Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar

Although previously considered entirely reversible, general anaesthesia is now being viewed as a potentially significant risk to cognitive performance at both extremes of age. A large body of preclinical as well as some retrospective clinical evidence suggest that exposure to general anaesthesia could be detrimental to cognitive development in young subjects, and might also contribute to accelerated cognitive decline in the elderly. A group of experts in anaesthetic neuropharmacology and neurotoxicity convened in Salzburg, Austria for the BJA Salzburg Seminar on Anaesthetic Neurotoxicity and Neuroplasticity. This focused workshop was sponsored by the British Journal of Anaesthesia to review and critically assess currently available evidence from animal and human studies, and to consider the direction of future research. It was concluded that mounting evidence from preclinical studies reveals general anaesthetics to be powerful modulators of neuronal development and function, which could contribute to detrimental behavioural outcomes. However, definitive clinical data remain elusive. Since general anaesthesia often cannot be avoided regardless of patient age, it is important to understand the complex mechanisms and effects involved in anaesthesia-induced neurotoxicity, and to develop strategies for avoiding or limiting potential brain injury through evidence-based approache

Host And Geography Together Drive Early Adaptive Radiation Of Hawaiian Planthoppers

The interactions between insects and their plant host have been implicated in driving diversification of both players. Early arguments highlighted the role of ecological opportunity, with the idea that insects escape and radiate on new hosts, with subsequent hypotheses focusing on the interplay between host shifting and host tracking, coupled with isolation and fusion, in generating diversity. Because it is rarely possible to capture the initial stages of diversification, it is particularly difficult to ascertain the relative roles of geographic isolation versus host shifts in initiating the process. The current study examines genetic diversity between populations and hosts within a single species of endemic Hawaiian planthopper, Nesosydne umbratica (Hemiptera, Delphacidae). Given that the species was known as a host generalist occupying unrelated hosts, Clermontia (Campanulaceae) and Pipturus (Urticaceae), we set out to determine the relative importance of geography and host in structuring populations in the early stages of differentiation on the youngest islands of the Hawaiian chain. Results from extensive exon capture data showed that N. umbratica is highly structured, both by geography, with discrete populations on each volcano, and by host plant, with parallel radiations on Clermontia and Pipturus leading to extensive co-occurrence. The marked genetic structure suggests that populations can readily become established on novel hosts provided opportunity; subsequent adaptation allows monopolization of the new host. The results support the role of geographic isolation in structuring populations and with host shifts occurring as discrete events that facilitate subsequent parallel geographic range expansion

Modeling Abnormal Priming in Alzheimer's Patients with a Free Association Network

Alzheimer's Disease irremediably alters the proficiency of word search and retrieval processes even at its early stages. Such disruption can sometimes be paradoxical in specific language tasks, for example semantic priming. Here we focus in the striking side-effect of hyperpriming in Alzheimer's Disease patients, which has been well-established in the literature for a long time. Previous studies have evidenced that modern network theory can become a powerful complementary tool to gain insight in cognitive phenomena. Here, we first show that network modeling is an appropriate approach to account for semantic priming in normal subjects. Then we turn to priming in degraded cognition: hyperpriming can be readily understood in the scope of a progressive degradation of the semantic network structure. We compare our simulation results with previous empirical observations in diseased patients finding a qualitative agreement. The network approach presented here can be used to accommodate current theories about impaired cognition, and towards a better understanding of lexical organization in healthy and diseased patients

Global Scale Dissemination of ST93: A Divergent Staphylococcus aureus Epidemic Lineage That Has Recently Emerged From Remote Northern Australia.

Background: In Australia, community-associated methicillin-resistant Staphylococcus aureus (MRSA) lineage sequence type (ST) 93 has rapidly risen to dominance since being described in the early 1990s. We examined 459 ST93 genome sequences from Australia, New Zealand, Samoa, and Europe to investigate the evolutionary history of ST93, its emergence in Australia and subsequent spread overseas. Results: Comparisons with other S. aureus genomes indicate that ST93 is an early diverging and recombinant lineage, comprising of segments from the ST59/ST121 lineage and from a divergent but currently unsampled Staphylococcal population. However, within extant ST93 strains limited genetic diversity was apparent with the most recent common ancestor dated to 1977 (95% highest posterior density 1973-1981). An epidemic ST93 population arose from a methicillin-susceptible progenitor in remote Northern Australia, which has a proportionally large Indigenous population, with documented overcrowded housing and a high burden of skin infection. Methicillin-resistance was acquired three times in these regions, with a clade harboring a staphylococcal cassette chromosome mec (SCCmec) IVa expanding and spreading to Australia's east coast by 2000. We observed sporadic and non-sustained introductions of ST93-MRSA-IVa to the United Kingdom. In contrast, in New Zealand, ST93-MRSA-IVa was sustainably transmitted with clonal expansion within the Pacific Islander population, who experience similar disadvantages as Australian Indigenous populations. Conclusion: ST93 has a highly recombinant genome including portions derived from an early diverging S. aureus population. Our findings highlight the need to understand host population factors in the emergence and spread of antimicrobial resistant community pathogens

Inducible and constitutive heat shock gene expression responds to modification of Hsp70 copy number in Drosophila melanogaster but does not compensate for loss of thermotolerance in Hsp70 null flies

<p>Abstract</p> <p>Background</p> <p>The heat shock protein Hsp70 promotes inducible thermotolerance in nearly every organism examined to date. Hsp70 interacts with a network of other stress-response proteins, and dissecting the relative roles of these interactions in causing thermotolerance remains difficult. Here we examine the effect of <it>Hsp70 </it>gene copy number modification on thermotolerance and the expression of multiple stress-response genes in <it>Drosophila melanogaster</it>, to determine which genes may represent mechanisms of stress tolerance independent of Hsp70.</p> <p>Results</p> <p><it>Hsp70 </it>copy number in four strains is positively associated with <it>Hsp70 </it>expression and inducible thermotolerance of severe heat shock. When assayed at carefully chosen temperatures, <it>Hsp70 </it>null flies are almost entirely deficient in thermotolerance. In contrast to expectations, increasing <it>Hsp70 </it>expression levels induced by thermal pretreatment are associated with increasing levels of seven other inducible <it>Hsps </it>across strains. In addition, complete <it>Hsp70 </it>loss causes upregulation of the inducible <it>Hsps </it>and six constitutive stress-response genes following severe heat shocks.</p> <p>Conclusion</p> <p>Modification of <it>Hsp70 </it>copy number quantitatively and qualitatively affects the expression of multiple other stress-response genes. A positive association between absolute expression levels of <it>Hsp70 </it>and other <it>Hsps </it>after thermal pretreatment suggests novel regulatory mechanisms. Severe heat shocks induce both novel gene expression patterns and almost total mortality in the <it>Hsp70 </it>null strain: alteration of gene expression in this strain does not compensate for <it>Hsp70 </it>loss but suggests candidates for overexpression studies.</p

2021 Update of the International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants

International audienceIn 2018, the International Council for Standardization in Haematology (ICSH) published a consensus document providing guidance for laboratories on measuring direct oral anticoagulants (DOACs). Since that publication, several significant changes related to DOACs have occurred, including the approval of a new DOAC by the Food and Drug Administration, betrixaban, and a specific DOAC reversal agent intended for use when the reversal of anticoagulation with apixaban or rivaroxaban is needed due to life-threatening or uncontrolled bleeding, andexanet alfa. In addition, this ICSH Working Party recognized areas where additional information was warranted, including patient population considerations and updates in point-of-care testing. The information in this manuscript supplements our previous ICSH DOAC laboratory guidance document. The recommendations provided are based on (1) information from peer-reviewed publications about laboratory measurement of DOACs, (2) contributing author's personal experience/expert opinion and (3) good laboratory practice

Effects of reduced soil functionality in European vineyards

Improper or excessive land preparation methods in vineyards before planting can have a considerable impact on soil functionality. They include excessive levelling and deep ploughing leading to disturbances of the natural contour of slopes and destruction, truncation and burial of soil horizons. Manipulations may significantly modify chemical, physical, biological and hydrological balance of soils. Problems that may arise from these interventions relate to the reduction of organic substances, enrichment of calcium carbonate and soluble salts, impacting development and health of grapevines. Reduced water retention capacity can lead to increased water stress during dry season, decreased water permeability and circulation of oxygen in the soil, increased runoff volume, surface erosion and landslide risk, reduced biodiversity and limitation of biochemical processes (organic matter mineralization, bioavailability of nutrients, etc.). Soil degradations can lead to the loss of soil functionality even after the planting as a result of accelerated erosion, compaction by agricultural vehicles, excessive loss of organic matter and nutrients, and the accumulation of heavy metals such as copper. In both conventional and organic vineyards, it is quite common to have areas with reduced soil functionality that have negative impact on vine health and grape production and quality. In the framework of the Core organic RESOLVE project, a study was conducted in organic vineyards showing areas with reduced and good soil functionality. Degraded soils resulted in significantly lower amounts of grapes. The chlorophyll index (SPAD) of the grapevine during veraison was significantly lower in areas of degraded soils compared with the situation in areas of the same vineyard with non-degraded soils. In general, causes of soil malfunctioning were related to a lower fertility, including reduced organic carbon, total nitrogen and cation exchange capacity, higher concentrations of carbonates, and increased stoniness in the topsoil. Degraded soils showed lower structure quality and rooting depth limited by shallow saprolite or horizon features such as compaction, scarce fertility and high content of carbonates. The soils in the non-degraded areas showed significant higher content of total nitrogen and higher carbon/nitrogen ratios, thus a better stability of organic matter. On the other hand, biological diversity and activity, monitored by different proxies (microarthropods, nematodes, enzymes, organic matter turnover by Tea bag index) in some vineyards, all managed organically, did not show any clear and significant differences between degraded and not degraded areas. Similarly, no clear difference in overall microbial diversity indices (Shannon, Simpson) and diversity evenness (Pielou) were observed between non-degraded and degraded areas. All indices were relatively high and indicative for rich occurrence of abundant and rare microbial species, high diversity and low abundance of individual species and high species evenness

Distinct Mechanisms Underlying Tolerance to Intermittent and Constant Hypoxia in Drosophila melanogaster

BACKGROUND: Constant hypoxia (CH) and intermittent hypoxia (IH) occur during several pathological conditions such as asthma and obstructive sleep apnea. Our research is focused on understanding the molecular mechanisms that lead to injury or adaptation to hypoxic stress using Drosophila as a model system. Our current genome-wide study is designed to investigate gene expression changes and identify protective mechanism(s) in D. melanogaster after exposure to severe (1% O(2)) intermittent or constant hypoxia. METHODOLOGY/PRINCIPAL FINDINGS: Our microarray analysis has identified multiple gene families that are up- or down-regulated in response to acute CH or IH. We observed distinct responses to IH and CH in gene expression that varied in the number of genes and type of gene families. We then studied the role of candidate genes (up-or down-regulated) in hypoxia tolerance (adult survival) for longer periods (CH-7 days, IH-10 days) under severe CH or IH. Heat shock proteins up-regulation (specifically Hsp23 and Hsp70) led to a significant increase in adult survival (as compared to controls) of P-element lines during CH. In contrast, during IH treatment the up-regulation of Mdr49 and l(2)08717 genes (P-element lines) provided survival advantage over controls. This suggests that the increased transcript levels following treatment with either paradigm play an important role in tolerance to severe hypoxia. Furthermore, by over-expressing Hsp70 in specific tissues, we found that up-regulation of Hsp70 in heart and brain play critical role in tolerance to CH in flies. CONCLUSIONS/SIGNIFICANCE: We observed that the gene expression response to IH or CH is specific and paradigm-dependent. We have identified several genes Hsp23, Hsp70, CG1600, l(2)08717 and Mdr49 that play an important role in hypoxia tolerance whether it is in CH or IH. These data provide further clues about the mechanisms by which IH or CH lead to cell injury and morbidity or adaptation and survival

Mechanical Bonds and Topological Effects in Radical Dimer Stabilization

While mechanical bonding stabilizes tetrathiafulvalene (TTF) radical dimers, the question arises: what role does topology play in catenanes containing TTF units? Here, we report how topology, together with mechanical bonding, in isomeric [3]- and doubly interlocked [2]catenanes controls the formation of TTF radical dimers within their structural frameworks, including a ring-in-ring complex (formed between an organoplatinum square and a {2+2} macrocyclic polyether containing two 1,5-dioxynaphthalene (DNP) and two TTF units) that is topologically isomeric with the doubly interlocked [2]catenane. The separate TTF units in the two {1+1} macrocycles (each containing also one DNP unit) of the isomeric [3]catenane exhibit slightly different redox properties compared with those in the {2+2} macrocycle present in the [2]catenane, while comparison with its topological isomer reveals substantially different redox behavior. Although the stabilities of the mixed-valence (TTF2)^(•+) dimers are similar in the two catenanes, the radical cationic (TTF^(•+))_2 dimer in the [2]catenane occurs only fleetingly compared with its prominent existence in the [3]catenane, while both dimers are absent altogether in the ring-in-ring complex. The electrochemical behavior of these three radically configurable isomers demonstrates that a fundamental relationship exists between topology and redox properties