Markovian analysis of phasic measures of REM sleep in normal, depressed, and schizophrenic subjects

Rapid eye movement (REM) phasic activity refers to brief events that occur in periods of REM sleep, such as individual eye movements (EMs). REM density (RD) is the bestknown measure of such activity, although reports of RD differences among normal, depressed, and schizophrenic subjects have been equivocal. RD is a measure with a large variability, and its physiological substrate is not known. We sought a more consistent measure which might also suggest the underlying physiology. Using the time intervals between individual EMs, we calculated empirical probability distributions which showed that EMs fell into two subgroups or states: "burst" and "isolated". Then, a novel Markov chain model of sequential transition between the states was calculated for nine normal, eight schizophrenic, and seven depressed male veterans. A significantly higher probability of remaining in the burst state was observed in both patient groups. The actual number of EMs in the isolated state was nearly identical in the three groups. Possible pontine neurochemical explanations involving cholinergic and serotonergic mechanisms are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30151/1/0000528.pd

High-resolution quantitative imaging of mammalian and bacterial cells using stable isotope mass spectrometry

Background: Secondary-ion mass spectrometry (SIMS) is an important tool for investigating isotopic composition in the chemical and materials sciences, but its use in biology has been limited by technical considerations. Multi-isotope imaging mass spectrometry (MIMS), which combines a new generation of SIMS instrument with sophisticated ion optics, labeling with stable isotopes, and quantitative image-analysis software, was developed to study biological materials. Results: The new instrument allows the production of mass images of high lateral resolution (down to 33 nm), as well as the counting or imaging of several isotopes simultaneously. As MIMS can distinguish between ions of very similar mass, such as ^{12}C^{15}N^{-} and ^{13}C^{14}N^{-}, it enables the precise and reproducible measurement of isotope ratios, and thus of the levels of enrichment in specific isotopic labels, within volumes of less than a cubic micrometer. The sensitivity of MIMS is at least 1,000 times that of ^{14}C autoradiography. The depth resolution can be smaller than 1 nm because only a few atomic layers are needed to create an atomic mass image. We illustrate the use of MIMS to image unlabeled mammalian cultured cells and tissue sections; to analyze fatty-acid transport in adipocyte lipid droplets using ^{13}C-oleic acid; to examine nitrogen fixation in bacteria using ^{15}N gaseous nitrogen; to measure levels of protein renewal in the cochlea and in post-ischemic kidney cells using ^{15}N-leucine; to study DNA and RNA co-distribution and uridine incorporation in the nucleolus using ^{15}N-uridine and ^{81}Br of bromodeoxyuridine or ^{14}C-thymidine; to reveal domains in cultured endothelial cells using the native isotopes ^{12}C, ^{16}O, ^{14}N and ^{31}P; and to track a few ^{15}N-labeled donor spleen cells in the lymph nodes of the host mouse. Conclusion: MIMS makes it possible for the first time to both image and quantify molecules labeled with stable or radioactive isotopes within subcellular compartments

No reserve in isokinetic cycling power at intolerance during ramp incremental exercise in endurance-trained men.

During whole-body exercise in health, maximal oxygen uptake (V̇O2max) is typically attained at or immediately prior to the limit of tolerance (LoT). At the V̇O2max and LoT of incremental exercise, a fundamental, but unresolved, question is whether maximal evocable power can increase above the task requirement, i.e. whether there is a "power reserve" at the LoT. Using an instantaneous switch from cadence-independent to isokinetic cycle ergometry, we determined maximal evocable power at the limit of ramp-incremental exercise. We hypothesized that in endurance-trained men at LoT, maximal (4s) isokinetic power would not differ from power required by the task. Baseline isokinetic power at 80rpm (PISO; measured at the pedals) and summed integrated EMG from 5 leg muscles (∑iEMG) were measured in 12 endurance-trained men (V̇O2max=4.2±1.0 l•min(-1)). Participants then completed a ramp-incremental exercise test (20-25W•min(-1)), with instantaneous measurement of PISO and ∑iEMG at the LoT. PISO decreased from 788±103W at baseline to 391±72W at LoT, which was not different from the required ramp-incremental flywheel power (352±58W; p>0.05). At LoT, the relative reduction in PISO was greater than the relative reduction in the isokinetic ∑iEMG (50±9 vs. 63±10% of baseline; p<0.05). During maximal ramp incremental exercise in endurance-trained men, maximum voluntary power is not different from the power required by the task, and is consequent to both central and peripheral limitations in evocable power. The absence of a power reserve suggests both the perceptual and physiological limits of maximum voluntary power production are not widely dissociated at LoT in this population

Cerebrovascular Risk Factors, Vascular Disease, and Neuropsychological Outcomes in Adults With Major Depression

To investigate the relationship of cerebrovascular risk factors (CVRFs), endothelial function, carotid artery intima medial thickness (IMT), and neuropsychological performance in a sample of 198 middle-aged and older individuals with major depressive disorder (MDD). Neuropsychological deficits are common among adults with MDD, particularly among those with CVRFs and potentially persons with subclinical vascular disease

Effects of Coping Skills Training on Quality of Life, Disease Biomarkers and Clinical Outcomes in Patients with Heart Failure: A Randomized Clinical Trial

Heart failure (HF) is a chronic disease that compromises patients’ quality of life (QoL). Interventions designed to reduce distress and improve disease self-management are needed. We evaluated the efficacy of a telephone-based coping skills training (CST) intervention

Intima-media thickness and age of first depressive episode

Late life depression, including patients with vascular depression, has been associated with higher levels of intima-media thickness (IMT). Although individuals with vascular depression tend to report a later onset of depression, the relationship of IMT and age of first depressive episode is uncertain in younger adults. We therefore investigated the relationship between IMT and age of first depressive episode in a sample of 202 adults (age range 40−81 years) with major depression (MDD)

Sustainability appraisal: Jack of all trades, master of none?

Sustainable development is a commonly quoted goal for decision making and supports a large number of other discourses. Sustainability appraisal has a stated goal of supporting decision making for sustainable development. We suggest that the inherent flexibility of sustainability appraisal facilitates outcomes that often do not adhere to the three goals enshrined in most definitions of sustainable development: economic growth, environmental protection and enhancement, and the wellbeing of the human population. Current practice is for sustainable development to be disenfranchised through the interpretation of sustainability, whereby the best alternative is good enough even when unsustainable. Practitioners must carefully and transparently review the frameworks applied during sustainability appraisal to ensure that outcomes will meet the three goals, rather than focusing on a discourse that emphasises one or more goals at the expense of the other(s)

Cerebrovascular Risk Factors and Cerebral Hyperintensities among Middle-Aged and Older Adults With Major Depression

To examine the association between cerebral hyperintensities and cerebrovascular risk factors (CVRF) among middle-aged and older adults with major depressive disorder (MDD)

Data collection, handling and fitting strategies to optimize accuracy and precision of oxygen uptake kinetics estimation from breath-by-breath measurements.

Phase 2 pulmonary oxygen uptake kinetics (ϕ2 τVO2P) reflect muscle oxygen consumption dynamics and are sensitive to changes in state of training or health. This study identified an unbiased method for data collection, handling and fitting to optimize VO2P kinetics estimation. A validated computational model of VO2P kinetics and a Monte Carlo approach simulated 2 x 10(5) moderate intensity transitions using a distribution of metabolic and circulatory parameters spanning normal health. Effects of averaging (interpolation, binning, stacking or separate fitting of up to 10 transitions) and fitting procedures (bi-exponential fitting, or ϕ2 isolation by time removal, statistical or derivative methods followed by mono-exponential fitting) on accuracy and precision of ϕ2 τVO2P estimation were assessed. The optimal strategy to maximize accuracy and precision of τVO2P estimation was 1-s interpolation of 4 bouts, ensemble averaged, with the first 20 s of exercise data removed. Contradictory to previous advice, we found optimal fitting procedures removed no more than 20 s of ϕ1 data. Averaging method was less critical: interpolation, bin averaging and stacking gave similar results, each with greater accuracy compared to analyzing repeated bouts separately. The optimal procedure resulted in ϕ2 τVO2P estimates for transitions from an unloaded or loaded baseline that averaged 1.97±2.08 and 1.04±2.30 s from true, but were within 2 s of true in only 47-62% of simulations. Optimized 95% confidence intervals for τVO2P ranged from 4.08-4.51 s, suggesting a minimally important difference of ~5 s to determine significant changes in τVO2P during interventional and comparative studies