Are there functional consequences of a reduction in selenium intake in UK subjects?

Dietary Se levels in the UK have fallen over the last 20 years and recent surveys indicate that average Se intakes are 30-40 microg/d, which is well below the current UK reference nutrient intake for adult men (75 microg/d) or women (60 microg/d). Functional consequences of this decline have not been recognised, although epidemiological data suggest it may contribute to increased risk of infections and incidence of some cancers. Previous data have indicated that biochemical changes in Se-dependent proteins occur in otherwise healthy UK subjects given small Se supplements. The current studies have focused on the effect of small Se supplements on the immune response since there is evidence of specific interactions between Se intake and viral replication, and since the potential anti-cancer effects of Se may be mediated by non-antioxidant effects of Se such as changes in immune function. Data indicate that subjects given small Se supplements (50 or 100 microg Se/d) have changes in the activity of Se-dependent enzymes and evidence of improved immune function and clearance of an administered live attenuated virus in the form of poliovirus vaccine. Responses of individual subjects to Se supplements are variable, and current work is evaluating potential explanations for this variability, including genetic variability and pre-existing Se status

Implications of the formation of small polarons in Li2O2 for Li-air batteries

Lithium-air batteries (LABs) are an intriguing next-generation technology due to their high theoretical energy density of similar to 11 kWh/kg. However, LABs are hindered by both poor rate capability and significant polarization in cell voltage, primarily due to the formation of Li2O2 in the air cathode. Here, by employing hybrid density functional theory, we show that the formation of small polarons in Li2O2 limits electron transport. Consequently, the low electron mobility mu = 10(-10)-10(-9) cm(2)/Vs contributes to both the poor rate capability and the polarization that limit the LAB power and energy densities. The self-trapping of electrons in the small polarons arises from the molecular nature of the conduction band states of Li2O2 and the strong spin polarization of the O 2p state. Our understanding of the polaronic electron transport in Li2O2 suggests that designing alternative carrier conduction paths for the cathode reaction could significantly improve the performance of LABs at high current densities.open20

Antimicrobial Resistance in Neisseria gonorrhoeae: Proceedings of the STAR Sexually Transmitted Infection-Clinical Trial Group Programmatic Meeting.

The goal of the Sexually Transmitted Infection Clinical Trial Group's Antimicrobial Resistance (AMR) in Neisseria gonorrhoeae (NG) meeting was to assemble experts from academia, government, nonprofit and industry to discuss the current state of research, gaps and challenges in research and technology and priorities and new directions to address the continued emergence of multidrug-resistant NG infections. Topics discussed at the meeting, which will be the focus of this article, include AMR NG global surveillance initiatives, the use of whole genome sequencing and bioinformatics to understand mutations associated with AMR, mechanisms of AMR, and novel antibiotics, vaccines and other methods to treat AMR NG. Key points highlighted during the meeting include: (i) US and International surveillance programs to understand AMR in NG; (ii) the US National Strategy for combating antimicrobial-resistant bacteria; (iii) surveillance needs, challenges, and novel technologies; (iv) plasmid-mediated and chromosomally mediated mechanisms of AMR in NG; (v) novel therapeutic (eg, sialic acid analogs, factor H [FH]/Fc fusion molecule, monoclonal antibodies, topoisomerase inhibitors, fluoroketolides, LpxC inhibitors) and preventative (eg, peptide mimic) strategies to combat infection. The way forward will require renewed political will, new funding initiatives, and collaborations across academic and commercial research and public health programs

Midgut microbiota of the malaria mosquito vector Anopheles gambiae and Interactions with plasmodium falciparum Infection

The susceptibility of Anopheles mosquitoes to Plasmodium infections relies on complex interactions between the insect vector and the malaria parasite. A number of studies have shown that the mosquito innate immune responses play an important role in controlling the malaria infection and that the strength of parasite clearance is under genetic control, but little is known about the influence of environmental factors on the transmission success. We present here evidence that the composition of the vector gut microbiota is one of the major components that determine the outcome of mosquito infections. A. gambiae mosquitoes collected in natural breeding sites from Cameroon were experimentally challenged with a wild P. falciparum isolate, and their gut bacterial content was submitted for pyrosequencing analysis. The meta-taxogenomic approach revealed a broader richness of the midgut bacterial flora than previously described. Unexpectedly, the majority of bacterial species were found in only a small proportion of mosquitoes, and only 20 genera were shared by 80% of individuals. We show that observed differences in gut bacterial flora of adult mosquitoes is a result of breeding in distinct sites, suggesting that the native aquatic source where larvae were grown determines the composition of the midgut microbiota. Importantly, the abundance of Enterobacteriaceae in the mosquito midgut correlates significantly with the Plasmodium infection status. This striking relationship highlights the role of natural gut environment in parasite transmission. Deciphering microbe-pathogen interactions offers new perspectives to control disease transmission.Institut de Recherche pour le Developpement (IRD); French Agence Nationale pour la Recherche [ANR-11-BSV7-009-01]; European Community [242095, 223601]info:eu-repo/semantics/publishedVersio

When Antibiotics Fail: The Expert Panel on the Potential Socio-Economic Impacts of Antimicrobial Resistance in Canada

Antimicrobials are life savers in Canada, enabling modern healthcare and playing a central role in agriculture. They have reduced the economic, medical, and social burden of infectious diseases and are part of many routine medical interventions, such as caesarean sections, joint replacements, and tonsillectomies. As use of antimicrobials has increased, bacteria evolved to become resistant, resulting in drugs that are no longer effective at treating infections. Antimicrobial resistance (AMR) is increasing worldwide, and with widespread trade and travel, resistance can spread quickly, posing a serious threat to all countries. For Canada, the implications of AMR are stark. When Antibiotics Fail examines the current impacts of AMR on our healthcare system, projects the future impact on Canada’s GDP, and looks at how widespread resistance will influence the day-to-day lives of Canadians. The report examines these issues through a One Health lens, recognizing the interconnected nature of AMR, from healthcare settings to the environment to the agriculture sector. It is the most comprehensive report to date on the economic impact of AMR in Canada

Suv4-20h Histone Methyltransferases Promote Neuroectodermal Differentiation by Silencing the Pluripotency-Associated Oct-25 Gene

Post-translational modifications (PTMs) of histones exert fundamental roles in regulating gene expression. During development, groups of PTMs are constrained by unknown mechanisms into combinatorial patterns, which facilitate transitions from uncommitted embryonic cells into differentiated somatic cell lineages. Repressive histone modifications such as H3K9me3 or H3K27me3 have been investigated in detail, but the role of H4K20me3 in development is currently unknown. Here we show that Xenopus laevis Suv4-20h1 and h2 histone methyltransferases (HMTases) are essential for induction and differentiation of the neuroectoderm. Morpholino-mediated knockdown of the two HMTases leads to a selective and specific downregulation of genes controlling neural induction, thereby effectively blocking differentiation of the neuroectoderm. Global transcriptome analysis supports the notion that these effects arise from the transcriptional deregulation of specific genes rather than widespread, pleiotropic effects. Interestingly, morphant embryos fail to repress the Oct4-related Xenopus gene Oct-25. We validate Oct-25 as a direct target of xSu4-20h enzyme mediated gene repression, showing by chromatin immunoprecipitaton that it is decorated with the H4K20me3 mark downstream of the promoter in normal, but not in double-morphant, embryos. Since knockdown of Oct-25 protein significantly rescues the neural differentiation defect in xSuv4-20h double-morphant embryos, we conclude that the epistatic relationship between Suv4-20h enzymes and Oct-25 controls the transit from pluripotent to differentiation-competent neural cells. Consistent with these results in Xenopus, murine Suv4-20h1/h2 double-knockout embryonic stem (DKO ES) cells exhibit increased Oct4 protein levels before and during EB formation, and reveal a compromised and biased capacity for in vitro differentiation, when compared to normal ES cells. Together, these results suggest a regulatory mechanism, conserved between amphibians and mammals, in which H4K20me3-dependent restriction of specific POU-V genes directs cell fate decisions, when embryonic cells exit the pluripotent state

A lived experience co-designed study protocol for a randomised control trial: the Attempted Suicide Short Intervention Program (ASSIP) or Brief Cognitive Behavioural Therapy as additional interventions after a suicide attempt compared to a standard Suicide Prevention Pathway (SPP)

BACKGROUND: Despite being preventable, suicide is a leading cause of death and a major global public health problem. For every death by suicide, many more suicide attempts are undertaken, and this presents as a critical risk factor for suicide. Currently, there are limited treatment options with limited underpinning research for those who present to emergency departments with suicidal behaviour. The aim of this study is to assess if adding one of two structured suicide-specific psychological interventions (Attempted Suicide Short Intervention Program [ASSIP] or Brief Cognitive Behavioural Therapy [CBT] for Suicide Prevention) to a standardised clinical care approach (Suicide Prevention Pathway [SPP]) improves the outcomes for consumers presenting to a Mental Health Service with a suicide attempt. METHODS: This is a randomised controlled trial with blinding of those assessing the outcomes. People who attempt suicide or experience suicidality after a suicide attempt, present to the Gold Coast Mental Health and Specialist Services, are placed on the Suicide Prevention Pathway (SPP), and meet the eligibility criteria, are offered the opportunity to participate. A total of 411 participants will be recruited for the study, with 137 allocated to each cohort (participants are randomised to SPP, ASSIP + SPP, or CBT + SPP). The primary outcomes of this study are re-presentation to hospitals with suicide attempts. Presentations with suicidal ideation will also be examined (in a descriptive analysis) to ascertain whether a rise in suicidal ideation is commensurate with a fall in suicide attempts (which might indicate an increase in help-seeking behaviours). Death by suicide rates will also be examined to ensure that representations with a suicide attempt are not due to participants dying, but due to a potential improvement in mental health. For participants without a subsequent suicide attempt, the total number of days from enrolment to the last assessment (24 months) will be calculated. Self-reported levels of suicidality, depression, anxiety, stress, resilience, problem-solving skills, and self- and therapist-reported level of therapeutic engagement are also being examined. Psychometric data are collected at baseline, end of interventions, and 6,12, and 24 months. DISCUSSION: This project will move both ASSIP and Brief CBT from efficacy to effectiveness research, with clear aims of assessing the addition of two structured psychological interventions to treatment as usual, providing a cost-benefit analysis of the interventions, thus delivering outcomes providing a clear pathway for rapid translation of successful interventions. TRIALS REGISTRATION: ClinicalTrials.govNCT04072666. Registered on 28 August 201

'To live and die [for] Dixie': Irish civilians and the Confederate States of America

Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism