Exposure to dioxins and related persistent organic pollutants likely contributes to cardiovascular disease (CVD) risk through multiple mechanisms including the induction of chronic inflammation. Epidemiological studies have shown that leaner individuals may be more susceptible to the detrimental effects of lipophilic toxicants because they lack large adipose tissue depots that can accumulate and sequester these pollutants. This phenomenon complicates efforts to study mechanisms of pollutant-accelerated atherosclerosis in experimental animal models where high-fat feeding and adipose expansion limit the bioavailability of lipophilic pollutants.
View Article and Find Full Text PDFThe human kynurenine 3-monooxygenase (hKMO) is a potential therapeutic target for neurodegenerative and neurologic disorders. Inhibition of KMO by Ro 61-8048, a potent, selective, and the most widely used inhibitor of KMO, was shown effective in various models of neurodegenerative or neurologic disorders. However, the molecular basis of hKMO inhibition by Ro 61-8048 is not clearly understood.
View Article and Find Full Text PDFRecent discoveries of broadly neutralizing antibodies (bnAbs) in HIV-1-infected individuals have led to the identification of several major "vulnerable sites" on the HIV-1 envelope (Env) glycoprotein. These sites have provided precise targets for HIV-1 vaccine development, but identifying and utilizing many of these targets remain technically challenging. Using a yeast surface display-based approach, we sought to identify epitope-focused antigenic domains (EADs) containing one of the "vulnerable sites," the CD4-binding site (CD4bs), through screening and selection of a combinatorial antigen library of the HIV-1 envelope glycoprotein with the CD4bs bnAb VRC01.
View Article and Find Full Text PDFLiver cancer is the fifth most common cancer with extremely low five year survival rate. Early diagnosis is of great importance for cancer therapy. In this work, stable isotope labeling-based relative quantitative proteomics and parallel reaction monitoring-based target proteomics were combined for cancer biomarker screening and validation.
View Article and Find Full Text PDFObjective: To evaluate the disease burden of placental maternal vascular malperfusion pathology in a low-risk nulliparous population and test the hypothesis that a multiparameter model in the second trimester can predict maternal vascular malperfusion with high precision.
Methods: A single-center, prospective cohort study was conducted in healthy nulliparous women. Maternal vascular malperfusion disease burden was estimated by incidence, relative risk (RR), and population-attributable risk percent.
Objective: The objective of this study was to examine the association between umbilical catheters and a composite outcome of mortality or major neonatal morbidity in extremely preterm infants.
Study Design: Data were abstracted from the Canadian Neonatal Network database for infants born at <29 weeks' gestational age and admitted to 29 neonatal intensive care units between January 2010 and December 2012. Four groups were identified: those with no umbilical catheters, umbilical venous catheters (UVCs), umbilical artery catheters (UACs), and those with both UVCs and UACs.
To understand the source-to-sink of pollutants in the Kelantan River estuary and the adjacent shelf area in Malaysia, a total of 42 surface sediment samples were collected in the Kelantan River-estuary-shelf system to analyze for grain size, total organic carbon (TOC) content, Al and heavy metals (Cr, Ni, Cu, Zn, Cd and Pb). The surficial sediments were mainly composed of clayey silt and the TOC content in sediments decreased from the river to the shelf. The surficial sediments experienced Pb pollution; Cr only showed a certain level of pollution in the coastal area of the estuary but not in other areas, and Ni, Cu, Zn, and Cd showed no pollution.
View Article and Find Full Text PDFBackground: Use, timing and doses of surfactant in preterm infants are variable in practice in modern NICUs.
Objective: The objective of this study is to explore the association between use and timing of surfactant administration and common neonatal adverse outcomes in preterm infants with gestational age (GA) < 28 weeks.
Material And Methods: Neonates admitted to a participating Canadian Neonatal Network NICU between 2013 and 2015 were studied.
Background: Compared to very low gestational age (<32 weeks, VLGA) cohorts, very low birth weight (<1500 g; VLBW) cohorts are more prone to selection bias toward small-for-gestational age (SGA) infants, which may impact upon the validity of data for benchmarking purposes.
Method: Data from all VLGA or VLBW infants admitted in the 3 Networks between 2008 and 2011 were used. Two-thirds of each network cohort was randomly selected to develop prediction models for mortality and composite adverse outcome (CAO: mortality or cerebral injuries, chronic lung disease, severe retinopathy or necrotizing enterocolitis) and the remaining for internal validation.
Gynecol Endocrinol
January 2018
The objective of this study was to assess the effects of elevated luteal-phase progesterone levels (PE) and high progesterone/estradiol ratio ('P/E2' ratio) on IVF outcomes, exclusively in GnRH-antagonist cycles with day-5 embryo transfer. PE was not found to have a significant effect on implantation or clinical pregnancy rate (CPR) (OR 0.56, 95% CI 0.
View Article and Find Full Text PDFBackground: Airway guidelines recommend the use of ultrasound to localize the cricothyroid membrane prior to airway manipulation in difficult airways. In this study, we aimed to determine the amount of training anesthesia trainees would need to achieve competence in bedside ultrasound to identify the cricothyroid membrane.
Methods: This is a prospective non-randomized cohort study in the Department of Anesthesia at Mount Sinai Hospital (Toronto, Ontario, Canada).
During HIV-associated neurocognitive disorder (HAND), decreasing in excitatory amino acid transporter 2 (EAAT-2) in astrocyte plasma membranes leads to elevated levels of extracellular glutamate and, in turn, neuronal apoptosis. We used immunohistochemistry, western blot, qRT-PCR, and RNA interference to elucidate the molecular mechanisms underlying the decreased EAAT-2 expression during HAND at the tissue and cellular levels. We used simian immunodeficiency virus-human immunodeficiency virus chimeric virus (SHIV)-infected macaques as an in vivo model of HAND.
View Article and Find Full Text PDFThe bacteriophage ϕ29 infects Gram-positive with a short noncontractile tail. Recent studies showed that the ϕ29 tail protein gp9 forms a hexameric tube with six long loops of membrane-active peptides blocking in the tube at the distal end of the tail. The long loops exit on genome release and form a membrane pore for passage of the genome.
View Article and Find Full Text PDFJ Matern Fetal Neonatal Med
June 2018
Background: Failure of first course of indomethacin (FCI) for patent ductus arteriosus (PDA) treatment in preterm neonates often prompts clinicians to consider a second course (SCI).
Objective: To identify factors including baseline characteristics and response to FCI that are associated with non-response to SCI for PDA treatment in preterm neonates.
Methods: In this retrospective observational study, neonates ≤32 weeks admitted to a tertiary NICU over 5 years who received two indomethacin courses for PDA treatment were reviewed.
Nanoscale Res Lett
December 2017
First-principles density functional theory (DFT) simulations were carried out to study the strain dependence on the electronic and optical properties of cadmium selenide (CdSe) nanowires (NWs). The band structures, effective masses of electron and holes, dielectric properties, and other optical properties (such as extinction coefficient, optical reflectivity, and absorption coefficient) were calculated under both compressive and tensile uniaxial strains. Size-dependence was also discussed by comparing results among CdSe wires with various diameters.
View Article and Find Full Text PDFBackground: The use of phenylephrine as the first-line agent for prevention and treatment of maternal hypotension during cesarean delivery (CD) may reduce cardiac output, posing a theoretical risk to mother and fetus. Norepinephrine has been suggested as a potential alternative, because its β-adrenergic effects might result in greater heart rate and cardiac output than phenylephrine. The use of norepinephrine to prevent and treat hypotension during CD is new, and its use as a bolus has not been fully determined in this context.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
February 2017
Purpose: The retina has an important role in the signal transmission related to eye development and myopia. Glutamate (Glu) and γ-aminobutyric acid (GABA) are the major excitatory and inhibitory neurotransmitters in the retina, which can affect the development of both the eye and myopia. Nevertheless, change in the balance between the excitatory and inhibitory neurotransmitters still is unclear during development of eyes and myopia.
View Article and Find Full Text PDFThe geochemical compositions of sediments in the Dongshan Bay, a semi-enclosed bay on the southeast coast of China, were obtained to identify pollutant sources and evaluate the anthropogenic impacts over the last 100 years. The results indicated that the metal flux had been increasing since the 1980s. Enrichment factor values (Pb, Zn and Cu) suggested only slight enrichment.
View Article and Find Full Text PDFThe molecular mechanisms involved in human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) remain poorly understood. It has been recently reported that HIV-1 Tat transactivation requires menin, suggesting that menin may be involved in HAND pathogenesis. But the role of menin is not clear.
View Article and Find Full Text PDFCullin 4B (CUL4B), a scaffold protein that assembles CRL4B ubiquitin ligase complexes, is overexpressed in many types of cancers and represses many tumor suppressors through epigenetic mechanisms. However, the mechanisms by which CUL4B is upregulated remain to be elucidated. Here, we show that CUL4B is upregulated in non-small-cell lung carcinoma (NSCLC) tissues and is critically required for cell proliferation and migration in vitro and for xenograft tumor formation in vivo.
View Article and Find Full Text PDFUntil recently most researches on myopia mechanisms have mainly been focused on the eye ball and few investigations were explored on the upper visual pathway, such as the visual cortex. The roles of gamma-aminobutyric acid (GABA) in the retinal and in the upper visual pathway are inter-correlated. As the retinal glutamate decarboxylase (GAD), GABA, and the mRNA levels of GABA receptors increased during the concave lens induced myopia formation, however, whether GABA alterations also occurred in the visual cortex during the concave lens induction is still unknown.
View Article and Find Full Text PDFThe present study examines the uptake of the heavy metal cadmium (Cd) by Microcystis aeruginosa in the presence of dissolved organic matter (DOM) from different origins. The DOM used in the present study were extracted from soil, sediment taken from Meiliang Bay at Taihu Lake, and from M. aeruginosa cultured in the laboratory.
View Article and Find Full Text PDFHeavy metal contamination of aquatic environment has attracted global attention owing to its abundance, persistence, and environmental toxicity, especially in developing countries like Bangladesh. Five heavy metals, namely chromium (Cr), copper (Cu), nickel (Ni), lead (Pb) and zinc (Zn) were investigated in surface and core sediments of the Karnaphuli River (KR) estuary in Chittagong, Bangladesh, in order to reveal the heavy metal contamination history in estuarine sediments and its response to catastrophic events and human activities. The surface sediment was predominantly composed of silt and sand, and the surface sediment was contaminated with Cr and Pb.
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