The interaction of cancer cells with the stromal cells and matrix in the tumor
microenvironment plays a key role in progression to metastasis. A better
understanding of the mechanisms underlying ...these interactions would aid in
developing new therapeutic approaches to inhibit this progression. Here, we
describe the fabrication of a simple microfluidic bioreactor capable of
recapitulating the three-dimensional breast tumor microenvironment. Cancer cell
spheroids, fibroblasts, and endothelial cells co-cultured in this device create
a robust microenvironment suitable for studying in real time the migration of
cancer cells along matrix structures laid down by fibroblasts within the 3D
tumor microenvironment. This system allows for ready evaluation of response to
targeted therapy.
It is still an open challenge to find a biodegradable metallic material exhibiting sufficient mechanical properties and degradation behavior to serve as an arterial stent. In this study, Zn-Mg alloys ...of 0.002 (Zn-002Mg), 0.005 (Zn-005Mg) and 0.08wt% Mg (Zn-08Mg) content were cast, extruded and drawn to 0.25mm diameter, and evaluated as potential biodegradable stent materials. Structural analysis confirmed formation of Mg2Zn11 intermetallic in all three alloys with the average grain size decreasing with increasing Mg content. Tensile testing, fractography analysis and micro hardness measurements showed the best integration of strength, ductility and hardness for the Zn-08Mg alloy. Yield strength, tensile strength, and elongation to failure values of >200–300MPa, >300–400MPa, and >30% respectively, were recorded for Zn-08Mg. This metal appears to be the first formulated biodegradable material that satisfies benchmark values desirable for endovascular stenting. Unfortunately, the alloy reveals signs of age hardening and strain rate sensitivity, which need to be addressed before using this metal for stenting. The explants of Zn-08Mg alloy residing in the abdominal aorta of adult male Sprague-Dawley rats for 1.5, 3, 4.5, 6 and 11months demonstrated similar, yet slightly elevated inflammation and neointimal activation for the alloy relative to what was recently reported for pure zinc.
•Minor alloying with Mg additions improves Zn strength.•Novel micro-alloy exceeds benchmark values desirable for vascular scaffolding.•Minor alloying with Mg additions does not compromise Zn biocompatibility.•Micro-alloys showed age-hardening and strain rate sensitivity.
The study aimed at investigating Gram-positive and Gram-negative bacteria in moldy and non-moldy homes, as defined by the home's Environmental Relative Moldiness Index (ERMI) value. The ERMI values ...were determined from floor dust samples in 2010 and 2011 and homes were classified into low (<5) and high (>5) ERMI groups based on the average ERMI values as well as 2011 ERMI values. Dust and air samples were collected from the homes in 2011 and all samples were analyzed for Gram-positive and Gram-negative bacteria using QPCR assays, endotoxin by the LAL assay, and N-acetyl-muramic acid using HPLC. In addition, air samples were analyzed for culturable bacteria. When average ERMI values were considered, the concentration and load of Gram-positive bacteria determined with QPCR in house dust, but not air, were significantly greater in high ERMI homes than in low ERMI homes. Furthermore, the concentration of endotoxin, but not muramic acid, in the dust was significantly greater in high ERMI than in low ERMI homes. In contrast, when ERMI values of 2011 were considered, Gram-negative bacteria determined with QPCR in air, endotoxin in air, and muramic acid in dust were significantly greater in high ERMI homes. The results suggest that both short-term and long-term mold contamination in homes could be linked with the bacterial concentrations in house dust, however, only the current mold status was associated with bacterial concentrations in air. Although correlations were found between endotoxin and Gram-negative bacteria as well as between muramic acid and Gram-positive bacteria in the entire data set, diverging associations were observed between the different measures of bacteria and the home moldiness. It is likely that concentrations of cells obtained by QPCR and concentrations of cell wall components are not equivalent and represent too broad categories to understand the bacterial composition and sources of the home microbiota.
•High ERMI and low ERMI homes differ in bacterial contaminant levels.•Only the current mold status is associated with bacterial concentrations in air.•Dust versus air samples provide different perspectives of bacterial contamination.•Occupancy in homes correlates with total Gram-positive bacterial cells in air.•Correlations of temperature and RH with culturable and total bacteria are unalike.
Our team searches for the signature of cosmological shocks in stacked gas pressure profiles of galaxy clusters using data from the South Pole Telescope (SPT). Specifically, we stack the latest ...Compton-y maps from the 2500 deg2 SPT-SZ survey on the locations of clusters identified in that same dataset. The sample contains 516 clusters with mean mass $\langle$M200m$\rangle$ = 1014.9 M⊙ and redshift $\langle$z$\rangle$ = 0.55. We analyse in parallel a set of zoom-in hydrodynamical simulations from THE THREE HUNDRED project. The SPT-SZ data show two features: (i) a pressure deficit at R/R200m = 1.08 ± 0.09, measured at 3.1σ significance and not observed in the simulations, and; (ii) a sharp decrease in pressure at R/R200m = 4.58 ± 1.24 at 2.0σ significance. The pressure deficit is qualitatively consistent with a shock-induced thermal non-equilibrium between electrons and ions, and the second feature is consistent with accretion shocks seen in previous studies. We split the cluster sample by redshift and mass, and find both features exist in all cases. There are also no significant differences in features along and across the cluster major axis, whose orientation roughly points towards filamentary structure. As a consistency test, we also analyse clusters from the Planck and Atacama Cosmology Telescope Polarimeter surveys and find quantitatively similar features in the pressure profiles. Finally, we compare the accretion shock radius (Rsh, acc) with existing measurements of the splashback radius (Rsp) for SPT-SZ and constrain the lower limit of the ratio, Rsh, acc/Rsp > 2.16 ± 0.59.
Multidrug-resistant Acinetobacter baumannii is among the most prevalent bacterial pathogens associated with trauma-related wound and bloodstream infections. Although septic shock and disseminated ...intravascular coagulation have been reported following fulminant A. baumannii sepsis, little is known about the protective host immune response to this pathogen. In this study, we examined the role of PTX3, a soluble pattern recognition receptor with reported antimicrobial properties and stored within neutrophil granules. PTX3 production by murine J774a.1 macrophages was assessed following challenge with A. baumannii strains ATCC 19606 and clinical isolates (CI) 77, 78, 79, 80, and 86. Interestingly, only CI strains 79, 80, and 86 induced PTX3 synthesis in murine J774a.1 macrophages, with greatest production observed following CI 79 and 86 challenge. Subsequently, C57BL/6 mice were challenged intraperitoneally with CI 77 and 79 to assess the role of PTX3 in vivo. A. baumannii strain CI 79 exhibited significantly (P < 0.0005) increased mortality, with an approximate 50% lethal dose (LD50) of 10(5) CFU, while an equivalent dose of CI 77 exhibited no mortality. Plasma leukocyte chemokines (KC, MCP-1, and RANTES) and myeloperoxidase activity were also significantly elevated following challenge with CI 79, indicating neutrophil recruitment/activation associated with significant elevation in serum PTX3 levels. Furthermore, 10-fold-greater PTX3 levels were observed in mouse serum 12 h postchallenge, comparing CI 79 to CI 77 (1,561 ng/ml versus 145 ng/ml), with concomitant severe pathology (liver and spleen) and coagulopathy. Together, these results suggest that elevation of PTX3 is associated with fulminant disease during A. baumannii sepsis.
In response to critical care nurses' perceptions of increasing stress and conflict in difficult end-of-life (EOL) situations, the researchers conducted a study to identify perceived obstacles, ...supports, and knowledge needed to provide quality EOL care. The conclusions were as follows(1) families and patients need clear, direct, and consistent information to make EOL decisions; (2) physician-related issues affect nurses' ability to provide quality EOL care; (3) critical care nurses need more knowledge, skill, and a sense of cultural competency to provide quality care; and (4) having properly completed advance directives can reduce confusion about the goals of care. Recommendations for improving EOL care were made as a result of the study.
Background
Follow-up of tests pending at discharge (TPADs) is poor. We previously demonstrated a twofold increase in awareness of
any
TPAD by attendings and primary care physicians (PCPs) using an ...automated email intervention
Objective
To determine whether automated notification improves documented follow-up for
actionable
TPADs
Design
Cluster-randomized controlled trial
Subjects
Attendings and PCPs caring for adult patients discharged from general medicine and cardiology services with at least one actionable TPAD between June 2011 and May 2012
Intervention
An automated system that notifies discharging attendings and network PCPs of finalized TPADs by email
Main Measures
The primary outcome was the proportion of actionable TPADs with documented action determined by independent physician review of the electronic health record (EHR). Secondary outcomes included documented acknowledgment, 30-day readmissions, and adjusted median days to documented follow-up.
Key Results
Of the 3378 TPADs sampled, 253 (7.5%) were determined to be actionable by physician review. Of these, 150 (123 patients discharged by 53 attendings) and 103 (90 patients discharged by 44 attendings) were assigned to intervention and usual care groups, respectively, and underwent chart review. The proportion of actionable TPADs with documented action was 60.7 vs. 56.3% (
p
= 0.82) in the intervention vs. usual care groups, similar for documented acknowledgment. The proportion of patients with actionable TPADs readmitted within 30 days was 22.8 vs. 31.1% in the intervention vs. usual care groups (
p
= 0.24). The adjusted median days 95% CI to documented action was 9 6.2, 11.8 vs. 14 10.2, 17.8 (
p
= 0.04) in the intervention vs. usual care groups, similar for documented acknowledgment. In sub-group analysis, the intervention had greater impact on documented action for patients with network PCPs compared with usual care (70 vs. 50%,
p
= 0.03).
Conclusions
Automated notification of actionable TPADs shortened time to action but did not significantly improve documented follow-up, except for network-affiliated patients. The high proportion of actionable TPADs without
any
documented follow-up (~ 40%) represents an ongoing safety concern.
Clinical Trials Identifier
NCT01153451
Peer review is the bedrock of modern academic research and its lasting contributions to science and society. And yet, reviewers can submit “poor” peer review reports, authors can blatantly ignore ...referee advice, and editors can contravene and undermine the peer review process itself. In this paper, we, the Editors of Energy Research & Social Science (ER&SS), seek to establish peer review codes of practice for the general energy and social science research community. We include suggestions for three of the most important roles: peer reviewers or referees, editors, and authors. We base our 33 recommendations on a collective 60 years of editorial experience at ER&SS. Our hope is that such codes of practice can enable the academic community to navigate the peer review process more effectively, more meaningfully, and more efficiently.
Melon (
Cucumis melo
L.) is a global crop in terms of economic importance and nutritional quality. The aim of this study was to explore the variability in metabolite and elemental composition of ...several commercial varieties of melon in various environmental conditions. Volatile and non-volatile metabolites as well as mineral elements were profiled in the flesh of mature fruit, employing a range of complementary analytical technologies. More than 1,000 metabolite signatures and 19 mineral elements were determined. Data analyses revealed variations related to factors such as variety, growing season, contrasting agricultural management practices (greenhouse vs. field with or without fruit thinning) and planting date. Two hundred and ninety-one analytes discriminated two contrasting varieties, one from the var. inodorous group and the other from the var. cantaloupensis group. Two hundred and eighty analytes discriminated a short shelf-life from a mid-shelf-life variety within the var. cantaloupensis group. Three hundred and twenty-seven analytes discriminated two seasons, and two hundred and fifty-two analytes discriminated two contrasting agricultural management practices. The affected compound families greatly depended on the factor studied. The compositional variability of identified or partially identified compounds was used to study metabolite and mineral element co-regulation using correlation networks. The results confirm that metabolome and mineral element profiling are useful diagnostic tools to characterize the quality of fruits cultivated under commercial conditions. They can also provide knowledge on fruit metabolism and the mechanisms of plant response to environmental modifications, thereby paving the way for metabolomics-guided improvement of cultural practices for better fruit quality.
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