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Tomas Thiel, Charlotta Ryk, Lotta Renström-Koskela, Gunnar Steineck, Martin C Schumacher, N Peter Wiklund, Petra J de Verdier
PURPOSE: To analyse if BCG treatment leads to long-term reduction of recurrence, progression, and cancer-specific mortality (CSM) in patients with high-risk NMIBC. MATERIALS AND METHODS: 140 patients with high-risk NMIBC were drawn from a population-based cohort of 538 patients with newly diagnosed bladder cancer in the Stockholm County between 1995 and 1996. Data were collected prospectively, and a final follow-up for recurrence, progression, and CSM was performed after 15 years...
June 15, 2018: World Journal of Urology
Viktoria Gusarova, Colm O'Dushlaine, Tanya M Teslovich, Peter N Benotti, Tooraj Mirshahi, Omri Gottesman, Cristopher V Van Hout, Michael F Murray, Anubha Mahajan, Jonas B Nielsen, Lars Fritsche, Anders Berg Wulff, Daniel F Gudbjartsson, Marketa Sjögren, Connor A Emdin, Robert A Scott, Wen-Jane Lee, Aeron Small, Lydia C Kwee, Om Prakash Dwivedi, Rashmi B Prasad, Shannon Bruse, Alexander E Lopez, John Penn, Anthony Marcketta, Joseph B Leader, Christopher D Still, H Lester Kirchner, Uyenlinh L Mirshahi, Amr H Wardeh, Cassandra M Hartle, Lukas Habegger, Samantha N Fetterolf, Teresa Tusie-Luna, Andrew P Morris, Hilma Holm, Valgerdur Steinthorsdottir, Patrick Sulem, Unnur Thorsteinsdottir, Jerome I Rotter, Lee-Ming Chuang, Scott Damrauer, David Birtwell, Chad M Brummett, Amit V Khera, Pradeep Natarajan, Marju Orho-Melander, Jason Flannick, Luca A Lotta, Cristen J Willer, Oddgeir L Holmen, Marylyn D Ritchie, David H Ledbetter, Andrew J Murphy, Ingrid B Borecki, Jeffrey G Reid, John D Overton, Ola Hansson, Leif Groop, Svati H Shah, William E Kraus, Daniel J Rader, Yii-Der I Chen, Kristian Hveem, Nicholas J Wareham, Sekar Kathiresan, Olle Melander, Kari Stefansson, Børge G Nordestgaard, Anne Tybjærg-Hansen, Goncalo R Abecasis, David Altshuler, Jose C Florez, Michael Boehnke, Mark I McCarthy, George D Yancopoulos, David J Carey, Alan R Shuldiner, Aris Baras, Frederick E Dewey, Jesper Gromada
Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0...
June 13, 2018: Nature Communications
Maxime O Baud, Thomas Perneger, Attila Rácz, Max C Pensel, Christian Elger, Bertil Rydenhag, Kristina Malmgren, J Helen Cross, Grainne McKenna, Martin Tisdall, Herm J Lamberink, Sylvain Rheims, Philippe Ryvlin, Jean Isnard, François Mauguière, Alexis Arzimanoglou, Serdar Akkol, Kaancan Deniz, Cigdem Ozkara, Morten Lossius, Ivan Rektor, Reetta Kälviäinen, Lotta-Maria Vanhatalo, Petia Dimova, Krassimir Minkin, Anke Maren Staack, Bernhard J Steinhoff, Adam Kalina, Pavel Krsek, Petr Marusic, Zsofia Jordan, Daniel Fabo, Evelien Carrette, Paul Boon, Saulius Rocka, Rūta Mameniškienė, Serge Vulliemoz, Francesca Pittau, Kees P J Braun, Margitta Seeck
OBJECTIVE: Resective surgery is effective in treating drug-resistant focal epilepsy, but it remains unclear whether improved diagnostics influence postsurgical outcomes. Here, we compared practice and outcomes over 2 periods 15 years apart. METHODS: Sixteen European centers retrospectively identified 2 cohorts of children and adults who underwent epilepsy surgery in the period of 1997 to 1998 (n = 562) or 2012 to 2013 (n = 736). Data collected included patient (sex, age) and disease (duration, localization and diagnosis) characteristics, type of surgery, histopathology, Engel postsurgical outcome, and complications, as well as imaging and electrophysiologic tests performed for each case...
June 13, 2018: Neurology
Lotta Purkamo, Riikka Kietäväinen, Hanna Miettinen, Elina Sohlberg, Ilmo Kukkonen, Merja Itävaara, Malin Bomberg
The diversity and metabolic functions of deep subsurface ecosystems remain relatively unexplored. Microbial communities in previously studied deep subsurface sites of the Fennoscandian Shield are distinctive to each site. Thus, we hypothesized that the microbial communities of the deep Archaean bedrock fracture aquifer in Romuvaara, northern Finland, differ both in community composition and metabolic functionality from the other sites in the Fennoscandian Shield. We characterized the composition, functionality and substrate preferences of the microbial communities at different depths in a 600-m deep borehole...
June 11, 2018: FEMS Microbiology Ecology
Ming-Dong Zhang, Jie Su, Csaba Adori, Valentina Cinquina, Katarzyna Malenczyk, Fatima Girach, Changgeng Peng, Patrik Ernfors, Peter Löw, Lotta Borgius, Ole Kiehn, Masahiko Watanabe, Mathias Uhlén, Nicholas Mitsios, Jan Mulder, Tibor Harkany, Tomas Hökfelt
Painful signals are transmitted by mutisynaptic glutamatergic pathways. Their first synapse between primary nociceptors and excitatory spinal interneurons gates sensory load. Glutamate release herein is orchestrated by Ca2+ sensor proteins with neuronal calcium-binding protein 2 (NECAB2) being particularly abundant. However, neither the importance of NECAB2+ neuronal contingents in dorsal root ganglia (DRG) and spinal cord nor function-determination by NECAB2 has been defined. A combination of histochemistry and single-cell RNA-seq showed NECAB2 in small/medium-sized C- and Aδ D-hair low threshold mechanoreceptors in DRG, as well as in protein kinase γ-positive excitatory spinal interneurons...
June 12, 2018: Journal of Clinical Investigation
Anna-Maria Larsson, Sara Jansson, Pär-Ola Bendahl, Charlotte Levin Tykjaer Jörgensen, Niklas Loman, Cecilia Graffman, Lotta Lundgren, Kristina Aaltonen, Lisa Rydén
BACKGROUND: Circulating tumor cells (CTCs) carry independent prognostic information in patients with metastatic breast cancer (MBC) on different lines of therapy. Moreover, CTC clusters are suggested to add prognostic information to CTC enumeration alone but their significance is unknown in patients with newly diagnosed MBC. We aimed to evaluate whether longitudinal enumeration of circulating tumor cells (CTCs) and CTC clusters could improve prognostication and monitoring of patients with metastatic breast cancer (MBC) starting first-line therapy...
June 8, 2018: Breast Cancer Research: BCR
Lotta M Ahveninen, Julie C Stout, Nellie Georgiou-Karistianis, Valentina Lorenzetti, Yifat Glikmann-Johnston
In Huntington's disease (HD), the presence of neurodegeneration in brain regions other than the striatum has been recently gaining attention. The amygdala is one such area, which has been investigated in only eight structural magnetic resonance imaging studies to date, but with inconsistent findings. This is the largest MRI study to date examining manually traced amygdala volumes in HD participants and the relationship of amygdala volumes to clinical measures of HD. Our study included 35 healthy control participants, and groups of 35 pre-symptomatic, and 36 symptomatic HD participants...
2018: NeuroImage: Clinical
Alfredo Iardino, Orlando Garner, Gabriella Lorusso, Franco Lotta
Ergotism is an ischaemic complication due to vasoconstriction throughout the body due to ingestion of ergotamine. A 34-year-old Hispanic man with HIV infection treated with saquinavir, ritonavir and abacavir/lamivudine presented to the emergency department complaining of left foot pain 1 week prior to admission. The affected extremity was cold with absence of pedal and tibial pulses. Arterial Doppler revealed absent arterial flow from the popliteal artery later confirmed by arteriography. Medication reconciliation revealed a recent prescription for migraine headache containing ergotamine...
June 4, 2018: BMJ Case Reports
Carl Sjödin, Soren Sondergaard, Lotta Johansson
BACKGROUND: The phlebostatic axis is the most commonly used anatomical external reference point for central venous pressure measurements. Deviation in the central venous pressure transducer alignment from the phlebostatic axis causes inadequate pressure readings, which may affect treatment decisions for critically ill patients in intensive care units. AIM: The primary aim of the study was to assess the variability in central venous pressure transducer levelling in the intensive care unit...
June 1, 2018: Australian Critical Care: Official Journal of the Confederation of Australian Critical Care Nurses
Gabriel Mf Almeida, Miika Leppänen, Ilari J Maasilta, Lotta-Riina Sundberg
The visualization of viral particles only became possible after the advent of the electron microscope. The first bacteriophage images were published in 1940 and were soon followed by many other publications that helped to elucidate the structure of the particles and their interaction with the bacterial hosts. As sample preparation improved and new technologies were developed, phage imaging became important approach to morphologically classify these viruses and helped to understand its importance in the biosphere...
May 28, 2018: Research in Microbiology
Heikki Joensuu, Judith Fraser, Hans Wildiers, Riikka Huovinen, Päivi Auvinen, Meri Utriainen, Paul Nyandoto, Kenneth K Villman, Päivi Halonen, Helena Granstam-Björneklett, Lotta Lundgren, Liisa Sailas, Taina Turpeenniemi-Hujanen, Minna Tanner, Jeffrey Yachnin, Diana Ritchie, Oskar Johansson, Teppo Huttunen, Patrick Neven, Peter Canney, Vernon J Harvey, Pirkko-Liisa Kellokumpu-Lehtinen, Henrik Lindman
Importance: Trastuzumab plus chemotherapy is the standard adjuvant treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. While the standard duration of trastuzumab treatment is 12 months, the benefits and harms of trastuzumab continued beyond the chemotherapy are unclear. Objective: To evaluate the efficacy and safety of adjuvant trastuzumab continued beyond chemotherapy in women treated with up-front chemotherapy containing a taxane and trastuzumab...
May 31, 2018: JAMA Oncology
Anna Kock, Karin Larsson, Filip Bergqvist, Nina Eissler, Lotta H M Elfman, Joan Raouf, Marina Korotkova, John Inge Johnsen, Per-Johan Jakobsson, Per Kogner
Despite recent progress in diagnosis and treatment, survival for children with high-risk metastatic neuroblastoma is still poor. Prostaglandin E2 (PGE2 )-driven inflammation promotes tumor growth, immune suppression, angiogenesis and resistance to established cancer therapies. In neuroblastoma, cancer-associated fibroblasts (CAFs) residing in the tumor microenvironment are the primary source of PGE2 . However, clinical targeting of PGE2 with current non-steroidal anti-inflammatory drugs or cyclooxygenase inhibitors has been limited due to risk of adverse side effects...
May 24, 2018: EBioMedicine
Gabriele Bolte, Madlen David, Małgorzata Dębiak, Lotta Fiedel, Claudia Hornberg, Marike Kolossa-Gehring, Ute Kraus, Rebecca Lätzsch, Tatjana Paeck, Kerstin Palm, Alexandra Schneider
The comprehensive consideration of sex/gender in health research is essential to increase relevance and validity of research results. Contrary to other areas of health research, there is no systematic summary of the current state of research on the significance of sex/gender in environmental health. Within the interdisciplinary research network Sex/Gender-Environment-Health (GeUmGe-NET) the current state of integration of sex/gender aspects or, respectively, gender theoretical concepts into research was systematically assessed within selected topics of the research areas environmental toxicology, environmental medicine, environmental epidemiology and public health research on environment and health...
May 22, 2018: Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz
James Yarmolinsky, Carolina Bonilla, Philip C Haycock, Ryan J Q Langdon, Luca A Lotta, Claudia Langenberg, Caroline L Relton, Sarah J Lewis, David M Evans, George Davey Smith, Richard M Martin
In the Selenium and Vitamin E Cancer Prevention Trial (SELECT), selenium supplementation (causing a median 114 μg/L increase in circulating selenium) did not lower overall prostate cancer risk, but increased risk of high-grade prostate cancer and type 2 diabetes. Mendelian randomization analysis uses genetic variants to proxy modifiable risk factors and can strengthen causal inference in observational studies. We constructed a genetic instrument comprising 11 single nucleotide polymorphisms robustly (P < 5 × 10-8) associated with circulating selenium in genome-wide association studies...
May 17, 2018: Journal of the National Cancer Institute
Mats Eriksson, Lotta Samuelson, Linnéa Jägrud, Eskil Mattsson, Thorsten Celander, Anders Malmer, Klas Bengtsson, Olof Johansson, Nicolai Schaaf, Ola Svending, Anna Tengberg
A growing world population and rapid expansion of cities increase the pressure on basic resources such as water, food and energy. To safeguard the provision of these resources, restoration and sustainable management of landscapes is pivotal, including sustainable forest and water management. Sustainable forest management includes forest conservation, restoration, forestry and agroforestry practices. Interlinkages between forests and water are fundamental to moderate water budgets, stabilize runoff, reduce erosion and improve biodiversity and water quality...
May 21, 2018: Environmental Management
Laura B L Wittemans, Luca A Lotta, Claudia Langenberg
PURPOSE OF THE REVIEW: Causality has been demonstrated for few of the many putative risk factors for type 2 diabetes (T2D) emerging from observational epidemiology. Genetic approaches are increasingly being used to infer causality, and in this review, we discuss how genetic discoveries have shaped our understanding of the causal role of factors associated with T2D. RECENT FINDINGS: Genetic discoveries have led to the identification of novel potential aetiological factors of T2D, including the protective role of peripheral fat storage capacity and specific metabolic pathways, such as the branched-chain amino acid breakdown...
May 19, 2018: Current Diabetes Reports
Lotta Siira, Hanne Nøkleby, Regine Barlinn, Øystein R Riise, Ingeborg S Aaberge, Susanne G Dudman
Limited data exist on the immunogenicity of a third dose of the measles, mumps, and rubella vaccine (MMR). In this study, our aim was to evaluate the long-term rubella immunogenicity afforded by two childhood MMR doses of the Norwegian vaccination program in a cohort of conscripts and to determine the effect of an additional dose of MMR vaccine, in order to inform vaccination policy. Blood samples from Norwegian conscripts (n = 495) taken both before and eight months after administration of a dose of MMR vaccine were tested using an enzyme immunoassay to measure anti-rubella IgG...
May 17, 2018: Human Vaccines & Immunotherapeutics
Rachel K Okolicsanyi, Lotta E Oikari, Chieh Yu, Lyn R Griffiths, Larisa M Haupt
Background: Due to their relative ease of isolation and their high ex vivo and in vitro expansive potential, human mesenchymal stem cells (hMSCs) are an attractive candidate for therapeutic applications in the treatment of brain injury and neurological diseases. Heparan sulfate proteoglycans (HSPGs) are a family of ubiquitous proteins involved in a number of vital cellular processes including proliferation and stem cell lineage differentiation. Methods: Following the determination that hMSCs maintain neural potential throughout extended in vitro expansion, we examined the role of HSPGs in mediating the neural potential of hMSCs...
2018: Frontiers in Molecular Neuroscience
Lotta Kinnunen, Mika Niemelä, Helinä Hakko, Jouko Miettunen, Marko Merikukka, Vesa Karttunen, Tiina Ristikari, Mika Gissler, Sami Räsänen
OBJECTIVE: To investigate whether parental TBI increases the overall risk for psychiatric disorders and the risk for specific psychiatric diagnoses in the children affected by parental TBI. METHODS: The 1987 Finnish Birth Cohort (n = 59 476) were followed up through national registers from birth to the end of 2008. The diagnoses of cohort members and their parents were obtained from the Care Register of Health Care, provided by the National Institute of Health and Welfare...
May 8, 2018: Brain Injury: [BI]
Dessislava Mladenova, Guy Barry, Lyndsey M Konen, Sandy S Pineda, Boris Guennewig, Lotta Avesson, Raphael Zinn, Nicole Schonrock, Maina Bitar, Nicky Jonkhout, Lauren Crumlish, Dominik C Kaczorowski, Andrew Gong, Mark Pinese, Gloria R Franco, Carl R Walkley, Bryce Vissel, John S Mattick
The amount of regulatory RNA encoded in the genome and the extent of RNA editing by the post-transcriptional deamination of adenosine to inosine (A-I) have increased with developmental complexity and may be an important factor in the cognitive evolution of animals. The newest member of the A-I editing family of ADAR proteins, the vertebrate-specific ADAR3, is highly expressed in the brain, but its functional significance is unknown. In vitro studies have suggested that ADAR3 acts as a negative regulator of A-I RNA editing but the scope and underlying mechanisms are also unknown...
2018: Frontiers in Neuroscience
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