Diet is a major contributor to metabolic disease risk, but there is controversy as to whether increased incidences of diseases such as non-alcoholic fatty liver disease arise from consumption of ...saturated fats or free sugars. Here, we investigate whether a sub-set of triacylglycerols (TAGs) were associated with hepatic steatosis and whether they arise from de novo lipogenesis (DNL) from the consumption of carbohydrates.
We conduct direct infusion mass spectrometry of lipids in plasma to study the association between specific TAGs and hepatic steatosis assessed by ultrasound and fatty liver index in volunteers from the UK-based Fenland Study and evaluate clustering of TAGs in the National Survey of Health and Development UK cohort. We find that TAGs containing saturated and monounsaturated fatty acids with 16-18 carbons are specifically associated with hepatic steatosis. These TAGs are additionally associated with higher consumption of carbohydrate and saturated fat, hepatic steatosis, and variations in the gene for protein phosphatase 1, regulatory subunit 3b (PPP1R3B), which in part regulates glycogen synthesis. DNL is measured in hyperphagic ob/ob mice, mice on a western diet (high in fat and free sugar) and in healthy humans using stable isotope techniques following high carbohydrate meals, demonstrating the rate of DNL correlates with increased synthesis of this cluster of TAGs. Furthermore, these TAGs are increased in plasma from patients with biopsy-confirmed steatosis.
A subset of TAGs is associated with hepatic steatosis, even when correcting for common confounding factors. We suggest that hepatic steatosis risk in western populations is in part driven by increased DNL following carbohydrate rich meals in addition to the consumption of saturated fat.
The Guatemalan National Revolutionary Unit (URNG) fought one of the longest and bloodiest civil wars in recent Latin American history. In 1996, the URNG and the Government of Guatemala signed a Firm ...and Lasting Agreement ending the country's civil war and initiating the URNG's post-war life as a political party. After finishing third in its initial electoral competition, the URNG has since been unable to capture more than 4% of the vote, on its own or in coalition, leaving it a minor political party. What explains the poor electoral performance of the URNG as a political party? Based upon fieldwork, elite interviews, and analysis of electoral data, I argue that the URNG's minor party performance was caused by both organizational and institutional factors.
Abstract Background & Aims The association between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) is well recognised. However, the relationship between IBD and recurrent ...PSC (rPSC) is less well understood. We assessed the prevalence of rPSC and analysed the factors associated with rPSC post-liver transplantation and its influence on graft and patient survival. Methods This is a UK multicentre observational cohort study across six of the seven national liver transplant units. All patients undergoing a first liver transplant for PSC between January 1 1990 and December 31 2010 were included. Prospectively collected liver transplant data was obtained from NHSBT and colitis data was retrospectively collected from individual units. Results There were 679 (8.8%) first transplants for PSC. 347 patients (61.4%) had IBD, of which 306 (88.2%) had ulcerative colitis (UC). 81 (14.3%) patients developed rPSC and 37 (48.7%) of them developed graft failure from rPSC. Presence of UC post-liver transplant (HR = 2.40, 95% CI 1.44–4.02) and younger age (HR = 0.78, 95% CI 0.66–0.93) were the only factors significantly associated with rPSC. rPSC was associated with over a 4-fold increase in the risk of death (HR = 4.71, 95% CI 3.39, 6.56) with 1, 5, and 10-year graft survival rates of 98%, 84%, and 56% respectively compared to 95%, 88%, and 72% in patients who did not develop rPSC. Conclusion The presence of UC post-liver transplant is associated with a significantly increased risk of rPSC. Furthermore, the presence of rPSC increases the rate of graft failure and death, with higher re-transplantation rates.
The bestselling guide to nonprofit planning, with proven, practical advice Strategic Planning for Nonprofit Organizations describes a proven method for creating an effective, organized, actionable ...strategy, tailored to the unique needs of the nonprofit organization. Now in its third edition, this bestselling manual contains new information about the value of plans, specific guidance toward business planning, and additional information about the strategic plan document itself. Real-world case studies illustrate different planning and implementation scenarios and techniques, and the companion website offers templates, tools, and worksheets that streamline the process. The book provides expert insight, describing common misperceptions and pitfalls to avoid, helping readers craft a strategic plan that adheres to the core values of the organization. A well-honed strategic plan helps nonprofit managers set priorities, and acquire and allocate the resources necessary to achieve their goals. It also provides a framework for handling challenges, and keeps the focus on the organization's priorities. Strategic Planning for Nonprofit Organizations is an excellent source of guidance for managers at nonprofits of every size and budget, helping readers to: Identify the reasons for planning, and gather information from internal and external stakeholders Assess the current situation accurately, and agree on priorities, mission, values, and vision Prioritize goals and objectives for the plan, and develop a detailed implementation strategy Evaluate and monitor a changing environment, updating roles, goals, and parameters as needed Different organizations have different needs, processes, resources, and priorities. The one thing they have in common is the need for a no-nonsense approach to planning with practical guidance and a customizable framework. Strategic Planning for Nonprofit Organizations takes the fear out of planning, with expert guidance on the nonprofit's most vital management activity.
Abstract
Several genetic discoveries robustly implicate five single-nucleotide variants in the progression of non-alcoholic fatty liver disease to non-alcoholic steatohepatitis and fibrosis ...(NASH-fibrosis), including a recently identified variant in MTARC1. To better understand these variants as potential therapeutic targets, we aimed to characterize their impact on metabolism using comprehensive metabolomics data from two population-based studies. A total of 9135 participants from the Fenland study and 9902 participants from the EPIC-Norfolk cohort were included in the study. We identified individuals with risk alleles associated with NASH-fibrosis: rs738409C>G in PNPLA3, rs58542926C>T in TM6SF2, rs641738C>T near MBOAT7, rs72613567TA>T in HSD17B13 and rs2642438A>G in MTARC1. Circulating levels of 1449 metabolites were measured using targeted and untargeted metabolomics. Associations between NASH-fibrosis variants and metabolites were assessed using linear regression. The specificity of variant-metabolite associations were compared to metabolite associations with ultrasound-defined steatosis, gene variants linked to liver fat (in GCKR, PPP1R3B and LYPLAL1) and gene variants linked to cirrhosis (in HFE and SERPINA1). Each NASH-fibrosis variant demonstrated a specific metabolite profile with little overlap (8/97 metabolites) comprising diverse aspects of lipid metabolism. Risk alleles in PNPLA3 and HSD17B13 were both associated with higher 3-methylglutarylcarnitine and three variants were associated with lower lysophosphatidylcholine C14:0. The risk allele in MTARC1 was associated with higher levels of sphingomyelins. There was no overlap with metabolites that associated with HFE or SERPINA1 variants. Our results suggest a link between the NASH-protective variant in MTARC1 to the metabolism of sphingomyelins and identify distinct molecular patterns associated with each of the NASH-fibrosis variants under investigation.
Aims
Liver pathology is a challenging subspeciality, with histopathologists frequently seeking specialist opinions. This study aims to determine the impact of specialist reviews on the final ...diagnosis and patient management.
Methods and results
Agreement with the initial reporting centre in the histopathological diagnosis of 1265 liver biopsies was determined. The nature of differences was explored in more depth for 103 discrepant cases. Differences in the histopathological interpretation were present in 749 of 1265 (59%) biopsies, of which 505 of 749 (67%) were predicted at the time of reporting to impact upon patient management. Agreement was good in cases with chronic viral hepatitis, fatty liver disease, malignancy and minimal pathological changes, while diagnostic differences occurred in more than 70% with biliary disease, autoimmune hepatitis or vascular/architectural changes. A clinical review of a subset of reports with histopathological differences predicted changes in patient management in 63 of 103 (61%).
Conclusions
Clinically significant differences in liver biopsy interpretation between local pathologists and subspecialists are common. Diagnoses with frequent discrepancies, such as biliary disease, may benefit from a specialist review as standard when diagnosed initially, while cases requiring specialist advice from disease subgroups where discrepancies are less common, such as chronic viral hepatitis, could be selected during the clinicopathological conference process.
Diagnostic tools for liver disease can now include estimation of the grade of hepatic steatosis (S0 to S3). Controlled attenuation parameter (CAP) is a non-invasive method for assessing hepatic ...steatosis that has become available for patients who are obese (FibroScan XL probe), but a consensus has not yet been reached regarding cutoffs and its diagnostic performance. We aimed to assess diagnostic properties and identify relevant covariates with use of an individual patient data meta-analysis.
We did an individual patient data meta-analysis, in which we searched PubMed and Web of Science for studies published from database inception until April 30, 2019. Studies reporting original biopsy-controlled data of CAP for non-invasive grading of steatosis were eligible. Probe recommendation was based on automated selection, manual assessment of skin-to-liver-capsule distance, and a body-mass index (BMI) criterion. Receiver operating characteristic methods and mixed models were used to assess diagnostic properties and covariates. Patients with non-alcoholic fatty liver disease (NAFLD) were analysed separately because they are the predominant patient group when using the XL probe. This study is registered with PROSPERO, CRD42018099284.
16 studies reported histology-controlled CAP including the XL probe, and individual data from 13 papers and 2346 patients were included. Patients with a mean age of 46·5 years (SD 14·5) were recruited from 20 centres in nine countries. 2283 patients had data for BMI; 673 (29%) were normal weight (BMI <25 kg/m
), 530 (23%) were overweight (BMI ≥25 to <30 kg/m
), and 1080 (47%) were obese (BMI ≥30 kg/m
). 1277 (54%) patients had NAFLD, 474 (20%) had viral hepatitis, 285 (12%) had alcohol-associated liver disease, and 310 (13%) had other liver disease aetiologies. The XL probe was recommended in 1050 patients, 930 (89%) of whom had NAFLD; among the patients with NAFLD, the areas under the curve were 0·819 (95% CI 0·769-0·869) for S0 versus S1 to S3 and 0·754 (0·720-0·787) for S0 to S1 versus S2 to S3. CAP values were independently affected by aetiology, diabetes, BMI, aspartate aminotransferase, and sex. Optimal cutoffs differed substantially across aetiologies. Risk of bias according to QUADAS-2 was low.
CAP cutoffs varied according to cause, and can effectively recognise significant steatosis in patients with viral hepatitis. CAP cannot grade steatosis in patients with NAFLD adequately, but its value in a NAFLD screening setting needs to be studied, ideally with methods beyond the traditional histological reference standard.
The German Federal Ministry of Education and Research and Echosens.
SEP-1: A Sepsis Measure in Need of Resuscitation? Allison, Michael G.; Schenkel, Stephen M.
Annals of emergency medicine,
January 2018, 2018-Jan, 2018-01-00, 20180101, Letnik:
71, Številka:
1
Journal Article
The latitude‐altitude map of ammonia mixing ratio shows an ammonia‐rich zone at 0–5°N, with mixing ratios of 320–340 ppm, extending from 40–60 bars up to the ammonia cloud base at 0.7 bars. ...Ammonia‐poor air occupies a belt from 5–20°N. We argue that downdrafts as well as updrafts are needed in the 0–5°N zone to balance the upward ammonia flux. Outside the 0–20°N region, the belt‐zone signature is weaker. At latitudes out to ±40°, there is an ammonia‐rich layer from cloud base down to 2 bars that we argue is caused by falling precipitation. Below, there is an ammonia‐poor layer with a minimum at 6 bars. Unanswered questions include how the ammonia‐poor layer is maintained, why the belt‐zone structure is barely evident in the ammonia distribution outside 0–20°N, and how the internal heat is transported through the ammonia‐poor layer to the ammonia cloud base.
Key Points
The altitude‐latitude map of Jupiter's ammonia reveals unexpected evidence of large‐scale circulation down at least to the 50‐bar level
A narrow equatorial band is the only region where ammonia‐rich air from below the 50‐bar level can reach the ammonia cloud at 0.7 bars
At higher latitudes the ammonia‐rich air appears to be blocked by a layer of ammonia‐poor air between 3 and 15 bars
Plain Language Summary
Jupiter is a fluid planet. It has no solid continents to stabilize the weather. Scientists have wondered what the weather is like below the clouds because it might explain why storms last for decades or hundreds of years on Jupiter. The Juno spacecraft is the first chance we have had to take a look beneath the clouds, and this is the first analysis of the Juno data. The surprise is that, deep down, Jupiter's weather looks a lot like Earth's, with ammonia gas taking the place of water vapor. There is a band of high humidity at the equator and bands of low humidity on either side of the equator, like Earth's tropical and subtropical bands. What is different is that the bands go much deeper than anyone expected and this is all taking place on a planet without an ocean or a solid surface.
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