Acute Inflammatory Responses of Nanoparticles in an Intra-Tracheal Instillation Rat Model

Exposure to hard metal tungsten carbide cobalt (WC-Co) “dusts” in enclosed industrial environments is known to contribute to the development of hard metal lung disease and an increased risk for lung cancer. Currently, the influence of local and systemic inflammation on disease progression following WC-Co exposure remains unclear. To better understand the relationship between WC-Co nanoparticle (NP) exposure and its resultant effects, the acute local pulmonary and systemic inflammatory responses caused by WC-Co NPs were explored using an intra-tracheal instillation (IT) model and compared to those of CeO2 (another occupational hazard) NP exposure. Sprague-Dawley rats were given an IT dose (0-500 μg per rat) of WC-Co or CeO2 NPs. Following 24-hr exposure, broncho-alveolar lavage fluid and whole blood were collected and analyzed. A consistent lack of acute local pulmonary inflammation was observed in terms of the broncho-alveolar lavage fluid parameters examined (i.e. LDH, albumin, and macrophage activation) in animals exposed to WC-Co NP; however, significant acute pulmonary inflammation was observed in the CeO2 NP group. The lack of acute inflammation following WC-Co NP exposure contrasts with earlier in vivo reports regarding WC-Co toxicity in rats, illuminating the critical role of NP dose and exposure time and bringing into question the potential role of impurities in particle samples. Further, we demonstrated that WC-Co NP exposure does not induce acute systemic effects since no significant increase in circulating inflammatory cytokines were observed. Taken together, the results of this in vivostudy illustrate the distinct differences in acute local pulmonary and systemic inflammatory responses to NPs composed of WC-Co and CeO2; therefore, it is important that the outcomes of pulmonary exposure to one type of NPs may not be implicitly extrapolated to other types of NPs

Mentoring, Training, and Scholarly Productivity Experiences of Cancer-Related Health Disparities Research Trainees: Do Outcomes Differ for Underrepresented Scientists?

The study aims to explore variation in scholarly productivity outcomes by underrepresented status among a diverse sample of researchers in a community-engaged training program. We identified 141 trainees from a web-based survey of researchers in the National Cancer Institute-funded, Community Networks Program Centers (CNPCs) (2011-2016). We conducted a series of multiple logistic regression models to estimate the effect of National Institutes of Health (NIH)-defined underrepresented status on four, self-reported, scholarly productivity outcomes in the previous 5 years: number of publications (first-authored and total) and funded grants (NIH and any agency). Sixty-five percent (n = 92) indicated NIH underrepresented status. In final adjusted models, non-NIH underrepresented (vs. underrepresented) trainees reported an increased odds of having more than the median number of total publications (> 9) (OR = 3.14, 95% CI 1.21-8.65) and any grant funding (OR = 5.10, 95% CI 1.77-14.65). Reporting ≥ 1 mentors (vs. none) was also positively associated (p < 0.05) with these outcomes. The CNPC underrepresented trainees had similar success in first-authored publications and NIH funding as non-underrepresented trainees, but not total publications and grants. Examining trainees' mentoring experiences over time in relation to scholarly productivity outcomes is needed

Perivascular Expression and Potent Vasoconstrictor Effect of Dynorphin A in Cerebral Arteries

BACKGROUND: Numerous literary data indicate that dynorphin A (DYN-A) has a significant impact on cerebral circulation, especially under pathophysiological conditions, but its potential direct influence on the tone of cerebral vessels is obscure. The aim of the present study was threefold: 1) to clarify if DYN-A is present in cerebral vessels, 2) to determine if it exerts any direct effect on cerebrovascular tone, and if so, 3) to analyze the role of κ-opiate receptors in mediating the effect. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistochemical analysis revealed the expression of DYN-A in perivascular nerves of rat pial arteries as well as in both rat and human intraparenchymal vessels of the cerebral cortex. In isolated rat basilar and middle cerebral arteries (BAs and MCAs) DYN-A (1-13) and DYN-A (1-17) but not DYN-A (1-8) or dynorphin B (DYN-B) induced strong vasoconstriction in micromolar concentrations. The maximal effects, compared to a reference contraction induced by 124 mM K(+), were 115±6% and 104±10% in BAs and 113±3% and 125±9% in MCAs for 10 µM of DYN-A (1-13) and DYN-A (1-17), respectively. The vasoconstrictor effects of DYN-A (1-13) could be inhibited but not abolished by both the κ-opiate receptor antagonist nor-Binaltorphimine dihydrochloride (NORBI) and blockade of G(i/o)-protein mediated signaling by pertussis toxin. Finally, des-Tyr(1) DYN-A (2-13), which reportedly fails to activate κ-opiate receptors, induced vasoconstriction of 45±11% in BAs and 50±5% in MCAs at 10 µM, which effects were resistant to NORBI. CONCLUSION/SIGNIFICANCE: DYN-A is present in rat and human cerebral perivascular nerves and induces sustained contraction of rat cerebral arteries. This vasoconstrictor effect is only partly mediated by κ-opiate receptors and heterotrimeric G(i/o)-proteins. To our knowledge our present findings are the first to indicate that DYN-A has a direct cerebral vasoconstrictor effect and that a dynorphin-induced vascular action may be, at least in part, independent of κ-opiate receptors

Introgression Mapping in The Grasses

Key points Lolium perenne/Festuca pratensis hybrids and their derivatives provide an ideal system for intergeneric introgression. The Lolium perenne/Festuca pratensis system is being exploited to elucidate genome organisation in the grasses, determination of the genetic control of target traits and the isolation of markers for MAS in breeding programmes. The potential of the system as an aid to contig the Lolium and Festuca genomes and for gene isolation is discussed

Coloration in different areas of facial skin is a cue to health: The role of cheek redness and periorbital luminance in health perception

Looking healthy is a desirable trait, and facial skin color is a predictor of perceived health. However, skin conditions that cause dissatisfaction with appearance are specific to particular facial areas. We investigated whether color variation in facial skin is related to perceived health. Study 1 defined three areas based on color differences between faces perceived as healthy or unhealthy: the forehead, periorbital areas, and the cheeks. Periorbital luminance and cheek redness predicted perceived health, as did global skin yellowness. In Study 2, increased luminance and redness caused faces to be perceived as healthier, but only when the increase was in the periorbital and cheek areas, respectively. Manipulating each area separately in Study 3 revealed cheek redness and periorbital luminance equally increased perceived health, with low periorbital luminance more negatively affecting perceptions. These findings show that color variation in facial skin is a cue for health perception in female faces

Neonatal cerebrovascular autoregulation.

Cerebrovascular pressure autoregulation is the physiologic mechanism that holds cerebral blood flow (CBF) relatively constant across changes in cerebral perfusion pressure (CPP). Cerebral vasoreactivity refers to the vasoconstriction and vasodilation that occur during fluctuations in arterial blood pressure (ABP) to maintain autoregulation. These are vital protective mechanisms of the brain. Impairments in pressure autoregulation increase the risk of brain injury and persistent neurologic disability. Autoregulation may be impaired during various neonatal disease states including prematurity, hypoxic-ischemic encephalopathy (HIE), intraventricular hemorrhage, congenital cardiac disease, and infants requiring extracorporeal membrane oxygenation (ECMO). Because infants are exquisitely sensitive to changes in cerebral blood flow (CBF), both hypoperfusion and hyperperfusion can cause significant neurologic injury. We will review neonatal pressure autoregulation and autoregulation monitoring techniques with a focus on brain protection. Current clinical therapies have failed to fully prevent permanent brain injuries in neonates. Adjuvant treatments that support and optimize autoregulation may improve neurologic outcomes

Electron Transmission Spectroscopy in Atomic Hydrogen

An electron transmission experiment is used to study the resonances in the total scattering cross section of atomic hydrogen below the threshold of the first excited state. The three lowest resonances, designated 1S, 3P, and 1D, are observed and their energies and decay widths are found to be in good agreement with the values predicted theoretically using close coupling with correlation

Natural carriers for application in tuberculosis treatment

Tuberculosis remains the leading cause of preventable deaths worldwide and unsuccessful therapy is mainly due to non-compliance with very prolonged treatments, often associated with severe side-effects. Overcoming this problem demands the introduction of drug carriers releasing the antimicrobial agents in a targeted and sustained manner, allowing reduction in frequency and dosing numbers. Nano and microparticles have taken the forefront of this approach, providing the means for the desired improvement of therapeutic schedules. Natural polymers are strong candidates as matrix forming materials, usually exhibiting biocompatibility, biodegradability, low cost and some technological advantages as compared with synthetic counterparts. In this review, natural particulate carriers developed for tuberculosis therapy are presented, mainly focusing on the use of polysaccharides and lipids. Their effectiveness is discussed taking into account their composition. Finally, considerations on the general potential of natural materials for this application, as well as key factors still to be addressed, are discussed

Differential responses of osteoblasts and macrophages upon Staphylococcus aureus infection

Background Staphylococcus aureus (S. aureus) is one of the primary causes of bone infections which are often chronic and difficult to eradicate. Bacteria like S. aureus may survive upon internalization in cells and may be responsible for chronic and recurrent infections. In this study, we compared the responses of a phagocytic cell (i.e. macrophage) to a non-phagocytic cell (i.e. osteoblast) upon S. aureus internalization. Results We found that upon internalization, S. aureus could survive for up to 5 and 7 days within macrophages and osteoblasts, respectively. Significantly more S. aureus was internalized in macrophages compared to osteoblasts and a significantly higher (100 fold) level of live intracellular S. aureus was detected in macrophages compared to osteoblasts. However, the percentage of S. aureus survival after infection was significantly lower in macrophages compared to osteoblasts at post-infection days 1–6. Interestingly, macrophages had relatively lower viability in shorter infection time periods (i.e. 0.5-4 h; significant at 2 h) but higher viability in longer infection time periods (i.e. 6–8 h; significant at 8 h) compared to osteoblasts. In addition, S. aureusinfection led to significant changes in reactive oxygen species production in both macrophages and osteoblasts. Moreover, infected osteoblasts had significantly lower alkaline phosphatase activity at post-infection day 7 and infected macrophages had higher phagocytosis activity compared to non-infected cells. Conclusions S. aureus was found to internalize and survive within osteoblasts and macrophages and led to differential responses between osteoblasts and macrophages. These findings may assist in evaluation of the pathogenesis of chronic and recurrent infections which may be related to the intracellular persistence of bacteria within host cells