Primary biliary cirrhosis (PBC) is generally a slowly progressive disease that may lead to cirrhosis and liver failure. However, patients with PBC often suffer from a variety of symptoms long before ...the development of cirrhosis that include issues of daily living that have an impact on their work environment and their individual quality of life. We therefore examined multiple parameters by taking advantage of the database of our cohort of 1032 patients with PBC and 1041 matched controls. The data were obtained from patients from 23 tertiary referral centers throughout the United States and from rigorously matched controls by age, sex, ethnicity, and random‐digit dialing. The data showed that patients with PBC were more likely than controls to have significant articular symptoms, a reduced ability to perform household chores, and the need for help with routine activities. Patients with PBC rated their overall activity similar or superior to that of controls; however, more of them reported limitations in their ability to carry out activities at work or at home and difficulties in everyday activities. PBC cases also more frequently reported limitations in participating in certain sports or exercises and pursuing various hobbies; however, they did not report significant limitations in social activities. In a multivariable analysis, household income, a diagnosis of systemic lupus erythematosus, limitations in work activities, a reduction in work secondary to disability, and church attendance were independently increased in PBC cases with respect to controls. Conclusion: Our data indicate that the quality of life of patients with PBC in the United States is generally well preserved. Nevertheless, patients with PBC suffer significantly more than controls from a variety of symptoms that are beyond the immediate impact of liver failure and affect their lifestyle, personal relationships, and work activities. (HEPATOLOGY 2008.)
Background Low vitamin D status has been associated with markers of cardiovascular disease risk. Objective This cross-sectional study assessed the relationships between serum 25-hydroxyvitamin D ...25(OH)D and selected markers for cardiovascular disease risk, including metabolic syndrome and its components, in adult men and women. Methods Fasting blood samples, anthropometric measurements, and blood pressure were assessed in 257 men and women. Dietary intake was assessed with food frequency and dietary supplement questionnaires. Results Total vitamin D intake and that from dietary supplements were significantly associated with increasing serum 25(OH)D tertile (both P < .001). Mean ± SEM serum high-density lipoprotein cholesterol (HDL-C) increased in a graded fashion ( P < .001) from the lowest (48.4 ± 1.8 mg/dL) to the highest (62.3 ± 2.1 mg/dL) 25(OH)D tertile. The relationship between 25(OH)D and HDL-C remained significant ( P < .001) after adjustment for established determinants of the HDL-C, with each 10-ng/mL increase in 25(OH)D associated with a 4.2-mg/dL increase in HDL-C concentration. Serum triglycerides ( P = .008), waist circumference ( P < .001), and body mass index ( P < .001) showed graded, inverse relationships with 25(OH)D tertile, and the prevalence of metabolic syndrome decreased significantly from the lowest to the highest 25(OH)D tertile (31%, 14%, and 10%, respectively, P for trend = .001). Conclusions Lower serum 25(OH)D is associated with the metabolic syndrome and adverse values for some metabolic syndrome risk factors, particularly the HDL-C concentration. Research is warranted to assess whether increasing vitamin D intake will improve the metabolic cardiovascular risk factor profile.
Assessing the trophic role and interaction of an animal is key to understanding its general ecology and dynamics. Conventional techniques used to elucidate diet, such as stomach content analysis, are ...not suitable for large threatened marine species. Non-lethal sampling combined with biochemical methods provides a practical alternative for investigating the feeding ecology of these species. Stable isotope and signature fatty acid analyses of muscle tissue were used for the first time to examine assimilated diet of the reef manta ray Manta alfredi, and were compared with different zooplankton functional groups (i.e. near-surface zooplankton collected during manta ray feeding events and non-feeding periods, epipelagic zooplankton, demersal zooplankton and several different zooplankton taxa). Stable isotope delta 15N values confirmed that the reef manta ray is a secondary consumer. This species had relatively high levels of docosahexaenoic acid (DHA) indicating a flagellate-based food source in the diet, which likely reflects feeding on DHA-rich near-surface and epipelagic zooplankton. However, high levels of omega 6 polyunsaturated fatty acids and slightly enriched delta 13C values in reef manta ray tissue suggest that they do not feed solely on pelagic zooplankton, but rather obtain part of their diet from another origin. The closest match was with demersal zooplankton, suggesting it is an important component of the reef manta ray diet. The ability to feed on demersal zooplankton is likely linked to the horizontal and vertical movement patterns of this giant planktivore. These new insights into the habitat use and feeding ecology of the reef manta ray will assist in the effective evaluation of its conservation needs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The American Gastroenterological Association (AGA) Institute Future Trends Committee (FTC) developed this report based on a consensus conference it convened on March 8–9, 2008, in Washington, DC. The ...report was prepared for the FTC by Carol Regueiro, MD, MSc, a medical writer under contract to the AGA Institute, and Michael Stolar, PhD, staff liaison to the FTC. This report was approved by the FTC on July 1, 2008, and accepted by the AGA Institute Governing Board on July 26, 2008.
Cell-type-specific transcriptional profiling often requires the isolation of specific cell types from complex tissues. We have developed “TaDa,” a technique that enables cell-specific profiling ...without cell isolation. TaDa permits genome-wide profiling of DNA- or chromatin-binding proteins without cell sorting, fixation, or affinity purification. The method is simple, sensitive, highly reproducible, and transferable to any model system. We show that TaDa can be used to identify transcribed genes in a cell-type-specific manner with considerable temporal precision, enabling the identification of differential gene expression between neuroblasts and the neuroepithelial cells from which they derive. We profile the genome-wide binding of RNA polymerase II in these adjacent, clonally related stem cells within intact Drosophila brains. Our data reveal expression of specific metabolic genes in neuroepithelial cells, but not in neuroblasts, and highlight gene regulatory networks that may pattern neural stem cell fates.
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•TaDa is a method for cell-type-specific profiling of chromatin binding proteins•TaDa does not require cell sorting, fixation, or affinity purification•This is a highly sensitive and robust technique for transcriptional profiling•We report differential RNA Pol II binding in clonally related stem cells
Southall et al. developed “TaDa,” a technique that enables cell-specific genome-wide profiling of DNA- or chromatin-binding proteins without cell isolation, fixation, or affinity purification. TaDa genome-wide profiles of RNA polymerase II binding reveal spatially and temporally precise distinctions between adjacent, clonally related neural stem cells in intact Drosophila brains.
AbstractObjectivesTo report reliable estimates of short term and long term survival rates for people with a diagnosis of heart failure and to assess trends over time by year of diagnosis, hospital ...admission, and socioeconomic group.DesignPopulation based cohort study.SettingPrimary care, United Kingdom.ParticipantsPrimary care data for 55 959 patients aged 45 and overwith a new diagnosis of heart failure and 278 679 age and sex matched controls in the Clinical Practice Research Datalink from 1 January 2000 to 31 December 2017 and linked to inpatient Hospital Episode Statistics and Office for National Statistics mortality data.Main outcome measuresSurvival rates at one, five, and 10 years and cause of death for people with and without heart failure; and temporal trends in survival by year of diagnosis, hospital admission, and socioeconomic group.ResultsOverall, one, five, and 10 year survival rates increased by 6.6% (from 74.2% in 2000 to 80.8% in 2016), 7.2% (from 41.0% in 2000 to 48.2% in 2012), and 6.4% (from 19.8% in 2000 to 26.2% in 2007), respectively. There were 30 906 deaths in the heart failure group over the study period. Heart failure was listed on the death certificate in 13 093 (42.4%) of these patients, and in 2237 (7.2%) it was the primary cause of death. Improvement in survival was greater for patients not requiring admission to hospital around the time of diagnosis (median difference 2.4 years; 5.3 v 2.9 years, P<0.001). There was a deprivation gap in median survival of 0.5 years between people who were least deprived and those who were most deprived (4.6 v 4.1 years, P<0.001).ConclusionsSurvival after a diagnosis of heart failure has shown only modest improvement in the 21st century and lags behind other serious conditions, such as cancer. New strategies to achieve timely diagnosis and treatment initiation in primary care for all socioeconomic groups should be a priority for future research and policy.
Disuse is a potent inducer of muscle atrophy, but the molecular mechanisms driving this loss of muscle mass are highly debated. In particular, the extent to which disuse triggers decreases in protein ...synthesis or increases in protein degradation, and whether these changes are uniform across muscles or influenced by age, is unclear. We aimed to determine the impact of disuse on protein synthesis and protein degradation in lower limb muscles of varied function and fiber type in adult and old rats. Alterations in protein synthesis and degradation were measured in the soleus, medial gastrocnemius, and tibialis anterior (TA) muscles of adult and old rats subjected to hindlimb unloading (HU) for 3, 7, or 14 days. Loss of muscle mass was progressive during the unloading period, but highly variable (-9 to -38%) across muscle types and between ages. Protein synthesis decreased significantly in all muscles, except for the old TA. Atrophy-associated gene expression was only loosely associated with protein degradation as muscle RING finger-1, muscle atrophy F-box (MAFbx), and Forkhead box O1 expression significantly increased in all muscles, but an increase in proteasome activity was only observed in the adult soleus. MAFbx protein levels were significantly higher in the old muscles compared with adult muscles, despite the old having higher expression of microRNA-23a. These results indicate that adult and old muscles respond similarly to HU, and the greatest loss in muscle mass occurs in predominantly slow-twitch extensor muscles due to a concomitant decrease in protein synthesis and increase in protein degradation.
In this study, we showed that age did not intensify the atrophy response to unloading in rats, but rather that the degree of atrophy was highly variable across muscles, indicating that changes in protein synthesis and protein degradation occur in a muscle-specific manner. Our data emphasize the importance of studying muscles of varying fiber-type and physiological function at multiple time points to fully understand the molecular mechanisms responsible for disuse atrophy.
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