed incomparability of hair growth promotion activity than others. Thus, the standardized Eclipta alba extract can be used as an effective, alternative, and complementary treatment against hair loss. Shahnaz Begum, Mi Ra Lee, Li Juan Gu, Md. Jamil Hossain, Hyun Kyoung Kim, and Chang Keun Sung Copyright © 2014 Shahnaz Begum et al. All rights reserved. Differentially Expressed MicroRNAs in Maternal Plasma for the Noninvasive Prenatal Diagnosis of Down Syndrome (Trisomy 21) Wed, 12 Nov 2014 08:46:15 +0000 Objectives. Most developmental processes are under the control of small regulatory RNAs called microRNAs (miRNAs). We hypothesize that different fetal developmental processes might be reflected by extracellular miRNAs in maternal plasma and may be utilized as biomarkers for the noninvasive prenatal diagnosis of chromosomal aneuploidies. In this proof-of-concept study, we report on the identification of extracellular miRNAs in maternal plasma of Down syndrome (DS) pregnancies. Methods. Using high-throughput quantitative PCR (HT-qPCR), 1043 miRNAs were investigated in maternal plasma via comparison of seven DS pregnancies with age and fetal sex matched controls. Results. Six hundred and ninety-five miRNAs were identified. Thirty-six significantly differentially expressed mature miRNAs were identified as potential biomarkers. Hierarchical cluster analysis of these miRNAs resulted in the clear discrimination of DS from euploid pregnancies. Gene targets of the differentially expressed miRNAs were enriched in signaling pathways such as mucin type-O-glycans, ECM-receptor interactions, TGF-beta, and endocytosis, which have been previously associated with DS. Conclusions. miRNAs are promising and stable biomarkers for a broad range of diseases and may allow a reliable, cost-efficient diagnostic tool for the noninvasive prenatal diagnosis of DS. Julian Kamhieh-Milz, Reham Fadl Hassan Moftah, Gürkan Bal, Matthias Futschik, Viktor Sterzer, Omid Khorramshahi, Martin Burow, Gundula Thiel, Annegret Stuke-Sontheimer, Rabih Chaoui, Sundrela Kamhieh-Milz, and Abdulgabar Salama Copyright © 2014 Julian Kamhieh-Milz et al. All rights reserved.