On the feasibility of a moving support for surgery on the beating heart

In this paper the use of a heart-tracking hand support is proposed to allow coronary artery bypass grafting surgery to take place on the beating heart. Requiring only a three-degree-of-freedom motion platform that tracks a point on the surgical site, this method eliminates the tissue damage associated with the use of physical heart stabilizers and provides a much cheaper alternative to six-degree-of-freedom masterslave systems. To demonstrate the feasibility of such an approach, a motion platform with a motion range and frequency typical of coronary motion was designed and built. A task typical of suture placement was executed on this platform by twenty six subjects, while (i) the platform was stationary, (ii) the platform was in motion with the subjects’ hands attached to it, and (iii) the platform was in motion but the subjects’ hands were not attached to it. This system simulates the use of a motion tracking platform with perfect tracking performance. Mono and stereo vision systems were also mounted to the platform to provide subjects with a visually stable view. Accuracy and task completion time were measured. Relative to the stationary platform case, only a 10% loss of accuracy and 40% increase in completion time were noted when the platform was in motion but the subjects’ hands were attached to it. When the hands were not attached, a significantly higher 50% loss of accuracy and 100% increase in task completion time were noted. Task completion time was improved when a visually stable view was also provided, but accuracy results were inconclusive due to problems with the vision systems used

Ariel - Volume 5 Number 1

Editors Mark Dembert J.D. Kanofskv Entertainment Editor Robert Breckenridge Gary Kaskey Editor Emeritus David A. Jacoby Photographer Scott Kastner Staff Richard Blutstein Bob Johnson John R. Cohn Joseph Sassani Ken Jaffe Bob Sklarof

Plasma Carotenoid Concentrations of Incubating American Kestrels (\u3cem\u3eFalco sparverius\u3c/em\u3e) Show Annual, Seasonal, and Individual Variation and Explain Reproductive Outcome

In wild birds, the proximate and ultimate factors that affect circulating carotenoid concentrations remain poorly understood. We studied variation in plasma carotenoid concentrations across several scales: annual, seasonal, pair, territory and individual, and evaluated whether plasma carotenoid concentrations explained reproductive outcome of wild American kestrels (Falco sparverius). We sampled plasma carotenoid concentrations of 99 female and 80 male incubating kestrels from April to June in 2008 to 2012. Plasma carotenoid concentrations were explained by an interaction between year and sex, date, and random effects for pair and individual identity. In general, plasma carotenoid concentrations of males were significantly higher than females, but this depended on year. Within a breeding season, earlier nesting kestrels had higher carotenoid concentrations than later nesting kestrels, a pattern that is coincident with seasonal trends in local fitness. Pair and individual identity explained variation in carotenoid concentrations suggesting that carotenoid concentrations of mated birds were correlated, and some individuals consistently maintained higher carotenoid levels than others. Male carotenoid concentrations were positively associated with number of young fledged per pair. These results are consistent with the hypothesis that higher quality individuals have higher carotenoid levels compared to lower quality individuals, despite annual variations in carotenoid availability

Ursodeoxycholic acid as a novel disease-modifying treatment for Parkinson’s disease: protocol for a two-centre, randomised, double-blind, placebo-controlled trial, The 'UP' study

Introduction There are no disease-modifying treatments for Parkinson’s disease (PD). We undertook the first drug screen in PD patient tissue and idntified ursodeoxycholic acid (UDCA) as a promising mitochondrial rescue agent. The aims of this trial are to determine safety and tolerability of UDCA in PD at 30 mg/kg, confirm the target engagement of UDCA, apply a novel motion sensor-based approach to quantify disease progression objectively, and estimate the mean effect size and its variance on the change in motor severity. Methods and analysis This is a phase II, two-centre, double-blind, randomised, placebo-controlled trial of UDCA at a dose of 30 mg/kg in 30 participants with early PD. Treatment duration is 48 weeks, followed by an 8-week washout phase. Randomisation is 2:1, drug to placebo. Assessments are performed at baseline, week 12, 24, 36, 48 and 56. The primary outcome is safety and tolerability. Secondary outcomes will compare the change between baseline and week 48 using the following three approaches: the Movement Disorders Society Unified Parkinson’s Disease Rating Scale Part 3 in the practically defined ‘OFF’ medication state; confirmation of target engagement, applying 31Phosphorus MR Spectroscopy to assess the levels of ATP and relevant metabolites in the brain; and objective quantification of motor impairment, using a validated, motion sensor-based approach. The primary outcome will be reported using descriptive statistics and comparisons between treatment groups. For each secondary outcome, the change from baseline will be summarised within treatment groups using summary statistics and appropriate statistical tests assessing for significant differences. All outcomes will use an intention-to-treat analysis population. Ethics and dissemination This trial has been approved by the East of England – Cambridgeshire and Hertfordshire Research Ethics committee. Results will be disseminated in peer-reviewed journals, presentations at scientific meetings and to patients in a lay-summary format. Trial registration number NCT03840005

A review of ECG-based diagnosis support systems for obstructive sleep apnea

Humans need sleep. It is important for physical and psychological recreation. During sleep our consciousness is suspended or least altered. Hence, our ability to avoid or react to disturbances is reduced. These disturbances can come from external sources or from disorders within the body. Obstructive Sleep Apnea (OSA) is such a disorder. It is caused by obstruction of the upper airways which causes periods where the breathing ceases. In many cases, periods of reduced breathing, known as hypopnea, precede OSA events. The medical background of OSA is well understood, but the traditional diagnosis is expensive, as it requires sophisticated measurements and human interpretation of potentially large amounts of physiological data. Electrocardiogram (ECG) measurements have the potential to reduce the cost of OSA diagnosis by simplifying the measurement process. On the down side, detecting OSA events based on ECG data is a complex task which requires highly skilled practitioners. Computer algorithms can help to detect the subtle signal changes which indicate the presence of a disorder. That approach has the following advantages: computers never tire, processing resources are economical and progress, in the form of better algorithms, can be easily disseminated as updates over the internet. Furthermore, Computer-Aided Diagnosis (CAD) reduces intra- and inter-observer variability. In this review, we adopt and support the position that computer based ECG signal interpretation is able to diagnose OSA with a high degree of accuracy

Multimodal assessment of mitochondrial function in Parkinson's disease

The heterogenous aetiology of Parkinson's disease is increasingly recognized; both mitochondrial and lysosomal dysfunction have been implicated. Powerful, clinically applicable tools are required to enable mechanistic stratification for future precision medicine approaches. The aim of this study was to characterize bioenergetic dysfunction in Parkinson's disease by applying a multimodal approach, combining standardized clinical assessment with midbrain and putaminal 31-phosphorus magnetic resonance spectroscopy (31P-MRS) and deep phenotyping of mitochondrial and lysosomal function in peripheral tissue in patients with recent-onset Parkinson's disease and control subjects. Sixty participants (35 patients with Parkinson's disease and 25 healthy controls) underwent 31P-MRS for quantification of energy-rich metabolites [ATP, inorganic phosphate (Pi) and phosphocreatine] in putamen and midbrain. In parallel, skin biopsies were obtained from all research participants to establish fibroblast cell lines for subsequent quantification of total intracellular ATP and mitochondrial membrane potential (MMP) as well as mitochondrial and lysosomal morphology, using high content live cell imaging. Lower MMP correlated with higher intracellular ATP (r = −0.55, P = 0.0016), higher mitochondrial counts (r = −0.72, P < 0.0001) and higher lysosomal counts (r = −0.62, P = 0.0002) in Parkinson's disease patient-derived fibroblasts only, consistent with impaired mitophagy and mitochondrial uncoupling. 31P-MRS-derived posterior putaminal Pi/ATP ratio variance was considerably greater in Parkinson's disease than in healthy controls (F-tests, P = 0.0036). Furthermore, elevated 31P-MRS-derived putaminal, but not midbrain Pi/ATP ratios (indicative of impaired oxidative phosphorylation) correlated with both greater mitochondrial (r = 0.37, P = 0.0319) and lysosomal counts (r = 0.48, P = 0.0044) as well as lower MMP in both short (r = −0.52, P = 0.0016) and long (r = −0.47, P = 0.0052) mitochondria in Parkinson's disease. Higher 31P-MRS midbrain phosphocreatine correlated with greater risk of rapid disease progression (r = 0.47, P = 0.0384). Our data suggest that impaired oxidative phosphorylation in the striatal dopaminergic nerve terminals exceeds mitochondrial dysfunction in the midbrain of patients with early Parkinson's disease. Our data further support the hypothesis of a prominent link between impaired mitophagy and impaired striatal energy homeostasis as a key event in early Parkinson's disease

Sleep Disorders and Demand for Medical Services: Evidence from a Population-Based Longitudinal Study

Background: The aim of this study was to investigate whether insomnia and obstructive sleep apnea (OSA) were predictors of hospitalizations or emergency department visits during two years following the Sao Paulo Epidemiologic Sleep Study (EPISONO) sample. Methods and Findings: All participants (n = 1,101) who underwent a baseline evaluation between July and December 2007 were contacted in December 2009 and asked to fill out a questionnaire about body weight changes, number of hospitalizations and visits to the emergency department. Participants lost during the follow-up period represented 3.2 % (n = 35) and 7 subjects had died. Hospitalizations were reported by 116 volunteers (10.5%) and emergency department visits were reported by 136 participants (12.4%). The average body mass index (BMI) did not vary significantly between the first and the second assessment [26.7(95%CI:26.3–27.1) vs. 26.9(26.5–27.4) kg/m2]. After adjusting for confounders, a multiple logistic regression model revealed that female gender [1.4(1.0–1.9)], age $40 years, insomnia diagnosed according to the DSM-IV criteria [1.6(1.0–2.6)], and apneahypopnea index$15 [1.5(1.0–2.2)] were predictors of hospitalizations and/or demand for emergency services. Conclusion: Our study of a probabilistic sample of the Sao Paulo inhabitants shows that over a period of two years, insomnia and OSA were both associated with health impairment. Considering the high prevalence and public health burden of slee

A novel delta current method for transport stoichiometry estimation

BACKGROUND: The ion transport stoichiometry (q) of electrogenic transporters is an important determinant of their function. q can be determined by the reversal potential (E(rev)) if the transporter under study is the only electrogenic transport mechanism or a specific inhibitor is available. An alternative approach is to calculate delta reversal potential (ΔE(rev)) by altering the concentrations of the transported substrates. This approach is based on the hypothesis that the contributions of other channels and transporters on the membrane to E(rev) are additive. However, E(rev) is a complicated function of the sum of different conductances rather than being additive. RESULTS: We propose a new delta current (ΔI) method based on a simplified model for electrogenic secondary active transport by Heinz (Electrical Potentials in Biological Membrane Transport, 1981). ΔI is the difference between two currents obtained from altering the external concentration of a transported substrate thereby eliminating other currents without the need for a specific inhibitor. q is determined by the ratio of ΔI at two different membrane voltages (V(1) and V(2)) where q = 2RT/(F(V(2) –V(1)))ln(ΔI(2)/ΔI(1)) + 1. We tested this ΔI methodology in HEK-293 cells expressing the elctrogenic SLC4 sodium bicarbonate cotransporters NBCe2-C and NBCe1-A, the results were consistent with those obtained with the E(rev) inhibitor method. Furthermore, using computational simulations, we compared the estimates of q with the ΔE(rev) and ΔI methods. The results showed that the ΔE(rev) method introduces significant error when other channels or electrogenic transporters are present on the membrane and that the ΔI equation accurately calculates the stoichiometric ratio. CONCLUSIONS: We developed a ΔI method for estimating transport stoichiometry of electrogenic transporters based on the Heinz model. This model reduces to the conventional reversal potential method when the transporter under study is the only electrogenic transport process in the membrane. When there are other electrogenic transport pathways, ΔI method eliminates their contribution in estimating q. Computational simulations demonstrated that the ΔE(rev) method introduces significant error when other channels or electrogenic transporters are present and that the ΔI equation accurately calculates the stoichiometric ratio. This new ΔI method can be readily extended to the analysis of other electrogenic transporters in other tissues