Feasibility Study of a Sensor-Based Autonomous Load Control Exercise Training System for COPD Patients

Decision support systems (DSSs) which are able to automatically supervise and control physical exercise training of patients affected by chronic obstructive pulmonary disease (COPD) are regarded as a novel method to promote rehabilitation. The objective of our research work for this paper was to evaluate the feasibility of a rule-based DSS for autonomous bicycle ergometer training of COPD patients. Load control is based on real-time analysis of sensor parameters oxygen saturation and heart rate. Ten COPD patients have participated in a study, performing altogether 18 training sessions. On average, 7.4 rules were fired in each training session. Four sessions had to be stopped for different reasons. The average ergometer training load ranged between 31 and 47 W. The average percentage of heart rate in or lower than the intended target zone was 45.9 and 41.6 %, respectively. The average patient-perceived Borg value was 12.6?±?2.4. Patients reported a high satisfaction for the automatically controlled training. With the help of the DSS, patients may change their training place from a rehabilitation center to their own homes. More studies are needed to assess long-term clinical and motivational effects of the DSS in home environment.     

The predictive value of heart-type fatty acid-binding protein is independent from symptom duration in normotensive patients with pulmonary embolism

Background

Heart-type fatty acid-binding protein (H-FABP) is a useful biomarker for risk stratification of patients with pulmonary embolism (PE). In patients with acute myocardial infarction, H-FABP plasma concentrations rise after 30 minutes and return to normal within 20-24 hours. We tested whether the predictive value of H-FABP is affected by the duration of symptoms prior to diagnosis in patients with PE.

Material and Methods

We prospectively studied 257 consecutive normotensive patients with confirmed symptomatic PE.

Results

Patients with acute (< 24 hours; n = 150) symptom onset presented more often with syncope (28.7% vs. 6.5%; p < 0.001) compared to patients with symptoms ≥ 24 hours (n = 107); other baseline characteristics, comorbidities, and risk factors were distributed equally. Patients with an adverse 30-day outcome (6.6%) had higher H-FABP levels (11.84 [3.57-19.62] ng/ml) compared to patients with a favorable course (3.42 [1.92-5.42] ng/ml; p < 0.001). However, the proportion of patients with H-FABP levels ≥ 6 ng/ml did not differ among patients with acute symptom onset and late presentation (p = 0.104). Only tachycardia and elevation of H-FABP were associated with an increased risk of an adverse 30-day outcome both in patients with acute symptom onset (H-FABP: OR, 5.8; 95% CI, 1.4-24.5; p = 0.016; tachycardia: 7.0 [1.4-36.0]; p = 0.018) and late presentation (H-FABP: 9.3 [2.0-43.2]; p = 0.004 and tachycardia: 12.3 [1.5-103.6]; p = 0.021). The prognostic value could further be improved by the use of a simple H-FABP-based clinical prediction score.

Conclusions

Our findings indicate that H-FABP is a useful biomarker for risk stratification of normotensive patients with PE regardless of symptom duration prior to diagnosis.     

Physical Activity,Decision-Making Abilities,and Eating Disturbances in Pre- and Postbariatric Surgery Patients

Background

Physical activity (PA) is considered to have a beneficial influence on executive functioning, including decision-making. Enhanced decision-making after bariatric surgery may strengthen patients’ ability to delay gratification, helping to establish appropriate eating behavior. The objectives of this study were to (1) compare a preoperative group with a postoperative group with regard to daily PA, decision-making, and eating disturbances; and (2) investigate the relationship between these variables.

Methods

The study included 71 bariatric surgery candidates (55 % women, BMI [kg/m²] M?=?46.9, SD?=?6.0) and 73 postoperative patients (57 % women, BMI M?=?32.0, SD?=?4.1; 89 % Roux-en-Y gastric bypass, 11 % sleeve gastrectomy; months postoperative M?=?8.2, SD?=?3.5; total weight loss [%] M?=?33.2, SD?=?8.9) who completed SenseWear Pro₂ activity monitoring. Decision-making was assessed using a computerized version of the Iowa Gambling Task and eating disorder psychopathology using the Eating Disorder Examination-Questionnaire.

Results

The number of patients who were classified as physically inactive was similarly high in the pre- and postoperative groups. No group differences emerged with regard to decision-making, but the postoperative group exhibited less eating disturbances than the preoperative group. No significant associations were found between PA, decision-making, and eating behavior.

Conclusions

Patients after bariatric surgery were not more physically active than bariatric surgery candidates, which should be considered in care programs. Additionally, future research is needed to explore the possible link between PA, patients’ decision-making abilities, and eating disturbances concerning dose-response questions.

     

Efficacy of Bariatric Surgery in Type 2 Diabetes Mellitus Remission: the Role of Mini Gastric Bypass/One Anastomosis Gastric Bypass and Sleeve Gastrectomy at 1 Year of Follow-up. A European survey

Background

A retrospective study was undertaken to define the efficacy of both mini gastric bypass or one anastomosis gastric bypass (MGB/OAGB) and sleeve gastrectomy (SG) in type 2 diabetes mellitus (T2DM) remission in morbidly obese patients (pts).

Methods

Eight European centers were involved in this survey. T2DM was preoperatively diagnosed in 313/3252 pts (9.62 %). In 175/313 patients, 55.9 % underwent MGB/OAGB, while in 138/313 patients, 44.1 % received SG between January 2006 and December 2014.

Results

Two hundred six out of 313 (63.7 %) pts reached 1 year of follow-up. The mean body mass index (BMI) for MGB/OAGB pts was 33.1?±?6.6, and the mean BMI for SG pts was 35.9?±?5.9 (p?<?0.001). Eighty-two out of 96 (85.4 %) MGB/OAGB pts vs. 67/110 (60.9 %) SG pts are in remission (p?<?0.001). No correlation was found in the % change vs. baseline values for hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) in relation to BMI reduction, for both MGB/OAGB or SG (ΔFPG 0.7 and ΔHbA1c 0.4 for MGB/OAGB; ΔFPG 0.7 and ΔHbA1c 0.1 for SG). At multivariate analysis, high baseline HbA1c [odds ratio (OR)?=?0.623, 95 % confidence interval (CI) 0.419–0.925, p?=?0.01], preoperative consumption of insulin or oral antidiabetic agents (OR?=?0.256, 95 % CI 0.137–0.478, p?=?<0.001), and T2DM duration >10 years (OR?=?0.752, 95 % CI 0.512–0.976, p?=?0.01) were negative predictors whereas MGB/OAGB resulted as a positive predictor (OR?=?3.888, 95 % CI 1.654–9.143, p?=?0.002) of diabetes remission.

Conclusions

A significant BMI decrease and T2DM remission unrelated from weight loss were recorded for both procedures if compared to baseline values. At univariate and multivariate analyses, MGB/OAGB seems to outperform significantly SG. Four independent variables able to influence T2DM remission at 12 months have been identified.

     

Verhaltensprävention im betrieblichen Setting

Background

The office routine of many employees restrains physical activity and is full of one-sided work-load and stressful cognitive events. Tension in neck and shoulder, back pain, headaches, fatigue, difficulties in concentrating, skin and gastrointestinal problems may result. In order to contribute to employee’s physical and mental well-being, a 15-minute work-place activity program (“Break in Motion”) was implemented in the Schwäbisch Gmünd plant of ZF Lenksysteme.

Method

To assess whether “Break in Motion” reduces physical complaints, adds to subjective well-being and improves the working atmosphere, a longitudinal study was carried out. Written questionnaires were utilize before and after the intervention to screen possible effects (n?=?68 and 79).

Results

Comparison of means revealed reduction in health problems in the neck, the back and the shoulder and the dorsal spine area. Improved subjective well-being was statistically significant only for female participants. Almost all participants stated that the activity program strengthens social cohesion on the work floor.

Conclusion

The results suggest that, if regularly conducted, even a relatively short and as such amendable to the work-place demands and moreover demonstrably scalable exercise and activity program shows positive effects.     

Comparison of Longitudinal and Apical Foetal Speckle Tracking Echocardiography Using Tissue Motion Annular Displacement and Segmental Longitudinal Strain

The aim of our prospective pilot study with exploratory analysis was to compare longitudinal and apical foetal speckle tracking echocardiography (STE) using tissue motion annular displacement (TMAD) and segmental longitudinal strain (SLS). We compared two different STE quantification tools in a longitudinal and apical four-chamber view in 57 normal foetuses between 20 and 40 wk of gestation. Myocardial mechanical dyssynchrony and strain were assessed using offline quantification software (QLab Version 10.3, Philips Medical Systems, Andover, MA, USA). We compared the dyssynchrony measurements with TMAD and SLS in longitudinal and apical four-chamber views. Furthermore, we examined the segmental strain values of both ventricles with SLS and compared the differences between longitudinal and apical measurements. Dyssynchrony measurements with TMAD and SLS and strain measurements with SLS were feasible in all cases. In the apical view, the dyssynchrony measurements with TMAD were systematically greater than those achieved with SLS (p < 0.001). For the longitudinal view, no differences were observed between tools (p?=?0.153). The application of SLS provided similar results for dyssynchrony in both views (intra-class correlation coefficient [ICC]?=?0.281, p?=?0.623), but the strain measurements in the left and right ventricles differed significantly between views (ICC?=?–0.082, p?=?0.011, and ICC?=?–0.061, p?=?0.024, respectively). For TMAD, we found large differences in the dyssynchrony values between longitudinal and apical assessment (ICC?=?–0.060, p?=?0.03). Furthermore, TMAD exhibited reduced accuracy in the system's automatic tracking algorithm, limiting the data quality. The dyssynchrony assessment is affected less by the foetal position in SLS than in TMAD. The strain readings in SLS varied depending on the view in which they were assessed. The application of TMAD cannot be recommended for foetal STE.     

The genomics of ecological flexibility,large brains,and long lives in capuchin monkeys revealed with fecalFACS

Ecological flexibility, extended lifespans, and large brains have long intrigued evolutionary biologists, and comparative genomics offers an efficient and effective tool for generating new insights into the evolution of such traits. Studies of capuchin monkeys are particularly well situated to shed light on the selective pressures and genetic underpinnings of local adaptation to diverse habitats, longevity, and brain development. Distributed widely across Central and South America, they are inventive and extractive foragers, known for their sensorimotor intelligence. Capuchins have among the largest relative brain size of any monkey and a lifespan that exceeds 50 y, despite their small (3 to 5 kg) body size. We assemble and annotate a de novo reference genome for Cebus imitator. Through high-depth sequencing of DNA derived from blood, various tissues, and feces via fluorescence-activated cell sorting (fecalFACS) to isolate monkey epithelial cells, we compared genomes of capuchin populations from tropical dry forests and lowland rainforests and identified population divergence in genes involved in water balance, kidney function, and metabolism. Through a comparative genomics approach spanning a wide diversity of mammals, we identified genes under positive selection associated with longevity and brain development. Additionally, we provide a technological advancement in the use of noninvasive genomics for studies of free-ranging mammals. Our intra- and interspecific comparative study of capuchin genomics provides insights into processes underlying local adaptation to diverse and physiologically challenging environments, as well as the molecular basis of brain evolution and longevity.

Large brains, long lifespans, extended juvenescence, tool use, and problem solving are hallmark characteristics of great apes, and are of enduring interest in studies of human evolution (1–4). Similar suites of traits have arisen in other lineages, including some cetaceans, corvids and, independently, in another radiation of primates, the capuchin monkeys. Like great apes, they have diverse diets, consume and seek out high-energy resources, engage in complex extractive foraging techniques (5, 6) to consume difficult-to-access invertebrates and nuts (6), and have an extended lifespan, presently recorded up to 54 y in captivity (7, 8). While they do not show evidence of some traits linked with large brain size in humans (e.g., human-like social networks and cultural and technological transmission from older to younger groupmates), their propensity for tool use and their ecological flexibility may have contributed to their convergence with the great apes (9), offering opportunities for understanding the evolution of key traits via the comparative method (10–12). Similar approaches have revealed positive selection on genes related to brain size and long lives in great apes and other mammals (13, 14), but our understanding of the genetic underpinnings of these traits remains far from complete.Capuchins also offer excellent opportunities to study local adaptation to challenging seasonal biomes. They occupy diverse habitats, including rainforests and, in the northern extent of their range, tropical dry forests. Particular challenges of the tropical dry forest are staying hydrated during the seasonally prominent droughts, high temperatures in the absence of foliage, and coping metabolically with periods of fruit dearth (Fig. 1). The long-term study of white-faced capuchins (Cebus imitator) occupying these seasonal forests has demonstrated that high infant mortality rates accompany periods of intense drought, illustrating the strength of this selective pressure (15). Furthermore, the seasonally low abundance of fruit is associated with muscular wasting and low circulating levels of urinary creatinine among these capuchins (16). Additionally, the sensory challenges of food search in dry versus humid biomes are also distinct. Odor detection and propagation is affected by temperature and humidity (17), and color vision is hypothesized to be adaptive in the search for ripe fruits and young reddish leaves against a background of thick, mature foliage (18), which is absent for long stretches in dry deciduous forests. The behavioral plasticity of capuchins is widely acknowledged as a source of their ability to adapt to these dramatically different habitats (19–21). However, physiological processes, including water balance and metabolic adaptations to low caloric intake, and sensory adaptations to food search, are also anticipated to be targets of natural selection, as seen in other mammals (22–24). Understanding population-level differences between primates inhabiting different biomes, contextualized by their demographic history, genomic diversity, and historical patterns of migration, will generate new insights.Open in a separate windowFig. 1.SSR during wet (Left) and dry (Center) seasons. (Right) Map of sampling locations in Costa Rica. The two northern sites, SSR and Cañas, have tropical dry-forest biomes, whereas the two southern sites, Quepos and Manuel Antonio, are tropical wet forests. Photos courtesy of A.D.M. Drawing of white-faced capuchin monkey by Alejandra Tejada-Martinez; map courtesy of Eric Gaba–Wikimedia Commons user: Sting.Unfortunately, high-quality biological specimens from wild capuchins are not readily available. As is the case with most of the world’s primates, many of which are rare or threatened (25), this has limited the scope of questions about their biology that can be answered. Although recent advances in noninvasive genomics have allowed for the sequencing of partial genomes by enriching the proportion of endogenous DNA in feces (26–29), it has not yet been feasible to sequence whole genomes from noninvasive samples at high coverage; this has limited the extent to which noninvasive samples can be used to generate genomic resources for nonmodel organisms, such as capuchins.Toward identifying the genetic underpinnings of local adaptation to seasonally harsh environments, large brains, and long lifespans, we assembled and annotated a reference genome of C. imitator (SI Appendix, Table S1). Additionally, we sequenced the genomes of individuals inhabiting two distinct environments in Costa Rica: Lowland evergreen rainforest (southern population) and lowland tropical dry forest (northern population). We conducted high-coverage resequencing (10× to 47×) for 10 of these individuals, and sequenced an additional 13 at low-coverage (0.1× to 4.4×). Importantly, to facilitate the population-wide analyses without the need for potentially harmful invasive sampling of wild primates, we developed a method for minimally biased, whole-genome sequencing of fecal DNA using fluorescence-activated cell sorting (fecalFACS) that we used to generate both high- and low-coverage genomes (Fig. 2). With these genomes, we assess the genetic underpinnings of capuchin-specific biology and adaptation in a comparative framework. First, we scanned the high-coverage genomes (six from the northern dry forest and four from the southern rainforest) for regions exhibiting population specific divergence to assess the extent of local adaptation to dry forest and rainforest environments. We examine how genes related to water balance, metabolism, muscular wasting, and chemosensation have diverged between populations. Second, we conduct an analysis of positive selection on the white-faced capuchin genome through codon-based models of evolution and enrichment tests focusing on genes that may underlie brain development and lifespan. Third, we identify the population structure, genomic diversity, and demographic history of the species using a mixture of traditional and noninvasive fecalFACS genomes (n = 23).Open in a separate windowFig. 2.Mapping percentages of sequencing reads from RNAlater preserved fecal DNA libraries prepared with FACS for (A) all samples (box-plot elements: center line, median; box limits, upper and lower quartiles; whiskers, 1.5× interquartile range; points, outliers), and (B) individual libraries. (C) Increase in mapping rate for RNAlater preserved samples. (D) Relationship between mapped read duplication and number of cells with LOESS smoothing. The duplication rate decreases sharply once a threshold of about 1,000 cells is reached.     

SAC phosphoinositide phosphatases at the tonoplast mediate vacuolar function in Arabidopsis

Phosphatidylinositol (PtdIns) is a structural phospholipid that can be phosphorylated into various lipid signaling molecules, designated polyphosphoinositides (PPIs). The reversible phosphorylation of PPIs on the 3, 4, or 5 position of inositol is performed by a set of organelle-specific kinases and phosphatases, and the characteristic head groups make these molecules ideal for regulating biological processes in time and space. In yeast and mammals, PtdIns3P and PtdIns(3,5)P₂ play crucial roles in trafficking toward the lytic compartments, whereas the role in plants is not yet fully understood. Here we identified the role of a land plant-specific subgroup of PPI phosphatases, the suppressor of actin 2 (SAC2) to SAC5, during vacuolar trafficking and morphogenesis in Arabidopsis thaliana. SAC2–SAC5 localize to the tonoplast along with PtdIns3P, the presumable product of their activity. In SAC gain- and loss-of-function mutants, the levels of PtdIns monophosphates and bisphosphates were changed, with opposite effects on the morphology of storage and lytic vacuoles, and the trafficking toward the vacuoles was defective. Moreover, multiple sac knockout mutants had an increased number of smaller storage and lytic vacuoles, whereas extralarge vacuoles were observed in the overexpression lines, correlating with various growth and developmental defects. The fragmented vacuolar phenotype of sac mutants could be mimicked by treating wild-type seedlings with PtdIns(3,5)P₂, corroborating that this PPI is important for vacuole morphology. Taken together, these results provide evidence that PPIs, together with their metabolic enzymes SAC2–SAC5, are crucial for vacuolar trafficking and for vacuolar morphology and function in plants.Polyphosphoinositides (PPIs) are a class of signaling membrane lipids, comprising the phosphorylated products of phosphatidylinositol (PtdIns). PPIs perform a dual function as scaffolding signals and precursors for other molecular messengers, which, together with their specific distribution at different intracellular membranes, makes PPIs important mediators of a wide variety of cellular processes, such as membrane trafficking and homeostasis, cytoskeleton organization, nuclear signaling, and stress responses (1–5). The metabolism of PPIs is regulated by specific kinases, phosphatases, and phospholipases to tightly control the concentration and intracellular localization of different lipid pools (2, 6, 7).In yeast, two phosphoinositide (PI) types, PtdIns3P and PtdIns(3,5)P₂, and their interconversion have been shown to play crucial roles in trafficking toward the vacuole, regulation of vacuolar pH, and vacuolar membrane fusion and fission (8–11). In yeast and mammals, production and degradation of PtdIns(3,5)P₂ involve the PtdIns3P 5-kinase Fab1p/PIKfyve and the antagonistic phosphatase factor-induced gene/suppressor of actin 3 (Fig4/Sac3), respectively (8, 12–14). Impairment of genes implicated in PtdIns(3,5)P₂ metabolism has deleterious consequences in yeast, plants, and mammals (8, 15–19), demonstrating an essential function of this minor phospholipid. Recent observations also hint at a role for PPIs in plant vacuoles (18–20), but the data are scarce and remain inconclusive.Advances in deciphering various cellular roles of PIs include insights into the phosphatases responsible for hydrolyzing PPIs. A group of phosphatases, designated suppressor of actin (SAC) domain phosphatases, has been identified in lower eukaryotes, mammals, and plants (21). Whereas yeast and humans have only five genes harboring the SAC domain, the genome of the model plant Arabidopsis thaliana contains nine genes, of which some have been functionally characterized and demonstrated to be involved in the regulation of stress responses (22–24), polarized root hair expansion (3), or cell wall formation (25).Here we show that the functionally uncharacterized group of Arabidopsis SAC2–SAC5 proteins that is orthologous to the yeast Fig4p is involved in PPI metabolism. SAC2–SAC5 localize along with PtdIns3P to the tonoplast and maintain the morphology of storage and lytic vacuoles. Our results demonstrate the crucial role of PPIs and SAC domain phosphatases in the function and morphology of vacuoles in plants.