IMPORTANCE: Soft drinks are frequently consumed, but whether this consumption is associated with mortality risk is unknown and has been understudied in European populations to date. OBJECTIVE: To ...examine the association between total, sugar-sweetened, and artificially sweetened soft drink consumption and subsequent total and cause-specific mortality. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study involved participants (n = 451 743 of the full cohort) in the European Prospective Investigation into Cancer and Nutrition (EPIC), an ongoing, large multinational cohort of people from 10 European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom), with participants recruited between January 1, 1992, and December 31, 2000. Excluded participants were those who reported cancer, heart disease, stroke, or diabetes at baseline; those with implausible dietary intake data; and those with missing soft drink consumption or follow-up information. Data analyses were performed from February 1, 2018, to October 1, 2018. EXPOSURE: Consumption of total, sugar-sweetened, and artificially sweetened soft drinks. MAIN OUTCOMES AND MEASURES: Total mortality and cause-specific mortality. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional hazards regression models adjusted for other mortality risk factors. RESULTS: In total, 521 330 individuals were enrolled. Of this total, 451 743 (86.7%) were included in the study, with a mean (SD) age of 50.8 (9.8) years and with 321 081 women (71.1%). During a mean (range) follow-up of 16.4 (11.1 in Greece to 19.2 in France) years, 41 693 deaths occurred. Higher all-cause mortality was found among participants who consumed 2 or more glasses per day (vs consumers of <1 glass per month) of total soft drinks (hazard ratio HR, 1.17; 95% CI, 1.11-1.22; P < .001), sugar-sweetened soft drinks (HR, 1.08; 95% CI, 1.01-1.16; P = .004), and artificially sweetened soft drinks (HR, 1.26; 95% CI, 1.16-1.35; P < .001). Positive associations were also observed between artificially sweetened soft drinks and deaths from circulatory diseases (≥2 glasses per day vs <1 glass per month; HR, 1.52; 95% CI, 1.30-1.78; P < .001) and between sugar-sweetened soft drinks and deaths from digestive diseases (≥1 glass per day vs <1 glass per month; HR, 1.59; 95% CI, 1.24-2.05; P < .001). CONCLUSIONS AND RELEVANCE: This study found that consumption of total, sugar-sweetened, and artificially sweetened soft drinks was positively associated with all-cause deaths in this large European cohort; the results are supportive of public health campaigns aimed at limiting the consumption of soft drinks.
Abstract Many developments have occurred since the publication of the widely-used 2009 Canadian Cardiovascular Society (CCS) Dyslipidemia guidelines. Here, we present an updated version of the ...guidelines, incorporating new recommendations based on recent findings and harmonizing CCS guidelines with those from other Societies. The G rading of R ecommendations A ssessment, D evelopment and E valuation (GRADE) system was used, per present standards of the CCS. The total cardiovascular disease Framingham Risk Score (FRS), modified for a family history of premature coronary disease, is recommended for risk assessment. Low-density lipoprotein cholesterol remains the primary target of therapy. However, non-high density lipoprotein cholesterol has been added to apolipoprotein B as an alternate target. There is an increased emphasis on treatment of higher risk patients, including those with chronic kidney disease and high risk hypertension. The primary panel has recommended a judicious use of secondary testing for subjects in whom the need for statin therapy is unclear. Expanded information on health behaviours is presented and is the backbone of risk reduction in all subjects. Finally, a systematic approach to statin intolerance is advocated to maximize appropriate use of lipid-lowering therapy. This document presents the recommendations and principal conclusions of this process. Along with associated Supplementary Material that can be accessed online, this document will be part of a program of knowledge translation. The goal is to increase the appropriate use of evidence-based cardiovascular disease event risk assessment in the management of dyslipidemia as a fundamental means of reducing global risk in the Canadian population.
This study wants to give a contribution to the semi-automatic evaluation of rock mass discontinuities, orientation and spacing, as important parameters used in Engineering. In complex and ...inaccessible study areas, a traditional geological survey is hard to conduct, therefore, remote sensing techniques have proven to be a very useful tool for discontinuity analysis. However, critical expert judgment is necessary to make reliable analyses. For this reason, the open-source Python tool named DCS (Discontinuities Classification and Spacing) was developed to manage point cloud data. The tool is written in Python and is based on semi-supervised clustering. By this approach the users can: (a) estimate the number of discontinuity sets (here referred to as “clusters”) using the Error Sum of Squares (SSE) method and the K-means algorithm; (b) evaluate step by step the quality of the classification visualizing the stereonet and the scatterplot of dip vs. dip direction from the clustering; (c) supervise the clustering procedure through a manual initialization of centroids; (d) calculate the normal spacing. In contrast to other algorithms available in the literature, the DCS method does not require complex parameters as inputs for the classification and permits the users to supervise the procedure at each step. The DCS approach was tested on the steep coastal cliff of Ancona town (Italy), called the Cardeto–Passetto cliff, which is characterized by a complex fracturing and is largely affected by rockfall phenomena. The results of discontinuity orientation were validated with the field survey and compared with the ones of the FACETS plug-in of CloudCompare. In addition, the algorithm was tested and validated on regular surfaces of an anthropic wall located at the bottom of the cliff. Eventually, a kinematic analysis of rock slope stability was performed, discussing the advantages and limitations of the methods considered and making fundamental considerations on their use.
The thylakoid lumen houses proteins that are vital for photosynthetic electron transport, including water-splitting at photosystem (PS) II and shuttling of electrons from cytochrome b6f to PSI. Other ...lumen proteins maintain photosynthetic activity through biogenesis and turnover of PSII complexes. Although all lumen proteins are soluble, these known details have highlighted interactions of some lumen proteins with thylakoid membranes or thylakoid-intrinsic proteins. Meanwhile, the functional details of most lumen proteins, as well as their distribution between the soluble and membrane-associated lumen fractions, remain unknown. The current study isolated the soluble free lumen (FL) and membrane-associated lumen (MAL) fractions from Arabidopsis thaliana, and used gel- and mass spectrometry-based proteomics methods to analyze the contents of each proteome. These results identified 60 lumenal proteins, and clearly distinguished the difference between the FL and MAL proteomes. The most abundant proteins in the FL fraction were involved in PSII assembly and repair, while the MAL proteome was enriched in proteins that support the oxygen-evolving complex (OEC). Novel proteins, including a new PsbP domain-containing isoform, as well as several novel post-translational modifications and N-termini, are reported, and bi-dimensional separation of the lumen proteome identified several protein oligomers in the thylakoid lumen.
Abstract Diabetes mellitus (DM), a chronic metabolic disease characterized by hyperglycemia, is a profound cardiovascular (CV) risk factor. It compounds the effects of all other risk factors, leads ...to premature micro- and macrovascular disease, facilitates development of heart failure, worsens the clinical course of all CV diseases, and shortens life expectancy. Established DM, unrecognized DM, and dysglycemia that may progress to DM are all commonly present at the time of presentation of overt CV disease. Thus, CV specialists and trainees frequently treat patients with dysglycemia. The traditional and proven role of cardiologists in reducing the risk of macrovascular events in this population is through aggressive lipid and blood pressure treatment. However, a more proactive role in the detection and management of DM is likely to become increasingly important as the prevalence continues to increase and therapies continue to improve. The latter include antihyperglycemic therapies with proven cardiovascular safety profiles and CV event reduction properties not yet fully elucidated and not necessarily related to glycemic control. Accordingly, the purpose of this article is to (1) expand the interest of cardiologists in earlier stages of the natural history of DM, when prevention or early detection might help achieve greatest benefit; (2) highlight principles of optimal glycemic management, with an emphasis on add-on choices showing promising reduction of CV events and lacking CV adverse effects; and (3) encourage cardiologists to become proactive partners in the multidisciplinary care needed to ensure optimal lifelong vascular health in patients with, or who are at risk of, DM.
We present the detection of CO (5−4) with signal-to-noise ratio (S/N) > 7-13 and a lower CO transition with S/N > 3 (CO (4−3) for four galaxies, and CO (3−2) for one) with the Atacama Large ...Millimeter/submillimeter Array in bands 3 and 4 in five main-sequence (MS) star-forming galaxies with stellar masses (3-6) × 1010M at 3 < z < 3.5. We find a good correlation between the total far-infrared luminosity LFIR and the luminosity of the CO (5−4) transition , where increases with star formation rate (SFR), indicating that CO (5−4) is a good tracer of the obscured SFR in these galaxies. The two galaxies that lie closer to the star-forming MS have CO spectral line energy distribution (SLED) slopes that are comparable to other star-forming populations, such as local submillimeter galaxies and BzK star-forming galaxies; the three objects with higher specific star formation rates have far steeper CO SLEDs, which possibly indicates a more concentrated episode of star formation. By exploiting the CO SLED slopes to extrapolate the luminosity of the CO (1−0) transition and using a classical conversion factor for MS galaxies of , we find that these galaxies are very gas-rich, with molecular gas fractions between 60% and 80% and quite long depletion times, between 0.2 and 1 Gyr. Finally, we obtain dynamical masses that are comparable to the sum of stellar and gas mass (at least for four out of five galaxies), allowing us to put a first constraint on the CO parameter for MS galaxies at an unprecedented redshift.
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•Diet represents the main exposure route of dioxins and PCBs for the general population.•Dietary exposure to dioxins and PCBs were assessed combining EPIC Cohort food consumption and ...food contamination levels from European monitoring program.•Overall, no association were identified between dietary intakes of dioxins and PCBs and breast cancer risk in 9 European countries.•This prospective study is the largest ever conducted to assess dietary exposure to dioxins and PCBs.
Dioxins and polychlorobiphenyls (PCBs) are persistent organic pollutants that have demonstrated endocrine disrupting properties. Several of these chemicals are carcinogenic and positive associations have been suggested with breast cancer risk. In general population, diet represents the main source of exposure.
Associations between dietary intake of 17 dioxins and 35 PCBs and breast cancer were evaluated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from nine European countries using multivariable Cox regressions. The present study included 318,607 women (mean ± SD age: 50.7 ± 9.7) with 13,241 incident invasive breast cancers and a median follow-up of 14.9 years (IQR = 13.5–16.4). Dietary intake of dioxins and PCBs was assessed combining EPIC food consumption data with food contamination data provided by the European Food Safety Authority.
Exposure to dioxins, dioxins + Dioxin-Like-PCBs, Dioxin-Like-PCBs (DL-PCBs), and Non-Dioxin-Like-PCBs (NDL-PCBs) estimated from reported dietary intakes were not associated with breast cancer incidence, with the following hazard ratios (HRs) and 95% confidence intervals for an increment of 1 SD: HRdioxins = 1.00 (0.98 to 1.02), HRdioxins+DL-PCB = 1.01 (0.98 to 1.03), HRDL-PCB = 1.01 (0.98 to 1.03), and HRNDL-PCB = 1.01 (0.99 to 1.03). Results remained unchanged when analyzing intakes as quintile groups, as well as when analyses were run separately per country, or separating breast cancer cases based on estrogen receptor status or after further adjustments on main contributing food groups to PCBs and dioxins intake and nutritional factors.
This large European prospective study does not support the hypothesis of an association between dietary intake of dioxins and PCBs and breast cancer risk.
In all eukaryotes, protein phosphorylation is a key regulatory mechanism in several cellular processes, including the acclimation of photosynthesis to environmental cues. Despite being a ...well-conserved regulatory mechanism in the chloroplasts of land plants, distinct differences in thylakoid protein phosphorylation patterns have emerged from studies on species of different phylogenetic groups. Here, we analyzed thylakoid protein phosphorylation in the moss
, assessing the thylakoid phospho-protein profile and dynamics in response to changes in white light intensity. Compared with Arabidopsis (
), parallel characterization of wild-type
and the knockout mutant
(depleted in SER/THR PROTEIN KINASE8 STN8) disclosed a moss-specific pattern of thylakoid protein phosphorylation, both with respect to specific targets and to their dynamic phosphorylation in response to environmental cues. Unlike vascular plants, (1) phosphorylation of the PSII protein D1 in
was negligible under all light conditions, (2) phosphorylation of the PSII core subunits CP43 and D2 showed only minor changes upon fluctuations in light intensity, and (3) absence of STN8 completely abolished all PSII core protein phosphorylation. Further, we detected light-induced phosphorylation in the minor light harvesting complex (LHC) antenna protein LHCB6, which was dependent on STN8 kinase activity, and found specific phosphorylations on LHCB3. Data presented here provide further insights into the appearance and physiological role of thylakoid protein phosphorylation during evolution of oxygenic photosynthetic organisms and their colonization of land.
Nuclear deubiquitinase BAP1 (BRCA1-associated protein 1) is a core component of multiprotein complexes that promote transcription by reversing the ubiquitination of histone 2A (H2A). BAP1 is a tumor ...suppressor whose germline loss-of-function variants predispose to cancer. To our knowledge, there are very rare examples of different germline variants in the same gene causing either a neurodevelopmental disorder (NDD) or a tumor predisposition syndrome. Here, we report a series of 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic NDD. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. In T cells isolated from two affected children, H2A deubiquitination was impaired. In matching peripheral blood mononuclear cells, histone H3 K27 acetylation ChIP-seq indicated that these BAP1 variants induced genome-wide chromatin state alterations, with enrichment for regulatory regions surrounding genes of the ubiquitin-proteasome system (UPS). Altogether, these results define a clinical syndrome caused by rare germline missense BAP1 variants that alter chromatin remodeling through abnormal histone ubiquitination and lead to transcriptional dysregulation of developmental genes.
Gene-diet interactions have been reported to contribute to the development of type 2 diabetes (T2D). However, to our knowledge, few examples have been consistently replicated to date.
We aimed to ...identify existing evidence for gene-macronutrient interactions and T2D and to examine the reported interactions in a large-scale study.
We systematically reviewed studies reporting gene-macronutrient interactions and T2D. We searched the MEDLINE, Human Genome Epidemiology Network, and WHO International Clinical Trials Registry Platform electronic databases to identify studies published up to October 2015. Eligibility criteria included assessment of macronutrient quantity (e.g., total carbohydrate) or indicators of quality (e.g., dietary fiber) by use of self-report or objective biomarkers of intake. Interactions identified in the review were subsequently examined in the EPIC (European Prospective Investigation into Cancer)-InterAct case-cohort study (
= 21,148, with 9403 T2D cases; 8 European countries). Prentice-weighted Cox regression was used to estimate country-specific HRs, 95% CIs, and
-interaction values, which were then pooled by random-effects meta-analysis. A primary model was fitted by using the same covariates as reported in the published studies, and a second model adjusted for additional covariates and estimated the effects of isocaloric macronutrient substitution.
Thirteen observational studies met the eligibility criteria (
< 1700 cases). Eight unique interactions were reported to be significant between macronutrients carbohydrate, fat, saturated fat, dietary fiber, and glycemic load derived from self-report of dietary intake and circulating n-3 (ω-3) polyunsaturated fatty acids and genetic variants in or near transcription factor 7-like 2 (
), gastric inhibitory polypeptide receptor (
), caveolin 2 (
), and peptidase D (
) (
-interaction < 0.05). We found no evidence of interaction when we tried to replicate previously reported interactions. In addition, no interactions were detected in models with additional covariates.
Eight gene-macronutrient interactions were identified for the risk of T2D from the literature. These interactions were not replicated in the EPIC-InterAct study, which mirrored the analyses undertaken in the original reports. Our findings highlight the importance of independent replication of reported interactions.
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