The Relationship of Indoor, Outdoor and Personal Air (RIOPA) study was designed to investigate residential indoor, outdoor and personal exposures to several classes of air pollutants, including volatile organic compounds, carbonyls and fine particles (PM 2.5 ). Samples were collected from summer, 1999 to spring, 2001 in Houston (TX), Los Angeles (CA) and Elizabeth (NJ). Indoor, outdoor and personal PM 2.5 samples were collected at 212 nonsmoking residences, 162 of which were sampled twice. Some homes were chosen due to close proximity to ambient sources of one or more target analytes, while others were farther from sources. Median indoor, outdoor and personal PM 2.5 mass concentrations for these three sites were 14.4, 15.5 and 31.4 mg/m 3 , respectively. The contributions of ambient (outdoor) and nonambient sources to indoor and personal concentrations were quantified using a single compartment box model with measured air exchange rate and a random component superposition (RCS) statistical model. The median contribution of ambient sources to indoor PM 2.5 concentrations using the mass balance approach was estimated to be 56% for all study homes (63%, 52% and 33% for California, New Jersey and Texas study homes, respectively). Reasonable variations in model assumptions alter median ambient contributions by less than 20%. The mean of the distribution of ambient contributions across study homes agreed well for the mass balance and RCS models, but the distribution was somewhat broader when calculated using the mass balance model with measured air exchange rates.

Effects of physical/environmental factors on fine particle (PM2.5) exposure, outdoor-to-indoor transport and air exchange rate (AER) were examined. The fraction of ambient PM2.5 found indoors (FINF) and the fraction to which people are exposed (α) modify personal exposure to ambient PM2.5. Because FINF, α, and AER are infrequently measured, some have used air conditioning (AC) as a modifier of ambient PM2.5 exposure. We found no single variable that was a good predictor of AER. About 50% and 40% of the variation in FINF and α, respectively, was explained by AER and other activity variables. AER alone explained 36% and 24% of the variations in FINF and α, respectively. Each other predictor, including Central AC Operation, accounted for less than 4% of the variation. This highlights the importance of AER measurements to predict FINF and α. Evidence presented suggests that outdoor temperature and home ventilation features affect particle losses as well as AER, and the effects differ. Total personal exposures to PM2.5 mass/species were reconstructed using personal activity and microenvironmental methods, and compared to direct personal measurement. Outdoor concentration was the dominant predictor of (partial R2 = 30–70%) and the largest contributor to (20–90%) indoor and personal exposures for PM2.5 mass and most species. Several activities had a dramatic impact on personal PM2.5 mass/species exposures for the few study participants exposed to or engaged in them, including smoking and woodworking. Incorporating personal activities (in addition to outdoor PM2.5) improved the predictive power of the personal activity model for PM2.5 mass/species; more detailed information about personal activities and indoor sources is needed for further improvement (especially for Ca, K, OC). Adequate accounting for particle penetration and persistence indoors and for exposure to non-ambient sources could potentially increase the power of epidemiological analyses linking health effects to particulate exposures.

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Residential indoor and outdoor fine particle (PM 2.5 ) organic (OC) and elemental carbon (EC) concentrations (48 h) were measured at 173 homes in Houston, TX, Los Angeles County, CA, and Elizabeth, NJ as part of the Relationship of Indoor, Outdoor and Personal Air (RIOPA) study. The adsorption of organic vapors on the quartz fiber sampling filter (a positive artifact) was substantial indoors and out, accounting for 36% and 37% of measured OC at the median indoor (8.2 mg C/m 3 ) and outdoor (5.0 mg C/m 3 ) OC concentrations, respectively. Uncorrected, adsorption artifacts would lead to substantial overestimation of particulate OC both indoors and outdoors. After artifact correction, the mean particulate organic matter (OM ¼ 1.4 OC) concentration indoors (9.8 mg/m 3 ) was twice the mean outdoor concentration (4.9 mg/m 3 ). The mean EC concentration was 1.1 mg/m 3 both indoors and outdoors. OM accounted for 29%, 30% and 29% of PM 2.5 mass outdoors and 48%, 55% and 61% of indoor PM 2.5 mass in Los Angeles Co., Elizabeth and Houston study homes, respectively. Indirect evidence provided by species mass balance results suggests that PM 2.5 nitrate (not measured) was largely lost during outdoor-to-indoor transport, as reported by Lunden et al. This results in dramatic changes with outdoor-to-indoor transport in the mass and composition of ambient-generated PM 2.5 at California homes. On average, 71% to 76% of indoor OM was emitted or formed indoors, calculated by (1) Random Component Superposition (RCS) model and (2) non-linear fit of OC and air exchange rate data to the mass balance model. Assuming that all particles penetrate indoors (P ¼ 1) and there is no particle loss indoors (k ¼ 0), a lower bound estimate of 41% of indoor OM was indoor-generated (mean). OM appears to be the predominant species in indoor-generated PM 2.5 , based on species mass balance results. Particulate OM emitted or formed indoors is substantial enough to alter the concentration, composition and behavior of indoor PM 2.5 . One interesting effect of increased indoor OM concentrations is a shift in the gas-particle partitioning of polycyclic aromatic hydrocarbons (PAHs) from the gas to the particle phase with outdoor-to-indoor transport.

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Epidemiological studies routinely use central-site particulate matter (PM) as a surrogate for exposure to PM of ambient (outdoor) origin. Below we quantify exposure errors that arise from variations in particle infiltration to aid evaluation of the use of this surrogate, rather than actual exposure, in PM epidemiology. Measurements from 114 homes in 3 cities from the Relationship of Indoor, Outdoor and Personal Air (RIOPA) study were used. Indoor PM 2.5 of outdoor origin was calculated: 1) assuming a constant infiltration factor, as would be the case if central-site PM were a "perfect surrogate" for exposure to outdoor particles; 2) including variations in measured air exchange rates across homes; 3) also incorporating home-to-home variations in particle composition, and 4) calculating sample-specific infiltration factors. The final estimates of PM 2.5 of outdoor origin take into account variations in building construction, ventilation practices, and particle properties that result in home-to-home and day-to-day variations in particle infiltration. As assumptions became more realistic (from the first, most constrained model to the fourth, least constrained model), the mean concentration of PM 2.5 of outdoor origin increased. Perhaps more importantly, the bandwidth of the distribution increased. These results quantify several ways in which the use of central site PM results in underestimates of the ambient PM 2.5 exposure distribution bandwidth. The result is larger uncertainties in relative risk factors for PM 2.5 than would occur if epidemiological studies used more accurate exposure measures. In certain situations this can lead to bias.

BackgroundThe p53 tumor suppressor gene is mutated or deleted in nearly half of human cancers. The murine double minute 2 (Mdm2) and Mdmx represent two important cellular regulators of p53. The aim of this study was to evaluate the abnormalities of p53, Mdmx and Mdm2 genes in archived breast cancers.MethodsWe assessed the genetic instability at p53, Mdmx and Mdm2 using high resolution multi-color fluorescent in situ hybridization (FISH) protocol and detected the expression status of the tumor protein p53 (TP53), MDMx and MDM2 by immunohistochemistry in 115 archived samples of infiltrating ductal breast carcinomas with foci of ductal carcinoma in situ (DCIS) components.ResultsThe presence of p53 allelic loss and/or TP53 overexpression was observed in 38% out of all patients, and was significantly more often in larger, high grade, ER negative and high ki67 tumors. Mdmx amplification with low-level increase of gene copy number is at high frequency while Mdm2 amplification is rare in primary breast cancer. Mdmx amplification was seen in more invasive carcinomas than preinvasive lesions. MDMx and MDM2 overexpression were detected in 65% and 38% of all cases respectively. Moreover it was showed that most tumors contained either p53 dysfunction or Mdm2 alteration, but not both. This distribution was significant (P < 0.05). Inverse correlation between Mdmx amplification/overexpression and p53 disfunction was also observed (P < 0.05).ConclusionsOur results suggest the involvement of Mdm2 and Mdmx in p53-independent breast carcinogenesis and Mdmx may contribute to the regulation of p53 independently of Mdm2.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1450529994118798.

Lacking of treatment methods for the patients with triple negative breast cancer (TNBC) underscores the pivotal needs to further understand its biology as well as to find better biomarkers and develop novel therapeutic strategies. Increasing evidences support that aberrantly expressed microRNAs (miRNAs) are involved in tumorigenesis and may serve as biomarkers for diagnostic and prognostic purposes of various cancers. In current study, we found that miR-455-3p and miR-196a-5p were intensively overexpressed in TNBC compared with the hormone receptor (HR) positive breast cancer whereas miR-425-5p was down-regulated by miRNA microarray analysis. qRT-PCR analysis confirmed that the expression of miR-455-3p in TNBC cell lines MDA-MB-231 and MDA-MB-468 was higher than that in HR positive breast cancer cell line MCF-7(p<0.01). Functional experiments in vitro showed that miR-455-3p enhanced cell proliferative, invasive and migrational abilities in TNBC cell lines. miRNA targets prediction showed SMAD2, LTBR and etoposide induced 2.4 (EI24) were potential target genes of miR-455-3p, and then it was confirmed by qRT-PCR assay. Dual luciferase reporter assay showed the specific binding of miR-455-3p to 3′ UTR of EI24 in TNBC. Then we found miR-455-3p inhibited the EI24 expression at the levels of mRNA and protein. Through small interfering RNA (siRNA) targeting EI24 gene, there were strengthened capabilities of invasion and migration of TNBC cells, and increased expression of EI24 had the inverse effects. In conclusion, the data suggest that miRNA455-3p promotes invasion and migration by targeting tumor suppressor EI24 and might be a potential prognostic biomarker and therapeutic target in TNBC.