Decidual natural killer cell interactions with trophoblasts are impaired in pregnancies at increased risk of preeclampsia.

Transformation of the uterine spiral arteries (SAs) during pregnancy is critical to support the developing fetus, and is impaired in some pregnancy disorders, including preeclampsia. Decidual natural killer (dNK) cells play a role in SA remodeling, although their interactions with fetal trophoblast remain unclear. A uterine artery Doppler resistance index (RI) in the first trimester of pregnancy can be used as a proxy measure of the extent of SA remodeling; we have used this technique to characterize dNK cells from pregnancies with normal (normal RI) and impaired (high RI) SA remodeling, which display least and highest risk of developing preeclampsia, respectively. We examined the impact of dNK cell secreted factors on trophoblast motility, chemoattraction, and signaling pathways to determine the contribution of dNK cells to SA transformation. We demonstrated that the chemoattraction of the trophoblast by dNK cells is impaired in pregnancies with high RI, as is the ability to induce trophoblast outgrowth from placental villous explants. These processes are dependent on activation of the extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3-kinase-Akt signaling pathways, which were altered in trophoblasts incubated with secreted factors from dNK cells from high RI pregnancies. Therefore, by characterizing pregnancies using uterine artery Doppler RI before dNK cell isolation, we have identified that impaired dNK-trophoblast interactions may lead to poor placentation. These findings have implications for pregnancy pathological conditions, such as preeclampsia

"Now he walks and walks, as if he didn't have a home where he could eat": food, healing, and hunger in Quechua narratives of madness

In the Quechua-speaking peasant communities of southern Peru, mental disorder is understood less as individualized pathology and more as a disturbance in family and social relationships. For many Andeans, food and feeding are ontologically fundamental to such relationships. This paper uses data from interviews and participant observation in a rural province of Cuzco to explore the significance of food and hunger in local discussions of madness. Carers’ narratives, explanatory models, and theories of healing all draw heavily from idioms of food sharing and consumption in making sense of affliction, and these concepts structure understandings of madness that differ significantly from those assumed by formal mental health services. Greater awareness of the salience of these themes could strengthen the input of psychiatric and psychological care with this population and enhance knowledge of the alternative treatments that they use. Moreover, this case provides lessons for the global mental health movement on the importance of openness to the ways in which indigenous cultures may construct health, madness, and sociality. Such local meanings should be considered by mental health workers delivering services in order to provide care that can adjust to the alternative ontologies of sufferers and carers

Survey of women's experiences of care in a new freestanding midwifery unit in an inner city area of London, England - 1: Methods and women׳s overall ratings of care

Objective: To describe and compare women’s choices and experiences of maternity care before and after the opening of the Barkantine Birth Centre, a new freestanding midwifery unit in an inner city area. Design: Telephone surveys undertaken in late pregnancy and about six weeks after birth in two separate time periods, Phase 1 before the birth centre opened and Phase 2 after it had opened. Setting: Tower Hamlets, a deprived inner city borough in east London, England, 2007-2010. Participants: 620 women who were resident in Tower Hamlets and who satisfied the Barts and the London NHS Trust’s eligibility criteria for using the birth centre. Of these, 259 women were recruited to Phase 1 and 361 to Phase 2. Measurements and findings: Women who satisfied the criteria for birth centre care and who booked antenatally for care at the birth centre were significantly more likely to rate their care as good or very good overall than corresponding women who also satisfied these criteria but booked initially at the hospital. Women who started labour care in spontaneous labour at the birth centre were significantly more likely to be cared for by a midwife they had already met, have one to one care in labour and have the same midwife with them throughout their labour. They were also significantly more likely to report that the staff were kind and understanding, that they were treated with respect and dignity and that their privacy was respected. Key conclusions and implications for practice: This survey in an inner city area showed that women who chose the freestanding midwifery unit care had positive experiences to report. Taken together with the findings of the Birthplace Programme, It adds further weight to the evidence in support of freestanding midwifery unit care for women without obstetric complications

Erratum to: Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case–control study

No abstract available

The moderating role of transformational leadership on HR practices in M&A integration

Scant research exists examining the effect of HRM practices on employee behavior in M&A integration and the role that leaders play within this. This paper develops a conceptual framework that focuses on the moderating role of transformational leadership on the achievement of human integration and organizational identification in M&A integration. We argue that communication, employee involvement, teamwork, and training and development have a positive effect on employee behavior and their identification with the newly formed organization. Moreover, we argue that transformational leadership behaviors will moderate the implementation of HRM practices in M&As, leading to positive employee behavior and employee identification in the new organization. We suggest that further research is necessary to test propositions of the present study in order to achieve finer-grained understanding of the role of transformational leadership on the achievement of human integration and organizational identification in M&A integration

Altimetric observation of wave attenuation through the Antarctic marginal ice zone using ICESat-2

The Antarctic marginal ice zone (MIZ) is a highly dynamic region where sea ice interacts with ocean surface waves generated in ice-free areas of the Southern Ocean. Improved large-scale (satellite-based) estimates of MIZ extent and variability are crucial for understanding atmosphere–ice–ocean interactions and biological processes and detection of change therein. Legacy methods for defining the MIZ are typically based on sea ice concentration thresholds and do not directly relate to the fundamental physical processes driving MIZ variability. To address this, new techniques have been developed to measure the spatial extent of significant wave height attenuation in sea ice from variations in Ice, Cloud and land Elevation Satellite-2 (ICESat-2) surface heights. The poleward wave penetration limit (boundary) is defined as the location where significant wave height attenuation equals the estimated error in significant wave height. Extensive automated and manual acceptance/rejection criteria are employed to ensure confidence in along-track wave penetration width estimates due to significant cloud contamination of ICESat-2 data or where wave attenuation is not observed. Analysis of 304 ICESat-2 tracks retrieved from four months of 2019 (February, May, September and December) reveals that sea-ice-concentration-derived MIZ width estimates are far narrower (by a factor of ∼ 7 on average) than those from the new technique presented here. These results suggest that indirect methods of MIZ estimation based on sea ice concentration are insufficient for representing physical processes that define the MIZ. Improved large-scale measurements of wave attenuation in the MIZ will play an important role in increasing our understanding of this complex sea ice zone

A trial assessing N-3 as treatment for injury-induced cachexia (ATLANTIC trial): does a moderate dose fish oil intervention improve outcomes in older adults recovering from hip fracture?

<p>Abstract</p> <p>Background</p> <p>Proximal femoral fractures are associated with increased morbidity and mortality. Pre-existing malnutrition and weight loss amongst this patient group is of primary concern, with conventional nutrition support being largely ineffective. The inflammatory response post proximal femoral fracture surgery and the subsequent risk of cachexia may explain the inability of conventional high energy high protein management to produce an anabolic response amongst these patients. Omega-3 fatty acids derived from fish oils have been extensively studied for their anti-inflammatory benefits. Due to their anti-inflammatory properties, the benefit of fish oil combined with individualized nutrition support amongst proximal femoral fracture patients post surgery is an attractive potential therapeutic strategy. The aim of the ATLANTIC trial is to assess the potential benefits of an anti-inflammatory dose of fish oil within the context of a 12 week individualised nutrition program, commencing seven days post proximal femoral fracture surgery.</p> <p>Methods/Design</p> <p>This randomized controlled, double blinded trial, will recruit 150 community dwelling elderly patients aged ≥65 years, within seven days of surgery for proximal femoral fracture. Participants will be randomly allocated to receive either a 12 week individualized nutrition support program complemented with 20 ml/day anti-inflammatory dose fish oil (~3.6 g eicosapentaenoic acid, ~2.4 g docosahexanoic acid; intervention), or, a 12 week individualized nutrition support program complemented with 20 ml/day low dose fish oil (~0.36 g eicosapentaenoic acid, ~0.24 g docosahexanoic acid; control).</p> <p>Discussion</p> <p>The ATLANTIC trial is the first of its kind to provide fish oil combined with individualized nutrition therapy as an intervention to address the inflammatory response experienced post proximal femoral fracture surgery amongst elderly patients. The final outcomes of this trial will assist clinicians in the development of effective and alternative treatment methods post proximal femoral fracture surgery which may ultimately result in a reduction in systemic inflammation, loss of weight and lean muscle and improvements in nutritional status, mobility, independence and quality of life among elderly patients.</p> <p>Trial Registration</p> <p>ACTRN12609000241235</p

Targeting early changes in the synovial microenvironment:a new class of immunomodulatory therapy?

Objectives: Controlled immune responses rely on integrated crosstalk between cells and their microenvironment. We investigated whether targeting proinflammatory signals from the extracellular matrix that persist during pathological inflammation provides a viable strategy to treat rheumatoid arthritis (RA). Methods: Monoclonal antibodies recognising the fibrinogen-like globe (FBG) of tenascin-C were generated by phage display. Clones that neutralised FBG activation of toll-like receptor 4 (TLR4), without impacting pathogenic TLR4 activation, were epitope mapped by crystallography. Antibodies stained synovial biopsies of patients at different stages of RA development. Antibody efficacy in preventing RA synovial cell cytokine release, and in modulating collagen-induced arthritis in rats, was assessed. Results: Tenascin-C is expressed early in the development of RA, even before disease diagnosis, with higher levels in the joints of people with synovitis who eventually developed RA than in people whose synovitis spontaneously resolved. Anti-FBG antibodies inhibited cytokine release by RA synovial cells and prevented disease progression and tissue destruction during collagen-induced arthritis. Conclusions: Early changes in the synovial microenvironment contribute to RA progression; blocking proinflammatory signals from the matrix can ameliorate experimental arthritis. These data highlight a new drug class that could offer early, disease-specific immune modulation in RA, without engendering global immune suppression

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.Peer reviewe