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Zishaan Farooqui, Kelly M Bakulski, Melinda C Power, Marc G Weisskopf, David Sparrow, Avron Spiro, Pantel S Vokonas, Linda H Nie, Howard Hu, Sung Kyun Park
BACKGROUND: Lead (Pb) exposure has been associated with poorer cognitive function cross-sectionally in aging adults, however the association between cumulative Pb exposure and longitudinal changes in cognition is little characterized. METHODS: In a 1993-2007 subcohort of the VA Normative Aging Study (Mini-mental status exam (MMSE) n=741; global cognition summary score n=715), we used linear mixed effects models to test associations between cumulative Pb exposure (patella or tibia bone Pb) and repeated measures of cognition (MMSE, individual cognitive tests, and global cognition summary)...
October 19, 2016: Environmental Research
Marco Muth, Stefanie Rothkötter, Steven Paprosch, Reiner P Schmid, Klaus Schnitzlein
Lipase-catalyzed hydrolysis of triglycerides yields glycerol and free fatty-acids, provided that the enzyme is non-regioselective. For an Sn-1,3 regioselective enzyme, such as lipase from Thermomyces lanuginosus, the final product is no longer glycerol but Sn-2 monoglyceride instead. However, surface active molecules generated by lipolysis may have a detrimental effect on the interfacial biocatalysis since it is known that low molecular weight surfactants can displace proteins from interfaces. By using drop profile analysis tensiometry, we evaluated the interfacial properties of the lipase-generated molecules and their competitive effect on the adsorption behavior of the lipase and on the proceeding lipolysis...
October 12, 2016: Colloids and Surfaces. B, Biointerfaces
K S Weber, K Strassburger, G Pacini, B Nowotny, K Müssig, J Szendroedi, C Herder, M Roden
AIMS: To examine the hypothesis that changes in serum adiponectin concentration inversely relate to changes in glucose tolerance and β-cell function already during the early stage of disease progression in recently diagnosed Type 1 and Type 2 diabetes mellitus. METHODS: Participants in the prospective observational German Diabetes Study (Type 2 diabetes, n = 94; Type 1 diabetes, n =42) underwent i.v. glucose tolerance and glucagon stimulation testing to assess pre-hepatic β-cell function, glucose tolerance index and C-peptide secretion within the first year of diabetes diagnosis and 2 years later...
October 22, 2016: Diabetic Medicine: a Journal of the British Diabetic Association
Y H Cho, M E Craig, A S Januszewski, P Benitez-Aguirre, S Hing, A J Jenkins, K C Donaghue
AIM: To test the hypothesis that non-invasive skin autofluorescence, a measure of advanced glycation end products, would provide a surrogate measure of long-term glycaemia and be associated with early markers of microvascular complications in adolescents with Type 1 diabetes. METHODS: Forearm skin autofluorescence (arbitrary units) was measured in a cross-sectional study of 135 adolescents with Type 1 diabetes [mean ± sd age 15.6 ± 2.1 years, diabetes duration 8...
October 22, 2016: Diabetic Medicine: a Journal of the British Diabetic Association
Christel Häggström, Mieke Van Hemelrijck, Björn Zethelius, David Robinson, Birgitta Grundmark, Lars Holmberg, Soffia Gudbjörnsdottir, Hans Garmo, Pär Stattin
Type 2 diabetes mellitus (T2DM) has consistently been associated with decreased risk of prostate cancer, however, if this decrease is related to the use of anti-diabetic drugs is unknown. We prospectively studied men in the comparison cohort in the Prostate Cancer data Base Sweden (PCBaSe) 3.0, with data on T2DM, use of metformin, sulphonylurea, and insulin retrieved from national health care registers and demographic databases. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) of prostate cancer, adjusted for confounders...
October 22, 2016: International Journal of Cancer. Journal International du Cancer
Hilde de Kluiver, Jacobine E Buizer-Voskamp, Conor V Dolan, Dorret I Boomsma
We review the hypotheses concerning the association between the paternal age at childbearing and childhood psychiatric disorders (autism spectrum- and attention deficit/hyperactive disorder) and adult disorders (schizophrenia, bipolar-, obsessive-compulsive-, and major depressive disorder) based on epidemiological studies. Several hypotheses have been proposed to explain the paternal age effect. We discuss the four main-not mutually exclusive-hypotheses. These are the de novo mutation hypothesis, the hypothesis concerning epigenetic alterations, the selection into late fatherhood hypothesis, and the environmental resource hypothesis...
October 22, 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Raimund Weitgasser, Michaela Ratzinger, Margit Hemetsberger, Peter Siostrzonek
For over 30 years, intensive research efforts investigated the role of LDL cholesterol in the pathogenesis of cardiovascular disease. In various settings, large statin trials showed an association between LDL cholesterol levels and cardiovascular event rates. This association is often referred to as the 'LDL cholesterol hypothesis'. More recent trials on agents with totally different modes of action confirmed this association and indicated a causal relationship between lower LDL cholesterol levels and improved cardiovascular outcomes...
October 21, 2016: Wiener Medizinische Wochenschrift
Yumiko Ohbayashi, Fumi Nakai, Akinori Iwasaki, Takaaki Ogawa, Yuka Yamamoto, Yoshihiro Nishiyama, Minoru Miyake
The duration of antiresorptive therapy is an important risk factor for medication-related osteonecrosis of the jaw. We performed a pilot study using quantitative analysis by bone scintigraphy to test the hypothesis that mandibular metabolism is affected by long-term bisphosphonate (BP) therapy. Our primary objectives were to assess changes in bone metabolism of the mandible in response to long-term BP therapy and compare the bone metabolism changes of the mandible with other bone sites. We compared the metabolic difference at the site in the mandible unaffected by disease, the humerus and the femur between 14 osteoporosis patients who were being treated with BP (BP group) and 14 patients who were not being treated with BP (control group) using a quantitative analysis and bone scintigraphy...
October 21, 2016: Odontology
Malin E M Mörner, Gustaf Edgren, Anna Martling, Ulf Gunnarsson, Monika Egenvall
PURPOSE: The hypothesis in this study was that anaemia prior to surgery and perioperative red blood cell transfusion increases the risk for recurrence and overall mortality in patients with stages I-III colorectal cancer after abdominal resection with curative intent. METHODS: This is a Swedish single centre retrospective cohort study. Data on 496 consecutive radical abdominal resections stages I-III colorectal cancer performed at the Karolinska University Hospital 2007-2010 were extracted from the Swedish Colorectal Cancer Registry...
October 21, 2016: International Journal of Colorectal Disease
David J Koss, Glynn Jones, Anna Cranston, Heidi Gardner, Nicholas M Kanaan, Bettina Platt
Post-mortem investigations of human Alzheimer's disease (AD) have largely failed to provide unequivocal evidence in support of the original amyloid cascade hypothesis, which postulated deposition of β-amyloid (Aβ) aggregates to be the cause of a demented state as well as inductive to tau neurofibrillary tangles (NFTs). Conflicting evidence suggests, however, that Aβ plaques and NFTs, albeit to a lesser extent, are present in a substantial subset of non-demented individuals. Hence, a range of soluble tau and Aβ species has more recently been implicated as the disease-relevant toxic entities...
October 21, 2016: Acta Neuropathologica
Jie Gao, John L Williams, Esra Roan
Growth plate chondrocytes are responsible for bone growth through proliferation and differentiation. However, the way they experience physiological loads and regulate bone formation, especially during the later developmental phase in the mature growth plate, is still under active investigation. In this study, a previously developed multiscale finite element model of the growth plate is utilized to study the stress and strain distributions within the cartilage at the cellular level when rapidly compressed to 20 %...
October 21, 2016: Biomechanics and Modeling in Mechanobiology
Georgie Powell, Zoe Meredith, Rebecca McMillin, Tom C A Freeman
According to Bayesian models, perception and cognition depend on the optimal combination of noisy incoming evidence with prior knowledge of the world. Individual differences in perception should therefore be jointly determined by a person's sensitivity to incoming evidence and his or her prior expectations. It has been proposed that individuals with autism have flatter prior distributions than do nonautistic individuals, which suggests that prior variance is linked to the degree of autistic traits in the general population...
October 21, 2016: Psychological Science
Shu-Yu Wu, Ping Zou, Alexandra W Fuller, Sanjay Mishra, Zhen Wang, Kevin L Schey, Hassane S Mchaourab
The refractivity and transparency of the ocular lens is dependent on the stability and solubility of the crystallins in the fiber cells. A number of mutations of lens crystallins have been associated with dominant cataracts in humans and mice. Of particular interest were γB- and γD-crystallin mutants linked to dominant cataracts in mouse models. While thermodynamically destabilized and aggregation-prone, these mutants were found to have weak affinity to the resident chaperone α-crystallin in vitro To better understand the mechanism of the cataract phenotype, we transgenically expressed different γD-crystallin mutants in the zebrafish lens, and observed a range of lens defects that arise primarily from the aggregation of the mutant proteins...
October 21, 2016: Journal of Biological Chemistry
David F Woodward, Jenny W Wang, Ming Ni, Alex Bauer, Jose L Martos, Robert W Carling, Neil J Poloso
The purpose of these studies was to test the hypothesis that a selected polypharmacological approach for treating the prostanoid-mediated component of inflammatory diseases would produce a therapeutic effect superior to global inhibition of prostaglandin (PG) biosynthesis by aspirin-like drugs. The compound studied was AGN 211377, which had been previously shown to produce a superior effect on cytokine release from human macrophages compared with cyclooxygenase (COX) inhibitors. AGN 211377 antagonizes prostanoid prostaglandin D2 (DP)1, DP2, prostaglandin E2 (EP)1, EP4, prostaglandin F2α, and thromboxane A2 receptors but not anti-inflammatory EP2, prostaglandin I2, or EP3 receptors...
October 21, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Hung-Yi Liu, Tanja Greene, Tsai-Yu Lin, Camron S Dawes, Murray Korc, Chien-Chi Lin
: The complex network of biochemical and biophysical cues in the pancreatic desmoplasia not only presents challenges to the fundamental understanding of tumor progression, but also hinders the development of therapeutic strategies against pancreatic cancer. Residing in the desmoplasia, pancreatic stellate cells (PSCs) are the major stromal cells affecting the growth and metastasis of pancreatic cancer cells by means of paracrine effects and extracellular matrix protein deposition. PSCs remain in a quiescent/dormant state until they are 'activated' by various environmental cues...
October 18, 2016: Acta Biomaterialia
A R Fetoni, R Rolesi, F Paciello, S L M Eramo, C Grassi, D Troiani, G Paludetti
Experimental and human investigations have raised the level of concern about the potential ototoxicity of organic solvents and their interaction with noise. The main objective of this study was to characterize the effects of the combined noise and styrene exposure on hearing focusing on the mechanism of damage on the sensorineural cells and supporting cells of the organ of Corti and neurons of the ganglion of Corti. The impact of single and combined exposures on hearing was evaluated by auditory functional testing and histological analyses of cochlear specimens...
October 18, 2016: Free Radical Biology & Medicine
Masaaki Iwata, Hisahito Ishida, Koichi Kaneko, Yukihiko Shirayama
An accumulating body of evidence has demonstrated that inflammation is associated with the pathology of depression. We recently found that psychological stress induces inflammation in the hippocampus of the rat brain through the inflammasome, a component of the innate immune system. Microglia, the resident macrophages in the brain, play a central role in the innate immune system and express inflammasomes; thus, we hypothesized that hippocampal microglia would be key mediators in the development of depression via stress-induced inflammation...
October 18, 2016: Pharmacology, Biochemistry, and Behavior
Alissa B Forman-Alberti, J Benjamin Hinnant
The somatic marker hypothesis posits that autonomic activity occurring in response to specific stimuli aids in implicit learning, the learning of information without explicit awareness of what has been learned. This study investigated whether respiratory sinus arrhythmia (RSA), a measure of autonomic nervous system activity, predicted changes in implicit learning. The interaction of resting RSA and RSA reactivity (change in RSA during the implicit learning task) was associated with changes in implicit learning, with those who had higher resting RSA and greater RSA withdrawal during the task performing better...
October 18, 2016: International Journal of Psychophysiology
Alan P Brown, Philip Drew, Brian Knight, Philippe Marc, Sean Troth, Kuno Wuersch, Joyce Zandee
Histopathology data comprise a critical component of pharmaceutical toxicology studies and are typically presented as finding incidence counts and severity scores per organ, tabulated on multiple pages which can be challenging for review and aggregation of results. However, the SEND (Standard for Exchange of Nonclinical Data) standard provides a means for collecting and managing histopathology data in a uniform fashion which can allow informatics systems to archive, display and analyze data in novel ways. Various software applications have become available to convert histopathology data into graphical displays for analyses...
October 18, 2016: Regulatory Toxicology and Pharmacology: RTP
Qiang Tan, Qianwei Chen, Zhou Feng, Xia Shi, Jun Tang, Yihao Tao, Bing Jiang, Liang Tan, Hua Feng, Gang Zhu, Yunfeng Yang, Zhi Chen
Fibrosis in ventricular system has a role in hydrocephalus following intraventricular hemorrhage (IVH). The cannabinoid receptor 2 (CB2) has been reported to participate in alleviating the fibrosis process of many diseases. However, its role in fibrosis after IVH was unclear so far, and we hypothesized that CB2 activation has potential to attenuate hydrocephalus after IVH via restricting fibrosis. So the present study was designed to investigate this hypothesis in a modified rat IVH model. Autologous non-anticoagulative blood injection model was induced to mimic ventricular extension of hemorrhage in adult Sprague-Dawley rats...
October 18, 2016: Brain Research
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