Closed loop stimulation helps with weaning from chronotropic incompetence-related ventilator dependence

Journal of Interventional Cardiac Electrophysiology -     

Cell-sized liposomes reveal how actomyosin cortical tension drives shape change

Animal cells actively generate contractile stress in the actin cortex, a thin actin network beneath the cell membrane, to facilitate shape changes during processes like cytokinesis and motility. On the microscopic scale, this stress is generated by myosin molecular motors, which bind to actin cytoskeletal filaments and use chemical energy to exert pulling forces. To decipher the physical basis for the regulation of cell shape changes, here, we use a cell-like system with a cortex anchored to the outside or inside of a liposome membrane. This system enables us to dissect the interplay between motor pulling forces, cortex–membrane anchoring, and network connectivity. We show that cortices on the outside of liposomes either spontaneously rupture and relax built-up mechanical stress by peeling away around the liposome or actively compress and crush the liposome. The decision between peeling and crushing depends on the cortical tension determined by the amount of motors and also on the connectivity of the cortex and its attachment to the membrane. Membrane anchoring strongly affects the morphology of cortex contraction inside liposomes: cortices contract inward when weakly attached, whereas they contract toward the membrane when strongly attached. We propose a physical model based on a balance of active tension and mechanical resistance to rupture. Our findings show how membrane attachment and network connectivity are able to regulate actin cortex remodeling and membrane-shape changes for cell polarization.Animal cells constantly adapt their shape as they move and divide. Events like cytokinesis (1) and motility (2) require concerted remodeling of the actin cytoskeleton and the plasma membrane. A crucial cell module that drives cellular shape changes is the actomyosin cortex beneath the cell membrane, which produces contractile forces that squeeze the cell forward during migration or constrict it during division. The cell cortex is a thin actin network of thickness ∼0.2 µm (3), which is tightly attached to the plasma membrane (4, 5). On the molecular scale, contractile forces are generated by myosin II motor proteins, associated into bipolar filaments (6), which use adenosine 5′-triphosphate (ATP) to exert pulling forces on actin filaments.To drive cell-shape changes, these forces must be communicated to the plasma membrane, which requires membrane–actin attachment (7–9) through, for example, proteins from the ERM (ezrin, radixin, moesin) family (10–13). Several in vivo studies provide evidence that cortex–membrane attachment strongly influences contractile processes. For instance, blebbing at the cell poles due to transient detachment of the cortex from the membrane serves to release excess cortical tension during cytokinesis, which is crucial to achieve proper division (14). In early Caenorhabditis elegans embryos, myosin-driven contraction drives long-range cortical flow of actin along the membrane, which is crucial to establish cell polarity and asymmetric cell division (15). It is increasingly recognized that cortex remodeling and cell-shape changes depend on a balance between the active forces generated by motors and the passive forces originating from cortex (visco)elasticity and cortex–membrane adhesion (16). However, the microscopic basis of this force balance remains unclear. It is difficult to resolve this question directly in cells, because manipulation by drugs or genetic methods can also affect the dynamics of the underlying cytoskeleton via specific signaling pathways (17).An alternative approach is to use either cell-free extracts (18, 19) or systems reconstituted from a minimal set of purified cellular components (20). These approaches have been successfully used to show that contractility of bulk actomyosin networks depends on the kinetic parameters of the motors (21–23), as well as on the presence of actin cross-linkers that allow build-up of stress (24, 25). A recent study of 2D actomyosin networks attached to flat model biomembranes showed that actin–membrane anchoring also influences cortex contractility (26). However, although this biomimetic assay can address actin–membrane adhesion, it cannot address the influence of membrane deformability on cortex remodeling and shape change.Here, we reproduce active contractility in a cell-like system, where actomyosin cortical networks are anchored to a liposome membrane. Cortices linked to the outer leaflet of the liposome membrane mimic the cell cortex as well as intracellular organelles like endosomes (27). Low linkage or cross-link density promote active cortex rupture, which breaks the symmetry and causes passive elastic retraction of the network to one pole of the liposome. In contrast, high membrane anchorage and high network cross-link density promote active compression of the liposomes by cortex contraction. We further show that when the cortices are instead connected to the inner leaflet of the liposome membrane, actin–membrane linkage strongly biases the directionality of cortex contraction. Our results shed light on the physical mechanisms that control contraction events during cell division, motility and endosome-shape changes.     

Emergency nurses' knowledge of perceived barriers in pain management in Taiwan

Aims and objectives. To explore knowledge of and perceived barriers to pain management among emergency nurses in Taiwan. Background. Pain is the most common patient complaint in emergency departments. Quality care of these patients depends on the pain knowledge and pain management skills of emergency nurses. However, no studies have explored emergency nurses’ knowledge of and perceived barriers to pain management in Taiwan. Design and methods. Nurse subjects (n = 249) were recruited from nine hospitals chosen by stratified sampling across Taiwan. Data were collected using the Nurses’ Knowledge and Attitudes Survey‐Taiwanese version, a scale to assess perceived barriers to pain management and a background information form. Results. The overall average correct response rate for the knowledge scale was 49·2%, with a range of 4·8–89·2% for each survey question. The top barrier to managing pain was identified by these nurses as ‘the responsibility of caring for other acutely ill patients in addition to a patient with pain. Knowledge of pain management had a significant, negative relationship with perceived barriers to pain management and a significant, positive relationship with extent of clinical care experience and total hours of prior pain management education. In addition, scores for knowledge and perceived barriers differed significantly by the nursing clinical ladder. Perceived barriers also differed significantly by hospital accreditation category. Conclusions. Our results indicate an urgent need to strengthen pain education for emergency nurses in Taiwan. Relevance to clinical practice. The pain education should target knowledge deficits and barriers to changing pain management approaches for Taiwanese emergency nurses.     

The relationship between quality of life and posttraumatic stress disorder or major depression for firefighters in Kaohsiung,Taiwan

Objective The work of firefighters involves the risk of exposure to the harmful effects of toxic substances as well as the possibility of enormous emotional shock from disasters, which may result in psychiatric impairments and a lower quality of life. Therefore, we examined quality of life, prevalence of posttraumatic stress disorder (PTSD) and major depression, and the related risk factors for firefighters in Kaohsiung, Taiwan. Methods This is a two-stage survey study. During the first stage, we used the 36-item Short-Form Health Survey (SF-36) and the Disaster-Related Psychological Screening Test (DRPST) to assess quality of life, probable PTSD, probable major depression, and the related risk factors for 410 firefighters. During the second stage, psychiatrists categorized these probable cases according to self-reported questionnaires against DSM-IV into PTSD or major depression group, subclinical group, and health group. All the data were analyzed with SPSS 10.0 Chinese version. Results The estimated current prevalence rates for major depression and PTSD were 5.4% (22/410) and 10.5% (43/410), respectively. The firefighters with estimated PTSD or major depression scored significantly lower on quality of life measures than subclinical PTSD/major depression and mentally healthy groups, which was evident in eight concepts and two domains of the SF-36. The major predictors of poor quality of life and PTSD/major depression were mental status, psychosocial stressors, or perceived physical condition. Conclusion Firefighters have a higher estimated rate of PTSD, and the risk factors that affect quality of life and PTSD/major depression should encourage intervention from mental health professionals.