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Find video protocols related to scientific articles indexed in Pubmed.
Circumventing Seizure Activity in a Series of G Protein Coupled Receptor 119 (GPR119) Agonists.
J. Med. Chem.
PUBLISHED: 11-03-2014
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Agonism of GPR119 is viewed as a potential therapeutic approach for the treatment of type II diabetes and other elements of metabolic syndrome. During progression of a previously disclosed candidate 1 through mice toxicity studies, we observed tonic-clonic convulsions in several mice at high doses. An in vitro hippocampal brain slice assay was used to assess the seizure liability of subsequent compounds, leading to the identification of an aryl sulfone as a replacement for the 3-cyano pyridyl group. Subsequent optimization to improve the overall profile, specifically with regard to hERG activity, led to alkyl sulfone 16. This compound did not cause tonic-clonic convulsions in mice, had a good pharmacokinetic profile, and displayed in vivo efficacy in murine models. Importantly, it was shown to be effective in wild-type (WT) but not GPR119 knockout (KO) animals, consistent with the pharmacology observed being due to agonism of GPR119.
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Immunotherapy for recurrent miscarriage.
Cochrane Database Syst Rev
PUBLISHED: 10-22-2014
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Because immunological aberrations might be the cause of miscarriage in some women, several immunotherapies have been used to treat women with otherwise unexplained recurrent pregnancy loss.
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The predictive value of single-photon emission computed tomography/computed tomography for sentinel lymph node localization in head and neck cutaneous malignancy.
Laryngoscope
PUBLISHED: 10-15-2014
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Preoperative localization of sentinel lymph nodes in head and neck cutaneous malignancies can be aided by single-photon emission computed tomography/computed tomography (SPECT/CT); however, its true predictive value for identifying lymph nodes intraoperatively remains unquantified. This study aims to understand the sensitivity, specificity, and positive and negative predictive values of SPECT/CT in sentinel lymph node biopsy for cutaneous malignancies of the head and neck.
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Religiosity and the Transition to Nonmarital Parity.
Sex Res Social Policy
PUBLISHED: 10-10-2014
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Nonmarital parity is associated with several negative outcomes, including health problems, educational problems, and poverty. Understanding the risk and protective factors associated with nonmarital parenthood can inform policy and interventions, reducing both the incidences and associated consequences. The current study focuses on how intrinsic and extrinsic religiosity (the degree to which individuals or groups employ religious ideology in forming values and making decisions) are related to the timing of nonmarital parity using discrete time hazard modeling of a nationally representative sample of adolescent females (N=7,367) from the National Longitudinal Study of Adolescent Health. The majority of the sample (86 %) claimed a religious affiliation and almost a third (32 %) had a nonmarital birth during the study. Even though the majority of the sample is White (67 %), Black and Hispanic females were more likely to experience a nonmarital birth. Results indicate that intrinsic and extrinsic religiosity and religious affiliation assert protective effects for some populations while religious affiliation increases risk in the full model. Recommendations for policy, intervention, and future research are offered.
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Asthma & Allergy Development: Contrasting Influences of Yeasts & Other Fungal Exposures.
Clin. Exp. Allergy
PUBLISHED: 09-10-2014
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Infancy is a developmental stage with heightened susceptibility to environmental influences on the risk of chronic childhood disease. Few birth cohort studies have detailed measures of fungal diversity data in infants' bedrooms, limiting the potential to measure long-term associations of these complex exposures with development of asthma or allergy.
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Maternal psychological distress mediates the relationship between asthma and physician visits in a population-based sample of adolescents.
J Asthma
PUBLISHED: 08-28-2014
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Abstract Objective: This study examined whether maternal psychological distress mediates the relationship between presence of adolescent asthma and number of physician visits and whether the association between maternal psychological distress and physician visits is moderated by adolescent general health. Methods: Data were obtained from the Mater University Study of Pregnancy and included 4025 adolescents. Path analysis was used to examine mediating and moderating effects. Results: Maternal psychological distress was found to partially mediate the relationship between adolescent asthma and number of physician visits, accounting for 25% of the effect of adolescent asthma on physician visits (p?=?0.046). There was no evidence to suggest that adolescent general health moderated the association between maternal psychological distress and physician visits (p?=?0.093). Conclusions: These findings suggest that maternal psychological distress is associated with increased physician visits, regardless of adolescents' general health. Lowering maternal psychological distress may serve to reduce health care utilization and costs among adolescents with asthma.
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Western Cold and Flu (WeCoF) aerosol study--preliminary results.
BMC Res Notes
PUBLISHED: 08-23-2014
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Influenza virus is responsible for annual deaths due to seasonal epidemics and is the cause of major pandemics which have claimed millions of human lives over the last century. Knowledge about respiratory virus transmission is advancing. Spread is likely through the air, but much work remains to be done to characterize the aerosols produced by infected individuals, including viral particle survival and infectivity. Although coughs have been characterized, little work has been done to examine coughs from infected individuals. The WeCoF project aims at providing evidence to support prevention measures to mitigate person-to-person influenza transmission in critical locations, such as hospitals, and during pandemics.
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Exposure to stressful life events during pregnancy predicts psychotic experiences via behaviour problems in childhood.
J Psychiatr Res
PUBLISHED: 08-20-2014
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Exposure to stressful life events during pregnancy has been associated with later schizophrenia in offspring. We explore how prenatal stress and neurodevelopmental abnormalities in childhood associate to increase the risk of later psychotic experiences.
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The South Asian genome.
PLoS ONE
PUBLISHED: 08-12-2014
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The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.
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Exploring vertex interactions in ferroelectric flux-closure domains.
Nano Lett.
PUBLISHED: 07-31-2014
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Using piezoresponse force microscopy, we have observed the progressive development of ferroelectric flux-closure domain structures and Landau-Kittel-type domain patterns, in 300 nm thick single-crystal BaTiO3 platelets. As the microstructural development proceeds, the rate of change of the domain configuration is seen to decrease exponentially. Nevertheless, domain wall velocities throughout are commensurate with creep processes in oxide ferroelectrics. Progressive screening of macroscopic destabilizing fields, primarily the surface-related depolarizing field, successfully describes the main features of the observed kinetics. Changes in the separation of domain-wall vertex junctions prompt a consideration that vertex-vertex interactions could be influencing the measured kinetics. However, the expected dynamic signatures associated with direct vertex-vertex interactions are not resolved. If present, our measurements confine the length scale for interaction between vertices to the order of a few hundred nanometers.
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Successful recruitment to a study of first-episode psychosis by clinicians: a qualitative account of outcomes and influences on process.
J Ment Health
PUBLISHED: 06-20-2014
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Abstract Background: Strategies proposed to promote recruitment of representative samples to trials and mental health research have focused on researchers external to clinical services. How clinicians approach recruitment as researchers and particularities of recruiting people with first episode of psychosis warrant investigation.
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Auditory verbal hallucinations in persons with and without a need for care.
Schizophr Bull
PUBLISHED: 06-18-2014
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Auditory verbal hallucinations (AVH) are complex experiences that occur in the context of various clinical disorders. AVH also occur in individuals from the general population who have no identifiable psychiatric or neurological diagnoses. This article reviews research on AVH in nonclinical individuals and provides a cross-disciplinary view of the clinical relevance of these experiences in defining the risk of mental illness and need for care. Prevalence rates of AVH vary according to measurement tool and indicate a continuum of experience in the general population. Cross-sectional comparisons of individuals with AVH with and without need for care reveal similarities in phenomenology and some underlying mechanisms but also highlight key differences in emotional valence of AVH, appraisals, and behavioral response. Longitudinal studies suggest that AVH are an antecedent of clinical disorders when combined with negative emotional states, specific cognitive difficulties and poor coping, plus family history of psychosis, and environmental exposures such as childhood adversity. However, their predictive value for specific psychiatric disorders is not entirely clear. The theoretical and clinical implications of the reviewed findings are discussed, together with directions for future research.
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Validity of the diagnostic criteria for chronic cerebrospinal venous insufficiency and association with multiple sclerosis.
CMAJ
PUBLISHED: 06-02-2014
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The chronic cerebrospinal venous insufficiency theory proposes that altered cerebral venous hemodynamics play a role in the pathophysiology of multiple sclerosis. We aimed to explore the validity of this hypothesis by assessing the diagnostic criteria for chronic cerebrospinal venous insufficiency in persons with and without multiple sclerosis.
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Do young people with comorbid mental and alcohol disorders experience worse behavioural problems?
Psychiatry Res
PUBLISHED: 05-23-2014
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This article examines whether young individuals in the general population with comorbid alcohol use and mental health disorders experience worse internalizing and externalizing behaviour problems than those with single disorders. A large cohort of women at the Mater Misericordiae Hospital in Brisbane, Australia, was enroled during pregnancy in a longitudinal study. Mother/offspring dyads were followed over 21 years. At age 21, offspring behaviour problems were examined using the Young Adult Self Report, alcohol and mental health disorders with the Composite International Diagnostic Interview. Associations between comorbidity and behaviour problems were assessed using multinomial logistic regression, accounting for life-course factors. Twelve per cent of young adults had alcohol/mental health DSM-IV disorders with significant temporal overlap. A further 16% had alcohol disorders only and 23% mental health disorders only. The comorbid group scored significantly higher on total and externalizing behaviour problems but not internalizing behaviour problems. Stronger associations of aggression/delinquency with comorbidity were not fully accounted for by factors known to influence separate development of mental health and alcohol disorders. Young adults with comorbid alcohol/mental health disorders experience more, and more severe, behavioural problems than those with single disorder types, indicating an increased burden from comorbidity, with implications for treatment and public order.
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Current and future therapies for herpes simplex virus infections: mechanism of action and drug resistance.
Curr Opin Virol
PUBLISHED: 05-15-2014
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Forty years after the discovery of acyclovir (ACV), it remains the mainstay of therapy for herpes simplex virus (HSV) infections. Since then, other antiviral agents have also been added to the armamentarium for these infections but ACV remains the therapy of choice. As the efficacy of ACV is reassessed, however, it is apparent that a therapy with increased efficacy, reduced potential for resistance, and improved pharmacokinetics would improve clinical outcome, particularly in high risk patients. Inhibitors of viral targets other than the DNA polymerase, such as the helicase primase complex, are of particular interest and will be valuable as new therapeutic approaches are conceived. This review focuses on currently approved HSV therapies as well as new systemic therapies in development.
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Factors influencing the likelihood of instrumental delivery success.
Obstet Gynecol
PUBLISHED: 05-03-2014
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To evaluate risk factors for unsuccessful instrumental delivery when variability between individual obstetricians is taken into account.
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Use of restrictive interventions in a child and adolescent inpatient unit - predictors of use and effect on patient outcomes.
Australas Psychiatry
PUBLISHED: 05-01-2014
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Restrictive interventions (seclusion, physical restraint, and use of acute/p.r.n. sedation) may have negative effects on patients. Identifying factors associated with use of restrictive interventions and examining their effect on admission outcomes is important for optimising inpatient psychiatric care.
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Giant room-temperature elastocaloric effect in ferroelectric ultrathin films.
Adv. Mater. Weinheim
PUBLISHED: 04-29-2014
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Environmentally friendly ultrathin BaTiO3 capacitors can exhibit a giant stress-induced elastocaloric effect without hysteresis loss or Joule heating. By combining this novel elastocaloric effect with the intrinsic electrocaloric effect, an ideal refrigeration cycle with high performance (temperature change over 10 K with a wide working-temperature window of 60 K) at room temperature is proposed for future cooling applications.
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Mother-to-Child Transmission of Herpes Simplex Virus.
J Pediatric Infect Dis Soc
PUBLISHED: 03-17-2014
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Infections with herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2), both alpha herpesviruses, are highly prevalent worldwide. Both HSV types commonly cause genital infection, which, when acquired or reactivated during pregnancy, carries with it the risk of transmission to the fetus or neonate. Women who acquire primary or first-episode genital herpes during pregnancy are at greater risk for transmitting the infection than are women with recurrent genital herpes. Because viral infection and reactivation are frequently asymptomatic, many affected women are unaware of their infection and risk of transmission to their infants. Neonatal HSV infection can have devastating long-term consequences, especially when the central nervous system (CNS) is involved. Treatment of affected neonates with intravenous acyclovir has improved outcomes but there is room for further improvement, especially in regard to CNS disease. Working with pregnant women to prevent mother-to-child transmission of HSV is an important component in reducing the overall disease burden of neonatal HSV infections.
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Maternal prenatal infection, early susceptibility to illness and adult psychotic experiences: a birth cohort study.
Schizophr. Res.
PUBLISHED: 03-09-2014
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Existing evidence has established that maternal infection during pregnancy and illness during early life are associated with later schizophrenia. No research has examined how the combination of these prenatal and postnatal exposures is linked to an increased risk to later schizophrenia and psychotic disorders.
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Longitudinal stability of RBANS profiles in a geriatric community-dwelling sample.
Clin Neuropsychol
PUBLISHED: 02-17-2014
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This investigation is an extension of a previous study that identified four neurocognitive RBANS groups via cluster analysis in a geriatric community-dwelling sample of 699 individuals who were at least 65 years of age. Groups were examined longitudinally over a 2-year interval to establish if they exhibited marked score changes over three assessment periods. Dropout rates, onset of medical pathology, and self-reported functioning were tracked at each evaluation. Results confirmed that cluster scores were generally stable over time although the Low Immediate Memory group's Immediate Memory index score regressed upward toward the mean by the third assessment. Of interest, individuals in the Below Average group had substantial dropout between the first and third assessments. Results are interpreted through a clinical framework to explore how RBANS cluster profiles may have predictive value in general neurocognitive functioning over the observed time period and be potentially influenced by general health factors.
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Trends in health status and chronic disease risk factors over 10-14 years in a remote Australian community: a matched pair study.
Aust N Z J Public Health
PUBLISHED: 02-06-2014
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To determine trends in health status over a 10-year interval in a high-risk remote Australian Aboriginal community.
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Optimization of brain penetrant 11?-hydroxysteroid dehydrogenase type I inhibitors and in vivo testing in diet-induced obese mice.
J. Med. Chem.
PUBLISHED: 01-27-2014
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11?-Hydroxysteroid dehydrogenase type 1 (11?-HSD1) has been widely considered by the pharmaceutical industry as a target to treat metabolic syndrome in type II diabetics. We hypothesized that central nervous system (CNS) penetration might be required to see efficacy. Starting from a previously reported pyrimidine compound, we removed hydrogen-bond donors to yield 3, which had modest CNS penetration. More significant progress was achieved by changing the core to give 40, which combines good potency and CNS penetration. Compound 40 was dosed to diet-induced obese (DIO) mice and gave excellent target engagement in the liver and high free exposures of drug, both peripherally and in the CNS. However, no body weight reduction or effects on glucose or insulin were observed in this model. Similar data were obtained with a structurally diverse thiazole compound 51. This work casts doubt on the hypothesis that localized tissue modulation of 11?-HSD1 activity alleviates metabolic syndrome.
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The global burden of conduct disorder and attention-deficit/hyperactivity disorder in 2010.
J Child Psychol Psychiatry
PUBLISHED: 01-22-2014
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The Global Burden of Disease Study 2010 (GBD 2010) is the first to include conduct disorder (CD) and attention-deficit/hyperactivity disorder (ADHD) for burden quantification.
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Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.
, Anubha Mahajan, Min Jin Go, Weihua Zhang, Jennifer E Below, Kyle J Gaulton, Teresa Ferreira, Momoko Horikoshi, Andrew D Johnson, Maggie C Y Ng, Inga Prokopenko, Danish Saleheen, Xu Wang, Eleftheria Zeggini, Gonçalo R Abecasis, Linda S Adair, Peter Almgren, Mustafa Atalay, Tin Aung, Damiano Baldassarre, Beverley Balkau, Yuqian Bao, Anthony H Barnett, Inês Barroso, Abdul Basit, Latonya F Been, John Beilby, Graeme I Bell, Rafn Benediktsson, Richard N Bergman, Bernhard O Boehm, Eric Boerwinkle, Lori L Bonnycastle, Noel Burtt, Qiuyin Cai, Harry Campbell, Jason Carey, Stéphane Cauchi, Mark Caulfield, Juliana C N Chan, Li-Ching Chang, Tien-Jyun Chang, Yi-Cheng Chang, Guillaume Charpentier, Chien-Hsiun Chen, Han Chen, Yuan-Tsong Chen, Kee-Seng Chia, Manickam Chidambaram, Peter S Chines, Nam H Cho, Young Min Cho, Lee-Ming Chuang, Francis S Collins, Marylin C Cornelis, David J Couper, Andrew T Crenshaw, Rob M Van Dam, John Danesh, Debashish Das, Ulf de Faire, George Dedoussis, Panos Deloukas, Antigone S Dimas, Christian Dina, Alex S Doney, Peter J Donnelly, Mozhgan Dorkhan, Cornelia van Duijn, Josée Dupuis, Sarah Edkins, Paul Elliott, Valur Emilsson, Raimund Erbel, Johan G Eriksson, Jorge Escobedo, Tonu Esko, Elodie Eury, Jose C Florez, Pierre Fontanillas, Nita G Forouhi, Tom Forsén, Caroline Fox, Ross M Fraser, Timothy M Frayling, Philippe Froguel, Philippe Frossard, Yutang Gao, Karl Gertow, Christian Gieger, Bruna Gigante, Harald Grallert, George B Grant, Leif C Grrop, Chrisropher J Groves, Elin Grundberg, Candace Guiducci, Anders Hamsten, Bok-Ghee Han, Kazuo Hara, Neelam Hassanali, Andrew T Hattersley, Caroline Hayward, Asa K Hedman, Christian Herder, Albert Hofman, Oddgeir L Holmen, Kees Hovingh, Astradur B Hreidarsson, Cheng Hu, Frank B Hu, Jennie Hui, Steve E Humphries, Sarah E Hunt, David J Hunter, Kristian Hveem, Zafar I Hydrie, Hiroshi Ikegami, Thomas Illig, Erik Ingelsson, Muhammed Islam, Bo Isomaa, Anne U Jackson, Tazeen Jafar, Alan James, Weiping Jia, Karl-Heinz Jöckel, Anna Jonsson, Jeremy B M Jowett, Takashi Kadowaki, Hyun Min Kang, Stavroula Kanoni, Wen Hong L Kao, Sekar Kathiresan, Norihiro Kato, Prasad Katulanda, Kirkka M Keinanen-Kiukaanniemi, Ann M Kelly, Hassan Khan, Kay-Tee Khaw, Chiea-Chuen Khor, Hyung-Lae Kim, Sangsoo Kim, Young Jin Kim, Leena Kinnunen, Norman Klopp, Augustine Kong, Eeva Korpi-Hyövälti, Sudhir Kowlessur, Peter Kraft, Jasmina Kravic, Malene M Kristensen, S Krithika, Ashish Kumar, Jesus Kumate, Johanna Kuusisto, Soo Heon Kwak, Markku Laakso, Vasiliki Lagou, Timo A Lakka, Claudia Langenberg, Cordelia Langford, Robert Lawrence, Karin Leander, Jen-Mai Lee, Nanette R Lee, Man Li, Xinzhong Li, Yun Li, Junbin Liang, Samuel Liju, Wei-Yen Lim, Lars Lind, Cecilia M Lindgren, Eero Lindholm, Ching-Ti Liu, Jian Jun Liu, Stéphane Lobbens, Jirong Long, Ruth J F Loos, Wei Lu, Jian'an Luan, Valeriya Lyssenko, Ronald C W Ma, Shiro Maeda, Reedik Mägi, Satu Mannisto, David R Matthews, James B Meigs, Olle Melander, Andres Metspalu, Julia Meyer, Ghazala Mirza, Evelin Mihailov, Susanne Moebus, Viswanathan Mohan, Karen L Mohlke, Andrew D Morris, Thomas W Mühleisen, Martina Müller-Nurasyid, Bill Musk, Jiro Nakamura, Eitaro Nakashima, Pau Navarro, Peng-Keat Ng, Alexandra C Nica, Peter M Nilsson, Inger Njølstad, Markus M Nöthen, Keizo Ohnaka, Twee Hee Ong, Katharine R Owen, Colin N A Palmer, James S Pankow, Kyong Soo Park, Melissa Parkin, Sonali Pechlivanis, Nancy L Pedersen, Leena Peltonen, John R B Perry, Annette Peters, Janini M Pinidiyapathirage, Carl G Platou, Simon Potter, Jackie F Price, Lu Qi, Venkatesan Radha, Loukianos Rallidis, Asif Rasheed, Wolfgang Rathman, Rainer Rauramaa, Soumya Raychaudhuri, N William Rayner, Simon D Rees, Emil Rehnberg, Samuli Ripatti, Neil Robertson, Michael Roden, Elizabeth J Rossin, Igor Rudan, Denis Rybin, Timo E Saaristo, Veikko Salomaa, Juha Saltevo, Maria Samuel, Dharambir K Sanghera, Jouko Saramies, James Scott, Laura J Scott, Robert A Scott, Ayellet V Segrè, Joban Sehmi, Bengt Sennblad, Nabi Shah, Sonia Shah, A Samad Shera, Xiao Ou Shu, Alan R Shuldiner, Gunnar Sigurđsson, Eric Sijbrands, Angela Silveira, Xueling Sim, Suthesh Sivapalaratnam, Kerrin S Small, Wing Yee So, Alena Stančáková, Kari Stefansson, Gerald Steinbach, Valgerdur Steinthorsdottir, Kathleen Stirrups, Rona J Strawbridge, Heather M Stringham, Qi Sun, Chen Suo, Ann-Christine Syvänen, Ryoichi Takayanagi, Fumihiko Takeuchi, Wan Ting Tay, Tanya M Teslovich, Barbara Thorand, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Emmi Tikkanen, Joseph Trakalo, Elena Tremoli, Mieke D Trip, Fuu Jen Tsai, Tiinamaija Tuomi, Jaakko Tuomilehto, André G Uitterlinden, Adán Valladares-Salgado, Sailaja Vedantam, Fabrizio Veglia, Benjamin F Voight, Congrong Wang, Nicholas J Wareham, Roman Wennauer, Ananda R Wickremasinghe, Tom Wilsgaard, James F Wilson, Steven Wiltshire, Wendy Winckler, Tien Yin Wong, Andrew R Wood, Jer-Yuarn Wu, Ying Wu, Ken Yamamoto, Toshimasa Yamauchi, Mingyu Yang, Loïc Yengo, Mitsuhiro Yokota, Robin Young, Delilah Zabaneh, Fan Zhang, Rong Zhang, Wei Zheng, Paul Z Zimmet, David Altshuler, Donald W Bowden, Yoon Shin Cho, Nancy J Cox, Miguel Cruz, Craig L Hanis, Jaspal Kooner, Jong-Young Lee, Mark Seielstad, Yik Ying Teo, Michael Boehnke, Esteban J Parra, Jonh C Chambers, E Shyong Tai, Mark I McCarthy, Andrew P Morris.
Nat. Genet.
PUBLISHED: 01-17-2014
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To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.
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The numbers game: evaluation of statistics by obstetrics & gynecology.
Obstet Gynecol
PUBLISHED: 01-10-2014
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Statistical analysis has become integral to the planning, conduct, and reporting of modern medical research. Attention to the statistical aspects of manuscripts submitted to Obstetrics & Gynecology goes back approximately 40 years and the process used in their evaluation has evolved over that time. For the past 20 years, submissions with any type of statistics and being seriously considered for acceptance have routinely been reviewed by a Statistical Editor who judges the work on a number of statistical and design characteristics. Findings of the statistical design review (which has been done by one Statistical Editor over the entire 20-year period) are integrated into the editorial decision about acceptance. The statistical review generally leads to rejection of approximately 16-25% of manuscripts and in a larger proportion, it identifies less serious problems, the correction of which improves the final product.
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MRI texture heterogeneity in the optic nerve predicts visual recovery after acute optic neuritis.
Neuroimage Clin
PUBLISHED: 01-01-2014
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To test the feasibility of using multi-scale MRI texture analysis to assess optic nerve pathology and to investigate how visual recovery relates to the severity of acute tissue damage in the optic nerve in patients after optic neuritis (ON).
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Coronary heart disease in Indian Asians.
Glob Cardiol Sci Pract
PUBLISHED: 01-01-2014
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The Indian Asian population accounts for a fifth of all global deaths from coronary heart disease (CHD). CHD deaths on the Indian subcontinent have doubled since 1990, and are predicted to rise a further 50% by 2030. Reasons underlying the increased CHD mortality among Indian Asians remain unknown. Although conventional cardiovascular risk factors contribute to CHD in Indian Asians as in other populations, these do not account for their increased risk. Type-2 diabetes, insulin resistance and related metabolic disturbances are more prevalent amongst Indian Asians than Europeans, and have been proposed as major determinants of higher CHD risk among Indian Asians. However, this view is not supported by prospective data. Genome-wide association studies have not identified differences in allele frequencies or effect sizes in known loci to explain the increased CHD risk in Indian Asians. Limited knowledge of mechanisms underlying higher CHD risk amongst Indian Asians presents a major obstacle to reducing the burden of CHD in this population. Systems biology approaches such as genomics, epigenomics, metabolomics and transcriptomics, provide a non-biased approach for discovery of novel biomarkers and disease pathways underlying CHD. Incorporation of these 'omic' approaches in prospective Indian Asian cohorts such as the London Life Sciences Population Study (LOLIPOP) provide an exciting opportunity for the identification of new risk factors underlying CHD in this high risk population.
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Exposure to Beta-(1,3)-d-glucan in house dust at age 7-10 is associated with airway hyperresponsiveness and atopic asthma by age 11-14.
PLoS ONE
PUBLISHED: 01-01-2014
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Mould exposure has been linked to childhood asthma and bronchial hyper-responsiveness. Few studies have assessed beta-(1,3)-d-glucan (beta-glucan), a significant fungal cell wall constituent, in relation to asthma in adolescence.
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Adaptive expression of microRNA-125a in adipose tissue in response to obesity in mice and men.
PLoS ONE
PUBLISHED: 01-01-2014
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MicroRNAs are emerging as new mediators in the regulation of adipose tissue biology and the development of obesity. An important role of microRNA-125a has been suggested in the pathogenesis of insulin resistance (IR). Here, we characterized the function of microRNA-125a in adipose tissue in a context of experimentally-induced IR and obesity in mice and in obese patients. We showed time dependent overexpression of the microRNA in adipose tissue of BALB/c and C57BL/6J mice in response to high fat diet (HFD) feeding. MicroRNA-125a expression was downregulated in vitro in insulin resistant 3T3-L1 adipocytes and ex vivo in adipose tissue of obese patients. In vitro modulation of microRNA-125a expression in 3T3-L1 adipocytes did not affect glucose uptake. Gene set enrichment analysis (GSEA) identified significantly altered expression patterns of predicted microRNA-125a gene targets in transcriptomic datasets of adipose tissue from HFD-fed mice and obese patients. Among genes that contributed to global enrichment of altered expression of microRNA-125a targets, Thyrotroph embryonic factor (Tef), Mannan-binding lectin serine peptidase 1, Reticulon 2 and Ubiquitin-conjugating enzyme E2L3 were significantly differentially expressed in adipose tissue in these groups. We showed that Tef expression is reduced in adipose tissue of obese patients following gastric bypass surgery. Our findings indicate that microRNA-125a expression in adipose tissue adapts to IR and may play a role in the development of obesity in mice and obese subjects through uncoupled regulation of the expression of microRNA-125a and its targets.
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Medicinal Chemistry of Inhibitors of 11?-Hydroxysteroid Dehydrogenase Type 1 (11?-HSD1).
J. Med. Chem.
PUBLISHED: 12-13-2013
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11?-Hydroxysteroid dehydrogenase type 1 (11?-HSD1) is the enzyme primarily responsible for the regulation of intracellular cortisol levels. Inhibition of 11?-HSD1 is an attractive mechanism for the treatment of obesity and other elements of the metabolic syndrome. Emerging literature also supports a potential role in the treatment of other unmet medical needs including Alzheimers disease, vascular inflammation, cardiovascular disease, and glaucoma. The aim of this article is to review the medicinal chemistry literature around small molecule approaches to developing synthetic inhibitors of 11?-HSD1 and to highlight key compounds that have resulted from the efforts of both industrial and academic groups. The reported data from 11?-HSD1 inhibitors that have progressed into the clinic are summarized followed by a perspective from the authors.
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Case of the Massachusetts General Hospital: Case 35-2013: a 77-year-old man with confusion and malaise.
N. Engl. J. Med.
PUBLISHED: 11-15-2013
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A 77-year-old man was admitted to this hospital because of confusion and malaise after resection of a papillary urothelial cancer. He reported abdominal pain, facial and jaw pain, anorexia, lethargy, weakness, and night sweats; imaging revealed generalized lymphadenopathy.
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Risky Sexual Behavior Among Young Adult Latinas: Are Acculturation and Religiosity Protective?
J Sex Res
PUBLISHED: 10-31-2013
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A sexual health disparity exists among U.S. Latinas, who have rates of sexually transmitted infections (STIs) that are more than double their peers. Previous research has identified acculturation and religiosity as key social determinants of sexual health, but such findings have been inconsistent, with some researchers identifying protective benefits and other researchers noting increased risk. The purpose of this study was to explain how intrinsic and extrinsic religiosity as well as acculturation predict risky sexual behavior using Structural Equation Modeling of a nationally representative sample of self-identified Latinas (N = 1,168) from the National Longitudinal Survey of Adolescent Health. Results indicated that intrinsic religiosity and acculturation assert protective effects while extrinsic religiosity increases risk. Recommendations for policy, intervention, and future research are offered.
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A multi-center, observational study shows high proportion of Australian rheumatoid arthritis patients have inadequate disease control.
Int J Rheum Dis
PUBLISHED: 10-30-2013
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To evaluate the disease activity and current pharmacological interventions used to achieve remission in rheumatoid arthritis (RA) patients in Australia.
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A retrospective chart review of the use of rituximab for the treatment of rheumatoid arthritis in Australian rheumatology practice.
Int J Rheum Dis
PUBLISHED: 10-18-2013
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Rituximab is one of nine biologic agents approved for the treatment of rheumatoid arthritis (RA) in Australia. The primary study objective was to analyze the factors that lead to the therapeutic decision to use rituximab in RA.
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Raising the Bar on Achieving Racial Diversity in Higher Education: The United States Supreme Courts Decision in Fisher v University of Texas.
Acad Med
PUBLISHED: 10-17-2013
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In Fisher v University of Texas, the U.S. Supreme Court revisited the constitutionality of race-conscious admissions practices aimed at fostering student diversity in university programs. Although it concluded that student diversity remains the type of compelling state interest that justifies consideration of race in admissions, the court nonetheless raised the bar on the use of such practices by requiring universities to prove that no workable race-neutral methods can produce the same result. Whether this standard of proof is one that can be met-and whether challenges will mount against universities that continue to use the holistic methods sanctioned 10 years ago in Grutter v Bollinger-remains to be seen. In this commentary, the authors review the background and history of the Supreme Courts decisions on race as a factor in university admissions decisions and examine the potential effects of Fisher on medical education specifically.
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CDKN2B expression in adipose tissue of familial combined hyperlipidemia patients.
J. Lipid Res.
PUBLISHED: 10-08-2013
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The purpose of this study was to determine the core biological processes perturbed in the subcutaneous adipose tissue of familial combined hyperlipidemia (FCHL) patients. Annotation of FCHL and control microarray datasets revealed a distinctive FCHL transcriptome, characterized by gene expression changes regulating five overlapping systems: the cytoskeleton, cell adhesion and extracellular matrix; vesicular trafficking; lipid homeostasis; and cell cycle and apoptosis. Expression values for the cell-cycle inhibitor CDKN2B were increased, replicating data from an independent FCHL cohort. In 3T3-L1 cells, CDKN2B knockdown induced C/EBP? expression and lipid accumulation. The minor allele at SNP site rs1063192 (C) was predicted to create a perfect seed for the human miRNA-323b-5p. A miR-323b-5p mimic significantly reduced endogenous CDKN2B protein levels and the activity of a CDKN2B 3UTR luciferase reporter carrying the rs1063192 C allele. Although the allele displayed suggestive evidence of association with reduced CDKN2B mRNA in the MuTHER adipose tissue dataset, family studies suggest the association between increased CDKN2B expression and FCHL-lipid abnormalities is driven by factors external to this gene locus. In conclusion, from a comparative annotation analysis of two separate FCHL adipose tissue transcriptomes and a subsequent focus on CDKN2B, we propose that dysfunctional adipogenesis forms an integral part of FCHL pathogenesis.
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Research review: The role of cytokines in depression in adolescents: a systematic review.
J Child Psychol Psychiatry
PUBLISHED: 09-13-2013
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While cytokines have been implicated in the pathophysiology of depression in adults, the potential role in younger age groups such as adolescents is less clear. This article therefore reviews the literature (a) to explore the relationship between cytokines and depression in adolescents, and (b) to examine how cytokines may be related to adolescent depression in the context of other neurobiological theories of depression.
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The Child Behavior Checklist and Youth Self-Report in adolescents with epilepsy: Testing measurement invariance of the Attention and Thought Problems subscales.
Epilepsy Behav
PUBLISHED: 08-28-2013
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The objective of this study was to test for the measurement invariance of the Attention and Thought Problems subscales of the Child Behavior Checklist (CBCL) and Youth Self-Report (YSR) in a population-based sample of adolescents with and without epilepsy. Data were obtained from the 14-year follow-up of the Mater University Study of Pregnancy in which 33 adolescents with epilepsy and 1068 healthy controls were included for analysis. Confirmatory factor analysis was used to test for measurement invariance between adolescents with and without epilepsy. Structural equation modeling was used to test for group differences in attention and thought problems as measured with the CBCL and YSR. Measurement invariance was demonstrated for the original CBCL Attention Problems and YSR Thought Problems. After the removal of ambiguous items ("confused" and "daydreams"), measurement invariance was established for the YSR Attention Problems. The original and reduced CBCL Thought Problems were noninvariant. Adolescents with epilepsy had significantly more symptoms of behavioral problems on the CBCL Attention Problems, ?=0.51, p=0.002, compared with healthy controls. In contrast, no significant differences were found for the YSR Attention and Thought Problems, ?=-0.11, p=0.417 and ?=-0.20, p=0.116, respectively. In this population-based sample of adolescents with epilepsy, the CBCL Attention Problems and YSR Thought Problems appear to be valid measures of behavioral problems, whereas the YSR Attention Problems was valid only after the removal of ambiguous items. Replication of these findings in clinical samples of adolescents with epilepsy that overcome the limitations of the current study is warranted.
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Isotretinoin and mental health in adolescents: Australian consensus.
Australas. J. Dermatol.
PUBLISHED: 08-18-2013
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Acne is a common condition among adolescents and has the potential to negatively impact on the psychological well-being of those who suffer from it. In particular, depression and suicidal ideation are more common in adolescents with acne. Successful treatment of acne can improve the quality of life and reduce levels of anxiety and depression in these individuals. The current treatment of choice for severe or refractive acne is isotretinoin, a retinoid. While the possible causal association between isotretinoin and mental illness remains a controversial topic, a recent systematic review has presented evidence to support this relationship. In light of this evidence, a group of dermatologists and psychiatrists have collaborated to develop these recommendations to aid the safe prescribing of isotretinoin in adolescents. These clinical suggestions are aimed at practitioners in both disciplines to increase awareness of the current evidence in support of the association between isotretinoin and adolescent depression.
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Endotoxin in concentrated coarse and fine ambient particles induces acute systemic inflammation in controlled human exposures.
Occup Environ Med
PUBLISHED: 08-16-2013
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Knowledge of the inhalable particulate matter components responsible for health effects is important for developing targeted regulation.
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Ferroelectric Domain Wall Injection.
Adv. Mater. Weinheim
PUBLISHED: 07-31-2013
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Ferroelectric domain wall injection has been demonstrated by engineering of the local electric field, using focused ion beam milled defects in thin single crystal lamellae of KTiOPO4 (KTP). The electric field distribution (top) displays localized field hot-spots, which correlate with nucleation events (bottom). Designed local field variations can also dictate subsequent domain wall mobility, demonstrating a new paradigm in ferroelectric domain wall control.
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National trends in the community prescribing of second-generation antipsychotic medications in Australian children and youth: the incomplete story.
Australas Psychiatry
PUBLISHED: 07-29-2013
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The objective of this article is to examine national trends in prescribing second-generation antipsychotic (SGA) medications to Australian children and youth (0-24 years) and to report deficiencies in available data.
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Epidemiological modelling of attention-deficit/hyperactivity disorder and conduct disorder for the Global Burden of Disease Study 2010.
J Child Psychol Psychiatry
PUBLISHED: 07-24-2013
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The most recent Global Burden of Disease Study (GBD 2010) is the first to include attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) for burden quantification. We present the epidemiological profiles of ADHD and CD across three time periods for 21 world regions.
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NIH consensus development conference: diagnosing gestational diabetes mellitus.
NIH Consens State Sci Statements
PUBLISHED: 06-11-2013
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To provide healthcare providers, patients, and the general public with a responsible assessment of currently available data on diagnosing gestational diabetes mellitus (GDM).
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Adolescent peer aggression and its association with mental health and substance use in an Australian cohort.
J Adolesc
PUBLISHED: 06-04-2013
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Prospective longitudinal birth cohort data was used to examine the association between peer aggression at 14 years and mental health and substance use at 17 years. A sample of 1590 participants from the Western Australian Pregnancy Cohort (Raine) study were divided into mutually exclusive categories (victims, perpetrators, victim-perpetrators and uninvolved). Involvement in any type of peer aggression as a victim (10.1%), perpetrator (21.4%), or a victim-perpetrator (8.7%) was reported by 40.2% of participants. After adjusting for confounding factors, those who were a victim of peer aggression had increased odds of later depression and internalising symptoms whilst perpetrators of peer aggression were found to be at increased risk of depression and harmful alcohol use. Victim-perpetrators of peer aggression were more likely to have externalising behaviours at 17 years. These results show an independent temporal relationship between peer aggression and later mental health and substance use problems in adolescence.
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Compensatory asymmetric hemidiaphragmatic uptake secondary to contralateral hemidiaphragmatic paresis.
Clin Nucl Med
PUBLISHED: 05-23-2013
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A 59-year-old man with diffuse large B-cell lymphoma presenting as an anterior mediastinal mass underwent PET/CT after 2 cycles of chemotherapy. PET/CT shows moderately increased FDG uptake in a predominantly left prevascular mass, consistent with partially treated lymphoma. The left hemidiaphragm is elevated. PET shows asymmetric uptake along the right hemidiaphragm, which is hypothesized to represent compensatory increased workload related to contralateral left diaphragmatic paresis. The left diaphragmatic paresis is likely caused by phrenic nerve involvement by left prevascular mass.
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The association between adult attachment style and delusional-like experiences in a community sample of women.
J. Nerv. Ment. Dis.
PUBLISHED: 05-21-2013
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Community-based surveys have found that many otherwise well individuals endorse delusional-like experiences (DLEs). There is extensive literature that describes the demographic and psychosocial correlates of DLE; however, we know little about the association between DLE and attachment style. The association between DLEs (assessed by the Peters Delusional Inventory [PDI]) and interpersonal relationship style (as assessed by the Adult Attachment Questionnaire and the Dyadic Adjustment Scale) was examined in 3360 women. When adjusted for the presence of depressive and anxiety symptoms, high scores on the PDI (lowest versus highest quartiles) were associated with a) difficulties in adult attachment style particularly in the discomfort with closeness and preoccupation with relationships subscales and b) conflictual dyadic adjustment (adjusted odds ratios and 95% confidence intervals, 2.43 and 1.94-3.04, 2.50 and 1.99-3.14, and 2.90 and 1.38-6.06, respectively). The association between adult attachment style and DLE provides new clues into the causal pathway underpinning these common experiences.
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Towards a unified paradigm for sequence-based identification of fungi.
Mol. Ecol.
PUBLISHED: 05-10-2013
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The nuclear ribosomal internal transcribed spacer (ITS) region is the formal fungal barcode and in most cases the marker of choice for the exploration of fungal diversity in environmental samples. Two problems are particularly acute in the pursuit of satisfactory taxonomic assignment of newly generated ITS sequences: (i) the lack of an inclusive, reliable public reference data set and (ii) the lack of means to refer to fungal species, for which no Latin name is available in a standardized stable way. Here, we report on progress in these regards through further development of the UNITE database (http://unite.ut.ee) for molecular identification of fungi. All fungal species represented by at least two ITS sequences in the international nucleotide sequence databases are now given a unique, stable name of the accession number type (e.g. Hymenoscyphus pseudoalbidus|GU586904|SH133781.05FU), and their taxonomic and ecological annotations were corrected as far as possible through a distributed, third-party annotation effort. We introduce the term species hypothesis (SH) for the taxa discovered in clustering on different similarity thresholds (97-99%). An automatically or manually designated sequence is chosen to represent each such SH. These reference sequences are released (http://unite.ut.ee/repository.php) for use by the scientific community in, for example, local sequence similarity searches and in the QIIME pipeline. The system and the data will be updated automatically as the number of public fungal ITS sequences grows. We invite everybody in the position to improve the annotation or metadata associated with their particular fungal lineages of expertise to do so through the new Web-based sequence management system in UNITE.
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Selection and recombinant phenotyping of a novel CMX001 and cidofovir resistance mutation in human cytomegalovirus.
Antimicrob. Agents Chemother.
PUBLISHED: 05-06-2013
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CMX001 is an orally available lipid acyclic nucleotide phosphonate that delivers high intracellular levels of cidofovir (CDV)-diphosphate and exhibits enhanced in vitro antiviral activity against a wide range of double-stranded DNA viruses, including cytomegalovirus (CMV). Mutations in the DNA polymerase of CMV that impart resistance to CDV also render the virus resistant to CMX001. Here, we report a novel resistance mutation that arose under the selective pressure of CMX001. The wild-type CMV strain AD169 was propagated in human foreskin fibroblasts under increasing concentrations of CMX001 over 10 months, and the resulting strain (named CMX001(R)) was less susceptible to CDV and CMX001 in a plaque reduction assay. Genotypic analysis of virus strain CMX001(R) via conventional sequencing of the genes encoding the CMV DNA polymerase (UL54) and UL97 kinase (UL97) demonstrated one mutation that changed the wild-type aspartate to glutamate at position 542 in UL54. A recombinant virus with this novel D542E mutation was generated via bacterial artificial chromosome-mediated marker transfer experiments. Subsequent phenotypic resistance analysis of the D542E mutant demonstrated reductions in susceptibility of greater than 10-fold to CMX001 and CDV, but no resistance to foscarnet (FOS) or ganciclovir (GCV). Analysis of replicative fitness showed that both strain CMX001(R) and the D542E mutant viruses demonstrated a smaller plaque phenotype and slower replication kinetics than their respective parent viruses. These data describe the first resistance mutation generated under the selective pressure of CMX001 and suggest that CMX001 may have a unique resistance profile associated with reduced viral replication and maintenance of sensitivity to FOS and GCV.
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The co-occurrence of common mental and physical disorders within Australian families: a national population-based study.
Aust N Z J Psychiatry
PUBLISHED: 04-29-2013
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Because comorbidity between mental and physical disorders is commonly found in patients, it would be expected that this pattern would also be reflected at the family level. During a recent population-based survey of common mental disorders, respondents were asked about the presence of selected mental and physical disorders in their relatives. The aim of this research was to describe the within-family co-occurrence of selected common physical and mental disorders in a population-based sample.
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PET and PET-CT imaging findings of peritoneal and omental involvement in patients with lymphoma.
Clin Imaging
PUBLISHED: 04-21-2013
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A retrospective institutional-review-board-approved study was performed evaluating positron emission tomography (PET)-computed tomography (CT) imaging findings of peritoneal and omental involvement of lymphoma. Twelve patients were identified with a wide spectrum of imaging findings on PET-CT including but not limited to peritoneal thickening, ascites, and serosal involvement. Lymphoma is among the rare causes of malignant peritoneal or omental involvement. The most common manifestations of peritoneal lymphomatosis are peritoneal 2-[fluorine 18] fluoro-2-deoxy-D-glucose uptake with corresponding peritoneal thickening and nonobstructive serosal masses on CT.
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Meeting report: fungal its workshop (october 2012).
Stand Genomic Sci
PUBLISHED: 04-15-2013
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This report summarizes a meeting held in Boulder, CO USA (19-20 October 2012) on fungal community analyses using ultra-high-throughput sequencing of the internal transcribed spacer (ITS) region of the nuclear ribosomal RNA (rRNA) genes. The meeting was organized as a two-day workshop, with the primary goal of supporting collaboration among researchers for improving fungal ITS sequence resources and developing recommendations for standard ITS primers for the research community.
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RBANS cluster profiles in a geriatric community-dwelling sample.
Clin Neuropsychol
PUBLISHED: 04-03-2013
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Neuropsychological heterogeneity is prevalent in geriatric individuals and is due to a number of factors including the onset of neuropathology, increased risk of emotional complications, and normal cognitive changes associated with aging. In order to better characterize normal neurocognitive variability in this population, cluster analysis was used on a sample of 699 community-dwelling geriatric patients who completed The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Three-, four-, five-, and six-cluster solutions were examined and based on a number of criteria, the four-cluster solution was selected for further analysis. Clusters were defined primarily by measures of immediate memory, delayed memory, and processing speed, and differed on self-reported measures of functioning. These findings provide insights on normal neuropsychological variation in community-dwelling geriatric individuals.
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A novel approach to incorporating evidence-based medicine into an emergency medicine clerkship.
Acad Emerg Med
PUBLISHED: 03-23-2013
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Despite the growing emphasis of evidence-based medicine (EBM) in the medical school curriculum, and the recognition of EBMs role in the practice of emergency medicine (EM), there are no current guidelines on how to teach EBM to fourth-year medical students during their EM rotations. The goal was to create a unique EM clerkship curriculum that teaches students to incorporate EBM into their clinical decision-making and complies with the core curriculum recommendations of the Clerkship Directors in Emergency Medicine (CDEM).
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Does depression experienced by mothers leads to a decline in marital quality: a 21-year longitudinal study.
Soc Psychiatry Psychiatr Epidemiol
PUBLISHED: 03-19-2013
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Marital conflict and/or marital breakdown are known pathways to the onset of depression. Few studies however have examined the possibility that depression can lead to a decrease in marital quality and an increase in marital breakdown. Depression may be an important pathway to a decline in martial quality.
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Environmental exposures: an underrecognized contribution to noncommunicable diseases.
Rev Environ Health
PUBLISHED: 03-14-2013
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Previous attempts to determine the degree to which exposure to environmental factors contribute to noncommunicable diseases (NCDs) have been very conservative and have significantly underestimated the actual contribution of the environment for at least two reasons. Firstly, most previous reports have excluded the contribution of lifestyle behavioral risk factors, but these usually involve significant exposure to environmental chemicals that increase risk of disease. Secondly, early life exposure to chemical contaminants is now clearly associated with an elevated risk of several diseases later in life, but these connections are often difficult to discern. This is especially true for asthma and neurodevelopmental conditions, but there is also a major contribution to the development of obesity and chronic diseases. Most cancers are caused by environmental exposures in genetically susceptible individuals. In addition, new information shows significant associations between cardiovascular diseases and diabetes and exposure to environmental chemicals present in air, food, and water. These relationships likely reflect the combination of epigenetic effects and gene induction. Environmental factors contribute significantly more to NCDs than previous reports have suggested. Prevention needs to shift focus from individual responsibility to societal responsibility and an understanding that effective prevention of NCDs ultimately relies on improved environmental management to reduce exposure to modifiable risks.
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Conformational restriction in a series of GPR119 agonists: differences in pharmacology between mouse and human.
Bioorg. Med. Chem. Lett.
PUBLISHED: 03-04-2013
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A series of conformationally restricted GPR119 agonists were prepared based around a 3,8-diazabicyclo[3.2.1]octane scaffold. Examples were found to have markedly different pharmacology in mouse and human despite similar levels of binding to the receptor. This highlights the large effects on GPCR phamacology that can result from small structural changes in the ligand, together with inter-species differences between receptors.
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A new exposure metric for traffic-related air pollution? An analysis of determinants of hopanes in settled indoor house dust.
Environ Health
PUBLISHED: 02-25-2013
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Exposure to traffic-related air pollution (TRAP) can adversely impact health but epidemiologic studies are limited in their abilities to assess long-term exposures and incorporate variability in indoor pollutant infiltration.
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Brief screening for psychosis-like experiences.
Schizophr. Res.
PUBLISHED: 02-21-2013
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Psychotic-like experiences (PLEs) are common, and are markers of poor mental health. This study examined the internal structure of a screening test, the Community Assessment of Psychic Experiences-Positive scale (CAPE-P) in a young Australian sample.
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Child maltreatment and adolescent mental health problems in a large birth cohort.
Child Abuse Negl
PUBLISHED: 02-04-2013
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To examine whether notified child maltreatment is associated with adverse psychological outcomes in adolescence, and whether differing patterns of psychological outcome are seen depending on the type of maltreatment.
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E-learning in medical education in resource constrained low- and middle-income countries.
Hum Resour Health
PUBLISHED: 01-23-2013
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In the face of severe faculty shortages in resource-constrained countries, medical schools look to e-learning for improved access to medical education. This paper summarizes the literature on e-learning in low- and middle-income countries (LMIC), and presents the spectrum of tools and strategies used.
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Palladium catalyzed cyclizations of oxime esters with 1,1-disubstituted alkenes: synthesis of ?,?-disubstituted dihydropyrroles and studies towards an asymmetric protocol.
Chem. Commun. (Camb.)
PUBLISHED: 01-17-2013
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We report efficient Pd-catalyzed cyclizations of oxime esters with 1,1-disubstituted alkenes as the basis of a general entry to ?,?-disubstituted pyrrolidine derivatives. We also demonstrate that catalytic asymmetric variants of this chemistry are feasible by employing a suitable chiral ligand.
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The SMILE study -- safety of methotrexate in combination with leflunomide in rheumatoid arthritis.
J. Rheumatol.
PUBLISHED: 01-15-2013
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To assess the safety of treating patients with rheumatoid arthritis with a combination of methotrexate (MTX) and leflunomide (LEF) in comparison to MTX monotherapy, in clinical practice.
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Nutrigenomics of High Fat Diet Induced Obesity in Mice Suggests Relationships between Susceptibility to Fatty Liver Disease and the Proteasome.
PLoS ONE
PUBLISHED: 01-01-2013
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Nutritional factors play important roles in the etiology of obesity, type 2 diabetes mellitus and their complications through genotype x environment interactions. We have characterised molecular adaptation to high fat diet (HFD) feeding in inbred mouse strains widely used in genetic and physiological studies. We carried out physiological tests, plasma lipid assays, obesity measures, liver histology, hepatic lipid measurements and liver genome-wide gene transcription profiling in C57BL/6J and BALB/c mice fed either a control or a high fat diet. The two strains showed marked susceptibility (C57BL/6J) and relative resistance (BALB/c) to HFD-induced insulin resistance and non alcoholic fatty liver disease (NAFLD). Global gene set enrichment analysis (GSEA) of transcriptome data identified consistent patterns of expression of key genes (Srebf1, Stard4, Pnpla2, Ccnd1) and molecular pathways in the two strains, which may underlie homeostatic adaptations to dietary fat. Differential regulation of pathways, including the proteasome, the ubiquitin mediated proteolysis and PPAR signalling in fat fed C57BL/6J and BALB/c suggests that altered expression of underlying diet-responsive genes may be involved in contrasting nutrigenomic predisposition and resistance to insulin resistance and NAFLD in these models. Collectively, these data, which further demonstrate the impact of gene x environment interactions on gene expression regulations, contribute to improved knowledge of natural and pathogenic adaptive genomic regulations and molecular mechanisms associated with genetically determined susceptibility and resistance to metabolic diseases.
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Service use for mental health problems in people with delusional-like experiences: a nationwide population based survey.
PLoS ONE
PUBLISHED: 01-01-2013
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Previous population-based studies have found that delusional-like experiences (DLEs) are prevalent in the community, and are associated with a wide range of mental health disorders. The aim of the study was to investigate mental health service use by people with DLEs.
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No control genes required: Bayesian analysis of qRT-PCR data.
PLoS ONE
PUBLISHED: 01-01-2013
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Model-based analysis of data from quantitative reverse-transcription PCR (qRT-PCR) is potentially more powerful and versatile than traditional methods. Yet existing model-based approaches cannot properly deal with the higher sampling variances associated with low-abundant targets, nor do they provide a natural way to incorporate assumptions about the stability of control genes directly into the model-fitting process.
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Infant gut microbiota and the hygiene hypothesis of allergic disease: impact of household pets and siblings on microbiota composition and diversity.
Allergy Asthma Clin Immunol
PUBLISHED: 01-01-2013
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BACKGROUND: Multiple studies have demonstrated that early-life exposure to pets or siblings affords protection against allergic disease; these associations are commonly attributed to the "hygiene hypothesis". Recently, low diversity of the infant gut microbiota has also been linked to allergic disease. In this study, we characterize the infant gut microbiota in relation to pets and siblings. METHODS: The study population comprised a small sub-sample of 24 healthy, full term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Mothers reported on household pets and siblings. Fecal samples were collected at 4 months of age, and microbiota composition was characterized by high-throughput signature gene sequencing. RESULTS: Microbiota richness and diversity tended to be increased in infants living with pets, whereas these measures were decreased in infants with older siblings. Infants living with pets exhibited under-representation of Bifidobacteriaceae and over-representation of Peptostreptococcaceae; infants with older siblings exhibited under-representation of Peptostreptococcaceae. CONCLUSIONS: This study provides new evidence that exposure to pets and siblings may influence the early development of the gut microbiota, with potential implications for allergic disease. These two traditionally protective "hygiene hypothesis" factors appear to differentially impact gut microbiota composition and diversity, calling into question the clinical significance of these measures. Further research is required to confirm and expand these findings.
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Untargeted metabolome quantitative trait locus mapping associates variation in urine glycerate to mutant glycerate kinase.
J. Proteome Res.
PUBLISHED: 11-28-2011
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With successes of genome-wide association studies, molecular phenotyping systems are developed to identify genetically determined disease-associated biomarkers. Genetic studies of the human metabolome are emerging but exclusively apply targeted approaches, which restricts the analysis to a limited number of well-known metabolites. We have developed novel technical and statistical methods for systematic and automated quantification of untargeted NMR spectral data designed to perform robust and accurate quantitative trait locus (QTL) mapping of known and previously unreported molecular compounds of the metabolome. For each spectral peak, six summary statistics were calculated and independently tested for evidence of genetic linkage in a cohort of F2 (129S6xBALB/c) mice. The most significant evidence of linkages were obtained with NMR signals characterizing the glycerate (LOD10-42) at the mutant glycerate kinase locus, which demonstrate the power of metabolomics in quantitative genetics to identify the biological function of genetic variants. These results provide new insights into the resolution of the complex nature of metabolic regulations and novel analytical techniques that maximize the full utilization of metabolomic spectra in human genetics to discover mappable disease-associated biomarkers.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.