Zinc in innate and adaptive tumor immunity

Zinc is important. It is the second most abundant trace metal with 2-4 grams in humans. It is an essential trace element, critical for cell growth, development and differentiation, DNA synthesis, RNA transcription, cell division, and cell activation. Zinc deficiency has adverse consequences during embryogenesis and early childhood development, particularly on immune functioning. It is essential in members of all enzyme classes, including over 300 signaling molecules and transcription factors. Free zinc in immune and tumor cells is regulated by 14 distinct zinc importers (ZIP) and transporters (ZNT1-8). Zinc depletion induces cell death via apoptosis (or necrosis if apoptotic pathways are blocked) while sufficient zinc levels allows maintenance of autophagy. Cancer cells have upregulated zinc importers, and frequently increased zinc levels, which allow them to survive. Based on this novel synthesis, approaches which locally regulate zinc levels to promote survival of immune cells and/or induce tumor apoptosis are in order

Landlabs: An Integrated Approach to Creating Agricultural Enterprises That Meet the Triple Botom Line

Global demand is increasing for food, feed, and fiber; for additional agricultural outputs, such as biofuels; and for ecosystem services, such as clean water and outdoor recreation. In response, new agricultural enterprises are needed that produce more outputs from existing lands while meeting the triple bottom line of high performance in economic, environmental, and social terms. Establishing such enterprises requires coordination and development within three critical domains: landscape configurations (i.e., types and arrangements of land uses), supply/value chains (i.e., processing and utilization), and policy and governance. In this essay, we describe our efforts, as land-grant university scientists, to support coordinated innovation and enterprise development in integrated place-based institutions, which we term landlabs. We describe our experiences in three prototyping efforts and outline key features of landlabs that are emerging from these efforts. Land-grant universities have a central and crucial role to play in organizing and operating landlabs

Rehabilitation following shoulder arthroplasty in the United Kingdom National Health Service: A survey of publicly facing information.

INTRODUCTION:The prevalence of shoulder arthroplasty (SA) is rising, but there is limited research evaluating rehabilitation following SA and whether there is an optimal approach remains unknown. The aim of this study was to understand current National Health Service (NHS) practice for rehabilitation following SA as a platform for conducting much needed further research. METHODS:Two reviewers independently undertook electronic searches for publicly available information sheets (PIS) from websites of NHS Trusts that included detail about rehabilitation following SA, for example, duration of immobilisation. One reviewer extracted data, and a second reviewer verified this. ETHICAL APPROVAL:Not required. RESULTS:Forty-three PIS from 40 Trusts were identified. Twenty-four referred to more than one type of arthroplasty (anatomic, reverse and hemiarthroplasty) but did not describe different approaches to rehabilitation based on prosthesis type. Twenty-five PIS provided some instruction regarding movement restrictions, which varied considerably. All PIS referred to postoperative immobilisation, typically with a sling, with median duration of 4 weeks (range 0 to 8). Thirty-four PIS reported commencing passive exercise immediately. Median time to commencing active exercise was 4 weeks (range 1 to 6) and 5 weeks (range 1 to 16) for resisted exercise. Median time expected to return to driving was 6 weeks (range 3 to 12) and general work 12 weeks (range 3 to 26). CONCLUSION:This study has highlighted significant heterogeneity between rehabilitation approaches following SA, not previously reported in the United Kingdom, with a lack of specific rehabilitation PIS for different prosthesis types. Our results will facilitate evaluation of rehabilitation strategies in future research

Landlabs: An Integrated Approach to Creating Agricultural Enterprises That Meet the Triple Bottom Line

Global demand is increasing for food, feed, and fiber; for additional agricultural outputs, such as biofuels; and for ecosystem services, such as clean water and outdoor recreation. In response, new agricultural enterprises are needed that produce more outputs from existing lands while meeting the triple bottom line of high performance in economic, environmental, and social terms. Establishing such enterprises requires coordination and development within three critical domains: landscape configurations (i.e., types and arrangements of land uses), supply/value chains (i.e., processing and utilization), and policy and governance. In this essay, we describe our efforts, as land-grant university scientists, to support coordinated innovation and enterprise development in integrated place-based institutions, which we term landlabs. We describe our experiences in three prototyping efforts and outline key features of landlabs that are emerging from these efforts. Land-grant universities have a central and crucial role to play in organizing and operating landlabs

Ресурсосберегающая деятельность предприятия: содержание и направления повышения эффективности (на примере филиала Мозырского управления ОАО «Белтеплоизоляция»)

Countries representing more than 90 percent of global greenhouse gas emissions and population have submitted intendednationally determined contributions (INDCs) in anticipation of the 21st COP in Paris. In parallel, developing countries are designing at least 152 nationally appropriate mitigation actions (NAMAs) and 13 have secured implementation funding. Connecting these two concepts, more than a third of developing countries communicate a role for NAMAs in their INDCs.  It is therefore vital to understand the potential role of NAMAs (here understood as specific actions) with respect to INDCs (which are often broader targets) and vice versa. This paper explores the links between NAMAs and INDCs with regard to various elements central to their implementation, including: access to finance; stakeholder engagement; sustainable development impacts; measurement, reporting and verification (MRV); and institutional frameworks. To avoid delaying mitigation action any further, it is important to keep momentum behind NAMAs. They represent one of the few tools at our disposal for countries to undertake mitigation actions, be recognised for these efforts, and mobilise climate finance and investment. The skills and learning on NAMA development can be seen more fundamentally as capacity for the design of bottom-up actions. Attention should be paid now to ensure that this capacity is maintained in the future. To do this, continued attention must be paid to NAMAs in Paris, as a key implementation tool for INDCs and, therefore, a key element of the success of a new global climate agreement

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Trans-Epithelial Immune Cell Transfer during Suckling Modulates Delayed-Type Hypersensitivity in Recipients as a Function of Gender

INTRODUCTION: Breast feeding has long term effects on the developing immune system which outlive passive immunization of the neonate. We have investigated the transfer of milk immune cells and examined the result of transfer once the recipients were adult. METHODS: Non-transgenic mouse pups were foster-nursed by green fluorescent protein (GFP) transgenic dams for 3 weeks and the fate of GFP+ cells was followed by FACS analysis, immunohistochemistry and RT-PCR for GFP and appropriate immune cell markers. Pups suckled by non-transgenic dams served as controls. RESULTS: Despite a preponderance of B cells and macrophages in the stomach contents of the pups, most cells undergoing trans-epithelial migration derived from the 3-4% of milk cells positive for T lymphocyte markers. These cells homed to the spleen and thymus, with maximal accumulation at 3-4 weeks. By sensitizing dams with an antigen which elicits a T cell-mediated delayed-type-hypersensitivity (DTH) response, we determined that nursing by a sensitized dam (compared to a non-sensitized dam) amplified a subsequent DTH response in females and yet suppressed one in males. DISCUSSION: These results suggest that clinical evaluation weighing the pros and cons of nursing male versus female children by mothers with genetically-linked hypersensitivity diseases, such as celiac disease and eczema, or those in regions of the world with endemic DTH-eliciting diseases, such as tuberculosis, may be warranted

Operation Moonshot: rapid translation of a SARS-CoV-2 targeted peptide immunoaffinity liquid chromatography-tandem mass spectrometry test from research into routine clinical use

OBJECTIVES: During 2020, the UK's Department of Health and Social Care (DHSC) established the Moonshot programme to fund various diagnostic approaches for the detection of SARS-CoV-2, the pathogen behind the COVID-19 pandemic. Mass spectrometry was one of the technologies proposed to increase testing capacity. METHODS: Moonshot funded a multi-phase development programme, bringing together experts from academia, industry and the NHS to develop a state-of-the-art targeted protein assay utilising enrichment and liquid chromatography tandem mass spectrometry (LC-MS/MS) to capture and detect low levels of tryptic peptides derived from SARS-CoV-2 virus. The assay relies on detection of target peptides, ADETQALPQRK (ADE) and AYNVTQAFGR (AYN), derived from the nucleocapsid protein of SARS-CoV-2, measurement of which allowed the specific, sensitive, and robust detection of the virus from nasopharyngeal (NP) swabs. The diagnostic sensitivity and specificity of LC-MS/MS was compared with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) via a prospective study. RESULTS: Analysis of NP swabs (n=361) with a median RT-qPCR quantification cycle (Cq) of 27 (range 16.7-39.1) demonstrated diagnostic sensitivity of 92.4% (87.4-95.5), specificity of 97.4% (94.0-98.9) and near total concordance with RT-qPCR (Cohen's Kappa 0.90). Excluding Cq>32 samples, sensitivity was 97.9% (94.1-99.3), specificity 97.4% (94.0-98.9) and Cohen's Kappa 0.95. CONCLUSIONS: This unique collaboration between academia, industry and the NHS enabled development, translation, and validation of a SARS-CoV-2 method in NP swabs to be achieved in 5 months. This pilot provides a model and pipeline for future accelerated development and implementation of LC-MS/MS protein/peptide assays into the routine clinical laboratory

Ten years of external quality assessment (EQA) of Neisseria gonorrhoeae antimicrobial susceptibility testing in Europe elucidate high reliability of data

BACKGROUND: Confidence in any diagnostic and antimicrobial susceptibility testing data is provided by appropriate and regular quality assurance (QA) procedures. In Europe, the European Gonococcal Antimicrobial Susceptibility Programme (Euro-GASP) has been monitoring the antimicrobial susceptibility in Neisseria gonorrhoeae since 2004. Euro-GASP includes an external quality assessment (EQA) scheme as an essential component for a quality-assured laboratory-based surveillance programme. Participation in the EQA scheme enables any problems with the performed antimicrobial susceptibility testing to be identified and addressed, feeds into the curricula of laboratory training organised by the Euro-GASP network, and assesses the capacity of individual laboratories to detect emerging new, rare and increasing antimicrobial resistance phenotypes. Participant performance in the Euro-GASP EQA scheme over a 10 year period (2007 to 2016, no EQA in 2013) was evaluated. METHODS: Antimicrobial susceptibility category and MIC results from the first 5 years (2007-2011) of the Euro-GASP EQA were compared with the latter 5 years (2012-2016). These time periods were selected to assess the impact of the 2012 European Union case definitions for the reporting of antimicrobial susceptibility. RESULTS: Antimicrobial susceptibility category agreement in each year was ≥91%. Discrepancies in susceptibility categories were generally because the MICs for EQA panel isolates were on or very close to the susceptibility or resistance breakpoints. A high proportion of isolates tested over the 10 years were within one (≥90%) or two (≥97%) MIC log2 dilutions of the modal MIC, respectively. The most common method used was Etest on GC agar base. There was a shift to using breakpoints published by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in the latter 5 years, however overall impact on the validity of results was limited, as the percentage categorical agreement and MIC concordance changed very little between the two five-year periods. CONCLUSIONS: The high level of comparability of results in this EQA scheme indicates that high quality data are produced by the Euro-GASP participants and gives confidence in susceptibility and resistance data generated by laboratories performing decentralised testing.The study was funded by the European Centre for Disease Prevention and Control (Framework Contract No. ECDC/2013/015). The funding body contributed to the design of the study, the interpretation of the data and to the writing of the manuscript.S