ACEI angiotensin-converting enzyme inhibitor ARB angiotensin receptor blocker BP blood pressure CCB calcium channel blocker CKD chronic kidney disease CVD cardiovascular disease ESRD end-stage renal disease GFR glomerular filtration rate HF heart failure

OBJECTIVEWe examined the role of butyric acid, a short-chain fatty acid formed by fermentation in the large intestine, in the regulation of insulin sensitivity in mice fed a high-fat diet.RESEARCH DESIGN AND METHODSIn dietary-obese C57BL/6J mice, sodium butyrate was administrated through diet supplementation at 5% wt/wt in the high-fat diet. Insulin sensitivity was examined with insulin tolerance testing and homeostasis model assessment for insulin resistance. Energy metabolism was monitored in a metabolic chamber. Mitochondrial function was investigated in brown adipocytes and skeletal muscle in the mice.RESULTSOn the high-fat diet, supplementation of butyrate prevented development of insulin resistance and obesity in C57BL/6 mice. Fasting blood glucose, fasting insulin, and insulin tolerance were all preserved in the treated mice. Body fat content was maintained at 10% without a reduction in food intake. Adaptive thermogenesis and fatty acid oxidation were enhanced. An increase in mitochondrial function and biogenesis was observed in skeletal muscle and brown fat. The type I fiber was enriched in skeletal muscle. Peroxisome proliferator–activated receptor-γ coactivator-1α expression was elevated at mRNA and protein levels. AMP kinase and p38 activities were elevated. In the obese mice, supplementation of butyrate led to an increase in insulin sensitivity and a reduction in adiposity.CONCLUSIONSDietary supplementation of butyrate can prevent and treat diet-induced insulin resistance in mouse. The mechanism of butyrate action is related to promotion of energy expenditure and induction of mitochondria function.

Abstract-Improving diet and lifestyle is a critical component of the American Heart Association's strategy for cardiovascular disease risk reduction in the general population. This document presents recommendations designed to meet this objective. Specific goals are to consume an overall healthy diet; aim for a healthy body weight; aim for recommended levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides; aim for normal blood pressure; aim for a normal blood glucose level; be physically active; and avoid use of and exposure to tobacco products. The recommendations are to balance caloric intake and physical activity to achieve and maintain a healthy body weight; consume a diet rich in vegetables and fruits; choose whole-grain, high-fiber foods; consume fish, especially oily fish, at least twice a week; limit intake of saturated fat to Ͻ7% of energy, trans fat to Ͻ1% of energy, and cholesterol to Ͻ300 mg/day by choosing lean meats and vegetable alternatives, fat-free (skim) or low-fat (1% fat) dairy products and minimize intake of partially hydrogenated fats; minimize intake of beverages and foods with added sugars; choose and prepare foods with little or no salt; if you consume alcohol, do so in moderation; and when you eat food prepared outside of the home, follow these Diet and Lifestyle Recommendations. By adhering to these diet and lifestyle recommendations, Americans can substantially reduce their risk of developing cardiovascular disease, which remains the leading cause of morbidity and mortality in the United States.

Peer reviewed eScholarship.orgPowered by the California Digital Library University of California Screening for Colorectal Cancer US Preventive Services Task Force Recommendation Statement US Preventive Services Task ForceT he US Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without obvious related signs or symptoms.It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment.The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms. Summary of Recommendations and EvidenceThe USPSTF recommends screening for colorectal cancer starting at age 50 years and continuing until age 75 years (A recommendation) (Figure 1).The risks and benefits of different screening methods vary. See the Clinical Considerations section later in this article and the Table for details about screening strategies.The decision to screen for colorectal cancer in adults aged 76 to 85 years should be an individual one, taking into account the patient's overall health and prior screening history (C recommendation).• Adults in this age group who have never been screened for colorectal cancer are more likely to benefit. IMPORTANCE Colorectal cancer is the second leading cause of cancer death in the United States. In 2016, an estimated 134 000 persons will be diagnosed with the disease, and about 49 000 will die from it. Colorectal cancer is most frequently diagnosed among adults aged 65 to 74 years; the median age at death from colorectal cancer is 73 years.OBJECTIVE To update the 2008 US Preventive Services Task Force (USPSTF) recommendation on screening for colorectal cancer.EVIDENCE REVIEW The USPSTF reviewed the evidence on the effectiveness of screening with colonoscopy, flexible sigmoidoscopy, computed tomography colonography, the guaiac-based fecal occult blood test, the fecal immunochemical test, the multitargeted stool DNA test, and the methylated SEPT9 DNA test in reducing the incidence of and mortality from colorectal cancer or all-cause mortality; the harms of these screening tests; and the test performance characteristics of these tests for detecting adenomatous polyps, advanced adenomas based on size, or both, as well as colorectal cancer. The USPSTF also commissioned a comparative modeling study to provide information on optimal starting and stopping ages and screening intervals across the different available screening methods.FINDINGS The USPSTF concludes with high certainty that screening for colorectal cancer in average-risk, asymptomatic adults aged 50 to 75 years is of substantial net benefit. Multiple screen...

Abstract-High intakes of dietary sugars in the setting of a worldwide pandemic of obesity and cardiovascular disease have heightened concerns about the adverse effects of excessive consumption of sugars. In 2001 to 2004, the usual intake of added sugars for Americans was 22.2 teaspoons per day (355 calories per day). Between 1970 and 2005, average annual availability of sugars/added sugars increased by 19%, which added 76 calories to Americans' average daily energy intake. Soft drinks and other sugar-sweetened beverages are the primary source of added sugars in Americans' diets. Excessive consumption of sugars has been linked with several metabolic abnormalities and adverse health conditions, as well as shortfalls of essential nutrients. Although trial data are limited, evidence from observational studies indicates that a higher intake of soft drinks is associated with greater energy intake, higher body weight, and lower intake of essential nutrients. National survey data also indicate that excessive consumption of added sugars is contributing to overconsumption of discretionary calories by Americans. On the basis of the 2005 US Dietary Guidelines, intake of added sugars greatly exceeds discretionary calorie allowances, regardless of energy needs. In view of these considerations, the American Heart Association recommends reductions in the intake of added sugars. A prudent upper limit of intake is half of the discretionary calorie allowance, which for most American women is no more than 100 calories per day and for most American men is no more than 150 calories per day from added sugars. (Circulation. 2009; 120:1011-1020.)Key Words: AHA Scientific Statements Ⅲ cardiovascular diseases Ⅲ carbohydrates, dietary Ⅲ diet Ⅲ beverages Ⅲ carbonated beverages Ⅲ lipids N ew evidence on the relationship between intake of sugars and cardiovascular health has emerged since the last American Heart Association (AHA) scientific statement was published in 2002. 1 In 2006, the AHA published revised diet and lifestyle recommendations that recommend minimizing the intake of beverages and foods with added sugars. 2 The present statement expands on that recommendation by reviewing the evidence for recommending a specific upper limit of intake for added sugars. Because the focus of the present statement is on added sugars, recommendations for intake of naturally occurring sugars and complex carbohydrates are beyond its scope. Consumption of Sugars in the United StatesSugars are a ubiquitous component of our food supply and are consumed as a naturally occurring component of many foods and as additions to foods during processing, preparation, or at the table. 3 There are various definitions for sugar. Table 1 The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclos...

Insulin resistance contributes importantly to the pathophysiology of type 2 diabetes mellitus. One mechanism mediating insulin resistance may involve the phosphorylation of serine residues in insulin receptor substrate-1 (IRS-1), leading to impairment in the ability of IRS-1 to activate downstream phosphatidylinositol 3-kinase-dependent pathways. Insulin-resistant states and serine phosphorylation of IRS-1 are associated with the activation of the inhibitor B kinase (IKK) complex. However, the precise molecular mechanisms by which IKK may contribute to the development of insulin resistance are not well understood. In this study, using phosphospecific antibodies against rat IRS-1 phosphorylated at Ser 307 (equivalent to Ser 312 in human IRS-1), we observed serine phosphorylation of IRS-1 in response to TNF-␣ or calyculin A treatment that paralleled surrogate markers for IKK activation. The phosphorylation of human IRS-1 at Ser 312 in response to tumor necrosis factor-␣ was significantly reduced in cells pretreated with the IKK inhibitor 15 deoxy-prostaglandin J 2 as well as in cells derived from IKK knock-out mice. We observed interactions between endogenous IRS-1 and IKK in intact cells using a co-immunoprecipitation approach. Moreover, this interaction between IRS-1 and IKK in the basal state was reduced upon IKK activation and increased serine phosphorylation of IRS-1. Data from in vitro kinase assays using recombinant IRS-1 as a substrate were consistent with the ability of IRS-1 to function as a direct substrate for IKK with multiple serine phosphorylation sites in addition to Ser 312 . Taken together, our data suggest that IRS-1 is a novel direct substrate for IKK and that phosphorylation of IRS-1 at Ser 312 (and other sites) by IKK may contribute to the insulin resistance mediated by activation of inflammatory pathways.Many factors implicated in the development of insulin resistance such as TNF-␣ 1 (1, 2), free fatty acids (3, 4), and serine phosphatase inhibitors (5, 6) are able to activate the inhibitor B kinase (IKK) complex and its downstream effector, NFB (7-10). Interestingly, insulin-sensitizing drugs such as thiazolidinediones inhibit NFB activity (11). Adiponectin, a cytokine secreted by adipose cells whose plasma levels are negatively correlated with insulin resistance (12), inhibits IKK activity in cells (13). Moreover, diet-induced insulin resistance is ameliorated in IKK2-deficient mice (14). Because IKK and NFB are major components of the intracellular inflammatory pathway, a cross-talk between metabolic and inflammatory signaling pathways may play an important role in the development of insulin resistance and the pathophysiology of major public health problems such as diabetes and obesity. However, molecular mechanisms by which IKK may specifically interact with metabolic insulin signaling pathways are not well understood. IKK is a serine kinase that controls the activation of NFB, a ubiquitous transcription factor closely associated with inflammation (15-18). In addition to inflammation, NF...

The USPSTF recommends against routine screening mammography in women aged 40 to 49 years. The decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take into account patient context, including the patient's values regarding specific benefits and harms. (Grade C recommendation) The USPSTF recommends biennial screening mammography for women between the ages of 50 and 74 years. (Grade B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the additional benefits and harms of screening mammography in women 75 years or older. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the additional benefits and harms of clinical breast examination beyond screening mammography in women 40 years or older. (I statement) The USPSTF recommends against clinicians teaching women how to perform breast self-examination. (Grade D recommendation) The USPSTF concludes that the current evidence is insufficient to assess additional benefits and harms of either digital mammography or magnetic resonance imaging instead of film mammography as screening modalities for breast cancer. (I statement).

The USPSTF recommends the use of low-dose aspirin (81 mg/d) as preventive medication after 12 weeks of gestation in women who are at high risk for preeclampsia. (B recommendation).