Resilient anatomy and local plasticity of naive and stress haematopoiesis.

The bone marrow adjusts blood cell production to meet physiological demands in response to insults. The spatial organization of normal and stress responses are unknown owing to the lack of methods to visualize most steps of blood production. Here we develop strategies to image multipotent haematopoiesis, erythropoiesis and lymphopoiesis in mice. We combine these with imaging of myelopoiesis1 to define the anatomy of normal and stress haematopoiesis. In the steady state, across the skeleton, single stem cells and multipotent progenitors distribute through the marrow enriched near megakaryocytes. Lineage-committed progenitors are recruited to blood vessels, where they contribute to lineage-specific microanatomical structures composed of progenitors and immature cells, which function as the production sites for each major blood lineage. This overall anatomy is resilient to insults, as it was maintained after haemorrhage, systemic bacterial infection and granulocyte colony-stimulating factor (G-CSF) treatment, and during ageing. Production sites enable haematopoietic plasticity as they differentially and selectively modulate their numbers and output in response to insults. We found that stress responses are variable across the skeleton: the tibia and the sternum respond in opposite ways to G-CSF, and the skull does not increase erythropoiesis after haemorrhage. Our studies enable in situ analyses of haematopoiesis, define the anatomy of normal and stress responses, identify discrete microanatomical production sites that confer plasticity to haematopoiesis, and uncover unprecedented heterogeneity of stress responses across the skeleton.

In situ mapping identifies distinct vascular niches for myelopoiesis.

In contrast to nearly all other tissues, the anatomy of cell differentiation in the bone marrow remains unknown. This is owing to a lack of strategies for examining myelopoiesis-the differentiation of myeloid progenitors into a large variety of innate immune cells-in situ in the bone marrow. Such strategies are required to understand differentiation and lineage-commitment decisions, and to define how spatial organizing cues inform tissue function. Here we develop approaches for imaging myelopoiesis in mice, and generate atlases showing the differentiation of granulocytes, monocytes and dendritic cells. The generation of granulocytes and dendritic cells-monocytes localizes to different blood-vessel structures known as sinusoids, and displays lineage-specific spatial and clonal architectures. Acute systemic infection with Listeria monocytogenes induces lineage-specific progenitor clusters to undergo increased self-renewal of progenitors, but the different lineages remain spatially separated. Monocyte-dendritic cell progenitors (MDPs) map with nonclassical monocytes and conventional dendritic cells; these localize to a subset of blood vessels expressing a major regulator of myelopoiesis, colony-stimulating factor 1 (CSF1, also known as M-CSF)1. Specific deletion of Csf1 in endothelium disrupts the architecture around MDPs and their localization to sinusoids. Subsequently, there are fewer MDPs and their ability to differentiate is reduced, leading to a loss of nonclassical monocytes and dendritic cells during both homeostasis and infection. These data indicate that local cues produced by distinct blood vessels are responsible for the spatial organization of definitive blood cell differentiation.

The Role of the Bone Marrow Microenvironment in the Response to Infection.

Hematopoiesis in the bone marrow (BM) is the primary source of immune cells. Hematopoiesis is regulated by a diverse cellular microenvironment that supports stepwise differentiation of multipotent stem cells and progenitors into mature blood cells. Blood cell production is not static and the bone marrow has evolved to sense and respond to infection by rapidly generating immune cells that are quickly released into the circulation to replenish those that are consumed in the periphery. Unfortunately, infection also has deleterious effects injuring hematopoietic stem cells (HSC), inefficient hematopoiesis, and remodeling and destruction of the microenvironment. Despite its central role in immunity, the role of the microenvironment in the response to infection has not been systematically investigated. Here we summarize the key experimental evidence demonstrating a critical role of the bone marrow microenvironment in orchestrating the bone marrow response to infection and discuss areas of future research.

Anxiety experienced by individuals with cancer in remission.

For this qualitative research study, we interviewed 25 individuals who survived cancer regarding the sentiments they experienced in adjusting to having their condition in remission. Among other findings that we reported elsewhere, two themes emerged from the in-depth interviews relating to apprehensive percepts. One was that participants spoke of their tendency to battle worrisome thoughts. Although they used a variety of words in describing the construct, anxiety repeatedly appeared as a cogent emotion when facing cancer. Second, anniversaries were said to have continued cogence for the participants as they triggered memories and tended to generate degrees of anxiety.

A survey of policies and local ordinances supporting physical activity in Hawaii counties.

BACKGROUND: Features of the built environment that influence physical activity behavior characterize Active Community Environments. CONTEXT: Whether Active Community Environments policies exist in the state of Hawaii's four counties is unknown. The purpose of this study was to provide a baseline assessment of these policies in Hawaii. METHODS: A survey assessing policies in six domains (i.e., sidewalks, bike lanes, greenways, recreational facilities, commercial buildings, and shared-use paths) was completed by employees of Hawaii planning departments. CONSEQUENCES: Honolulu County had the most policies (n = 13), followed by Maui County (n = 6), Kauai County (n = 2), and Hawaii County (n = 1). Written policies were most prevalent in Honolulu County (n = 15), followed by Kauai County (n = 14), Hawaii County, (n = 4), and Maui County (n = 3). Sidewalk policies were reported for Honolulu County, Maui County (no written policies were found for Maui County), and Kauai County. Bike lane and greenway policies were found for Honolulu County (reported and written) and Kauai County (written). Recreation facility and pedestrian shared-use path policies existed for all counties, although only Honolulu and Kauai counties had written policies for commercial buildings (Maui County reported having policies). Few policies directly addressed physical activity promotion. INTERPRETATION: The most populous county, Honolulu, had the most policies in place, although discrepancies existed between reported and written policies. This baseline measure of physical activity-related policies will help focus efforts of county coalitions to increase opportunities for physical activity. Additional policies should be tracked with population behavior surveillance.

Food security issues for low-income Hawaii residents.

Support provided by the US Food Stamp Program (FSP) is intended to promote health. The objective of this qualitative study was to examine food security for low-income Hawaii residents. A sample of low-income Hawaii residents (n = 86) were recruited to participate in a series of focus group discussions. Most participants were female (73.5%), Native Hawaiian/Pacific Islander (61.6%), ages 18-39 (62.7%), high school educated (80.5%), low-income (50.6% < $10,000), used food stamps (73.5%), and had 4.07 +/- 2.89 persons per household. At 2 hour focus groups, participants received a healthy meal and a monetary incentive. Audio recordings were transcribed verbatim and analyzed using NVivo. Over 50% indicated FSP assistance was not enough. When this happened, most participants had alternatives including food banks, churches, friends and family members. Shopping strategies included budgeting, buying in bulk, or smarter shopping practices. Several participants were concerned about high living costs. Food insecurity should be addressed for FSP participants in Hawaii, with many residents not being able to meet nutritional and economic needs on their own.