A modular spring-loaded actuator for mechanical activation of membrane proteins.

How cells respond to mechanical forces by converting them into biological signals underlie crucial cellular processes. Our understanding of mechanotransduction has been hindered by technical barriers, including limitations in our ability to effectively apply low range piconewton forces to specific mechanoreceptors on cell membranes without laborious and repetitive trials. To overcome these challenges we introduce the Nano-winch, a robust, easily assembled, programmable DNA origami-based molecular actuator. The Nano-winch is designed to manipulate multiple mechanoreceptors in parallel by exerting fine-tuned, low- piconewton forces in autonomous and remotely activated modes via adjustable single- and double-stranded DNA linkages, respectively. Nano-winches in autonomous mode can land and operate on the cell surface. Targeting the device to integrin stimulated detectable downstream phosphorylation of focal adhesion kinase, an indication that Nano-winches can be applied to study cellular mechanical processes. Remote activation mode allowed finer extension control and greater force exertion. We united remotely activated Nano-winches with single-channel bilayer experiments to directly observe the opening of a channel by mechanical force in the force responsive gated channel protein, BtuB. This customizable origami provides an instrument-free approach that can be applied to control and explore a diversity of mechanotransduction circuits on living cells.

Physiological effects of adding ECCO2R to invasive mechanical ventilation for COPD exacerbations.

BACKGROUND: Extracorporeal CO2 removal (ECCO2R) could be a valuable additional modality for invasive mechanical ventilation (IMV) in COPD patients suffering from severe acute exacerbation (AE). We aimed to evaluate in such patients the effects of a low-to-middle extracorporeal blood flow device on both gas exchanges and dynamic hyperinflation, as well as on work of breathing (WOB) during the IMV weaning process. STUDY DESIGN AND METHODS: Open prospective interventional study in 12 deeply sedated IMV AE-COPD patients studied before and after ECCO2R initiation. Gas exchange and dynamic hyperinflation were compared after stabilization without and with ECCO2R (Hemolung, Alung, Pittsburgh, USA) combined with a specific adjustment algorithm of the respiratory rate (RR) designed to improve arterial pH. When possible, WOB with and without ECCO2R was measured at the end of the weaning process. Due to study size, results are expressed as median (IQR) and a non-parametric approach was adopted. RESULTS: An improvement in PaCO2, from 68 (63; 76) to 49 (46; 55) mmHg, p = 0.0005, and in pH, from 7.25 (7.23; 7.29) to 7.35 (7.32; 7.40), p = 0.0005, was observed after ECCO2R initiation and adjustment of respiratory rate, while intrinsic PEEP and Functional Residual Capacity remained unchanged, from 9.0 (7.0; 10.0) to 8.0 (5.0; 9.0) cmH2O and from 3604 (2631; 4850) to 3338 (2633; 4848) mL, p = 0.1191 and p = 0.3013, respectively. WOB measurements were possible in 5 patients, indicating near-significant higher values after stopping ECCO2R: 11.7 (7.5; 15.0) versus 22.6 (13.9; 34.7) Joules/min., p = 0.0625 and 1.1 (0.8; 1.4) versus 1.5 (0.9; 2.8) Joules/L, p = 0.0625. Three patients died in-ICU. Other patients were successfully hospital-discharged. CONCLUSIONS: Using a formalized protocol of RR adjustment, ECCO2R permitted to effectively improve pH and diminish PaCO2 at the early phase of IMV in 12 AE-COPD patients, but not to diminish dynamic hyperinflation in the whole group. A trend toward a decrease in WOB was also observed during the weaning process. Trial registration ClinicalTrials.gov: Identifier: NCT02586948.

A 2-year multicenter, observational, prospective, cohort study on extracorporeal CO2 removal in a large metropolis area.

BACKGROUND: Extracorporeal carbon dioxide removal (ECCO2R) is a promising technique for the management of acute respiratory failure, but with a limited level of evidence to support its use outside clinical trials and/or data collection initiatives. We report a collaborative initiative in a large metropolis. METHODS: To assess on a structural basis the rate of utilization as well as efficacy and safety parameters of 2 ECCO2R devices in 10 intensive care units (ICU) during a 2-year period. RESULTS: Seventy patients were recruited in 10 voluntary and specifically trained centers. The median utilization rate was 0.19 patient/month/center (min 0.04; max 1.20). ECCO2R was started under invasive mechanical ventilation (IMV) in 59 patients and non-invasive ventilation in 11 patients. The Hemolung Respiratory Assist System (Alung) was used in 53 patients and the iLA Activve iLA kit (Xenios Novalung) in 17 patients. Main indications were ultraprotective ventilation for ARDS patients (n = 24), shortening the duration of IMV in COPD patients (n = 21), preventing intubation in COPD patients (n = 9), and controlling hypercapnia and dynamic hyperinflation in mechanically ventilated patients with severe acute asthma (n = 6). A reduction in median V T was observed in ARDS patients from 5.9 to 4.1 ml/kg (p <0.001). A reduction in PaCO2 values was observed in AE-COPD patients from 67.5 to 51 mmHg (p< 0.001). Median duration of ECCO2R was 5 days (IQR 3-8). Reasons for ECCO2R discontinuation were improvement (n = 33), ECCO2R-related complications (n = 18), limitation of life-sustaining therapies or measures decision (n = 10), and death (n = 9). Main adverse events were hemolysis (n = 21), bleeding (n = 17), and lung membrane clotting (n = 11), with different profiles between the devices. Thirty-five deaths occurred during the ICU stay, 3 of which being ECCO2R-related. CONCLUSIONS: Based on a registry, we report a low rate of ECCO2R device utilization, mainly in severe COPD and ARDS patients. Physiological efficacy was confirmed in these two populations. We confirmed safety concerns such as hemolysis, bleeding, and thrombosis, with different profiles between the devices. Such results could help to design future studies aiming to enhance safety, to demonstrate a still-lacking strong clinical benefit of ECCO2R, and to guide the choice between different devices. TRIAL REGISTRATION: ClinicalTrials.gov: Identifier: NCT02965079 retrospectively registered https://clinicaltrials.gov/ct2/show/NCT02965079.

[The role of extracorporeal removal of CO2 (ECCO2R) in the management of respiratory diseases]. / Place de l'épuration extracorporelle de CO2 (ECCO2R) dans la prise en charge des pathologies respiratoires.

INTRODUCTION: The aim of extracorporeal removal of CO2 (ECCO2R) is to ensure the removal of CO2 without any significant effect on oxygenation. ECCO2R makes use of low to moderate extracorporeal blood flow rates, whereas extracorporeal membrane oxygenation (ECMO) requires high blood flows. STATE OF THE ART: For each ECCO2R device it is important to consider not only performance in terms of CO2 removal, but also cost and safety, including the incidence of hemolysis and of hemorrhagic and thrombotic complications. In addition, it is possible that the benefits of such techniques may extend beyond simple removal of CO2. There have been preliminary reports of benefits in terms of reduced respiratory muscle workload. Mobilization of endothelial progenitor cells could also occur, in analogy to the data reported with ECMO, with a potential benefit in term of pulmonary repair. The most convincing clinical experience has been reported in the context of the acute respiratory distress syndrome (ARDS) and severe acute exacerbations of chronic obstructive pulmonary disease (COPD), especially in patients at high risk of failure of non-invasive ventilation. PERSPECTIVES: Preliminary results prompt the initiation of randomized controlled trials in these two main indications. Finally, the development of these technologies opens new perspectives in terms of long-term ventilatory support.

[Acute myocardial infarction in women. Initial characteristics, management and early outcome. The FAST-MI registry]. / L'infarctus du myocarde chez la femme. Caractéristiques spécifiques, prise en charge et pronostic. Données de FAST-MI 2010.

AIM: To assess gender differences in characteristics, management, and hospital outcomes in patients participating in the French FAST-MI 2010 registry. POPULATION: Three thousand and seventy-nine patients hospitalised for ST-elevation (STEMI) or non-ST-elevation (NSTEMI) myocardial infarction in 213 French centres during a 1-month period at the end of 2010. RESULTS: Women account for 27% of the population and more frequently present with NSTEMI. They are 9 years older than men on average, although 25% of women with STEMI are less than 60 years of age. Management of STEMI is similar, after adjustment for baseline characteristics. However, fewer women are treated with primary percutaneous coronary angioplasty. In NSTEMI, although use of coronary angiography is similar, fewer women get treated with angioplasty. Most medications are used in a similar way in men and women, except thienopyridines, with fewer women receive prasugrel. After adjustment, in-hospital mortality is similar for men and women. CONCLUSION: Myocardial infarction is not specific to men: one out of four patients admitted for myocardial infarction is a woman. Initial management is rather similar for men and women, after taking into account differences in baseline characteristics. Percutaneous coronary angioplasty, however, remains less frequently used in women. In-hospital complications have become rarer and do not differ according to sex.

Fatigue in patients with ankylosing spondylitis: prevalence and relationships with disease-specific variables, psychological status, and sleep disturbance.

This study aims to evaluate the frequency of fatigue in Moroccan patients with ankylosing spondylitis (AS), and its relationships with disease-specific variables, psychological status, and sleep disturbance. A cross-sectional study included patients fulfilled the modified New York classification criteria for ankylosing spondylitis. To assess fatigue, the first item of Bath ankylosing spondylitis disease activity index (BASDAI) and the multidimensional assessment of fatigue (MAF) was used. The evaluation included the activity of the disease (BASDAI), global well-being (Bath ankylosing spondylitis global index), functional status (Bath ankylosing spondylitis functional index), metrologic measurements (Bath ankylosing spondylitis metrological index), and visual analog scale of axial or joint pain. The erythrocyte sedimentation rate and C-reactive protein were measured. To assess psychological status, the hospital anxiety and depression scale (HADS) was used. Sleep disturbance was assessed by the fourth item of Hamilton anxiety scale. One hundred and ten patients were included, of average age 38.0 years ± 12.6. In our data, 66.4% experienced severe fatigue (BASDAI fatigue ≥ 5). The mean total score of MAF was 26 ± 12.77. The disease-specific variables contributed significantly with both BASDAI fatigue and MAF as dependent variables, accounting for 71.3 and 65.6% of the variance, respectively. The contribution of the depression, anxiety, and sleep disturbance were 24.9, 18.4 and 15.4%, respectively. This study state the importance of fatigue in AS patients. Even though disease activity was the most powerful predictor of fatigue, the effects of psychogenic factors and sleep disturbance, should be taken into consideration in the management of AS.

Neurogenic heterotopic ossification of the hands in a patient with spinal cord injury: a case report.

STUDY DESIGN: The study was designed as a case report. OBJECTIVE: The objective of this study was to report an unusual case of bilateral neurogenic heterotopic ossification of the hands in a patient with spinal cord injury. SETTING: Physical Medicine and Rehabilitation department in Sale, Morocco. METHODS: A 47-year-old male patient with C5 quadriparesis was admitted in our department for rehabilitation. He had severe spasticity, characterized by extensors predominance in the upper extremities, and an aspect of pudgy fingers at the proximal phalanges in both hands. RESULTS: A plain radiograph of hands demonstrated ossification parallel to the proximal phalanx of the third and fourth digits on the right and of the second and third digits on the left. Serum alkaline phosphatase rate was increased. The diagnosis of heterotopic ossification of hands was retained. CONCLUSION: Neurogenic heterotopic ossification of hands can occur in quadriplegic patients. Finger extensors spasticity might help toward its development.

Hyponatremie en reanimation

La natremie reflete l'etat d'hydratation du patient. L'hyponatremie represente l'anomalie hydro-electrolytique la plus frequente en reanimation. Ce trouble entraine souvent une diminution de la tonicite extracellulaire avec un passage d'eau en intracellulaire. La gravite de l'hyponatremie resulte de l'installation d'un oedeme cerebral avec hypertension intracranienne. Les vraies hyponatremies sont a distinguees des pseudo hyponatremies secondaires a une hyperglycemie; une hyper protidemie ou a une hypertriglyceridemie. La correction de la natremie doit etre progressive a raison de 1;5 a 2 mmol.L-1.h-1 pour eviter une myelinolyse centropontique. L'objectif de ce travail est de faire une mise au point sur les principales etiologies de l'hyponatremie en milieu de reanimation et leur prise en charge

[Epidemiology of acute coronary syndromes in France and in Europe]. / Épidémiologie des syndromes coronaires aigus en France et en Europe.

In France, the incidence of myocardial infarctions leading to hospitalisations can be estimated between 60,000 and 65,000 each year. With the addition of cases of unstable angina, about 80,000 to 100,000 hospital stays each year are caused by acute coronary syndromes. Cases of out-of-hospital cardiac arrest of ischaemic origin should also be taken into account when estimating the annual incidence of myocardial infarction. In Europe, a North-South gradient, and even more an East-West gradient is observed for the incidence of ischaemic heart disease, with the highest figures found in central and eastern European countries. A consistent trend to a decrease in the incidence of myocardial infarction is observed on both sides of the Atlantic. In parallel, progress in the management of acute coronary syndromes has led to a marked decrease in early case fatality rates. Overall, these trends explain the spectacular decrease in cardiovascular mortality observed over the past 25 years in most European countries. Acute coronary syndromes, however, remain severe clinical conditions, which carry a high mid-term and long-term morbi-mortality and deserve further efforts to develop new therapeutic tools.