Dietary inflammatory index and the aging kidney in older women: a 10‑year prospective cohort study

Purpose: Chronic inflammation plays a role in the pathogenesis of age-related renal disease and the diet can moderate systemic inflammation. The primary objective of this study was to examine the associations between a dietary inflammatory index ( DII®) score and renal function, the trajectory of renal function decline, and renal disease-related hospitalizations and/or mortality over 10 years. Methods: The study was conducted in 1422 Western Australian women without prevalent chronic kidney disease and aged ≥ 70 years. Baseline dietary data, obtained from a validated food frequency questionnaire, were used to calculate a DII score for each individual. Results: In this cohort, the mean [range] DII score was 0.19 [− 6.14 to 6.39]. A higher DII score was associated with poorer renal function at baseline and a greater renal function decline over 10 years; after multivariable adjustments, a one unit higher DII score was associated with a 0.55 mL/min/1.73 m2 lower eGFR at baseline (p = 0.01) and a 0.06 mL/min/1.73 m2 greater annual decline in eGFR over 10 years (p = 0.05). Restricted cubic splines provide evidence of a non-linear association between baseline DII score and risk of a renal disease-related event. Compared to participants in the lowest quintile, those in the highest quintile of DII score were at a higher risk of experiencing a renal disease-related event (adjusted HR 2.06, 95% CI 0.97, 4.37). Conclusion: Recommending an increased consumption of foods with a higher anti-inflammatory potential could form part of a multifaceted approach to reduce the risk of renal disease through diet and lifestyle changes

Opportunities to engage health system leaders in whole systems approaches to physical activity in England

Background: Physical activity plays an important role in maintaining good health and wellbeing, non-communicable disease prevention and can improve healthcare outcomes. Some progress is being made on incorporating physical activity into routine care, but less on engaging health system leaders in the ‘whole systems’ approaches which are increasingly recognised as important for addressing complex public health challenges such as physical inactivity. This commentary builds upon the findings of a recent study and aims to identify opportunities for engaging National Health Service (NHS) systems leaders in whole systems approaches to physical activity. Opportunities for action in England: Pockets of good practice exist from which lessons can be learned, but there are systemic issues that discourage and create barriers, and a need for meaningful engagement, leadership and action at national, regional and local levels. National and regional actors like Sport England, NHS England, health professional bodies, Active Partnerships, the Local Government Association and the Office for Health Improvement and Disparities can encourage and support government and the NHS to change policy drivers, culture and practices. Emerging opportunities include the 2021 White Paper Integration and Innovation, development of local integrated care systems, leadership from health charities and investment in non-clinical interventions (‘social prescribing’). At local level, public health and physical activity specialists and other organisations have a key role as champions and facilitators of local whole systems approaches and engagement of local NHS leaderships. Finally, although whole systems action is about collaborative leadership, individual champions of physical activity can make a difference in influencing NHS leaders at every level towards whole systems working

Suppressor of cytokine signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling

© Kedzierski et al. Influenza virus infections have a significant impact on global human health. Individuals with suppressed immunity, or suffering from chronic inflammatory conditions such as COPD, are particularly susceptible to influenza. Here we show that suppressor of cytokine signaling (SOCS) five has a pivotal role in restricting influenza A virus in the airway epithelium, through the regulation of epidermal growth factor receptor (EGFR). Socs5-deficient mice exhibit heightened disease severity, with increased viral titres and weight loss. Socs5 levels were differentially regulated in response to distinct influenza viruses (H1N1, H3N2, H5N1 and H11N9) and were reduced in primary epithelial cells from COPD patients, again correlating with increased susceptibility to influenza. Importantly, restoration of SOCS5 levels restricted influenza virus infection, suggesting that manipulating SOCS5 expression and/or SOCS5 targets might be a novel therapeutic approach to influenza

Treatment and Intervention for Opiate Dependence in the United Kingdom:Lessons from Triumph and Failure

The history of opiate treatment in the United Kingdom (UK) since the early 1980s is a rich source of learning about the benefits and pitfalls of drug treatment policy. We present five possible lessons to be learnt about how factors outside the clinic, including government, charities and researchers can influence treatment and outcomes. First, do not let a crisis go to waste. The philosophical shift from abstinence to harm reduction in the 1980s, in response to an HIV outbreak in injecting users, facilitated expansion in addiction services and made a harm reduction approach more acceptable. Second, studies of drug-related deaths can lead to advances in care. By elucidating the pattern of mortality, and designing interventions to address the causes, researchers have improved patient safety in certain contexts, though significant investment in Scotland has not arrested rising mortality. Third, collection of longitudinal data and its use to inform clinical guidelines, as pursued from the mid-1990s, can form an enduring evidence base and shape policy, sometimes in unintended ways. Fourth, beware of the presentation of harm reduction and recovery as in conflict. At the least, this reduces patient choice, and at worst, it has caused some services to be redesigned in a manner that jeopardises patient safety. Fifth, the relationship between the third and state sectors must be carefully nurtured. In the UK, early collaboration has been replaced by competition, driven by changes in funding, to the detriment of service provision

Gaze sensitivity: function and mechanisms from sensory and cognitive perspectives

Sensitivity to the gaze of other individuals has long been a primary focus in sociocognitive research on humans and other animals. Information about where others are looking may often be of adaptive value in social interactions and predator avoidance, but studies across a range of taxa indicate there are substantial differences in the extent to which animals obtain and use information about other individuals' gaze direction. As the literature expands, it is becoming increasingly difficult to make comparisons across taxa as experiments adopt and adjust different methodologies to account for differences between species in their socioecology, sensory systems and possibly also their underlying cognitive mechanisms. Furthermore, as more species are found to exhibit gaze sensitivity, more terminology arises to describe the behaviours. To clarify the field, we propose a restricted nomenclature that defines gaze sensitivity in terms of observable behaviour, independent of the underlying mechanisms. This is particularly useful in nonhuman animal studies where cognitive interpretations are ambiguous. We then describe how socioecological factors may influence whether species will attend to gaze cues, and suggest links between ultimate factors and proximate mechanisms such as cognition and perception. In particular, we argue that variation in sensory systems, such as retinal specializations and the position of the eyes, will determine whether gaze cues (e.g. head movement) are perceivable during visual fixation. We end by making methodological recommendations on how to apply these variations in socioecology and visual systems to advance the field of gaze research

Early Priming Minimizes the Age-Related Immune Compromise of CD8+ T Cell Diversity and Function

The elderly are particularly susceptible to influenza A virus infections, with increased occurrence, disease severity and reduced vaccine efficacy attributed to declining immunity. Experimentally, the age-dependent decline in influenza-specific CD8+ T cell responsiveness reflects both functional compromise and the emergence of ‘repertoire holes’ arising from the loss of low frequency clonotypes. In this study, we asked whether early priming limits the time-related attrition of immune competence. Though primary responses in aged mice were compromised, animals vaccinated at 6 weeks then challenged >20 months later had T-cell responses that were normal in magnitude. Both functional quality and the persistence of ‘preferred’ TCR clonotypes that expand in a characteristic immunodominance hierarchy were maintained following early priming. Similar to the early priming, vaccination at 22 months followed by challenge retained a response magnitude equivalent to young mice. However, late priming resulted in reduced TCRβ diversity in comparison with vaccination earlier in life. Thus, early priming was critical to maintaining individual and population-wide TCRβ diversity. In summary, early exposure leads to the long-term maintenance of memory T cells and thus preserves optimal, influenza-specific CD8+ T-cell responsiveness and protects against the age-related attrition of naïve T-cell precursors. Our study supports development of vaccines that prime CD8+ T-cells early in life to elicit the broadest possible spectrum of CD8+ T-cell memory and preserve the magnitude, functionality and TCR usage of responding populations. In addition, our study provides the most comprehensive analysis of the aged (primary, secondary primed-early and secondary primed-late) TCR repertoires published to date

Net Work: an interactive artwork designed using an interdisciplinary performative approach

In this paper we outline an interdisciplinary col- laborative approach to problem solving that can be characterised as performative as both the goals and solutions develop over time through an open-ended process of trial-and-error. We describe two projects where this methodology has been successfully applied. We first give an overview of the CELL project where the perfor- mative approach led to a significant change in the way that scientist Neil Theise investigated stem cells. The success of this project directly led to the work which is the main focus of this paper: the design of Net Work, an interactive artwork that consists of a grid of autonomous buoys that emit different coloured light in response to the environment and the state of neighbouring buoys. We describe our performative approach to building the Net Work prototype and outline in detail its control system which is based on Ashby’s homeostat model. The paper concludes with a short discussion of some of the benefits and pitfalls of an interdisciplinary collaborative approach to problem solvin

Fifteen years of the Australian imaging, biomarkers and lifestyle (AIBL) study: Progress and observations from 2,359 older adults spanning the spectrum from cognitive normality to Alzheimer\u27s disease

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study commenced in 2006 as a prospective study of 1,112 individuals (768 cognitively normal (CN), 133 with mild cognitive impairment (MCI), and 211 with Alzheimer\u27s disease dementia (AD)) as an \u27Inception cohort\u27 who underwent detailed ssessments every 18 months. Over the past decade, an additional 1247 subjects have been added as an \u27Enrichment cohort\u27 (as of 10 April 2019). Objective: Here we provide an overview of these Inception and Enrichment cohorts of more than 8,500 person-years of investigation. Methods: Participants underwent reassessment every 18 months including comprehensive cognitive testing, neuroimaging (magnetic resonance imaging, MRI; positron emission tomography, PET), biofluid biomarkers and lifestyle evaluations. Results: AIBL has made major contributions to the understanding of the natural history of AD, with cognitive and biological definitions of its three major stages: preclinical, prodromal and clinical. Early deployment of Aβ-amyloid and tau molecular PET imaging and the development of more sensitive and specific blood tests have facilitated the assessment of genetic and environmental factors which affect age at onset and rates of progression. Conclusion: This fifteen-year study provides a large database of highly characterized individuals with longitudinal cognitive, imaging and lifestyle data and biofluid collections, to aid in the development of interventions to delay onset, prevent or treat AD. Harmonization with similar large longitudinal cohort studies is underway to further these aims

Defining functional diversity for lignocellulose degradation in a microbial community using multi-omics studies

Abstract\ud \ud Background\ud Lignocellulose is one of the most abundant forms of fixed carbon in the biosphere. Current industrial approaches to the degradation of lignocellulose employ enzyme mixtures, usually from a single fungal species, which are only effective in hydrolyzing polysaccharides following biomass pre-treatments. While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform “community-level” metabolism of lignocellulose. Single-species approaches are, therefore, likely to miss important aspects of lignocellulose degradation that will be central to optimizing commercial processes.\ud \ud \ud Results\ud Here, we investigated the microbial degradation of wheat straw in liquid cultures that had been inoculated with wheat straw compost. Samples taken at selected time points were subjected to multi-omics analysis with the aim of identifying new microbial mechanisms for lignocellulose degradation that could be applied in industrial pre-treatment of feedstocks. Phylogenetic composition of the community, based on sequenced bacterial and eukaryotic ribosomal genes, showed a gradual decrease in complexity and diversity over time due to microbial enrichment. Taxonomic affiliation of bacterial species showed dominance of Bacteroidetes and Proteobacteria and high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera. The eukaryotic members of the community were enriched in peritrich ciliates from genus Telotrochidium that thrived in the liquid cultures compared to fungal species that were present in low abundance. A targeted metasecretome approach combined with metatranscriptomics analysis, identified 1127 proteins and showed the presence of numerous carbohydrate-active enzymes extracted from the biomass-bound fractions and from the culture supernatant. This revealed a wide array of hydrolytic cellulases, hemicellulases and carbohydrate-binding modules involved in lignocellulose degradation. The expression of these activities correlated to the changes in the biomass composition observed by FTIR and ssNMR measurements.\ud \ud \ud Conclusions\ud A combination of mass spectrometry-based proteomics coupled with metatranscriptomics has enabled the identification of a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks. In addition to the expected carbohydrate-active enzymes, our studies reveal a large number of unknown proteins, some of which may play a crucial role in community-based lignocellulose degradation.This work was funded by Biotechnology and Biological Sciences Research\ud Council (BBSRC) Grants BB/1018492/1, BB/K020358/1 and BB/P027717/1, the\ud BBSRC Network in Biotechnology and Bioenergy BIOCATNET and São Paulo\ud Research Foundation (FAPESP) Grant 10/52362-5. ERdA thanks EMBRAPA\ud Instrumentation São Carlos and Dr. Luiz Alberto Colnago for providing the\ud NMR facility and CNPq Grant 312852/2014-2. The authors would like to thank\ud Deborah Rathbone and Susan Heywood from the Biorenewables Develop‑\ud ment Centre for technical assistance in rRNA amplicon sequencing