Mechanosensitive membrane domains regulate calcium entry in arterial endothelial cells to protect against inflammation.

Endothelial cells (ECs) in the descending aorta are exposed to high laminar shear stress, and this supports an antiinflammatory phenotype. High laminar shear stress also induces flow-aligned cell elongation and front-rear polarity, but whether these are required for the antiinflammatory phenotype is unclear. Here, we showed that caveolin-1-rich microdomains polarize to the downstream end of ECs that are exposed to continuous high laminar flow. These microdomains were characterized by high membrane rigidity, filamentous actin (F-actin), and raft-associated lipids. Transient receptor potential vanilloid (TRPV4) ion channels were ubiquitously expressed on the plasma membrane but mediated localized Ca2+ entry only at these microdomains where they physically interacted with clustered caveolin-1. These focal Ca2+ bursts activated endothelial nitric oxide synthase within the confines of these domains. Importantly, we found that signaling at these domains required both cell body elongation and sustained flow. Finally, TRPV4 signaling at these domains was necessary and sufficient to suppress inflammatory gene expression and exogenous activation of TRPV4 channels ameliorated the inflammatory response to stimuli both in vitro and in vivo. Our work revealed a polarized mechanosensitive signaling hub in arterial ECs that dampened inflammatory gene expression and promoted cell resilience.

"It's all about cultural understanding": A reflexive thematic analysis of women's experiences at a dedicated refugee midwifery group practice service.

BACKGROUND: Inequitable maternity care provision in high-income countries contributes to ongoing poor outcomes for women of refugee backgrounds. To address barriers to quality maternity care and improve health equity, a co-designed maternity service incorporating community-based group antenatal care, onsite social worker and interpreters, continuity of midwifery carer through a caseload design with 24/7 phone access was implemented for women of refugee background. OBJECTIVE: To explore and describe women's experiences and perceptions of care from a dedicated Refugee Midwifery Group Practice service. DESIGN: Qualitative exploratory descriptive study using focus group discussions and interpreters. SETTING: The study was conducted at a community-based Refugee Midwifery Group Practice service in a tertiary maternity hospital in Brisbane, Australia. METHODS: We conducted three focus group discussions (June - December 2020) with 16 women, born in six different countries, in three language groups: Sudanese Arabic, Somali, and English. We used reflexive thematic analysis to interpret women's perspectives and generate informed meanings of experiences of care. RESULTS: We generated four themes 1) accessibility of care, 2) women feeling accepted, 3) value of relationality, and 4), service expansion and promotion. Results demonstrate positive experiences and acceptability due to easy access, strong woman-midwife relationships, and culturally safe care. CONCLUSION: The service addressed concerns raised in an early evaluation and provides evidence that redesigning maternity services to meet the needs of women with a refugee background speaking multiple languages from many countries is possible and promotes access, use, and satisfaction with care, contributing to improved health equity and perinatal outcomes.

Effect of an Australian community-based caseload midwifery group practice service on maternal and neonatal outcomes for women from a refugee background.

BACKGROUND: Women from a refugee background who resettle in high-income countries experience poorer perinatal outcomes in comparison to women from host countries. There is a paucity of research on how best to improve these outcomes. AIM: To report on the effectiveness of an Australian Refugee Midwifery Group Practice service on perinatal outcomes. METHODS: We used inverse probability of treatment weighting to balance confounders and calculate treatment effect and compare maternal and neonatal outcomes for women from a refugee background who received Refugee Midwifery Group Practice care (n = 625), to those receiving standard care (n = 634) at a large tertiary hospital (1 January 2016-31 December 2019). Prespecified primary outcomes included: proportion of women attending ≥ 5 antenatal visits, preterm birth (<37 weeks), spontaneous onset of labour, epidural analgesia in the first stage of labour, normal birth (term, spontaneous onset, vertex, spontaneous vaginal birth, no epidural, no episiotomy), and exclusively breast-feeding at discharge. FINDINGS: Women who received Refugee Midwifery Group Practice care were more likely to have spontaneous onset of labour (adjusted odds ratio 2·20, 95% CI 1·71-2·82; p < 0·0001), normal birth (1·55, 1·23-1·95; p < 0·0001), and less likely to use epidural analgesia (0·67, 0·50-0·89; p = 0·0067) and have a preterm baby (0·60, 0·36-0·99; p = 0·047). There was no difference between groups in women attending ≥ 5 antenatal visits and exclusive breastfeeding at discharge from hospital. DISCUSSION: A Refugee Midwifery Group Practice is feasible and clinically effective. CONCLUSION: Similar services could potentially improve outcomes for women from a refugee background who resettle in high-income countries.

A multi-step transcriptional cascade underlies vascular regeneration in vivo.

The molecular mechanisms underlying vascular regeneration and repair are largely unknown. To gain insight into this process, we developed a method of intima denudation, characterized the progression of endothelial healing, and performed transcriptome analysis over time. Next-generation RNA sequencing (RNAseq) provided a quantitative and unbiased gene expression profile during in vivo regeneration following denudation injury. Our data indicate that shortly after injury, cells immediately adjacent to the wound mount a robust and rapid response with upregulation of genes like Jun, Fos, Myc, as well as cell adhesion genes. This was quickly followed by a wave of proliferative genes. After completion of endothelial healing a vigorous array of extracellular matrix transcripts were upregulated. Gene ontology enrichment and protein network analysis were used to identify transcriptional profiles over time. Further data mining revealed four distinct stages of regeneration: shock, proliferation, acclimation, and maturation. The transcriptional signature of those stages provides insight into the regenerative machinery responsible for arterial repair under normal physiologic conditions.

Women from refugee backgrounds and their experiences of attending a specialist antenatal clinic. Narratives from an Australian setting.

PROBLEM: In response to an identified need, a specialist antenatal clinic for women from refugee backgrounds was introduced in 2008, with an evaluation planned and completed in 2010. QUESTION: Can maternity care experiences for women from refugee backgrounds, attending a specialist antenatal clinic in a tertiary Australian public hospital, be improved? METHODS: The evaluation employed mixed methods, generating qualitative and quantitative data from two hospital databases, a chart audit, surveys and interviews with service users, providers and stakeholders. Contributions were received from 202 participants. FINDINGS: The clinic was highly regarded by all participants. Continuity of care throughout the antenatal period was particularly valued by newly arrived women as it afforded them security and support to negotiate an unfamiliar Western maternity system. Positive experiences decreased however; as women transitioned from the clinic to labour and postnatal wards where they reported that their traditional birthing and recuperative practices were often interrupted by the imposition of Western biomedical notions of appropriate care. The centrally located clinic was problematic, frequently requiring complex travel arrangements. Appointment schedules often impacted negatively on traditional spousal and family obligations. CONCLUSIONS: Providing comprehensive and culturally responsive maternity care for women from refugee backgrounds is achievable, however it is also resource intensive. The production of translated information which is high quality in terms of production and content, whilst also taking account of languages which are only rarely encountered, is problematic. Cultural competency programmes for staff, ideally online, require regular updating in light of new knowledge and changing political sensitivities.

Theoretical investigation of the formation of a new series of antioxidant depsides from the radiolysis of flavonoid compounds.

This paper deals with the formation of a series of antioxidant depsides obtained from flavonoid solutions irradiated with gamma rays. These reactions take place in radiolyzed alcohol solutions, a medium that is very rich in many different highly reactive species and that hosts specific reactions. We focus on the first step of those reactions, i.e., reactivity of the solute (flavonoid) with the alkoxy radicals CH(3)O(*) and CH(3)CH(2)O(*) formed in methanol and ethanol, respectively, and their carbon-centered isomers: the 1-hydroxy-methyl ((*)CH(2)OH) and the 1-hydroxy-ethyl (CH(3)(*)CHOH) radicals. Among the different flavonoid groups of molecules, only flavonols are transformed. To establish the structure-reactivity relationship that explains why the radiolytic transformation occurs only for those compounds, the process is rationalized theoretically, with Density Functional Theory calculations, taking into account the solvent effects by a Polarizable Continuum Model and a microhydrated environment (one or two water molecules surrounding the active center). The first redox reaction, occurring between the flavonol and the reactive species formed upon irradiation of the solvent, is studied in terms of (1) the O-H bond dissociation enthalpy of each OH group of the flavonoids and (2) electron abstraction from the molecule. We conclude that the reaction, initiated preferentially by the alkoxy radicals, first occurs at the 3-OH group of the flavonol. It is then followed by the formation of a peroxyl radical (after molecular oxygen or superoxide addition). The different cascades of reactions, which lead to the formation of depsides via C-ring opening, are discussed on the basis of the corresponding calculated energetic schemes.

Photoinduced charge generation and recombination dynamics in model donor/acceptor pairs for organic solar cell applications: a full quantum-chemical treatment.

This work focuses on two fundamental processes in organic solar cells-exciton dissociation and charge recombination-and describes how quantum-chemical calculations can be exploited to estimate the molecular parameters that determine the rates of these processes. The general concepts behind our approach are illustrated by considering a donor-acceptor complex made of a phthalocyanine (electron donor) molecule and a perylene (acceptor) molecule. The results highlight how the relative rates of the two processes depend on the dimensionality of the molecules, their relative positions, the symmetry of the relevant electronic levels, and the polarity of the medium. It is shown, for instance, that highly symmetric configurations of the complex can strongly limit charge recombination; this emphasizes the need for a fine control of the supramolecular organization at organic-organic interfaces in donor-acceptor blends.