GM-CSF is a marker of compartmentalised intrathecal inflammation in multiple sclerosis.

BACKGROUND: Granulocyte-macrophage colony stimulating factor (GM-CSF) is a pro-inflammatory cytokine secreted by various immune cells. Several studies have demonstrated an expansion of GM-CSF producing T cells in the blood or CSF of people with MS (pwMS). However, whether this equates to greater concentrations of circulating cytokine remains unknown as quantification is difficult with traditional assays. OBJECTIVE: To determine whether GM-CSF can be quantified and whether GM-CSF levels are elevated in pwMS. METHODS: We employed Single Molecule Array (Simoa) to measure GM-CSF in both CSF and blood. We then investigated relationships between GM-CSF levels and measures of blood-CSF-barrier integrity. RESULTS: GM-CSF was quantifiable in all samples and was significantly higher in the CSF of pwMS compared with controls. No association was found between CSF GM-CSF levels and Q-Albumin - a measure of blood-CSF-barrier integrity. CSF GM-CSF correlated with measures of intrathecal inflammation, and these relationships were greater in primary progressive MS compared with relapsing-remitting MS. CONCLUSION: GM-CSF levels are elevated specifically in the CSF of pwMS. Our results suggest that elevated cytokine levels may reflect (at least partial) intrathecal production, as opposed to simple diffusion across a dysfunctional blood-CSF-barrier.

Size rather than complexity of sexual ornaments prolongs male metamorphosis and explains sexual size dimorphism in sepsid flies.

Male sexual ornaments often evolve rapidly and are thought to be costly, thus contributing to sexual size dimorphism. However, little is known about their developmental costs, and even less about costs associated with structural complexity. Here, we quantified the size and complexity of three morphologically elaborate sexually dimorphic male ornaments that starkly differ across sepsid fly species (Diptera: Sepsidae): (i) male forelegs range from being unmodified, like in most females, to being adorned with spines and large cuticular protrusions; (ii) the fourth abdominal sternites are either unmodified or are converted into complex de novo appendages; and (iii) male genital claspers range from small and simple to large and complex (e.g. bifurcated). We tracked the development of 18 sepsid species from egg to adult to determine larval feeding and pupal metamorphosis times of both sexes. We then statistically explored whether pupal and adult body size, ornament size and/or ornament complexity are correlated with sex-specific development times. Larval growth and foraging periods of male and female larvae did not differ, but the time spent in the pupal stage was ca 5% longer for sepsid males despite emerging 9% smaller than females on average. Surprisingly, we found no evidence that sexual trait complexity prolongs pupal development beyond some effects of trait size. Evolving more complex traits thus does not incur developmental costs at least in this system.

Microsporidia: a new taxonomic, evolutionary, and ecological synthesis.

Microsporidian diversity is vast. There is a renewed drive to understand how microsporidian pathological, genomic, and ecological traits relate to their phylogeny. We comprehensively sample and phylogenetically analyse 125 microsporidian genera for which sequence data are available. Comparing these results with existing phylogenomic analyses, we suggest an updated taxonomic framework to replace the inconsistent clade numbering system, using informal taxonomic names: Glugeida (previously clades 5/3), Nosematida (4a), Enterocytozoonida (4b), Amblyosporida (3/5), Neopereziida (1), and Ovavesiculida (2). Cellular, parasitological, and ecological traits for 281 well-defined species are compared with identify clade-specific patterns across long-branch Microsporidia. We suggest that future taxonomic circumscriptions of Microsporidia should involve additional markers (SSU/ITS/LSU), and that a comprehensive suite of phenotypic and ecological traits help to predict broad microsporidian functional and lineage diversity.

Deformed wing virus variant shift from 2010 to 2016 in managed and feral UK honey bee colonies.

Deformed wing virus (DWV) has been linked to the global decline of honey bees. DWV exists as three master variants (DWV-A, DWV-B, and DWV-C), each with differing outcomes for the honey bee host. Research in the USA showed a shift from DWV-A to DWV-B between 2010 to 2016 in honey bee colonies. Likewise, in the UK, a small study in 2007 found only DWV-A, whereas in 2016, DWV-B was the most prevalent variant. This suggests a shift from DWV-A to DWV-B might have occurred in the UK between 2007 and 2016. To investigate this further, data from samples collected in 2009/10 (n = 46) were compared to existing data from 2016 (n = 42). These samples also allowed a comparison of DWV variants between Varroa-untreated (feral) and Varroa-treated (managed) colonies. The results revealed that, in the UK, DWV-A was far more prevalent in 2009/10 (87%) than in 2016 (43%). In contrast, DWV-B was less prevalent in 2009/10 (76%) than in 2016 (93%). Regardless if colonies had been treated for Varroa (managed) or not (feral), the same trend from DWV-A to DWV-B occurred. Overall, the results reveal a decrease in DWV-A and an increase in DWV-B in UK colonies.

Podocotyle atomon (Trematoda: Digenea) impacts reproductive behaviour, survival and physiology in Gammarus zaddachi (Amphipoda).

The Trematoda are a group of phylogenetically diverse metazoan parasites that exhibit complex life cycles that often pass through invertebrate and vertebrate hosts. Some trematodes influence their host's behaviour to benefit transmission. Their parasitic influence may impact host population size by inhibiting an individual's reproductive capacity. We assessed the impact of infection by Podocotyle atomon on the reproductive behaviour and fecundity of its amphipod intermediate host, Gammarus zaddachi, using laboratory and field studies. Parasite prevalence was high in the field, with males more likely to be infected (prevalence in males 64%, in females 39%). Males also suffered a higher parasite burden than females. Infected females were less active, but we found no evidence for a reduction in female reproductive success. Infected females also had comparable pairing success to uninfected females. In males, infection reduced survival and fecundity, with mortality being highest, and sperm numbers lowest, in heavily infected individuals. Trematode parasites are sometimes associated with altered host fecundity, but studies often lack the relevant experimental data to explore the evolution of the trait. We discuss this among information specific to the effect of P. atomon infection in G. zaddachi.

INFOGEST static in vitro simulation of gastrointestinal food digestion.

Developing a mechanistic understanding of the impact of food structure and composition on human health has increasingly involved simulating digestion in the upper gastrointestinal tract. These simulations have used a wide range of different conditions that often have very little physiological relevance, and this impedes the meaningful comparison of results. The standardized protocol presented here is based on an international consensus developed by the COST INFOGEST network. The method is designed to be used with standard laboratory equipment and requires limited experience to encourage a wide range of researchers to adopt it. It is a static digestion method that uses constant ratios of meal to digestive fluids and a constant pH for each step of digestion. This makes the method simple to use but not suitable for simulating digestion kinetics. Using this method, food samples are subjected to sequential oral, gastric and intestinal digestion while parameters such as electrolytes, enzymes, bile, dilution, pH and time of digestion are based on available physiological data. This amended and improved digestion method (INFOGEST 2.0) avoids challenges associated with the original method, such as the inclusion of the oral phase and the use of gastric lipase. The method can be used to assess the endpoints resulting from digestion of foods by analyzing the digestion products (e.g., peptides/amino acids, fatty acids, simple sugars) and evaluating the release of micronutrients from the food matrix. The whole protocol can be completed in ~7 d, including ~5 d required for the determination of enzyme activities.

Formation of a morphine-conditioned place preference does not change the size of evoked potentials in the ventral hippocampus-nucleus accumbens projection.

In opioid addiction, cues and contexts associated with drug reward can be powerful triggers for drug craving and relapse. The synapses linking ventral hippocampal outputs to medium spiny neurons of the accumbens may be key sites for the formation and storage of associations between place or context and reward, both drug-related and natural. To assess this, we implanted rats with electrodes in the accumbens shell to record synaptic potentials evoked by electrical stimulation of the ventral hippocampus, as well as continuous local-field-potential activity. Rats then underwent morphine-induced (10 mg/kg) conditioned-place-preference training, followed by extinction. Morphine caused an acute increase in the slope and amplitude of accumbens evoked responses, but no long-term changes were evident after conditioning or extinction of the place preference, suggesting that the formation of this type of memory does not lead to a net change in synaptic strength in the ventral hippocampal output to the accumbens. However, analysis of the local field potential revealed a marked sensitization of theta- and high-gamma-frequency activity with repeated morphine administration. This phenomenon may be linked to the behavioral changes-such as psychomotor sensitization and the development of drug craving-that are associated with chronic use of addictive drugs.

The barriers to linkage and retention in care for women living with HIV in an high income setting where they comprise a minority group.

Women comprise a minority population of individuals living with HIV in Australia, and are often poorly represented in research and clinical trials so their needs remain largely unknown. Data suggests that they are diagnosed later than men and start antiretroviral therapy at a lower CD4 cell count. This raises the question whether there are sex specific barriers to linkage and retention in care. This study analyzed 484 surveys received from clinicians collecting demographic, virological, and reproductive health data along with perceived barriers to linkage and retention in care. Most women (67%) were estimated to have been linked into care within 28 days of diagnosis. For women who were not linked into care for more than 28 days, the most commonly reason cited was fear of disclosure to others, followed by fear of disclosure to their partner. The main reasons given for non-retention in care were related to transport, carer responsibilities, financial pressure, health beliefs and concern about stigma or disclosure.

Origins of Vespa velutina hornets that recently invaded Iki Island, Japan and Jersey Island, UK.

The native distribution of the yellow-legged hornet, Vespa velutina, is throughout East Asia. Around 15 years ago this species was accidentally introduced into South Korea and France, where it became established and then spread into neighbouring countries. Previous mitochondrial DNA studies showed that the South Korean, Japanese, and French populations all originated from Eastern China. Recently, the hornet has invaded Iki Island, Japan and Jersey Island, UK. In this study, we analyze the complete mitochondrial DNA sequence of V. velutina to trace the origin of these two populations. The mitochondrial DNA haplotypes (COI, Cytb, and 16S rRNA) of V. velutina in Iki Island matched the unique haplotype present in China, South Korea, and Japan, while the haplotype from Jersey Island matched that of V. velutina found in France and China. These findings were supported by data from the complete mitochondrial DNA sequence of V. velutina from Iki Island, which was consistent with the sequence from South Korea and Tsushima, whereas V. velutina in Jersey was most similar to the French population.

Osmoadaptation of wine yeast (Saccharomyces cerevisiae) during Icewine fermentation leads to high levels of acetic acid.

AIMS: Volatile acidity (VA) production along with gene expression patterns, encoding enzymes involved in both acetic acid production and utilization, were investigated to relate gene expression patterns to the production of undesired VA during Icewine fermentation. METHODS AND RESULTS: Icewine juice and diluted Icewine juice were fermented using the Saccharomyces cerevisiae wine yeast K1-V1116. Acetic acid production increased sixfold during the Icewine fermentation vs the diluted juice condition, while ethyl acetate production increased 2·4-fold in the diluted fermentation relative to the Icewine. Microarray analysis profiled the transcriptional response of K1-V1116 under both conditions. ACS1 and ACS2 were downregulated 19·0-fold and 11·2-fold, respectively, in cells fermenting Icewine juice compared to diluted juice. ALD3 expression was upregulated 14·6-fold, and gene expressions involved in lipid and ergosterol synthesis decreased during Icewine fermentation. CONCLUSIONS: Decreased expression of ACS1 and ACS2 together with increased ALD3 expression contributes to the higher acetic acid and lower ethyl acetate levels generated by K1-V1116 fermenting under hyperosmotic stress. SIGNIFICANCE AND IMPACT OF THE STUDY: This work represents a more comprehensive understanding of how and why commercial wine yeast respond at the transcriptional and metabolic level during fermentation of Icewine juice, and how these responses contribute to increased acetic acid and decreased ethyl acetate production.

Oldest Varroa tolerant honey bee population provides insight into the origins of the global decline of honey bees.

The ecto-parasitic mite Varroa destructor has transformed the previously inconsequential Deformed Wing Virus (DWV) into the most important honey bee viral pathogen responsible for the death of millions of colonies worldwide. Naturally, DWV persists as a low level covert infection transmitted between nest-mates. It has long been speculated that Varroa via immunosuppression of the bees, activate a covert infection into an overt one. Here we show that despite Varroa feeding on a population of 20-40 colonies for over 30 years on the remote island of Fernando de Noronha, Brazil no such activation has occurred and DWV loads have remained at borderline levels of detection. This supports the alternative theory that for a new vector borne viral transmission cycle to start, an outbreak of an overt infection must first occur within the host. Therefore, we predict that this honey bee population is a ticking time-bomb, protected by its isolated position and small population size. This unique association between mite and bee persists due to the evolution of low Varroa reproduction rates. So the population is not adapted to tolerate Varroa and DWV, rather the viral quasispecies has simply not yet evolved the necessary mutations to produce a virulent variant.

Satiety Impact of Different Potato Products Compared to Pasta Control.

OBJECTIVE: A variety of potato dishes are regularly consumed worldwide, but the satiety value of these foods is not well established. The primary objective of this study was to compare the satiating effects of 4 equi-energy meals containing different potato preparations with an equi-energy pasta control meal. METHODS: This study used a randomized crossover design to assess the impact of 4 equi-energy potato-based meals (fried French fries, baked potato, mashed potato, or potato wedges) on subjective satiety sensations (visual analogue scale [VAS] ratings) and subsequent energy intake (ad libitum meal [kcal]), compared to a control pasta-based meal. Thirty-three healthy nonobese men and women participated in the study. RESULTS: VAS ratings indicated that the meal containing fried french fries was perceived to be substantially more satiating than the equi-energy pasta control meal, with all other potato-based meals not differing overall from control. All test meals had a comparable effect on energy intake at a later ad libitum meal. CONCLUSIONS: Consumers reported higher levels of satiety following a meal where the principal carbohydrate source was fried french fries, compared to when they had consumed an energy-matched meal containing carbohydrate in the form of pasta. All other potato preparations had similar effects on satiety as pasta. It is concluded that participants perceived a meal with fried french fries as providing greater satiety than a pasta control meal.

Deformed wing virus is a recent global epidemic in honeybees driven by Varroa mites.

Deformed wing virus (DWV) and its vector, the mite Varroa destructor, are a major threat to the world's honeybees. Although the impact of Varroa on colony-level DWV epidemiology is evident, we have little understanding of wider DWV epidemiology and the role that Varroa has played in its global spread. A phylogeographic analysis shows that DWV is globally distributed in honeybees, having recently spread from a common source, the European honeybee Apis mellifera. DWV exhibits epidemic growth and transmission that is predominantly mediated by European and North American honeybee populations and driven by trade and movement of honeybee colonies. DWV is now an important reemerging pathogen of honeybees, which are undergoing a worldwide manmade epidemic fueled by the direct transmission route that the Varroa mite provides.

Engineering Digestion: Multiscale Processes of Food Digestion.

Food digestion is a complex, multiscale process that has recently become of interest to the food industry due to the developing links between food and health or disease. Food digestion can be studied by using either in vitro or in vivo models, each having certain advantages or disadvantages. The recent interest in food digestion has resulted in a large number of studies in this area, yet few have provided an in-depth, quantitative description of digestion processes. To provide a framework to develop these quantitative comparisons, a summary is given here between digestion processes and parallel unit operations in the food and chemical industry. Characterization parameters and phenomena are suggested for each step of digestion. In addition to the quantitative characterization of digestion processes, the multiscale aspect of digestion must also be considered. In both food systems and the gastrointestinal tract, multiple length scales are involved in food breakdown, mixing, absorption. These different length scales influence digestion processes independently as well as through interrelated mechanisms. To facilitate optimized development of functional food products, a multiscale, engineering approach may be taken to describe food digestion processes. A framework for this approach is described in this review, as well as examples that demonstrate the importance of process characterization as well as the multiple, interrelated length scales in the digestion process.

Lowering levels of bed occupancy is associated with decreased inhospital mortality and improved performance on the 4-hour target in a UK District General Hospital.

OBJECTIVE: To evaluate whether there is an association between an intervention to reduce medical bed occupancy and performance on the 4-hour target and hospital mortality. METHODS: This before-and-after study was undertaken in a large UK District General Hospital over a 32 month period. A range of interventions were undertaken to reduce medical bed occupancy within the Trust. Performance on the 4-hour target and hospital mortality (hospital standardised mortality ratio (HSMR), summary hospital-level mortality indicator (SHMI) and crude mortality) were compared before, and after, intervention. Daily data on medical bed occupancy and percentage of patients meeting the 4-hour target was collected from hospital records. Segmented regression analysis of interrupted time-series method was used to estimate the changes in levels and trends in average medical bed occupancy, monthly performance on the target and monthly mortality measures (HSMR, SHMI and crude mortality) that followed the intervention. RESULTS: Mean medical bed occupancy decreased significantly from 93.7% to 90.2% (p=0.02). The trend change in target performance, when comparing preintervention and postintervention, revealed a significant improvement (p=0.019). The intervention was associated with a mean reduction in all markers of mortality (range 4.5-4.8%). SHMI (p=0.02) and crude mortality (p=0.018) showed significant trend changes after intervention. CONCLUSIONS: Lowering medical bed occupancy is associated with reduced patient mortality and improved ability of the acute Trust to achieve the 95% 4-hour target. Whole system transformation is required to create lower average medical bed occupancy.

Digestibility of gluten proteins is reduced by baking and enhanced by starch digestion.

SCOPE: Resistance of proteins to gastrointestinal digestion may play a role in determining immune-mediated adverse reactions to foods. However, digestion studies have largely been restricted to purified proteins and the impact of food processing and food matrices on protein digestibility is poorly understood. METHODS AND RESULTS: Digestibility of a total gliadin fraction (TGF), flour (cv Hereward), and bread was assessed using in vitro batch digestion with simulated oral, gastric, and duodenal phases. Protein digestion was monitored by SDS-PAGE and immunoblotting using monoclonal antibodies specific for celiac-toxic sequences (QQSF, QPFP) and starch digestion by measuring undigested starch. Whereas the TGF was rapidly digested during the gastric phase the gluten proteins in bread were virtually undigested and digested rapidly during the duodenal phase only if amylase was included. Duodenal starch digestion was also slower in the absence of duodenal proteases. CONCLUSION: The baking process reduces the digestibility of wheat gluten proteins, including those containing sequences active in celiac disease. Starch digestion affects the extent of protein digestion, probably because of gluten-starch complex formation during baking. Digestion studies using purified protein fractions alone are therefore not predictive of digestion in complex food matrices.

Necroptosis suppresses inflammation via termination of TNF- or LPS-induced cytokine and chemokine production.

TNF promotes a regulated form of necrosis, called necroptosis, upon inhibition of caspase activity in cells expressing RIPK3. Because necrosis is generally more pro-inflammatory than apoptosis, it is widely presumed that TNF-induced necroptosis may be detrimental in vivo due to excessive inflammation. However, because TNF is intrinsically highly pro-inflammatory, due to its ability to trigger the production of multiple cytokines and chemokines, rapid cell death via necroptosis may blunt rather than enhance TNF-induced inflammation. Here we show that TNF-induced necroptosis potently suppressed the production of multiple TNF-induced pro-inflammatory factors due to RIPK3-dependent cell death. Similarly, necroptosis also suppressed LPS-induced pro-inflammatory cytokine production. Consistent with these observations, supernatants from TNF-stimulated cells were more pro-inflammatory than those from TNF-induced necroptotic cells in vivo. Thus necroptosis attenuates TNF- and LPS-driven inflammation, which may benefit intracellular pathogens that evoke this mode of cell death by suppressing host immune responses.

A mid-morning snack of almonds generates satiety and appropriate adjustment of subsequent food intake in healthy women.

PURPOSE: To assess the effect of consuming a mid-morning almond snack (28 and 42 g) tested against a negative control of no almonds on acute satiety responses. METHOD: On three test days, 32 healthy females consumed a standard breakfast followed by 0, 28 or 42 g of almonds as a mid-morning snack and then ad libitum meals at lunch and dinner. The effect of the almond snacks on satiety was assessed by measuring energy intake (kcal) at the two ad libitum meals and subjective appetite ratings (visual analogue scales) throughout the test days. RESULTS: Intake at lunch and dinner significantly decreased in a dose-dependent manner in response to the almond snacks. Overall, a similar amount of energy was consumed on all three test days indicating that participants compensated for the 173 and 259 kcals consumed as almonds on the 28 and 42 g test days, respectively. Subjective appetite ratings in the interval between the mid-morning snack and lunch were consistent with dose-dependent enhanced satiety following the almond snacks. However, in the interval between lunch and dinner, appetite ratings were not dependent on the mid-morning snack. CONCLUSION: Almonds might be a healthy snack option since their acute satiating effects are likely to result in no net increase in energy consumed over a day.

Hydrothermal carbonisation of sewage sludge: effect of process conditions on product characteristics and methane production.

Hydrothermal carbonisation of primary sewage sludge was carried out using a batch reactor. The effect of temperature and reaction time on the characteristics of solid (hydrochar), liquid and gas products, and the conditions leading to optimal hydrochar characteristics were investigated. The amount of carbon retained in hydrochars decreased as temperature and time increased with carbon retentions of 64-77% at 140 and 160°C, and 50-62% at 180 and 200°C. Increasing temperature and treatment time increased the energy content of the hydrochar from 17 to 19 MJ/kg but reduced its energy yield from 88% to 68%. Maillard reaction products were identified in the liquid fractions following carbonisations at 180 and 200°C. Theoretical estimates of the methane yields resulting from the anaerobic digestion of the liquid by-products are also presented and optimal reaction conditions to maximise these identified.