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Anecdotal data suggest great variation in breadth and depth of skeletal muscle coverage between undergraduate human anatomy (HA) and anatomy and physiology (A&P) courses. This manuscript is the second in a series (Reynolds A, Goodwin M, O'Loughlin V. D. "Adv Physiol Educ" 46: 309-318, 2022. doi:https://doi.org/10.1152/advan.00084.2021) that methodically assesses skeletal muscle content coverage across undergraduate HA and A&P courses. The authors developed an online skeletal muscle coverage survey and collected 342 responses worldwide, 156 from instructors of HA courses and 186 from A&P course instructors. Demographic results showed that HA courses are primarily taught at 4-year baccalaureate institutions, have relatively larger class sizes, and are more likely to use human (vs. animal) prosections or dissections. In contrast, A&P courses are primarily taught at community colleges, have relatively smaller class sizes, and are more likely to use animal (vs. human) dissections. HA courses tend to require their students to learn all skeletal muscle aspects (i.e., identification, action, attachments, innervation), whereas A&P courses tend to focus on muscle identification or action only. The proportions of courses that require identification of large, superficial skeletal muscles are similar between the two course types. However, HA courses are more likely to require their students to identify deeper and smaller muscles, including more distal appendicular muscles and pelvic muscles. These differences likely are due, in part, to the more anatomical focus of HA courses and the slightly different student populations between these courses. These findings provide much-needed information about muscular system coverage between HA and A&P courses and may guide instructor discussions about curricula. [For the first article in the series, "General Trends in Skeletal Muscle Coverage in Undergraduate Human Anatomy and Anatomy and Physiology Courses," see EJ1347509.]

Background: Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder with profound cognitive, behavioral, and psychosocial impairments with persistence across the life cycle. Our initial genome-wide screening approach for copy number variants (CNVs) in ADHD implicated a duplication of "SLC2A3," encoding glucose transporter-3 (GLUT3). GLUT3 plays a critical role in cerebral glucose metabolism, providing energy for the activity of neurons, which, in turn, moderates the excitatory-inhibitory balance impacting both brain development and activity-dependent neural plasticity. We therefore aimed to provide additional genetic and functional evidence for GLUT3 dysfunction in ADHD. Methods: Case-control association analyses of "SLC2A3" single-nucleotide polymorphisms (SNPs) and CNVs were conducted in several European cohorts of patients with childhood and adult ADHD (SNP, n = 1,886 vs. 1,988; CNV, n = 1,692 vs. 1,721). These studies were complemented by "SLC2A3" expression analyses in peripheral cells, functional EEG recordings during neurocognitive tasks, and ratings of food energy content. Results: Meta-analysis of all cohorts detected an association of SNP rs12842 with ADHD. While CNV analysis detected a population-specific enrichment of "SLC2A3" duplications only in German ADHD patients, the CNV + rs12842 haplotype influenced ADHD risk in both the German and Spanish cohorts. Duplication carriers displayed elevated "SLC2A3" mRNA expression in peripheral blood cells and altered event-related potentials reflecting deficits in working memory and cognitive response control, both endophenotypic traits of ADHD, and an underestimation of energy units of high-caloric food. Conclusions: Taken together, our results indicate that both common and rare "SLC2A3" variation impacting regulation of neuronal glucose utilization and energy homeostasis may result in neurocognitive deficits known to contribute to ADHD risk.

Open educational resources (OERs) are becoming increasingly common as a tool in education, particularly in medical and biomedical education. However, three key barriers have been identified to their use: 1) lack of awareness of OERs, 2) lack of motivation to use OERs, and 3) lack of training in the use of OERs. Here, we explore these three barriers with teachers of medical and biomedical science to establish how best to enhance the use of OERs to improve pedagogical outcomes. An online survey was completed by 209 educators, many of whom (68.4%) reported using OERs in their teaching and almost all (99.5%) showing awareness of at least one OER. The results suggest that key problems that prevent educators from adopting OERs in their teaching include suitability for particular classes, time, and copyright. Most (81.8%) educators were somewhat, very, or extremely comfortable with OERs so there is no innate motivational barrier to adoption. A lack of training was reported by 13.9% of respondents, and 40% of respondents stated that there was little or no support from their institutions. OER users were no more comfortable with technology or better supported by departments but tended to be aware of a greater number of sources of OERs. Our study illustrates key opportunities for the expansion of OER use in physiology and medical teaching: increased breadth of awareness, increased institutional support (including time, training, and copyright support), and greater sharing of diverse OERs to suit the range of teaching challenges faced by staff in different subdisciplines.

Floral nectar sugar composition is assumed to reflect the nutritional demands and foraging behaviour of pollinators, but the relative contributions of evolutionary and abiotic factors to nectar sugar composition remain largely unknown across the angiosperms. We compiled a comprehensive dataset on nectar sugar composition for 414 insect-pollinated plant species across central Europe, along with phylogeny, paleoclimate, flower morphology, and pollinator dietary demands, to disentangle their relative effects. We found that phylogeny was strongly related with nectar sucrose content, which increased with the phylogenetic age of plant families, but even more strongly with historic global surface temperature. Nectar sugar composition was also defined by floral morphology, though it was not related to our functional measure of pollinator dietary demands. However, specialist pollinators of current plant-pollinator networks predominantly visited plant species with sucrose-rich nectar. Our results suggest that both physiological mechanisms related to plant water balance and evolutionary effects related to paleoclimatic changes have shaped floral nectar sugar composition during the radiation and specialisation of plants and pollinators. As a consequence, the high velocity of current climate change may affect plant-pollinator interaction networks due to a conflicting combination of immediate physiological responses and phylogenetic conservatism. [ABSTRACT FROM AUTHOR]

The coexistence of sexual and asexual lineages is rarely documented in vertebrates. Various ecological and evolutionary mechanisms have been proposed to explain their stable coexistence. Gibel carp (Carassius gibelio), a highly invasive freshwater fish in Europe, is one such example of a sexual and asexual vertebrate, combining gynogenesis (sperm-dependent parthenogenesis) and sexual reproduction. In this study, we focused on vigour-related traits in gynogenetic and sexual forms of gibel carp coexisting in the same habitat, to reveal whether there is a link between parasite load and vigour-related traits reflecting the potential advantage of one reproductive form over another, which may eventually facilitate the obligatory coexistence of sperm-dependent gynogenetic females with sexual males. Using physiological parameters (indexes of somatic condition, energetic condition, and reproductive performance; glucose levels; and erythrocytes-related variables), diploid sexual males, diploid sexual females, and triploid gynogenetic females were found to be differentiated from one another. However, based on immune variables representing innate immunity, specific immunity, and index of immunocompetence, mostly sexual males were found to be weakly differentiated from both groups of females. We revealed different patterns of interactions between parasite abundance and immune variables between sexual and gynogenetic forms. Using parasite assemblage composition, different relationships between parasite assemblage and immunity or physiology in sexual males and sexual females were evidenced, potentially related to male reproduction biology. In contrast, gynogenetic females exhibited the advantage that parasite assemblage composition did not affect their immunity or physiology. Our study suggests that reproduction mode-associated costs of physiology and immunity may facilitate the coexistence of the asexual-sexual complex. We highlight that multiple ecological processes and evolutionary mechanisms contribute to the coexistence of asexual and sexual gibel carp. [ABSTRACT FROM AUTHOR]

The neritid snail Theodoxus fluviatilis is found across habitats differing in salinity, from shallow waters along the coast of the Baltic Sea to lakes throughout Europe. Living close to the water surface makes this species vulnerable to changes in salinity in their natural habitat, and the lack of a free-swimming larval stage limits this species' dispersal. Together, these factors have resulted in a patchy distribution of quite isolated populations differing in their salinity tolerances. In preparation for investigating the mechanisms underlying the physiological differences in osmoregulation between populations that cannot be explained solely by phenotypic plasticity, we present here an annotated draft genome assembly for T. fluviatilis , generated using PacBio long reads, Illumina short reads, and transcriptomic data. While the total assembly size (1045 kb) is similar to those of related species, it remains highly fragmented (N scaffolds = 35,695; N50 = 74 kb) though moderately high in complete gene content (BUSCO single copy complete: 74.3%, duplicate: 2.6%, fragmented: 10.6%, missing: 12.5% using metazoa n = 954). Nevertheless, we were able to generate gene annotations of 21,220 protein-coding genes (BUSCO single copy complete: 65.1%, duplicate: 16.7%, fragmented: 9.1%, missing: 9.1% using metazoa n = 954). Not only will this genome facilitate comparative evolutionary studies across Gastropoda, as this is the first genome assembly for the basal snail family Neritidae, it will also greatly facilitate the study of salinity tolerance in this species. Additionally, we discuss the challenges of working with a species where high molecular weight DNA isolation is very difficult. [ABSTRACT FROM AUTHOR]

The European chestnut (Castanea sativa Mill.), is an environmentally and economically important species in Europe, mainly for fruit production. The chestnut fruit is well-known for its nutritional properties, namely its high concentration of carbohydrates (starch) and its low-fat content, as well as being one of the few fruits that do not contain gluten. Due to its chemical and nutritional characteristics beneficial to health, the sweet chestnut is a food recommended at different levels. The biochemistry of the mouth and nose of a human being is very complex. However, understanding the different interactions between the biochemistry of our sensory organs and food helps us to comprehend certain concepts, such as flavor and how it is involved in the sensory evaluation of the chestnuts. For the selection of high-quality products, it is necessary to develop reliable methods both from a qualitative and sensory point of view, and chestnut is a fruit with unique sensory characteristics that can be used in various gastronomic dishes, from main courses to desserts. [ABSTRACT FROM AUTHOR]

Simple Summary: Artisanal fishing constitutes a subsistence activity in much of the world. Changes in fishing legislation can damage the sector if rapid adaptations are not achieved. As Europe demands landing of all catches, except those whose survival is scientifically proven, this study proposes possible improvements for the sector through a pilot study. We evaluated the survival of discarded fish and the possible recapture once they have reached a commercially profitable size. Europe calls for the end to fisheries discards, which means bringing all caught fish (subject to minimum sizes or quotas) to land. This decision is beneficial to the ecosystem, since it forces the selectivity of the fishing gears to improve. However, artisanal fishermen find themselves in a vulnerable situation where their subsistence depends on catches with small profit margins. An exemption to this landing obligation exists, as it is also ruled that those animals whose survival is scientifically guaranteed may be returned to the sea. Here we study the survival of Plectorhinchus mediterraneus captured by hookline and gillnet, as well as their physiological recovery. Survival exceeds 93% in both cases. The physiological assessment of primary (cortisol) and secondary (energy mobilization, acid-base and hydromineral balance, and immune system) stress responses indicates that surviving animals are able to recover after fishing. Thus, we propose the optimal size of capture of this species to achieve greater economic benefit. For this, we rely on the prices according to size in recent years, as well as on the growth curves of the species. In this way, by releasing fish of less than 1 kg, the current benefits could be multiplied between 2.3 and 9.6 times. This pilot study lays the groundwork for regulating artisanal fisheries through scientific data related to survival of discards along with information on the sale prices. [ABSTRACT FROM AUTHOR]

There are now 108.4 million forcibly displaced people worldwide, many of whom endure adversities that result in trauma, toxic stress, and potentially, altered epigenetic development. This paper provides a comprehensive review of current literature on the biological signatures of war and forced migration among refugee populations. To consolidate evidence and identify key concerns and avenues for future research, we reviewed 36 publications and one article under review, published since 2000, most of which focused on refugees relocated in Europe and the Middle East. This body of work - including cross-sectional, observational, and experimental studies - reveals heterogenous findings regarding human biological responses to war-related adversities and their associations with health outcomes. We conclude with four main observations, regarding why genomic and physiological biomarkers are valuable, what study designs advance understanding of causality and health-promoting interventions, how to prepare for ethical challenges, and why theoretical frameworks and research procedures need more detailed consideration in scientific publications., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Septoria tritici blotch (STB), caused by the fungus Zymoseptoria tritici , is among the most threatening wheat diseases in Europe. Genetic resistance remains one of the main environmentally sustainable strategies to efficiently control STB. However, the molecular and physiological mechanisms underlying resistance are still unknown, limiting the implementation of knowledge-driven management strategies. Among the 22 known major resistance genes (Stb), the recently cloned Stb16q gene encodes a cysteine-rich receptor-like kinase conferring a full broad-spectrum resistance against Z. tritici. Here, we showed that an avirulent Z. tritici inoculated on Stb16q quasi near isogenic lines (NILs) either by infiltration into leaf tissues or by brush inoculation of wounded tissues partially bypasses Stb16q -mediated resistance. To understand this bypass, we monitored the infection of GFP-labeled avirulent and virulent isolates on Stb16q NILs, from germination to pycnidia formation. This quantitative cytological analysis revealed that 95% of the penetration attempts were unsuccessful in the Stb16q incompatible interaction, while almost all succeeded in compatible interactions. Infectious hyphae resulting from the few successful penetration events in the Stb16q incompatible interaction were arrested in the sub-stomatal cavity of the primary-infected stomata. These results indicate that Stb16q -mediated resistance mainly blocks the avirulent isolate during its stomatal penetration into wheat tissue. Analyses of stomatal aperture of the Stb16q NILs during infection revealed that Stb16q triggers a temporary stomatal closure in response to an avirulent isolate. Finally, we showed that infiltrating avirulent isolates into leaves of the Stb6 and Stb9 NILs also partially bypasses resistances, suggesting that arrest during stomatal penetration might be a common major mechanism for Stb -mediated resistances. [ABSTRACT FROM AUTHOR]

Aquaponics, a circular agri-aquaculture system, offers the potential to enhance food production resilience across diverse environmental contexts. Plant physiological processes that regulate water and nutrient fluxes in decoupled aquaponics are responsive to environmental dynamics such as stomatal behaviour. In greenhouses, these dynamics are largely driven by changes in natural solar radiation. This research investigates plant physiological dynamics of lettuce traits to various natural light conditions in a fully climate-controlled environment mimicking geographic latitude-based light variations and lighting application modes. We explored the physiological and resource utilisation effects of these regimes as basis for a geographic-adjusted planning of climate-resilient aquaponic systems. For that, four lighting scenarios were applied in a climate chamber over a period of 21 days in decoupled aquaponic setups, involving two daily light integrals (DLIs) and two daily light dynamics (DLDs) for lighting application modes: North (LAT 59° 54' 41.37'' N) natural sunlight dynamics, North static, South (LAT 40° 25' 0.39'' N) natural sunlight dynamics (Sn), and South static (Ss). DLIs and natural sunlight dynamics were derived from Northern (Oslo, Norway) and Southern (Madrid, Spain) Europe in March 2022. Observed plant physiological variables were plant growth, chlorophyll and carotenoid contents, stomatal conductance and morphology, and net photosynthesis (P n). Resource-use variables at leaf level, including CO 2 , light, water, and nutrient utilisation, were also estimated. Latitude-dependent DLIs, in general, significantly affected lettuce growth, quality, and physiological responses; with lower latitudes (Sn, Ss) improving P n by 68% compared to North-DLI treatments. Resource utilisation was also positively impacted in South-DLI treatments, e.g., light use efficiency was in average 2.2 times higher in South-DLI (0.75 g [CO 2 ] mol−1 [PPFD]) than in North-DLI (1.62 g [CO 2 ] mol−1 [PPFD]) treatments. Lighting modes had limited effects, and interactions between DLIs and DLDs were largely absent. These findings indicate the significance of geographic differences in natural solar radiation dynamics on designing climate-resilient aquaponics facilities, and highlight the influence of geography on crop productivity and resource efficiency. • Latitude-based lighting impacts aquaponic lettuce physiology and resource use. • South-DLI treatments improved photosynthesis by 68% compared to North-DLI treatments. • Lighting application modes had limited influence on aquaponics lettuce responses. • Geographic light variation is key for planning climate-resilient aquaponic facility. [ABSTRACT FROM AUTHOR]

Picea abies (L.) Karst. and Fagus sylvatica (L.) are important tree species in Europe, and the foreseen increase in temperature and vapour pressure deficit (VPD) could increase the vulnerability of these species. However, their physiological performance under climate change at temperate and productive sites is not yet fully understood, especially in uneven-aged stands. Therefore, we investigated tree-ring width and stable isotope chronologies (δ13C/δ18O) of these two species at 10 sites along a climate gradient in Central Europe. In these uneven-aged stands, we compared the year-to-year variability of dominant and suppressed trees for the last 80 years in relation to the sites' spatial distribution and climate. δ18O and δ13C were generally consistent across sites and species, showing high sensitivity to summer VPD, whereas climate correlations with radial growth varied much more and depended on mean local climate. We found no significant differences between dominant and suppressed trees in the response of stable isotope ratios to climate variability, especially within the annual high-frequency signals. In addition, we observed a strikingly high coherence of the high-frequency δ18O variations across long distances with significant correlations above 1500 km, whereas the spatial agreement of δ13C variations was weaker (~700 km). We applied a dual-isotope approach that is based on known theoretical understanding of isotope fractionations to translate the observed changes into physiological components, mainly photosynthetic assimilation rate and stomatal conductance. When separating the chronologies in two time windows and investigating the shifts in isotopes ratios, a significant enrichment of either or both isotope ratios over the last decades can be observed. These results, translated by the dual-isotope approach, indicate a general climate-driven decrease in stomatal conductance. This improved understanding of the physiological mechanisms controlling the short-term variation of the isotopic signature will help to define the performance of these tree species under future climate. [ABSTRACT FROM AUTHOR]

Annually resolved tree-ring records extending back to pre-industrial conditions have the potential to constrain the responses of global land surface models at interannual to centennial timescales. Here, we demonstrate a framework to simultaneously constrain the representation of tree growth and physiology in the ORCHIDEE global land surface model using the simulated variability of tree-ring width and carbon (Δ13 C) and oxygen (δ18 O) stable isotopes in six sites in boreal and temperate Europe. We exploit the resulting tree-ring triplet to derive integrative constraints for leaf physiology and growth from well-known mechanistic relationships among the variables. ORCHIDEE simulates Δ13 C (r=0.31 –0.80) and δ18 O (r=0.36 –0.74) better than tree-ring width (r<0.55), with an overall skill similar to that of a tree-ring model (MAIDENiso) and another isotope-enabled global vegetation model (LPX-Bern). The comparison with tree-ring data showed that growth variability is not well represented in ORCHIDEE and that the parameterization of leaf-level physiological responses (stomatal control) to drought stress in the temperate region can be constrained using the interannual variability of tree-ring stable isotopes. The representation of carbon storage and remobilization dynamics emerged as a critical process to improve the realism of simulated growth variability, temporal carryover, and recovery of forest ecosystems after climate extremes. Simulated forest gross primary productivity (GPP) correlates with simulated tree-ring Δ13 C and δ18 O variability, but the origin of the correlations with tree-ring δ18 O is not entirely physiological. The integration of tree-ring data and land surface models as demonstrated here should guide model improvements and contribute towards reducing current uncertainties in forest carbon and water cycling. [ABSTRACT FROM AUTHOR]

Background: Current techniques for measuring absolute lung volumes rely on bulky and expensive equipment and are complicated to use for the operator and the patient. A novel method for measurement of absolute lung volumes, the MiniBox method, is presented.Research Question: Across a population of patients and healthy participants, do values for total lung capacity (TLC) determined by the novel compact device (MiniBox, PulmOne Advanced Medical Devices, Ltd.) compare favorably with measurements determined by traditional whole body plethysmography?Study Design and Methods: A total of 266 participants (130 men) and respiratory patients were recruited from five global centers (three in Europe and two in the United States). The study population comprised individuals with obstructive (n = 197) and restrictive (n = 33) disorders as well as healthy participants (n = 36). TLC measured by conventional plethysmography (TLCPleth) was compared with TLC measured by the MiniBox (TLCMB).Results: TLC values ranged between 2.7 and 10.9 L. The normalized root mean square difference (NSD) between TLCPleth and TLCMB was 7.0% in healthy participants. In obstructed patients, the NSD was 7.9% in mild obstruction and 9.1% in severe obstruction. In restricted patients, the NSD was 7.8% in mild restriction and 13.9% in moderate and severe restriction. No significant differences were found between TLC values obtained by the two measurement techniques. Also no significant differences were found in results obtained among the five centers.Interpretation: TLC as measured by the novel MiniBox system is not significantly different from TLC measured by conventional whole body plethysmography, thus validating the MiniBox method as a reliable method to measure absolute lung volumes. [ABSTRACT FROM AUTHOR]

Annually-resolved tree-ring records extending back to pre-industrial conditions have the potential to constrain the responses of global land surface models at interannual to centennial time scales. Here, we demonstrate a framework to constrain the representation of tree growth and physiology in the ORCHIDEE global land surface model using the simulated variability of tree-ring width and carbon (Δ13C) and oxygen (δ18O) stable isotopes in six sites in boreal and temperate Europe. We exploit the tree-ring triplet to derive integrative constraints for leaf physiology and growth from well-known mechanistic relationships among the variables. The model simulates Δ13C (r = 0.31-0.80) and δ18O (r = 0.36-0.74) better than tree-ring width (r < 0.55), with an overall skill similar to that of other models. The results show that growth variability is not well represented, and that the parameterization of leaf-level physiological responses to drought stress in the temperate region can be improved with tree-ring data. The representation of carbon storage and remobilization dynamics is critical to improve the realism of simulated growth variability, temporal carrying over and recovery of forest ecosystems after climate extremes. The simulated physiological response to rising CO2 over the 20th century is consistent with tree-ring data in the temperate region, despite an overestimation of seasonal drought stress and stomatal control on photosynthesis. Photosynthesis correlates directly with isotopic variability, but the origin of correlations with δ18O is not entirely physiological. The integration of tree-ring data and land surface models as demonstrated here should contribute towards reducing current uncertainties in forest carbon and water cycling. [ABSTRACT FROM AUTHOR]

About 1-2% of European population are redheaded, meaning they synthesize more pheomelanin than eumelanin, the main melanin pigment in humans. Several mutations could be responsible for this phenotype. It has been suggested that corresponding mutations spread in Europe due to a founder effect shaped either by a relaxation of selection for dark, UV-protective phenotypes or by sexual selection in favour of rare phenotypes. In our study, we investigated the levels of vitamin D precursor 25(OH)D3 (calcidiol) and folic acid in the blood serum of 73 redheaded and 130 non-redheaded individuals. In redheaded individuals, we found higher 25(OH)D3 concentrations and approximately the same folic acid concentrations as in non-redheaded subjects. 25(OH)D3 concentrations correlated with the intensity of hair redness measured by two spectrophotometric methods and estimated by participants themselves and by independent observers. In non-redheaded individuals, 25(OH)D3 levels covaried with the amount of sun exposure and intensity of suntan while in redheaded individuals, this was not the case. It suggests that increased 25(OH)D3 levels in redheaded individuals are due to differences in physiology rather than in behaviour. We also found that folic acid levels increased with age and the intensity of baldness and decreased with the frequency of visiting tanning salons. Our results suggest that the redheaded phenotype could be an evolutionary adaptation for sufficient photosynthesis of provitamin D in conditions of low intensity of UVB radiation in central and northern parts of Europe. [ABSTRACT FROM AUTHOR]

Roe deer (Capreolus capreolus) is the most abundant cervid in Europe and, as such, has a considerable impact over several human activities. Accurate roe deer population size estimates are useful to ensure their proper management. We tested 3 methods for estimating roe deer abundance (drive counts, pellet-group counts, and camera trapping) during two consecutive years (2012 and 2013) in the Apennines (Italy) in order to assess their precision and applicability. During the study period, population density estimates were: drive counts 21.89±12.74 roe deer/km2 and pellet-group counts 18.74±2.31 roe deer/km2 in 2012; drive counts 19.32±11.12 roe deer/km2 and camera trapping 29.05±7.48 roe deer/km2 in 2013. Precision of the density estimates differed widely among the 3 methods, with coefficients of variation ranging from 12% (pellet-group counts) to 58% (drive counts). Drive counts represented the most demanding method on account of the higher number of operators involved. Pellet-group counts yielded the most precise results and required a smaller number of operators, though the sampling effort was considerable. When compared to the other two methods, camera trapping resulted in an intermediate level of precision and required the lowest sampling effort. We also discussed field protocols of each method, considering that volunteers, rather than technicians, will more likely be appointed for these tasks in the near future. For this reason, we strongly suggest that for each method managers of population density monitoring projects take into account ease of use as well as the quality of the results obtained and the resources required. [ABSTRACT FROM AUTHOR]

European sea bass were fed four low FM/FO (10%/6%) diets containing galactomannan oligosaccharides (GMOS), a mixture of garlic oil and labiatae plants oils (PHYTO), or a combination of both functional products (GMOSPHYTO) for 63 days before exposing the fish to an intestinal Vibrio anguillarum infection combined with crowding stress. In order to evaluate functional diets efficacy in terms of gut health maintenance, structural, cellular, and immune intestinal status were evaluated by optical and electron microscopy and gene expression analyses. A semi-automated software was adapted to determine variations in goblet cell area and mucosal mucus coverage during the challenge test. Feeding with functional diets did not affect growth performance; however, PHYTO and GMOS dietary inclusion reduced European sea bass susceptibility to V. anguillarum after 7 days of challenge testing. Rectum (post-ileorectal valve) showed longer (p = 0.001) folds than posterior gut (pre-ileorectal valve), whereas posterior gut had thicker submucosa (p = 0.001) and higher mucus coverage as a result of an increased cell density than rectum. Functional diets did not affect mucosal fold length or the grade of granulocytes and lymphocytes infiltration in either intestinal segment. However, the posterior gut fold area covered by goblet cells was smaller in fish fed GMOS (F = 14.53; p = 0.001) and PHYTO (F = 5.52; p = 0.019) than for the other diets. PHYTO (F = 3.95; p = 0.049) reduced posterior gut goblet cell size and increased rodlet cell density (F = 3.604; p = 0.068). Dietary GMOS reduced submucosal thickness (F = 51.31; p = 0.001) and increased rodlet cell density (F = 3.604; p = 0.068) in rectum. Structural TEM analyses revealed a normal intestinal morphological pattern, but the use of GMOS increased rectum microvilli length, whereas the use of PHYTO increased (p≤0.10) Ocln, N-Cad and Cad-17 posterior gut gene expression. After bacterial intestinal inoculation, posterior gut of fish fed PHYTO responded in a more controlled and belated way in terms of goblet cell size and mucus coverage in comparison to other treatments. For rectum, the pattern of response was similar for all dietary treatments, however fish fed GMOS maintained goblet cell size along the challenge test. [ABSTRACT FROM AUTHOR]

Over the last decades, the European hare (Lepus europaeus) has become the subject of many interdisciplinary studies due to the sharp Europe-wide population decline. In European hares, the first stage of life until weaning and the subsequent dispersal have been sparsely studied, in particular, habitat selection, movements and survival rate, as juveniles´ precocial lifestyle is dominated by concealment, motionlessness and inconspicuousness. In this study, free-living juvenile European hares (leverets) were detected systematically by thermography (n = 394), radio-tagged or marked (n = 122) from birth until the fifth week of life to research their habitat usage and pre-dispersal movements. The day-resting places and night locations, as well as the distance moved by leverets with aging, were evaluated by generalized linear mixed effect models. In addition, the habitat preference was assessed by a conservative use-availability analysis. Up to the fifth week of life, 30.5% of all leverets used cultivated areas in the daytime. In contrast, the remaining 69.4% animals inhabitated linear or small planar structures in the daytime, with the edges of field tracks, hedges and some ruderal structures clearly being preferred. At nighttime, 93% of all juveniles, which occupied linear structures in the daytime, used the adjoining fields up to 20 m away from the next linear structure. Nocturnal distances of more than 60 m to the next edge rarely occurred before the end of the pre-weaning phase. The time of day and age have a significant influence on the distance moved by juvenile hares. With increasing age, leverets moved less during the day and roamed further at night. The results are largely consistent with the behavioral patterns found in the few previous studies on pre-weaning European hares and show the importance of hiding places for leverets in early life stages. This study should contribute to a better understanding of behavior in juvenile life-history stages of European hares that may help to identify vulnerable phases in their lifecycle. In addition, the findings can refine existing population models and improve conservation efforts. [ABSTRACT FROM AUTHOR]

We here describe the first fossil remains of a green lizard of the Lacerta group from the late Miocene (MN 13) of the Solnechnodolsk locality in southern European Russia. This region of Europe is crucial for our understanding of the paleobiogeography and evolution of these middle-sized lizards. Although this clade has a broad geographical distribution across the continent today, its presence in the fossil record has only rarely been reported. In contrast to that, the material described here is abundant, consists of a premaxilla, maxillae, frontals, parietals, jugals, quadrate, pterygoids, dentaries and vertebrae. The comparison of these elements to all extant green lizard species shows that these fossils are indistinguishable from Lacerta trilineata. Thus, they form the first potential evidence of the occurrence of this species in the Miocene. This may be also used as a potential calibration point for further studies. Together with other lizard fossils, Solnechnodolsk shows an interesting combination of survivors and the dawn of modern species. This locality provides important evidence for the transition of an archaic Miocene world to the modern diversity of lizards in Europe. In addition, this article represents a contribution to the knowledge of the comparative osteological anatomy of the selected cranial elements in lacertids. This study gives special emphasis to the green lizards, but new data are also presented for related taxa, e.g., Timon lepidus, Podarcis muralis or Zootoca vivipara. Although the green lizards include several cryptic species for which determination based on isolated osteological material would be expected to be difficult, our comparisons show several important morphological differences, although a high degree of variability is present. [ABSTRACT FROM AUTHOR]

Background: Maternal iodine deficiency is related to high neonatal thyroid-stimulating hormone (TSH) values, with the threshold of 5 mIU/L recommended as an indicator of iodine nutrition status. The objective of this study was to analyse possible risk factors for increased TSH that could distort its validity as a marker of iodine status. The clinical relevance of this research question is that if the factors associated with iodine deficiency are known, iodine supplementation can be introduced in risk groups, both during pregnancy and in newborns. Methods: A case-control study was carried out in a sample of 46,622 newborns in 2002–2015 in Spain. Of these, 45,326 had a neonatal TSH value ≥5 mIU/L. The main variable was having TSH ≥5 mIU/L and the secondary variables were: sex, gestational age, day of sample extraction and maternal origin. Associated factors were analysed through a logistic regression model, calculating the odds ratio (OR). Results: The factors associated with this outcome were: male sex (OR = 1.34, 95% CI: 1.20–1.50, p<0.001), originating from an Asian/Oceanic country (OR = 0.80, 95% CI: 0.54–1.20, p = 0.536) or Europe (OR = 0.80, 95% CI: 0.66–0.96, p = 0.285) (including Spain, OR = 1) [p<0.001 for America (OR = 0.54, 95% CI: 0.44–0.68) and p = 0.025 for Africa (OR = 0.78, 95% CI: 0.62–0.97)] and fewer days from birth to sampling (OR = 0.80, 95% CI: 0.77–0.82, p<0.001). Conclusions: The risk of high neonatal TSH without congenital hypothyroidism is higher in males, decreases with a greater number of days from birth to extraction, and is dependent on maternal ethnicity but not on gestational age. [ABSTRACT FROM AUTHOR]

Introduction: The study presents the results of the genomic surveillance of invasive meningococcal disease (IMD) in the Czech Republic for the period of 2015–2017. Material and methods: The study set includes all available IMD isolates recovered in the Czech Republic and referred to the National Reference Laboratory for Meningococcal Infections in 2015–2017, a total of 89 Neissseria meningitidis isolates—from 2015 (n = 20), 2016 (n = 27), and from 2017 (n = 42). All isolates were studied by whole genome sequencing (WGS). Results: Serogroup B (MenB) was the most common, followed by serogroups C, W, and Y. Altogether 17 clonal complexes were identified, the most common of which was hypervirulent complex cc11, followed by complexes cc32, cc41/44, cc269, and cc865. Over the three study years, hypervirulent cc11 (MenC) showed an upward trend. The WGS method showed two clearly differentiated clusters of N. meningitidis C: P1.5,2:F3-3:ST-11 (cc11). The first cluster is represented by nine isolates, all of which are from 2017. The second cluster consisted of five isolates from 2016 and eight isolates from 2017. Their genetic discordance is illustrated by the changing nadA allele and subsequently by the variance in BAST type. Clonal complex cc269 (MenB) also increased over the time frame. WGS identified the presence of MenB vaccine antigen genes in all B and non-B isolates of N. meningitidis. Altogether 49 different Bexsero antigen sequence types (BAST) were identified and 10 combinations of these have not been previously described in the PubMLST database. Conclusions: The genomic surveillance of IMD in the Czech Republic provides data needed to update immunisation guidelines for this disease. WGS showed a higher discrimination power and provided more accurate data on molecular characteristics and genetic relationships among invasive N. meningitidis isolates. [ABSTRACT FROM AUTHOR]

Linden (Tilia spp.), a profusely flowering temperate tree that provides bees with vital pollen and nectar, has been associated with bumble bee (Bombus spp.) mortality in Europe and North America. Bee deaths have been attributed, with inadequate evidence, to toxicity from mannose in nectar or starvation due to low nectar in late blooming linden. Here, we investigated both factors via untargeted metabolomic analyses of nectar from five T. cordata trees beneath which crawling/dead bumble bees (B. vosnesenskii) were observed, and of thoracic muscle of 28 healthy foraging and 29 crawling bees collected from linden trees on cool mornings (< 30°C). Nectar contained the pyridine alkaloid trigonelline, a weak acetylcholinesterase inhibitor, but no mannose. Principal component analysis of muscle metabolites produced distinct clustering of healthy and crawling bees, with significant differences (P<0.05) in 34 of 123 identified metabolites. Of these, TCA (Krebs) cycle intermediates were strongly represented (pathway analysis; P<0.01), suggesting that the central metabolism is affected in crawling bees. Hence, we propose the following explanation: when ambient temperature is low, bees with energy deficit are unable to maintain the thoracic temperature required for flight, and consequently fall, crawl, and ultimately, die. Energy deficit could occur when bees continue to forage on linden despite limited nectar availability either due to loyalty to a previously energy-rich source or trigonelline-triggered memory/learning impairment, documented earlier with other alkaloids. Thus, the combination of low temperature and nectar volume, resource fidelity, and alkaloids in nectar could explain the unique phenomenon of bumble bee mortality associated with linden. [ABSTRACT FROM AUTHOR]

Legionella spp. are considered an important cause of potentially preventable morbidity and mortality, making environmental surveillance a crucial component of risk assessment plans. In this work, 20,319 water samples were collected in 3,983 environmental surveys during a 16-year period by ARPA, the Regional Agency for Environmental Protection, Friuli Venezia Giulia, and the results were studied to better understand the diffusion mechanisms of Legionella. The data showed a strong seasonal signal, a prevalence of L. pneumophila serogroup 2–15 in most environments (63% of positive samples), a prevalence of L. pneumophila serogroup 1 in swimming pool-associated environments (82% of positive samples), a persistent presence of Legionella in hospitals and a recurrent presence of Legionella in other facilities such as hotels, possibly years after interventions, highlighting the difficulty of eradicating the bacteria. Retrospective spatio-temporal analyses on geocoded historical data were carried out with SaTScan using an ordinal model with risk as a covariate to identify potential clusters with an excess of cases in the higher-risk categories. Although no outbreaks occurred during the period of study, such analyses identified spatially restricted zones with unusual contamination, which sometimes were also areas in which several surveys triggered by notifications of clinical cases were performed. Simulations of periodic prospective analyses permitted the assessment of the efficacy of the method in early detection of such clusters. The proposed method may be a useful tool in environmental surveillance, prevention and control of Legionella. [ABSTRACT FROM AUTHOR]

In fish, the circadian clock represents a key regulator of many aspects of biology and is controlled by combinations of abiotic and biotic factors. These environmental factors are frequently manipulated in fish farms as part of strategies designed to maximize productivity. The flatfish turbot, Scophthalmus maximus, represents one of the most important species within the aquaculture sector in Asia and Europe. Despite the strategic importance of this species, the function and regulation of the turbot circadian system remains poorly understood. Here, we have characterized the core circadian clock genes, clock1, per1, per2 and cry1 in turbot and have studied their daily expression in various tissues under a range of lighting conditions and feeding regimes. We have also explored the influence of light and feeding time on locomotor activity. Rhythmic expression of the four core clock genes was observed in all tissues studied under light dark (LD) cycle conditions. Rhythmicity of clock gene expression persisted upon transfer to artificial free running, constant conditions confirming their endogenous circadian clock control. Furthermore, turbot showed daily cycles of locomotor activity and food anticipatory activity (FAA) under LD and scheduled-feeding, with the activity phase as well as FAA coinciding with and being dependent upon exposure to light. Thus, while FAA was absent under constant dark (DD) conditions, it was still detected in constant light (LL). In contrast, general locomotor activity was arrhythmic in both constant darkness and constant light, pointing to a major contribution of light, in concert with the circadian clock, in timing locomotor activity in this species. Our data represents an important contribution to our understanding of the circadian timing system in the turbot and thereby the optimization of rearing protocols and the improvement of the well-being of turbot within fish farming environments. [ABSTRACT FROM AUTHOR]

Background: From 2014 to 2017, the number of migrants who came to Italy via the Mediterranean route has reached an unprecedented level. The majority of refugees and migrants were rescued in the Central Mediterranean and disembarked at ports in the Sicily region. Rapid on-spot active TB screening intervention at the point of arrival will cover most migrants arriving in EU and by detecting TB prevalent cases will limit further transmission of the disease. Material and methods: Between November 2016 and December 2017 newly arrived migrants at point of arrivals in Sicily, were screened for active Tuberculosis using a smartphone application, followed in symptomatic individuals by fast molecular test, Xpert MTB/RIF Ultra, on collected sputum samples. Results: In the study period 3787 migrants received a medical evaluation. Eight hundred and ninety-one (23.5%) reported at least one protocol-defined Tuberculosis symptom. Fifteen (2.7%) were positive to at least one microbiological test revealing a post-entry screening prevalence rate of 396 per 100.000 individuals screened (95% CI: 2.22–6.53). In logistic regression analysis, those with cough and at least one other symptom had an increased probability of testing positive compared to persons with symptoms other than cough. Whole-genome-sequencing demonstrate two separate cases of transmission. Discussion: To our knowledge this study reports first-time results of an active TB case finding strategy based on on-spot symptom screening using a smartphone application, followed by fast molecular test on collected sputum samples. Our preliminary findings reveal a post-entry screening prevalence rate of 396 per 100.000 individuals screened (95% CI: 2.22–6.53). [ABSTRACT FROM AUTHOR]

Schmallenberg virus (SBV), an orthobunyavirus infecting ruminants, emerged in 2011 in Central Europe, spread very rapidly throughout the continent and established an endemic status, thereby representing a constant threat not only to the European livestock population, but also to neighboring countries. Hence, in endemically infected regions, the maintenance and regular verification of diagnostics is needed and in not yet affected regions, suitable diagnostic systems should be established to be prepared for a potential introduction of the disease. In addition, also for the trade of animals into free regions, highly reliable and sensitive diagnostics are of utmost importance. Therefore, a laboratory proficiency trial was initiated to allow for performance evaluations of test systems available for SBV-diagnostics, but also for evaluation of veterinary diagnostic laboratories performing those tests. Ten serum samples (six seropositive, four seronegative) were provided for serological analysis, four of the seropositive samples were provided undiluted, while the remaining samples represented 1/2 and 1/4 dilutions of one of the aforementioned samples in negative serum. Ten further sera (five virus-positive, five negative) were sent to the participants to be analyzed by SBV genome detection methods. A total of 48 diagnostic laboratories from 15 countries of three continents (Europe, Asia, North America) and three kit manufacturers participated in the SBV proficiency test, thereby generating 131 result sets, corresponding to 1310 individual results. The sample panel aimed for serological analysis was tested 72 times; the applied diagnostic methods comprised different commercial ELISAs and standard micro-neutralization tests. The sample set aimed for genome detection was analyzed in 59 approaches by various commercial or in-house (real-time) RT-PCR protocols. Antibody or genome positive samples were correctly identified in every case, independent of the applied diagnostic test system. For seronegative samples, three incorrect, false-positive test results were produced. Virus-negative samples tested false-positive in two cases. Thus, a very high diagnostic accuracy of 99.58% and 99.66% was achieved by the serological and virological methods, respectively. Hence, this ring trial demonstrated that reliable and robust SBV-diagnostics has been established in veterinary diagnostic laboratories in affected and non-affected countries. [ABSTRACT FROM AUTHOR]

Background: In Kazakhstan, a live plague vaccine EV 76 NIIEG has been used for plague prophylaxis since the mid-1930s. Vaccination is administered yearly among people living in plague-enzootic areas. Similar practices are used in other former Soviet Union countries. Yet, to this day, the effectiveness period of the vaccine is unknown. It is also not clear how different factors can affect the effectiveness of the vaccine over time. Methods: We surveyed changes in antibody levels specific for F1 antigens of Yersinia pestis among vaccinated people 4, 8, and 12 months post- vaccination. Blood samples were taken from the participants of the study for producing sera, which was later analyzed using indirect hemagglutination reaction with antigenic erythrocyte assay (micromethod) for identifying antibodies to F1 Y.pestis. Results: In first-time-receivers of the plague vaccine, antibody titer reached the highest level of antibody that represents a conditionally protective titer after 4 months, dropped drastically after 8 months, and dropped again after 12 months. Similar results were obtained among those who have been vaccinated previously. However, in that group, the percentage of people with a level of antibody that represents a conditionally protective titer remained statistically significant even after 8 and 12 months. Conclusion: Based on the results of this study, we recommend initiating vaccination campaigns for the medical and veterinary staff, as well as the general population four months prior to the springtime epizootics of plague among wild rodents. [ABSTRACT FROM AUTHOR]

Introduction: Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder primarily affecting children and adolescents. It can lead to chronic pain, bony deformities and fractures. The pathophysiology of CNO is incompletely understood. Scientific evidence suggests dysregulated expression of pro- and anti-inflammatory cytokines to be centrally involved. Currently, treatment is largely based on retrospective observational studies and expert opinion. Treatment usually includes nonsteroidal anti-inflammatory drugs and/or glucocorticoids, followed by a range of drugs in unresponsive cases. While randomised clinical trials are lacking, retrospective and prospective non-controlled studies suggest effectiveness of TNF inhibitors and bisphosphonates. The objective of the Bayesian consensus meeting was to quantify prior expert opinion. Methods: Twelve international CNO experts were randomly chosen to be invited to a Bayesian prior elicitation meeting. Results: Results showed that a typical new patient treated with pamidronate would have an 84% chance of improvement in their pain score relative to baseline at 26 weeks and an 83% chance on adalimumab. Experts thought there was a 50% chance that a new typical patient would record a pain score of 28mm (pamidronate) to 30mm (adalimumab) or better at 26 weeks. There was a modest trend in prior opinion to indicate an advantage of pamidronate vs adalimumab, with a 68% prior chance that pamidronate is superior to adalimumab by some margin. However, it is clear that there is considerable uncertainty about the precise relative merits of the two treatments. Conclusions: The rarity of CNO leads to challenges in conducting randomised controlled trials with sufficient power to provide a definitive outcome. We address this using a Bayesian design, and here describe the process and outcome of the elicitation exercise to establish expert prior opinion. This opinion will be tested in the planned prospective CNO study. The process for establishing expert consensus opinion in CNO will be helpful for developing studies in other rare paediatric diseases. [ABSTRACT FROM AUTHOR]

Background and Aims: To review the regenerative technologies used in bone regeneration: bone grafts, barrier membranes, bioactive factors and cell therapies. Material and Methods: Four background review publications served to elaborate this consensus report. Results and Conclusions: Biomaterials used as bone grafts must meet specific requirements: biocompatibility, porosity, osteoconductivity, osteoinductivity, surface properties, biodegradability, mechanical properties, angiogenicity, handling and manufacturing processes. Currently used biomaterials have demonstrated advantages and limitations based on the fulfilment of these requirements. Similarly, membranes for guided bone regeneration (GBR) must fulfil specific properties and potential biological mechanisms to improve their clinical applicability. Pre‐clinical and clinical studies have evaluated the added effect of bone morphogenetic proteins (mainly BMP‐2) and autologous platelet concentrates (APCs) when used as bioactive agents to enhance bone regeneration. Three main approaches using cell therapies to enhance bone regeneration have been evaluated: (a) "minimally manipulated" whole tissue fractions; (b) ex vivo expanded "uncommitted" stem/progenitor cells; and (c) ex vivo expanded "committed" bone‐/periosteum‐derived cells. Based on the evidence from clinical trials, transplantation of cells, most commonly whole bone marrow aspirates (BMA) or bone marrow aspirate concentrations (BMAC), in combination with biomaterial scaffolds has demonstrated an additional effect in sinus augmentation and horizontal ridge augmentation, and comparable bone regeneration to autogenous bone in alveolar cleft repair. [ABSTRACT FROM AUTHOR]

Background and Aims: To describe the biology of alveolar bone regeneration. Material and Methods: Four comprehensive reviews were performed on (a) mesenchymal cells and differentiation factors leading to bone formation; (b) the critical interplay between bone resorbing and formative cells; (c) the role of osteoimmunology in the formation and maintenance of alveolar bone; and (d) the self‐regenerative capacity following bone injury or tooth extraction were prepared prior to the workshop. Results and Conclusions: This summary information adds to the fuller understanding of the alveolar bone regenerative response with implications to reconstructive procedures for patient oral rehabilitation. The group collectively formulated and addressed critical questions based on each of the reviews in this consensus report to advance the field. The report concludes with identified areas of future research. [ABSTRACT FROM AUTHOR]

Crop yields are projected to decrease under future climate conditions, and recent research suggests that yields have already been impacted. However, current impacts on a diversity of crops subnationally and implications for food security remains unclear. Here, we constructed linear regression relationships using weather and reported crop data to assess the potential impact of observed climate change on the yields of the top ten global crops–barley, cassava, maize, oil palm, rapeseed, rice, sorghum, soybean, sugarcane and wheat at ~20,000 political units. We find that the impact of global climate change on yields of different crops from climate trends ranged from -13.4% (oil palm) to 3.5% (soybean). Our results show that impacts are mostly negative in Europe, Southern Africa and Australia but generally positive in Latin America. Impacts in Asia and Northern and Central America are mixed. This has likely led to ~1% average reduction (-3.5 X 1013 kcal/year) in consumable food calories in these ten crops. In nearly half of food insecure countries, estimated caloric availability decreased. Our results suggest that climate change has already affected global food production. [ABSTRACT FROM AUTHOR]

Human T-cell lymphotropic virus (HTLV) belongs to a larger group of primate T-cell lymphotropic viruses (PTLVs) within the family Retroviridae. It is estimated that 10 to 20 million people worldwide may be infected with HTLV-1. Although most of them are asymptomatic, around 5% of infected individuals may develop either HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) or Adult T-cell Leukaemia/Lymphoma (ATLL). Public Health authorities in many countries have implemented routine blood-donor tests for HTLV-specific antibodies; but this is not the case for Germany since the reported prevalence is very low (7/100,000). With the aim to evaluate retrospectively the presence of HTLV-1 among oncology patients in this country, samples stored at the Universitätsklinikum Freiburg, were analyzed. For this purpose, two different nested-PCR (n-PCR) protocols have been modified and set up for HTLV-1 detection. One positive case was detected by n-PCR among 406 samples (0,25%) in a period of 5 years (2008–2012) corresponding to a T-Cell Lymphoma. Despite the low prevalence, this virus is circulating in Germany, probably due to the increasing numbers of immigrants in these last years. Physicians should consider HTLV-1 infection and suspect it taking in account the ethnic and relation to endemic regions regardless the patient's residence. [ABSTRACT FROM AUTHOR]

Background: NTZ is approved in Russia for the treatment of highly active relapsing remitting multiple sclerosis and is reimbursed via federal budget program. However, no data about NTZ treatment in Russia and the effect of federal reimbursement have been performed so far. Objective: To characterize the population of patients receiving natalizumab and assess the efficacy and risk-management plan (RMP) implementation of NTZ therapy in routine clinical practice in Russia. Methods: We analyzed data for 334 patients, who received at least one infusion of NTZ. Relapse rate, MRI activity, NEDA-3 status after 2 years were assessed. Anti-JC virus antibodies status and RMP implementation were evaluated. Drop-out rate and reasons for therapy discontinuation were analyzed. Results: Patients switched to natalizumab in Russia are mainly female (63%), with median EDSS score of 3.5 and high disease activity: 93% had at least 1 relapse and 58% had both T1Gd+ and new T2 lesion a year before therapy initiation. Introduction of federal reimbursement allowed patients with less relapses to start therapy with natalizumab. The only predictor of 6-month progression was EDSS score at the baseline of therapy (HR = 2.1375, 95%CI 1.0026–4.5570, p = 0.0492). 82% patients reached NEDA-3 at 24 month of therapy. 25% of patients discontinued NTZ for reasons: tolerability (14.5%), JCV antibody status (61%), and patient’s decision (17%). RMP was implemented in only 36% patients. Conclusion: Natalizumab appeared to have high efficacy in Russian clinical practice. Federal reimbursement allowed less active patients to start natalizumab. More efforts should be done to improve RMP implementation. [ABSTRACT FROM AUTHOR]

Background: Serological assays to determine HIV incidence have contributed to estimates of HIV incidence, monitoring of HIV spread, and evaluation of prevention strategies. Two frequently used incidence assays are the Sedia HIV-1 LAg-Avidity EIA (LAg) and the Bio-Rad avidity incidence (BRAI) assays with a mean duration of recent infection (MDRI) of 130 and 240 days for subtype B infections, respectively. Little is known about how these assays perform with recombinant HIV-1 strains. We evaluated the concordance of these assays in a population infected mainly with HIV-1 CRF06_cpx. Material/Methods: Remnant serum samples (n = 288) collected from confirmed, newly-diagnosed HIV-positive persons from Estonia in 2013 were tested. Demographic and clinical data were extracted from clinical databases. LAg was performed according to the manufacturer’s protocol and BRAI testing was done using a validated protocol. Samples with LAg-pending or BRAI-invalid results were reclassified as recent if they were from persons with viral loads <1000 copies/mL or were reclassified as long-term if presenting with AIDS. Results: In total 325 new HIV infections were diagnosed in 2013 in Estonia. Of those 276 persons were tested with both LAg and BRAI. Using assay results only, the recency rate was 44% and 70% by LAg and BRAI, respectively. The majority of samples (92%) recent by LAg were recent by BRAI. Similarly, 89% of samples long-term by BRAI were long-term by LAg. After clinical information was included in the analysis, the recency rate was 44% and 62% for LAg and BRAI, respectively. The majority of samples (86%) recent by LAg were recent by BRAI and 91% of long-term infections by BRAI were long-term by LAg. Conclusions: Comparison of LAg and BRAI results in this mostly CRF06_cpx-infected population showed good concordance for incidence classification. Our finding of a higher recency rate with BRAI in this population is likely related to the longer MDRI for this assay. [ABSTRACT FROM AUTHOR]

Background: Image-based blood flow simulations have been increasingly applied to investigate intracranial aneurysm (IA) hemodynamics. However, the acceptance among physicians remains limited due to the high variability in the underlying assumptions and quality of results. Methods: To evaluate the vessel segmentation as one of the most important sources of error, the international Multiple Aneurysms AnaTomy CHallenge 2018 (MATCH) was announced. 26 research groups from 13 different countries segmented three datasets, which contained five IAs in total. Based on these segmentations, 73 time-dependent blood flow simulations under consistent conditions were carried out. Afterwards, relevant flow and shear parameters (e.g., neck inflow rate, parent vessel flow rate, spatial mean velocity, and wall shear stress) were analyzed both qualitatively and quantitatively. Results: Regarding the entire vasculature, the variability of the segmented vessel radius is 0.13 mm, consistent and independent of the local vessel radius. However, the centerline velocity shows increased variability in more distal vessels. Focusing on the aneurysms, clear differences in morphological and hemodynamic parameters were observed. The quantification of the segmentation-induced variability showed approximately a 14% difference among the groups for the parent vessel flow rate. Regarding the mean aneurysmal velocity and the neck inflow rate, a variation of 30% and 46% was observed, respectively. Finally, time-averaged wall shear stresses varied between 28% and 51%, depending on the aneurysm in question. Conclusions: MATCH reveals the effect of state-of-the-art segmentation algorithms on subsequent hemodynamic simulations for IA research. The observed variations may lead to an inappropriate interpretation of the simulation results and thus, can lead to inappropriate conclusions by physicians. Therefore, accurate segmentation of the region of interest is necessary to obtain reliable and clinically helpful flow information. [ABSTRACT FROM AUTHOR]

Despite considerable air pollution prevention and control measures that have been put into practice in recent years, outdoor air pollution remains one of the most important risk factors for health outcomes. To identify the potential research gaps, we conducted a scoping review focused on health outcomes affected by outdoor air pollution across the broad research area. Of the 5759 potentially relevant studies, 799 were included in the final analysis. The included studies showed an increasing publication trend from 1992 to 2008, and most of the studies were conducted in Asia, Europe, and North America. Among the eight categorized health outcomes, asthma (category: respiratory diseases) and mortality (category: health records) were the most common ones. Adverse health outcomes involving respiratory diseases among children accounted for the largest group. Out of the total included studies, 95.2% reported at least one statistically positive result, and only 0.4% showed ambiguous results. Based on our study, we suggest that the time frame of the included studies, their disease definitions, and the measurement of personal exposure to outdoor air pollution should be taken into consideration in any future research. The main limitation of this study is its potential language bias, since only English publications were included. In conclusion, this scoping review provides researchers and policy decision makers with evidence taken from multiple disciplines to show the increasing prevalence of outdoor air pollution and its adverse effects on health outcomes. [ABSTRACT FROM AUTHOR]

Vaginal lubricants are commonly used by couples trying-to-conceive. However, most vaginal lubricants are sperm toxic and therefore should not be used by couples trying-to-conceive. Despite this, lubricant sperm toxicity is insufficiently reported and guidance for healthcare professionals (HCPs) is absent. In this study, lubricant-related practices of fertility-based HCPs in Scotland were sampled via an online survey. Lubricants identified as being utilised in the fertility setting were subsequently incubated with prepared sperm samples to establish effects on sperm motility. HCP recommendations (n = 32) on lubricant use were varied although knowledge related to sperm toxicity was generally poor. HCPs infrequently asked about lubricant use and were unaware of guidance in this area. Aquagel, the only prescribed lubricant identified in this study, reduced sperm progressive motility to 49% of control after 10 minutes, even at concentrations as low as 5%. Vitality testing suggested the deterioration in progressive motility with Aquagel was not as a result of cell death. Conversely, Pré Vaginal Lubricant, a ‘sperm-safe’ lubricant, did not significantly affect any markers of sperm function assessed. Development of clinical guidance in this area is recommended to ensure HCPs deliver informed advice as lubricant use in couples trying-to-conceive may inadvertently contribute to delay in conception. [ABSTRACT FROM AUTHOR]

Objective: To compare the differences in the use of healthcare services: visits to the doctor and hospitalisation, performance of routine tests, and preventive influenza vaccination, between users and non-users of homeopathic products. Methods: We used the microdata for adults over 15 years old from three waves of the Spanish National Health Survey, corresponding to the years 2011, 2014 and 2017. We proposed a comparative design of a quasi-experimental type, considering as the treatment group the respondents who said that they had used homeopathic products in the past two weeks; and another group, for control, comprising respondents who said that they had not used this type of products, but only conventional medicines, with observable characteristics similar to those of the treatment group. We used a model for rare events logistics regression (relogit) to estimate the probability of using homeopathy. From the propensity score and a vector of control variables, we used techniques of genetic matching to match individuals from the treatment group with similar individuals belonging to the control group. Results: There are no statistically significant differences between users and non-users of homeopathy in visits to the general practitioner (P>|z| 0.387), to the specialist (P>|z| 0.52), in hospitalisations (P>|z| 0.592) or in the use of emergency services (P>|z| 0.109). Nor were there any statistically significant differences in the performance of routine tests, except for the faecal occult blood test, which is more prevalent in users of homeopathic products. 20.9% of users of homeopathy had done this test compared with 15.3% of non-users (P>|z| 0.022). There are also significant differences in vaccination against influenza with 12.6% of homeopathy users stating that they had been vaccinated in the last influenza campaign, against 21.0% of non-users (P>|z| <0.001). The health conditions which homeopathy users reported were constipation (OR: 1.65 CI: 1.16–2.36), malignant tumour (OR: 1.60 CI: 1.09–2.36) osteoporosis (OR: 1.49 CI: 1.05–2.10), varicose veins (OR: 1.35 CI: 1.05–1.74) and allergy (OR: 1.35 CI: 1.06–1.72). Conclusions: Differences in the use of healthcare resources between users and non-users of homeopathic products have not been found to be statistically significant in Spain. It has been shown that most homeopathic products are used as a complement to treatment with conventional medicine. Nevertheless, our results highlight some warning signs which should raise the attention of healthcare authorities. The use of these therapies in patients with malignant tumours and the rejection of vaccines are warning signs of a possible health hazard in the long term. [ABSTRACT FROM AUTHOR]

Hantaan virus (HTNV) and Puumala virus (PUUV) are rodent-borne hantaviruses that are the primary causes of hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia. The development of well characterized animal models of HTNV and PUUV infection is critical for the evaluation and the potential licensure of HFRS vaccines and therapeutics. In this study we present three animal models of HTNV infection (hamster, ferret and marmoset), and two animal models of PUUV infection (hamster, ferret). Infection of hamsters with a ~3 times the infectious dose 99% (ID99) of HTNV by the intramuscular and ~1 ID99 of HTNV by the intranasal route leads to a persistent asymptomatic infection, characterized by sporadic viremia and high levels of viral genome in the lung, brain and kidney. In contrast, infection of hamsters with ~2 ID99 of PUUV by the intramuscular or ~1 ID99 of PUUV by the intranasal route leads to seroconversion with no detectable viremia, and a transient detection of viral genome. Infection of ferrets with a high dose of either HTNV or PUUV by the intramuscular route leads to seroconversion and gradual weight loss, though kidney function remained unimpaired and serum viremia and viral dissemination to organs was not detected. In marmosets a 1,000 PFU HTNV intramuscular challenge led to robust seroconversion and neutralizing antibody production. Similarly to the ferret model of HTNV infection, no renal impairment, serum viremia or viral dissemination to organs was detected in marmosets. This is the first report of hantavirus infection in ferrets and marmosets. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance and related metabolic disturbances are major risk factors for the higher T2D risk and associated morbidity and mortality amongst South Asians. The contribution of physical activity to the increased prevalence of insulin resistance and related disturbances amongst South Asians is unknown. Methods: We recruited 902 South Asian and European men and women, aged 35–85 years from the ongoing LOLIPOP study. Clinical characterisation comprised standardised questionnaire and measurement of height, weight, waist and hip circumference and blood pressure. Fasting bloods were taken for assessment of glucose, insulin, lipids and HbA1c. Physical activity was quantified using a validated accelerometer, Actigraph GT3X+, worn for 7 days. Univariate and multivariate approaches were used to investigate the relationship between ethnicity, physical activity, insulin resistance and related metabolic disturbances. Results: Total physical activity was ~31% (P = 0.01) lower amongst South Asians compared to Europeans (Mean MET.minutes [SD]: 1505.2 [52] vs. 2050.9 [86.6], P<0.001). After adjusting for age and sex, total physical activity had a negative association with HOMA-IR (B [SE]: -0.18 [0.08], P = 0.04) and fasting glucose levels (B[SE]: -0.11 [0.04], P = 0.02). There was no association between physical activity and other glycemic and lipid parameters. Total physical activity per week contributed towards the differences in insulin resistance and associated metabolic disturbances between South Asians and Europeans. Conclusion: Lower levels of physical activity may contribute to the increased insulin resistance in South Asians compared to Europeans. Our results suggest that lifestyle modification through increased physical activity may help to improve glucose metabolism and reduce the burden of excess T2D and related complications amongst South Asians. [ABSTRACT FROM AUTHOR]

Background: Previous ischemic stroke is a predictor of recurrent ischemic stroke after an acute myocardial infarction (AMI). Dual antiplatelet therapy, including a P2Y12-inhibitor, is important in secondary prevention after AMI. Ticagrelor, a P2Y12-inhibitor, is more potent than the commonly used clopidogrel. Here, we evaluated the impact of ticagrelor on the risk of ischemic stroke following AMI in patients with previous ischemic stroke. Methods: Data for patients with AMI that had a previous ischemic stroke were obtained from the Swedish Registry of Information and Knowledge about Swedish Heart Intensive Care Admissions. Patients were assigned to early and late cohorts, each covering a two-year time period before and after, respectively, the introduction of ticagrelor prescriptions (20 Dec 2011). Patients in the early cohort (n = 1633) were treated with clopidogrel (100%); those in the late cohort (n = 1642) were treated with either clopidogrel (66.3%) or ticagrelor (33.7%). We assessed the risk of ischemic stroke and intracranial bleeding over time with Kaplan-Meier analyses. We identified predictors of ischemic stroke with multivariable Cox regression analyses. Results: Of 3275 patients, 311 experienced ischemic stroke after AMI. Cumulative Kaplan-Meier incidence estimates of ischemic stroke within one year after AMI were 12.1% versus 8.6% for the early and late cohorts, respectively (p<0.01). Intracranial bleeding incidences (1.2% versus 1.5%) were similar between the two cohorts. Conclusions: Ticagrelor introduction was associated with a lower rate of ischemic stroke, with no increase in intracranial bleeding, in an AMI population with a history of ischemic stroke. [ABSTRACT FROM AUTHOR]

Given the high prevalence of common mental disorders (CMDs) and individuals living alone in the United Kingdom, the goal of this study using English nationally representative data was to examine the association between living alone and CMDs, and to identify potential mediating factors of this association. The data were drawn from the 1993, 2000 and 2007 National Psychiatric Morbidity Surveys. CMDs were assessed using the Clinical Interview Schedule-Revised (CIS-R), a questionnaire focusing on past week neurotic symptoms. The presence of CMDs was defined as a CIS-R total score of 12 and above. Multivariable logistic regression and mediation analyses were conducted to analyze the association between living alone and CMDs, and to identify mediators in this association. The prevalence of CMDs was higher in individuals living alone than in those not living alone in all survey years. Multivariable analysis showed a positive association between living alone and CMDs in all survey years (1993: odds ratio [OR] = 1.69; 2000: OR = 1.63; and 2007: OR = 1.88). Overall, loneliness explained 84% of the living alone-CMD association. Living alone was positively associated with CMDs. Interventions addressing loneliness among individuals living alone may be particularly important for the mental wellbeing of this vulnerable population. [ABSTRACT FROM AUTHOR]

Effective global collaboration is crucial to achieving the UN Sustainable Development Goals (SDGs). It requires an understanding of the needs of individual countries and their expectations related to bioeconomy. With the aim to explore the prospective developments in the global bioeconomy over the next 20 years, the German Bioeconomy Council, an independent advisory body to the German Federal Government, commissioned BIOCOM-AG to invite experts from around the globe to share their insights in a global expert survey. The survey was conducted online in autumn 2017. 345 experts from 46 countries completed the questionnaire about future developments and strategies in the global bioeconomy. As claimed by the experts, the upcoming bioeconomy must primarily meet humanity’s needs in the energy, agriculture, and food sectors. Moreover, innovative products based on renewable resources are anticipated to be of great importance. Even though all UN SDGs will be affected by future bioeconomy success stories, five SDGs stood out within the sample: SDG 12: ‘responsible consumption and production’; SDG 9: ‘industry, innovation and infrastructure’; SDG 13: ‘climate action’; SDG 7: ‘affordable and clean energy’; and SDG 11: ‘sustainable cities and communities’. About three quarters of the experts emphasized the need to specifically address three conflicting goals in any future bioeconomy strategy: non-food uses of arable land, use of crop land to produce feedstock for meat, milk and egg production and, finally, the conversion of virgin forests into agricultural land. Most experts stated that reducing food loss and waste is crucial to eradicating the world hunger problem. The proposed solutions relied greatly on innovation and technological development. Bioeconomy expertise and know-how should be shared in close cooperation between developed and developing economies to reach UN SDGs. A supportive political framework would be the ultimate goal towards furthering the progress of a future bioeconomy all over the world. [ABSTRACT FROM AUTHOR]

The fibularis tertius muscle (FTM) is a rare anatomic variation. The prevalence of this exclusively human structure, which is found in the anterior compartment of the leg, is often underestimated, and it is believed that foot and ankle conditions are more difficult to manage in patients with an FTM. The aim of this study was to assess the presence of the FTM palpation and determine whether its presence is associated with an individual’s sex, because the exact prevalence in males and females is unclear. An observational cross-sectional study was carried out. The study included 481 people (23.49% men and 76.51% women) with a mean age of 23.51±5.369 years, who were recruited from a Podiatric Medicine and Surgery Clinic (Spain). Data on routine demographic and clinical factors were recorded, and the presence or absence of the FTM was determined based on surface visual or palpated localization of the tendon (using a consistent protocol). The FTM was present in 38.25% (184/481) of the participants. Furthermore, FTM were present in 38.6% (142/481) of females and 37.2% (42/481) of males. The study revealed that the presence of the FTM varies between individuals and does not depend on an individual’s sex. Significant differences in the prevalence of the FTM between countries should be carefully evaluated rather than generalizing the results of this Spanish study to other non-Spanish populations. Larger numbers of participants should be enrolled in future studies in order to meet the statistical criteria. [ABSTRACT FROM AUTHOR]

Tick-borne encephalitis virus (TBEV) is the most important tick-transmitted pathogen. It belongs to the Flaviviridae family and causes severe human neuroinfections. In this study, protective efficacy of the chimeric antibody chFVN145 was examined in mice infected with strains belonging to the Far-Eastern, European, and Siberian subtypes of TBEV, and the antibody showed clear therapeutic efficacy when it was administered once one, two, or three days after infection. The efficacy was independent of the TBEV strain used to infect the mice; however, the survival rate of the mice was dependent on the dose of TBEV and of the antibody. No enhancement of TBEV infection was observed when the mice were treated with non-protective doses of chFVN145. Using a panel of recombinant fragments of the TBEV glycoprotein E, the neutralizing epitope for chFVN145 was localized in domain III of the TBEV glycoprotein E, in a region between amino acid residues 301 and 359. In addition, three potential sites responsible for binding with chFVN145 were determined using peptide phage display libraries, and 3D modeling demonstrated that the sites do not contact the fusion loop and, hence, their binding with chFVN145 does not result in increased attachment of TBEV to target cells. [ABSTRACT FROM AUTHOR]

Background: Folate and homocysteine are involved in DNA synthesis and methylation processes, which are deregulated during carcinogenesis. Objectives: The aim of this study was to assess the relationship between folate/homocysteine concentrations, the functional polymorphisms of folate/homocysteine genes and lung cancer risk among cigarette smokers. Study design: The study included 132 lung cancer patients and 396 controls from northern Poland, matched by sex, age and smoking status. The median cigarette pack-years of smoking among both cases and controls was 30.0. Serum, red blood cell (RBC) folates and serum homocysteine concentrations were measured. The genotypes in selected polymorphic sites of the MTHFR, CBS, SHMT1, MTHFD1, MTRR, MTR, TYMS DHFR, TCN2, and SLC19A1 genes were determined. All study participants underwent scanning with low-dose computed tomography. Results: Serum folate concentrations above the median (> 17.5 nmol/l among the healthy controls) were associated with an increased lung cancer risk (odds ratio [OR], 1.54, 95% confidence intervals [CI], 1.04–2.29, P = 0.031). An analogous trend was observed when the population was analysed after subdivision according to RBC folate concentrations, that is, above a value of 506.5 nmol/l (OR, 1.53; 95% CI, 0.95–2.47; P = 0.084). Additionally, in a subset of women, an increased risk of lung cancer development was associated with the SLC19A1 c.80AA genotype (c.80AA versus GG OR, 3.14; 95% CI, 1.32–7.46; P = P = 0.010). Conclusion: These results suggest that, in the population consisting of heavy smokers, high folate levels add to the cancerogenic effect of smoking. [ABSTRACT FROM AUTHOR]

Background: Despite the clinical utility of echocardiography to measure left atrial (LA) structure and function, there are scarcities of data about the percentiles of LA diameter (LAD), LA volume (LAVOL), and LA volume indexed by body surface area (LAVOL/BSA) from prospective population‐based studies in healthy children and adolescents from the Southern Cone of Latin America. Methods: Echocardiographic studies were obtained in 1095 healthy subjects nonexposed to cardiovascular risk factors (5–24 years). Age‐ and sex‐specific reference values of LAD, LAVOL, and LAVOL/BSA were generated using parametric regression based on fractional polynomials. Results: After covariate analysis (ie, adjusting by age, body surface area), specific sex‐specific percentiles were evidenced as necessaries. Age‐ and sex‐specific 1st, 2.5th, 5th, 10th, 25th, 50th, 75th, 90th, 95th, 97.5th, and 99th percentile and curves were reported. Our percentiles showed high concordance and complementarity with what was previously reported for the population of North American, European, and Asiatic Populations. Conclusions: In children and adolescents, the interpretation of the LA size requires sex‐related percentiles. This study provides the largest Argentinean database concerning percentile curves of LAD, LAVOL, and LAVOL/BSA obtained in healthy children and adolescents. These data are valuable in that they provide values with which data of populations of children, adolescents, and young adults can be compared. [ABSTRACT FROM AUTHOR]