Highlights • MVPA is often used to detect static fMRI activation patterns. • Adapting MVPA to time-resolved signals can characterize the dynamics of neural responses. • The temporal generalization ...matrix reveals a repertoire of canonical brain dynamics.
The aim of this meta‐analysis was to quantify the effects of high‐intensity interval training (HIIT) on markers of glucose regulation and insulin resistance compared with control conditions (CON) or ...continuous training (CT). Databases were searched for HIIT interventions based upon the inclusion criteria: training ≥2 weeks, adult participants and outcome measurements that included insulin resistance, fasting glucose, HbA1c or fasting insulin. Dual interventions and participants with type 1 diabetes were excluded. Fifty studies were included. There was a reduction in insulin resistance following HIIT compared with both CON and CT (HIIT vs. CON: standardized mean difference SMD = −0.49, confidence intervals CIs −0.87 to −0.12, P = 0.009; CT: SMD = −0.35, −0.68 to −0.02, P = 0.036). Compared with CON, HbA1c decreased by 0.19% (−0.36 to −0.03, P = 0.021) and body weight decreased by 1.3 kg (−1.9 to −0.7, P < 0.001). There were no statistically significant differences between groups in other outcomes overall. However, participants at risk of or with type 2 diabetes experienced reductions in fasting glucose (−0.92 mmol L⁻¹, −1.22 to −0.62, P < 0.001) compared with CON. HIIT appears effective at improving metabolic health, particularly in those at risk of or with type 2 diabetes. Larger randomized controlled trials of longer duration than those included in this meta‐analysis are required to confirm these results.
In neurological diseases, the actions of microglia, the resident myeloid cells of the CNS parenchyma, may diverge from, or intersect with, those of recruited monocytes to drive immune-mediated ...pathology. However, defining the precise roles of each cell type has historically been impeded by the lack of discriminating markers and experimental systems capable of accurately identifying them. Our ability to distinguish microglia from monocytes in neuroinflammation has advanced with single-cell technologies, new markers and drugs that identify and deplete them, respectively. Nevertheless, the focus of individual studies on particular cell types, diseases or experimental approaches has limited our ability to connect phenotype and function more widely and across diverse CNS pathologies. Here, we critically review, tabulate and integrate the disease-specific functions and immune profiles of microglia and monocytes to provide a comprehensive atlas of myeloid responses in viral encephalitis, demyelination, neurodegeneration and ischemic injury. In emphasizing the differential roles of microglia and monocytes in the severe neuroinflammatory disease of viral encephalitis, we connect inflammatory pathways common to equally incapacitating diseases with less severe inflammation. We examine these findings in the context of human studies and highlight the benefits and inherent limitations of animal models that may impede or facilitate clinical translation. This enables us to highlight common and contrasting, non-redundant and often opposing roles of microglia and monocytes in disease that could be targeted therapeutically.
Diabetes is a disease characterized by a relative or absolute lack of insulin, leading to hyperglycaemia. There are two main types of diabetes: type 1 diabetes and type 2 diabetes. Type 1 diabetes is ...due to an autoimmune destruction of the insulin‐producing pancreatic beta cells, and type 2 diabetes is caused by insulin resistance coupled by a failure of the beta cell to compensate. Animal models for type 1 diabetes range from animals with spontaneously developing autoimmune diabetes to chemical ablation of the pancreatic beta cells. Type 2 diabetes is modelled in both obese and non‐obese animal models with varying degrees of insulin resistance and beta cell failure. This review outlines some of the models currently used in diabetes research. In addition, the use of transgenic and knock‐out mouse models is discussed. Ideally, more than one animal model should be used to represent the diversity seen in human diabetic patients.
LINKED ARTICLES
Animal Models
This paper is the latest in a series of publications on the use of animal models in pharmacology research. Readers might be interested in the previous papers.
Robinson V (2009). Less is more: reducing the reliance on animal models for nausea and vomiting research.
Holmes AM, Rudd JA, Tattersall FD, Aziz Q, Andrews PLR (2009). Opportunities for the replacement of animals in the study of nausea and vomiting.
Giacomotto J and Ségalat L (2010). High‐throughput screening and small animal models, where are we?
McGrath JC, Drummond GB, McLachlan EM, Kilkenny C, Wainwright CL (2010). Guidelines for reporting experiments involving animals: the ARRIVE guidelines.
Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG (2010). The ARRIVE guidelines.
Emerson M (2010). Refinement, reduction and replacement approaches to in vivo cardiovascular research.
Berge O‐G (2011). Predictive validity of behavioural animal models for chronic pain.
Vickers SP, Jackson HC and Cheetham SC (2011). The utility of animal models to evaluate novel anti‐obesity agents.
Percie du Sert N, Holmes AM, Wallis R, Andrews PLR (2012). Predicting the emetic liability of novel chemical entities: a comparative study.
The complete series including future publications, as they occur, can be found at http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1476‐5381/homepage/animal_models.htm.
Renal cyst development and expansion in autosomal dominant polycystic kidney disease (ADPKD) involves both fluid secretion and abnormal proliferation of cyst-lining epithelial cells. The chloride ...channel of the cystic fibrosis transmembrane conductance regulator (CFTR) participates in secretion of cyst fluid, and the mammalian target of rapamycin (mTOR) pathway may drive proliferation of cyst epithelial cells. CFTR and mTOR are both negatively regulated by AMP-activated protein kinase (AMPK). Metformin, a drug in wide clinical use, is a pharmacological activator of AMPK. We find that metformin stimulates AMPK, resulting in inhibition of both CFTR and the mTOR pathways. Metformin induces significant arrest of cystic growth in both in vitro and ex vivo models of renal cystogenesis. In addition, metformin administration produces a significant decrease in the cystic index in two mouse models of ADPKD. Our results suggest a possible role for AMPK activation in slowing renal cystogenesis as well as the potential for therapeutic application of metformin in the context of ADPKD.
To develop methods guidance to support the conduct of rapid reviews (RRs) produced within Cochrane and beyond, in response to requests for timely evidence syntheses for decision-making purposes ...including urgent health issues of high priority.
Interim recommendations were informed by a scoping review of the underlying evidence, primary methods studies conducted, and a survey sent to 119 representatives from 20 Cochrane entities, who were asked to rate and rank RR methods across stages of review conduct. Discussions among those with expertise in RR methods further informed the list of recommendations with accompanying rationales provided.
Based on survey results from 63 respondents (53% response rate), 26 RR methods recommendations are presented for which there was a high or moderate level of agreement or scored highest in the absence of such agreement. Where possible, how recommendations align with Cochrane methods guidance for systematic reviews is highlighted.
The Cochrane Rapid Reviews Methods Group offers new, interim guidance to support the conduct of RRs. Because best practice is limited by the lack of currently available evidence for some RR methods shortcuts taken, this guidance will need to be updated as additional abbreviated methods are evaluated.
Heart failure (HF)-a serious and costly condition-is increasingly prevalent. We estimated the US burden including emergency department (ED) visits, inpatient hospitalizations and associated costs, ...and mortality.
We analyzed 2006 to 2014 data from the Healthcare Cost and Utilization Project Nationwide Emergency Department Sample, the Healthcare Cost and Utilization Project National (nationwide) Inpatient Sample, and the National Vital Statistics System. International Classification of Disease codes identified HF and comorbidities. Burden was estimated separately for ED visits, hospitalizations, and mortality. In addition, criteria were applied to identify total unique acute events. Rates of primary HF (primary diagnosis or underlying cause of death) and comorbid HF (comorbid diagnosis or contributing cause of death) were calculated, age standardized to the 2010 US population. In 2014, there were an estimated 1 068 412 ED visits, 978 135 hospitalizations, and 83 705 deaths with primary HF. There were 4 071 546 ED visits, 3 370 856 hospitalizations, and 230 963 deaths with comorbid HF. Between 2006 and 2014, the total unique acute event rate for primary HF declined from 536 to 449 per 100 000 (relative percent change of -16%; P for trend, <0.001) but increased for comorbid HF from 1467 to 1689 per 100 000 (relative percentage change, 15%; P for trend, <0.001). HF-related mortality decreased significantly from 2006 to 2009 but did not change meaningfully after 2009. For hospitalizations with primary HF, the estimated mean cost was $11 552 in 2014, totaling an estimated $11 billion.
Given substantial healthcare and mortality burden of HF, rising healthcare costs, and the aging US population, continued improvements in HF prevention, management, and surveillance are important.
Emotions evoked by products mainly enhance the pleasure of buying, owning, and using them. More recently, food-elicited emotion is increasingly becoming critical for product differentiation as many ...food products are produced with similar characteristics, packaging, and price. Attempts to measure emotions have been done in the psychology and sociology fields, but measurement of food-elicited emotions is more recent and not well established. This review paper discusses emotion lexicon development, measurement of food-elicited emotions, some factors affecting emotional responses to foods, how emotions affect eating behavior, and how this information can be utilized for marketing and increasing acceptability of foods.
•Emotions are elicited by food.•Emotions are associated with eating behavior and purchase intent of foods.•Sensory, food type, psychological state and experience associate with emotional response to food.•Lexicons/measurement method of emotions elicited by food are important for representative data.
The multiscale nature of turbulent combustion necessitates accurate and computationally efficient methods for direct numerical simulations (DNS). The field has long been dominated by high-order ...finite differences, which lack the flexibility and adaptivity for simulations of complex geometries and flame-turbulence-structure interactions in realistic settings. In this work I introduce a new approach to DNS of premixed combustion, based on a high-order mesh-free discretisation in combination with finite differences, enabling high-order simulations in non-trivial geometries. The approach is validated against a range of two- and three-dimensional flows, both laminar and turbulent, and reacting and inert. The present method (a) has the resolving power for DNS of both laminar flames and inert turbulence with comparable accuracy to high-order finite differences, (b) can capture the dynamics of unsteady bluff body stabilised flames, and (c) is capable of simulating flame-turbulence interactions, with results comparing qualitatively well with published data. This work paves the way for DNS of combustion in complex geometries, offering an alternative approach to methods based on structured grids with immersed boundaries, or unstructured meshes. Further studies with the present method are proposed, which will aid understanding of fundamental flame dynamics in non-trivial geometries. Planned developments in adaptivity and extension of the mesh-free construction to all three dimensions will increase the value of the method, and support the push towards DNS of real geometries.
•A mesh-free approach to direct numerical simulations (DNS) of combustion.•Capable of spatially varying resolution and complex geometries, without loss of accuracy.•Extremely high order (up to 10th) difference schemes on unstructured disordered node sets.•Coupled with high-order finite differences for efficient three-dimensional simulations.•Solves the fully compressible multi-species reacting Navier–Stokes equations with finite rate chemistry.
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