Background: Although high-quality nutrition systematic reviews (SRs) are important for clinical decision making, there remains debate on their methodological quality and reporting transparency.
Objectives: The objective of this study was to assess the reliability and reproducibility of a sample of SRs produced by the Nutrition Evidence Systematic Review (NESR) team to inform the 2020-2025 Dietary Guidelines for Americans (DGAs).
Methods: We evaluated a sample of 8 SRs from the DGA dietary patterns subcommittee for methodological quality using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) tool and for reporting transparency using the PRISMA 2020 and PRISMA literature search extension (PRISMA-S) checklists.
Mutations of isocitrate dehydrogenase 1 (IDH1) are key biomarkers for glioma classification, but current methods for detection of mutated IDH1 (mIDH1) require invasive tissue sampling and cannot be used for longitudinal studies. Positron emission tomography (PET) imaging with mIDH1-selective radioligands is a promising alternative approach that could enable non-invasive assessment of the IDH status. In the present work, we developed efficient protocols for the preparation of four F-labeled derivatives of the mIDH1-selective inhibitor olutasidenib.
View Article and Find Full Text PDFImaging of the A adenosine receptor (AR) by positron emission tomography (PET) with 8-cyclopentyl-3-(3-[F]fluoropropyl)-1-propyl-xanthine ([F]CPFPX) has been widely used in preclinical and clinical studies. However, this radioligand suffers from rapid peripheral metabolism and subsequent accumulation of radiometabolites in the vascular compartment. In the present work, we prepared four derivatives of CPFPX by replacement of the cyclopentyl group with norbornane moieties.
View Article and Find Full Text PDFTozadenant (4-hydroxy--(4-methoxy-7-morpholinobenzo[]thiazol-2-yl)-4-methylpiperidine-1-carboxamide) is a highly selective adenosine A receptor (AR) antagonist and a promising lead structure for the development of AR-selective positron emission tomography (PET) probes. Although several F-labelled tozadenant derivatives showed favorable in vitro properties, recent in vivo PET studies observed poor brain penetration and lower specific binding than anticipated from the in vitro data. While these findings might be attributable to the structural modification associated with F-labelling, they could also reflect inherent properties of the parent compound.
View Article and Find Full Text PDFObjectives: To present an application of specification curve analysis-a novel analytic method that involves defining and implementing all plausible and valid analytic approaches for addressing a research question-to nutritional epidemiology.
Study Design And Setting: We reviewed all observational studies addressing the effect of red meat on all-cause mortality, sourced from a published systematic review, and documented variations in analytic methods (eg, choice of model, covariates, etc.).
Background: Beginning in 1977, the U.S. Government began formally issuing dietary advice, a main objective of which was to reduce and prevent the prevalence of obesity in the American population.
View Article and Find Full Text PDFIdentifying ligands targeting G protein coupled receptors (GPCRs) with novel chemotypes other than the physiological ligands is a challenge for screening campaigns. Here we present an approach that identifies novel chemotype ligands by combining structural data with a random forest agonist/antagonist classifier and a signal-transduction kinetic model. As a test case, we apply this approach to identify novel antagonists of the human adenosine transmembrane receptor type 2A, an attractive target against Parkinson's disease and cancer.
View Article and Find Full Text PDFCalcium (Ca) batteries are attractive post-lithium battery technologies, due to their potential to provide high-voltage and high-energy systems in a sustainable manner. We investigated herein 1,5-poly(anthraquinonylsulfide) (PAQS) for Ca-ion storage with calcium tetrakis(hexafluoroisopropyloxy)borate Ca[B(hfip) ] [hfip=OCH(CF ) ] electrolytes. It is demonstrated that PAQS could be synthesized in a cost-effective approach and be processed environmentally friendly into the electrodes.
View Article and Find Full Text PDFPurpose And Methods: This summary is based on a scientific symposium organized by the Mediterranean Diet Roundtable and the American Italian Food Coalition titled, 'Positive Nutrition: shifting focus from nutrients to diet for a healthy lifestyle.' It was held at the Embassy of Italy in Washington DC in September of 2022. The panel of experts discussed how science can inform policy, what insights may be gleaned from different countries' approaches to healthy eating and what principles of the Mediterranean diet will inform strategies for a healthy future.
View Article and Find Full Text PDFThe US Dietary Guidelines for Americans is an enormously influential policy that has guided US nutrition programs since 1980. During these last 40 years, some researchers have expressed concern that the guidelines are based on an insufficiently rigorous assessment of the scientific evidence, a view that was largely substantiated by a Congressionally mandated 2017 report by the National Academies of Sciences, Engineering, and Medicine, which identified a need for enhanced transparency, greater scientific rigor, and updates to the scientific methodology for the DGA process. This paper traces the history of these ideas and contextualizes the DGA within the law and regulations that govern its process.
View Article and Find Full Text PDFThe NOVA classification of food items has become increasingly popular and is being used in several observational studies as well as in nutritional guidelines and recommendations. We propose that there is a need for this classification and its use in the formulation of public health policies to be critically discussed and re-appraised. The terms 'processing' and 'ultra-processing', which are crucial to the NOVA classification, are ill-defined, as no scientific, measurable or precise reference parameters exist for them.
View Article and Find Full Text PDFThe last decade has seen nearly 20 papers reviewing the totality of the data on saturated fats and cardiovascular outcomes, which, altogether, have demonstrated a lack of rigorous evidence to support continued recommendations either to limit the consumption of saturated fatty acids or to replace them with polyunsaturated fatty acids. These papers were unfortunately not considered by the process leading to the most recent U.S.
View Article and Find Full Text PDFTo date, nutritional epidemiology has relied heavily on relatively weak methods including simple observational designs and substandard measurements. Despite low internal validity and other sources of bias, claims of causality are made commonly in this literature. Nutritional epidemiology investigations can be improved through greater scientific rigor and adherence to scientific reporting commensurate with research methods used.
View Article and Find Full Text PDFACS Chem Neurosci
September 2021
Selective inhibition of glycine transporter 1 (GlyT1) has emerged as a potential approach to alleviate -methyl-d-aspartate receptor (NMDAR) hypofunction in patients with schizophrenia and cognitive decline. ALX5407 is a potent and selective inhibitor of GlyT1 derived from the metabolic intermediate sarcosine (-methylglycine) that showed antipsychotic potential in a number of animal models. Whereas clinical application of ALX5407 is limited by adverse effects on motor performance and respiratory function, a suitably radiolabeled drug could represent a promising PET tracer for the visualization of GlyT1 in the brain.
View Article and Find Full Text PDFPhenylalanine and serine are amino acids used in dietary supplements and nutritional products consumed by healthy consumers; however, the safe level of phenylalanine or serine supplementation is unknown. The objective of this study was to conduct two 4-week clinical trials to evaluate the safety and tolerability of graded dosages of oral phenylalanine and oral serine. Healthy male adults ( = 60, 38.
View Article and Find Full Text PDFGiven the challenges with nutrition research, the Canadian Nutrition Society and Intertek Health Sciences Inc held an expert consultation in late 2019 to discuss the development and implementation of best practices for clinical trials on whole foods. Key challenges in the design, interpretation, and reporting of clinical efficacy studies on whole foods and opportunities for the future development of best practices are reported. Outlines existing tools, resources, and checklists for clinical nutrition trials and provides clear and tangible steps to develop best practices for studies on whole foods.
View Article and Find Full Text PDFTracer development for positron emission tomography (PET) requires thorough evaluation of pharmacokinetics, metabolism, and dosimetry of candidate radioligands in preclinical animal studies. Since variations in pharmacokinetics and metabolism of a compound occur in different species, careful selection of a suitable model species is mandatory to obtain valid data. This study focuses on species differences in the in vitro metabolism of three xanthine-derived ligands for the A adenosine receptor (AAR), which, in their F-labeled form, can be used to image AAR via PET.
View Article and Find Full Text PDFWith the aim to obtain potent adenosine A receptor (AR) ligands, a series of eighteen derivatives of 4-hydroxy-N-(4-methoxy-7-morpholin-4-yl-1,3-benzo[d]thiazol-2-yl)-4-methylpiperidine-1-carboxamide (SYN-115, Tozadenant) were designed and synthesized. The target compounds were obtained by a chemical building block principle that involved reaction of the appropriate aminobenzothiazole phenyl carbamates with either commercially available or readily synthesized functionalized piperidines. Their affinity and subtype selectivity with regard to human adenosine A-and A receptors were determined using radioligand binding assays.
View Article and Find Full Text PDFLiposomes are highly biocompatible and versatile drug carriers with an increasing number of applications in the field of nuclear medicine and diagnostics. So far, only negatively charged liposomes with intercalated radiometals, e.g.
View Article and Find Full Text PDFOver the course of evolution, Mother Nature preserved the ability of humans to make every sugar they need for metabolic functions. Glucose is the almost exclusive fuel preferred by the human brain. Human infants are born with sweet taste receptors, sugars are a significant energy source in human milk, and mammals have a direct gut-to-brain sugar-sensing system that enhances development of a preference for sugars.
View Article and Find Full Text PDFBased on research presented during the 10th Amino Acid Assessment Workshop, no observed adverse effect levels (NOAELs) for supplemental methionine at 46 mg/(kg·d) (∼3.2 g/d), for supplemental histidine at 8.0 g/d, and for supplemental lysine at 6.
View Article and Find Full Text PDFThe recommendation to limit dietary saturated fatty acid (SFA) intake has persisted despite mounting evidence to the contrary. Most recent meta-analyses of randomized trials and observational studies found no beneficial effects of reducing SFA intake on cardiovascular disease (CVD) and total mortality, and instead found protective effects against stroke. Although SFAs increase low-density lipoprotein (LDL) cholesterol, in most individuals, this is not due to increasing levels of small, dense LDL particles, but rather larger LDL particles, which are much less strongly related to CVD risk.
View Article and Find Full Text PDFDairy has been described as everything from a superfood to a poison; yet, arguments, assumptions, and data justifying these labels are not always clear. We used an issue-based information system, "dialogue mapping™," to summarize scientific points of a live panel discussion on the putative effects of dairy on cardiovascular diseases (CVD) from a day-long session among experts in nutrition and CVD. Dialogue mapping captures relations among ideas to explicitly, logically, and visually connect issues/questions, ideas, pro/con arguments, and agreements, even if discussed at different times.
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