BioMed Research International The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Overexpression of NTRK1 Promotes Differentiation of Neural Stem Cells into Cholinergic Neurons Mon, 05 Oct 2015 14:23:05 +0000 Neurotrophic tyrosine kinase type 1 (NTRK1) plays critical roles in proliferation, differentiation, and survival of cholinergic neurons; however, it remains unknown whether enhanced expression of NTRK1 in neural stem cells (NSCs) can promote their differentiation into mature neurons. In this study, a plasmid encoding the rat NTRK1 gene was constructed and transfected into C17.2 mouse neural stem cells (NSCs). NTRK1 overexpression in C17.2 cells was confirmed by western blot. The NSCs overexpressing NTRK1 and the C17.2 NSCs transfected by an empty plasmid vector were treated with or without 100 ng/mL nerve growth factor (NGF) for 7 days. Expression of the cholinergic cell marker, choline acetyltransferase (ChAT), was detected by florescent immunocytochemistry (ICC). In the presence of NGF induction, the NSCs overexpressing NTRK1 differentiated into ChAT-immunopositive cells at 3-fold higher than the NSCs transfected by the plasmid vector (26% versus 9%, ). The data suggest that elevated NTRK1 expression increases differentiation of NSCs into cholinergic neurons under stimulation of NGF. The approach also represents an efficient strategy for generation of cholinergic neurons. Limin Wang, Feng He, Zhuoyuan Zhong, Ruiyan Lv, Songhua Xiao, and Zhonglin Liu Copyright © 2015 Limin Wang et al. All rights reserved. Anti-Inflammatory and Anticancer Activities of Taiwanese Purple-Fleshed Sweet Potatoes (Ipomoea batatas L. Lam) Extracts Mon, 05 Oct 2015 14:11:02 +0000 Purple-fleshed sweet potato (PFSP) (Ipomoea batatas L. Lam) has been known to possess high amount of anthocyanins which contribute to its antioxidant activity. However, a few reports are available concerning its anti-inflammatory and anticancer properties. In this study, PFSP “Tainung 73,” which is locally grown in Taiwan, was steamed and extracted using acidified ethanol pH 3.5 under 80°C. Two kinds of crude anthocyanins extracts were obtained, namely, SP (Steamed, Peeled) and SNP (Steamed, No Peeled). Then, anti-inflammatory and anticancer activities of these extracts were investigated. Cell viability assay (MTT) showed that SP and SNP extracts were not toxic to RAW 264.7 cells. They even exhibited anti-inflammatory activities by suppressing the production of NO and proinflammatory cytokines, such as NF-κβ, TNF-α, and IL-6, in LPS-induced macrophage cells. Anticancer activities of these extracts were displayed through their ability to inhibit the growth of cancer cell lines, such as MCF-7 (breast cancer), SNU-1 (gastric cancer), and WiDr (colon adenocarcinoma), in concentration- and time-dependent manner. Further studies also revealed that SP extracts could induce apoptosis in MCF-7 and SNU-1 cancer cells through extrinsic and intrinsic pathway. In the future, PSFP extracts may have potential to be applied in nutraceutical, pharmaceutical, and food industries. Marcelia Sugata, Chien-Yih Lin, and Yang-Chia Shih Copyright © 2015 Marcelia Sugata et al. All rights reserved. The Demographic and Clinical Characteristics of Ulcerative Colitis in a Northeast Brazilian Population Mon, 05 Oct 2015 13:14:20 +0000 Introduction. The purpose of this study was to describe the clinical and demographic characteristics of UC in Bahia, a Brazilian state, and to identify the variables associated with extensive colitis, steroid therapy, immunosuppression, and colectomy. Methods. In this cross-sectional study UC patients were interviewed, and additional information was collected from the medical records. Descriptive statistics and multivariate Poisson regression analysis were used. Results. This study included 267 individuals, the mean age of whom was 39.4 years at diagnosis. There was a predominance of females and left-side colitis. Extensive colitis was positively associated with male gender, diarrhea, weight loss, and a younger age at diagnosis. In contrast, active smoking and a family history of IBD were negatively associated with extensive colitis. Positive associations were observed between steroid therapy and diarrhea, weight loss, urban patients, extraintestinal manifestations (EIMs), and hospitalization. Younger age and weight loss at diagnosis, a family history of IBD, extensive colitis, EIMs, hospitalization, and steroid therapy were all positively associated with immunosuppression. In contrast, Caucasian individuals, smokers, patients with rectal bleeding, and rural patients areas were all observed to have a decreased likelihood of immunosuppression. Conclusions. Our results corroborate the association between higher prevalence of extensive colitis and younger age at diagnosis. An association between steroid therapy and clinical presentation at diagnosis was observed. The observation that white individuals and rural patients use less immunosuppressive drugs highlights the need to study the influence of environmental and genetic factors on the behavior of UC in this population. Bruno César da Silva, Andre Castro Lyra, Carlos Maurício Cardeal Mendes, Camila Paula Oliveira Ribeiro, Sonyara Rauedys Oliveira Lisboa, Mariana Tinoco Lordello de Souza, Renata Cavalcanti Portela, and Genoile Oliveira Santana Copyright © 2015 Bruno César da Silva et al. All rights reserved. Evidential Value That Exercise Improves BMI -Score in Overweight and Obese Children and Adolescents Mon, 05 Oct 2015 11:54:12 +0000 Background. Given the cardiovascular disease (CVD) related importance of understanding the true effects of exercise on adiposity in overweight and obese children and adolescents, this study examined whether there is evidential value to rule out excessive and inappropriate reporting of statistically significant results, a major problem in the published literature, with respect to exercise-induced improvements in BMI -score among overweight and obese children and adolescents. Methods. Using data from a previous meta-analysis of 10 published studies that included 835 overweight and obese children and adolescents, a novel, recently developed approach (-curve) was used to test for evidential value and rule out selective reporting of findings. Chi-squared tests () were used to test for statistical significance with alpha () values <0.05 considered statistically significant. Results. Six of 10 findings (60%) were statistically significant. Statistically significant right-skew to rule out selective reporting was found ( = 38.8, = 0.0001). Conversely, studies neither lacked evidential value ( = 6.8, = 0.87) nor lacked evidential value and were intensely -hacked ( = 4.3, = 0.98). Conclusion. Evidential value results confirm that exercise reduces BMI -score in overweight and obese children and adolescents, an important therapeutic strategy for treating and preventing CVD. George A. Kelley and Kristi S. Kelley Copyright © 2015 George A. Kelley and Kristi S. Kelley. All rights reserved. Fabrication of an Amperometric Flow-Injection Microfluidic Biosensor Based on Laccase for In Situ Determination of Phenolic Compounds Mon, 05 Oct 2015 09:54:11 +0000 We aim to develop an in situ microfluidic biosensor based on laccase from Trametes pubescens with flow-injection and amperometry as the transducer method. The enzyme was directly immobilized by potential step chronoamperometry, and the immobilization was studied using cyclic voltammetry and electrochemical impedance spectroscopy. The electrode response by amperometry was probed using ABTS and syringaldazine. A shift of interfacial electron transfer resistance and the electron transfer rate constant from 18.1 kΩ to 3.9 MΩ and 4.6 × 10−2 cm s−1 to 2.1 × 10−4 cm s−1, respectively, evidenced that laccase was immobilized on the electrode by the proposed method. We established the optimum operating conditions of temperature (55°C), pH (4.5), injection flow rate (200 µL min−1), and applied potential (0.4 V). Finally, the microfluidic biosensor showed better lower limit of detection (0.149 µM) and sensitivity (0.2341 nA µM−1) for ABTS than previous laccase-based biosensors and the in situ operation capacity. Juan C. Gonzalez-Rivera and Johann F. Osma Copyright © 2015 Juan C. Gonzalez-Rivera and Johann F. Osma. All rights reserved. Are Endothelial Progenitor Cells the Real Solution for Cardiovascular Diseases? Focus on Controversies and Perspectives Mon, 05 Oct 2015 09:42:42 +0000 Advanced knowledge in the field of stem cell biology and their ability to provide a cue for counteracting several diseases are leading numerous researchers to focus their attention on “regenerative medicine” as possible solutions for cardiovascular diseases (CVDs). However, the lack of consistent evidence in this arena has hampered the clinical application. The same condition affects the research on endothelial progenitor cells (EPCs), creating more confusion than comprehension. In this review, this aspect is discussed with particular emphasis. In particular, we describe biology and physiology of EPCs, outline their clinical relevance as both new predictive, diagnostic, and prognostic CVD biomarkers and therapeutic agents, discuss advantages, disadvantages, and conflicting data about their use as possible solutions for vascular impairment and clinical applications, and finally underline a very crucial aspect of EPCs “characterization and definition,” which seems to be the real cause of large heterogeneity existing in literature data on this topic. Carmela R. Balistreri, Silvio Buffa, Calogera Pisano, Domenico Lio, Giovanni Ruvolo, and Giuseppe Mazzesi Copyright © 2015 Carmela R. Balistreri et al. All rights reserved. Comparison of Different Strategies for Selection/Adaptation of Mixed Microbial Cultures Able to Ferment Crude Glycerol Derived from Second-Generation Biodiesel Mon, 05 Oct 2015 09:38:56 +0000 Objective of this study was the selection and adaptation of mixed microbial cultures (MMCs), able to ferment crude glycerol generated from animal fat-based biodiesel and produce building-blocks and green chemicals. Various adaptation strategies have been investigated for the enrichment of suitable and stable MMC, trying to overcome inhibition problems and enhance substrate degradation efficiency, as well as generation of soluble fermentation products. Repeated transfers in small batches and fed-batch conditions have been applied, comparing the use of different inoculum, growth media, and Kinetic Control. The adaptation of activated sludge inoculum was performed successfully and continued unhindered for several months. The best results showed a substrate degradation efficiency of almost 100% (about 10 g/L glycerol in 21 h) and different dominant metabolic products were obtained, depending on the selection strategy (mainly 1,3-propanediol, ethanol, or butyrate). On the other hand, anaerobic sludge exhibited inactivation after a few transfers. To circumvent this problem, fed-batch mode was used as an alternative adaptation strategy, which led to effective substrate degradation and high 1,3-propanediol and butyrate production. Changes in microbial composition were monitored by means of Next Generation Sequencing, revealing a dominance of glycerol consuming species, such as Clostridium, Klebsiella, and Escherichia. C. Varrone, T. M. B. Heggeset, S. B. Le, T. Haugen, S. Markussen, I. V. Skiadas, and H. N. Gavala Copyright © 2015 C. Varrone et al. All rights reserved. High 15-F2t-Isoprostane Levels in Patients with a Previous History of Nonmelanoma Skin Cancer: The Effects of Supplementary Antioxidant Therapy Mon, 05 Oct 2015 09:38:17 +0000 Background. Phase I of this study was aimed at comparing the profiles of oxidative stress biomarkers in patients with history of nonmelanoma skin cancer (NMSC), previously treated with surgery, to the healthy subjects. Phase II aimed to evaluate the effects of supplementary antioxidant therapy on the levels of biomarkers in the case group. Materials and Methods. In Phase I, oxidative stress biomarkers were measured in blood samples obtained from 24 healthy subjects and 60 patients with history of NMSC previously treated with surgery. In Phase II, the 60 patients with history of NMSC were randomized into two subgroups, one receiving placebo () and the other () receiving vitamin C, vitamin E, and zinc supplementation for 8 weeks, followed by reevaluation of biomarkers. Results. In Phase I, patients with history of NMSC showed increased plasma concentrations of all biomarkers, but only 15--isoprostane was significantly higher than in the healthy subjects. Risk of NMSC increased by 4% for each additional 1 pg/mL increase in 15--isoprostane. In Phase II, supplementation did not significantly reduce levels of oxidative stress biomarkers. Conclusion. Patients with history of NMSC had significantly high 15--isoprostane plasma levels; supplementation did not result in significant reduction of oxidative stress biomarkers. This trial was registered with (ID NCT02248584). Betânia de Jesus e Silva de Almendra Freitas, Gustavo Rafaini Lloret, Marília Berlofa Visacri, Bruna Taliani Tuan, Lais Sampaio Amaral, Daniele Baldini, Vanessa Marcílio de Sousa, Laís Lima de Castro, Jordana Rayane Sousa Aguiar, Eder de Carvalho Pincinato, Priscila Gava Mazzola, and Patricia Moriel Copyright © 2015 Betânia de Jesus e Silva de Almendra Freitas et al. All rights reserved. A Media and Clinic Intervention to Increase Colorectal Cancer Screening in Ohio Appalachia Mon, 05 Oct 2015 09:36:41 +0000 Objective. To test the effectiveness of a colorectal cancer (CRC) screening intervention among adults living in Ohio Appalachia. Methods. We conducted a group-randomized trial of a county-level intervention among adults living in 12 Ohio Appalachian counties who received a media campaign and clinic intervention focused on either CRC screening or fruits and vegetables. Participants’ percentage within CRC screening guidelines was assessed with cross-sectional surveys conducted annually for four years, and validated with medical record review of screening. Results. On average, screening data were obtained on 564 intervention and 559 comparison participants per year. There was no difference in the Wave 4 CRC screening rates of intervention and comparison counties (35.2% versus 31.4%). Multivariate analyses found that high perceived risk of CRC, willingness to have a CRC test if recommended by a doctor, doctor recommendation of a CRC screening test, and patient-physician communication about changes in bowel habits, family history of CRC, and eating fruits and vegetables were significant () predictors of being within CRC screening guidelines. Conclusions. The intervention was not effective in increasing CRC rates among Ohio Appalachian adults. Future research should determine how media and clinic-based interventions can be modified to improve CRC screening rates among this underserved population. Jessica L. Krok-Schoen, Mira L. Katz, Jill M. Oliveri, Gregory S. Young, Michael L. Pennell, Paul L. Reiter, Jesse J. Plascak, Michael D. Slater, Janice L. Krieger, Cathy M. Tatum, and Electra D. Paskett Copyright © 2015 Jessica L. Krok-Schoen et al. All rights reserved. Macrophage-Targeting Gene Delivery Using a Micelle Composed of Mannose-Modified Lipid with Triazole Ring and Dioleoyl Trimethylammonium Propane Mon, 05 Oct 2015 09:35:15 +0000 Gene carriers with cell specific ligand molecules are needed for the treatment of several diseases. Mannose is known to be recognized and incorporated into the cells through mannose recognition lectins that are exclusively expressed on macrophages. In this study, we synthesized two types of mannose-modified lipids with different stereoisomer (α-mannose and β-mannose). To make a complex with plasmid DNA (pDNA), termed “lipoplex,” we prepared a two-component micelle made from cationic lipid; dioleoyltrimethylammoniumpropane (DOTAP); and mannose-modified lipid (D/α-Man or D/β-Man). The prepared D/α-Man lipoplexes were able to bind to one of the α-mannose lectins concanavalin A (ConA) immobilized on gold substrate in the quartz-crystal microbalance sensor cell. D/β-Man lipoplexes did not show any frequency changes. These results indicate that the mannose residues were exposed on the lipoplexes, leading to not only the binding to ConA but also the prevention of nonspecific interactions with proteins. Both lipoplexes showed high transfection efficiencies to RAW264.7 cells which have several kinds of mannose lectins. This delivery system to macrophages may overcome the problems for gene therapy and may be used for the treatment of immune diseases involved in macrophages. Ichiki Fukuda, Shinichi Mochizuki, and Kazuo Sakurai Copyright © 2015 Ichiki Fukuda et al. All rights reserved. A Current View of Functional Biomaterials for Wound Care, Molecular and Cellular Therapies Mon, 05 Oct 2015 08:38:15 +0000 The intricate process of wound healing involves activation of biological pathways that work in concert to regenerate a tissue microenvironment consisting of cells and external cellular matrix (ECM) with enzymes, cytokines, and growth factors. Distinct stages characterize the mammalian response to tissue injury: hemostasis, inflammation, new tissue formation, and tissue remodeling. Hemostasis and inflammation start right after the injury, while the formation of new tissue, along with migration and proliferation of cells within the wound site, occurs during the first week to ten days after the injury. In this review paper, we discuss approaches in tissue engineering and regenerative medicine to address each of these processes through the application of biomaterials, either as support to the native microenvironment or as delivery vehicles for functional hemostatic, antibacterial, or anti-inflammatory agents. Molecular therapies are also discussed with particular attention to drug delivery methods and gene therapies. Finally, cellular treatments are reviewed, and an outlook on the future of drug delivery and wound care biomaterials is provided. Francesco Piraino and Šeila Selimović Copyright © 2015 Francesco Piraino and Šeila Selimović. All rights reserved. Comparison of Pressure Changes by Head and Neck Position between High-Volume Low-Pressure and Taper-Shaped Cuffs: A Randomized Controlled Trial Mon, 05 Oct 2015 08:34:32 +0000 The present study compared changes in cuff pressure by head and neck position between high-volume low-pressure (HVLP) and taper-shaped (taper) cuffs in a prospective randomized clinical trial. Methods. Forty patients were intubated using tracheal tubes with either HVLP (; HVLP group) or taper-shaped (; Taper group) cuffs. Initial cuff pressure was adjusted to 15, 20, or 25 cmH2O in the neutral position. Cuff pressure was evaluated after changing the head and neck positions to flexion, extension, and rotation. Results. Cuff pressure significantly increased with flexion in both HVLP and Taper groups at all initial cuff pressures. It significantly increased with extension in the HVLP group, but not in the Taper group. Cuff pressure did not significantly differ with rotation in either group and was significantly smaller in the Taper group during flexion and extension than in the HVLP group, regardless of initial cuff pressure. Conclusion. Cuff pressure changes with head and neck flexion and extension were smaller in the Taper group than in the HVLP group. Our results highlight the potential for taper cuffs to prevent excessive cuff pressure increases with positional changes in the head and neck. This trial is registered with UMIN000016119. Nobuyasu Komasawa, Ryosuke Mihara, Kentaro Imagawa, Kazuo Hattori, and Toshiaki Minami Copyright © 2015 Nobuyasu Komasawa et al. All rights reserved. Biological Niches within Human Calcified Aortic Valves: Towards Understanding of the Pathological Biomineralization Process Mon, 05 Oct 2015 08:33:04 +0000 Despite recent advances, mineralization site, its microarchitecture, and composition in calcific heart valve remain poorly understood. A multiscale investigation, using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy dispersive X-ray spectrometry (EDS), from micrometre up to nanometre, was conducted on human severely calcified aortic and mitral valves, to provide new insights into calcification process. Our aim was to evaluate the spatial relationship existing between bioapatite crystals, their local growing microenvironment, and the presence of a hierarchical architecture. Here we detected the presence of bioapatite crystals in two different mineralization sites that suggest the action of two different growth processes: a pathological crystallization process that occurs in biological niches and is ascribed to a purely physicochemical process and a matrix-mediated mineralized process in which the extracellular matrix acts as the template for a site-directed nanocrystals nucleation. Different shapes of bioapatite crystallization were observed at micrometer scale in each microenvironment but at the nanoscale level crystals appear to be made up by the same subunits. Valentina Cottignoli, Michela Relucenti, Giovanna Agrosì, Elena Cavarretta, Giuseppe Familiari, Loris Salvador, and Adriana Maras Copyright © 2015 Valentina Cottignoli et al. All rights reserved. Biologic Agents for Periodontal Regeneration and Implant Site Development Mon, 05 Oct 2015 08:27:39 +0000 The advancement of molecular mediators or biologic agents has increased tremendously during the last decade in periodontology and dental implantology. Implant site development and reconstruction of the lost periodontium represent main fields in which these molecular mediators have been employed and investigated. Different growth factors trigger different reactions in the tissues of the periodontium at various cellular levels. Proliferation, migration, and differentiation constitute the main target areas of these molecular mediators. It was the purpose of this comprehensive review to describe the origin and rationale, evidence, and the most current understanding of the following biologic agents: Recombinant Human Platelet-Derived Growth Factor-BB (rhPDGF-BB), Enamel Matrix Derivate (EMD), Platelet-Rich Plasma (PRP) and Platelet-Rich Fibrin (PRF), Recombinant Human Fibroblast Growth Factor-2 (rhFGF-2), Bone Morphogenic Proteins (BMPs, BMP-2 and BMP-7), Teriparatide PTH, and Growth Differential Factor-5 (GDF-5). Fernando Suárez-López del Amo, Alberto Monje, Miguel Padial-Molina, ZhiHui Tang, and Hom-Lay Wang Copyright © 2015 Fernando Suárez-López del Amo et al. All rights reserved. Bone Regeneration from PLGA Micro-Nanoparticles Mon, 05 Oct 2015 08:23:55 +0000 Poly-lactic-co-glycolic acid (PLGA) is one of the most widely used synthetic polymers for development of delivery systems for drugs and therapeutic biomolecules and as component of tissue engineering applications. Its properties and versatility allow it to be a reference polymer in manufacturing of nano- and microparticles to encapsulate and deliver a wide variety of hydrophobic and hydrophilic molecules. It additionally facilitates and extends its use to encapsulate biomolecules such as proteins or nucleic acids that can be released in a controlled way. This review focuses on the use of nano/microparticles of PLGA as a delivery system of one of the most commonly used growth factors in bone tissue engineering, the bone morphogenetic protein 2 (BMP2). Thus, all the needed requirements to reach a controlled delivery of BMP2 using PLGA particles as a main component have been examined. The problems and solutions for the adequate development of this system with a great potential in cell differentiation and proliferation processes under a bone regenerative point of view are discussed. Inmaculada Ortega-Oller, Miguel Padial-Molina, Pablo Galindo-Moreno, Francisco O’Valle, Ana Belén Jódar-Reyes, and Jose Manuel Peula-García Copyright © 2015 Inmaculada Ortega-Oller et al. All rights reserved. Identification of Human Herpesvirus 8 Sequences in Conjunctiva Intraepithelial Neoplasia and Squamous Cell Carcinoma of Ugandan Patients Mon, 05 Oct 2015 08:18:16 +0000 The incidence of squamous cell carcinoma of the conjunctiva is particularly high in sub-Saharan Africa with temporal trends similar to those of Kaposi sarcoma (KS). Human herpesvirus type 8 (HHV8), has not yet been investigated in conjunctiva tumors. In this study biopsies and PBMCs of conjunctiva neoplasia patients along with nonneoplastic conjunctiva tissues have been analyzed for HHV8 sequences by PCR targeting ORF26. All amplimers were subjected to nucleotide sequencing followed by phylogenetic analysis. HHV8 DNA has been identified in 12 out of 48 (25%) HIV-positive, and in 2 out of 24 (8.3%) HIV-negative conjunctiva neoplastic tissues and in 4 out of 33 (12.1%) PBMC samples from conjunctiva neoplasia diseased patients as well as in 4 out of 60 (6.7%) nontumor conjunctiva tissues. The viral load ranged from 1 to 400 copies/105 cells. Phylogenetic analysis showed that the majority of HHV8 ORF26 amplimers clustered with subtypes R () and B2 (). This variant distribution is in agreement with that of HHV8 variants previously identified in Ugandan KS cases. The presence of HHV8 in conjunctiva tumors from HIV-positive patients warrants further studies to test whether HHV8 products released by infected cells may have paracrine effects on the growth of conjunctiva lesions. Noemy Starita, Clorinda Annunziata, Keith M. Waddell, Luigi Buonaguro, Franco M. Buonaguro, and Maria Lina Tornesello Copyright © 2015 Noemy Starita et al. All rights reserved. Perspective for Aquaponic Systems: “Omic” Technologies for Microbial Community Analysis Mon, 05 Oct 2015 08:15:48 +0000 Aquaponics is the combined production of aquaculture and hydroponics, connected by a water recirculation system. In this productive system, the microbial community is responsible for carrying out the nutrient dynamics between the components. The nutrimental transformations mainly consist in the transformation of chemical species from toxic compounds into available nutrients. In this particular field, the microbial research, the “Omic” technologies will allow a broader scope of studies about a current microbial profile inside aquaponics community, even in those species that currently are unculturable. This approach can also be useful to understand complex interactions of living components in the system. Until now, the analog studies were made to set up the microbial characterization on recirculation aquaculture systems (RAS). However, microbial community composition of aquaponics is still unknown. “Omic” technologies like metagenomic can help to reveal taxonomic diversity. The perspectives are also to begin the first attempts to sketch the functional diversity inside aquaponic systems and its ecological relationships. The knowledge of the emergent properties inside the microbial community, as well as the understanding of the biosynthesis pathways, can derive in future biotechnological applications. Thus, the aim of this review is to show potential applications of current “Omic” tools to characterize the microbial community in aquaponic systems. Perla Munguia-Fragozo, Oscar Alatorre-Jacome, Enrique Rico-Garcia, Irineo Torres-Pacheco, Andres Cruz-Hernandez, Rosalia V. Ocampo-Velazquez, Juan F. Garcia-Trejo, and Ramon G. Guevara-Gonzalez Copyright © 2015 Perla Munguia-Fragozo et al. All rights reserved. Pathologic Assessment of Rectal Carcinoma after Neoadjuvant Radio(chemo)therapy: Prognostic Implications Mon, 05 Oct 2015 08:10:42 +0000 Neoadjuvant radio(chemo)therapy is increasingly used in rectal cancer and induces a number of morphologic changes that affect prognostication after curative surgery, thereby creating new challenges for surgical pathologists, particularly in evaluating morphologic changes and tumour response to preoperative treatment. Surgical pathologists play an important role in determining the many facets of rectal carcinoma patient care after neoadjuvant treatment. These range from proper handling of macroscopic specimens to accurate microscopic evaluation of pathological features associated with patients’ prognosis. This review presents the well-established pathological prognostic indicators and discusses challenging features in order to provide both surgical pathologists and treating physicians with a checklist that is useful in a neoadjuvant setting. Monirath Hav, Louis Libbrecht, Liesbeth Ferdinande, Karen Geboes, Piet Pattyn, and Claude A. Cuvelier Copyright © 2015 Monirath Hav et al. All rights reserved. Angiotensinase C mRNA and Protein Downregulations Are Involved in Ethanol-Deteriorated Left Ventricular Systolic Dysfunction in Spontaneously Hypertensive Rats Mon, 05 Oct 2015 08:04:20 +0000 The influences of angiotensinase C on ethanol-induced left ventricular (LV) systolic function were assessed in spontaneously hypertensive rats (SHRs). SHRs were fed by a liquid diet with or without ethanol for 49 days. The normotensive Wistar Kyoto rats (WKY) were fed by the liquid diet without ethanol and used as control. We evaluated LV systolic function, angiotensinase C mRNA and protein expressions, activation of the renin-angiotensin system (RAS), and the gene expressions of LV collagen (Col) III a1 and matrix metalloproteinases- (MMP-) 9. Compared to the WKY, LV systolic dysfunction (expressed by decreased fractional shortening and ejection fraction) was observed in the SHRs before ethanol treatment and further deteriorated by ethanol treatment. In the ethanol-treated SHRs, the following were observed: downregulations of angiotensinase C mRNA and protein, increased RAS activity with low collagen production as evidenced by angiotensin II and angiotensin type 1 receptor (AT1R) protein upregulation, R mRNA downregulation, and an MMP-9 mRNA expression upregulation trend with the downregulation of Col III a1 mRNA expression in LV. We conclude that chronic ethanol regimen is sufficient to promote the enhanced RAS activity-induced decrease in the production of cardiac collagen via downregulated angiotensinase C, leading to the further deterioration of LV systolic dysfunction in SHRs. Jinyao Liu, Ayako Hakucho, and Tatsuya Fujimiya Copyright © 2015 Jinyao Liu et al. All rights reserved. Effects of P-15 Peptide Coated Hydroxyapatite on Tibial Defect Repair In Vivo in Normal and Osteoporotic Rats Mon, 05 Oct 2015 08:02:03 +0000 This study assessed the efficacy of anorganic bone mineral coated with P-15 peptide (ABM/P-15) on tibia defect repair longitudinally in both normal and osteoporotic rats in vivo. A paired design was used. 24 Norwegian brown rats were divided into normal and osteoporotic groups. 48 cylindrical defects were created in proximal tibias bilaterally. Defects were filled with ABM/P-15 or left empty. Osteoporotic status was assessed by microarchitectural analysis. Microarchitectural properties of proximal tibial defects were evaluated at 4 time points. 21 days after surgery, tibias were harvested for histology and histomorphometry. Significantly increased bone volume fraction, surface density, and connectivity were seen in all groups at days 14 and 21 compared with day 0. Moreover, the structure type of ABM/P-15 group was changed toward typical plate-like structure. Microarchitectural properties of ABM/P-15 treated newly formed bones at 21 days were similar in normal and osteoporotic rats. Histologically, significant bone formation was seen in all groups. Interestingly, significantly increased bone formation was seen in osteoporotic rats treated with ABM/P-15 indicating optimized healing potential. Empty defects showed lower healing potential in osteoporotic bone. In conclusion, ABM/P-15 accelerated bone regeneration in osteoporotic rats but did not enhance bone regeneration in normal rats. Rasmus Hestehave Pedersen, Marina Rasmussen, Søren Overgaard, and Ming Ding Copyright © 2015 Rasmus Hestehave Pedersen et al. All rights reserved. Diagnostic Options and Challenges for Dengue and Chikungunya Viruses Mon, 05 Oct 2015 07:59:30 +0000 Dengue virus (DENV) and Chikungunya virus (CHIKV) are arboviruses that share the same Aedes mosquito vectors and thus overlap in their endemic areas. These two viruses also cause similar clinical presentations, especially in the initial stages of infection, with neither virus possessing any specific distinguishing clinical features. Because the outcomes and management strategies for these two viruses are vastly different, early and accurate diagnosis is imperative. Diagnosis is also important for surveillance, outbreak control, and research related to vaccine and drug development. Available diagnostic tests are aimed at detection of the virus, its antigenic components, or the host immune antibody response. In this review, we describe the recent progress and continued challenges related to the diagnosis of DENV and CHIKV infections. Stacey K. Mardekian and Amity L. Roberts Copyright © 2015 Stacey K. Mardekian and Amity L. Roberts. All rights reserved. Naturally Occurring Extracellular Matrix Scaffolds for Dermal Regeneration: Do They Really Need Cells? Mon, 05 Oct 2015 07:55:49 +0000 The pronounced effect of extracellular matrix (ECM) scaffolds in supporting tissue regeneration is related mainly to their maintained 3D structure and their bioactive components. These decellularized matrix scaffolds could be revitalized before grafting via adding stem cells, fibroblasts, or keratinocytes to promote wound healing. We reviewed the online published literature in the last five years for the studies that performed ECM revitalization and discussed the results of these studies and the related literature. Eighteen articles met the search criteria. Twelve studies included adding cells to acellular dermal matrix (ADM), 3 studies were on small intestinal mucosa (SIS), one study was on urinary bladder matrix (UBM), one study was on amniotic membrane, and one study included both SIS and ADM loaded constructs. We believe that, in chronic and difficult-to-heal wounds, revitalizing the ECM scaffolds would be beneficial to overcome the defective host tissue interaction. This belief still has to be verified by high quality randomised clinical trials, which are still lacking in literature. A. M. Eweida and M. K. Marei Copyright © 2015 A. M. Eweida and M. K. Marei. All rights reserved. Shear Stress Induces Differentiation of Endothelial Lineage Cells to Protect Neonatal Brain from Hypoxic-Ischemic Injury through NRP1 and VEGFR2 Signaling Mon, 05 Oct 2015 07:45:17 +0000 Neonatal hypoxic-ischemic (HI) brain injuries disrupt the integrity of neurovascular structure and lead to lifelong neurological deficit. The devastating damage can be ameliorated by preserving the endothelial network, but the source for therapeutic cells is limited. We aim to evaluate the beneficial effect of mechanical shear stress in the differentiation of endothelial lineage cells (ELCs) from adipose-derived stem cells (ASCs) and the possible intracellular signals to protect HI injury using cell-based therapy in the neonatal rats. The ASCs expressed early endothelial markers after biochemical stimulation of endothelial growth medium. The ELCs with full endothelial characteristics were accomplished after a subsequential shear stress application for 24 hours. When comparing the therapeutic potential of ASCs and ELCs, the ELCs treatment significantly reduced the infarction area and preserved neurovascular architecture in HI injured brain. The transplanted ELCs can migrate and engraft into the brain tissue, especially in vessels, where they promoted the angiogenesis. The activation of Akt by neuropilin 1 (NRP1) and vascular endothelial growth factor receptor 2 (VEGFR2) was important for ELC migration and following in vivo therapeutic outcomes. Therefore, the current study demonstrated importance of mechanical factor in stem cell differentiation and showed promising protection of brain from HI injury using ELCs treatment. Chia-Wei Huang, Chao-Ching Huang, Yuh-Ling Chen, Shih-Chen Fan, Yuan-Yu Hsueh, Chien-Jung Ho, and Chia-Ching Wu Copyright © 2015 Chia-Wei Huang et al. All rights reserved. Comment on “The Role of Overweight and Obesity in In Vitro Fertilization Outcomes of Poor Ovarian Responders” Mon, 05 Oct 2015 07:32:37 +0000 Raoul Orvieto Copyright © 2015 Raoul Orvieto. All rights reserved. Molecular Characterization of Reactive Oxygen Species in Myocardial Ischemia-Reperfusion Injury Mon, 05 Oct 2015 07:25:14 +0000 Myocardial ischemia-reperfusion (I/R) injury is experienced by individuals suffering from cardiovascular diseases such as coronary heart diseases and subsequently undergoing reperfusion treatments in order to manage the conditions. The occlusion of blood flow to the tissue, termed ischemia, can be especially detrimental to the heart due to its high energy demand. Several cellular alterations have been observed upon the onset of ischemia. The danger created by cardiac ischemia is somewhat paradoxical in that a return of blood to the tissue can result in further damage. Reactive oxygen species (ROS) have been studied intensively to reveal their role in myocardial I/R injury. Under normal conditions, ROS function as a mediator in many cell signaling pathways. However, stressful environments significantly induce the generation of ROS which causes the level to exceed body’s antioxidant defense system. Such altered redox homeostasis is implicated in myocardial I/R injury. Despite the detrimental effects from ROS, low levels of ROS have been shown to exert a protective effect in the ischemic preconditioning. In this review, we will summarize the detrimental role of ROS in myocardial I/R injury, the protective mechanism induced by ROS, and potential treatments for ROS-related myocardial injury. Tingyang Zhou, Chia-Chen Chuang, and Li Zuo Copyright © 2015 Tingyang Zhou et al. All rights reserved. CT Perfusion Characteristics Identify Metastatic Sites in Liver Mon, 05 Oct 2015 07:23:23 +0000 Tissue perfusion plays a critical role in oncology because growth and migration of cancerous cells require proliferation of new blood vessels through the process of tumor angiogenesis. Computed tomography (CT) perfusion is an emerging functional imaging modality that measures tissue perfusion through dynamic CT scanning following intravenous administration of contrast medium. This noninvasive technique provides a quantitative basis for assessing tumor angiogenesis. CT perfusion has been utilized on a variety of organs including lung, prostate, liver, and brain, with promising results in cancer diagnosis, disease prognostication, prediction, and treatment monitoring. In this paper, we focus on assessing the extent to which CT perfusion characteristics can be used to discriminate liver metastases from neuroendocrine tumors from normal liver tissues. The neuroendocrine liver metastases were analyzed by distributed parameter modeling to yield tissue blood flow (BF), blood volume (BV), mean transit time (MTT), permeability (PS), and hepatic arterial fraction (HAF), for tumor and normal liver. The result reveals the potential of CT perfusion as a tool for constructing biomarkers from features of the hepatic vasculature for guiding cancer detection, prognostication, and treatment selection. Yuan Wang, Brian P. Hobbs, and Chaan S. Ng Copyright © 2015 Yuan Wang et al. All rights reserved. Glycosylation-Based Serum Biomarkers for Cancer Diagnostics and Prognostics Mon, 05 Oct 2015 07:18:43 +0000 Cancer is the second most common cause of death in developed countries with approximately 14 million newly diagnosed individuals and over 6 million cancer-related deaths in 2012. Many cancers are discovered at a more advanced stage but better survival rates are correlated with earlier detection. Current clinically approved cancer biomarkers are most effective when applied to patients with widespread cancer. Single biomarkers with satisfactory sensitivity and specificity have not been identified for the most common cancers and some biomarkers are ineffective for the detection of early stage cancers. Thus, novel biomarkers with better diagnostic and prognostic performance are required. Aberrant protein glycosylation is well known hallmark of cancer and represents a promising source of potential biomarkers. Glycoproteins enter circulation from tissues or blood cells through active secretion or leakage and patient serum is an attractive option as a source for biomarkers from a clinical and diagnostic perspective. A plethora of technical approaches have been developed to address the challenges of glycosylation structure detection and determination. This review summarises currently utilised glycoprotein biomarkers and novel glycosylation-based biomarkers from the serum glycoproteome under investigation as cancer diagnostics and for monitoring and prognostics and includes details of recent high throughput and other emerging glycoanalytical techniques. Alan Kirwan, Marta Utratna, Michael E. O’Dwyer, Lokesh Joshi, and Michelle Kilcoyne Copyright © 2015 Alan Kirwan et al. All rights reserved. A Review of Computational Methods to Predict the Risk of Rupture of Abdominal Aortic Aneurysms Mon, 05 Oct 2015 07:15:51 +0000 Computational methods have played an important role in health care in recent years, as determining parameters that affect a certain medical condition is not possible in experimental conditions in many cases. Computational fluid dynamics (CFD) methods have been used to accurately determine the nature of blood flow in the cardiovascular and nervous systems and air flow in the respiratory system, thereby giving the surgeon a diagnostic tool to plan treatment accordingly. Machine learning or data mining (MLD) methods are currently used to develop models that learn from retrospective data to make a prediction regarding factors affecting the progression of a disease. These models have also been successful in incorporating factors such as patient history and occupation. MLD models can be used as a predictive tool to determine rupture potential in patients with abdominal aortic aneurysms (AAA) along with CFD-based prediction of parameters like wall shear stress and pressure distributions. A combination of these computer methods can be pivotal in bridging the gap between translational and outcomes research in medicine. This paper reviews the use of computational methods in the diagnosis and treatment of AAA. Tejas Canchi, S. D. Kumar, E. Y. K. Ng, and Sriram Narayanan Copyright © 2015 Tejas Canchi et al. All rights reserved. Custom-Made Antibiotic Cement Nails in Orthopaedic Trauma: Review of Outcomes, New Approaches, and Perspectives Mon, 05 Oct 2015 07:12:44 +0000 Since the first description in 2002 by Paley and Herzenberg, antibiotic bone cement nails (ACNs) have become an effective tool in the orthopaedic trauma surgeons’ hands. They simultaneously elute high amounts of antibiotics into medullary canal dead space and provide limited stability to the debrided long bone. In this paper, we perform a systematic review of current evidence on ACNs in orthopaedic trauma and provide an up-to-date review of the indications, operative technique, failure mechanisms, complications, outcomes, and outlooks for the ACNs use in long bone infection. Marcin K. Wasko and Rafal Kaminski Copyright © 2015 Marcin K. Wasko and Rafal Kaminski. All rights reserved. Twelve-Month Results of a Single or Multiple Dexamethasone Intravitreal Implant for Macular Edema following Uncomplicated Phacoemulsification Mon, 05 Oct 2015 07:10:16 +0000 The clinical efficacy of one or two intravitreal injections of a continued deliverance dexamethasone 700 μg implant in ten patients with persistent macular edema following uncomplicated phacoemulsification was evaluated. Complete ophthalmological examination and spectral domain optical coherence tomography were carried out. Follow-up was at day 7 and months 1, 2, 4, 6, 8, and 12. At baseline mean best corrected visual acuity was 62 Early Treatment Diabetic Retinopathy Study Chart letters, which showed statistically significant improvement at each follow-up, except at month 6, to reach 79 letters at month 12 (). Prior to treatment mean central foveal thickness was 622 μm, which showed statistically significant improvement at each follow-up to reach a mean value of 282 μm () at month 12. Five patients received a second dexamethasone implant at month 7. Two patients were excluded from the study at months 4 and 8. Intraocular pressure remained stable during the study period with the exception of mild increase in two patients requiring topical therapy. In conclusion there was statistically significant improvement of best corrected visual acuity and mean central foveal thickness with one or two intravitreal dexamethasone implants over 12 months. Solmaz Abdolrahimzadeh, Vito Fenicia, Maurizio Maurizi Enrici, Pasquale Plateroti, Dora Cianfrone, and Santi Maria Recupero Copyright © 2015 Solmaz Abdolrahimzadeh et al. All rights reserved.