The GEF Trio controls endothelial cell size and arterial remodeling downstream of Vegf signaling in both zebrafish and cell models

Arterial networks enlarge in response to increase in tissue metabolism to facilitate flow and nutrient delivery. Typically, the transition of a growing artery with a small diameter into a large caliber artery with a sizeable diameter occurs upon the blood flow driven change in number and shape of endothelial cells lining the arterial lumen. Here, using zebrafish embryos and endothelial cell models, we describe an alternative, flow independent model, involving enlargement of arterial endothelial cells, which results in the formation of large diameter arteries. Endothelial enlargement requires the GEF1 domain of the guanine nucleotide exchange factor Trio and activation of Rho-GTPases Rac1 and RhoG in the cell periphery, inducing F-actin cytoskeleton remodeling, myosin based tension at junction regions and focal adhesions. Activation of Trio in developing arteries in vivo involves precise titration of the Vegf signaling strength in the arterial wall, which is controlled by the soluble Vegf receptor Flt1. Arterial flow regulates artery diameter but other mechanisms may also affect this. Here, the authors show that the guanine nucleotide exchange factor Trio and GTPases Rac1 and RhoG, triggers F-actin remodeling in arterial endothelial cells, independent of flow, to enhance lumen diameter in zebrafish and cell models.Peer reviewe

Higher quality of life and lower depression for people on art in Uganda as compared to a community control group

Provision of antiretroviral treatment (ART) to people living with HIV (PLWH) has increased globally. Research measuring whether ART restores subjective well-being to "normal" levels is lacking, particularly in resource limited settings. The study objectives are to compare quality of life and depression symptoms for PLWH on ART to a general community population and to explore factors to explain these differences, including socio-economic status and the impact of urban or rural residence. PLWH on ART (n = 263) were recruited from ART delivery sites and participants not on ART (n = 160) were recruited from communities in Wakiso District, Uganda. Participants were interviewed using the translated World Health Organisation Quality of Life brief measure, the Hopkins Symptom Checklist depression section, and questions about socioeconomic status, residence as urban or rural and, for PLWH on ART, self-reported adherence and use of HIV counselling. Compared to the community sample and controlling for location of residence, PLWH on ART had significantly higher quality of life (QOL) for physical, psychological and environment domains, but not the social domain. These differences were not due to socio-economic status alone. Depression scores were significantly lower for PLWH on ART. Both comparisons controlled for the effect of location of residence. People on ART self-reported high adherence and the majority had used HIV counselling services. Our findings show better QOL amongst PLWH on ART compared to a general community sample, which cannot be explained solely by differences in socio-economic status nor location of residence. The general community sample results point towards the challenges of life in this setting. Access to health services may underpin this difference and further research should explore this finding, in addition to identification of psychological mechanisms that relate to better QOL. ART provision infrastructure has clear benefits. Further work should consider sustainability and replication for other health conditions. © 2014 Martin et al

Perioperative echocardiography-guided hemodynamic therapy in high-risk patients:a practical expert approach of hemodynamically focused echocardiography

The number of high-risk patients undergoing surgery is growing. To maintain adequate hemodynamic functioning as well as oxygen delivery to the vital organs (DO2) amongst this patient population, a rapid assessment of cardiac functioning is essential for the anesthesiologist. Pinpointing any underlying cardiovascular pathophysiology can be decisive to guide interventions in the intraoperative setting. Various techniques are available to monitor the hemodynamic status of the patient, however due to intrinsic limitations, many of these methods may not be able to directly identify the underlying cause of cardiovascular impairment. Hemodynamic focused echocardiography, as a rapid diagnostic method, offers an excellent opportunity to examine signs of filling impairment, cardiac preload, myocardial contractility and the function of the heart valves. We thus propose a 6-step-echocardiographic approach to assess high-risk patients in order to improve and maintain perioperative DO2. The summary of all echocardiographic based findings allows a differentiated assessment of the patient's cardiovascular function and can thus help guide a (patho)physiological-orientated and individualized hemodynamic therapy

Hemodynamic parameters to guide fluid therapy

The clinical determination of the intravascular volume can be extremely difficult in critically ill and injured patients as well as those undergoing major surgery. This is problematic because fluid loading is considered the first step in the resuscitation of hemodynamically unstable patients. Yet, multiple studies have demonstrated that only approximately 50% of hemodynamically unstable patients in the intensive care unit and operating room respond to a fluid challenge. Whereas under-resuscitation results in inadequate organ perfusion, accumulating data suggest that over-resuscitation increases the morbidity and mortality of critically ill patients. Cardiac filling pressures, including the central venous pressure and pulmonary artery occlusion pressure, have been traditionally used to guide fluid management. However, studies performed during the past 30 years have demonstrated that cardiac filling pressures are unable to predict fluid responsiveness. During the past decade, a number of dynamic tests of volume responsiveness have been reported. These tests dynamically monitor the change in stroke volume after a maneuver that increases or decreases venous return (preload) and challenges the patients' Frank-Starling curve. These dynamic tests use the change in stroke volume during mechanical ventilation or after a passive leg raising maneuver to assess fluid responsiveness. The stroke volume is measured continuously and in real-time by minimally invasive or noninvasive technologies, including Doppler methods, pulse contour analysis, and bioreactance

Current quality of life and its determinants among opiate-dependent individuals five years after starting methadone treatment

This study explores the current QoL of opiate-dependent individuals who started outpatient methadone treatment at least 5 years ago and assesses the influence of demographic, psychosocial, drug and health-related variables on individuals' QoL. Participants (n = 159) were interviewed about their current QoL, psychological distress and severity of drug-related problems, using the Lancashire Quality of Life Profile, the Brief Symptom Inventory and the Addiction Severity Index. Potential determinants of QoL were assessed in a multiple linear regression analysis. Five years after the start of methadone treatment, opiate-dependent individuals report low QoL scores on various domains. No association was found between drug-related variables and QoL, but a significant negative impact of psychological distress was identified. Severity of psychological distress, taking medication for psychological problems and the inability to change one's living situation were associated with lower QoL. Having at least one good friend and a structured daily activity had a significant, positive impact on QoL. Opiate-dependent individuals' QoL is mainly determined by their psychological well-being and a number of psychosocial variables. These findings highlight the importance of a holistic approach to treatment and support in methadone maintenance treatment, which goes beyond fixing the negative physical consequences of opiate dependence

Fluid challenges in intensive care: the FENICE study A global inception cohort study

Fluid challenges (FCs) are one of the most commonly used therapies in critically ill patients and represent the cornerstone of hemodynamic management in intensive care units. There are clear benefits and harms from fluid therapy. Limited data on the indication, type, amount and rate of an FC in critically ill patients exist in the literature. The primary aim was to evaluate how physicians conduct FCs in terms of type, volume, and rate of given fluid; the secondary aim was to evaluate variables used to trigger an FC and to compare the proportion of patients receiving further fluid administration based on the response to the FC.This was an observational study conducted in ICUs around the world. Each participating unit entered a maximum of 20 patients with one FC.2213 patients were enrolled and analyzed in the study. The median [interquartile range] amount of fluid given during an FC was 500 ml (500-1000). The median time was 24 min (40-60 min), and the median rate of FC was 1000 [500-1333] ml/h. The main indication for FC was hypotension in 1211 (59 %, CI 57-61 %). In 43 % (CI 41-45 %) of the cases no hemodynamic variable was used. Static markers of preload were used in 785 of 2213 cases (36 %, CI 34-37 %). Dynamic indices of preload responsiveness were used in 483 of 2213 cases (22 %, CI 20-24 %). No safety variable for the FC was used in 72 % (CI 70-74 %) of the cases. There was no statistically significant difference in the proportion of patients who received further fluids after the FC between those with a positive, with an uncertain or with a negatively judged response.The current practice and evaluation of FC in critically ill patients are highly variable. Prediction of fluid responsiveness is not used routinely, safety limits are rarely used, and information from previous failed FCs is not always taken into account

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

HIV Disclosure Anxiety:A Systematic Review and Theoretical Synthesis

HIV disclosure can help people living with HIV to access social support, enhance antiretroviral adherence, facilitate engagement in care and reduce unprotected sex. Given interpersonal risks associated with HIV disclosure, however, anxiety about sharing one’s status is common. To investigate anxiety about HIV disclosure in HIV-positive populations, we conducted a systematic review of qualitative and quantitative studies, with 119 studies included. The review demonstrated that perceived interpersonal risks are associated with HIV disclosure and outlined evidence of associations with anxiety, fear and worry. We present a new cognitive model of HIV disclosure anxiety adapted from clinical theories of health and social anxiety, consistent with evidence from the review. The model attempts to explain the development and maintenance of anxiety in individuals whose functioning is most affected by concerns about sharing their status. Implications for helping people living with HIV struggling with significant levels of anxiety about HIV disclosure are discussed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10461-016-1453-3) contains supplementary material, which is available to authorized users