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Tao Xue, Tong Zhu
Epidemiological and toxicological studies suggest that exposure to ambient fine particles (PM2.5 ) can reduce human reproductive capacity. We previously reported, based on spatial epidemiology, that higher levels of PM2.5 exposure were associated with a lower fertility rate (FR) in China. However, that study was limited by a lack of temporal variation. Using first-difference regression, we linked temporal changes in FR and PM2.5 with adjustment for ecological covariates across 2806 counties in China during 2000-2010...
June 13, 2018: Science of the Total Environment
Shandilya Mahamuni Baira, Amit Khurana, Jaganmohan Somagoni, R Srinivas, Chandraiah Godugu, M V N Kumar Talluri
Nimbolide is a novel, natural compound with promising potential as a drug candidate for anticancer activity. It is isolated from the Indian traditional medicinal plant Azadirachta indica popularly known as neem. The present study was undertaken to explore the oral bioavailability and pharmacokinetic characteristics of nimbolide in rats using the LC/QTOF/MS method. A simple protein precipitation method using acetonitrile was employed for extracting nimbolide from rat plasma. The chromatographic separation of nimbolide and the internal standard (regorafenib) was attained on an Aquity BEH C18 column (100 × 2...
June 2, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Dalila Forte, Anabela Nabais, Carlos Pontinha, Manuela Mafra, Luís Mateus
BACKGROUND: Neurofibromatosis type 1 (NF1) is a tumour predisposing condition, being Pilocytic Astrocytomas (PA) a common benign central nervous system (CNS) tumour occurring in this setting. Although this is a common association, simultaneous development of multiple lesions is an infrequent finding, especially in non-optic or hypothalamic locations. CLINICAL CASE: A 41 year-old female patient with neurofibromatosis type 1 and uncontrolled human immunodeficiency virus (HIV) type 1 infection presents with a first generalized seizure and associated headache and ataxia...
June 13, 2018: World Neurosurgery
Marcia Triunfol, Stevens Rehen, Marina Simian, Troy Seidle
The 21 st century paradigm in toxicology, which emphasizes mechanistic understanding and species-relevant modeling of human biology and pathophysiology, is gaining traction in the wider biosciences through a global workshop series organized by the BioMed21 Collaboration. The second of this series, entitled Emerging Technology Toward Pathway-Based Human Brain Research, was held in Brazil in 2017, bringing together leading South American and international scientists, research funders and other stakeholders...
June 13, 2018: Drug Discovery Today
Emmanuel Katsanis, Lauren N Sapp, Nicole Varner, Shannon Koza, Baldassarre Stea, Yi Zeng
More than half of patients undergoing hematopoietic cell transplantation at our institution are ethnic or racial minorities, making the search for matched unrelated donors more challenging. Since the introduction of haploidentical bone marrow transplant (haplo-BMT) into our pediatric BMT program in 2015, 69.2% of the recipients have been minorities. Herein, we describe our experience with the first thirteen pediatric and young adult patients with hematologic malignancies who have undergone T-cell replete haplo-BMT following myeloablative conditioning (MAC) at our institution...
June 13, 2018: Biology of Blood and Marrow Transplantation
Paul A Lapchak, Paul D Boitano, Geoffrey de Couto, Eduardo Marbán
Acute ischemic stroke is devastating to patients and their families because of few viable therapeutic options to promote recovery after reperfusion windows close. Recent breakthroughs in biotechnology have resulted in a reproducible patented process for the purification of extracellular vesicles (EVs) from human cardiosphere-derived cells (CDCs). Because CDC-EVs have many features potentially beneficial to treat acute ischemic stroke, CDC-EVs were evaluated in an established small-clot rabbit embolic stroke model, where clinically relevant end points were used to assess recovery in a more translational large animal model...
June 13, 2018: Experimental Neurology
Sebastien Kenmoe, Jean Joel Bigna, Estelle Amandine Well, Fredy Brice N Simo, Véronique B Penlap, Astrid Vabret, Richard Njouom
AIM: The epidemiology of Human Respiratory Syncytial virus (HRSV) infection has not yet been systematically investigated in Africa. This systematic review and meta-analysis is to estimate the prevalence of HRSV infections in people with acute respiratory tract infections (ARTI) in Africa. METHOD: We searched PubMed, EMBASE, Africa Journal Online, and Global Index Medicus to identify observational studies published from Jan 1, 2000 to Aug 1, 2017. We used a random-effects model to estimate the prevalence across studies...
June 16, 2018: Influenza and Other Respiratory Viruses
Matthew Cardinal, Constantino Kantaridis, Tong Zhu, Pengling Sun, Debra D Pittman, John E Murphy, Steven Arkin
BACKGROUND: Tissue factor pathway inhibitor (TFPI) is a protease inhibitor of tissue factor-activated coagulation factor VII (TF-FVIIa) complex and activated factor X (FXa). PF-06741086 is a monoclonal antibody that targets TFPI to increase clotting activity. OBJECTIVES: This study was a randomized, double-blind, sponsor-open, placebo-controlled, single intravenous (IV) or subcutaneous (SC) dose escalation study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-06741086...
June 16, 2018: Journal of Thrombosis and Haemostasis: JTH
Durgesh Dubey, Smriti Chaurasia, Anupam Guleria, Sandeep Kumar, Dinesh Raj Modi, Ramnath Misra, Dinesh Kumar
Currently, there are no reliable clinical biomarkers available that can aid early differential diagnosis of reactive arthritis (ReA) from other inflammatory joint diseases. Metabolic profiling of synovial fluid (SF) -obtained from joints affected in ReA- holds great promise in this regard and will further aid monitoring treatment and improving our understanding about disease mechanism. As a first step in this direction, we report here the metabolite specific assignment of 1 H and 13 C resonances detected in the NMR spectra of SF samples extracted from human patients with established ReA...
June 15, 2018: Magnetic Resonance in Chemistry: MRC
Andrés Lizasoain, Fernanda M Burlandy, Matías Victoria, Luis F López Tort, Edson E da Silva, Rodney Colina
Information about Human Enterovirus circulation in Uruguay is scarce. The aim of this study was to generate the first description about their circulation in the country through the study of sewage samples collected before and after the switch from Oral Poliovirus Vaccine to Inactivated Poliovirus Vaccine. Viruses were concentrated by an adsorption-elution to a negatively charged membrane, and real-time quantitative PCR and qualitative PCR methods were used to detect, quantify, and characterize enteroviruses...
June 16, 2018: Food and Environmental Virology
Sofia Bougioukli, Osamu Sugiyama, Ram K Alluri, Robert Yoho, Daniel A Oakes, Jay R Lieberman
In this study, we developed a lentiviral two-step transcriptional amplification (TSTA) system expressing bone morphogenetic protein-2 (BMP-2) under the control of a GAL4FF transactivator to enhance gene expression and limit toxicity for bone repair applications. To this end human MSCs, isolated from bone marrow or adipose tissue, were transduced overnight with a LV-TSTA system (GAL4FF or GAL4vp16) expressing BMP-2 or GFP and evaluated in vitro for transduction efficiency, mean fluorescence intensity, cell viability, and BMP-2 production...
June 15, 2018: Gene Therapy
Jing Li, Chuxiong Zeng, Beishi Zheng, Chun Liu, Min Tang, Yan Jiang, Yizhong Chang, Weiping Song, Yingxin Wang, Changqing Yang
High-mobility group box-1 (HMGB1) plays a context-dependent role in autophagy, which is required for hepatic stellate cells (HSCs) activation. However, the significance of HMGB1-induced HSCs autophagy in liver fibrosis has not been elucidated. Here, we first documented an enrichment of peripheral and intra-hepatic HMGB1 signal in hepatitis B virus (HBV)-related liver fibrosis progression, and presented the direct evidence of anatomic proximity of HMGB1 with a-SMA (a marker for HSCs activation) in cirrhotic liver specimens...
June 15, 2018: Clinical Science (1979-)
Julia Saifetiarova, Qian Shi, Martin Paukert, Masayuki Komada, Manzoor A Bhat
Disorganization of nodes of Ranvier is associated with motor and sensory dysfunctions. Mechanisms that allow nodal recovery during pathological processes remain poorly understood. A highly enriched nodal cytoskeletal protein βIV Spectrin anchors and stabilizes the nodal complex to actin cytoskeleton. Loss of murine βIV Spectrin allows the initial nodal organization, but causes gradual nodal destabilization. Mutations in human βIV SPECTRIN cause auditory neuropathy and impairment in motor coordination and similar phenotypes are caused by nodal disruption due to demyelination...
June 15, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Vitali Sikirzhytski, Fioranna Renda, Irina Tikhonenko, Valentin Magidson, Bruce F McEwen, Alexey Khodjakov
For proper segregation during cell division, each chromosome must connect to the poles of the spindle via microtubule bundles termed kinetochore fibers (K-fibers). K-fibers form by two distinct mechanisms: (1) capture of astral microtubules nucleated at the centrosome by the chromosomes' kinetochores or (2) attachment of kinetochores to noncentrosomal microtubules with subsequent transport of the minus ends of these microtubules toward the spindle poles. The relative contributions of these alternative mechanisms to normal spindle assembly remain unknown...
June 15, 2018: Journal of Cell Biology
Xiaofei Song, Christine R Beck, Renqian Du, Ian M Campbell, Zeynep Coban-Akdemir, Shen Gu, Amy M Breman, Pawel Stankiewicz, Grzegorz Ira, Chad A Shaw, James R Lupski
Alu elements, the short interspersed element numbering >1 million copies per human genome, can mediate the formation of copy number variants (CNVs) between substrate pairs. These Alu/Alu-mediated rearrangements (AAMR) can result in pathogenic variants that cause diseases. To investigate the impact of AAMR on gene variation and human health, we first characterized Alus that are involved in mediating CNVs (CNV-Alus) and observed that these Alus tend to be evolutionarily younger. We then computationally generated, with the assistance of a supercomputer, a test dataset consisting of 78 million Alu pairs and predicted ~18% of them are potentially susceptible to AAMR...
June 15, 2018: Genome Research
Sarah E Hancock, Ramesh Ailuri, David L Marshall, Simon H J Brown, Jennifer T Saville, Venkateswara R Narreddula, Nathan R Boase, Berwyck L J Poad, Adam J Trevitt, Mark D P Willcox, Michael J Kelso, Todd W Mitchell, Stephen J Blanksby
The (O-acyl)-ω-hydroxy fatty acids (OAHFA) are an unusual lipid subclass present in the skin, vernix caseosa and meibomian gland secretions. While they are structurally related to the general class of fatty acid esters of hydroxy fatty acids (FAHFA), the ultra-long chain (30-34 carbons) and putative ω-substitution of the backbone hydroxy fatty acid suggest OAHFA have unique biochemistry. Complete structural elucidation of OAHFA has been challenging due to their low abundance within complex lipid matrices...
June 15, 2018: Journal of Lipid Research
Priyanka Jain, Subhash Chandra Sethi, Vavilala A Pratyusha, Pramita Garai, Nilofer Naqvi, Sonali Singh, Kalpana Pawar, Niti Puri, Sneha Sudha Komath
The ability of C. albicans to switch between yeast to hyphal form is a property that is primarily associated with the invasion and virulence of this human pathogenic fungus. Several GPI anchored proteins are expressed only during hyphal morphogenesis. One of the major pathways that controls hyphal morphogenesis is the Ras signaling pathway. We examine the cross-talk between GPI anchor biosynthesis and Ras signaling in C. albicans We show that the first step of GPI biosynthesis is activated by Ras in C. albicans This is diametrically opposite to what is reported in S...
June 15, 2018: Journal of Biological Chemistry
Jana Pipiková, Ingrid Papajová, Viktória Majláthová, Jindřich Šoltys, Júlia Bystrianska, Ingrid Schusterová, Veronika Vargová
BACKGROUND: Giardiasis is one of the most common gastrointestinal infections of humans and animals attributable to complex of eight morphologically identical genetic assemblages, further divided into sub-assemblages. Disease is common for a wide range of hosts and genetic characterization is needed for better understanding of multifaceted epidemiology for this protozoan parasite. The aim of this study was to identify genetic heterogeneity in assemblages and sub-assemblages of Giardiaduodenalis circulating among the children population living in deprived socioeconomic conditions...
June 2, 2018: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
Tom H Johnston, Alix M B Lacoste, Naomi P Visanji, Anthony E Lang, Susan H Fox, Jonathan M Brotchie
In this review, we discuss the opportunity for repurposing drugs for use in l-DOPA-induced dyskinesia (LID) in Parkinson's disease. LID is a particularly suitable indication for drug repurposing given its pharmacological diversity, translatability of animal-models, availability of Phase II proof-of-concept (PoC) methodologies and the indication-specific regulatory environment. A compound fit for repurposing is defined as one with appropriate human safety-data as well as animal safety, toxicology and pharmacokinetic data as found in an Investigational New Drug (IND) package for another indication...
June 1, 2018: Neuropharmacology
Jamie Golden, Jessica A Zagory, Michael Fenlon, Catherine J Goodhue, Yi Xiao, Xiaowei Fu, Kasper S Wang, Christopher P Gayer
BACKGROUND: Biliary atresia (BA) is difficult to distinguish from other causes of cholestasis. We evaluated the use of liquid chromatography-mass spectroscopy (LC-MS) and bile acid profiles in the rapid, noninvasive diagnosis of BA. MATERIALS AND METHODS: Following Institutional Animal Care and Use Committee and Institutional Review Board approval, we used LC-MS to measure 26 bile acids in serum and stool samples from experimental models of BA and in urine, stool, and serum samples from non-cholestatic and cholestatic human infants...
August 2018: Journal of Surgical Research
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