Fetal liver macrophages contribute to the hematopoietic stem cell niche by controlling granulopoiesis.

During embryogenesis, the fetal liver becomes the main hematopoietic organ, where stem and progenitor cells as well as immature and mature immune cells form an intricate cellular network. Hematopoietic stem cells (HSCs) reside in a specialized niche, which is essential for their proliferation and differentiation. However, the cellular and molecular determinants contributing to this fetal HSC niche remain largely unknown. Macrophages are the first differentiated hematopoietic cells found in the developing liver, where they are important for fetal erythropoiesis by promoting erythrocyte maturation and phagocytosing expelled nuclei. Yet, whether macrophages play a role in fetal hematopoiesis beyond serving as a niche for maturing erythroblasts remains elusive. Here, we investigate the heterogeneity of macrophage populations in the murine fetal liver to define their specific roles during hematopoiesis. Using a single-cell omics approach combined with spatial proteomics and genetic fate-mapping models, we found that fetal liver macrophages cluster into distinct yolk sac-derived subpopulations and that long-term HSCs are interacting preferentially with one of the macrophage subpopulations. Fetal livers lacking macrophages show a delay in erythropoiesis and have an increased number of granulocytes, which can be attributed to transcriptional reprogramming and altered differentiation potential of long-term HSCs. Together, our data provide a detailed map of fetal liver macrophage subpopulations and implicate macrophages as part of the fetal HSC niche.

Attitude and preventive practices of pressure ulcers among orthopedic nurses in a tertiary hospital in Ghana.

BACKGROUND: Pressure ulcers (PUs), which affect millions of people worldwide, are among the five most prevalent hospitalized cases causing adverse impairment. Nevertheless, pressure ulcers are largely preventable, and their management depends on their severity. The authors, therefore, explored the attitude and preventive practices of pressure ulcers among orthopedic nurses in a tertiary hospital in Ghana. METHODS: An exploratory descriptive qualitative approach was employed for this study to help researchers explore the attitude and practices toward PU (Pressure Ulcer). Purposive sampling approach was employed, and data was analyzed using thematic content analysis. The sample size for this study was 30 which was obtained based on saturation. Participants were engaged in face-to-face interviews which were transcribed verbatim. FINDINGS: Two themes and eight subthemes were generated from the analysis of this study. The two themes were preventive practices and attitude towards PU. The study identified that there were no specific protocols illustrated on the wards for managing pressure ulcers. Nevertheless, the study participants were keen on preventing pressure ulcers and hence engaged in practices such as early patients' ambulation, early identification of PU signs, removing creases and crumps from patient beds, nutritional management for PU prevention, and dressing of PU wounds. CONCLUSION: Practices of pressure ulcer management were highly valued by the orthopedics nurses. Hence, the nurses recommended the need for accepted guidelines on pressure ulcer management to be illustrated in the various orthopedic wards in the country.

Systemic alterations in neutrophils and their precursors in early-stage chronic obstructive pulmonary disease.

Systemic inflammation is established as part of late-stage severe lung disease, but molecular, functional, and phenotypic changes in peripheral immune cells in early disease stages remain ill defined. Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small-airway inflammation, emphysema, and severe breathing difficulties. Using single-cell analyses we demonstrate that blood neutrophils are already increased in early-stage COPD, and changes in molecular and functional neutrophil states correlate with lung function decline. Assessing neutrophils and their bone marrow precursors in a murine cigarette smoke exposure model identified similar molecular changes in blood neutrophils and precursor populations that also occur in the blood and lung. Our study shows that systemic molecular alterations in neutrophils and their precursors are part of early-stage COPD, a finding to be further explored for potential therapeutic targets and biomarkers for early diagnosis and patient stratification.

Alveolar macrophages in early stage COPD show functional deviations with properties of impaired immune activation.

Despite its high prevalence, the cellular and molecular mechanisms of chronic obstructive pulmonary disease (COPD) are far from being understood. Here, we determine disease-related changes in cellular and molecular compositions within the alveolar space and peripheral blood of a cohort of COPD patients and controls. Myeloid cells were the largest cellular compartment in the alveolar space with invading monocytes and proliferating macrophages elevated in COPD. Modeling cell-to-cell communication, signaling pathway usage, and transcription factor binding predicts TGF-ß1 to be a major upstream regulator of transcriptional changes in alveolar macrophages of COPD patients. Functionally, macrophages in COPD showed reduced antigen presentation capacity, accumulation of cholesteryl ester, reduced cellular chemotaxis, and mitochondrial dysfunction, reminiscent of impaired immune activation.

Enzymatic Activity of HPGD in Treg Cells Suppresses Tconv Cells to Maintain Adipose Tissue Homeostasis and Prevent Metabolic Dysfunction.

Regulatory T cells (Treg cells) are important for preventing autoimmunity and maintaining tissue homeostasis, but whether Treg cells can adopt tissue- or immune-context-specific suppressive mechanisms is unclear. Here, we found that the enzyme hydroxyprostaglandin dehydrogenase (HPGD), which catabolizes prostaglandin E2 (PGE2) into the metabolite 15-keto PGE2, was highly expressed in Treg cells, particularly those in visceral adipose tissue (VAT). Nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ)-induced HPGD expression in VAT Treg cells, and consequential Treg-cell-mediated generation of 15-keto PGE2 suppressed conventional T cell activation and proliferation. Conditional deletion of Hpgd in mouse Treg cells resulted in the accumulation of functionally impaired Treg cells specifically in VAT, causing local inflammation and systemic insulin resistance. Consistent with this mechanism, humans with type 2 diabetes showed decreased HPGD expression in Treg cells. These data indicate that HPGD-mediated suppression is a tissue- and context-dependent suppressive mechanism used by Treg cells to maintain adipose tissue homeostasis.

"We'll check vital signs only till we finish the school": experiences of student nurses regarding intra-semester clinical placement in Ghana.

BACKGROUND: Clinical practicum is an integral part of nursing education because it provides students with opportunities to perform nursing care and practice specific nursing tasks. In Ghana, little is known about the experiences of baccalaureate student nurses with regard to intra-semester clinical practicum. This study therefore, explored perceptions, challenges, and how the intra-semester clinical practicum affects the learning process of student nurses in a private university in Ghana. METHODS: Exploratory descriptive phenomenological design was used. Nine in-depth interviews and three focus group discussions were conducted for baccalaureate student nurses in their second, third and fourth years of study. Only those who have attended intra-semester clinical practicum for at least two semesters in the course of their study were recruited. Purposive sampling technique was used to select the participants. The sample size was based on data saturation, however, a total of 33 participants were recruited. Data was analysed using content analysis technique. RESULTS: The findings show that baccalaureate student nurses perceive the intra-semester clinical practicum as beneficial. It affords the opportunity to translate theoretical knowledge into practice concurrently. However, students recounted their stressful experiences during the clinical period which negatively affected their academic work. Additionally, staff nurses assigned the students to do menial jobs instead of appropriate nursing tasks. CONCLUSIONS: A review of the "block" method in which students will go to clinicals for a stipulated number of consecutive days in a month and then resume lectures, is worth considering.