BioMed Research International The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . 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. Effects of Combined Anisodamine and Neostigmine Treatment on the Inflammatory Response and Liver Regeneration of Obstructive Jaundice Rats after Hepatectomy Wed, 12 Nov 2014 06:22:39 +0000 Background. Cholestasis is associated with high rates of morbidity and mortality in patients undergoing major liver resection. This study aimed to evaluate the effects of a combined anisodamine and neostigmine (Ani+Neo) treatment on the inflammatory response and liver regeneration in rats with obstructive jaundice (OJ) after partial hepatectomy. Materials and Methods. OJ was induced in the rats by bile duct ligation. After 7 days biliary drainage and partial hepatectomy were performed. These rats were assigned to a saline group or an Ani+Neo treatment group. The expressions of inflammatory mediators, liver regeneration, and liver damage were assessed at 48 h after hepatectomy. Results. The mRNA levels of TNF-α, IL-1β, IL-6, MCP-1, and MIP-1α, in the remnant livers, and the serum levels of TNF-α and IL-1β were substantially reduced in the Ani+Neo group compared with saline group . The Ani+Neo treatment obviously promoted liver regeneration as indicated by the liver weights and Ki-67 labeling index . The serum albumin and γ-GT levels and liver neutrophil infiltration also significantly improved in the Ani+Neo group compared with the saline group. Conclusions. These results demonstrate that the combined anisodamine and neostigmine treatment is able to improve the liver regeneration in rats with OJ by substantially alleviating the inflammatory response. Chong-Hui Li, Xuan Zhang, Xin-Lan Ge, Xin Huang, Ai-Qun Zhang, and Wan-Qing Gu Copyright © 2014 Chong-Hui Li et al. All rights reserved. The Effects of Cryotherapy on Proprioception System Wed, 12 Nov 2014 00:00:00 +0000 Proprioception plays an important role in the complex mechanism of joint control. Contemporary sport activities impose extremely high physical demands on athletes. Winter sports are played in areas with excessively low temperatures. Moreover, many athletes are subjected to treatments that involve local lowering of the body temperature before, during, and after physical activity. This work reviews the current knowledge regarding the influence of local cryotherapy on the proprioception system. The reviewed literature identified several tests that evaluate different aspects of proprioception. There is no universally agreed protocol, or clear set of criteria for test conditions. The outcomes of different tests and assessments of cryotherapy procedures using different cold modalities are poorly correlated. In general, the published results on the mechanism of cryotherapy effects on proprioception are not uniquely conclusive and are frequently contradictory. Additional high-quality research is required to explicitly answer the following questions: (1) whether local cryotherapy influences all aspects of proprioception; (2) whether the current methods of evaluation are adequate for the exploration of the relationship between cryotherapy and proprioception; and (3) whether the application of local cryotherapy is safe for athletes regarding proprioception. The review clearly showed that there is no comprehensive model relating cryotherapy and proprioception. Mariusz Paweł Furmanek, Kajetan Słomka, and Grzegorz Juras Copyright © 2014 Mariusz Paweł Furmanek et al. All rights reserved. Mechanisms of Action and Efficacy of Statins against Influenza Tue, 11 Nov 2014 13:40:24 +0000 The influenza virus (IV) is known to be a resistant virus with frequent mutations, causing severe respiratory diseases in the upper respiratory system. Public health concerns about clinical efficacy of all conventional drugs are ambiguous; therefore, finding additional therapeutic agents is critical to prevent and control influenza outbreaks. Influenza is associated with the induction of proinflammatory cytokines. Scientists have reported that anti-inflammatory drugs, with pleiotropic effects, reduce the burden of severe influenza diseases. Therefore, statins, which are cardioprotective drugs with anti-inflammatory and immunomodulatory effects, may help patients suffering from influenza virus (IV). This review delineates the potential use of statins as an alternative therapy in treating influenza related illness. Parvaneh Mehrbod, Abdul Rahman Omar, Mohd Hair-Bejo, Amin Haghani, and Aini Ideris Copyright © 2014 Parvaneh Mehrbod et al. All rights reserved. Efficacy of Alendronate for Preventing Collapse of Femoral Head in Adult Patients with Nontraumatic Osteonecrosis Tue, 11 Nov 2014 13:23:55 +0000 The purpose of the current review was to determine the efficacy of alendronate for preventing collapse of femoral head in adult patients with nontraumatic avascular osteonecrosis of femoral head (ANFH). Five randomized controlled trials (RCTs) involving 305 hips were included in this review, of which 3 studies investigated alendronate versus control/placebo and the other 2 studies compared the combination of alendronate and extracorporeal shockwave therapy (ESWT) with ESWT alone. Our results suggested that even the patients with extensive necrosis encountered much less collapse in the alendronate group than control group. In these RCTs, their data also indicated a positive short- and middle-term efficacy of alendronate treatment in joint function improvement and hip pain diminishment. With the presence of the outlier study, only insignificant overall efficacy of alendronate could be observed with substantial heterogeneities. In addition, we did not find any additive benefits of alendronate in combination with ESWT for preventing collapse compared to ESWT alone. In conclusion, there is still lack of strong evidence for supporting application of alendronate in adult patients with nontraumatic ANFH, which justified that large scale, randomized, and double-blind studies should be developed to demonstrate the confirmed efficacies, detailed indication, and optimized strategy of alendronate treatment. Yu-Cai Hong, Ru-Bin Luo, Tiao Lin, Hui-Ming Zhong, and Jian-Bin Shi Copyright © 2014 Yu-Cai Hong et al. All rights reserved. Periodontal Ligament Mesenchymal Stromal Cells Increase Proliferation and Glycosaminoglycans Formation of Temporomandibular Joint Derived Fibrochondrocytes Mon, 10 Nov 2014 14:01:28 +0000 Objectives. Temporomandibular joint (TMJ) disorders are common disease in maxillofacial surgery. The aim of this study is to regenerate fibrocartilage with a mixture of TMJ fibrochondrocytes and periodontal ligament derived mesenchymal stem cells (PD-MSCs). Materials and Methods. Fibrochondrocytes and PD-MSC were cocultured (ratio 1 : 1) for 3 weeks. Histology and glycosaminoglycans (GAGs) assay were performed to examine the deposition of GAG. Green florescent protein (GFP) was used to track PD-MSC. Conditioned medium of PD-MSCs was collected to study the soluble factors. Gene expression of fibrochondrocytes cultured in conditioned medium was tested by quantitative PCR (qPCR). Results. Increased proliferation of TMJ-CH was observed in coculture pellets when compared to monoculture. Enhanced GAG production in cocultures was shown by histology and GAG quantification. Tracing of GFP revealed the fact that PD-MSC disappears after coculture with TMJ-CH for 3 weeks. In addition, conditioned medium of PD-MSC was also shown to increase the proliferation and GAG deposition of TMJ-CH. Meanwhile, results of qPCR demonstrated that conditioned medium enhanced the expression levels of matrix-related genes in TMJ-CH. Conclusions. Results from this study support the mechanism of MSC-chondrocyte interaction, in which MSCs act as secretor of soluble factors that stimulate proliferation and extracellular matrix deposition of chondrocytes. Jianli Zhang, Fujun Guo, Jianqiang Mi, and Zhiye Zhang Copyright © 2014 Jianli Zhang et al. All rights reserved. Long-Term Effects and Prognosis in Acute Heart Failure Treated with Tolvaptan: The AVCMA Trial Mon, 10 Nov 2014 10:48:22 +0000 Background. Diuresis is a major therapy for the reduction of congestive symptoms in acute decompensated heart failure (ADHF) patients. We previously reported the efficacy and safety of tolvaptan compared to carperitide in hospitalized patients with ADHF. There were some reports of cardio- and renal-protective effects in carperitide; therefore, the purpose of this study was to compare the long-term effects of tolvaptan and carperitide on cardiorenal function and prognosis. Methods and Results. One hundred and five ADHF patients treated with either tolvaptan or carperitide were followed after hospital discharge. Levels of plasma B-type natriuretic peptide, serum sodium, potassium, creatinine, and estimated glomerular filtration rate were measured before administration of tolvaptan or carperitide at baseline, the time of discharge, and one year after discharge. These data between tolvaptan and carperitide groups were not different one year after discharge. Kaplan-Meier survival curves demonstrated that the event-free rate regarding all events, cardiac events, all cause deaths, and rehospitalization due to worsening heart failure was not significantly different between tolvaptan and carperitide groups. Conclusions. We demonstrated that tolvaptan had similar effects on cardiac and renal function and led to a similar prognosis in the long term, compared to carperitide. Satoshi Suzuki, Akiomi Yoshihisa, Takayoshi Yamaki, Koichi Sugimoto, Hiroyuki Kunii, Kazuhiko Nakazato, Yukihiko Abe, Tomiyoshi Saito, Takayuki Ohwada, Hitoshi Suzuki, Shu-ichi Saitoh, Isao Kubota, and Yasuchika Takeishi Copyright © 2014 Satoshi Suzuki et al. All rights reserved. Diseases of Pregnancy and Fetal Programming: Cell and Molecular Mechanisms Mon, 10 Nov 2014 06:38:46 +0000 Luis Sobrevia, Leslie Myatt, and Gregory Rice Copyright © 2014 Luis Sobrevia et al. All rights reserved. Unaffected Arm Muscle Hypercatabolism in Dysphagic Subacute Stroke Patients: The Effects of Essential Amino Acid Supplementation Sun, 09 Nov 2014 13:53:12 +0000 Alterations in muscle protein turnover of the unaffected side of stroke patients could contribute to physical disability. We investigated whether hypercatabolic activity occurred in unaffected arm muscle and whether supplemented essential amino acids (EAAs) could limit muscle hypercatabolism (MH). Thirty-eight dysphagic subacute stroke subjects (<3 months after acute event) (29 males + 9 females; 69.7 ± 11.4 yrs) were enrolled and randomized to receive 8 g/day EAAs (n = 19; EAA group) or isocaloric placebo (maltodextrin; n = 19, Plac group). Before randomization, all patients had their arterial (A) and venous (V) amino acids measured and muscle (A − V) differences calculated in the unaffected arm. Eight matched and healthy subjects served as controls. When compared to healthy controls, the entire stroke population showed significant muscle release (= negative value A − V) of the amino acid phenylalanine (phenyl-) indicating a prevalence of MH. Moreover, randomized EAA and Plac groups had similar rates of MH. After 38 days from the start of the protocol, the EAA group but not the Plac group had MH converted to balanced protein turnover or anabolic activity. We concluded that muscle protein metabolism of the unaffected arm of dysphagic subacute stroke individuals could be characterized by MH which can be corrected by supplemented EAAs. Roberto Aquilani, Mirella Boselli, Giuseppe D’Antona, Paola Baiardi, Federica Boschi, Simona Viglio, Paolo Iadarola, Evasio Pasini, Annalisa Barbieri, Maurizia Dossena, Andria Innocenza Bongiorno, and Manuela Verri Copyright © 2014 Roberto Aquilani et al. All rights reserved. Comparison of Low Urinary Tract Symptoms during Pregnancy between Primiparous and Multiparous Women Sun, 09 Nov 2014 13:25:11 +0000 Background and Purpose. Low urinary tract symptoms (LUTS) are a common problem during pregnancy. This study aimed to compare changes in the prevalence of LUTS during pregnancy between primiparous and multiparous women. Methods. A chart review of consecutive pregnant women who attended our antenatal clinic from March 2002 to January 2006 was performed. All of the women were asked to respond to a LUTS questionnaire in either of the three trimesters. Results. Of the 270 women included, 164 were nullipara and 106 were multipara. The most common LUTS during pregnancy were frequency (77%), followed by nocturia (75.6%), stress urinary incontinence (SUI) (51.1%), incomplete emptying (43.7%), dysuria (17.8%), and urgency incontinence (10.4%). There was a significantly higher prevalence of SUI () and urgency incontinence () in the multiparous compared to the nulliparous women. Increasing prevalence rates of frequency, nocturia, SUI, and incomplete emptying were reported with gestational age in both the nulliparous and multiparous women. Conclusions. Frequency and nocturia were the two most common LUTS during pregnancy. The prevalence rates of all LUTS increased with increasing gestational age except for frequency in the nulliparous women during the second trimester. In addition, multipara was a predictor of SUI during pregnancy. Kun-Ling Lin, Ching-Ju Shen, Ming-Ping Wu, Cheng-Yu Long, Chin-Hu Wu, and Chiu-Lin Wang Copyright © 2014 Kun-Ling Lin et al. All rights reserved. Heat Shock Protein 70 in Alzheimer’s Disease Thu, 06 Nov 2014 13:02:25 +0000 Alzheimer’s disease (AD) is the most common neurodegenerative disease that caused dementia which has no effective treatment. Growing evidence has demonstrated that AD is a “protein misfolding disorder” that exhibits common features of misfolded, aggregation-prone proteins and selective cell loss in the mature nervous system. Heat shock protein 70 (HSP70) attracts extensive attention worldwide, because it plays a crucial role in preventing protein misfolding and inhibiting aggregation and represents a class of proteins potentially involved in AD pathogenesis. Numerous studies have indicated that HSP70 could suppress the progression of AD with in vitro and in vivo experiments. Thus, targeting HSP70 and the related compounds might represent a promising strategy for the treatment of AD. Rui-Chun Lu, Meng-Shan Tan, Hao Wang, An-Mu Xie, Jin-Tai Yu, and Lan Tan Copyright © 2014 Rui-Chun Lu et al. All rights reserved. Long-Term Efficacy of Postpartum Intravenous Iron Therapy Thu, 06 Nov 2014 05:42:15 +0000 Background. The potential benefits of administering a dose of intravenous iron in patients with moderate postpartum anaemia rather than oral iron alone remains unproven. Aims. To determine whether a single injection of intravenous iron followed by a 6-week course of oral iron is as effective over 6 months in restoring normal haemoglobin levels and replenishing iron stores in women with moderate postpartum anaemia as a course of oral iron alone in women with mild postpartum anaemia. Materials and Methods. Retrospective two-arm cohort study in women with mild postpartum anaemia (haemoglobin 9.6–10.5 g/dL) prescribed iron daily for 6 weeks () and women with moderate postpartum anaemia (haemoglobin 8.5–9.5 g/dL), given a single 500 mg injection of intravenous iron followed by iron daily for 6 weeks (). Haemoglobin and ferritin were measured 6 months postpartum. Results. Haemoglobin returned to similar mean levels in both groups. Ferritin levels were statistically significantly higher in the intravenous + oral group ( μg/L versus  μg/L). Conclusions. Despite lower baseline haemoglobin, intravenous iron carboxymaltose was superior to oral iron alone in replenishing iron stores in moderate postpartum anaemia and may prove similarly beneficial in mild postpartum anaemia. Nadine Becuzzi, Roland Zimmermann, and Alexander Krafft Copyright © 2014 Nadine Becuzzi et al. All rights reserved.