Multidimentional proteomics for cell biology

The proteome is a dynamic system in which each protein has interconnected properties — dimensions — that together contribute to the phenotype of a cell. Measuring these properties has proved challenging owing to their diversity and dynamic nature. Advances in mass spectrometry-based proteomics now enable the measurement of multiple properties for thousands of proteins, including their abundance, isoform expression, turnover rate, subcellular localization, post-translational modifications and interactions. Complementing these experimental developments are new data analysis, integration and visualization tools as well as data-sharing resources. Together, these advances in the multidimensional analysis of the proteome are transforming our understanding of various cellular and physiological processes

Submaximal Oxygen Uptake Kinetics, Functional Mobility, and Physical Activity in Older Adults with Heart Failure and Reduced Ejection Fraction

Background: Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure (HF). We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, functional mobility, and physical activity in older adults with HF and reduced ejection fraction. Methods: Older adults with HF and reduced ejection fraction (n = 25, age 75 ± 7 years) were compared to 25 healthy age- and gender-matched controls. Assessments included a maximal treadmill test for peak oxygen uptake (VO2peak), oxygen uptake kinetics at onset of and on recovery from a submaximal treadmill test, functional mobility testing [Get Up and Go (GUG), Comfortable Gait Speed (CGS), Unipedal Stance (US)], and self-reported physical activity (PA). Results: Compared to controls, HF had worse performance on GUG, CGS, and US, greater delays in submaximal oxygen uptake kinetics, and lower PA. In controls, VO2peak was more strongly associated with functional mobility and PA than submaximal oxygen uptake kinetics. In HF patients, submaximal oxygen uptake kinetics were similarly associated with GUG and CGS as VO2peak, but weakly associated with PA. Conclusions: Based on their mobility performance, older HF patients with reduced ejection fraction are at risk for adverse functional outcomes. In this population, submaximal oxygen uptake measures may be equivalent to VO2 peak in predicting functional mobility, and in addition to being more feasible, may provide better insight into how aerobic function relates to mobility in older adults with HF

Pain and Physical and Psychological Symptoms in Ambulatory HIV Patients in the Current Treatment Era

Context HIV infection has become a manageable chronic disease. There are few studies of pain and symptoms in the current treatment era. Objectives The primary objective was to determine the prevalence of and risk factors for pain and physical and psychological symptoms in a population of ambulatory HIV patients. Methods We performed a cross-sectional study using the Brief Pain Inventory and the Memorial Symptom Assessment Scale. Results We evaluated 156 individuals with a median age of 47.5 years (range 21–71), median time since HIV diagnosis of 11 years (range 3(interquartile range [IQR] 308–683). The majority (125, 80.6%) had an undetectable viral load. Seventy-six (48.7%) reported pain, of whom 39 (51.3%) had moderate to severe pain, and 43 (57.3%) had pain that caused moderate to severe interference with their lives. The median number of symptoms was eight (IQR 5–14.5) of 32 queried. In multivariable analyses, patients with psychiatric illness were 39.8% more likely to have pain (P Conclusion Pain and other physical and psychological symptoms were common among ambulatory HIV patients. Pain and symptoms were strongly associated with psychiatric illness and IV drug use. Future investigation should evaluate interventions that include psychiatric and substance abuse components for HIV patients with pain

Myocardial bridging in the era of a drug epidemic: a case report addressing the need to revisit donor organ assessment

Abstract Background Myocardial bridging (MB), though typically a benign finding, may occasionally lead to syncope, myocardial infarction, arrhythmia, or sudden death. Surgical denervation of transplanted hearts complicates the management of such incidentally detected post-transplant coronary anomalies due to the lack of classic ischaemic symptoms. Case summary A middle-aged female underwent an uncomplicated cardiac transplantation from a healthy male donor in his early 20s who had suffered a cardiac arrest while using cocaine. Given the young donor age, a pre-transplant coronary angiogram (CAG) was deferred. However, 6-week post-transplant, routine CAG, and intravascular ultrasound revealed an extensive MB spanning a significant portion of the left anterior descending coronary artery with substantial myocardium at risk. A stress test with myocardial perfusion imaging performed to evaluate the functional significance of the bridge did not reveal any perfusion abnormalities in the myocardium at risk. Discussion In current practice, younger donors often do not undergo pre-transplantation CAG routinely performed in older donors given the lower prevalence of significant coronary disease. However, post-operatively this young donor was found to have passed on a potentially life-threatening MB to a denervated recipient, who cannot manifest typical anginal symptoms during ischaemia, thereby challenging providers to choose among strategies of watchful waiting, risk stratification, or pre-emptive intervention. In retrospect, the donor’s mode of death may have signalled an underlying structural abnormality that warranted further pre-transplant characterization. In order to ensure optimal quality of transplanted hearts, young donors may warrant pre-transplant CAG despite their age, particularly those with a history of drug use or suspicious mode of death. </jats:sec