"None of us was prepared"-Caring for vulnerable people during the heatwave in Sweden in 2018.

Climate change is increasing the risk for extreme weather events such as heatwaves, including in northern countries like Sweden, which until recent years has had limited experiences of coping with extreme heat. Based on predictions that Sweden will be more frequently exposed to heatwaves in the future, it is imperative to increase the societal resilience and adaptation measures. This paper presents a qualitative interview study involving 19 participants and their experiences of caring for vulnerable people during the heatwave in 2018. The participants represent four different organizations (working directly or indirectly with vulnerable people) in two municipalities in Sweden, including preschools, homes for the elderly, homecare services, and care homes for people with functional impairments, which were all impacted during the heatwave. This study contributes new empirical insights about the heatwave in 2018 and, in particular, similarities and differences in both experiences and adaptation measures across the four organizations. The findings show how both staff and vulnerable people suffered from the consequences of heat which increased vulnerability, how some organizations lacked enough (qualified) staff to secure routines, and that few evaluations and formal changes were done after the heatwave.

Healthcare workers' perceptions of how eHealth applications can support self-care for patients undergoing planned major surgery.

BACKGROUND: In planned major surgery the duration of inpatient hospital care during the last decade has decreased because of a combination of different perioperative interventions. It is expected that patients can manage the needed pre- and postoperative self-care to a large extent on their own. This entails challenges to healthcare system to deliver appropriate information to patients in a safe and efficient manner. The aim of this study was therefore to describe healthcare workers' perceptions of how eHealth applications can support patients' self-care in relation to planned major surgery. METHODS: Semi-structured interviews were performed with sixteen healthcare workers from different disciplines. The interviews were transcribed and analysed using the phenomenography approach. RESULTS: Healthcare workers perceived both positive aspects and challenges with eHealth applications for self-care. eHealth applications can work as an information source, affect patients' understanding of self-care, improve patients' participation in self-care, streamline communication with healthcare professionals and improve patient safety during the pre- and postoperative period. The challenges included perceptions of that eHealth applications may have negative impact on personal interaction in care. eHealth applications may not be useful to all patients because of lack of equipment or knowledge and may increase patients' suffering if physical visits are replaced by digital solutions. CONCLUSIONS: This study improves our understanding of healthcare workers' perceptions of how the use of self-care eHealth applications can support patients in performing pre- and postoperative self-care for major surgery. Access to appropriate and personalized information and instructions can improve patients' understanding of self-care and enhance the participation and safety of those who can afford and handle digital tools. All these aspects must be considered in future digital development of eHealth applications to guarantee a person-centered care.

Patients' and providers' perspectives on e-health applications designed for self-care in association with surgery - a scoping review.

BACKGROUND: Before and after major surgery, access to information in a user-friendly way is a prerequisite for patients to feel confident in taking on the responsibility for their surgical preparation and recovery. Several e-health applications have been developed to support patients perioperatively. The aim of this review was to give an overview of e-health applications designed for self-care associated with surgery by providing a scoping overview of perspectives from providers and patients. METHODS: We searched the following data sources to identify peer-reviewed quantitative and qualitative studies published between 2015 and 2020: CINAHL, Google Scholar, MEDLINE, PsycInfo, Web of Science, and Scopus. After identifying 960 titles, we screened 638 abstracts, of which 72 were screened in full text. Protocol register: https://doi.org/10.17605/OSF.IO/R3QND . RESULTS: We included 15 studies which met our inclusion criteria. Data from several surgical contexts revealed that the most common self-care actions in e-health applications were preoperative preparations and self-assessments of postoperative recovery. Motivational factors for self-care were information, combined with supportive reminders and messages, and chat features. Although there was great variance in research designs and technical solutions, a willingness to engage with and adhere to e-health seemed to increase patients' self-care activities and thereby accelerate return to work and normal activities. In addition, the need for physical visits seemed to decrease. Even though age groups were not primarily studied, the included studies showed that adult patients of any age engaged in surgical self-care supported by e-health. The providers' perspectives were not found. CONCLUSIONS: E-health applications supporting perioperative self-care indicated a positive impact on recovery. However, experiences of healthcare professionals delivering e-health associated with surgery are missing. Additionally, studies based on patients' perspectives regarding willingness, adherence, and motivation for self-care supported by e-health are sparse. A need for studies examining the supporting role of e-health for self-care in the surgical context is therefore needed.

Women's invisible work in disaster contexts: gender norms in speech on women's work after a forest fire in Sweden.

The aim of this study is to investigate what women do in disaster situations and how both men and women perceive and discuss the work of women. These patterns were evidenced in the stories that were told following the largest forest fire in the modern history of Sweden in July 2014. The study is based on 31 retrospective interviews with volunteers involved in combating the forest fire and concentrates on stories about the supportive work of women during this disaster. The results indicate that women were praised when they followed traditional norms but were denigrated when they performed what were viewed as male-coded tasks. The stories reveal norms concerning what a woman is and is not by focusing on women's age and clothing and by directly and indirectly questioning their abilities and authority. The norms are also rendered visible by the positive attention that women receive while describing doing what is expected of them.

Drawing lessons from the COVID-19 pandemic: Seven obstacles to learning from public inquiries in the wake of the crisis.

On March 11, 2020, the World Health Organization declared the emerging COVID-19 threat a pandemic following the global spread of the virus. A year later, a number of governments are being handed the concluding reports of national public inquiries tasked with investigating responses, mishaps, and identifying lessons for the future. The present article aims to identify a set of learning obstacles that may hinder effective lessons drawing from the COVID-19 pandemic responses. The seven obstacles discussed in this article are: (1) retaining lessons and implementing them effectively, (2) effectively drawing lessons from other countries, (3) the potential for reforms to introduce unanticipated vulnerabilities elsewhere in the system, (4) political pressure, (5) drawing the conclusions from observations, (6) experts versus decision makers, and (7) reforms may not be related to the actual crisis. Exploring these obstacles will be central to future discussions concerning which kinds of responses will set precedent for future pandemics and global health crises.

El 11 de marzo de 2020, la Organización Mundial de la Salud declaró que la amenaza emergente COVID­19 era una pandemia tras la propagación global del virus. Un año después, a varios gobiernos se les entregan los informes finales de las investigaciones públicas nacionales encargadas de investigar las respuestas, los percances e identificar las lecciones para el futuro. El presente artículo tiene como objetivo identificar un conjunto de obstáculos de aprendizaje que pueden dificultar la extracción de lecciones efectivas de las respuestas a la pandemia de COVID­19. Los siete obstáculos discutidos en este artículo son; (1) retener lecciones e implementarlas de manera efectiva; (2) extraer lecciones de otros países de manera eficaz; (3) la posibilidad de que las reformas introduzcan vulnerabilidades imprevistas en otras partes del sistema; (4) presión política; (5) sacar las conclusiones de las observaciones; (6) expertos versus tomadores de decisiones; y (7) las reformas pueden no estar relacionadas con la crisis real. Explorar estos obstáculos será fundamental para las discusiones futuras sobre qué tipos de respuestas sentarán un precedente para futuras pandemias y crisis de salud mundial.

The association of patients' daily summarized self-rated "real-time" pain scores with physical recovery after major surgery - A repeated measurement design.

Aim: To determine the associations of patients' documented self-rated pain with self-rated early postoperative physical recovery. Design: Observational with repeated measures. Methods: General and orthopaedic inpatients (N = 479) were during the period 2012-2015 screened for pain. Individual daily median pain scores at rest and during activity were based on 4-9 self-ratings on postoperative days 1 and 2, using the Numeric Rating Scale. Nine items reflecting physical recovery from the "Postoperative Recovery Profile" were used in a questionnaire. Results: Associations between median pain scores on postoperative day 1 and physical recovery (fatigue, sleeping difficulties, bladder function, mobilization, muscle weakness and personal hygiene) the same day were found. Additionally, associations were found between median pain scores on day 1 and physical recovery (fatigue, sleeping difficulties, mobilization and muscle weakness) on day 2.

Predictors for Early Physical Recovery for General and Orthopedic Patients after Major Surgery: Structural Equational Model Analyses.

BACKGROUND: Attention to factors that may affect patients' ability to experience enhanced recovery after surgery is essential in planning for postoperative care. AIMS: To create models of predefined pre,- peri-, and postoperative variables in order to analyze their impact on patients' physical recovery on postoperative days 1 and 2 after major orthopedic and general surgery. DESIGN: An exploratory design with repeated measures was used, including 479 patients who had undergone orthopedic (289) or general surgery (190) at three hospitals. METHODS: Pain, nausea, and level of physical ability were measured preoperatively and on postoperative days 1 and 2 by using the Numerical Rating Scale and items from the Postoperative Recovery Profile. Structural equation modeling was used to explore the impact of the predefined variables on patients' physical recovery. RESULTS: The orthopedic group contained significantly more women and significantly more patients with pain and opioid use. Although the models showed good fit, "traditional" preoperative (pain, nausea, physical abilities, chronic pain, opioid use) and perioperative variables (anesthesia, length of surgery) constituted few (orthopedic) or no (general surgery) predictive properties for physical recovery. Postoperative average pain intensity, average nausea intensity, and physical ability explained physical recovery on day 1, and physical recovery on day 1 predicted physical recovery on day 2. CONCLUSIONS: "Traditional" predictors had little effect on patients' postoperative physical recovery, while associations with common postoperative symptoms were shown. Further research is needed to explore additional variables affecting early physical recovery and to understand how soon patients are physically ready to return home.

Nausea intensity as a reflector of early physical recovery after surgery.

AIM: To compare different levels of self-rated average nausea intensity with early physical recovery and determine if nausea can reflect recovery in patients undergoing general or orthopaedic surgery. BACKGROUND: Nausea has been found to influence postoperative physical recovery. Despite the incidence of nausea in postoperative care, there is a knowledge gap about the possibility of using average nausea intensity to reflect recovery, motivating further investigation. DESIGN: An observational design with repeated measures. METHODS: General and orthopaedic patients answered a questionnaire (October 2012-January 2015) about nausea and impact on recovery on postoperative days 1 (N = 479) and 2 (N = 441). Questions about average nausea intensity at rest and during activity were answered based on the Numeric Rating Scale (NRS) (0-10). Impact on recovery was evaluated using three dimensions from the postoperative recovery profile tool. RESULTS: About one-fifth of the patients reported nausea intensity as moderate to severe on days 1 and 2. Nausea intensity was associated with eight of nine aspects of recovery on postoperative day 1. Nausea intensity on day 1 also reflected four of nine aspects of recovery on day 2. About reflecting physical recovery, the association was strongest between nausea intensity and appetite changes. CONCLUSIONS: As postoperative nausea is common, regular assessments by healthcare professionals are needed. Assessment of nausea is of importance since it reflects physical recovery. This also shows the importance of treating nausea without delay. Using the NRS to measure nausea intensity is a simple method that is easy to use in clinic.

Patients' self-reported nausea: Validation of the Numerical Rating Scale and of a daily summary of repeated Numerical Rating Scale scores.

AIM AND OBJECTIVES: To validate the Numeric Rating Scale (NRS) for postoperative nausea assessments, and determine whether a central tendency, median, based on patients' self-rated nausea is a clinically applicable daily measure to describe patients' nausea after major surgery. BACKGROUND: Postoperative nausea causes major discomfort, risks for complications and prolonged hospital stays. The NRS is recommended for the assessment of pain but is little explored for assessing nausea. DESIGN: A repeated measure design was carried out on patients who had undergone major surgery in three Swedish hospitals. METHODS: Nonparametric statistical methods were used to analyse (a) associations between the NRS and a verbal scale (no, mild, moderate and severe) and (b) to analyse associations between Measure 1 (nausea scores postoperative Day 1) and Measure 2 (retrospective nausea scores at rest and during activity, postoperative Day 2). Reporting of this research adheres to the Strobe Guidelines. RESULTS: The mean age of the 479 patients (44% women) in the sample was 65 years (range, 22-93 years). Self-assessed nausea scores from the NRS and the verbal scale correlated well (rS pearman  = 0.79). Correlation between nausea at rest and nausea during activity was rS pearman  = 0.81. The calculated median scores (Measure 1) showed only moderate correlations with retrospective nausea scores (Measure 2); 4-9 ratings, rS pearman  = 0.41; 6-9 ratings, rS pearman  = 0.54. CONCLUSIONS: Numeric Rating Scale scores showed strong associations with a verbal scale; therefore, the NRS seems to be a valid tool to measure nausea intensity. The quality of daily summarised median nausea scores needs to be further explored before clinical use. RELEVANCE TO CLINICAL PRACTICE: The use of the NRS in assessments of nausea in postoperative care will facilitate communication between patients and health care professionals regarding nausea intensity. When documenting nausea, it seems unnecessary to distinguish nausea at rest from nausea during activity.

Association of pain ratings with the prediction of early physical recovery after general and orthopaedic surgery-A quantitative study with repeated measures.

AIM: To compare different levels of self-rated pain and determine if they predict anticipated early physical recovery in patients undergoing general and orthopaedic surgery. BACKGROUND: Previous research has indicated that average self-rated pain reflects patients' ability to recover the same day. However, there is a knowledge gap about the feasibility of using average pain ratings to predict patients' physical recovery for the next day. DESIGN: Descriptive, quantitative repeated measures. METHODS: General and orthopaedic inpatients (n = 479) completed a questionnaire (October 2012-January 2015) about pain and recovery. Average pain intensity at rest and during activity was based on the Numeric Rating Scale and divided into three levels (0-3, 4-6, 7-10). Three out of five dimensions from the tool "Postoperative Recovery Profile" were used. Because few suffered severe pain, general and orthopaedic patients were analysed together. RESULTS: Binary logistic regression analysis showed that average pain intensity postoperative day 1 significantly predicted the impact on recovery day 2, except nausea, gastrointestinal function and bladder function when pain at rest and also nausea, appetite changes, and bladder function when pain during activity. High pain ratings (NRS 7-10) demonstrated to be a better predictor for recovery compared with moderate ratings (NRS 4-6), day 2, as it significantly predicted more items in recovery. CONCLUSION: Pain intensity reflected general and orthopaedic patients' physical recovery postoperative day 1 and predicted recovery for day 2. By monitoring patients' pain and impact on recovery, patients' need for support becomes visible which is valuable during hospital stays.

The clinical applicability of a daily summary of patients' self-reported postoperative pain-A repeated measure analysis.

AIM AND OBJECTIVES: (i) To determine whether a central tendency, median, based on patients' self-rated pain is a clinically applicable daily measure to show patients' postoperative pain on the first day after major surgery (ii) and to determine the number of self-ratings required for the calculation of this measure. BACKGROUND: Perioperative pain traits in medical records are difficult to overview. The clinical applicability of a daily documented summarising measure of patients' self-rated pain scores is little explored. DESIGN: A repeated measure design was carried out at three Swedish country hospitals. METHODS: Associations between the measures were analysed with nonparametric statistical methods; systematic and individual group changes were analysed separately. Measure I: pain scores at rest and activity postoperative day 1; measure II: retrospective average pain from postoperative day 1. RESULTS: The sample consisted of 190 general surgery patients and 289 orthopaedic surgery patients with a mean age of 65; 56% were men. Forty-four percent had a pre-operative daily intake of analgesia, and 77% used postoperative opioids. A range of 4-9 pain scores seem to be eligible for the calculation of the daily measures of pain. Rank correlations for individual median scores, based on four ratings, vs. retrospective self-rated average pain, were moderate and strengthened with increased numbers of ratings. A systematic group change towards a higher level of reported retrospective pain was significant. CONCLUSIONS: The median values were clinically applicable daily measures. The risk of obtaining a higher value than was recalled by patients seemed to be low. Applicability increased with increased frequency of self-rated pain scores and with high-quality pain assessments. RELEVANCE TO CLINICAL PRACTICE: The documenting of daily median pain scores at rest and during activity could constitute the basis for obtaining patients' experiences by showing their pain severity trajectories. The measures could also be an important key to predicting postoperative health-related consequences.

It's All in the Mix: Blend-Specific Behavioral Response to a Sexual Pheromone in a Butterfly.

Among insects, sexual pheromones are typically mixtures of two to several components, all of which are generally required to elicit a behavioral response. Here we show for the first time that a complete blend of sexual pheromone components is needed to elicit a response also in a butterfly. Males of the Green-veined White, Pieris napi, emit an aphrodisiac pheromone, citral, from wing glands. This pheromone is requisite for females to accept mating with a courting male. Citral is a mixture of the two geometric isomers geranial (E-isomer) and neral (Z-isomer) in an approximate 1:1 ratio. We found that both these compounds are required to elicit acceptance behavior, which indicates synergistic interaction between processing of the isomers. Using functional Ca(2+) imaging we found that geranial and neral evoke significantly different but overlapping glomerular activity patterns in the antennal lobe, which suggests receptors with different affinity for the two isomers. However, these glomeruli were intermingled with glomeruli responding to, for example, plant-related compounds, i.e., no distinct subpopulation of pheromone-responding glomeruli as in moths and other insects. In addition, these glomeruli showed lower specificity than pheromone-activated glomeruli in moths. We could, however, not detect any mixture interactions among four identified glomeruli, indicating that the synergistic effect may be generated at a higher processing level. Furthermore, correlations between glomerular activity patterns evoked by the single isomers and the blend did not change over time.

Patients' experiences and actions when describing pain after surgery--a critical incident technique analysis.

BACKGROUND: Postoperative pain assessment remains a significant problem in clinical care despite patients wanting to describe their pain and be treated as unique individuals. Deeper knowledge about variations in patients' experiences and actions could help healthcare professionals to improve pain management and could increase patients' participation in pain assessments. OBJECTIVE: The aim of this study was, through an examination of critical incidents, to describe patients' experiences and actions when needing to describe pain after surgery. METHODS: An explorative design involving the critical incident technique was used. Patients from one university and three county hospitals in both urban and rural areas were included. To ensure variation of patients a strategic sampling was made according to age, gender, education and surgery. A total of 25 patients who had undergone orthopaedic or general surgery was asked to participate in an interview, of whom three declined. FINDINGS: Pain experiences were described according to two main areas: "Patients' resources when in need of pain assessment" and "Ward resources for performing pain assessments". Patients were affected by their expectations and tolerance for pain. Ability to describe pain could be limited by a fear of coming into conflict with healthcare professionals or being perceived as whining. Furthermore, attitudes from healthcare professionals and their lack of adherence to procedures affected patients' ability to describe pain. Two main areas regarding actions emerged: "Patients used active strategies when needing to describe pain" and "Patients used passive strategies when needing to describe pain". Patients informed healthcare professionals about their pain and asked questions in order to make decisions about their pain situation. Selfcare was performed by distraction and avoiding pain or treating pain by themselves, while others were passive and endured pain or refrained from contact with healthcare professionals due to healthcare professionals' large work load.

Healthcare professionals' descriptions of care experiences and actions when assessing postoperative pain - a critical incident technique analysis.

BACKGROUND: Pain is a common postoperative symptom, and length of hospital stay after surgery is short which highlights the importance of pain assessments. Experiences of assessing pain are mainly described from the perspective of nurses. In postoperative care, enrolled nurses and physicians also assess pain. It is therefore important to take note of their experiences to improve postoperative pain assessments. OBJECTIVES: The aim of this study was, through considering critical incidents, to describe care experiences and actions taken by healthcare professionals when assessing postoperative pain. METHODS: An explorative design employing critical incidents technique analysis was used. A total of 24 strategically selected enrolled nurses, nurses and physicians employed at orthopaedic or general surgery wards in four Swedish hospitals were interviewed. The intention was to reach variation in age, sex, profession and professional experience. FINDINGS: In pain assessments, patient-related facilitators were patients' verbal and emotional expressions including pain ratings, while lack of consistency with observed behaviours was a barrier. Clinical competence, continuity in care and time were healthcare-related facilitators. The actions healthcare professionals took were gathering facts about patients' pain manifestations and adapting to patients' communication abilities. Patient observations, either passive or active were used to confirm or detect pain. Collaboration between healthcare professionals, including consultations with pain experts, social workers and relatives, strengthened understanding of pain. CONCLUSIONS: Communication skills and working conditions have an impact on performance of pain assessment. Patient comfort without compromising safety is reached by including healthcare professionals' dissimilar responsibilities when collecting patients' and relatives' perspectives on current pain.

Framework for crisis preparedness planning: Four required areas for developing a learning process.

OBJECTIVE: To outline a framework for preparedness planning at the organizational level. DESIGN: The study is based on a content analysis of research literature as well as an analysis of interviews with six preparedness planners working in Swedish local authorities. SETTING: The study setting included Swedish local authorities of different sizes. SUBJECTS, PARTICIPANTS: The participants are preparedness planners responsible for coordinating crisis management work in Swedish local authorities. The study includes preparedness planners with different backgrounds, education, experiences, and gender. INTERVENTIONS: A presentation of 19 factors of preparedness planning identified in the literature and a discussion around how preparedness planners perceive those factors. MAIN OUTCOME MEASURE(S): The main outcome measures are knowledge about how both researcher and practitioner understand and argue around different factors of preparedness planning. RESULTS: The result of this study is a framework for preparedness planning. As preparedness planning ought to be a learning process, the presented framework builds on four areas connected to learning: prerequisites for preparedness planning, who should be involved, what is to be learned, and how should the work be shaped. CONCLUSIONS: The analysis of factors identified in the literature and also in the interviews with preparedness planners illustrates that the four areas connected to learning are required for developing a preparedness planning process.

Healthcare professionals' perceptions of the use of pain scales in postoperative pain assessments.

AIM: To describe how healthcare professionals perceive the use of pain scales in postoperative care. BACKGROUND: Pain scales are important but not an obvious choice to use in postoperative care. No study has explored how healthcare professionals experience the use of pain scales. METHODS: An explorative design with a phenomenographic approach was used. The sample consisted of 25 healthcare professionals. Semistructured interviews were performed. RESULTS: Four descriptive categories emerged - the use of pain scales facilitated the understanding of postoperative pain, facilitated treatment, demanded a multidimensional approach and was affected by work situations. CONCLUSIONS: Healthcare professionals described that pain scales contribute to the understanding of patient's postoperative pain. It is important to ensure patient understanding and be aware about variations in pain ratings. Dialogue and observations are necessary to be certain what the ratings mean to the patient. The use of pain scales depends on patient's needs and organization.

Numeric rating scale: patients' perceptions of its use in postoperative pain assessments.

AIM: The purpose of this study was to describe how patients perceive the use of the numeric rating scale in postoperative pain assessments. BACKGROUND: There are recommendations to use a pain scale to follow patients' postoperative pain. Most patients prefer the NRS but there is a discrepancy between patients and healthcare professionals how to interpret the ratings from the pain assessments. METHODS: A descriptive design with a phenomenographic approach was used. Semi structured interviews were held with 25 patients. RESULTS: Three description categories emerged that illustrate patients' perceptions; use of the NRS facilitated communication of pain, it put demands on healthcare professionals and care routines and it contained interpretation difficulties. CONCLUSION: The NRS has a place in pain management according to the patients but there is a need for a dialogue to give the patients the opportunity to describe their pain and set a common goal.

Using mode and maximum values from the Numeric Rating Scale when evaluating postoperative pain management and recovery.

AIMS AND OBJECTIVES: To (1) examine the clinical applicability of compiled mode and maximum values from the Numeric Rating Scale (NRS) by comparing the correspondence between patient perceptions of pain and pain values from monitoring records, as well as (2) to study the relationship between mode and maximum values and self-assessed ability for early postoperative recovery. BACKGROUND: Documentation of pain remains a problem despite recommendations of quality improvements. To examine the correlation between patient perceptions and documented pain therefore becomes important. Few have studied how pain affects recovery. DESIGN: A quantitative cross-sectional design was used in which 157 postoperative patients answered a questionnaire on pain intensity and recovery. A parallel examination of pain in monitoring records was conducted. RESULTS: A total of 57% had a mode value calculated from records between 0 and 3 on postoperative day 1 and 69% on day 2. A maximum value between 4 and 10 was found in monitoring records for 73% on day 1 and for 67% on day 2. The correspondence between mode value from monitoring records and the patients' retrospective perceptions was 88% for NRS 0-3 and 92% between maximum value and NRS 4-10. The correlation between documented pain and retrospectively identified pain for mode value of the NRS in all (0-10) was rather weak (r = 0·37), while maximum value had a stronger correlation (r = 0·53). CONCLUSION: Mode and maximum values could be used as outcome measures when evaluating postoperative pain. Pain affects recovery negatively, but more research is needed to strengthen the evidence for the use and clarify the link between pain and recovery. RELEVANCE TO CLINICAL PRACTICE: International organisations emphasise the importance of improving pain assessment. Mode and maximum values are easy to compile for nurses and can, together with assessments of how experienced pain levels affect postoperative recovery, improve treatment of postoperative pain.

Angiostatin and endostatin inhibit endothelial cell migration in response to FGF and VEGF without interfering with specific intracellular signal transduction pathways.

The anti-angiogenic agents angiostatin and endostatin have been shown to affect endothelial cell migration in a number of studies. We have examined the effect of these agents on intracellular signalling pathways known to regulate endothelial cell migration and proliferation/survival. Both agents inhibited fibroblast growth factor (FGF)-, and vascular endothelial growth factor (VEGF)-mediated migration of primary human microvascular endothelial cells and affected vascular formation in the embryoid body model. However, using phosphospecific antibodies we could not detect any effect of angiostatin or endostatin on phospholipase C-gamma (PLC-gamma), Akt/PKB, p44/42 mitogen-activated protein kinase (MAPK), p38 MAPK and p21-activated kinase (PAK) activity. Furthermore, using a glutathione S-transferase (GST)-PAK pull-down assay, we could not detect any effect on Rac activity. We conclude that angiostatin and endostatin inhibit chemotaxis, without affecting intracellular signalling pathways known to regulate endothelial migration and proliferation/survival.