[Gut microbiome and anorexia nervosa : The relationship between microbiome and gut-brain interaction in the context of anorexia nervosa]. / Darmmikrobiom und Anorexia nervosa : Der Zusammenhang von Mikrobiom und Darm-Gehirn-Interaktion im Kontext der Anorexia nervosa.

In recent years the intestinal microbiome and its interaction with the brain has aroused a growing interest. The findings gained in the course of this research are of great relevance not only to basic scientists but also to clinicians, as studies suggest an association between an altered microbiome and various somatic (e.g. chronic inflammatory intestinal diseases, obesity and diabetes) as well as psychiatric diseases (e.g. anxiety disorders, depression). In addition to a direct influence of the microbiome on the brain and behavior, various mechanisms seem to be relevant, including altered energy intake from food, hormonal changes, probably increased intestinal permeability as well as inflammatory and immunological processes. Anorexia nervosa (AN) is the third most common chronic disease in adolescence and has the highest mortality rate among all mental disorders. In addition to extremely restrictive eating habits, weight loss and comorbid anxiety and depression symptoms, endocrine changes and an increased autoimmune and inflammatory response are characteristic. Since AN is particularly strongly linked to eating behavior and nutrition, research into the microbiome seems very promising, especially with respect to this disease. This article gives a first insight into the underlying processes that play a role in gut-brain interaction in the context of AN and summarizes the previous empirical findings on this topic. Finally, an outlook on future research and possible implications for the therapeutic practice and treatment of AN is given.

Preference Functions for Spatial Risk Analysis.

When outcomes are defined over a geographic region, measures of spatial risk regarding these outcomes can be more complex than traditional measures of risk. One of the main challenges is the need for a cardinal preference function that incorporates the spatial nature of the outcomes. We explore preference conditions that will yield the existence of spatial measurable value and utility functions, and discuss their application to spatial risk analysis. We also present a simple example on household freshwater usage across regions to demonstrate how such functions can be assessed and applied.

Pauling Entropy, Metastability, and Equilibrium in Dy_{2}Ti_{2}O_{7} Spin Ice.

Determining the fate of the Pauling entropy in the classical spin ice material Dy_{2}Ti_{2}O_{7} with respect to the third law of thermodynamics has become an important test case for understanding the existence and stability of ice-rule states in general. The standard model of spin ice-the dipolar spin ice model-predicts an ordering transition at T≈0.15 K, but recent experiments by Pomaranski et al. suggest an entropy recovery over long timescales at temperatures as high as 0.5 K, much too high to be compatible with the theory. Using neutron scattering and specific heat measurements at low temperatures and with long timescales (0.35 K/10^{6} s and 0.5 K/10^{5} s, respectively) on several isotopically enriched samples, we find no evidence of a reduction of ice-rule correlations or spin entropy. High-resolution simulations of the neutron structure factor show that the spin correlations remain well described by the dipolar spin ice model at all temperatures. Furthermore, by careful consideration of hyperfine contributions, we conclude that the original entropy measurements of Ramirez et al. are, after all, essentially correct: The short-time relaxation method used in that study gives a reasonably accurate estimate of the equilibrium spin ice entropy due to a cancellation of contributions.

Dipolar Spin Ice States with a Fast Monopole Hopping Rate in CdEr_{2}X_{4} (X=Se, S).

Excitations in a spin ice behave as magnetic monopoles, and their population and mobility control the dynamics of a spin ice at low temperature. CdEr_{2}Se_{4} is reported to have the Pauling entropy characteristic of a spin ice, but its dynamics are three orders of magnitude faster than the canonical spin ice Dy_{2}Ti_{2}O_{7}. In this Letter we use diffuse neutron scattering to show that both CdEr_{2}Se_{4} and CdEr_{2}S_{4} support a dipolar spin ice state-the host phase for a Coulomb gas of emergent magnetic monopoles. These Coulomb gases have similar parameters to those in Dy_{2}Ti_{2}O_{7}, i.e., dilute and uncorrelated, and so cannot provide three orders faster dynamics through a larger monopole population alone. We investigate the monopole dynamics using ac susceptometry and neutron spin echo spectroscopy, and verify the crystal electric field Hamiltonian of the Er^{3+} ions using inelastic neutron scattering. A quantitative calculation of the monopole hopping rate using our Coulomb gas and crystal electric field parameters shows that the fast dynamics in CdEr_{2}X_{4} (X=Se, S) are primarily due to much faster monopole hopping. Our work suggests that CdEr_{2}X_{4} offer the possibility to study alternative spin ice ground states and dynamics, with equilibration possible at much lower temperatures than the rare earth pyrochlore examples.

Polydomy enhances foraging performance in ant colonies.

Collective foraging confers benefits in terms of reduced predation risk and access to social information, but it heightens local competition when resources are limited. In social insects, resource limitation has been suggested as a possible cause for the typical decrease in per capita productivity observed with increasing colony size, a phenomenon known as Michener's paradox. Polydomy (distribution of a colony's brood and workers across multiple nests) is believed to help circumvent this paradox through its positive effect on foraging efficiency, but there is still little supporting evidence for this hypothesis. Here, we show experimentally that polydomy enhances the foraging performance of food-deprived Temnothorax nylanderi ant colonies via several mechanisms. First, polydomy influences task allocation within colonies, resulting in faster retrieval of protein resources. Second, communication between sister nests reduces search times for far away resources. Third, colonies move queens, brood and workers across available nest sites in response to spatial heterogeneities in protein and carbohydrate resources. This suggests that polydomy represents a flexible mechanism for space occupancy, helping ant colonies adjust to the environment.

Chitosan-based nanocomposites for the repair of bone defects.

Chitosan scaffolds of different deacetylation degrees, average molecular weights and concentrations reinforced with silica nanoparticles were prepared for bone tissue regeneration. The resulting nanocomposites showed similar pore sizes (<300 µm) regardless the deacetylation degree and concentration used in their formulation. Their mechanical compression resistance was increased by a 30% with the addition of silica nanoparticles as nanofillers. The biocompatibility of the three-dimensional chitosan scaffolds was confirmed by the Alamar Blue assay in human primary osteoblasts as well as the formation of cell spheroids indicative of their great potential for bone regeneration. In vivo implantation of the scaffolds in a mice calvaria defect model provided substantial evidences of the suitability of these nanocomposites for bone tissue engineering showing a mature and dense collagenous tissue with small foci of mineralization, vascularized areas and the infiltration of osteoblasts and osteoclasts. Nevertheless, mature bone tissue formation was not observed after eight weeks of implantation.

Information Presentation in Decision and Risk Analysis: Answered, Partly Answered, and Unanswered Questions.

For the last 30 years, researchers in risk analysis, decision analysis, and economics have consistently proven that decisionmakers employ different processes for evaluating and combining anticipated and actual losses, gains, delays, and surprises. Although rational models generally prescribe a consistent response, people's heuristic processes will sometimes lead them to be inconsistent in the way they respond to information presented in theoretically equivalent ways. We point out several promising future research directions by listing and detailing a series of answered, partly answered, and unanswered questions.

Phenotype-associated inbreeding biases estimates of inbreeding depression in a wild bird population.

Inbreeding depression is usually quantified by regressing individual phenotypic values on inbreeding coefficients, implicitly assuming there is no correlation between an individual's phenotype and the kinship coefficient to its mate. If such an association between parental phenotype and parental kinship exists, and if the trait of interest is heritable, estimates of inbreeding depression can be biased. Here we first derive the expected bias as a function of the covariance between mean parental breeding value and parental kinship. Subsequently, we use simulated data to confirm the existence of this bias, and show that it can be accounted for in a quantitative genetic animal model. Finally, we use long-term individual-based data for white-throated dippers (Cinclus cinclus), a bird species in which inbreeding is relatively common, to obtain an empirical estimate of this bias. We show that during part of the study period, parents of inbred birds had shorter wings than those of outbred birds, and as wing length is heritable, inbred individuals were smaller, independent of any inbreeding effects. This resulted in the overestimation of inbreeding effects. Similarly, during a period when parents of inbred birds had longer wings, we found that inbreeding effects were underestimated. We discuss how such associations may have arisen in this system, and why they are likely to occur in others, too. Overall, we demonstrate how less biased estimates of inbreeding depression can be obtained within a quantitative genetic framework, and suggest that inbreeding and additive genetic effects should be accounted for simultaneously whenever possible.

Genetic variance components and heritability of multiallelic heterozygosity under inbreeding.

The maintenance of genetic diversity in fitness-related traits remains a central topic in evolutionary biology, for example, in the context of sexual selection for genetic benefits. Among the solutions that have been proposed is directional sexual selection for heterozygosity. The importance of such selection is highly debated. However, a critical evaluation requires knowledge of the heritability of heterozygosity, a quantity that is rarely estimated in this context, and often assumed to be zero. This is at least partly the result of the lack of a general framework that allows for its quantitative prediction in small and inbred populations, which are the focus of most empirical studies. Moreover, while current predictors are applicable only to biallelic loci, fitness-relevant loci are often multiallelic, as are the neutral markers typically used to estimate genome-wide heterozygosity. To this end, we first review previous, but little-known, work showing that under most circumstances, heterozygosity at biallelic loci and in the absence of inbreeding is heritable. We then derive the heritability of heterozygosity and the underlying variances for multiple alleles and any inbreeding level. We also show that heterozygosity at multiallelic loci can be highly heritable when allele frequencies are unequal, and that this heritability is reduced by inbreeding. Our quantitative genetic framework can provide new insights into the evolutionary dynamics of heterozygosity in inbred and outbred populations.

Expression of foraging and Gp-9 are associated with social organization in the fire ant Solenopsis invicta.

The aim of this study was to investigate levels of expression of two major genes, the odorant binding protein Gp-9 (general protein-9) and foraging, that have been shown to be associated with behavioural polymorphisms in ants. We analysed workers and young nonreproductive queens collected from nests of the monogyne (single reproductive queen per nest) and polygyne (multiple reproductive queens) social forms of Solenopsis invicta. In workers but not young queens, the level of foraging expression was significantly associated with social form and the task performed (ie localization in the nest or foraging area). The level of expression of Gp-9 was also associated with social form and worker localization. In addition there was a higher level of expression of the Gp-9(b) allele compared with the Gp-9(B) allele in the heterozygote workers and the young nonreproductive queens. Finally, in the polygyne colonies the level of expression of foraging was not significantly associated with the Gp-9 genotype for either workers or young nonreproductive queens, suggesting that both genes have independent non-epistatic effects on behaviour in S. invicta.

A Markov model to evaluate cost-effectiveness of antiangiogenesis therapy using bevacizumab in advanced cervical cancer.

OBJECTIVE: To evaluate the cost-effectiveness of bevacizumab in recurrent/persistent and metastatic cervical cancer using recently reported updated survival and toxicology data. METHODS: A Markov decision tree based on the Gynecologic Oncology Group 240 randomized trial was created. The 2013 MediCare Services Drug Payment Table and Physician Fee Schedule provided costs. In the 5-year model subjects transitioned through the following states: response, progression, minor complications, severe complications, and death. Patients experiencing a health utility per month according to treatment effectiveness were calculated. Because cervical cancer survival is measured in months rather than years, results were reported in both quality adjusted cervical cancer life months and years (QALmonth, QALY), adjusted from a baseline of having advanced cervical cancer during a month. RESULTS: The estimated total cost of therapy with bevacizumab is approximately 13.2 times that for chemotherapy alone, adding $73,791 per 3.5months (0.29year) of life gained, resulting in an incremental cost-effectiveness ratio (ICER) of $21.083 per month of added life. The ICER increased to $5775 per month of added life and $24,597/QALmonth ($295,164/QALY) due to the smaller difference in QALmonths. With 75% bevacizumab cost reduction, the ICER is $6737/QALmonth ($80,844/QALY), which translates to $23,580 for the 3.5month (0.29year) gain in OS. CONCLUSIONS: Increased costs are primarily related to the cost of drug and not the management of bevacizumab-induced complications. Cost reductions in bevacizumab result in dramatic declines in the ICER, suggesting that cost reconciliation in advanced cervical cancer may be possible through the availability of biosimilars, and/or less expensive, equally efficacious anti-angiogenesis agents.

Population genomics of eusocial insects: the costs of a vertebrate-like effective population size.

The evolution of reproductive division of labour and social life in social insects has lead to the emergence of several life-history traits and adaptations typical of larger organisms: social insect colonies can reach masses of several kilograms, they start reproducing only when they are several years old, and can live for decades. These features and the monopolization of reproduction by only one or few individuals in a colony should affect molecular evolution by reducing the effective population size. We tested this prediction by analysing genome-wide patterns of coding sequence polymorphism and divergence in eusocial vs. noneusocial insects based on newly generated RNA-seq data. We report very low amounts of genetic polymorphism and an elevated ratio of nonsynonymous to synonymous changes ­ a marker of the effective population size ­ in four distinct species of eusocial insects, which were more similar to vertebrates than to solitary insects regarding molecular evolutionary processes. Moreover, the ratio of nonsynonymous to synonymous substitutions was positively correlated with the level of social complexity across ant species. These results are fully consistent with the hypothesis of a reduced effective population size and an increased genetic load in eusocial insects, indicating that the evolution of social life has important consequences at both the genomic and population levels.

An empirical study of the toxic capsule crisis in China: risk perceptions and behavioral responses.

The outbreak of the toxic capsule crisis during April 2012 aroused widespread public concern about the risk of chromium-contaminated capsules and drug safety in China. In this article, we develop a conceptual model to investigate risk perceptions of the pharmaceutical drug capsules and behavioral responses to the toxic capsule crisis and the relationship between associated factors and these two variables. An online survey was conducted to test the model, including questions on the measures of perceived efficacy of the countermeasures, trust in the State FDA (Food and Drug Administration), trust in the pharmaceutical companies, trust in the pharmaceutical capsule producers, risk perception, concern, need for information, information seeking, and risk avoidance. In general, participants reported higher levels of risk perception, concern, and risk avoidance, and lower levels of trust in the three different stakeholders. The results from the structural equation modeling procedure suggest that perceived efficacy of the countermeasures is a predictor of each of the three trust variables; however, only trust in the State FDA has a dampening impact on risk perception. Both risk perception and information seeking are significant determinants of risk avoidance. Risk perception is also positively related to concern. Information seeking is positively related to both concern and need for information. The theoretical and policy implications are also discussed.

PspK of Streptococcus pneumoniae increases adherence to epithelial cells and enhances nasopharyngeal colonization.

Streptococcus pneumoniae (the pneumococcus) colonizes the human nasopharynx and can cause invasive disease aided by the pneumococcal capsule. Group II nontypeable S. pneumoniae (NTSp) lacks a polysaccharide capsule, and a subgroup of NTSp carriage isolates has been found to have a novel gene, pneumococcal surface protein K (pspK), which replaces the capsule locus. A recent rise in the number of NTSp isolates colonizing the human nasopharynx has been observed, but the colonization factors of NTSp have not been well studied. PspK has been shown to play a role in mouse colonization. We therefore examined PspK-mediated immune evasion along with adherence to host cells and colonization. PspK bound human secretory immunoglobulin A (sIgA) but not the complement regulator factor H and did not decrease C3b deposition on the pneumococcal surface. PspK increased binding of pneumococci to epithelial cells and enhanced pneumococcal colonization independently of the genetic background. Understanding how NTSp colonizes and survives within the nasopharynx is important due to the increase in NTSp carriage. Our data suggest that PspK may aid in the persistence of NTSp within the nasopharynx but is not involved in invasion.

Dynamical splayed ferromagnetic ground state in the quantum spin ice Yb(2)Sn(2)O(7).

From magnetic, specific heat, (170)Yb Mössbauer effect, neutron diffraction, and muon spin relaxation measurements on polycrystalline Yb(2)Sn(2)O(7), we show that below the first order transition at 0.15 K all of the Yb(3+) ions are long-range magnetically ordered and each has a moment of 1.1 µ(B) which lies at ≃ 10° to a common fourfold cubic axis. The four sublattice moments have four different directions away from this axis and are therefore noncoplanar. We term this arrangement splayed ferromagnetism. This ground state has a dynamical component with a fluctuation rate in the megahertz range. The net ferromagnetic exchange interaction has an anisotropy that favors the local threefold axis. We discuss our results in terms of the phase diagram proposed by Savary and Balents [Phys. Rev. Lett. 108, 037202 (2012)] for a pyrochlore lattice of Kramers 1/2 effective spins.

Fungi and mycotoxins in silage: an overview.

The present revision shows the early and current knowledge in the field of silage fungi and mycotoxins explaining the relevance of fungi and mycotoxins in silage. The problem does not end in animal disease or production losses as mycotoxins in feed can lead to the presence of their metabolic products in dairy products, which will be eventually affecting human health, mainly infants. Silage is green forage preserved by lactic fermentation under anaerobic conditions. This ecosystem maintains its quality and nutritional value depending on interactions among physical, chemical and biological agents. Forages used for ensilage are naturally in contact with yeasts and filamentous fungi, and the contamination often occurs in the field and can also occur during harvesting, transport, storage. Moreover, postharvest poor management can lead to a rapid spoilage. Studies on fungal contamination of dairy cattle feed have shown how corn silage influences the contamination degree of feed supplied to livestock. Increasing knowledge in this area will help elucidate the influence that this microbiota exerts on production and/or degradation of mycotoxins present in silage. Some of these fungi, although opportunist pathogens, are relevant epidemiologically and represent a high risk of contamination to farm workers who handle them improperly.

Typing clinical and animal environment Aspergillus fumigatus gliotoxin producer strains isolated from Brazil by PCR-RFLP markers.

UNLABELLED: Aspergillus fumigatus, a well-known human and animal pathogen causing aspergillosis, has been historically identified by morphological and microscopic features. However, recent studies have shown that species identification on the basis of morphology alone is problematic. The aim of this work was to confirm the taxonomic state at specie level of a set of clinical (human and animal) and animal environment A. fumigatus strains identified by morphological criteria applying a PCR-RFLP assay by an in silico and in situ analysis with three restriction enzymes. The A. fumigatus gliotoxin-producing ability was also determined. Previous to the in situ PCR-RFLP analysis, an in silico assay with BccI, MspI and Sau3AI restriction enzymes was carried out. After that, these enzymes were used for in situ assay. All A. fumigatus strains isolated from corn silage, human aspergillosis and bovine mastitis and high per cent of the strains isolated from cereals, animal feedstuff and sorghum silage were able to produce high gliotoxin levels. Also, all these strains identified by morphological criteria as A. fumigatus, regardless of its isolation source, had band patterns according to A. fumigatus sensu stricto by PCR-RFLP markers. SIGNIFICANCE AND IMPACT OF THE STUDY: Aspergillus fumigatus is a well-known human and animal pathogen causing aspergillosis. In this study, clinical (human and animal) and animal environment strains were able to produce high gliotoxin levels and had band profiles according to A. fumigatus sensu stricto by PCR-RFLP markers. The results obtained here suggest that strains involved in human and animal aspergillosis could come from the animal environment in which A. fumigatus is frequently found. Its presence in animal environments could affect animal health and productivity; in addition, there are risks of contamination for rural workers during handling and storage of animal feedstuffs.

One-year clinical and MR imaging outcome after partial meniscal replacement in stabilized knees using a collagen meniscus implant.

PURPOSE: The purpose of the study was to evaluate the clinical and radiological outcomes after medial/lateral collagen meniscus substitution (CMI) at 12 months postoperatively. METHODS: Sixty-seven patients (m:f = 47:20, mean age 36 ± 10 years) underwent arthroscopic CMI after previous subtotal medial (n = 55) or lateral meniscectomy (n = 12) due to persistent joint line pain (n = 25) or to prophylactic reasons (n = 42). Clinical follow-up consisted of IKDC score, Tegner score, Lysholm score, and visual analog scale for pain and satisfaction (preinjury, preoperatively, and 12 months postoperatively; follow-up rate 90 %). MRI scans were analyzed according to the Genovese criteria. RESULTS: Nineteen patients (29 %) showed a normal (A), 35 nearly normal (B), 5 abnormal (C), and 1 patient severely abnormal total IKDC score (D). The median Tegner preinjury score was 7 (range 2-10) and at follow-up 6 (range 2-10). The mean Lysholm score before surgery was 68 ± 20 and 93 ± 9 at follow-up. Preoperatively, the mean VAS pain was 4.4 ± 3.1 and 2.0 ± 1.0 at follow-up. Clinical failure of the CMI occurred in 3 patients (n = 1 infection, n = 1 failure of the implant, n = 1 chronic synovitis). On MRI, the CMI was completely resorbed in 3 patients (5 %), partially resorbed in 55 (92 %), and entirely preserved in 3 (5 %) patients. In 5 patients (8 %) the CMI was isointense, in 54 (90 %) slightly and 1 (2 %) highly hyperintense. 43 (72 %) patients showed an extrusion of the CMI implant of more than 3 mm. CONCLUSIONS: Significant pain relief and functional improvement throughout all scores at 1 year was noted. The CMI undergoes significant remodeling, degradation, resorption, and extrusion in most of the patients. No difference in outcomes between the medial and lateral CMI was observed. LEVEL OF EVIDENCE: Prospective therapeutic study, Level IV.

Obligate chimerism in male yellow crazy ants.

Multicellular organisms typically develop from a single fertilized egg and therefore consist of clonal cells. We report an extraordinary reproductive system in the yellow crazy ant. Males are chimeras of haploid cells from two divergent lineages: R and W. R cells are overrepresented in the males' somatic tissues, whereas W cells are overrepresented in their sperm. Chimerism occurs when parental nuclei bypass syngamy and divide separately within the same egg. When syngamy takes place, the diploid offspring either develops into a queen when the oocyte is fertilized by an R sperm or into a worker when fertilized by a W sperm. This study reveals a mode of reproduction that may be associated with a conflict between lineages to preferentially enter the germ line.

Variation in the level of aggression, chemical and genetic distance among three supercolonies of the Argentine ant in Europe.

In their invasive ranges, Argentine ant populations often form one geographically vast supercolony, genetically and chemically uniform within which there is no intraspecific aggression. Here we present regional patterns of intraspecific aggression, cuticular hydrocarbons (CHCs) and population genetics of 18 nesting sites across Corsica and the French mainland. Aggression tests confirm the presence of a third European supercolony, the Corsican supercolony, which exhibits moderate to high levels of aggression, depending on nesting sites, with the Main supercolony, and invariably high levels of aggression with the Catalonian supercolony. The chemical analyses corroborated the behavioural data, with workers of the Corsican supercolony showing moderate differences in CHCs compared to workers of the European Main supercolony and strong differences compared to workers of the Catalonian supercolony. Interestingly, there were also clear genetic differences between workers of the Catalonian supercolony and the two other supercolonies at both nuclear and mitochondrial markers, but only very weak genetic differentiation between nesting sites of the Corsican and Main supercolonies (F(ST) = 0.06). A detailed comparison of the genetic composition of supercolonies also revealed that, if one of the last two supercolonies derived from the other, it is the Main supercolony that derived from the Corsican supercolony rather than the reverse. Overall, these findings highlight the importance of conducting more qualitative and quantitative analyses of the level of aggression between supercolonies, which has to be correlated with genetic and chemical data.