TREM-1 regulates neutrophil chemotaxis by promoting NOX-dependent superoxide production.

Neutrophil migration across tissue barriers to the site of injury involves integration of complex danger signals and is critical for host survival. Numerous studies demonstrate that these environmental signals fundamentally alter the responses of extravasated or "primed" neutrophils. Triggering receptor expressed on myeloid cells 1 (TREM-1) plays a central role in modulating inflammatory signaling and neutrophil migration into the alveolar airspace. Using a genetic approach, we examined the role of TREM-1 in extravasated neutrophil function. Neutrophil migration in response to chemoattractants is dependent upon multiple factors, including reactive oxygen species (ROS) generated either extracellularly by epithelial cells or intracellularly by NADPH oxidase (NOX). We, therefore, questioned whether ROS were responsible for TREM-1-mediated regulation of migration. Thioglycollate-elicited peritoneal neutrophils isolated from wild-type (WT) and TREM-1-deficient mice were stimulated with soluble and particulate agonists. Using electron paramagnetic resonance spectroscopy, we demonstrated that NOX2-dependent superoxide production is impaired in TREM-1-deficient neutrophils. Consistent with these findings, we confirmed with Clark electrode that TREM-1-deficient neutrophils consume less oxygen. Next, we demonstrated that TREM-1 deficient neutrophils have impaired directional migration to fMLP and zymosan-activated serum as compared to WT neutrophils and that deletion or inhibition of NOX2 in WT but not TREM-1-deficient neutrophils significantly impaired direction sensing. Finally, TREM-1 deficiency resulted in decreased protein kinase B (AKT) activation. Thus, TREM-1 regulates neutrophil migratory properties, in part, by promoting AKT activation and NOX2-dependent superoxide production. These findings provide the first mechanistic evidence as to how TREM-1 regulates neutrophil migration.

Women's views and experiences of having their mental health needs considered in the perinatal period.

OBJECTIVE: To explore women's views and experiences of having their mental health needs considered in the perinatal period in an Irish maternity hospital setting. DESIGN: A qualitative design using semi-structured interviews was used to explore women's views and experiences. Data were analysed using Thematic Analysis (Braun and Clarke, 2006). SETTING: A voluntary maternity hospital in Dublin, Ireland which had access to a perinatal mental health team. PARTICIPANTS: In total 8 women who met the inclusion criteria were recruited and participated in this study. The women were interviewed in the early postpartum period. FINDINGS: The study offers important insights into how women feel about having their mental health needs considered in the perinatal period. Women reported pregnancy was an emotional time, feeling expected to be happy, and women with significant mental health histories preferred not to be referred to available services unless they asked for help. Women reported barriers to disclosure including stigma/shame, lack of time. Screening tools were viewed with mixed opinions. In getting help, the baby was a motivator for some women, attitudes of healthcare professionals and lack of time affected this. KEY CONCLUSIONS: Women appreciated all methods of enquiry about their mental health and being given time to discuss concerns with healthcare professionals. Perceived busy staff workloads was a barrier in asking for help, as was lack of continuity of care. Screening tools were viewed as a tick box exercise, but also as a 'modality' to assist detection of women at risk. Mental health enquiry focused on depression and anxiety, with little or no enquiry about less common disorders. Women with significant histories were less likely to engage or accept referral to perinatal mental health services, preferring to access help if they felt they needed to. IMPLICATIONS FOR PRACTICE: HCPs should enquire regularly about women's emotional wellbeing at every antenatal and postnatal contact, offering support where required. Detailed enquiry about mental health should encompass the broad spectrum of perinatal mental health problems, including but not limited to depression and anxiety. Screening tools can assist in the identification of women at risk of developing perinatal mental health problems. A specialist mental health midwife should link with high-risk women at the first antenatal booking visit and provide information on early intervention and access to services.

Living with an unfixable heart: a qualitative study exploring the experience of living with advanced heart failure.

BACKGROUND: Nurses working with patients with advanced heart failure need knowledge that will help us to help patients cope with their situations of chronic illness. However, our knowledge bank is deficient due to the scarcity of inquiry that takes the affected person's point of view as its central focus. AIM: The aim of this study was to describe patients' experiences of living with advanced heart failure. METHODS: The study sample (N=9) consisted of male (N=6) and female (N=3) patients with advanced (NYHA classes III-IV) heart failure. The design was qualitative and open unstructured interviews were audio-taped and transcribed verbatim during 2006. RESULTS: Four main themes emerged: Living in the Shadow of Fear; Running on Empty; Living a Restricted life; and Battling the System. The experience of living with advanced heart failure was described as a fearful and tired sort of living characterised by escalating impotence and dependence. CONCLUSIONS: The findings suggest that there may be an illogical but enduring ethos of 'cure' pervading health care worker's attitudes to advanced heart failure care. This mindset might be working to hinder the application of additional or alternative therapies, which might better palliate the physical and psychosocial distress of patients.