Propagating Cell-Membrane Waves Driven by Curved Activators of Actin Polymerization

Cells exhibit propagating membrane waves which involve the actin cytoskeleton. One type of such membranal waves are Circular Dorsal Ruffles (CDR) which are related to endocytosis and receptor internalization. Experimentally, CDRs have been associated with membrane bound activators of actin polymerization of concave shape. We present experimental evidence for the localization of convex membrane proteins in these structures, and their insensitivity to inhibition of myosin II contractility in immortalized mouse embryo fibroblasts cell cultures. These observations lead us to propose a theoretical model which explains the formation of these waves due to the interplay between complexes that contain activators of actin polymerization and membrane-bound curved proteins of both types of curvature (concave and convex). Our model predicts that the activity of both types of curved proteins is essential for sustaining propagating waves, which are abolished when one type of curved activator is removed. Within this model waves are initiated when the level of actin polymerization induced by the curved activators is higher than some threshold value, which allows the cell to control CDR formation. We demonstrate that the model can explain many features of CDRs, and give several testable predictions. This work demonstrates the importance of curved membrane proteins in organizing the actin cytoskeleton and cell shape

Theoretical Model for Cellular Shapes Driven by Protrusive and Adhesive Forces

The forces that arise from the actin cytoskeleton play a crucial role in determining the cell shape. These include protrusive forces due to actin polymerization and adhesion to the external matrix. We present here a theoretical model for the cellular shapes resulting from the feedback between the membrane shape and the forces acting on the membrane, mediated by curvature-sensitive membrane complexes of a convex shape. In previous theoretical studies we have investigated the regimes of linear instability where spontaneous formation of cellular protrusions is initiated. Here we calculate the evolution of a two dimensional cell contour beyond the linear regime and determine the final steady-state shapes arising within the model. We find that shapes driven by adhesion or by actin polymerization (lamellipodia) have very different morphologies, as observed in cells. Furthermore, we find that as the strength of the protrusive forces diminish, the system approaches a stabilization of a periodic pattern of protrusions. This result can provide an explanation for a number of puzzling experimental observations regarding cellular shape dependence on the properties of the extra-cellular matrix

Avaliação da qualidade de vida em pacientes cirróticos com hérnia da parede abdominal Quality of life in patients with abdominal hernia and cirrhosis

RACIONAL: As hérnias de parede abdominal são um problema frequente no paciente cirrótico. Elas costumam ser volumosas e muito sintomáticas. OBJETIVO: Avaliar a qualidade de vida, através da aplicação do questionário Short Form-36 (SF-36), nos pacientes com hérnia e cirrose. MÉTODOS: Foram avaliados 39 pacientes cirróticos com hérnia de parede abdominal estratificados pela classificação de Child e submetidos ao questionário SF-36 por um mesmo profissional. RESULTADOS: A média dos escores obtidos no SF-36 mostra diminuição em todos os domínios nos pacientes cirróticos, principalmente no aspecto físico. O grupo Child B mostrou pior avaliação ao estado geral de saúde e capacidade funcional em relação ao grupo Child A, contudo não houve diferença em relação ao aspecto físico. CONCLUSÃO: A presença de hérnia de parede abdominal ocasiona piora na qualidade de vida do paciente cirrótico. A deterioração da função hepática está relacionada a pior qualidade de vida. A hérnia abdominal leva a restrição importante no aspecto físico também no Child A.<br>BACKGROUND: Abdominal hernias are frequent issue in cirrhotic patients. These hernias tend to be large and symptomatic. AIM: To analyze the quality of life using a Short Form-36 (SF-36) questionnaire in cirrhotic patients with abdominal hernia. METHODS: Thirty nine cirrhotic patients with abdominal wall hernia were analyzed. They were stratified according to Child´s classification and answered the SF-36 questionnaire administered by a same professional. RESULTS: The scores from SF-36 show impairment in all questionnaire domains in cirrhotic patients, especially in the physical aspect. The Child B group showed worse health general condition and functional capacity comparing with Child A group; however it did not show any significant difference related to physical aspect. CONCLUSION: The presence of abdominal hernia leads to worse quality of life in cirrhotic patients. Hepatic function deterioration is related to a worse quality of life. Abdominal hernia causes an important restriction in physical aspect even in Child A

Optimizing the care of malignant bowel obstruction in patients with advanced gynecologic cancer

PURPOSE Malignant bowel obstruction (MBO) is a common and distressing complication in women with advanced gynecologic cancer. A pilot, interprofessional MBO program was launched in 2016 at a large Canadian tertiary cancer center to integrate these patients’ complex care needs across multiple disciplines and support women with MBO. METHOD Retrospective analysis to evaluate the outcomes of women with advanced gynecologic cancer who were admitted to hospital because of MBO, before (2014 to 2016: baseline group) and after (2016 to 2018) implementation of the MBO program. RESULTS Of the 169 women evaluated, 106 and 63 were in the baseline group and MBO program group, respectively. Most had ovarian cancer (n = 124; 73%) and had small-bowel obstruction (n = 131; 78%). There was a significantly shorter cumulative hospital length of stay (LOSsum) within the first 60 days of MBO diagnosis in the MBO program group compared with the baseline group (13 v 22 days, respectively; adjusted P = .006). The median overall survival for women treated in the MBO program was also significantly longer compared with the baseline group (243 v 99 days, respectively; adjusted P = .002). Using the interprofessional MBO care platform, a greater proportion of patients received palliative chemotherapy (83% v 56%) and less surgery (11% v 21%) in the MBO program group than in the baseline group, respectively. A subgroup of women (n = 11) received total parenteral nutrition for longer than 6 months. CONCLUSION Implementation of a comprehensive, interprofessional MBO program significantly affects patient care and may improve outcomes. Unique to this MBO program is an integrated outpatient model of care and education that empowers patients to recognize MBO symptoms for early intervention

Malignant Bowel Obstruction in Advanced Gynecologic Cancers: An Updated Review from a Multidisciplinary Perspective

Malignant bowel obstruction (MBO) is a major complication in women with advanced gynecologic cancers which imposes a significant burden on patients, caregivers, and healthcare systems. Symptoms of MBO are challenging to palliate and result in progressive decompensation of already vulnerable patients with limited therapeutic options and a short prognosis. However, there is a paucity of guidelines or innovative approaches to improve the care of women who develop MBO. MBO is a complex clinical situation that requires a multidisciplinary approach to ensure the appropriate treatment modality and interprofessional care to optimally manage these patients. This review summarizes the current literature on the different approaches targeting MBO management including surgical intervention, chemotherapy, total parenteral nutrition, and pharmacological treatment. In addition, the impact of MBO management on patients’ quality of life (QOL) is examined. This article focuses on the challenges in developing evidence-based treatment guidelines for MBO and barriers in clinical trial design for MBO and proposes strategies to advance the MBO management. Collaboration is essential to design studies that may improve the overall care and quality of life for these patients. Prospective data are needed to inform clinical practice, establish a new benchmark for evidence-based MBO management, and better understand the biology of MBO.Peer Reviewe