Objective
Mortality statistics from the Centers for Disease Control and Prevention (CDC) are used for planning health care policy and allocating resources. The CDC uses these data to compile its ...annual ranking of leading causes of death based on a selected list of 113 causes. Systemic lupus erythematosus (SLE) is not included on this list. Since the ranking is a useful tool for assessing the relative burden of cause‐specific mortality, this study was undertaken to rank SLE deaths among the CDC's leading causes of death to see whether SLE is a significant cause of death among females.
Methods
Death counts for the female population of the US were obtained from the CDC's Wide‐ranging Online Data for Epidemiologic Research database and then grouped by age and race/ethnicity. Data on the leading causes of death were obtained from the Web‐based Injury Statistics Query and Reporting System database.
Results
During 2000–2015, there were 28,411 deaths of females with SLE recorded as an underlying or contributing cause of death. SLE ranked among the top 20 leading causes of death in females between 5 and 64 years of age. SLE ranked tenth among those ages 15–24 years, fourteenth among those ages 25–34 years and 35–44 years, and fifteenth among those ages 10–14 years. For African American and Hispanic females, SLE ranked fifth among those ages 15–24 years, sixth among those ages 25–34 years, and eighth or ninth among those ages 35–44 years, after the 3 common external injury causes of death were excluded from the analysis.
Conclusion
SLE is among the leading causes of death in young females, underscoring its impact as an important public health issue.
The intestine plays a prominent role in the biosynthesis of triacylglycerol (triglyceride; TAG). Digested dietary TAG is repackaged in the intestine to form the hydrophobic core of chylomicrons, ...which deliver metabolic fuels, essential fatty acids, and other lipid-soluble nutrients to the peripheral tissues. By controlling the flux of dietary fat into the circulation, intestinal TAG synthesis can greatly impact systemic metabolism. Genes encoding many of the enzymes involved in TAG synthesis have been identified. Among TAG synthesis enzymes, acyl-CoA:monoacylglycerol acyltransferase 2 and acyl-CoA:diacylglycerol acyltransferase (DGAT)1 are highly expressed in the intestine. Their physiological functions have been examined in the context of whole organisms using genetically engineered mice and, in the case of DGAT1, specific inhibitors. An emerging theme from recent findings is that limiting the rate of TAG synthesis in the intestine can modulate gut hormone secretion, lipid metabolism, and systemic energy balance. The underlying mechanisms and their implications for humans are yet to be explored. Pharmacological inhibition of TAG hydrolysis in the intestinal lumen has been employed to combat obesity and associated disorders with modest efficacy and unwanted side effects. The therapeutic potential of inhibiting specific enzymes involved in intestinal TAG synthesis warrants further investigation.
We aimed to assess SSc mortality by age in the general population over the past five decades.
This is a population-based study using a national mortality database and the census data for all US ...residents. We calculated the proportions of deaths for SSc and for all other causes (non-SSc) by age, and calculated age-standardized mortality rates (ASMRs) for SSc and non-SSc, and the ratio of SSc-ASMR to non-SSc-ASMR by age groups for each year from 1968 through 2015. We performed joinpoint regression to estimate the average annual percent change (AAPC) for each of these parameters.
SSc was recorded as the underlying cause of death in 5457 decedents aged ≤44 years, 18 395 aged 45-64, and 22 946 aged ≥65 from 1968 through 2015. At ages ≤44, the proportion of annual deaths decreased more for SSc than for non-SSc: AAPC, -2.2% (95% CI, -2.4% to -2.0%) for SSc vs -1.5% (-1.9% to -1.1%) for non-SSc. Consistently, SSc-ASMR decreased from 1.0 (95% CI, 0.8-1.2) in 1968 to 0.4 (0.3-0.5) per million persons in 2015, a cumulative decrease of 60% at an AAPC of -1.9% (95% CI, -2.5% to -1.2%) at ages ≤44. The SSc-ASMR:non-SSc-ASMR ratio also decreased cumulative -20%; AAPC -0.3% (95% CI, -1.15% to 0.55%) in the ≤44-years group. In contrast, those aged ≥65 experienced a steep increase in the SSc-ASMR cumulative 187.0%; AAPC 2.0% (95% CI, 1.8-2.2) and the SSc-ASMR:non-SSc-ASMR ratio cumulative 395.4%; AAPC 3.3% (95% CI, 2.9-3.7).
Mortality for SSc has steadily decreased at younger ages over the past five decades.
Key points
Several distinct strategies produce and conserve heat to maintain the body temperature of mammals, each associated with unique physiologies, with consequences for wellness and disease ...susceptibility
Highly regulated properties of skin offset the total requirement for heat production
We hypothesize that the adipose component of skin is primarily responsible for modulating heat flux; here we evaluate the relative regulation of adipose depots in mouse and human, to test their recruitment to heat production and conservation
We found that insulating mouse dermal white adipose tissue accumulates in response to environmentally and genetically induced cool stress; this layer is one of two adipose depots closely apposed to mouse skin, where the subcutaneous mammary gland fat pads are actively recruited to heat production
In contrast, the body‐wide adipose depot associated with human skin produces heat directly, potentially creating an alternative to the centrally regulated brown adipose tissue
Mammalian skin impacts metabolic efficiency system‐wide, controlling the rate of heat loss and consequent heat production. Here we compare the unique fat depots associated with mouse and human skin, to determine whether they have corresponding functions and regulation. For humans, we assay a skin‐associated fat (SAF) body‐wide depot to distinguish it from the subcutaneous fat pads characteristic of the abdomen and upper limbs. We show that the thickness of SAF is not related to general adiposity; it is much thicker (1.6‐fold) in women than men, and highly subject‐specific. We used molecular and cellular assays of β‐adrenergic‐induced lipolysis and found that dermal white adipose tissue (dWAT) in mice is resistant to lipolysis; in contrast, the body‐wide human SAF depot becomes lipolytic, generating heat in response to β‐adrenergic stimulation. In mice challenged to make more heat to maintain body temperature (either environmentally or genetically), there is a compensatory increase in thickness of dWAT: a corresponding β‐adrenergic stimulation of human skin adipose (in vivo or in explant) depletes adipocyte lipid content. We summarize the regulation of skin‐associated adipocytes by age, sex and adiposity, for both species. We conclude that the body‐wide dWAT depot of mice shows unique regulation that enables it to be deployed for heat preservation; combined with the actively lipolytic subcutaneous mammary fat pads they enable thermal defence. The adipose tissue that covers human subjects produces heat directly, providing an alternative to the brown adipose tissues.
Interactive visualization tools are being used by an increasing number of members of the general public; however, little is known about how, and how well, people use visualizations to infer ...causality. Adapted from the mediation causal model, we designed an analytic framework to systematically evaluate human performance, strategies, and pitfalls in a visual causal reasoning task. We recruited 24 participants and asked them to identify the mediators in a fictitious dataset using bar charts and scatter plots within our visualization interface. The results showed that the accuracy of their responses as to whether a variable is a mediator significantly decreased when a confounding variable directly influenced the variable being analyzed. Further analysis demonstrated how individual visualization exploration strategies and interfaces might influence reasoning performance. We also identified common strategies and pitfalls in their causal reasoning processes. Design implications for how future visual analytics tools can be designed to better support causal inference are discussed.
Objective
To identify secular trends associated with systemic sclerosis (SSc) mortality over a 48‐year period.
Methods
Using national mortality data compiled by the Centers for Disease Control and ...Prevention’s Wide‐Ranging Online Data for Epidemiologic Research, and population data from the US Census Bureau, we calculated an age‐standardized mortality rate (ASMR) for SSc and non‐SSc (all other causes), and we also calculated the ratio of the SSc ASMR to the non‐SSc ASMR for each year from 1968 to 2015. We then used a joinpoint regression model to evaluate mortality trends overall and by sex and race.
Results
From 1968 to 2015, there were 46,798 deaths with SSc recorded as the “underlying” cause of death and 106,058,839 non‐SSc deaths. There were an additional 9,063 deaths with SSc recorded as a “contributing” cause of death from 1999 to 2015. Whereas the non‐SSc ASMR decreased throughout the 48‐year time period, the SSc ASMR increased from 1968 to 2000, followed by decreases each year from 2001 to 2015. The SSc ASMR also decreased for deaths where SSc was a contributing cause from 1999 to 2015. Women and Black persons had higher SSc ASMRs and SSc ASMR to non‐SSc ASMR ratios than men and White persons, respectively. Additionally, SSc ASMRs and SSc ASMR to non‐SSc ASMR ratios increased at higher rates in women and White persons than in men and Black persons, respectively, during the initial three decades.
Conclusion
Mortality attributable to SSc increased from 1968 to 2000, followed by a steady decline from 2001 to 2015. However, SSc mortality relative to non‐SSc mortality remains high. SSc mortality has disproportionately changed by sex and race over the 48‐year period assessed in the present study.
The absorption of dietary fat involves the re-esterification of digested triacylglycerol in the enterocytes, a process catalyzed by acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2. Mice without a ...functional gene encoding MGAT2 (Mogat2−/−) are protected from diet-induced obesity. Surprisingly, these mice absorb normal amounts of dietary fat but increase their energy expenditure. MGAT2 is expressed in tissues besides intestine, including adipose tissue in both mice and humans. To test the hypothesis that intestinal MGAT2 regulates systemic energy balance, we generated and characterized mice deficient in MGAT2 specifically in the small intestine (Mogat2IKO). We found that, like Mogat2−/− mice, Mogat2IKO mice also showed a delay in fat absorption, a decrease in food intake, and a propensity to use fatty acids as fuel when first exposed to a high fat diet. Mogat2IKO mice increased energy expenditure although to a lesser degree than Mogat2−/− mice and were protected against diet-induced weight gain and associated comorbidities, including hepatic steatosis, hypercholesterolemia, and glucose intolerance. These findings illustrate that intestinal lipid metabolism plays a crucial role in the regulation of systemic energy balance and may be a feasible intervention target. In addition, they suggest that MGAT activity in extraintestinal tissues may also modulate energy metabolism.
Background: Global MGAT2 knock-out mice are protected from obesity.
Results: Intestine-specific MGAT2 knock-out mice showed increased energy expenditure and were protected against excess weight gain and metabolic disorders induced by high fat feeding.
Conclusion: Intestinal triacylglycerol metabolism is crucial in regulating systemic energy balance.
Significance: Intestinal MGAT2 may be a feasible intervention target for diseases associated with excess caloric intake.
Identifying the causal gene(s) that connects genetic variation to a phenotype is a challenging problem in genome-wide association studies (GWASs). Here, we develop a systematic approach that ...integrates mouse liver co-expression networks with human lipid GWAS data to identify regulators of cholesterol and lipid metabolism. Through our approach, we identified 48 genes showing replication in mice and associated with plasma lipid traits in humans and six genes on the X chromosome. Among these 54 genes, 25 have no previously identified role in lipid metabolism. Based on functional studies and integration with additional human lipid GWAS datasets, we pinpoint Sestrin1 as a causal gene associated with plasma cholesterol levels in humans. Our validation studies demonstrate that Sestrin1 influences plasma cholesterol in multiple mouse models and regulates cholesterol biosynthesis. Our results highlight the power of combining mouse and human datasets for prioritization of human lipid GWAS loci and discovery of lipid genes.
Display omitted
•Systematic method to combine mouse liver network and human lipid GWAS for discovery•Identification of a conserved liver cholesterol module across mouse populations•Prioritization of genes replicated in mouse and associated with human lipid traits•Validation of Sestrin1 as a gene that regulates cholesterol biosynthesis
Here, Li et al. develop a systematic approach that integrates mouse liver co-expression networks together with human lipid GWAS datasets to identify lipid metabolism genes. Using this approach, they pinpoint Sestrin1 as a gene associated with cholesterol levels in humans and demonstrate that Sestrin1 protein can regulate cholesterol biosynthesis.
No large population-based studies have been done on systemic lupus erythematosus (SLE) mortality trends in the United States.
To identify secular trends and population characteristics associated with ...SLE mortality.
Population-based study using a national mortality database and census data.
United States.
All U.S. residents, 1968 through 2013.
Joinpoint trend analysis of annual age-standardized mortality rates (ASMRs) for SLE and non-SLE causes by sex, race/ethnicity, and geographic region; multiple logistic regression analysis to determine independent associations of demographic variables and period with SLE mortality.
There were 50 249 SLE deaths and 100 851 288 non-SLE deaths from 1968 through 2013. Over this period, the SLE ASMR decreased less than the non-SLE ASMR, with a 34.6% cumulative increase in the ratio of the former to the latter. The non-SLE ASMR decreased every year starting in 1968, whereas the SLE ASMR decreased between 1968 and 1975, increased between 1975 and 1999, and decreased thereafter. Similar patterns were seen in both sexes, among black persons, and in the South. However, statistically significant increases in the SLE ASMR did not occur among white persons over the 46-year period. Females, black persons, and residents of the South had higher SLE ASMRs and larger cumulative increases in the ratio of the SLE to the non-SLE ASMR (31.4%, 62.5%, and 58.6%, respectively) than males, other racial/ethnic groups, and residents of other regions, respectively. Multiple logistic regression showed independent associations of sex, race, and region with SLE mortality risk and revealed significant racial/ethnic differences in associations of SLE mortality with sex and region.
Underreporting of SLE on death certificates may have resulted in underestimates of SLE ASMRs. Accuracy of coding on death certificates is difficult to ascertain.
Rates of SLE mortality have decreased since 1968 but remain high relative to non-SLE mortality, and significant sex, racial, and regional disparities persist.
None.
Although prenatal alcohol exposure (PAE) reduces offspring growth, it may increase obesity risk at adolescence. Animal models of PAE display glucose intolerance and increased adiposity, suggesting ...that PAE causes metabolic reprogramming. We tested this hypothesis in a mouse model of binge PAE, wherein pregnant C57Bl/6J females received 3 g/kg alcohol (ETOH) daily from gestational day 12.5 to 17.5; maltodextrin (MD) and medium chain triglycerides (MCT) served as isocaloric nutritional controls, and sham (H2O) treatment controlled for gavage stress. Our comprehensive assessment quantified body composition, energy expenditure, glucose tolerance, and cardiovascular function in offspring at age 17 weeks. Although ETOH pups were initially lighter than all other groups, they did not have a unique obesogenic phenotype. Instead, a similar obesogenic phenotype emerged in all three caloric groups (MCT, MD, ETOH), such that caloric groups had greater post-weaning weight gain (both sexes), reduced gonadal fat weight (males), and reduced glucose clearance (males) compared against H2O offspring. PAE did not affect body composition, respiratory exchange ratio, metabolic adaption to high-fat or low-fat diet, eating behavior, and blood pressure, and ETOH values did not differ from those obtained from isocaloric controls. Exposure to a higher alcohol dose (4.5 g/kg) or a high-fat (60%) diet did not exacerbate differences in body composition or glucose tolerance. "PAE-specific" effects on postnatal growth, glucose tolerance, adiposity, or hypertension only emerged when PAE offspring were compared just against H2O controls, or against MD controls. We conclude that prior reports of obesity and glucose intolerance in adult PAE offspring reflect the contribution of added gestational calories, and not alcohol's pharmacologic action. Results suggest that the increased adiposity risk in FASD is not caused by metabolic reprogramming, and instead originates from behavioral, medication, and/or dietary practices. This study highlights the importance of appropriate dietary controls in nutritional studies of PAE.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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