A Leptin-regulated Circuit Controls Glucose Mobilization During Noxious Stimuli

Adipocytes secrete the hormone leptin to signal the sufficiency of energy stores. Reductions in circulating leptin concentrations reflect a negative energy balance, which augments sympathetic nervous system (SNS) activation in response to metabolically demanding emergencies. This process ensures adequate glucose mobilization despite low energy stores. We report that leptin receptor–expressing neurons (LepRb neurons) in the periaqueductal gray (PAG), the largest population of LepRb neurons in the brain stem, mediate this process. Application of noxious stimuli, which often signal the need to mobilize glucose to support an appropriate response, activated PAG LepRb neurons, which project to and activate parabrachial nucleus (PBN) neurons that control SNS activation and glucose mobilization. Furthermore, activating PAG LepRb neurons increased SNS activity and blood glucose concentrations, while ablating LepRb in PAG neurons augmented glucose mobilization in response to noxious stimuli. Thus, decreased leptin action on PAG LepRb neurons augments the autonomic response to noxious stimuli, ensuring sufficient glucose mobilization during periods of acute demand in the face of diminished energy stores

The taxonomy of Enterobacter sakazakii: proposal of a new genus Cronobacter gen. nov. and descriptions of Cronobacter sakazakii comb. nov. Cronobacter sakazakii subsp. sakazakii, comb. nov., Cronobacter sakazakii subsp. malonaticus subsp. nov., Cronobacter turicensis sp. nov., Cronobacter muytjensii sp. nov., Cronobacter dublinensis sp. nov. and Cronobacter genomospecies 1

BACKGROUND: Enterobacter sakazakii is an opportunistic pathogen that can cause infections such as necrotizing enterocolitis, bacteraemia, meningitis and brain abscess/lesions. When the species was defined in 1980, 15 biogroups were described and it was suggested that these could represent multiple species. In this study the taxonomic relationship of strains described as E. sakazakii was further investigated. RESULTS: Strains identified as E. sakazakii were divided into separate groups on the basis of f-AFLP fingerprints, ribopatterns and full-length 16S rRNA gene sequences. DNA-DNA hybridizations revealed five genomospecies. The phenotypic profiles of the genomospecies were determined and biochemical markers identified. CONCLUSION: This study clarifies the taxonomy of E. sakazakii and proposes a reclassification of these organisms

Human Mars Mission Design - The Ultimate Systems Challenge

A human mission to Mars will occur at some time in the coming decades. When it does, it will be the end result of a complex network of interconnected design choices, systems analyses, technical optimizations, and non-technical compromises. This mission will extend the technologies, engineering design, and systems analyses to new limits, and may very well be the most complex undertaking in human history. It can be illustrated as a large menu, or as a large decision tree. Whatever the visualization tool, there are numerous design decisions required to assemble a human Mars mission, and many of these interconnect with one another. This paper examines these many decisions and further details a number of choices that are highly interwoven throughout the mission design. The large quantity of variables and their interconnectedness results in a highly complex systems challenge, and the paper illustrates how a change in one variable results in ripples (sometimes unintended) throughout many other facets of the design. The paper concludes with a discussion of some mission design variables that can be addressed first, and those that have already been addressed as a result of ongoing National Aeronautics and Space Administration (NASA) developments, or as a result of decisions outside the technical arena. It advocates the need for a 'reference design' that can be used as a point of comparison, and to illustrate the system-wide impacts as design variables change

The Moon as a Stepping Stone to Human Mars Missions

Human space mission designers stretching back to von Braun and beyond have envisioned the moon as a waypoint to the more challenging missions to Mars. The moon is seen as a potential proving ground for technologies, equipment and operations, and a venue upon which to learn the art of surface exploration. Mars missions are years in duration with very limited Earth return opportunities, but the moon provides the opportunity to perfect exploration concepts while being only a few days from Earth. Though the environment and gravity differ from Mars, and will thereby not provide a perfectly analogous environment, the remoteness, limited logistics, and harsh conditions on the Moon provide an environment that can be used to stress many systems that will be used or will be extensible to hardware and operations that will be used on Mars. This paper begins by describing the systems, or options for systems, that together comprise a human Mars architecture. With this human Mars operational concept as a basis of comparison, each of these systems is analyzed in the context of a range of potential exploration missions that first targets lunar exploration experience, examining how the lunar experience can be best used to prepare for the eventual human mission to Mars. The paper concludes with a concise summary of specific areas that have the strongest applicability between exploration experience on the lunar surface and extensibility to human Mars exploration

Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin

Pathological processes involved in the initiation of rheumatoid synovitis remain unclear. We undertook the present study to identify immune and stromal processes that are present soon after the clinical onset of rheumatoid arthritis ( RA) by assessing a panel of T cell, macrophage, and stromal cell related cytokines and chemokines in the synovial fluid of patients with early synovitis. Synovial fluid was aspirated from inflamed joints of patients with inflammatory arthritis of duration 3 months or less, whose outcomes were subsequently determined by follow up. For comparison, synovial fluid was aspirated from patients with acute crystal arthritis, established RA and osteoarthritis. Rheumatoid factor activity was blocked in the synovial fluid samples, and a panel of 23 cytokines and chemokines measured using a multiplex based system. Patients with early inflammatory arthritis who subsequently developed RA had a distinct but transient synovial fluid cytokine profile. The levels of a range of T cell, macrophage and stromal cell related cytokines ( e. g. IL-2, IL-4, IL-13, IL-17, IL-15, basic fibroblast growth factor and epidermal growth factor) were significantly elevated in these patients within 3 months after symptom onset, as compared with early arthritis patients who did not develop RA. In addition, this profile was no longer present in established RA. In contrast, patients with non-rheumatoid persistent synovitis exhibited elevated levels of interferon-gamma at initiation. Early synovitis destined to develop into RA is thus characterized by a distinct and transient synovial fluid cytokine profile. The cytokines present in the early rheumatoid lesion suggest that this response is likely to influence the microenvironment required for persistent RA

Exposure to Candida albicans Polarizes a T-Cell Driven Arthritis Model towards Th17 Responses, Resulting in a More Destructive Arthritis

BACKGROUND: Fungal components have been shown very effective in generating Th17 responses. We investigated whether exposure to a minute amount of C. albicans in the arthritic joint altered the local cytokine environment, leading to enhanced Th17 expansion and resulting in a more destructive arthritis. METHODOLOGY: Chronic SCW arthritis was induced by repeated injection with Streptococcus pyogenes (SCW) cell wall fragments into the knee joint of C57Bl/6 mice, alone or in combination with the yeast of C. albicans or Zymosan A. During the chronic phase of the arthritis, the cytokine levels, mRNA expression and histopathological analysis of the joints were performed. To investigate the phenotype of the IL-17 producing T-cells, synovial cells were isolated and analyzed by flowcytometry. PRINCIPAL FINDINGS: Intra-articular injection of either Zymosan A or C. albicans on top of the SCW injection both resulted in enhanced joint swelling and inflammation compared to the normal SCW group. However, only the addition of C. albicans during SCW arthritis resulted in severe chondrocyte death and enhanced destruction of cartilage and bone. Additionally, exposure to C. albicans led to increased IL-17 in the arthritic joint, which was accompanied by an increased synovial mRNA expression of T-bet and RORgammaT. Moreover, the C. albicans-injected mice had significantly more Th17 cells in the synovium, of which a large population also produced IFN-gamma. CONCLUSION: This study clearly shows that minute amounts of fungal components, like C. albicans, are very potent in interfering with the local cytokine environment in an arthritic joint, thereby polarizing arthritis towards a more destructive phenotype

Research priorities in pediatric parenteral nutrition: a consensus and perspective from ESPGHAN/ESPEN/ESPR/CSPEN

We acknowledge all the authors of the ESPGHAN/ESPR/ESPEN/CSPEN pediatric parenteral nutrition guidelines for their contributions and vote (Christian Braegger, University Children’s Hospital, Zurich, Switzerland; Jiri Bronsky, University Hospital Motol, Prague, Czech Republic; Cristina Campoy, Department of Paediatrics, School of Medicine, University of Granada, Granada, Spain; Magnus Domellof, Department of Clinical Sciences, Pediatrics, Umeå University, Sweden; Nicholas Embleton, Newcastle University, Newcastle upon Tyne, UK; Mary Fewtrell, UCL Great Ormond Street Institute of Child Health, London, UK; Natasa Fidler, University Medical Centre Ljubljana, Ljubljana, Slovenia; Axel Franz, University Children’s Hospital, Tuebingen, Germany; Oliver Goulet, University Sordonne-Paris-Cite; Paris-Descartes Medical School, Paris, France; Corina Hartmann, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel and Carmel Medical Center, Israel; Susan Hill, Great Ormond Street Hospital for Children, NHS Foundation Trust and UCL Institute of Child Health, London, UK; Iva Hojsak, Children’s Hospital Zagreb, University of Zagreb School of Medicine, University of J. J. Strossmayer School of Medicine Osijek, Croatia; Sylvia Iacobelli, CHU La Reunion, Saint Pierre, France; Frank Jochum, Ev. Waldkrankenhaus Spandau, Berlin, Germany; Koen Joosten, Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus MC Sophia Children’s Hospital, Rotterdam, The Netherlands; Sanja Kolacek, Children’s Hospital, University of Zagreb School of Medicine, Zagreb, Croatia; Alexandre Lapillone, Paris-Descartes University, Paris, France; Szimonetta Lohner, Department of Pediatrics, University of Pecs, Pecs, Hungary; Dieter Mesotten, KU Leuven, Leuven, Belgium; Walter Mihatsch, Ulm University, Ulm, and Helios Hospital, Pforzheim, Germany; Francis Mimouni, Department of Pediatrics, Division of Neonatology, The Wilf Children’s Hospital, the Shaare Zedek Medical Center, Jerusalem, and the Tel Aviv University, Tel Aviv, Israel; Christian Molgaard, Department of Nutrition, Exercise and Sports, University of Copenhagen, and Paediatric Nutrition Unit, Rigshospitalet, Copenhagen, Denmark; Sissel Moltu, Oslo University Hospital, Oslo, Norway; Antonia Nomayo, Ev. Waldkrankenhaus Spandau, Berlin, Germany; John Puntis, The General Infirmary at Leeds, Leeds, UK; Arieh Riskin, Bnai Zion Medical Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel; Miguel Saenz de Pipaon, Department of Neonatology, La Paz University Hospital, Red de Salud Materno Infantil y Desarrollo e SAMID, Universidad Autonoma de Madrid, Madrid, Spain; Raanan Shamir, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel; Tel Aviv University, Tel Aviv, Israel; Peter Szitanyi, General University Hospital, First Faculty of Medicine, Charles University in Prague, Czech Republic; Merit Tabbers, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, The Netherlands; Chris van den Akker, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, The Netherlands; Hans van Goudoever, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, The Netherlands; Sacha Verbruggen, Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands; Cai Wei, Shanghai Jiao Tong University, Shanghai, China; Weihui Yan, Department of Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China) and the members of the ESPR Section on Nutrition, Gastroenterology and Metabolism (Fredrik Ahlsson, Uppsala University Children’s Hospital and Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden; Sertac Arslanoglu, Division of Neonatology, Department of Pediatrics, Istanbul Medeniyet University, Istanbul, Turkey; Wolfgang Bernhard, Department of Neonatology, Children’s Hospital, Faculty of Medicine, Eberhard-Karls- University, Tübingen, Germany; Janet Berrington, Newcastle Neonatal Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; Signe Bruun, Hans Christian Andersen Hospital for Children and Adolescents, Odense University Hospital, Odense, Denmark; Christoph Fusch, Department of Pediatrics, Paracelsus Medical School, General Hospital of Nuremberg, Nuremberg, Germany; Shalabh Garg, South Tees Hospitals, Middlesborough, UK; Maria Gianni, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Ann Hellstrom, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Claus Klingenberg, Department of Pediatrics and Adolescence Medicine, University Hospital of North Norway, Tromsø, Norway; Helen Mactier, Neonatal Unit, Princess Royal Maternity Hospital, Glasgow, UK; Neena Modi, Section of Neonatal Medicine, Department of Medicine, Chelsea and Westminster Campus, Imperial College London, London, UK; Niels Rochow, Division of Neonatology, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada; Paola Rogerro, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Umberto Simeoni, Division of Pediatrics, CHUV & University of Lausanne, Lausanne, Switzerland; Atul Singhal, Paediatric Nutrition, UCL Great Ormond Street Institute of Child Health, London, UK.; Ulrich Thome, Department of Neonatology, Universitatsklinikum Leipzig, Leipzig, Germany; Anne Twomey, Department of Neonatology, The National Maternity Hospital, Dublin, Ireland; Mireille Vanpee, Karolinska University Hospital, Stockholm, Sweden; Gitte Zachariassen, Hans Christian Andersen Hospital for Children and Adolescents, Odense University Hospital, Odense, Denmark) for their vote.Parenteral nutrition is used to treat children that cannot be fully fed by the enteral route. While the revised ESPGHAN/ ESPEN/ESPR/CSPEN pediatric parenteral nutrition guidelines provide clear guidance on the use of parenteral nutrition in neonates, infants, and children based on current available evidence, they have helped to crystallize areas where research is lacking or more studies are needed in order to refine recommendations. This paper collates and discusses the research gaps identified by the authors of each section of the guidelines and considers each nutrient or group of nutrients in turn, together with aspects around delivery and organization. The 99 research priorities identified were then ranked in order of importance by clinicians and researchers working in the field using a survey methodology. The highest ranked priority was the need to understand the relationship between total energy intake, rapid catch-up growth, later metabolic function, and neurocognitive outcomes. Research into the optimal intakes of macronutrients needed in order to achieve optimal outcomes also featured prominently. Identifying research priorities in PN should enable research to be focussed on addressing key issues. Multicentre trials, better definition of exposure and outcome variables, and long-term metabolic and developmental follow-up will be key to achieving this