Community-level characteristics of high infant mortality: A tool to identify at-risk communities

Infant mortality (IM) rate is a key indicator of population health and has been gradually improving in the United States. However, it is still a public health problem among minority and low-income communities. Maternal factors explain some of the variation, but community-level factors may also be a contributor. This study examines measures to identify a set of indicators that explain variations in IM at the community-level. Data for 77 communities in a city were obtained from local health databases. We used multivariable linear regression models to examine the strength of the association between IM and maternal, population, community wealth, and social capital characteristics. Community-level IM rates ranged from 2.1 – 25.6 deaths per 1,000 live births in 2000-2002. The final model explained 75% of the variation in IM rates at the community-level (R2=0.75). The model included a high percentage of low birth weight babies, a decline in mothers who began prenatal care in the second trimester, an increase in the percentage of Hispanics, increased unemployment rates, an increase in the percentage of veterans, an increased rate of foreign-born residents, and smaller average family sizes. Social capital variables, homicide rate and vacant housing, were also significant in the final model. Identifying communities at risk for high IM rates is imperative to improve maternal and child health outcomes because of shortages in public health resources. The development of a parsimonious set of community-level indicators can assist public health practitioners in targeting their resources to prevent infant mortality in high-risk communities

Self-assembling nanoparticles containing dexamethasone as a novel therapy in allergic airways inflammation.

Nanocarriers can deliver a wide variety of drugs, target them to sites of interest, and protect them from degradation and inactivation by the body. They have the capacity to improve drug action and decrease undesirable systemic effects. We have previously developed a well-defined non-toxic PEG-dendritic block telodendrimer for successful delivery of chemotherapeutics agents and, in these studies, we apply this technology for therapeutic development in asthma. In these proof-of-concept experiments, we hypothesized that dexamethasone contained in self-assembling nanoparticles (Dex-NP) and delivered systemically would target the lung and decrease allergic lung inflammation and airways hyper-responsiveness to a greater degree than equivalent doses of dexamethasone (Dex) alone. We found that ovalbumin (Ova)-exposed mice treated with Dex-NP had significantly fewer total cells (2.78 ± 0.44 × 10(5) (n = 18) vs. 5.98 ± 1.3 × 10(5) (n = 13), P<0.05) and eosinophils (1.09 ± 0.28 × 10(5) (n = 18) vs. 2.94 ± 0.6 × 10(5) (n = 12), p<0.05) in the lung lavage than Ova-exposed mice alone. Also, lower levels of the inflammatory cytokines IL-4 (3.43 ± 1.2 (n = 11) vs. 8.56 ± 2.1 (n = 8) pg/ml, p<0.05) and MCP-1 (13.1 ± 3.6 (n = 8) vs. 28.8 ± 8.7 (n = 10) pg/ml, p<0.05) were found in lungs of the Dex-NP compared to control, and they were not lower in the Dex alone group. In addition, respiratory system resistance was lower in the Dex-NP compared to the other Ova-exposed groups suggesting a better therapeutic effect on airways hyperresponsiveness. Taken together, these findings from early-stage drug development studies suggest that the encapsulation and protection of anti-inflammatory agents such as corticosteroids in nanoparticle formulations can improve efficacy. Further development of novel drugs in nanoparticles is warranted to explore potential treatments for chronic inflammatory diseases such as asthma

Atypical chemokine receptor ACKR2 controls branching morphogenesis in the developing mammary gland

Macrophages are important regulators of branching morphogenesis during development and postnatally in the mammary gland. Regulation of macrophage dynamics during these processes can therefore have a profound impact on development. We demonstrate here that the developing mammary gland expresses high levels of inflammatory CC-chemokines, which are essential in vivo regulators of macrophage migration. We further demonstrate that the atypical chemokine receptor ACKR2, which scavenges inflammatory CC-chemokines, is differentially expressed during mammary gland development. We have previously shown that ACKR2 regulates macrophage dynamics during lymphatic vessel development. Here, we extend these observations to reveal a novel role for ACKR2 in regulating the postnatal development of the mammary gland. Specifically, we show that Ackr2−/− mice display precocious mammary gland development. This is associated with increased macrophage recruitment to the developing gland and increased density of the ductal epithelial network. These data demonstrate that ACKR2 is an important regulator of branching morphogenesis in diverse biological contexts and provide the first evidence of a role for chemokines and their receptors in postnatal development processes

Effect of post-thermal treatment on the density profile of rubberwood particleboard and its relation to mechanical properties

The objective of the study was to investigate the effect of heat treatment on the changes in density profile of rubberwood particleboard samples. The relationship between density profile and mechanical properties of particleboard samples was determined using regression analysis. Single layer particleboard made from rubberwood particles with dimensions of 340 mm × 340 mm × 12 mm and targeted density of 700 kg m-3 was heat-treated using oven and hot press at three different temperature levels, namely, 100, 150 and 200 °C for 30 min. All density profile attributes were significantly affected by heat treatment. Bending properties, internal bond strength and hardness were influenced by treatment temperature. However, samples treated using hot press had better mechanical properties compared with those treated using oven. Mean and peak densities exerted profound effects on mechanical properties of the samples

An ITAM-signaling pathway controls cross-presentation of particulate but not soluble antigens in dendritic cells

Dendritic cells (DC) possess a unique capacity for presenting exogenous antigen on major histocompatibility class I, a process that is referred to as cross-presentation, which serves a critical role in microbial and tumor immunity. During cross-presentation, antigens derived from pathogen-infected or tumor cells are internalized and processed by DCs for presentation to cytotoxic T lymphocytes (CTLs). We demonstrate that a signaling pathway initiated by the immunoreceptor tyrosine–based activation motif (ITAM)–containing adaptors DAP12 and FcRγ utilizes the Vav family of Rho guanine nucleotide exchange factors (GEFs) for processing and cross-presentation of particulate, but not soluble, antigens by DCs. Notably, this novel pathway is crucial for processing and presentation of particulate antigens, such as those associated with Listeria monocytogenes bacteria, yet it is not required for antigen uptake. Mechanistically, we provide evidence that in DCs, Vav GEFs are essential to link ITAM-dependent receptors with the activation of the NOX2 complex and production of reactive oxygen species (ROS), which regulate phagosomal pH and processing of particulate antigens for cross-presentation. Importantly, we show that genetic disruption of the DAP12/FcRγ–Vav pathway leads to antigen presentation defects that are more profound than in DCs lacking NOX2, suggesting that ITAM signaling also controls cross-presentation in a ROS-independent manner