bluuebunny/crossref_metadata_2025 huggingface dataset:
The Identification and Differentiation between Burkholderia mallei and Burkholderia pseudomallei Using One Gene Pyrosequencing
Authors: Gilling Damian H. , Luna Vicki Ann , Pflugradt Cori
Published: October 2014

The etiologic agents for melioidosis and glanders, Burkholderia mallei and Burkholderia pseudomallei respectively, are genetically similar making identification and differentiation from other Burkholderia species and each other challenging. We used pyrosequencing to determine the presence or absence of an insertion sequence IS407A within the flagellin P (fliP) gene and to exploit the difference in orientation of this gene in the two species. Oligonucleotide primers were designed to selectively target the IS407A-fliP interface in B. mallei and the fliP gene specifically at the insertion point in B. pseudomallei. We then examined DNA from ten B. mallei, ten B. pseudomallei, 14 B. cepacia, eight other Burkholderia spp., and 17 other bacteria. Resultant pyrograms encompassed the target sequence that contained either the fliP gene with the IS407A interruption or the fully intact fliP gene with 100% sensitivity and 100% specificity. These pyrosequencing assays based upon a single gene enable investigators to reliably identify the two species. The information obtained by these assays provides more knowledge of the genomic reduction that created the new species B. mallei from B. pseudomallei and may point to new targets that can be exploited in the future.
Natural Remedies for the Treatment of Beta-Thalassemia and Sickle Cell Anemia—Current Status and Perspectives in Fetal Hemoglobin Reactivation
Authors: Ng Noel Yat Hey , Ko Chun Hay
Published: October 2014

For the treatment of β-thalassemia and sickle cell disease (SCD), pharmacological induction of fetal hemoglobin (HbF) production may be a promising approach. To date, numerous studies have been done on identifying the novel HbF-inducing agents and understanding the underlying mechanism for stimulating the HbF production. In this review, we have summarized the identified HbF-inducing agents by far. By examining the action mechanisms of the HbF-inducing agents, various studies have suggested that despite the ability of stimulating HbF production, the chemotherapeutic agents could not be practically applied for treating β-hemoglobinopathies, especially β-thalassemia, due to the their cytotoxicity and growth-inhibitory effect. Owing to this therapeutic obstacle, much effort has been put on identifying new HbF-inducing agents from the natural world with the combination of efficacy, safety, and ease of use. Therefore, this review aims to (i) reveal the novel screening platforms for identifying potential inducers with high efficiency and accuracy and to (ii) summarize the new identified natural remedies for stimulating HbF production. Hopefully, this review can provide a new insight into the current status and future perspectives in fetal hemoglobin reactivation for treating β-thalassaemia and SCD.
Plant-Mediated Green Synthesis of Iron Nanoparticles
Authors: Herlekar Mihir , Barve Siddhivinayak , Kumar Rakesh
Published: October 2014

In the recent years, nanotechnology has emerged as a state-of-the-art and cutting edge technology with multifarious applications in a wide array of fields. It is a very broad area comprising of nanomaterials, nanotools, and nanodevices. Amongst nanomaterials, majority of the research has mainly focused on nanoparticles as they can be easily prepared and manipulated. Physical and chemical methods are conventionally used for the synthesis of nanoparticles; however, due to several limitations of these methods, research focus has recently shifted towards the development of clean and eco-friendly synthesis protocols. Magnetic nanoparticles constitute an important class of inorganic nanoparticles, which find applications in different areas by virtue of their several unique properties. Nevertheless, in comparison with biological synthesis protocols for noble metal nanoparticles, limited study has been carried out with respect to biological synthesis of magnetic nanoparticles. This review focuses on various studies outlining the novel routes for biosynthesis of these nanoparticles by plant resources along with outlining the future scope of work in this area.
GPCRs: Lipid-Dependent Membrane Receptors That Act as Drug Targets
Authors: Chattopadhyay Amitabha
Published: October 2014

G protein-coupled receptors (GPCRs) are the largest class of molecules involved in signal transduction across cell membranes and represent major targets in the development of novel drug candidates in all clinical areas. Although there have been some recent leads, structural information on GPCRs is relatively rare due to the difficulty associated with crystallization. A specific reason for this is the intrinsic flexibility displayed by GPCRs, which is necessary for their functional diversity. Since GPCRs are integral membrane proteins, interaction of membrane lipids with them constitutes an important area of research in GPCR biology. In particular, membrane cholesterol has been reported to have a modulatory role in the function of a number of GPCRs. The role of membrane cholesterol in GPCR function is discussed with specific example of theserotonin1Areceptor. Recent results show that GPCRs are characterized with structural motifs that preferentially associate with cholesterol. An emerging and important concept is oligomerization of GPCRs and its role in GPCR function and signaling. The role of membrane cholesterol in GPCR oligomerization is highlighted. Future research in GPCR biology would offer novel insight in basic biology and provide new avenues for drug discovery.
Photodynamic Therapy in Pediatric Dentistry
Authors: da Silva Barbosa Patricia , Duarte Danilo Antônio , Leite Mariana Ferreira , de Sant’ Anna Giselle Rodrigues
Published: October 2014

Conservation of deciduous teeth with pulp alterations caused by caries and trauma is a major therapeutic challenge in pediatric dentistry as a result of the internal anatomy and life cycle characteristic. It is essential that the root canal procedures sanitizers have a performance in eliminating bacterial. In this context, antimicrobial photodynamic therapy (PAT) is promising and emerging as adjuvant therapy in an attempt to eliminate the microorganisms persistent to chemi-mechanical preparation. Since there is presence of oxygen in cells, photosensitizer activated by light can react with molecules in its vicinity by electrons’ or hydrogen’s transfer, leading to microorganism death. This paper reports the case of 4-year-old patient, female, with early childhood caries. The proposed endodontic treatment incuded chemomechanical treatment allied to PAT in the decontamination of root canals using methylene blue dye 50 μg/mL during 3–5 minutes and 40 J/cm2as energy density, taking into account the need for tissue penetration and effectiveness of PAT inside the dentinal tubules.
Urethrogluteal Fistula Developing Secondary to the Use of Clean Intermittent Self-Catheterization: First Case Report in the Literature
Authors: Bozkurt Aliseydi , Karabakan Mehmet , Soyturk Mehmet , Hirik Erkan , Nuhoglu Barış
Published: October 2014

Clean intermittent self-catheterization is the standard method for bladder evacuation in these patients today. The patient was diagnosed with urethrogluteal fistula and gluteal-perineal abscess by radiological evaluation. Gluteal drainage decreased after cystostomy. In our paper, a case of urethrogluteal fistula and pelvic urinoma that developed as a result of the use of clean intermittent self-catheterization (CISC), which is rarely found in the literature, is presented.
Giant Lipoma of Posterior Cervical Region
Authors: Singh Mahendra , Saxena Ashish , Kumar Lovekesh , Karande Snehal K. , Kolhe Yuvraj
Published: October 2014

Lipomas are the slow growing soft tissue tumors of benign nature. They commonly grow on torso and extremities but may also develop in head and neck region. Rarely lipomas can grow to acquire gigantic proportions, turning into an entity termed as giant lipoma. Such lipomas are entitled to immediate attention as they have a relatively high malignant potential. We report a rare case of giant cervical lipoma in an elderly gentleman, followed by a brief discussion on diagnosis and management of the disorder.
Goodpasture’s Syndrome and p-ANCA Associated Vasculitis in a Patient of Silicosiderosis: An Unusual Association
Authors: Bal Amanjit , Das Ashim , Gupta Dheeraj , Garg Mandeep
Published: October 2014

Introduction.Goodpasture’s syndrome is a rare clinical entity and is characterized by circulating autoantibodies which are principally directed against the glomerular/alveolar basement membrane. The etiology of Goodpasture’s syndrome is still unknown. Lung involvement occurs as a result of lung injury and the exposure of new epitopes to the immune system. Recently, several studies have suggested the role of silica as one of etiological factors in ANCA associated vasculitis and glomerulonephritis.Materials and Methods.We present a case of a 40-year-old welder with silicosiderosis, who developed anti-GBM disease with p-ANCA positivity.Case Report.Patient presented to an emergency with gradually increasing breathlessness along with renal failure and died after short hospital stay. Autopsy pathology findings revealed crescentic glomerulonephritis with linear glomerular basement membrane antibody deposition, splenic vasculitis, pulmonary haemorrhage, and pulmonary silicosiderosis.Conclusion.This case reinforces the role of environmental triggers like exposure to silica, metal dust, and tobacco in pathogenesis of Goodpasture’s syndrome and p-ANCA associated vasculitis.
Role of Erythropoietin and Other Growth Factors inEx VivoErythropoiesis
Authors: Singh Vimal Kishor , Saini Abhishek , Chandra Ramesh
Published: October 2014

Erythropoiesis is a vital process governed through various factors. There is extreme unavailability of suitable donor due to rare phenotypic blood groups and other related complications like hemoglobinopathies, polytransfusion patients, and polyimmunization. Looking at the worldwide scarcity of blood, especially in low income countries and the battlefield, mimicking erythropoiesis usingex vivomethods can provide an efficient answer to various problems associated with present donor derived blood supply system. Fortunately, there are manyex vivoerythropoiesis methodologies being developed by various research groups using stem cells as the major source material for large scale blood production. Most of theseex vivoprotocols use a cocktail of similar growth factors under overlapping growth conditions. Erythropoietin (EPO) is a key regulator in mostex vivoprotocols along with other growth factors such as SCF, IL-3, IGF-1, and Flt-3. Now transfusable units of blood can be produced by using these protocols with their set of own limitations. The present paper focuses on the molecular mechanism and significance of various growth factors in these protocols that shall remain helpful for large scale production.
Maternal Weight Gain in Pregnancy and Risk of Obesity among Offspring: A Systematic Review
Authors: Lau Erica Y. , Liu Junxiu , Archer Edward , McDonald Samantha M. , Liu Jihong
Published: October 2014

Objectives. To systematically review the evidence from prospective and retrospective cohort studies on the association between gestational weight gain (GWG) and offspring’s body weight.Methods. Electronic databases PubMed, Web of Science, CINAHL, and Academic Search Premiere were searched from inception through March 18, 2013. Included studies (n=23) were English articles that examined the independent associations of GWG with body mass index (BMI) and/or overweight status in the offspring aged 2 to 18.9 years. Two authors independently extracted the data and assessed methodological quality of the included studies.Results. Evidence from cohort studies supports that total GWG and exceeding the Institute of Medicine maternal weight gain recommendation were associated with higher BMIz-score and elevated risk of overweight or obesity in offspring. The evidence of high rate of GWG during early- and mid-pregnancy is suggestive. Additionally, the evidence on inadequate GWG and net GWG in relation to body weight outcomes in offspring is insufficient to draw conclusions.Conclusions. These findings suggest that GWG is a potential risk factor for childhood obesity. However, findings should be interpreted with caution due to measurement issues of GWG and potential confounding effects of shared familial characteristics (i.e., genetics and maternal and child’s lifestyle factors).
Analysis of Occlusal Vertical Dimension and Mandibular Basal Bone Height in a Nigerian Population
Authors: Akinbami Babatunde O. , Nsirim Prince E.
Published: October 2014

Background. The actual basal bone height of the reconstructed mandible is relevant to achieve normal occlusal vertical dimension for the prosthesis fabricated. The purpose of the study was to determine the mean and baseline values of the occlusal vertical dimension and height of the mandibular basal bone in a Nigerian population. Method. Each participant was asked to bring the upper and lower teeth into contact, while the distance between the nasal sill and dimple on the lower lip was measured (OVD). The skin at lower border of the mandible was marked and the distance between this point and the landmark on the lower lip was measured, MBH. Result. 200 subjects were evaluated. Age range was 16–30 years, mean ± (SD), 21.6 ± (3.1) years. Males had mean ± (SD) of 42.10 ± (5.34) mm for OVD and females 39.72 ± (5.25) mm; acceptable baseline range of OVD for any population will be 34–48 mm (3.4–4.8) cm. All the males had a mean ± (SD), 30.54 ± (6.13) mm for MBH, and all the females 29.63 ± (5.23) mm. Acceptable baseline range of MBH for any population will be 24–37 mm (2.4–3.7) cm. Conclusion. To reconstruct the mandible and still maintain the OVD, heights of bone grafts must not be less than 2 cm or greater than 4 cm.
The Impact of Race in Male Breast Cancer Treatment and Outcome in the United States: A Population-Based Analysis of 4,279 Patients
Authors: Shin Jacob Y. , Kachnic Lisa A. , Hirsch Ariel E.
Published: October 2014

The purpose of this study is to compare the racial differences in treatment and overall survival (OS) of male breast cancer (MBC) patients. Data were extracted from the NCI SEER database that included population-based registries from 1988 to 2010 and analyzed using SPSS 20.0. 4,279 MBC patients were identified. 3,266 (76.3%) patients were White, 552 (12.9%) Black, 246 (5.7%) Hispanic, and 215 (5.0%) Asian. Black patients were more likely to be diagnosed at younger age(P<0.001), have advanced stage disease(P=0.001), and be unmarried(P<0.001)and less likely to undergo lymph node dissection(P=0.006). When stratified by stage, there was no difference in receipt of primary treatment by race. The 5-year OS for White, Black, Hispanic, and Asian races was 73.8%, 66.3%, 74.0%, and 85.3%(P<0.001). This significant worse 5-year OS for Blacks persisted regardless of age, stage II or III disease, and grade 2 or 3 disease. On multivariate analysis, Black race was a significant independent prognostic factor for worse OS. Blacks were less likely to receive lymph node dissection of which patients may derive benefit, though we did not observe receipt of primary treatment, after stratifying for disease stage, to be an underlying factor contributing to racial outcome differences.
Mucin Reactivity after Acute Exposure to Mercury and Zinc Chloride in Neurocytes of Freshwater Snail Bellamya bengalensis: A Histochemical Study
Authors: Londhe Sunil , Kamble Nitin
Published: October 2014

Central nervous system (CNS) of gastropods is extensively studied for its pathology and immunocytology; there is scanty information on histochemical alterations in neuronal cells due to heavy metal. This study was designed to investigate histochemical alterations in cerebral neurons of freshwater snail Bellamya bengalensis after intoxication with mercuric chloride (HgCl2) and zinc chloride (ZnCl2). As per chemical components cerebral ganglia of Bellamya bengalensis showed three different zones, namely, periganglionic connective tissue sheath, interperikaryonal space, and neuropil. After intoxication, increased acidic content in extracellular matrix (ECM) of neuronal cells was found. These alterations were directly proportional to time of exposure period. From results, HgCl2 proved its highly toxic nature over chemical composition of cerebral neuronal cells of freshwater snail Bellamya bengalensis compared to ZnCl2 intoxication.
Cardioembolic Sources in Stroke Patients in South of Brazil
Authors: Porcello Marrone Luiz Carlos , Farina Brunelli João Pedro , Lutzky Saute Ricardo , Henrique Tomasi Gustavo , Cecchele Madeira Bianca , Alves Martins William , Dupont Rohr Robson , Heck Ana Paula , Botton Luiz Ricardo , Martins de Castro Marilia , Bodanese Rodrigo , Bodanese Luiz Carlos , Huf Marrone Antônio Carlos , Costa da Costa Jaderson
Published: October 2014

Background. Stroke is a leading cause of mortality and disability in Brazil and around the world. Cardioembolism is responsible for nearly 30% of the origins of ischemic stroke. Methods. We analyzed data of 256 patients with cardioembolic ischemic stroke (according to TOAST classification) who were admitted into the Hospital São Lucas-PUCRS from October 2011 to January 2014. The cardioembolic subtype was divided into six subgroups: arrhythmias, valvular heart disease, coronary artery disease, cardiomyopathy, septal abnormalities, and intracardiac injuries. The prevalence of the most important cardiovascular risk factors and medications in use for prevention of systemic embolism by the time of hospital admission was analyzed in each patient. Results. Among 256 patients aged 60.2 +/− 6.9 years, 132 males, arrhythmias were the most common cause of cardioembolism corresponding to 50.7%, followed by valvular heart disease (17.5%) and coronary artery disease (16%). Hypertension (61.7%) and dyslipidemia (43.7%) were the most common risk factors. Less than 50% of patients with arrhythmias were using oral anticoagulants. Conclusions. Identifying the prevalence of cardioembolic stroke sources subgroups has become an increasingly important role since the introduction of new oral anticoagulants. In this study, arrhythmias (especially atrial fibrillation) were the main cause of cardioembolism.
An Atypical Presentation of Myopericytoma in Palmar Arch and Review of the Literature
Authors: Kara Adnan , Keskinbora Mert , Kayaalp Mahmut Enes , Şeker Ali , Erdil Mehmet , Bülbül Murat
Published: October 2014

Introduction. Myopericytoma is a very rare perivascular tumor that can be presented with painful mass in lower extremities. We aimed to present an atypical presentation and location of myopericytoma.Presentation of Case. An 18-year-old otherwise healthy individual was admitted to outpatient clinic with complaints of numbness and pain in his right hand. He has had no trauma. On volar aspect of his right hand, a well-circumscribed, painful mass was palpated. MRI results were related to hemangioma. Surgical excision was planned and performed. Pathological investigation revealed the mass is myopericytoma.Discussion. This case demonstrates a rare location and presentation of myopericytoma. Reviewing the literature, discussion was made to expand the horizon for diagnosis and treatment of patients with similar symptoms.Conclusion. Myopericytoma can rarely present with numbness and pain in affected region. Surgical excision is helpful for definitive diagnosis and symptom relief.
Existence of Solution and Approximate Controllability for Neutral Differential Equation with State Dependent Delay
Authors: Das Sanjukta , Pandey Dwijendra N. , Sukavanam N.
Published: October 2014

This paper is divided in two parts. In the first part we study a second order neutral partial differential equation with state dependent delay and noninstantaneous impulses. The conditions for existence and uniqueness of the mild solution are investigated via Hausdorff measure of noncompactness and Darbo Sadovskii fixed point theorem. Thus we remove the need to assume the compactness assumption on the associated family of operators. The conditions for approximate controllability are investigated for the neutral second order system with respect to the approximate controllability of the corresponding linear system in a Hilbert space. A simple range condition is used to prove approximate controllability. Thereby, we remove the need to assume the invertibility of a controllability operator used by authors in (Balachandran and Park, 2003), which fails to exist in infinite dimensional spaces if the associated semigroup is compact. Our approach also removes the need to check the invertibility of the controllability Gramian operator and associated limit condition used by the authors in (Dauer and Mahmudov, 2002), which are practically difficult to verify and apply. Examples are provided to illustrate the presented theory.
Two‐Key Dependent Permutation for Use in Symmetric Cryptographic System
Authors: Kuppusamy Arulmani , Pitchai Iyer Swaminathan , Krithivasan Kannan
Published: October 2014

This paper deals with a two‐key based novel approach for generating a permutation table that can be used in a symmetric cryptographic system to cause diffusion. It also discusses how the permutation table generated using the approach can be applied to character based encryption and binary data block produced at intermediate stages by symmetric cipher algorithms. It also describes the effect of our approach on characters of intermediate text as well as on bits of binary data block along with the impact of a single bit change in key information on producing permutation sequences applied to plaintexts to produce ciphertexts. The results are satisfactory and the proposed approach can be employed in any symmetric block cipher algorithm that uses the predefined permutation tables.
Prevalence and Determinants of Fall-Related Injuries among Older Adults in Ecuador
Authors: Orces Carlos H.
Published: October 2014

Objectives. To estimate the prevalence and determinants of fall-related injuries in the previous year among adults aged 60 years or older in Ecuador.Methods. The prevalence of fall-related injuries was estimated using cross-sectional data from the first national survey of Health, Wellbeing, and Aging study. Logistic regression models were used to examine the associations between participants’ demographic characteristics and fall-related injuries.Results. Of 5,227 participants with a mean age of 72.6 years, 11.4% (95% CI, 10.3%–12.7%) reported a fall-related injury in Ecuador, representing an estimated 136,000 adults aged 60 years or older. Fall-related injuries were more frequently reported among older adults residing in the most urbanized and populated provinces of the country. After controlling for potential confounders, self-reported race as Indigenous (OR 2.2; 95% CI, 2.11–2.31), drinking alcohol regularly (OR 2.54; 95% CI, 2.46–2.63), subjects with greater number of comorbid conditions (OR 2.03; 95% CI, 1.97–2.08), and urinary incontinence (OR 1.83; 95% CI, 1.79–1.87) were factors independently associated with increased odds of sustaining fall-related injuries.Conclusions. Fall-related injuries represent a considerable burden for older adults in Ecuador. The present findings may assist public health authorities to implement fall prevention programs among subjects at higher risk for this type of injury.
Arthroscopic Ankle Arthrodesis for Treating Osteoarthritis in a Patient with Kashin-Beck Disease
Authors: Iwasa Kenjiro , Kanzaki Noriyuki , Fujishiro Takaaki , Hayashi Shinya , Hashimoto Shingo , Kuroda Ryosuke , Kurosaka Masahiro
Published: October 2014

Kashin-Beck disease (KBD) is an endemic degenerative osteoarthritis. Death of cartilage and growth plate is the pathologic feature; therefore, KBD involves skeletal deformity and often results in osteoarthritis. Deficiency of selenium, high humic acid levels in water, and fungi on storage gains are considered the cause of KBD. The most frequently involved joints are ankles, knees, wrists, and elbows and symptoms are pain and limited motions of those joints. The main treatments for KBD are rehabilitation and osteotomy to correct the deformities because preventive treatment has not been established. In this report, we present a case of ankle osteoarthritis due to KBD and first describe arthroscopic ankle arthrodesis for treating osteoarthritis of KBD.
Retroesophageal Right Subclavian Artery
Authors: Kanaskar Neelesh , Vatsalaswamy P. , Sonje Preeti , Paranjape Vaishali
Published: October 2014

During routine dissection of head and neck region in a 65-year-old female cadaver variation in the origin of right subclavian artery was found. The right subclavian artery originated as a direct branch of arch of aorta distal to the origin of left subclavian artery and it was found passing behind esophagus (retroesophageal) and ascending upwards to the right side while the left subclavian artery originated normally from arch of aorta distal to the origin of left common carotid artery. Anomalous variations in the origin and course of arteries have serious implications in angiographic and surgical procedures; hence it is of great importance to be aware of such possibilities of variations.
RABL6A Promotes G1–S Phase Progression and Pancreatic Neuroendocrine Tumor Cell Proliferation in an Rb1-Dependent Manner
Authors: Hagen Jussara , Muniz Viviane P. , Falls Kelly C. , Reed Sara M. , Taghiyev Agshin F. , Quelle Frederick W. , Gourronc Francoise A. , Klingelhutz Aloysius J. , Major Heather J. , Askeland Ryan W. , Sherman Scott K. , O'Dorisio Thomas M. , Bellizzi Andrew M. , Howe James R. , Darbro Benjamin W. , Quelle Dawn E.
Published: October 2014

Mechanisms of neuroendocrine tumor (NET) proliferation are poorly understood, and therapies that effectively control NET progression and metastatic disease are limited. We found amplification of a putative oncogene, RABL6A, in primary human pancreatic NETs (PNET) that correlated with high-level RABL6A protein expression. Consistent with those results, stable silencing of RABL6A in cultured BON-1 PNET cells revealed that it is essential for their proliferation and survival. Cells lacking RABL6A predominantly arrested in G1 phase with a moderate mitotic block. Pathway analysis of microarray data suggested activation of the p53 and retinoblastoma (Rb1) tumor-suppressor pathways in the arrested cells. Loss of p53 had no effect on the RABL6A knockdown phenotype, indicating that RABL6A functions independent of p53 in this setting. By comparison, Rb1 inactivation partially restored G1 to S phase progression in RABL6A-knockdown cells, although it was insufficient to override the mitotic arrest and cell death caused by RABL6A loss. Thus, RABL6A promotes G1 progression in PNET cells by inactivating Rb1, an established suppressor of PNET proliferation and development. This work identifies RABL6A as a novel negative regulator of Rb1 that is essential for PNET proliferation and survival. We suggest RABL6A is a new potential biomarker and target for anticancer therapy in PNET patients. Cancer Res; 74(22); 6661–70. ©2014 AACR.
Transcriptome-wide Landscape of Pre-mRNA Alternative Splicing Associated with Metastatic Colonization
Authors: Lu Zhi-xiang , Huang Qin , Park Juw Won , Shen Shihao , Lin Lan , Tokheim Collin J. , Henry Michael D. , Xing Yi
Published: October 2014

Metastatic colonization is an ominous feature of cancer progression. Recent studies have established the importance of pre-mRNA alternative splicing (AS) in cancer biology. However, little is known about the transcriptome-wide landscape of AS associated with metastatic colonization. Both in vitro and in vivo models of metastatic colonization were utilized to study AS regulation associated with cancer metastasis. Transcriptome profiling of prostate cancer cells and derivatives crossing in vitro or in vivo barriers of metastasis revealed splicing factors with significant gene expression changes associated with metastatic colonization. These include splicing factors known to be differentially regulated in epithelial–mesenchymal transition (ESRP1, ESRP2, and RBFOX2), a cellular process critical for cancer metastasis, as well as novel findings (NOVA1 and MBNL3). Finally, RNA-seq indicated a large network of AS events regulated by multiple splicing factors with altered gene expression or protein activity. These AS events are enriched for pathways important for cell motility and signaling, and affect key regulators of the invasive phenotype such as CD44 and GRHL1.

Implications: Transcriptome-wide remodeling of AS is an integral regulatory process underlying metastatic colonization, and AS events affect the metastatic behavior of cancer cells. Mol Cancer Res; 13(2); 305–18. ©2014 AACR.
Cancer Patients under Maintenance Hemodialysis: Relationship between Quality of Life, Depression, Sleep Quality and Malnutrition-Inflammation Score
Authors: Castro Juliana Ramiro Luna , Silva Junior Geraldo B. , Carvalho André Ferrer , Hyphantis Thomas N. , Farias Luiza de Andrade Braga , Libório Alexandre B. , Daher Elizabeth F.
Published: October 2014

Background: The kidney is one major organ affected by cancer and its associated therapies. The aim of this study was to compare the levels of depression, quality of life and sleep quality in hemodialysis patients with or without cancer, and to analyze the associations with the malnutrition-inflammation score (MIS). Patients and Methods: In this cross-sectional study, 40 cancer patients under hemodialysis and 44 patients under hemodialysis without cancer who served as the control group were included. Participants underwent structured interviews to investigate depression, quality of life, sleep quality and restless legs syndrome. Results: Hemodialysis patients with cancer had a greater depression score (16.5 ± 4.8 vs. 10.8 ± 5.2, p < 0.001). Patients had similar physical and mental composite quality of life scores. Patients under hemodialysis with cancer had poor quality of sleep (mean score 8.8 ± 3.5 vs. 6.4 ± 4.1, p = 0.011) and a higher prevalence of restless leg syndrome (55.9 vs. 25.7%, p = 0.011). These features were associated with MIS in patients without cancer but not in patients with cancer. Conclusion: Cancer patients undergoing hemodialysis present a higher prevalence of depression, poor quality of life, sleep disorders; however, associations of these features with MIS are different in hemodialysis patients with or without cancer. These findings can change the clinical approach to these patients.
An Adenosine A1 Agonist 2-Chloro-N6 Cyclopentyladenosine Inhibits the Angiotensin II-Induced Cardiomyocyte Hypertrophy through the Calcineurin Pathway
Authors: Zhang Xingliang , Xia Juan , Qian Dandan , Wang Yang , Lin Yongwen , Huang Xiulan , Tan Jianxin
Published: October 2014

Objectives: The aim of this investigation was to study the underlying mechanism of an adenosine A1 receptor agonist 2-chloro-N6 cyclopentyladenosine (CCPA) inhibiting cardiomyocyte hypertrophy induced by angiotensin II (AngII). Methods: Neonatal rat cardiomyocytes were treated with AngII to generate a cardiomyocyte hypertrophy model. Cardiomyocyte cultures were randomized into 5 groups: control; AngII; AngII + cyclosporin A (CsA); AngII + CCPA, and AngII + CCPA + DPCPX. Cardiomyocyte viability was measured by MTT assay. Protein synthesis was assessed by the application of 3H leucine (3H-Leu) incorporation into protein. The mRNA expressions of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), β-myosin heavy chain (β-MHC) and calcineurin Aβ (CnAβ) were measured by real-time quantitative PCR. The protein level of CnAβ was dissected by Western blotting. Results: AngII administration at lower concentrations increased the cardiomyocytes viabilities gradually. Surface area, mRNA expressions of ANP, BNP and β-MHC, and 3H-Leu incorporation of AngII-induced cardiomyocytes were increased in a dose-dependent manner. As a calcineurin-specific inhibitor, CsA inhibited 3H-Leu incorporation, surface area, mRNA expressions of ANP, BNP, β-MHC, CnAβ and protein expression of CnAβ of AngII-induced cardiomyocytes. CCPA also suppressed the mRNA and protein expressions of CnAβ and exerted antihypertrophic effects to a greater degree than CsA. The inhibition of CCPA on cardiomyocyte hypertrophy was counteracted by the A1 receptor antagonist DPCPX. Conclusion: The A1 receptor agonist CCPA could significantly inhibit AngII-induced cardiomyocyte hypertrophy via the calcineurin signaling pathway.
Paternal Obesity, Interventions, and Mechanistic Pathways to Impaired Health in Offspring
Authors: McPherson Nicole O. , Fullston Tod , Aitken R. John , Lane Michelle
Published: October 2014

Background: The global rates of male overweight/obesity are rising, approaching 70% of the total adult population in Western nations. Overweight/obesity increases the risk of chronic diseases; however, there is increasing awareness that male obesity negatively impacts fertility, subsequent pregnancy, and the offspring health burden. Developmental programming is well defined in mothers; however, it is becoming increasingly evident that developmental programming can be paternally initiated and mediated through paternal obesity. Key Messages: Both human and rodent models have established that paternal obesity impairs sex hormones, basic sperm function, and molecular composition. This results in perturbed embryo development and health and an increased subsequent offspring disease burden in both sexes. The reversibility of obesity-induced parental programming has only recently received attention. Promising results in animal models utilizing diet and exercise interventions have shown improvements in sperm function and molecular composition, resulting in restorations of both embryo and fetal health and subsequent male offspring fertility. The direct mode for paternal inheritance is likely mediated via spermatozoa. We propose two main theories for the origin of male obesity-induced paternal programming: (1) accumulation of sperm DNA damage resulting in de novo mutations in the embryo and (2) changes in sperm epigenetic marks (microRNA, methylation, or acetylation) altering the access, transcription, and translation of paternally derived genes during early embryogenesis. Conclusions: Paternal overweight/obesity induces paternal programming of offspring phenotypes likely mediated through genetic and epigenetic changes in spermatozoa. These programmed changes to offspring health appear to be partially restored via diet/exercise interventions in obese fathers preconception, which have been shown to improve aspects of sperm DNA integrity. However, the majority of data surrounding paternal obesity and offspring phenotypes have come from rodent models; therefore, we contend that it will be increasingly important to study population-based data to determine the likely mode of inheritance in humans.
Association between Physical Activity in Obese Pregnant Women and Pregnancy Outcomes: The UPBEAT Pilot Study
Authors: Hayes Louise , Bell Ruth , Robson Steve , Poston Lucilla ,   on behalf of the UPBEAT Consortium
Published: October 2014

Background: Obesity in pregnancy is associated with fetal macrosomia, a raised neonatal fat mass and an increased risk of obesity and poor metabolic health in childhood which persists into adulthood. The offspring of obese women are more likely to be obese than the offspring of lean women when they become pregnant themselves, perpetuating a cycle of obesity and its associated negative metabolic consequences. Increasing physical activity during pregnancy could improve insulin sensitivity and reduce the risk of maternal and offspring adverse outcomes. The UK Pregnancy Better Eating and Activity Trial (UPBEAT) is a trial of a complex intervention designed to improve pregnancy outcomes through dietary changes and physical activity. Data from the pilot trial of 183 women were available for analysis. The relationship between the time spent at different physical activity levels and maternal and infant pregnancy outcomes was examined. Key Messages: Strong evidence exists that physical activity improves insulin sensitivity in non-pregnant populations, and lifestyle interventions of proven effectiveness in non-pregnant populations have been developed. Women who are active in pregnancy demonstrate better glucose control and favourable pregnancy outcomes. There is a lack of effective interventions to support obese pregnant women to be physically active. Conclusions: No difference was detected in objectively measured physical activity between women randomised to the intervention and control arms of the UPBEAT pilot trial. Light-intensity physical activity was lower in early pregnancy in women who delivered macrosomic infants. Maternal sedentary time at 35-36 weeks' gestation was positively associated and moderate-intensity physical activity was inversely associated with neonatal abdominal circumference. Maternal physical activity is associated with infant birth weight and abdominal circumference and is an appropriate target for intervention to improve infant outcomes. The challenge remains to develop an effective intervention to support obese pregnant women to be physically active.
Placental Fatty Acid Transfer: A Key Factor in Fetal Growth
Authors: Larqué Elvira , Pagán Ana , Prieto María Teresa , Blanco José Eliseo , Gil-Sánchez Alfonso , Zornoza-Moreno Matilde , Ruiz-Palacios María , Gázquez Antonio , Demmelmair Hans , Parrilla Juan José , Koletzko Berthold
Published: October 2014

The functionality of the placenta may affect neonatal adiposity and fetal levels of key nutrients such as long-chain polyunsaturated fatty acids. Fetal macrosomia and its complications may occur even in adequately controlled gestational diabetic (GDM) mothers, suggesting that maternal glycemia is not the only determinant of fetal glycemic status and wellbeing. We studied in vivo the placental transfer of fatty acids (FA) labeled with stable isotopes administered to 11 control and 9 GDM pregnant women (6 treated with insulin). Subjects received orally 13C-palmitic, 13C-oleic, and 13C-linoleic acids and 13C-docosahexaenoic acid (13C-DHA) 12 h before an elective caesarean section. FA were quantified by gas chromatography and 13C enrichments by gas chromatography-isotope ratio mass spectrometry. The 13C-FA concentration was higher in total lipids of maternal plasma in GDM patients versus controls, except for 13C-DHA. Moreover, 13C-DHA showed a lower placenta/maternal plasma ratio in GDM patients versus controls and a significantly lower cord/maternal plasma ratio. Other FA ratios studied were not different between GDM and controls. A disturbed 13C-DHA placental uptake occurred in GDM patients treated with diet or insulin, while the latter also had lower 13C-DHA levels in the venous cord. The tracer study pointed towards an impaired placental DHA uptake as a critical step, while the transfer of other 13C-FA was less affected. Patients with GDM treated with insulin could also have a greater fetal fat storage, which may have contributed to the reduced 13C-DHA in the venous cord observed. The DHA transfer to the fetus was reduced in GDM pregnancies compared to controls. This might have an influence on fetal neurodevelopment and long-term consequences for the child.
Early Infant Feeding and Adiposity Risk: From Infancy to Adulthood
Authors: Oddy Wendy H. , Mori Trevor A. , Huang Rae-Chi , Marsh Julie A. , Pennell Craig E. , Chivers Paola T. , Hands Beth P. , Jacoby Peter , Rzehak Peter , Koletzko Berthold V. , Beilin Lawrence J.
Published: October 2014

Introduction: Systematic reviews suggest that a longer duration of breast-feeding is associated with a reduction in the risk of later overweight and obesity. Most studies examining breast-feeding in relation to adiposity have not used longitudinal analysis. In our study, we aimed to examine early infant feeding and adiposity risk in a longitudinal cohort from birth to young adulthood using new as well as published data. Methods: Data from the Western Australian Pregnancy Cohort (Raine) Study in Perth, W.A., Australia, were used to examine associations between breast-feeding and measures of adiposity at 1, 2, 3, 6, 8, 10, 14, 17, and 20 years. Results: Breast-feeding was measured in a number of ways. Longer breast-feeding (in months) was associated with reductions in weight z-scores between birth and 1 year (β = -0.027; p < 0.001) in the adjusted analysis. At 3 years, breast-feeding for <4 months increased the odds of infants experiencing early rapid growth (OR 2.05; 95% CI 1.43-2.94; p < 0.001). From 1 to 8 years, children breast-fed for ≤4 months compared to ≥12 months had a significantly greater probability of exceeding the 95th percentile of weight. The age at which breast-feeding was stopped and a milk other than breast milk was introduced (introduction of formula milk) played a significant role in the trajectory of the BMI from birth to 14 years; the 4-month cutoff point was consistently associated with a higher BMI trajectory. Introduction of a milk other than breast milk before 6 months compared to at 6 months or later was a risk factor for being overweight or obese at 20 years of age (OR 1.47; 95% CI 1.12-1.93; p = 0.005). Discussion: Breast-feeding until 6 months of age and beyond should be encouraged and is recommended for protection against increased adiposity in childhood, adolescence, and young adulthood. Adverse long-term effects of early growth acceleration are fundamental in later overweight and obesity. Formula feeding stimulates a higher postnatal growth velocity, whereas breast-feeding promotes slower growth and a reduced likelihood of overweight and obesity. Biological mechanisms underlying the protective effect of breast-feeding against obesity are based on the unique composition and metabolic and physiological responses to human milk.
Excessive Weight Gain during Full Breast-Feeding
Authors: Grunewald Maria , Hellmuth Christian , Demmelmair Hans , Koletzko Berthold
Published: October 2014

Background: Breast-feeding is considered to offer optimal nutrition for healthy infant growth and development. Observational studies have linked breast-feeding to reduced obesity. Case Observation: We observed an infant who was born macrosomic (4.56 kg) and showed excessive weight gain markedly exceeding the 97th percentile of weight during full breast-feeding. At the age of 4 months, the weight was greater than 11 kg. Clinical evaluation did not reveal any underlying pathology. After the introduction of complementary feeding and hence reduction of the breast milk intake, the excessive weight gain was attenuated and the slope of the percentile curve paralleled upper percentiles. Since this pattern suggested full breast-feeding as the driver of excessive weight gain, we analyzed the human milk composition at the infant age of 1 year and compared the results with published data on composition at this stage of lactation. Results: The milk contents of lactose, fat, fatty acids, polar lipids, carnitine species, and insulin were similar to the reference data. The adiponectin content was increased. The most remarkable alteration was a high milk protein content (mean 1.25 g/dl, reference 0.8 g/dl). Conclusions: A very high protein supply in infancy has been previously shown to increase plasma concentrations of the growth factors insulin and IGF-1, weight gain, and later obesity. We speculate that interindividual variations in human milk adiponectin and protein contents may contribute to modulation of the growth of fully breast-fed infants and in this case may have contributed to excessive weight gain during full breast-feeding. This hypothesis merits being tested in future cohort studies.
Nutritional Challenges and Opportunities during the Weaning Period and in Young Childhood
Authors: Alles Martine S. , Eussen Simone R.B.M. , van der Beek Eline M.
Published: October 2014

The early years of life are a period of very rapid growth and development. In this critical phase, food preferences are formed which carry over into childhood and beyond and foundations are laid for a healthy adult life. Excess energy, imbalances in macronutrient quality, and nutritional deficiencies may form inappropriate nutritional signals, leading to metabolic disturbances and affecting the obesity risk. For instance, the intake of protein and sugar-sweetened beverages in young children has been associated with an increased risk of overweight and obesity. In reality, scientific reports have shown that the dietary intakes of vegetables, α-linolenic acid, docosahexaenoic acid, iron, vitamin D, and iodine are low and the intakes of protein, saturated fatty acids, and added sugar are high in young children living in Europe. A focus on improving feeding habits and approaches to support more balanced nutritional intakes early in life may have significant public health benefits.
Risk of Intracerebral Hemorrhage After Thrombolysis in Patients with Asymptomatic Hemorrhage on T2*
Authors: Aoki Junya , Shibazaki Kensaku , Saji Naoki , Uemura Junichi , Sakamoto Yuki , Kimura Kazumi
Published: October 2014

Background: Intravenous thrombolysis using the tissue-type plasminogen activator (t-PA) is contraindicated for patients with a history of intracerebral hemorrhage (ICH). T2*-weighted magnetic resonance imaging (MRI) is able to detect asymptomatic ICH. If there is an association between asymptomatic ICH on T2* before t-PA therapy and ICH after t-PA therapy, we may be able to take preventive measures before starting t-PA therapy in patients with MRI-proven hemorrhage. The aim of the present study was to investigate whether asymptomatic ICH seen on T2* increases the risk of new ICH after t-PA therapy. Methods: Patients who had consecutive stroke treated with t-PA between October 2005 and November 2013 were enrolled. A hypointense T2* signal with a diameter >5 mm was defined as asymptomatic ICH before t-PA therapy. The presence of new ICH at 24 h after t-PA therapy was assessed using T2*. Symptomatic ICH (sICH) was defined as new ICH combined with an increase in the National Institutes of Health Stroke Scale score ≥4. At 3 months after onset, good and poor outcomes were defined as modified Rankin Scale (mRS) scores of 0-1 and 4-6, respectively. Results: Of 300 patients (age 77 [68-83] years; 173 [58%] males), 25 (8%) had an asymptomatic ICH on T2* before t-PA therapy. Eleven (45%) patients showed an isolated asymptomatic ICH. Three (12%) patients had a round hypointense lesion similar to microbleeds. Nine (36%) patients had a hemorrhagic transformation within a prior infarcted area. Multiple asymptomatic ICHs were seen in 2 (8%) patients. The rates of good and poor outcomes at 3 months were 24 and 59% of patients with asymptomatic ICH and 38 and 41% of patients without asymptomatic ICH (p = 0.300 and 0.202, respectively). At 24 h after t-PA therapy, 11 (44%) of the 25 patients with asymptomatic ICH before t-PA therapy and 87 (32%) of 275 without asymptomatic ICH had new ICH (p = 0.265). Only 1 (4%) of 25 patients with asymptomatic ICH before t-PA therapy and 6 (2%) of 275 without asymptomatic ICH had sICH within 24 h (p = 0.460). On multivariate logistic regression analysis, neither new ICH (odds, 1.19; 95% CI, 0.40-3.54, p = 0.753) nor sICH (odds, 0.95; 95% CI, 0.08-11.90, p = 0.970) was related to asymptomatic ICH on T2* before t-PA therapy. Conclusion: The presence of T2* hypointensity as a marker of asymptomatic ICH may not be associated with new ICH and sICH after t-PA therapy.