It is commonly assumed that cardiovascular disease risk factors are associated with affluence and Westernization. We investigated the associations of body mass index (BMI), fasting plasma glucose, ...systolic blood pressure, and serum total cholesterol with national income, Western diet, and, for BMI, urbanization in 1980 and 2008.
Country-level risk factor estimates for 199 countries between 1980 and 2008 were from a previous systematic analysis of population-based data. We analyzed the associations between risk factors and per capita national income, a measure of Western diet, and, for BMI, the percentage of the population living in urban areas. In 1980, there was a positive association between national income and population mean BMI, systolic blood pressure, and total cholesterol. By 2008, the slope of the association between national income and systolic blood pressure became negative for women and zero for men. Total cholesterol was associated with national income and Western diet in both 1980 and 2008. In 1980, BMI rose with national income and then flattened at ≈Int$7000; by 2008, the relationship resembled an inverted U for women, peaking at middle-income levels. BMI had a positive relationship with the percentage of urban population in both 1980 and 2008. Fasting plasma glucose had weaker associations with these country macro characteristics, but it was positively associated with BMI.
The changing associations of metabolic risk factors with macroeconomic variables indicate that there will be a global pandemic of hyperglycemia and diabetes mellitus, together with high blood pressure in low-income countries, unless effective lifestyle and pharmacological interventions are implemented.
It is believed that milk production is determined by the number and activity of mammary secretory cells. Secretory activity, as assessed by milk volume, depends on secretion of the major osmole in ...milk, lactose, which is produced by lactose synthase. The amount of either of the two proteins in lactose synthase may regulate milk production. The objective of this study was to determine whether the concentrations in milk of the two components of lactose synthase, α-lactalbumin (α-LA) and β1,4-galactosyltransferase (B4GALT), were related to genetic background, stage of lactation, breed or parity of dairy cows. α-Lactalbumin and B4GALT concentrations were measured by ELISA and by enzyme assays, respectively, from single milk samples. Two herds with a total of 279 cows were used in the analysis. One herd contained Ayrshire, Brown Swiss, Holstein and Jersey cows; the second herd contained two groups of cows; Holsteins selected for high milk production and Holsteins with 1960s genetics. The α-LA concentration in milk was greater in Jerseys and Ayrshires than in Holsteins and Brown Swiss. However, no difference in α-LA concentration was observed in milk from high and low genetic merit cows in the Minnesota herd or among different genetic backgrounds in the Illinois herd. β1,4-Galactosyltransferase concentrations were similar for all groups that were analyzed. α-Lactalbumin concentrations were positively correlated with milk protein concentration, milk fat concentration and lactose concentration. β1,4-Galactosyltransferase concentration in milk exhibited a strong positive correlation with number of days in milk. Although the concentration of B4GALT increased as lactation progressed, the values did not show any correlation with persistency of lactation or late lactation milk production. In conclusion, this survey shows that the two components of lactose synthase are each correlated to protein concentration and individually correlated to the concentration of other milk components and stage of lactation.
Summary
The stringent starvation protein A (SspA), an Escherichia coli RNA polymerase (RNAP)‐associated protein, has been reported to be essential for lytic growth of bacteriophage P1. Unlike P1 ...early promoters, P1 late promoters are not recognized by RNAP alone. A phage‐encoded early protein, Lpa (late promoter activator protein, formerly called gp10), has been shown to be required for P1 late transcription in vivo. Here, we demonstrate that SspA is a transcription activator for P1 late genes. Our results indicated that Lpa is not limiting in an sspA mutant. However, the transcription of P1 late genes was deficient in an sspA mutant in vivo. We demonstrated that SspA/Lpa are required for transcription activation of the P1 late promoter Ps in vitro. In addition, SspA and Lpa were shown to facilitate the binding of RNAP to Ps late promoter DNA. Activation of late transcription by SspA/Lpa was dependent on holoenzyme containing σ70 but not σS, indicating that the two activators discriminate between the two forms of the holoenzyme. Furthermore, P1 early gene expression was downregulated in the wild‐type background, whereas it persisted in the sspA mutant background, indicating that SspA/Lpa mediate the transcriptional switch from the early to the late genes during P1 lytic growth. Thus, this work provides the first evidence for a function of the E. coli RNAP‐associated protein SspA.
A search optimized for new heavy particles decaying to two b-quarks and produced in association with additional b-quarks is reported. The sensitivity is improved by b-tagging at least one lower-pT ...jet in addition to the two highest-pT jets. The data used in this search correspond to an integrated luminosity of 103 fb–1 collected with a dedicated trijet trigger during the 2017 and 2018 √s = 13 TeV proton–proton collision runs with the ATLAS detector at the LHC. The search looks for resonant peaks in the b-tagged dijet invariant mass spectrum over a smoothly falling background. The background is estimated with an innovative data-driven method based on orthonormal functions. The observed b-tagged dijet invariant mass spectrum is compatible with the background-only hypothesis. Upper limits at 95% confidence level on a heavy vector-boson production cross section times branching ratio to a pair of b-quarks are derived.
Metformin might reduce insulin requirement and improve glycaemia in patients with type 1 diabetes, but whether it has cardiovascular benefits is unknown. We aimed to investigate whether metformin ...treatment (added to titrated insulin therapy) reduced atherosclerosis, as measured by progression of common carotid artery intima-media thickness (cIMT), in adults with type 1 diabetes at increased risk for cardiovascular disease.
REMOVAL was a double-blind, placebo-controlled trial undertaken at 23 hospital diabetes clinics in five countries (Australia, Canada, Denmark, the Netherlands, and the UK). Adults aged 40 years and older with type 1 diabetes of at least 5 years' duration and at least three of ten specific cardiovascular risk factors were randomly assigned (via an interactive voice response system) to oral metformin 1000 mg twice daily or placebo. Participants and site staff were masked to treatment allocation. The primary outcome was averaged mean far-wall cIMT, quantified annually for 3 years, analysed in a modified intention-to-treat population (all randomly assigned participants with post-randomisation data available for the outcome of interest at any given timepoint, irrespective of subsequent adherence or study participation), using repeated measures regression. Secondary outcomes were HbA
, LDL cholesterol, estimated glomerular filtration rate (eGFR), incident microalbuminuria (not reported), incident retinopathy, bodyweight, insulin dose, and endothelial function, also analysed in all participants with post-randomisation data available for the outcome of interest at any given timepoint. This trial is registered with ClinicalTrials.gov, number NCT01483560.
Between Dec 14, 2011, and June 24, 2014, 493 participants entered a 3 month run-in to optimise risk factor and glycaemic control (single-blind placebo in the final month). Of 428 randomly assigned patients, 219 were allocated to metformin and 209 to placebo. Progression of mean cIMT was not significantly reduced with metformin (-0·005 mm per year, 95% CI -0·012 to 0·002; p=0·1664), although maximal cIMT (a prespecified tertiary outcome) was significantly reduced (-0·013 mm per year, -0·024 to -0·003; p=0·0093). HbA
(mean 8·1% SD 0·9 for metformin and 8·0% 0·8 for placebo at baseline) was reduced on average over 3 years by metformin (-0·13%, 95% CI -0·22 to -0·037; p=0·0060), but this was accounted for by a reduction at the 3-month timepoint (-0·24%, -0·34 to -0·13; p<0·0001) that was not sustained thereafter (p=0·0163 for visit-by-treatment interaction). Bodyweight (-1·17 kg, 95% CI -1·66 to -0·69; p<0·0001) and LDL cholesterol (-0·13 mmol/L, -0·24 to -0·03; p=0·0117) were reduced with metformin over 3 years of treatment, and eGFR was increased (4·0 mL/min per 1·73m
, 2·19 to 5·82; p<0·0001). Insulin requirement was not reduced on average over 3 years (-0·005 units per kg, 95% CI -0·022 to 0·012; p=0·545), but there was a significant visit-by-treatment interaction (p=0·0018). There was no effect on endothelial function as measured by reactive hyperaemia index, or on retinopathy. Discontinuation of treatment in 59 (27%) participants on metformin versus 26 (12%) on placebo (p=0·0002) was mainly due to an excess of gastrointestinal adverse effects, and there was no increase in hypoglycaemia with metformin. Five deaths occurred among patients allocated to metformin and two occurred among those allocated to placebo; none were judged by site principal investigators to be related to study medication.
These data do not support use of metformin to improve glycaemic control in adults with long-standing type 1 diabetes as suggested by current guidelines, but suggest that it might have a wider role in cardiovascular risk management.
JDRF.
A search for charginos and neutralinos at the Large Hadron Collider using fully hadronic final states and missing transverse momentum is reported. Pair-produced charginos or neutralinos are explored, ...each decaying into a high-pT Standard Model weak boson. Fully hadronic final states are studied to exploit the advantage of the large branching ratio, and the efficient rejection of backgrounds by identifying the high-pT bosons using large-radius jets and jet substructure information. An integrated luminosity of 139 fb-1 of proton-proton collision data collected by the ATLAS detector at a center-of-mass energy of 13 TeV is used. No significant excess is found beyond the Standard Model expectation. Exclusion limits at the 95% confidence level are set on wino or higgsino production with various assumptions about the decay branching ratios and the type of lightest supersymmetric particle. A wino (higgsino) mass up to 1060 (900) GeV is excluded when the lightest supersymmetry particle mass is below 400 (240) GeV and the mass splitting is larger than 400 (450) GeV. The sensitivity to high-mass winos and higgsinos is significantly extended relative to previous LHC searches using other final states.
Expeditions 304 and 305 of the Integrated Ocean Drilling Program cored and logged a 1.4 km section of the domal core of Atlantis Massif. Postdrilling research results summarized here constrain the ...structure and lithology of the Central Dome of this oceanic core complex. The dominantly gabbroic sequence recovered contrasts with predrilling predictions; application of the ground truth in subsequent geophysical processing has produced self-consistent models for the Central Dome. The presence of many thin interfingered petrologic units indicates that the intrusions forming the domal core were emplaced over a minimum of 100-220 kyr, and not as a single magma pulse. Isotopic and mineralogical alteration is intense in the upper 100 m but decreases in intensity with depth. Below 800 m, alteration is restricted to narrow zones surrounding faults, veins, igneous contacts, and to an interval of locally intense serpentinization in olivine-rich troctolite. Hydration of the lithosphere occurred over the complete range of temperature conditions from granulite to zeolite facies, but was predominantly in the amphibolite and greenschist range. Deformation of the sequence was remarkably localized, despite paleomagnetic indications that the dome has undergone at least 45 degrees rotation, presumably during unroofing via detachment faulting. Both the deformation pattern and the lithology contrast with what is known from seafloor studies on the adjacent Southern Ridge of the massif. There, the detachment capping the domal core deformed a 100 m thick zone and serpentinized peridotite comprises similar to 70% of recovered samples. We develop a working model of the evolution of Atlantis Massif over the past 2 Myr, outlining several stages that could explain the observed similarities and differences between the Central Dome and the Southern Ridge.
This report describes a case of cardiac sarcoidosis in a 40-year-old man with minimal risk factors for coronary artery disease who was found to have a critical coronary lesion on angiography ...performed for declining left ventricular function. The case highlights the diagnostic and therapeutic issues surrounding cardiac sarcoidosis and raises the question of a possible link between sarcoidosis and premature coronary artery disease. It also stresses the importance of ruling out ischemia in any patient with declining left ventricular function.
BackgroundBecause changes in antiretroviral therapy in resource-limited settings (RLSs) are delayed until patients experience immunological or clinical failure, it is important to be able to estimate ...the consequences in terms of accumulation of thymidine analogue (TA) mutations (TAMs) MethodsThe study included patients in EuroSIDA with ⩾2 available genotypic resistance tests (GRTs) (human immunodeficiency virus HIV RNA level, >500 copies/mL in any measure between tests), provided that the first GRT was performed after the first virological failure of a TA and that the same TA was continued until the second GRT ResultsAt the time of the first GRT in a pair (t0), 1 year after virological failure, a median of 3 TAMs were detected, mutations 41L and 215Y in 65% of pairs and 67N in 52%. Overall, 126 TAMs were accumulated during 548 person-years of follow-up (PYFUs) (1/4.3 years; 95% confidence interval, 3.7–5.0 years). Greater predicted activity of the TA at t0, TAM profile 2 (TAM2; vs TAM profile 1 TAM1) profiles at t0, use of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) at t0 (vs combined NNRTI and protease inhibitor), and acquisition of HIV infection through heterosexual (vs homosexual) contacts were associated with a faster rate of TAM accumulation ConclusionsAlthough the estimated rate of TAM accumulation was lower than anticipated, all possible efforts should be continued to increase the availability of drug options in RLSs
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