Myeloid PTP1B deficiency protects against atherosclerosis by improving cholesterol homeostasis through an AMPK-dependent mechanism

Funding This study was funded by the Development Trust, University of Aberdeen.Peer reviewe

Comparison of intramyocellular lipid metabolism in patients with diabetes and male athletes

Contributions D.D., A.H., S.G., S.P. and M.D. conceived the study and together with L.v.L., G.L., F.T. obtained the grant funding. AM executed the patient screening, recruitment, intervention planning, carried out all study investigations under respective specialist supervision (A.H./D.C./D.D. for magnetic resonance spectroscopy, F.T./G.L./D.D. for stable isotope investigation, S.G. for exercise intervention, S.P. for clinical supervision/management of diabetes as required, M.D. for all molecular laboratory analyses, A.M. analysed all data and performed statistical analysis under the supervision of G.H. L.v.L. provided expert advice in athletic physiology. Lipidomic analyses were carried out in P.W. laboratory. Blood/skeletal muscle enrichment analyses were carried out in B.F./F.T.-G.L. laboratories respectively, with practical input from R.G. A.R. and L.C. contributed as overall help to deliver study assessments in a technical role. M.K.H. analysed the food diaries. D.E.N. contributed to manuscript writing. D.D. and M.D. were the PhD supervisors for A.M. whose PhD thesis was based on this work. All authors contributed their respective specialist sections in drafting the manuscript.Peer reviewe

Science Frontiers In Galaxy Evolution: Deep-Wide Surveys

Astro2010: The Astronomy and Astrophysics Decadal Survey : Science White Papers no 79. Available online : http://www8.nationalacademies.org/astro2010/DetailFileDisplay.aspx?id=24

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Allocation of physician time in ambulatory practice : a time and motion study in 4 specialties

Background: Little is known about how physician time is allocated in ambulatory care. Objective: To describe how physician time is spent in ambulatory practice. Design: Quantitative direct observational time and motion study (during office hours) and self-reported diary (after hours). Setting: U.S. ambulatory care in 4 specialties in 4 states (Illinois, New Hampshire, Virginia, and Washington). Participants: 57 U.S. physicians in family medicine, internal medicine, cardiology, and orthopedics who were observed for 430 hours, 21 of whom also completed after-hours diaries. Measurements: Proportions of time spent on 4 activities (direct clinical face time, electronic health record [EHR] and desk work, administrative tasks, and other tasks) and self-reported after-hours work. Results: During the office day, physicians spent 27.0% of their total time on direct clinical face time with patients and 49.2% of their time on EHR and desk work. While in the examination room with patients, physicians spent 52.9% of the time on direct clinical face time and 37.0% on EHR and desk work. The 21 physicians who completed after-hours diaries reported 1 to 2 hours of after-hours work each night, devoted mostly to EHR tasks. Limitations: Data were gathered in self-selected, high-performing practices and may not be generalizable to other settings. The descriptive study design did not support formal statistical comparisons by physician and practice characteristics. Conclusion: For every hour physicians provide direct clinical face time to patients, nearly 2 additional hours is spent on EHR and desk work within the clinic day. Outside office hours, physicians spend another 1 to 2 hours of personal time each night doing additional computer and other clerical work.8 page(s

Severe hypercalcemia in a patient with extrapulmonary Mycobacterium abscessus: granuloma or immune reconstitution inflammatory syndrome? First case of Mycobacterium abscessus presenting as retroperitoneal lymphadenopathy with severe hypercalcemia: a case report and literature review

Background: Nontuberculous mycobacterium is a recognized cause of hypercalcemia, particularly in patients with acquired immunodeficiency syndrome (AIDS). Here we describe a case of severe hypercalcemia secondary to Mycobacterium abscessus (M. abscessus) in a patient with AIDS. To the best of our knowledge this is the first case report describing a case of M. abscessus presenting as retroperitoneal lymphadenopathy and severe hypercalcemia. Case description: A 56-year-old man with AIDS presented with altered mental status and somnolence for four days. Laboratory investigations were significant for calcium 16.49 mg/dL (RI 8.9–10.3 mg/dL), 1,25 dihydroxyvitamin D level 44.1 pg/ml (RI 19.9–79.3 pg/ml) and parathyroid hormone (PTH) 4 pg/mL (RI 15–65 pg/mL). CT scan of Abdomen and Pelvis showed hepatosplenomegaly with large retroperitoneal, retrocrural, and mesenteric lymphadenopathy which had an intense focal uptake on Gallium scan. Bone marrow biopsy revealed mild plasmacytosis (5%) with no evidence of myelodysplasia, acute leukemia or lymphoma. A subsequent lymph node biopsy showed fragments of fibrous tissue with lymphohistiocytic infiltrate and many acid-fast bacilli. Pre-antibiotic blood cultures grew Mycobacterium which was identified later as M. abscessus at four weeks. Conclusion: hypercalcemia in HIV-infected patients may suggest malignancy or infectious etiology, among other causes. Clinicians should be aware of the risk of hypercalcemia with nontuberculous mycobacterium (NTM) infection, whether as first manifestation or a late presenter in the disease course after initiating antiretroviral therapy (ART). We suggest careful monitoring of serum calcium level upon diagnosis of NTM infection and after initiation of ART, NTM therapy or vitamin D supplementation

What’s in a Badge? A Computational Reproducibility Investigation of the Open Data Badge Policy in one Issue of Psychological Science

[Preprint; Manuscript accepted at Psychological Science] In April 2019, Psychological Science published its first issue in which all research articles received the Open Data badge. We used that issue to investigate the effectiveness of this badge, focusing on the adherence to its aim at Psychological Science: sharing both data and code to ensure reproducibility of results. Twelve researchers of varying experience levels attempted to reproduce the results of the empirical articles in the target issue (at least three researchers per article). We found that while all 14 articles provided at least some data and six provided analysis code, only one article was rated to be exactly reproducible, and three essentially reproducible with minor deviations. We suggest that researchers should be encouraged to adhere to the higher standard in force at Psychological Science. Moreover, a check of reproducibility during peer review may be preferable to the ‘disclosure method’ of awarding badges

Comparison of intramyocellular lipid metabolism in patients with diabetes and male athletes

Despite opposing insulin sensitivity and cardiometabolic risk, both athletes and patients with type 2 diabetes have increased skeletal myocyte fat storage: the so-called “athlete’s paradox”. In a parallel non-randomised, non-blinded trial (NCT03065140), we characterised and compared the skeletal myocyte lipid signature of 29 male endurance athletes and 30 patients with diabetes after undergoing deconditioning or endurance training respectively. The primary outcomes were to assess intramyocellular lipid storage of the vastus lateralis in both cohorts and the secondary outcomes were to examine saturated and unsaturated intramyocellular lipid pool turnover. We show that athletes have higher intramyocellular fat saturation with very high palmitate kinetics, which is attenuated by deconditioning. In contrast, type 2 diabetes patients have higher unsaturated intramyocellular fat and blunted palmitate and linoleate kinetics but after endurance training, all were realigned with those of deconditioned athletes. Improved basal insulin sensitivity was further associated with better serum cholesterol/triglycerides, glycaemic control, physical performance, enhanced post insulin receptor pathway signalling and metabolic sensing. We conclude that insulin-resistant, maladapted intramyocellular lipid storage and turnover in patients with type 2 diabetes show reversibility after endurance training through increased contributions of the saturated intramyocellular fatty acid pools. Clinical Trial Registration: NCT03065140: Muscle Fat Compartments and Turnover as Determinant of Insulin Sensitivity (MISTY)