Inter-individual differences in the nutrition response:from research to recommendations

The 2019 Nutrition Society Spring Conference, which convened in Dundee, focused on the challenges presented by inter-individual differences in the responses to nutrition and in conducting nutritional research. The programme brought together national and international experts to discuss the collective evidence on inter-individual nutritional responses and impacts on health. Speakers and delegates from across the UK, Europe and the USA debated new methods of conducting research in nutrition and discussed the development of appropriate dietary interventions to maintain health and prevent disease in diverse populations. Symposium 1 focused on the effects of ethnicity on nutrient availability and type 2 diabetes and cardio-metabolic disease. Symposium 2 explored sex differences in nutrient availability and health and metabolism. The final symposium examined genetic and phenotypic variation, nutrition and health. The meeting ended with a panel discussion about how we take research to recommendations and concluded with a need to consider inter-individual differences in planning, conducting and analysing nutritional research.</p

Challenges and opportunities in the development of novel antimicrobial therapeutics for cystic fibrosis

Chronic respiratory infection is the primary driver of mortality in individuals with cystic fibrosis (CF). Existing drug screening models utilised in preclinical antimicrobial development are unable to mimic the complex CF respiratory environment. Consequently, antimicrobials showing promising activity in preclinical models often fail to translate through to clinical efficacy in people with CF. Model systems used in CF anti-infective drug discovery and development range from antimicrobial susceptibility testing in nutrient broth, through to 2D and 3D in vitro tissue culture systems and in vivo models. No single model fully recapitulates every key aspect of the CF lung. To improve the outcomes of people with CF (PwCF) it is necessary to develop a set of preclinical models that collectively recapitulate the CF respiratory environment to a high degree of accuracy. Models must be validated for their ability to mimic aspects of the CF lung and associated lung infection, through evaluation of biomarkers that can also be assessed following treatment in the clinic. This will give preclinical models greater predictive power for identification of antimicrobials with clinical efficacy. The landscape of CF is changing, with the advent of modulator therapies that correct the function of the CFTR protein, while antivirulence drugs and phage therapy are emerging alternative treatments to chronic infection. This review discusses the challenges faced in current antimicrobial development pipelines, including the advantages and disadvantages of current preclinical models and the impact of emerging treatments

Primary reading exercises for use with the Durrell Analysis of Reading Difficulty

Thesis (Ed.M.)--Boston Universit

Secondary messenger signalling influences Pseudomonas aeruginosa adaptation to sinus and lung environments

Pseudomonas aeruginosa is a cause of chronic respiratory tract infections in people with cystic fibrosis (CF), non-CF bronchiectasis, and chronic obstructive pulmonary disease. Prolonged infection allows the accumulation of mutations and horizontal gene transfer, increasing the likelihood of adaptive phenotypic traits. Adaptation is proposed to arise first in bacterial populations colonizing upper airway environments. Here, we model this process using an experimental evolution approach. Pseudomonas aeruginosa PAO1, which is not airway adapted, was serially passaged, separately, in media chemically reflective of upper or lower airway environments. To explore whether the CF environment selects for unique traits, we separately passaged PAO1 in airway-mimicking media with or without CF-specific factors. Our findings demonstrated that all airway environments-sinus and lungs, under CF and non-CF conditions-selected for loss of twitching motility, increased resistance to multiple antibiotic classes, and a hyper-biofilm phenotype. These traits conferred increased airway colonization potential in an in vivo model. CF-like conditions exerted stronger selective pressures, leading to emergence of more pronounced phenotypes. Loss of twitching was associated with mutations in type IV pili genes. Type IV pili mediate surface attachment, twitching, and induction of cAMP signalling. We additionally identified multiple evolutionary routes to increased biofilm formation involving regulation of cyclic-di-GMP signalling. These included the loss of function mutations in bifA and dipA phosphodiesterase genes and activating mutations in the siaA phosphatase. These data highlight that airway environments select for traits associated with sessile lifestyles and suggest upper airway niches support emergence of phenotypes that promote establishment of lung infection.</p

Secondary messenger signalling influences Pseudomonas aeruginosa adaptation to sinus and lung environments.

Pseudomonas aeruginosa is a cause of chronic respiratory tract infections in people with cystic fibrosis (CF), non-CF bronchiectasis and chronic obstructive pulmonary disease. Prolonged infection allows accumulation of mutations and horizontal gene transfer, increasing the likelihood of adaptive phenotypic traits. Adaptation is proposed to arise first in bacterial populations colonising upper airway environments. Here, we model this process using an experimental evolution approach. P. aeruginosa PAO1, which is not airway adapted, was serially passaged, separately, in media chemically reflective of upper or lower airway environments. To explore whether the CF environment selects for unique traits, we separately passaged PAO1 in airway-mimicking media with or without CF-specific factors. Our findings demonstrated that all airway environments - sinus and lungs, under CF and non-CF conditions - selected for loss of twitching motility, increased resistance to multiple antibiotic classes and a hyper-biofilm phenotype. These traits conferred increased airway colonisation potential in an in vivo model. CF-like conditions exerted stronger selective pressures, leading to emergence of more pronounced phenotypes. Loss of twitching was associated with mutations in type IV pili genes. Type IV pili mediate surface attachment, twitching and induction of cAMP signalling. We additionally identified multiple evolutionary routes to increased biofilm formation involving regulation of cyclic-di-GMP signalling. These included loss of function mutations in bifA and dipA phosphodiesterase genes and activating mutations in the siaA phosphatase. These data highlight that airway environments select for traits associated with sessile lifestyles and suggest upper airway niches support emergence of phenotypes that promote establishment of lung infection

Characteristics and outcome of infants with candiduria in neonatal intensive care - a Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study

<p>Abstract</p> <p>Background</p> <p>There is limited information in the literature on the presentation and prognosis of candidal urinary tract infection (UTI) in infants in the neonatal intensive care unit (NICU).</p> <p>Methods</p> <p>This was a prospective cohort study performed in 13 Canadian NICUs. Infants with candidal UTI without extra-renal candidal infection at presentation were enrolled.</p> <p>Results</p> <p>Thirty infants fit the study criteria. Median birth weight and gestational age were 2595 grams (range 575-4255) and 35 weeks (range 24-41) with 10 infants being < 30 weeks gestation. The most common primary underlying diagnosis was congenital heart disease (n = 10). The median age at initial diagnosis was 16 days (range 6-84 days). Renal ultrasonography findings were compatible with possible fungal disease in 15 of the 26 infants (58%) in whom it was performed. Treatment was variable, but fluconazole and either amphotericin B deoxycholate or lipid-based amphotericin B in combination or sequentially were used most frequently. Extra-renal candidiasis subsequently developed in 4 infants. In 2 of these 4 infants, dissemination happened during prolonged courses of anti-fungal therapy. Three of 9 deaths were considered to be related to candidal infection. No recurrences of candiduria or episodes of invasive candidiasis following treatment were documented.</p> <p>Conclusion</p> <p>Candidal UTI in the NICU population occurs both in term infants with congenital abnormalities and in preterm infants, and is associated with renal parenchymal disease and extra-renal dissemination. A wide variation in clinical approach was documented in this multicenter study. The overall mortality rate in these infants was significant (30%). In one third of the deaths, <it>Candida </it>infection was deemed to be a contributing factor, suggesting the need for antifungal therapy with repeat evaluation for dissemination in infants who are slow to respond to therapy.</p

Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available

A warm Jet in a cold ocean

Unprecedented quantities of heat are entering the Pacific sector of the Arctic Ocean through Bering Strait, particularly during summer months. Though some heat is lost to the atmosphere during autumn cooling, a significant fraction of the incoming warm, salty water subducts (dives beneath) below a cooler fresher layer of near-surface water, subsequently extending hundreds of kilometers into the Beaufort Gyre. Upward turbulent mixing of these sub-surface pockets of heat is likely accelerating sea ice melt in the region. This Pacific-origin water brings both heat and unique biogeochemical properties, contributing to a changing Arctic ecosystem. However, our ability to understand or forecast the role of this incoming water mass has been hampered by lack of understanding of the physical processes controlling subduction and evolution of this this warm water. Crucially, the processes seen here occur at small horizontal scales not resolved by regional forecast models or climate simulations; new parameterizations must be developed that accurately represent the physics. Here we present novel high resolution observations showing the detailed process of subduction and initial evolution of warm Pacific-origin water in the southern Beaufort Gyre

White Matter Hyperintensities in Vascular Contributions to Cognitive Impairment and Dementia (VCID): Knowledge Gaps and Opportunities

White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer\u27s disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMHs? What do WMHs signify in people diagnosed with AD? What are the risk factors for developing WMHs? What preventive and therapeutic strategies target WMHs? Answering these questions will improve prevention and treatment of WMHs and dementia

Crop Updates 1999 - Lupins

This article contains twenty three papers 1998 LUPIN HIGHLIGHTS LUPIN ANTHRACNOSE 1. Anthracnose overview, Greg Shea, Geoff Thomas and Mark Sweetingham, Agriculture Western Australia 2. Anthracnose – Critical seed infection levels for resistant and susceptible varieties, Geoff Thomas, Mark Sweetingham, Bill O\u27Neill and Greg Shea, Agriculture Western Australia 3. Fungicide seed treatment for anthracnose and brown spot control in lupin, G. Thomas and M. Sweetingham, Agriculture Western Australia LUPIN BREEDING AND AGRONOMY 4. Anthracnose resistance in lupins – an innovative Australian research effort 1996-1998, Wallace Cowling1\u272, Bevan Buirchell1,2 Mark Sweetinqham1,2, Hua\u27an Yang2, Geoff Thomas 1, David Luckett3, Allan Brown4 and John Hamblin2, 1 Agriculture Western Australia, 2 Centre for Legumes in Mediterranean Agriculture, University of Western Australia, 3 NSW Agriculture, Agricultural Institute, Wagga Wagga, NSW, 4 Consultant, 16 Rochester Way, Dianella, WA 5. Gene transfer to pulses: Challenges through 1989-99. Joanne E. Barton, Centre for Legumes in Mediterranean Agriculture, University of Western Australia 6. Can we select for restricted branching in narrow-leafed lupin (Lupinus angustifolius) Kedar Adhikari1, Nick Galwey1and Miles Dracup2, 1Plant Sciences, Faculty of Agriculture, The University of Western Australia,2 Agriculture Western Australia 7. Getting the beat out of new lupin varieties, Dr Bob French, Grain Legume Agronomist, Agriculture Western Australia 8. Starter nitrogen on lupins, Dr Bob French, Grain Legume Agronomist, Agriculture Western Australia APHIDS AND VIRUS CONTROL 9. Forecasting aphid and virus risk in lupins, Debbie Thackray and Roger Jones, CRC for Legumes in Mediterranean Agriculture and Agriculture Western Australia 10. Screening for resistance to cucumber mosaic virus in lupins, Roger Jones, Brenda Coutts, Narelle Reeve, Wallace Cowling and Bevan Buirchell, Agriculture Western Australia and CRC for Legumes in Mediterranean Agriculture 11. The non-necrotic strain of bean yellow mosaic virus spreads faster than the necrotic strain in lupins, Y. Cheng 1 and R.A.C. Jones 1•2, 1 Cooperative Research Centre for Legumes in Mediterranean Agriculture, 2 Agriculture Western Australia 12. Spraying to control aphid feeding damage increases yields of some lupin varieties and faba bean, Francoise Berlandier and Linnet Cartwright, Entomology, Agriculture Western Australia LUPIN NUTRITION 13. Calculated lime requirements for rotations, James Fisher1, Art Diggle 1•2 and Bill Bowden 1•2, 1 Centre for Legumes in Mediterranean Agriculture, 2 Agriculture Western Australia 14. What does lime do to acidic soils – lupin nutrition, Chris Gazey, Research Officer, Agriculture Western Australia 15. Effect of application method of manganese fertiliser and manganese concentration of seed source on seed yield of lupins grown in the West Midlands, Luigi Moreschi, CSBP Area Manager HERBICIDE TOLERANCE AND WEED CONTROL 16. Herbicide tolerance of lupins, Terry Piper, Weed Science Group, Agriculture Western Australia 17. Weed control in Wodjil yellow lupins, Terry Piper, Weed Science Group, Agriculture Western Australia 18. Herbicide tolerance of new lupin varieties, Peter Newman, Agronomist, Elders Mingenew 19. Control of volunteer canola in lupins, Terry Piper and Dave Nicholson, Weed Science Group, Agriculture Western Australia LUPIN ESTABLISHMENT 20. A new seed pressing system for healthy lupin establishment and productivity, Mohammad Amjad, Glen Riethmuller and Ron Jarvis, Agriculture Western Australia 21. Encouragement for controlled traffic farming in the Northern Wheatbelt, Paul Blackwell, Agriculture Western Australia LUPIN HARVESTING 22. Improved lupin harvesting efficiency with different knife guard extensions, Glen Riethmuller, Agriculture Western Australia LUPIN AND PULSE UTILISATION 23. The value of pulse grains for sheep, C.L. White, CSIRO Division of Animal Productio