The migration of Ascaris suum larvae, and the associated pulmonary inflammatory response in susceptible C57BL/6j and resistant CBA/Ca mice

Ascariasis is an important infection in humans (Ascaris lumbricoides) and pigs (Ascaris suum) and individuals appear to be predisposed to either heavy or light worm burdens. These extremes of susceptibility and resistance are represented in a mouse model by 2 strains of mice, CBA mice showing high resistance to infection and C57BL/6 which are highly susceptible, as reflected in worm burdens in the lungs 6–7 days after infection. In an attempt to identify the point at which the difference between these 2 strains is first manifested, we quantified worm burdens at key stages during infection leading up to the pulmonary stage of development. Thus mice were inoculated with fully embryonated A. suum eggs and larval burdens were enumerated in the large intestine and rectum, liver and lungs of the 2 strains at 6 h post-inoculation (p.i.) and on each of days 1–8 p.i. inclusively. A higher percentage of the total inoculum was recovered from the intestine/rectum of C57BL/6j mice in contrast to CBA/Ca mice at 6 h p.i. Larvae were recovered from the intestinal contents and also whilst actively migrating through the large intestinal wall. The number of larvae recovered was significantly reduced in CBA/Ca mice in contrast to C57BL/6j mice between the phase of migration from the liver and arrival in the lungs. The combined results of the inoculation of mice with corticosteroids and the examination of the change in profile and number of leukocytes present in bronchoalveolar lavage fluid suggested that the pulmonary inflammatory immune response was not prominently involved in primary protection of mice to A. suum infection in the latter days of infection in the lungs. The susceptible C57BL/6j mice produced a BAL response almost twice as intense as that of resistant CBA/Ca mice with stronger neutrophil, lymphocyte and eosinophil but not macrophage components, suggesting that the difference in worm burdens between the strains was generated earlier in the course of infection. These results were further corroborated by a histological examination of the lung tissues which showed that the passage of the larval stages of A. suum through the mouse lungs was associated with a marked inflammatory response in both strains. Again, C57BL/6j mice exhibited increased inflammation relative to CBA/Ca mice. Hence some hepatic/post-hepatic factor that varies between the 2 strains, but exerts its effect before the lung phase plays a critical role in determining the success of larvae through the host tissues. The possible sites of this host defence are reviewed

From exercise intolerance to functional improvement: The second wind phenomenon in the identification of McArdle disease

McArdle disease is the most common of the glycogen storage diseases. Onset of symptoms is usually in childhood with muscle pain and restricted exercise capacity. Signs and symptoms are often ignored in children or put down to 'growing pains' and thus diagnosis is often delayed. Misdiagnosis is not uncommon because several other conditions such as muscular dystrophy and muscle channelopathies can manifest with similar symptoms. A simple exercise test performed in the clinic can however help to identify patients by revealing the second wind phenomenon which is pathognomonic of the condition. Here a patient is reported illustrating the value of using a simple 12 minute walk test.RSS is funded by Ciências sem Fronteiras/CAPES Foundation. The authors would like to thank the Association for Glycogen Storage Disease (UK), the EUROMAC Registry funded by the European Union, the Muscular Dystrophy Campaign, the NHS National Specialist Commissioning Group and the Myositis Support Group for funding

AMM15: a new high-resolution NEMO configuration for operational simulation of the European north-west shelf

This paper describes the next-generation ocean forecast model for the European north-west shelf, which will become the basis of operational forecasts in 2018. This new system will provide a step change in resolution and therefore our ability to represent small-scale processes. The new model has a resolution of 1.5 km compared with a grid spacing of 7 km in the current operational system. AMM15 (Atlantic Margin Model, 1.5 km) is introduced as a new regional configuration of NEMO v3.6. Here we describe the technical details behind this configuration, with modifications appropriate for the new high-resolution domain. Results from a 30-year non-assimilative run using the AMM15 domain demonstrate the ability of this model to represent the mean state and variability of the region. Overall, there is an improvement in the representation of the mean state across the region, suggesting similar improvements may be seen in the future operational system. However, the reduction in seasonal bias is greater off-shelf than on-shelf. In the North Sea, biases are largely unchanged. Since there has been no change to the vertical resolution or parameterization schemes, performance improvements are not expected in regions where stratification is dominated by vertical processes rather than advection. This highlights the fact that increased horizontal resolution will not lead to domain-wide improvements. Further work is needed to target bias reduction across the north-west shelf region

Substantial metabolic activity of human brown adipose tissue during warm conditions and cold-induced lipolysis of local triglycerides

Current understanding of in vivo human brown adipose tissue (BAT) physiology is limited by a reliance on positron emission tomography (PET)/computed tomography (CT) scanning, which has measured exogenous glucose and fatty acid uptake but not quantified endogenous substrate utilization by BAT. Six lean, healthy men underwent 18fluorodeoxyglucose-PET/CT scanning to localize BAT so microdialysis catheters could be inserted in supraclavicular BAT under CT guidance and in abdominal subcutaneous white adipose tissue (WAT). Arterial and dialysate samples were collected during warm (∼25°C) and cold exposure (∼17°C), and blood flow was measured by 133xenon washout. During warm conditions, there was increased glucose uptake and lactate release and decreased glycerol release by BAT compared with WAT. Cold exposure increased blood flow, glycerol release, and glucose and glutamate uptake only by BAT. This novel use of microdialysis reveals that human BAT is metabolically active during warm conditions. BAT activation substantially increases local lipolysis but also utilization of other substrates such as glutamate

Creation and implementation of a European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC registry)

BACKGROUND: International patient registries are of particular importance for rare disorders, as they may contribute to overcome the lack of knowledge derived from low number of patients and limited awareness of these diseases, and help to learn more about their geographical or population-based specificities, which is relevant for research purposes and for promoting better standards of care and diagnosis. Our objective was to create and implement a European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC) and to disseminate the knowledge of these disorders. RESULTS: Teams from nine different countries (United Kingdom, Spain, Italy, France, Germany, Denmark, Greece, Turkey and USA) created a consortium that developed the first European registry dedicated to rare muscle glycogenoses. A work plan was implemented to design the database and platform that constitute the registry, by choosing clinical, genetics and molecular variables of interest, based on experience gained from previous national registries for similar metabolic disorders. Among dissemination activities, several teaching events were organized in different countries, especially those where the consortium considered the awareness of these diseases needs to be promoted among health professionals and patients. CONCLUSION: EUROMAC represents a step forward in the knowledge of those disorders to which it is dedicated, and will have relevant clinical outcomes at the diagnostic, epidemiological, clinical and research level