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Retinoid orphan receptor gamma t (rorγt) promotes inflammatory eosinophilia but is dispensable for innate immune-mediated colitis

by Alvaro Torres-Huerta, Katelyn Ruley-Haase, Theodore Reed, Antonia Boger-May, Derek Rubadeux, Lauren Mayer, Arpitha Mysore Rajashekara, Morgan Hiller, Madeleine Frech, Connor Roncagli, Cameron Pedersen, Mary Catherine Camacho, Lauren Hollmer, Lauren English, Grace Kane, David L. Boone

Inflammatory bowel diseases (IBD) result from uncontrolled inflammation in the intestinal mucosa leading to damage and loss of function. Both innate and adaptive immunity contribute to the inflammation of IBD and innate and adaptive immune cells reciprocally activate each other in a forward feedback loop. In order to better understand innate immune contributions to IBD, we developed a model of spontaneous 100% penetrant, early onset colitis that occurs in the absence of adaptive immunity by crossing villin-TNFAIP3 mice to RAG1-/- mice (TRAG mice). This model is driven by microbes and features increased levels of innate lymphoid cells in the intestinal mucosa. To investigate the role of type 3 innate lymphoid cells (ILC3) in the innate colitis of TRAG mice, we crossed them to retinoid orphan receptor gamma t deficient (Rorγt-/-) mice. Rorγt-/- x TRAG mice exhibited markedly reduced eosinophilia in the colonic mucosa, but colitis persisted in these mice. Colitis in Rorγt-/- x TRAG mice was characterized by increased infiltration of the intestinal mucosa by neutrophils, inflammatory monocytes, macrophages and other innate cells. RNA and cellular profiles of Rorγt-/- x TRAG mice were consistent with a lack of ILC3 and ILC3 derived cytokines, reduced antimicrobial factors, increased activation oof epithelial repair processes and reduced activation of epithelial cell STAT3. The colitis in Rorγt-/- x TRAG mice was ameliorated by antibiotic treatment indicating that microbes contribute to the ILC3-independent colitis of these mice. Together, these gene expression and cell signaling signatures reflect the double-edged sword of ILC3 in the intestine, inducing both proinflammatory and antimicrobial protective responses. Thus, Rorγt promotes eosinophilia but Rorγt and Rorγt-dependent ILC3 are dispensable for the innate colitis in TRAG mice.

African Immigrants' perceptions and attitudes toward cardiovascular health

Abstract

Aim

To explore perceptions and attitudes of African immigrants (Ghanaians, Nigerians, Liberians, and Sierra Leoneans) in the Baltimore-Washington, DC, metropolitan area toward cardiovascular health.

Methods

This was a qualitative study among African immigrants recruited from religious and community-based organizations in the Baltimore-Washington metro area. A purposive sample of 66 African immigrants originally from Ghana, Nigeria, Liberia, and Sierra Leone completed a sociodemographic survey and participated in focus group discussions. Focus group data were analysed using qualitative description to develop emergent themes.

Results

A total of 66 African immigrants with a mean (±standard deviation) age of 51 (±11.8) years participated in the focus group discussions. Fifty percent were women, 91% had at least a bachelor's degree, 84% were employed, 80% had health insurance, and 75% were married/cohabitating. The majority of the participants (74%) had lived in the US for 10 years or more, 44% of them had hypertension, and 12% had diabetes. Findings from the focus group discussions revealed: gender differences in descriptions of cardiovascular health and healthiness, an emotional response associated with cardiovascular disease (evoking fear and anxiety and associated with family secrecy), positive and negative lifestyle changes after migration, cardiovascular screening behaviours, and facilitators and barriers to cardiovascular disease prevention practices and heart-healthy lifestyle.

Conclusions

Participants understood health to be a holistic state of well-being. Secrecy in disclosing their cardiovascular disease diagnoses informed by historical socio-cultural belief systems, perceived racial discrimination by healthcare providers, communication and health literacy barriers, economic barriers of holding multiple jobs and the exorbitant cost of heart-healthy foods were identified as some barriers to achieving optimal cardiovascular health in this immigrant population.

Impact

Our study expanded on the body of knowledge on African immigrants' perceptions and attitudes toward cardiovascular health. Addressing this knowledge gap will provide important intervention opportunities targeted at improving cardiovascular health outcomes in this population.

Patient or Public Contribution

No patient or public contribution.

Caregiving in the COVID‐19 pandemic: Family adaptations following an intensive care unit hospitalisation

Abstract

Aim and Objective

To identify how family caregivers adapt to the caregiving role following a relative's COVID-19-related intensive care unit (ICU) hospitalisation.

Background

Family caregiving is often associated with poor health amongst caregivers which may limit their capacity to effectively support patients. Though severe COVID-19 infection has necessitated increasing numbers of persons who require caregiver support, little is known about these caregivers, the persons they are caring for, or the strategies used to effectively adjust to the caregiving role.

Design

A qualitative descriptive study design was adopted, and findings are reported using COREQ.

Methods

A secondary analysis of transcripts from semi-structured interviews conducted with recently discharged ICU patients who had COVID-19 (n = 16) and their family caregivers (n = 16) was completed using thematic analysis. MAXQDA 2020 and Miro were used to organise data and complete coding. Analysis involved a structured process of open and closed coding to identify and confirm themes that elucidated adaptation to family caregiving.

Results

Six themes highlight how family caregivers adapt to the caregiving role following an ICU COVID-19-related hospitalisation including (1) engaging the support of family and friends, (2) increased responsibilities to accommodate caregiving, (3) managing emotions, (4) managing infection control, (5) addressing patient independence and (6) engaging support services. These themes were found to be congruent with the Roy adaptation model.

Conclusions

Family caregiving is a stressful transition following a patient's acute hospitalisation. Effective adaptation requires flexibility and sufficient support, beginning with the care team who can adequately prepare the family for the anticipated challenges of recovery.

Relevance to Clinical Practice

Clinical teams may improve post-hospitalisation care outcomes of patients by preparing families to effectively adjust to the caregiver role—particularly in identifying sufficient support resources.

Patient or Public Contribution

Participation of patients/caregivers in this study was limited to the data provided through participant interviews.

Cultural acceptability of STI screening guidelines and sexual positioning assessments among black sexual minority men

Abstract

Aim

To identify attitudes towards HIV/STI screening guidelines and explore the acceptability of assessing sexual positioning practices among Black sexual minority men (SMM).

Background

Risks for HIV/STIs vary by sexual positioning practices. However, clinicians and Black SMM do not always discuss sexuality with each other. Therefore, HIV/STI screening and testing remain suboptimal.

Design

Qualitative study using focus groups.

Methods

Data were obtained from 12 focus groups and one in-depth interview conducted in Baltimore, MD among HIV-negative Black SMM between October 2019 and May 2020 (N = 39). Groups were stratified into three age categories: 18–24, 25–34 and 35+. Participants were given the “5 P's” from the CDC's 2015 Sexual History Screening Guidelines and asked to discuss attitudes towards existing questions regarding sexual positioning practices. Themes were identified using an electronic pile sorting approach.

Results

Most identified as homosexual/gay/same gender-loving (68%), were employed (69%) and single (66%). Additionally, 34% had ever been diagnosed with an STI, of whom 38% had a history of repeated STI acquisition in their lifetime. Participants across age groups said clinicians should use the words “top” and “bottom” to demonstrate cultural familiarity and build trust. Some said that screening for sexual positioning was unnecessary and intrusive; others said that questions should be justified. Younger men wanted clinicians to ask questions in ways that make them feel cared for.

Discussion

Guidelines should include language for clinicians to use culturally specific language and better ways to prepare Black SMM patients for screening.

Impact to Nursing Practice

Some Black SMM will not discuss sexual positioning practices without clinicians' demonstration of cultural understanding and respect. Screening should incorporate culturally responsive language, justification and convey care.

Reporting Method

Consolidated criteria for reporting qualitative research (COREQ).

No Patient or Public Contribution

There was no patient or public involvement in the design or drafting of this discursive paper.

Qualitative interview study exploring the perspectives of pregnant women on participating in controlled human infection research in the UK

Por: Dorey · R. B. · Theodosiou · A. A. · Read · R. C. · Vandrevala · T. · Jones · C. E.
Introduction

Pregnant women have been historically excluded from interventional research. While recent efforts have been made to improve their involvement, there remains a disparity in the evidence base for treatments available to pregnant women compared with the non-pregnant population. A significant barrier to the enrolment of pregnant women within research is risk perception and a poor understanding of decision-making in this population.

Objective

Assess the risk perception and influences on decision-making in pregnant women, when considering whether to enrol in a hypothetical interventional research study.

Design

Semistructured interviews were undertaken, and thematic analysis was undertaken of participant responses.

Participants

Twelve pregnant women were enrolled from an antenatal outpatient clinic.

Results

Participants were unanimously positive about enrolling in the proposed hypothetical interventional study. Risk perception was influenced by potential risks to their fetus and their previous experiences of healthcare and research. Participants found the uncertainty in quantifying risk for new research interventions challenging. They were motivated to enrol in research by altruism and found less invasive research interventions more tolerable.

Conclusion

It is vital to understand how pregnant women balance the perceived risks and benefits of interventional research. This may help clinicians and scientists better communicate risk to pregnant women and address the ongoing under-representation of pregnant women in interventional research.

The role and outcomes of music listening for women in childbirth: An integrative review

To synthesise primary research on the role and use of music listening for women in childbirth.
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