OBJECTIVETo examine whether a pistachio-rich diet reduces the prediabetes stage and improves its metabolic risk profile. RESEARCH DESIGN AND METHODSPrediabetic subjects were recruited to participate in this Spanish randomized clinical trial between 20 September 2011 and 4 February 2013. In a crossover manner, 54 subjects consumed two diets, each for 4 months: a pistachio-supplemented diet (PD) and a control diet (CD). A 2-week washout period separated study periods. Diets were isocaloric and matched for protein, fiber, and saturated fatty acids. A total of 55% of the CD calories came from carbohydrates and 30% from fat, whereas for the PD, these percentages were 50 and 35%, respectively (including 57 g/day of pistachios). RESULTSFasting glucose, insulin, and HOMA of insulin resistance decreased significantly after the PD compared with the CD. Other cardiometabolic risk markers such as fibrinogen, oxidized LDL, and platelet factor 4 significantly decreased under the PD compared with the CD (P < 0.05), whereas glucagon-like peptide-1 increased. Interleukin-6 mRNA and resistin gene expression decreased by 9 and 6%, respectively, in lymphocytes after the pistachio intervention (P < 0.05, for PD vs. CD). SLC2A4 expression increased by 69% in CD (P = 0.03, for PD vs. CD). Cellular glucose uptake by lymphocytes decreased by 78.78% during the PD (P = 0.01, PD vs. CD). CONCLUSIONSChronic pistachio consumption is emerging as a useful nutritional strategy for the prediabetic state. Data suggest that pistachios have a glucose-and insulin-lowering effect, promote a healthier metabolic profile, and reverse certain metabolic deleterious consequences of prediabetes.

A recent publication by Sun H. and colleagues in the Proceedings of the National Academy of Science (PNAS) has drown global attention to the predominant genotype "G4" Eurasian (EA) avian-like H1N1 In uenza A virus that has been spreading among pigs in China since 2016, which is predicted to have a signi cant pandemic potential. Since pigs are hosts for the generation of pandemic In uenza A viruses (IAVs), surveillance and preparedness are critical to prevent pandemics. In this regards, one distinguishing feature of the QIAstat-Dx ® Respiratory SARS-CoV-2 panel is the double target approach In uenza A detection of seasonal strains affecting humans, by ampli cation of a generic In uenza A assay plus one of the speci c assays discriminating H3, H1 and H1N1pdm09 subtypes. The generic In uenza A assay is designed to amplify any IAV, a key feature for preparedness. Here we report an initial in-silico analysis that predicts that the G4 EA avian-like H1N1 strains tested in the QIAstat-Dx ® Respiratory SARS-CoV-2 Panel would be detected yielding a positive result for the generic In uenza A assay and negative results for the seasonal H3, H1 and H1N1pdm09 assays. This prediction was con rmed in-vitro using dsDNA fragments mixed to mimic the genomes of the different reported G4 EA IAV strains. In conclusion, the QIAstat-Dx ® Respiratory SARS-CoV-2 Panel could be a useful tool to differentially diagnose zoonotic strains from the seasonal In uenza A strains commonly affecting humans.

A low-GI and energy-restricted diet containing moderate amounts of carbohydrates may be more effective than a high-GI and low-fat diet at reducing body weight and controlling glucose and insulin metabolism. This trial was registered at Current Controlled Trials (www.controlled-trials.com) as ISRCTN54971867.

Objective Thymidine kinase 2 (TK2), a critical enzyme in the mitochondrial pyrimidine salvage pathway, is essential for mitochondrial DNA (mtDNA) maintenance. Mutations in the nuclear gene TK2 cause TK2 deficiency, which manifests predominantly in children as myopathy with mtDNA depletion. Molecular bypass therapy with the TK2 products, dCMP and dTMP, prolongs the lifespan of Tk2-deficient (Tk2-/-) mice by 2-3 fold. Because we observed rapid catabolism of the deoxynucleoside monophosphates to deoxythymidine (dT) and deoxycytidine (dC), we hypothesized that: 1) deoxynucleosides might be the major active agents and 2) inhibition of deoxycytidine deamination might enhance dTMP+dCMP therapy. Methods To test these hypotheses, we assessed two therapies in Tk2-/- mice: 1) dT+dC and 2) co-administration of the deaminase inhibitor, tetrahydrouridine (THU), with dTMP+dCMP. Results We observed that dC+dT delayed disease onset, prolonged lifespan of Tk2-deficient mice, and restored mtDNA copy number as well as respiratory chain enzyme activities and levels. In contrast, dCMP+dTMP+THU therapy decreased lifespan of Tk2-/- animals compared to dCMP+dTMP. Interpretation Our studies demonstrate that deoxynucleoside substrate enhancement is a novel therapy, which may ameliorate TK2 deficiency in patients.

SummaryMitochondrial diseases produce profound neurological dysfunction via mutations affecting mitochondrial energy production, including the relatively common Leigh syndrome (LS). We recently described an LS case caused by a pathogenic mutation in USMG5, encoding a small supernumerary subunit of mitochondrial ATP synthase. This protein is integral for ATP synthase dimerization, and patient fibroblasts revealed an almost total loss of ATP synthase dimers. Here, we utilize in situ cryoelectron tomography (cryo-ET) in a clinical case-control study of mitochondrial disease to directly study mitochondria within cultured fibroblasts from a patient with LS and a healthy human control subject. Through tomographic analysis of patient and control mitochondria, we find that loss of ATP synthase dimerization due to the pathogenic mutation causes profound disturbances of mitochondrial crista ultrastructure. Overall, this work supports the crucial role of ATP synthase in regulating crista architecture in the context of human disease.

In a population at high cardiovascular risk, low concentrations of serum cOC and ucOC were strongly associated with an increased risk of incident diabetes.

Epidemiological and/or clinical trials have suggested that nut consumption has a beneficial impact on health outcomes such as hypertension, diabetes, CVD, cancer, other inflammatory conditions and total mortality. Nuts are nutrient-dense foods with a healthy fatty acid profile, as well as provide other bioactive compounds with recognised health benefits. Among nuts, pistachios have a lower fat and energy content and the highest levels of K, g-tocopherol, vitamin K, phytosterols, xanthophyll carotenoids, certain minerals (Cu, Fe and Mg), vitamin B 6 and thiamin. Pistachios have a high antioxidant and anti-inflammatory potential. The aforementioned characteristics and nutrient mix probably contribute to the growing body of evidence that consumption of pistachios improves health. The present review examines the potential health effects of nutrients and phytochemicals in pistachios, as well as epidemiological and clinical evidence supporting these health benefits.

Vitamin K has been related to cardiovascular disease and cancer risk. However, data on total mortality are scarce. The aim of the present study was to assess the association between the dietary intake of different types of vitamin K and mortality in a Mediterranean population at high cardiovascular disease risk. A prospective cohort analysis was conducted in 7216 participants from the PREDIMED (Prevención con Dieta Mediterránea) study (median follow-up of 4.8 y). Energy and nutrient intakes were evaluated using a validated 137-item food frequency questionnaire. Dietary vitamin K intake was calculated annually using the USDA food composition database and other published sources. Deaths were ascertained by an end-point adjudication committee unaware of the dietary habits of participants after they had reviewed medical records and linked up to the National Death Index. Cox proportional hazard models were fitted to assess the RR of mortality. Energy-adjusted baseline dietary phylloquinone intake was inversely associated with a significantly reduced risk of cancer and all-cause mortality after controlling for potential confounders (HR: 0.54; 95% CI: 0.30, 0.96; and HR: 0.64; 95% CI: 0.45, 0.90, respectively). In longitudinal assessments, individuals who increased their intake of phylloquinone or menaquinone during follow-up had a lower risk of cancer (HR: 0.64; 95% CI: 0.43, 0.95; and HR: 0.41; 95% CI: 0.26, 0.64, respectively) and all-cause mortality (HR: 0.57; 95% CI: 0.44, 0.73; and HR: 0.55; 95% CI: 0.42, 0.73, respectively) than individuals who decreased or did not change their intake. Also, individuals who increased their intake of dietary phylloquinone had a lower risk of cardiovascular mortality risk (HR: 0.52; 95% CI: 0.31, 0.86). However, no association between changes in menaquinone intake and cardiovascular mortality was observed (HR: 0.76; 95% CI: 0.44, 1.29). An increase in dietary intake of vitamin K is associated with a reduced risk of cardiovascular, cancer, or all-cause mortality in a Mediterranean population at high cardiovascular disease risk. This trial was registered at http://www.controlled-trials.com as ISRCTN35739639.