Automated diagnosis of tuberculosis (TB) from chest X-Rays (CXR) has been tackled with either hand-crafted algorithms or machine learning approaches such as support vector machines (SVMs) and ...convolutional neural networks (CNNs). Most deep neural network applied to the task of tuberculosis diagnosis have been adapted from natural image classification. These models have a large number of parameters as well as high hardware requirements, which makes them prone to overfitting and harder to deploy in mobile settings. We propose a simple convolutional neural network optimized for the problem which is faster and more efficient than previous models but preserves their accuracy. Moreover, the visualization capabilities of CNNs have not been fully investigated. We test saliency maps and grad-CAMs as tuberculosis visualization methods, and discuss them from a radiological perspective.
Large prospective cohort studies consistently show associations of a high dietary fiber intake (>25 g/d in women and >38 g/d in men) with a 20–30% reduced risk of developing type 2 diabetes (T2D), ...after correction for confounders. It is less well recognized that these effects appear to be mainly driven by high intakes of whole grains and insoluble cereal fibers, which typically are nonviscous and do not relevantly influence postprandial glucose responses i.e., glycemic index (GI) or are strongly fermented by the gut microbiota in the colon. In contrast, a dietary focus on soluble, viscous, gel-forming, more readily fermentable fiber intakes derived from fruit and certain vegetables yields mixed results and generally does not appear to reduce T2D risk. Although disentangling types of fiber-rich foods and separating these from possible effects related to the GI is an obvious challenge, the common conclusion that key metabolic effects of high-fiber intake are explained by mechanisms that should mainly apply to the soluble, viscous type can be challenged. More recently, studies in humans and animal models focused on gaining mechanistic insights into why especially high-cereal-fiber (HCF) diets appear to improve insulin resistance (IR) and diabetes risk. Although effects of HCF diets on weight loss are only moderate and comparable to other types of dietary fibers, possible novel mechanisms have emerged, which include the prevention of the absorption of dietary protein and modulation of the amino acid metabolic signature. Here we provide an update of our previous review from 2008, with a focus on mechanistic insights of how HCF diets may improve IR and the risk of developing T2D.
The Health Benefits of Dietary Fibre Barber, Thomas M; Kabisch, Stefan; Pfeiffer, Andreas F H ...
Nutrients,
10/2020, Letnik:
12, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Dietary fibre consists of non-digestible forms of carbohydrate, usually as polysaccharides that originate from plant-based foods. Over recent decades, our diet within Westernised societies has ...changed radically from that of our hominid ancestors, with implications for our co-evolved gut microbiota. This includes increased ingestion of ultra-processed foods that are typically impoverished of dietary fibre, and associated reduction in the intake of fibre-replete plant-based foods. Over recent decades, there has been a transformation in our understanding of the health benefits of dietary fibre.
To explore the current medical literature on the health benefits of dietary fibre, with a focus on overall metabolic health.
We performed a narrative review, based on relevant articles written in English from a PubMed search, using the terms 'dietary fibre and metabolic health'.
In the Western world, our diets are impoverished of fibre. Dietary fibre intake associates with overall metabolic health (through key pathways that include insulin sensitivity) and a variety of other pathologies that include cardiovascular disease, colonic health, gut motility and risk for colorectal carcinoma. Dietary fibre intake also correlates with mortality. The gut microflora functions as an important mediator of the beneficial effects of dietary fibre, including the regulation of appetite, metabolic processes and chronic inflammatory pathways.
Multiple factors contribute to our fibre-impoverished modern diet. Given the plethora of scientific evidence that corroborate the multiple and varied health benefits of dietary fibre, and the risks associated with a diet that lacks fibre, the optimization of fibre within our diets represents an important public health strategy to improve both metabolic and overall health. If implemented successfully, this strategy would likely result in substantial future health benefits for the population.
The incretin hormones glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) have their main physiological role in augmenting insulin secretion after their ...nutrient‐induced secretion from the gut. A functioning entero‐insular (gut‐endocrine pancreas) axis is essential for the maintenance of a normal glucose tolerance. This is exemplified by the incretin effect (greater insulin secretory response to oral as compared to “isoglycaemic” intravenous glucose administration due to the secretion and action of incretin hormones). GIP and GLP‐1 have additive effects on insulin secretion. Local production of GIP and/or GLP‐1 in islet α‐cells (instead of enteroendocrine K and L cells) has been observed, and its significance is still unclear. GLP‐1 suppresses, and GIP increases glucagon secretion, both in a glucose‐dependent manner. GIP plays a greater physiological role as an incretin. In type 2‐diabetic patients, the incretin effect is reduced despite more or less normal secretion of GIP and GLP‐1. While insulinotropic effects of GLP‐1 are only slightly impaired in type 2 diabetes, GIP has lost much of its acute insulinotropic activity in type 2 diabetes, for largely unknown reasons. Besides their role in glucose homoeostasis, the incretin hormones GIP and GLP‐1 have additional biological functions: GLP‐1 at pharmacological concentrations reduces appetite, food intake, and—in the long run—body weight, and a similar role is evolving for GIP, at least in animal studies. Human studies, however, do not confirm these findings. GIP, but not GLP‐1 increases triglyceride storage in white adipose tissue not only through stimulating insulin secretion, but also by interacting with regional blood vessels and GIP receptors. GIP, and to a lesser degree GLP‐1, play a role in bone remodelling. GLP‐1, but not GIP slows gastric emptying, which reduces post‐meal glycaemic increments. For both GIP and GLP‐1, beneficial effects on cardiovascular complications and neurodegenerative central nervous system (CNS) disorders have been observed, pointing to therapeutic potential over and above improving diabetes complications. The recent finding that GIP/GLP‐1 receptor co‐agonists like tirzepatide have superior efficacy compared to selective GLP‐1 receptor agonists with respect to glycaemic control as well as body weight has renewed interest in GIP, which previously was thought to be without any therapeutic potential. One focus of this research is into the long‐term interaction of GIP and GLP‐1 receptor signalling. A GLP‐1 receptor antagonist (exendin 9‐39) and, more recently, a GIP receptor agonist (GIP 3‐30 NH2) and, hopefully, longer‐acting GIP receptor agonists for human use will be helpful tools to shed light on the open questions. A detailed knowledge of incretin physiology and pathophysiology will be a prerequisite for designing more effective incretin‐based diabetes drugs.
There is a growing interest in the role of inflammageing for chronic disease development. Cytokines are potent soluble immune mediators that can be used as target biomarkers of inflammageing; ...however, their measurement in human samples has been challenging. This study aimed to assess the reliability of a pro- and anti-inflammatory cytokine panel in a sample of healthy people measured with a novel electrochemiluminescent multiplex immunoassay platform (Meso Scale Discovery, MSD), and to characterize their associations with metabolic and inflammatory phenotypes.
Overall, the majority of cytokines were above the limit of detection (in at least 85.3% of the samples). Cytokines IL-6, IL-8, TNF-α, IL-10, IL-13, and IFN-γ showed overall good to fair reliability (ICC > 0.40), whereas IL-1β, IL-2, IL-4, and IL-12p70 showed poor reliability (ICC < 0.40). The reliability estimates were not substantially influenced by participants' age, sex, obesity and C-reactive protein (CRP) levels. As expected, cytokine concentrations were elevated with advanced age most pronouncedly for IL-6, IL-8, Il-2, IFN- γ, and TNF-α. No major associations with metabolic phenotypes were observed for most cytokines, with the exception of a positive association between IL-6 and TNF-α with body mass index and CRP (ρ: 0.36; ρ: 0.20; ρ: 0.53; ρ: 0.22, respectively), and IFN-γ and IL-10 with CRP (ρ: 0.23 and ρ: 0.19, respectively).
Single measurements of selected cytokines using MSD platform, including IL-6, IL-8, IL-10, IL-13, TNF-α, and IFN-γ have shown to be representative of an individual's average level over time and could be suitable for use in prospective epidemiological and clinical studies. Such studies are highly warranted to characterize associations of cytokines with phenotypes and diseases associated with ageing.
Overweight adults who had lost weight on a low-calorie diet were randomly assigned to a maintenance diet and followed for 26 weeks. Diets with a higher protein content, a lower glycemic index, or ...both appeared to improve the diet-completion rate and weight-loss maintenance.
The importance of the composition of a diet for the prevention and management of obesity is debated. Ad libitum consumption of low-fat diets results in short-term weight loss,
1
and low-carbohydrate, high-protein, and high-fat diets (e.g., the Atkins diet) may result in substantial weight loss as compared with that achieved with other types of diets.
2
However, the weight loss is generally not sustained beyond 1 year.
3
Greater weight loss with low-carbohydrate diets may be ascribed to the satiating effects of high protein content,
4
and there is increasing interest in the efficacy of diets that have a high protein content with a . . .
Context:
Measurement of IGF-I is a cornerstone in diagnosis and monitoring of GH-related diseases, but considerable discrepancies exist between analytical methods. A recent consensus conference ...defined criteria for validation of IGF-I assays and for establishment of normative data.
Objectives:
Our objectives were development and validation of a novel automated IGF-I immunoassay (iSYS; Immunodiagnostic Systems) according to international guidelines and establishment of method-specific age- and sex-adjusted reference intervals and analysis of their robustness.
Setting and Participants:
We conducted a multicenter study with samples from 12 cohorts from the United States, Canada, and Europe including 15 014 subjects (6697 males and 8317 females, 0–94 years of age).
Main Outcome Measures:
We measured concentrations of IGF-I as determined by the IDS iSYS IGF-I assay.
Results:
A new IGF-I assay calibrated against the recommended standard (02/254) and insensitive to the 6 high-affinity IGF binding proteins was developed and rigorously validated. Age- and sex-adjusted reference intervals derived from a uniquely large cohort reflect the age-related pattern of IGF-I secretion: a decline immediately after birth followed by an increase until a pubertal peak (at 15 years of age). Later in life, values decrease continuously. The impact of gender is small, although across the lifespan, women have lower mean IGF-I concentrations. Geographical region, sampling setting (community or hospital based), and rigor of exclusion criteria in our large cohort did not affect the reference intervals.
Conclusions:
Using large cohorts of well-characterized subjects from different centers allowed construction of robust reference ranges for a new automated IGF-I assay. The strict adherence to recent consensus criteria for IGF-I assays might facilitate clinical application of the results.
Summary Our understanding of dysfunction of the gastrointestinal system in patients with Parkinson's disease has increased substantially in the past decade. The entire gastrointestinal tract is ...affected in these patients, causing complications that range from oral issues, including drooling and swallowing problems, to delays in gastric emptying and constipation. Additionally, small intestinal bacterial overgrowth and Helicobacter pylori infection affect motor fluctuations by interfering with the absorption of antiparkinsonian drugs. The multifaceted role of the gastrointestinal system in Parkinson's disease necessitates a specific and detailed assessment and treatment plan. The presence of pervasive α-synuclein deposition in the gastrointestinal tract strongly implicates this system in the pathogenesis of Parkinson's disease. Future studies elucidating the role of the gastrointestinal tract in the pathological progression of Parkinson's disease might hold potential for early disease detection and development of neuroprotective approaches.
The exceptional mechanical properties of the load-bearing connection of tendon to bone rely on an intricate interplay of its biomolecular composition, microstructure and micromechanics. Here we ...identify that the Achilles tendon-bone insertion is characterized by an interface region of ∼500 μm with a distinct fibre organization and biomolecular composition. Within this region, we identify a heterogeneous mechanical response by micromechanical testing coupled with multiscale confocal microscopy. This leads to localized strains that can be larger than the remotely applied strain. The subset of fibres that sustain the majority of loading in the interface area changes with the angle of force application. Proteomic analysis detects enrichment of 22 proteins in the interfacial region that are predominantly involved in cartilage and skeletal development as well as proteoglycan metabolism. The presented mechanisms mark a guideline for further biomimetic strategies to rationally design hard-soft interfaces.
X-ray phase-contrast imaging has recently led to a revolution in resolving power and tissue contrast in biomedical imaging, microscopy and materials science. The necessary high spatial coherence is ...currently provided by either large-scale synchrotron facilities with limited beamtime access or by microfocus X-ray tubes with rather limited flux. X-rays radiated by relativistic electrons driven by well-controlled high-power lasers offer a promising route to a proliferation of this powerful imaging technology. A laser-driven plasma wave accelerates and wiggles electrons, giving rise to a brilliant keV X-ray emission. This so-called betatron radiation is emitted in a collimated beam with excellent spatial coherence and remarkable spectral stability. Here we present a phase-contrast microtomogram of a biological sample using betatron X-rays. Comprehensive source characterization enables the reconstruction of absolute electron densities. Our results suggest that laser-based X-ray technology offers the potential for filling the large performance gap between synchrotron- and current X-ray tube-based sources.
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