BioMed Research International The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. ECR-MAPK Regulation in Liver Early Development Thu, 18 Dec 2014 00:11:25 +0000 Early growth is connected to a key link between embryonic development and aging. In this paper, liver gene expression profiles were assayed at postnatal day 22 and week 16 of age. Meanwhile another independent animal experiment and cell culture were carried out for validation. Significance analysis of microarrays, qPCR verification, drug induction/inhibition assays, and metabonomics indicated that alpha-2u globulin (extracellular region)-socs2 (-SH2-containing signals/receptor tyrosine kinases)-ppp2r2a/pik3c3 (MAPK signaling)-hsd3b5/cav2 (metabolism/organization) plays a vital role in early development. Taken together, early development of male rats is ECR and MAPK-mediated coordination of cancer-like growth and negative regulations. Our data represent the first comprehensive description of early individual development, which could be a valuable basis for understanding the functioning of the gene interaction network of infant development. Xiu-Ju Zhao and Hexian Zhuo Copyright © 2014 Xiu-Ju Zhao and Hexian Zhuo. All rights reserved. Iron as the Key Modulator of Hepcidin Expression in Erythroid Antibody-Mediated Hypoplasia Thu, 18 Dec 2014 00:11:23 +0000 Erythroid hypoplasia (EH) is a rare complication associated with recombinant human erythropoietin (rHuEPO) therapies, due to development of anti-rHuEPO antibodies; however, the underlying mechanisms remain poorly clarified. Our aim was to manage a rat model of antibody-mediated EH induced by rHuEPO and study the impact on iron metabolism and erythropoiesis. Wistar rats treated during 9 weeks with a high rHuEPO dose (200 IU) developed EH, as shown by anemia, reduced erythroblasts, reticulocytopenia, and plasmatic anti-rHuEPO antibodies. Serum iron was increased and associated with mRNA overexpression of hepatic hepcidin and other iron regulatory mediators and downregulation of matriptase-2; overexpression of divalent metal transporter 1 and ferroportin was observed in duodenum and liver. Decreased EPO expression was observed in kidney and liver, while EPO receptor was overexpressed in liver. Endogenous EPO levels were normal, suggesting that anti-rHuEPO antibodies blunted EPO function. Our results suggest that anti-rHuEPO antibodies inhibit erythropoiesis causing anemia. This leads to a serum iron increase, which seems to stimulate hepcidin expression despite no evidence of inflammation, thus suggesting iron as the key modulator of hepcidin synthesis. These findings might contribute to improving new therapeutic strategies against rHuEPO resistance and/or development of antibody-mediated EH in patients under rHuEPO therapy. J. C. Fernandes, P. Garrido, S. Ribeiro, P. Rocha-Pereira, E. Bronze-da-Rocha, L. Belo, E. Costa, F. Reis, and A. Santos-Silva Copyright © 2014 J. C. Fernandes et al. All rights reserved. Sequential Coordination between Lingual and Pharyngeal Pressures Produced during Dry Swallowing Thu, 18 Dec 2014 00:11:21 +0000 The aim of this study was to investigate oropharyngeal pressure flow dynamics during dry swallowing in ten healthy subjects. Tongue pressure (TP) was measured using a sensor sheet system with five measuring points on the hard palate, and pharyngeal pressure (PP) was measured using a manometric catheter with four measuring points. The order and correlations of sequential events, such as onset, peak, and offset times of pressure production, at each pressure measuring point were analyzed on the synchronized waveforms. Onset of TP was earlier than that of PP. The peak of TP did not show significant differences with the onset of PP, and it was earlier than that of PP. There was no significant difference between the offset of TP and PP. The onset of PP was temporally time-locked to the peak of TP, and there was an especially strong correlation between the onset of PP and TP at the posterior-median part on the hard palate. The offset of PP was temporally time-locked to that of TP. These results could be interpreted as providing an explanation for the generation of oropharyngeal pressure flow to ensure efficient bolus transport and safe swallowing. Jitsuro Yano, Yoichiro Aoyagi, Takahiro Ono, Kazuhiro Hori, Wakami Yamaguchi, Shigehiro Fujiwara, Isami Kumakura, Shogo Minagi, and Akio Tsubahara Copyright © 2014 Jitsuro Yano et al. All rights reserved. Risk Factors for Hospital and Long-Term Mortality of Critically Ill Elderly Patients Admitted to an Intensive Care Unit Tue, 16 Dec 2014 06:51:02 +0000 Background. Data on long-term outcomes of elderly (≥65 years) patients in ICU are sparse. Materials and Methods. Adult patients (, 45.4% elderly) admitted over 28 months were analyzed by competing risks regression model to determine independent factors related to in-hospital and long-term mortality. Results. 414 (26.5%) and 337 (21.6%) patients died in-hospital and during the 52 months following discharge, respectively; the elderly group had higher mortality during both periods. After discharge, elderly patients had 2.3 times higher mortality compared to the general population of the same age-group. In-hospital mortality was independently associated with mechanical ventilation (subdistribution hazard ratio (SHR) 2.74), vasopressors (SHR 2.56), neurological disease (SHR 1.77), and Mortality Prediction Model II score (SHR 1.01) regardless of age and with malignancy (SHR, hematological 3.65, nonhematological 3.4) and prior renal replacement therapy (RRT, SHR 2.21) only in the elderly. Long-term mortality was associated with low hemoglobin concentration (SHR 0.94), airway disease (SHR 2.23), and malignancy (SHR hematological 1.11, nonhematological 2.31) regardless of age and with comorbidities especially among the nonelderly. Conclusions. Following discharge, elderly ICU patients have higher mortality compared to the nonelderly and general population. In the elderly group, prior RRT and malignancy contribute additionally to in-hospital mortality risk. In the long-term, comorbidities (age-related), anemia, airway disease, and malignancy were significantly associated with mortality. A. Mukhopadhyay, B. C. Tai, K. C. See, W. Y. Ng, T. K. Lim, S. Onsiong, S. Ee, M. J. Chua, P. R. Lee, M. L. Loh, and J Phua Copyright © 2014 A. Mukhopadhyay et al. All rights reserved. Understanding Host-Adherent-Invasive Escherichia coli Interaction in Crohn’s Disease: Opening Up New Therapeutic Strategies Mon, 15 Dec 2014 14:43:49 +0000 A trillion of microorganisms colonize the mammalian intestine. Most of them have coevolved with the host in a symbiotic relationship and some of them have developed strategies to promote their replication in the presence of competing microbiota. Recent evidence suggests that perturbation of the microbial community favors the emergence of opportunistic pathogens, in particular adherent-invasive Escherichia coli (AIEC) that can increase incidence and severity of gut inflammation in the context of Crohn’s disease (CD). This review will report the importance of AIEC as triggers of intestinal inflammation, focusing on their impact on epithelial barrier function and stimulation of mucosal inflammation. Beyond manipulation of immune response, restoration of gut microbiota as a new treatment option for CD patients will be discussed. Allison Agus, Sébastien Massier, Arlette Darfeuille-Michaud, Elisabeth Billard, and Nicolas Barnich Copyright © 2014 Allison Agus et al. All rights reserved. Specific Genomic Fingerprints of Phosphate Solubilizing Pseudomonas Strains Generated by Box Elements Mon, 15 Dec 2014 12:08:11 +0000 Primers corresponding to conserved bacterial repetitive of BOX elements were used to show that BOX-DNA sequences are widely distributed in phosphate solubilizing Pseudomonas strains. Phosphate solubilizing Pseudomonas was isolated from oil palm fields (tropical soil) in Malaysia. BOX elements were used to generate genomic fingerprints of a variety of Pseudomonas isolates to identify strains that were not distinguishable by other classification methods. BOX-PCR, that derived genomic fingerprints, was generated from whole purified genomic DNA by liquid culture of phosphate solubilizing Pseudomonas. BOX-PCR generated the phosphate solubilizing Pseudomonas specific fingerprints to identify the relationship between these strains. This suggests that distribution of BOX elements’ sequences in phosphate solubilizing Pseudomonas strains is the mirror image of their genomic structure. Therefore, this method appears to be a rapid, simple, and reproducible method to identify and classify phosphate solubilizing Pseudomonas strains and it may be useful tool for fast identification of potential biofertilizer strains. Mohammad Bagher Javadi Nobandegani, Halimi Mohd Saud, and Wong Mui Yun Copyright © 2014 Mohammad Bagher Javadi Nobandegani et al. All rights reserved. Impact of Medical and Surgical Treatment of Endometriosis on the Cure of Endometriosis and Pain Mon, 15 Dec 2014 09:03:29 +0000 This endometriosis study evaluates three different treatment strategies (hormonal medication, surgical, or combined treatment) and discusses the influence of endometriosis on the cure of this disease and pain relief. Four hundred and fifty patients with genital endometriosis, aged 18–44 years, were randomly distributed to three treatment groups at the first laparoscopy. They were reevaluated at a second-look laparoscopy (D 426/10), one to two months after the three-month hormonal therapy for groups 1 and 3 and five to six months later for group 2 (surgical treatment alone). Outcome data focussed on the recurrence of symptoms and pain. The three treatment options independent of the initial endoscopic endometriosis classification (EEC) stage including deep infiltrating endometriosis (DIE) achieved an overall cure rate of 50% or higher. The highest cure rate of 60% was achieved by the combined treatment, 55% by the exclusively hormonal therapy, and 50% by the exclusively surgical treatment. An overall pregnancy rate between 55% and 65% was achieved with no significant difference in relation to the therapeutical option. Liselotte Mettler, R. Ruprai, and Ibrahim Alkatout Copyright © 2014 Liselotte Mettler et al. All rights reserved. Phenomics Research on Coronary Heart Disease Based on Human Phenotype Ontology Mon, 15 Dec 2014 06:53:45 +0000 The characteristics of holistic, dynamics, complexity, and spatial and temporal features enable “Omics” and theories of TCM to interlink with each other. HPO, namely, “characterization,” can be understood as a sorting and generalization of the manifestations shown by people with diseases on the basis of the phenomics. Syndrome is the overall “manifestation” of human body pathological and physiological changes expressed by four diagnostic methods’ information. The four diagnostic methods’ data could be the most objective and direct manifestations of human body under morbid conditions. In this aspect, it is consistent with the connation of “characterization.” Meanwhile, the four diagnostic methods’ data also equip us with features of characterization in HPO. In our study, we compared 107 pieces of four diagnostic methods’ information with the “characterization database” to further analyze data of four diagnostic methods’ characterization in accordance with the common characteristics of four diagnostic methods’ information and characterization and integrated 107 pieces of four diagnostic methods’ data to relevant items in HPO and finished the expansion of characterization information in HPO. Qi Shi, Kuo Gao, Huihui Zhao, Juan Wang, Xing Zhai, Peng Lu, Jianxin Chen, and Wei Wang Copyright © 2014 Qi Shi et al. All rights reserved. Preparation and Characterization of Gelatin-Based Mucoadhesive Nanocomposites as Intravesical Gene Delivery Scaffolds Mon, 15 Dec 2014 00:11:02 +0000 This study aimed to develop optimal gelatin-based mucoadhesive nanocomposites as scaffolds for intravesical gene delivery to the urothelium. Hydrogels were prepared by chemically crosslinking gelatin A or B with glutaraldehyde. Physicochemical and delivery properties including hydration ratio, viscosity, size, yield, thermosensitivity, and enzymatic degradation were studied, and scanning electron microscopy (SEM) was carried out. The optimal hydrogels (H), composed of 15% gelatin A175, displayed an 81.5% yield rate, 87.1% hydration ratio, 42.9 Pa·s viscosity, and 125.8 nm particle size. The crosslinking density of the hydrogels was determined by performing pronase degradation and ninhydrin assays. In vitro lentivirus (LV) release studies involving p24 capsid protein analysis in 293T cells revealed that hydrogels containing lentivirus (H-LV) had a higher cumulative release than that observed for LV alone (3.7-, 2.3-, and 2.3-fold at days 1, 3, and 5, resp.). Lentivirus from lentivector constructed green fluorescent protein (GFP) was then entrapped in hydrogels (H-LV-GFP). H-LV-GFP showed enhanced gene delivery in AY-27 cells in vitro and to rat urothelium by intravesical instillation in vivo. Cystometrogram showed mucoadhesive H-LV reduced peak micturition and threshold pressure and increased bladder compliance. In this study, we successfully developed first optimal gelatin-based mucoadhesive nanocomposites as intravesical gene delivery scaffolds. Ching-Wen Liu, Li-Ching Chang, Kai-Jen Lin, Tsan-Jung Yu, Ching-Chung Tsai, Hao-Kuang Wang, and Tong-Rong Tsai Copyright © 2014 Ching-Wen Liu et al. All rights reserved. Association Analysis between g.18873C>T and g.27522G>A Genetic Polymorphisms of OPG and Bone Mineral Density in Chinese Postmenopausal Women Mon, 15 Dec 2014 00:10:59 +0000 Several studies report that the OPG is an important candidate gene in the pathogenesis of osteoporosis. This study aimed to detect the potential association of OPG gene polymorphisms with osteoporosis in postmenopausal women. We recruited 928 subjects containing 463 with primary postmenopausal osteoporosis and 465 healthy volunteers as controls. The BMD of neck hip, lumbar spine (), and total hip were assessed by dual-energy X-ray absorptiometry (DEXA). Through the created restriction site-polymerase chain reaction (CRS-PCR), PCR-restriction fragment length polymorphism (PCR-RFLP), and DNA sequencing methods, the g.18873C>T and g.27522G>A have been investigated. As for g.18873C>T, our data indicated that subjects with CC genotype have significantly higher BMD value than those of CT and TT genotypes (all values < 0.05). As for g.27522G>A, the BMD values of subjects with GG genotype were significantly higher than those of GA and AA genotypes (all values < 0.05). Our findings suggest that the OPG g.18873C>T and g.27522G>A genetic polymorphisms are associated with the decreased risk for osteoporosis in Chinese postmenopausal women. Fei Wang, Yi Cao, Fang Li, Jianlin Shan, and Tianlin Wen Copyright © 2014 Fei Wang et al. All rights reserved. Emodin Augments Cisplatin Cytotoxicity in Platinum-Resistant Ovarian Cancer Cells via ROS-Dependent MRP1 Downregulation Sun, 14 Dec 2014 13:15:10 +0000 The intracellular level of reactive oxygen species (ROS) is closely associated with chemosensitivity of cancer cells. Overexpression of ATP binding cassette transporter MRP1 is correlated with resistance to platinum drugs. In this study, we tested the hypothesis that emodin, a potent ROS generator, may increase sensitivity of cisplatin-(cDDP-) resistant ovarian carcinoma cells to cDDP cytotoxicity via ROS-mediated suppression of MRP1 expression. Using the isogenic pair of the human ovarian carcinoma cell line COC1 and its cDDP resistant variant COC1/DDP, we found that ROS level in the cDDP-sensitive ovarian cancer cells was significantly higher than that in the cDDP-resistant cells. Emodin enhanced ROS production in COC1/DDP cells and consequently sensitized them to cDDP-induced apoptosis. These effects were reversed by addition of the antioxidant N-acetyl-L-cysteine (NAC). Cotreatment with emodin and cDDP inhibited the tumor growth in vivo by increasing tumor cell apoptosis. The emodin-enhanced cDDP cytotoxicity was attributable to downregulation of multidrug resistance-related protein 1 (MRP1) expression. Together, these results suggest that emodin could act as an adjunct to enhance the anticancer effect of cDDP likely through ROS-related downregulation of MRP1 expression, and may be of therapeutic potential in cDDP-refractory ovarian carcinomas. Jun Ma, Jie Yang, Chao Wang, Nan Zhang, Ying Dong, Chengjie Wang, Yu Wang, and Xinjian Lin Copyright © 2014 Jun Ma et al. All rights reserved. Common Polymorphism in the LRP5 Gene May Increase the Risk of Bone Fracture and Osteoporosis Sun, 14 Dec 2014 12:34:06 +0000 The low-density lipoprotein receptor-related protein 5 gene (LRP5) was identified to be linked to the variation in bone mineral density and types of bone diseases. The present study was aimed at examining the association of LRP5 rs3736228 C>T gene with bone fracture and osteoporosis by meta-analysis. A systematic electronic search of literature was conducted to identify all published studies in English or Chinese on the association of the LRP5 gene with bone fracture and osteoporosis risks. All analyses were calculated using the Version 12.0 STATA software. Odds ratios (ORs) and their corresponding 95% confidence interval (95% CI) were calculated. An updated meta-analysis was currently performed, including seven independent case-control studies. Results identified that carriers of rs3736228 C>T variant in the LRP5 gene were associated with an increased risk of developing osteoporosis and fractures under 4 genetic models but not under the dominant model (OR = 1.19, 95% CI = 0.97~1.46, and ). Ethnicity-subgroup analysis implied that LRP5 rs3736228 C>T mutation was more likely to develop osteoporosis and fractures among Asians and Caucasians in majority of subgroups. These results suggest that there is a modest effect of the LRP5 rs3736228 C>T on the increased susceptibility of bone fracture and osteoporosis. Guang-Yue Xu, Yong Qiu, and Hai-Jun Mao Copyright © 2014 Guang-Yue Xu et al. All rights reserved. A Single Imaging Modality in the Diagnosis, Severity, and Prognosis of Pulmonary Embolism Sun, 14 Dec 2014 12:19:42 +0000 Introduction. This study aimed to investigate the currency of computerized tomography pulmonary angiography-based parameters as pulmonary artery obstruction index (PAOI), as well as right ventricular diameters for pulmonary embolism (PE) risk evaluation and prediction of mortality and intensive care unit (ICU) requirement. Materials and Methods. The study retrospectively enrolled 203 patients hospitalized with acute PE. PAOI was calculated according to Qanadli score. Results. Forty-three patients (23.9%) were hospitalized in the ICU. Nineteen patients (10.6%) died during the 30-day follow-up period. The optimal cutoff value of PAOI for PE 30th day mortality and ICU requirement were found as 36.5% in ROC curve analysis. The pulmonary artery systolic pressure had a significant positive correlation with right/left ventricular diameter ratio (, ), PAOI (, ), and pulmonary artery diameter (, ). The patients with PAOI values higher than 36.5% have a 5.7-times increased risk of death. Conclusion. PAOI is a fast and promising parameter for risk assessment in patients with acute PE. With greater education of clinicians in this radiological scoring, a rapid assessment for diagnosis, clinical risk evaluation, and prognosis may be possible in emergency services without the need for echocardiography. Hadice Selimoglu Sen, Özlem Abakay, Mehmet Güli Cetincakmak, Cengizhan Sezgi, Süreyya Yilmaz, Melike Demir, Mahsuk Taylan, and Hatice Gümüs Copyright © 2014 Hadice Selimoglu Sen et al. All rights reserved. Identification of a Marine Bacillus Strain C5 and Parathion-Methyl Degradation Characteristics of the Extracellular Esterase B1 Thu, 11 Dec 2014 07:01:29 +0000 A bacterial strain C5 that can produce new type of marine esterase was isolated and screened from marine sludge. According to 16S rRNA sequence analysis and physiological and biochemical experiments, the strain was identified as Bacillus subtilis. A single isozyme with a molecular weight of 86 kDa was observed by SDS-PAGE and native-PAGE. On this basis, the mechanism of esterase B1 secreted by strain C5 degrading parathion-methyl was explored, and the effects of temperature and pH on the degradation rate were investigated. From the results, p-nitrophenol was one of the degradation products of B1 degrading parathion-methyl, and the best degradation effect could be achieved at the temperature of 40°C and the neutral pH value. Jianhua Hao, Junzhong Liu, and Mi Sun Copyright © 2014 Jianhua Hao et al. All rights reserved. DBC1/CCAR2 and CCAR1 Are Largely Disordered Proteins that Have Evolved from One Common Ancestor Thu, 11 Dec 2014 00:10:50 +0000 Deleted in breast cancer 1 (DBC1, CCAR2, KIAA1967) is a large, predominantly nuclear, multidomain protein that modulates gene expression by inhibiting several epigenetic modifiers, including the deacetylases SIRT1 and HDAC3, and the methyltransferase SUV39H1. DBC1 shares many highly conserved protein domains with its paralog cell cycle and apoptosis regulator 1 (CCAR1, CARP-1). In this study, we examined the full-length sequential and structural properties of DBC1 and CCAR1 from multiple species and correlated these properties with evolution. Our data shows that the conserved domains shared between DBC1 and CCAR1 have similar domain structures, as well as similar patterns of predicted disorder in less-conserved intrinsically disordered regions. Our analysis indicates similarities between DBC1, CCAR1, and the nematode protein lateral signaling target 3 (LST-3), suggesting that DBC1 and CCAR1 may have evolved from LST-3. Our data also suggests that DBC1 emerged later in evolution than CCAR1. DBC1 contains regions that show less conservation across species as compared to the same regions in CCAR1, suggesting a continuously evolving scenario for DBC1. Overall, this study provides insight into the structure and evolution of DBC1 and CCAR1, which may impact future studies on the biological functions of these proteins. Jessica Brunquell, Jia Yuan, Aqeela Erwin, Sandy D. Westerheide, and Bin Xue Copyright © 2014 Jessica Brunquell et al. All rights reserved. Treatment for Intramuscular Lipoma Frequently Confused with Sarcoma: A 6-Year Restrospective Study and Literature Review Wed, 10 Dec 2014 00:11:22 +0000 Introduction. Intramuscular lipoma is a very rare form of lipoma, known to be categorized as an infiltrating lipoma due to its tendencies to infiltrate the muscle or the synovium. Contrary to other subcutaneous lipomas, even after surgical removal, the rate of local recurrence ranges at a high rate from 50∼80% and differential diagnosis with liposarcoma is very difficult. Patients and Methods. A retrospective chart review was conducted for a total of 27 patients. Before performing a surgery based on the types of mass, a radiologic imaging study was performed. An intraoperative frozen biopsy was performed on every patient and the results were compared. The progress was monitored every 3 to 6 months for recurrence or struggles with rehabilitation. Results. There were 13 male and 14 female patients with an average age of 54.6. The average tumor size was 8.2 cm (1.1 cm∼31.6 cm). Excision was performed using a wide excision. All 27 individuals were initially diagnosed as intramuscular lipoma; however, 1 of the patients was rediagnosed as liposarcoma in the final checkup. The patients had an average of 3 years and 1 month of follow-up and did not suffer recurrences. Conclusion. Thus, it is essential that a frozen biopsy is performed during the surgery in order to identify its malignancy. And a wide excision like malignant tumor operation is a principle of treatment. Hyun Ho Han, Jong Yun Choi, Bommie F. Seo, Suk-Ho Moon, Deuk Young Oh, Sang Tae Ahn, and Jong Won Rhie Copyright © 2014 Hyun Ho Han et al. All rights reserved. Hypoglossal-Facial Nerve Reconstruction Using a Y-Tube-Conduit Reduces Aberrant Synkinetic Movements of the Orbicularis Oculi and Vibrissal Muscles in Rats Tue, 09 Dec 2014 09:30:15 +0000 The facial nerve is the most frequently damaged nerve in head and neck trauma. Patients undergoing facial nerve reconstruction often complain about disturbing abnormal synkinetic movements of the facial muscles (mass movements, synkinesis) which are thought to result from misguided collateral branching of regenerating motor axons and reinnervation of inappropriate muscles. Here, we examined whether use of an aorta Y-tube conduit during reconstructive surgery after facial nerve injury reduces synkinesis of orbicularis oris (blink reflex) and vibrissal (whisking) musculature. The abdominal aorta plus its bifurcation was harvested () for Y-tube conduits. Animal groups comprised intact animals (Group 1), those receiving hypoglossal-facial nerve end-to-end coaptation alone (HFA; Group 2), and those receiving hypoglossal-facial nerve reconstruction using a Y-tube (HFA-Y-tube, Group 3). Videotape motion analysis at 4 months showed that HFA-Y-tube group showed a reduced synkinesis of eyelid and whisker movements compared to HFA alone. Yasemin Kaya, Umut Ozsoy, Murat Turhan, Doychin N. Angelov, and Levent Sarikcioglu Copyright © 2014 Yasemin Kaya et al. All rights reserved. Scotopic Microperimetry in the Early Diagnosis of Age-Related Macular Degeneration: Preliminary Study Tue, 09 Dec 2014 00:10:30 +0000 Background. Recent clinical studies have shown that, in some degenerative retinal diseases, like age-related macular degeneration (AMD), the sensitivity of the rods decreases more rapidly than the sensitivity of the cones. The aim of this study was to evaluate if there is a correlation between the presence of hard drusen at the macular level and the rod damage responsible for the reduction in scotopic retinal sensitivity in subjects at risk for AMD. Methods. The authors selected 24 subjects (14 men and 10 women) with an average age of 67.25 ± 5.7 years. Macular hard drusen were present in 50% of the subjects at the fundus oculi exam. The researchers evaluated the retinal sensitivity to light in mesopic and scotopic conditions of each subject with an MP-1 scotopic microperimeter (MP-1S). Results. In subjects with hard drusen in the fundus oculi examination, there was a statistically significant reduction in scotopic retinal sensitivity, while the mesopic retinal sensitivity was not compromised. Conclusion. This study revealed how the presence of hard drusen at the macular level is associated with a reduction in scotopic retinal sensitivity compared to a control group of healthy subjects. Retinal functionality in a scotopic setting examined with MP-1S could be useful in early diagnosis of AMD. Marcella Nebbioso, Andrea Barbato, and Nicola Pescosolido Copyright © 2014 Marcella Nebbioso et al. All rights reserved. Molecular and Cellular Basis of Autosomal Recessive Primary Microcephaly Mon, 08 Dec 2014 00:10:43 +0000 Autosomal recessive primary microcephaly (MCPH) is a rare hereditary neurodevelopmental disorder characterized by a marked reduction in brain size and intellectual disability. MCPH is genetically heterogeneous and can exhibit additional clinical features that overlap with related disorders including Seckel syndrome, Meier-Gorlin syndrome, and microcephalic osteodysplastic dwarfism. In this review, we discuss the key proteins mutated in MCPH. To date, MCPH-causing mutations have been identified in twelve different genes, many of which encode proteins that are involved in cell cycle regulation or are present at the centrosome, an organelle crucial for mitotic spindle assembly and cell division. We highlight recent findings on MCPH proteins with regard to their role in cell cycle progression, centrosome function, and early brain development. Marine Barbelanne and William Y. Tsang Copyright © 2014 Marine Barbelanne and William Y. Tsang. All rights reserved. Barcoding Melting Curve Analysis for Rapid, Sensitive, and Discriminating Authentication of Saffron (Crocus sativus L.) from Its Adulterants Sun, 07 Dec 2014 14:22:31 +0000 Saffron (Crocus sativus L.) is one of the most important and expensive medicinal spice products in the world. Because of its high market value and premium price, saffron is often adulterated through the incorporation of other materials, such as Carthamus tinctorius L. and Calendula officinalis L. flowers, Hemerocallis L. petals, Daucus carota L. fleshy root, Curcuma longa L. rhizomes, Zea may L., and Nelumbo nucifera Gaertn. stigmas. To develop a straightforward, nonsequencing method for rapid, sensitive, and discriminating detection of these adulterants in traded saffron, we report here the application of a barcoding melting curve analysis method (Bar-MCA) that uses the universal chloroplast plant DNA barcoding region trnH-psbA to identify adulterants. When amplified at DNA concentrations and annealing temperatures optimized for the curve analysis, peaks were formed at specific locations for saffron (81.92°C) and the adulterants: D. carota (81.60°C), C. tinctorius (80.10°C), C. officinalis (79.92°C), Dendranthema morifolium (Ramat.) Tzvel. (79.62°C), N. nucifera (80.58°C), Hemerocallis fulva (L.) L. (84.78°C), and Z. mays (84.33°C). The constructed melting curves for saffron and its adulterants have significantly different peak locations or shapes. In conclusion, Bar-MCA could be a faster and more cost-effective method to authenticate saffron and detect its adulterants. Chao Jiang, Liang Cao, Yuan Yuan, Min Chen, Yan Jin, and Luqi Huang Copyright © 2014 Chao Jiang et al. All rights reserved. Vinpocetine and Pyritinol: A New Model for Blood Rheological Modulation in Cerebrovascular Disorders—A Randomized Controlled Clinical Study Sun, 07 Dec 2014 14:15:04 +0000 Blood and plasma viscosity are the major factors affecting blood flow and normal circulation. Whole blood viscosity is mainly affected by plasma viscosity, red blood cell deformability/aggregation and hematocrit, and other physiological factors. Thirty patients (twenty males + ten females) with age range 50–65 years, normotensive with history of cerebrovascular disorders, were selected according to the American Heart Stroke Association. Blood viscosity and other rheological parameters were measured after two-day abstinence from any medications. Dual effects of vinpocetine and pyritinol exhibit significant effects on all hemorheological parameters (), especially on low shear whole blood viscosity (), but they produced insignificant effects on total serum protein and high shear whole blood viscosity (). Therefore, joint effects of vinpocetine and pyritinol improve blood and plasma viscosity in patients with cerebrovascular disorders. Hayder M. Alkuraishy, Ali I. Al-Gareeb, and Ali K. Albuhadilly Copyright © 2014 Hayder M. Alkuraishy et al. All rights reserved. Increased Serum Levels of Inflammatory Mediators and Low Frequency of Regulatory T Cells in the Peripheral Blood of Preeclamptic Mexican Women Sun, 07 Dec 2014 12:01:26 +0000 Regulatory T cells (; CD4+CD2Foxp3+) are critical in maintaining immune tolerance during pregnancy and uterine vascularization. In this study, we show that, in Mexican women with different preeclamptic severity levels, the number of and the subset of CD4+CD2Foxp3+ are decreased compared with those of normotensive pregnant women (NP). Moreover, a systemic inflammatory state is a pivotal feature in the pathogenesis of this disorder and could be related to hypertension and endothelial dysfunction. Likewise, we observed elevated levels of IL-6, TNF-α, and IL-8 in the serum of severe preeclamptic patients (SPE); no differences were found in the IL-1β and IL-10 levels compared with those of NP patients. An analysis of chemokines in the preeclamptic serum samples showed high levels of CXCL10, CCL2, and CXCL9. Our findings suggest that the preeclamptic state is linked with systemic inflammation and reduced numbers of . Mario Adan Moreno-Eutimio, José María Tovar-Rodríguez, Karina Vargas-Avila, Nayeli Goreti Nieto-Velázquez, María Guadalupe Frías-De-León, Mónica Sierra-Martinez, and Gustavo Acosta-Altamirano Copyright © 2014 Mario Adan Moreno-Eutimio et al. All rights reserved. Protective Effect of a Lipid-Based Preparation from Mycobacterium smegmatis in a Murine Model of Progressive Pulmonary Tuberculosis Sun, 07 Dec 2014 11:57:00 +0000 A more effective vaccine against tuberculosis (TB) is urgently needed. Based on its high genetic homology with Mycobacterium tuberculosis (Mtb), the nonpathogenic mycobacteria, Mycobacterium smegmatis (Ms), could be an attractive source of potential antigens to be included in such a vaccine. We evaluated the capability of lipid-based preparations obtained from Ms to provide a protective response in Balb/c mice after challenge with Mtb H37Rv strain. The intratracheal model of progressive pulmonary TB was used to assess the level of protection in terms of bacterial load as well as the pathological changes in the lungs of immunized Balb/c mice following challenge with Mtb. Mice immunized with the lipid-based preparation from Ms either adjuvanted with Alum (LMs-AL) or nonadjuvanted (LMs) showed significant reductions in bacterial load () compared to the negative control group (animals immunized with phosphate buffered saline (PBS)). Both lipid formulations showed the same level of protection as Bacille Calmette and Guerin (BCG). Regarding the pathologic changes in the lungs, mice immunized with both lipid formulations showed less pneumonic area when compared with the PBS group () and showed similar results compared with the BCG group. These findings suggest the potential of LMs as a promising vaccine candidate against TB. Maria de los Angeles García, Reinier Borrero, Maria E. Lanio, Yanely Tirado, Nadine Alvarez, Alina Puig, Alicia Aguilar, Liem Canet, Dulce Mata Espinoza, Jorge Barrios Payán, María Elena Sarmiento, Rogelio Hernández-Pando, Mohd-Nor Norazmi, and Armando Acosta Copyright © 2014 Maria de los Angeles García et al. All rights reserved. Dental Wear: A Scanning Electron Microscope Study Sun, 07 Dec 2014 10:50:45 +0000 Dental wear can be differentiated into different types on the basis of morphological and etiological factors. The present research was carried out on twelve extracted human teeth with dental wear (three teeth showing each type of wear: erosion, attrition, abrasion, and abfraction) studied by scanning electron microscopy (SEM). The study aimed, through analysis of the macro- and micromorphological features of the lesions (considering the enamel, dentin, enamel prisms, dentinal tubules, and pulp), to clarify the different clinical and diagnostic presentations of dental wear and their possible significance. Our results, which confirm current knowledge, provide a complete overview of the distinctive morphology of each lesion type. It is important to identify the type of dental wear lesion in order to recognize the contributing etiological factors and, consequently, identify other more complex, nondental disorders (such as gastroesophageal reflux, eating disorders). It is clear that each type of lesion has a specific morphology and mechanism, and further clinical studies are needed to clarify the etiological processes, particularly those underlying the onset of abfraction. Luca Levrini, Giulia Di Benedetto, and Mario Raspanti Copyright © 2014 Luca Levrini et al. All rights reserved. Interfractional Variations of Tumor Centroid Position and Tumor Regression during Stereotactic Body Radiotherapy for Lung Tumor Sun, 07 Dec 2014 10:44:34 +0000 Purpose. To determine interfractional changes of lung tumor centroid position and tumor regression during stereotactic body radiation therapy (SBRT). Methods and Materials. 34 patients were treated by SBRT in 4-5 fractions to a median dose of 50 Gy. The CT scans acquired for verification were registered with simulation CT scans. The gross target volume (GTV) was contoured on all verification CT scans and compared to the initial GTV in treatment plan system. Results. The mean (standard deviation, SD) three-dimension vector shift was  mm. The mean interfractional variations of tumor centroid position were  mm in anterior-posterior (AP) direction,  mm in superior-inferior (SI) direction, and  mm in right-left (RL) direction. Large interfractional variations (5 mm) were observed in 5 fractions (3.3%) in RL direction, 16 fractions (10.5%) in SI direction, and 36 fractions (23.5%) in AP direction. Tumor volume did not decrease significantly during lung SBRT. Conclusions. Small but insignificant tumor volume regression was observed during lung SBRT. While the mean interfractional variations of tumor centroid position were minimal in three directions, variations more than 5 mm account for approximately a third of all, indicating additional margin for PTV, especially in AP direction. Yanan Sun, Yufei Lu, Siguo Cheng, Wei Guo, Ke Ye, Huiyun Zhao, Xiaoli Zheng, Dingjie Li, Shujuan Wang, Chengliang Yang, and Hong Ge Copyright © 2014 Yanan Sun et al. All rights reserved. Maternal Obesity and Occurrence of Fetal Macrosomia: A Systematic Review and Meta-Analysis Sun, 07 Dec 2014 00:10:53 +0000 Objective. To determine a precise estimate for the contribution of maternal obesity to macrosomia. Data Sources. The search strategy included database searches in 2011 of PubMed, Medline (In-Process & Other Non-Indexed Citations and Ovid Medline, 1950–2011), and EMBASE Classic + EMBASE. Appropriate search terms were used for each database. Reference lists of retrieved articles and review articles were cross-referenced. Methods of Study Selection. All studies that examined the relationship between maternal obesity (BMI ≥30 kg/m2) (pregravid or at 1st prenatal visit) and fetal macrosomia (birth weight ≥4000 g, ≥4500 g, or ≥90th percentile) were considered for inclusion. Tabulation, Integration, and Results. Data regarding the outcomes of interest and study quality were independently extracted by two reviewers. Results from the meta-analysis showed that maternal obesity is associated with fetal overgrowth, defined as birth weight ≥ 4000 g (OR 2.17, 95% CI 1.92, 2.45), birth weight ≥4500 g (OR 2.77,95% CI 2.22, 3.45), and birth weight ≥90% ile for gestational age (OR 2.42, 95% CI 2.16, 2.72). Conclusion. Maternal obesity appears to play a significant role in the development of fetal overgrowth. There is a critical need for effective personal and public health initiatives designed to decrease prepregnancy weight and optimize gestational weight gain. Laura Gaudet, Zachary M. Ferraro, Shi Wu Wen, and Mark Walker Copyright © 2014 Laura Gaudet et al. All rights reserved. Advanced Extrauterine Pregnancy at 33 Weeks with a Healthy Newborn Wed, 03 Dec 2014 13:32:01 +0000 Abdominal pregnancy is a very rare form of ectopic pregnancy, associated with high morbidity and mortality for both fetus and mother. It is, and often, seen in poor resource nations, where early diagnosis is often a major challenge due to poor prenatal care and lack of medical resources. An advanced abdominal pregnancy with a good fetal and maternal outcome is therefore a more extraordinary occurrence in the modern developed world. We present a case of an abdominal pregnancy at 33.4 weeks in an individual with no documented prenatal care, who arrived in a hospital in the Bronx, in June 25th 2014, with symptoms of generalized, severe lower abdominal pain. Upon examination it was found that due to category III fetal tracing an emergent cesarean section was performed. At the time of laparotomy the fetus was located in the pelvis covered by the uterine serosa, with distortion of the entire right adnexa and invasion to the right parametrium. The placenta invaded the pouch of Douglas and the lower part of the sigmoid colon. A massive hemorrhage followed, followed by a supracervical hysterectomy. A viable infant was delivered and mother discharged on postoperative day 4. Tajudeen Dabiri, Guillermo A. Marroquin, Boleslaw Bendek, Enyonam Agamasu, and Magdy Mikhail Copyright © 2014 Tajudeen Dabiri et al. All rights reserved. Development of a Provisional Model to Improve Transitional Care for Female Adolescents with a Rare Genital Malformation as an Example for Orphan Diseases Wed, 03 Dec 2014 11:34:56 +0000 Deficits of care exist during the transitional period, when young people with ongoing needs of support to achieve their physical, social, and psychological potential are entering adulthood. This study aims to develop a patient oriented, structured provisional model to improve transitional care for adolescents with Mayer-Rokitansky-Kuester-Hauser-Syndrome as an example for orphan diseases, where problems of access and continuity are even more complex. The study is funded by the German Federal Ministry of Education and Research (BMBF-Funding Code 01GY1125). The target patient group are young females with this disorder, treated at the Centre for Rare Genital Malformations in Women (ZSGF), University Hospital of Tuebingen. The study comprises five phases: an appraisal of literature, assessment of patients (), parents’, partners’, and health and social care providers’ () needs and experienced deficits in care and support in a qualitative approach, construction of a provisional model via scenario technique, followed by communicative validation (including interested public, ), preference finding, and identification of patient-oriented quality aims for follow-up. Quantitative data from questionnaires and chart review (as sociodemographic data, nonresponder analysis, and preference rating) are worked up for descriptive statistics. The results provide a platform for the development of future multidisciplinary transitional intervention programs in orphan diseases. Elisabeth Simoes, Andrea Kronenthaler, Christine Emrich, Monika A. Rieger, Kristin Katharina Rall, Norbert Schäffeler, Hanna Hiltner, Esther Ueding, and Sara Y. Brucker Copyright © 2014 Elisabeth Simoes et al. All rights reserved. Ethnopharmacological Assessment of Medicinal Plants Used against Livestock Infections by the People Living around Indus River Wed, 03 Dec 2014 08:03:50 +0000 The present study was aimed to document detailed ethnopharmacological knowledge of medicinal plants against livestock infections of an unexplored remote region of Pakistan. Semistructured questionnaires were used for data collection. Total 43 plants belonging to 26 families were found to be used in ethnoveterinary practices. Seeds (29%) were found to be the most frequent plant part used followed by leaves (22%). Ethnoveterinary recipes were mostly prepared in the form of decoction and powdering. Informant consensus factor (Fic) results revealed high consensus for gastrointestinal (0.81), mastitis (0.82), and dermatological infections (0.80). Curcuma longa ranked first with highest fidelity level (FL) value (66%) followed by Trachyspermum ammi that ranked second (58%). Preference ranking (PR) results showed that Zingiber officinale, Punica granatum, Triticum aestivum, Gossypium hirsutum, and Withania coagulans were the most preferred species for the treatment of diarrhea. Direct matrix ranking (DMR) results showed that Morus alba, Melia azedarach, Withania coagulans, Cassia fistula, Azadirachta indica, and Tamarix aphylla were the multipurpose species of the region. We invite the attention of pharmacologists and chemists for further exploration of plants having high Fic, FL, and PR values in the present study. Conservation strategies should be adopted for the protection of multipurpose plant species. Sakina Mussarat, Rahila Amber, Akash Tariq, Muhammad Adnan, Naser M. AbdElsalam, Riaz Ullah, and Roqaia Bibi Copyright © 2014 Sakina Mussarat et al. All rights reserved. Final Gleason Score Prediction Using Discriminant Analysis and Support Vector Machine Based on Preoperative Multiparametric MR Imaging of Prostate Cancer at 3T Tue, 02 Dec 2014 10:38:21 +0000 Objective. This study aimed at evaluating linear discriminant analysis (LDA) and support vector machine (SVM) classifiers for estimating final Gleason score preoperatively using multiparametric magnetic resonance imaging (mp-MRI) and clinical parameters. Materials and Methods. Thirty-three patients who underwent mp-MRI on a 3T clinical MR scanner and radical prostatectomy were enrolled in this study. The input features for classifiers were age, the presence of a palpable prostate abnormality, prostate specific antigen (PSA) level, index lesion size, and Likert scales of T2 weighted MRI (T2w-MRI), diffusion weighted MRI (DW-MRI), and dynamic contrast enhanced MRI (DCE-MRI) estimated by an experienced radiologist. SVM based recursive feature elimination (SVM-RFE) was used for eliminating features. Principal component analysis (PCA) was applied for data uncorrelation. Results. Using a standard PCA before final Gleason score classification resulted in mean sensitivities of 51.19% and 64.37% and mean specificities of 72.71% and 39.90% for LDA and SVM, respectively. Using a Gaussian kernel PCA resulted in mean sensitivities of 86.51% and 87.88% and mean specificities of 63.99% and 56.83% for LDA and SVM, respectively. Conclusion. SVM classifier resulted in a slightly higher sensitivity but a lower specificity than LDA method for final Gleason score prediction for prostate cancer for this limited patient population. Fusun Citak-Er, Metin Vural, Omer Acar, Tarik Esen, Aslihan Onay, and Esin Ozturk-Isik Copyright © 2014 Fusun Citak-Er et al. All rights reserved.