Urban air pollution and chronic obstructive pulmonary disease-related emergency department visits

Background: Patients with chronic obstructive pulmonary disease (COPD) can have recurrent disease exacerbations triggered by several factors, including air pollution. Visits to the emergency respiratory department can be a direct result of short-term exposure to air pollution. The aim of this study was to investigate the relationship between the daily number of COPD emergency department visits and the daily environmental air concentrations of PM(10), SO(2), NO(2), CO and O(3) in the City of Sao Paulo, Brazil. Methods: The sample data were collected between 2001 and 2003 and are categorised by gender and age. Generalised linear Poisson regression models were adopted to control for both short-and long-term seasonal changes as well as for temperature and relative humidity. The non-linear dependencies were controlled using a natural cubic spline function. Third-degree polynomial distributed lag models were adopted to estimate both lag structures and the cumulative effects of air pollutants. Results: PM(10) and SO(2) readings showed both acute and lagged effects on COPD emergency department visits. Interquartile range increases in their concentration (28.3 mg/m(3) and 7.8 mg/m(3), respectively) were associated with a cumulative 6-day increase of 19% and 16% in COPD admissions, respectively. An effect on women was observed at lag 0, and among the elderly the lag period was noted to be longer. Increases in CO concentration showed impacts in the female and elderly groups. NO(2) and O(3) presented mild effects on the elderly and in women, respectively. Conclusion: These results indicate that air pollution affects health in a gender-and age-specific manner and should be considered a relevant risk factor that exacerbates COPD in urban environments.

Association between intratumoral lymphatic microvessel density (LMVD) and clinicopathologic features in endometrial cancer: a retrospective cohort study

Background: Lymph node metastasis in endometrial cancer significantly decreases survival rate. Few data on the influence of intratumoral lymphatic microvessel density (LMVD) on survival in endometrial cancer are available. Our aim was to assess the intratumoral LMVD of endometrial carcinomas and to investigate its association with classical pathological factors, lymph node metastasis and survival. Methods: Fifty-seven patients with endometrial carcinoma diagnosed between 2000 and 2008 underwent complete surgical staging and evaluation of intratumoral LMVD and other histologic variables. Lymphatic microvessels were identified by immunohistochemical staining using monoclonal antibody against human podoplanin (clone D2-40) and evaluated by counting the number of immunostained lymphatic vessels in 10 hot spot areas at 400x magnification. The LMVD was expressed by the mean number of vessels in these 10 hot spot microscopic fields. We next investigated the association of LMVD with the clinicopathologic findings and prognosis. Results: The mean number of lymphatic vessels counted in all cases ranged between 0 and 4.7. The median value of mean LMVD was 0.5, and defined the cut-off for low and high LMVD. We identified low intratumoral LMVD in 27 (47.4%) patients and high LMVD in 30 (52.6%) patients. High intratumoral LMVD was associated with lesser miometrial and adnaexal infiltration, lesser cervical and peritoneal involvement, and fewer fatal cases. Although there was lower lymph node involvement among cases with high LMVD, the difference did not reach significance. No association was seen between LMVD and FIGO staging, histological type, or vascular invasion. On the other hand, low intratumoral LMVD was associated with poor outcome. Seventy-five percent of deaths occurred in patients with low intratumoral LMVD. Conclusion: Our results show association of high intratumoral LMVD with features related to more localized disease and better outcome. We discuss the role of lymphangiogenesis as an early event in the endometrial carcinogenesis.

Expression of Monocarboxylate Transporters 1, 2, and 4 in Human Tumours and Their Association with CD147 and CD44

Monocarboxylate transporters (MCTs) are important cellular pH regulators in cancer cells; however, the value of MCT expression in cancer is still poorly understood. In the present study, we analysed MCT1, MCT2, and MCT4 protein expression in breast, colon, lung, and ovary neoplasms, as well as CD147 and CD44. MCT expression frequency was high and heterogeneous among the different tumours. Comparing with normal tissues, there was an increase in MCT1 and MCT4 expressions in breast carcinoma and a decrease in MCT4 plasma membrane expression in lung cancer. There were associations between CD147 and MCT1 expressions in ovarian cancer as well as between CD147 and MCT4 in both breast and lung cancers. CD44 was only associated with MCT1 plasma membrane expression in lung cancer. An important number of MCT1 positive cases are negative for both chaperones, suggesting that MCT plasma membrane expression in tumours may depend on a yet nonidentified regulatory protein.

Variability in Estrogen-Metabolizing Genes and Their Association with Genomic Instability in Untreated Breast Cancer Patients and Healthy Women

In the present study, we investigated the relationship between polymorphisms in the estrogen-metabolizing genes CYP17, CYP1B1, CYP1A1, and COMT and genomic instability in the peripheral blood lymphocytes of 62 BC patients and 62 controls considering that increased or prolonged exposure to estrogen can damage the DNA molecule and increase the genomic instability process in breast tissue. Our data demonstrated increased genomic instability in BC patients and that individuals with higher frequencies of MN exhibited higher risk to BC when belonging Val/Met genotype of the COMT gene. We also observed that CYP17 and CYP1A1 polymorphisms can modify the risk to BC depending on the menopause status. We can conclude that the genetic background in estrogen metabolism pathway can modulate chromosome damage in healthy controls and patients and thereby influence the risk to BC. These findings suggest the importance to ally biomarkers of susceptibility and effects to estimate risk groups.

Influence of Aluminum Oxide Sandblasting Associated with Nd:YAG or Er:YAG Lasers on Shear Bond Strength of a Feldspathic Ceramic to Resin Cements

Objective: This in vitro study evaluated the influence of the surface pretreatment of a feldspathic ceramic on the shear bond strength of two different resin cements. Background Data: Although several conventional surface treatments have been used on feldspathic ceramic, few studies have investigated the effects of an alternative surface treatment, the association of aluminum oxide sandblasting with Nd:YAG and Er:YAG lasers. Methods: Sixty samples made of a feldspathic ceramic were divided into three groups (n = 20) and treated with (1) controlled-air abrasion with Al(2)O(3) + 10% hydrofluoric acid (HF), (2) Al(2)O(3) + Er:YAG laser, and (3) Al(2)O(3) + Nd:YAG laser. Afterward, silane (Dentsply) was applied on each treated surface. Each of the three main groups was divided into two subgroups (n = 10), where a different resin cement was employed for each subgroup. It was built a cylinder with resin cement (RelyX Arc) in subgroup (A) and with self-adhesive cement (RelyX U100) in subgroup (B). After 24 h at 37 degrees C, the prepared specimens were submitted to shear bond strength test and stereoscopic evaluation to determine the type of failure. Results: Bond strength mean values were not statistically significant for the surface treatment methods or resin cements. Conclusion: The null surface treatment proposed with aluminum oxide sandblasting associated with the Er:YAG or Nd:YAG laser and using cementation with self-adhesive cement can be an alternative bonding technique for feldspathic ceramic, since it was as effective as the conventional treatment with aluminum oxide sandblasting and hydrofluoric acid using the conventional resin cement.

A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10(-8); rs1229984-ADH1B, p = 7 x 10(-9); and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

Characterization of mitochondrial genotypes in the foundation herd of the Canchim beef cattle breed

The Canchim (5/8 Charolais + 3/8 Zebu) beef cattle breed was developed at Southeast-Embrapa Cattle to take advantage of hybrid vigor and to combine the higher growth rate and beef quality of Charolais with tropical adaptations of Zebu. The development of three lineages (old, new, and crossbred) has increased its genetic basis. The genotypic origin (Bos taurus or Bos indicus) of the mitochondrial DNA (mtDNA) of the Canchim breed was unknown. We characterized the mtDNA genotype of this founder herd by allele-specific polymerase chain reaction. The 173 founder Zebu females (62 Indubrasil, 3 Guzerat, and 108 Nellore) and their 6749 offspring were identified. The frequency of B. indicus mtDNA ranged from 1.15 to 2.05% among the descendants (N = 6404) of each maternal line with available DNA, and among animals that were alive (N = 689) in December 2007 among the three lineages. Though mtDNA characterization can be used to direct animal selection, the low frequency of B. indicus mtDNA impairs the evaluation of its effects on production traits in these animals. The high prevalence of B. taurus mtDNA in Canchim proves that the founder Zebu females from the Indubrasil, Guzerat and Nellore breeds were obtained from crosses of Zebu sires with local B. taurus dams.

Estimates of genetic trend for carcass traits in a commercial broiler line

Data from the slaughter of 24,001 chickens that were part of a selection program for the production of commercial broilers were used to estimate genetic trend for absolute carcass (CW), breast meat (BRW), and leg (LW) weights, and relative carcass (CY), breast meat (BRY), and leg (LY) weights. The components of (co) variance and breeding values of individuals were obtained by the restricted maximum likelihood method applied to animal models. The relationship matrix was composed of 132,442 birds. The models included as random effects, maternal additive genetic and permanent environmental for CW, BRW, LW, CY, and BRY, and only maternal permanent environmental for LY, besides the direct additive genetic and residual effects, and as fixed effects, hatch week, parents' mating group and sex. The estimates of genetic trend were obtained by average regression of breeding value on generation, and the average genetic trend was estimated by regression coefficients. The genetic trends for CW (+ 6.0336 g/generation), BRW (+ 3.6723 g/generation), LW (+ 1.5846 g/generation), CY (+ 0.1195%/generation), and BRY (+ 0.1388%/generation) were positive, and they were in accordance with the objectives of the selection program for these traits. The genetic trend for LY(-0.0019%/generation) was negative, possibly due to the strong emphasis on selection for BRY and the negative correlations between these two traits.

Association of SNPs on CAPN1 and CAST genes with tenderness in Nellore cattle

We examined whether single-nucleotide polymorphisms (SNPs) in the calpain (CAPN) and calpastatin (CAST) genes, described from Bos primigenius taurus, are polymorphic in Nellore cattle. We also looked for a possible association of linkage disequilibrium of this polymorphism with tenderness of the longissimus dorsi muscle after 7, 14 and 21 days of postmortem aging in 638 purebred Nellore bulls. Meat tenderness was measured as Warner-Bratzler shear force. Additive and dominance effects were tested for SNPs of the three genotypic classes; the substitution effect was tested for SNPs with missing genotypic classes. Genotypic and gene frequencies were also calculated for the different SNPs. An increase in tenderness was observed from 7 to 21 days; the average values for shear force at 7, 14 and 21 days of aging were 5.92 +/- 0.06, 4.92 +/- 0.05, and 4.38 +/- 0.04 kg, respectively. All markers showed polymorphism, but there was no CC genotype for CAPN316, and few animals showed the AA genotype for CAPN530. The alleles CAPN4751, UOGCAST1, and WSUCAST were found to have additive and dominance effects for shear force at 7, 14 and 21 days, while CAPN316 showed a substitution effect for shear force at 7 and 21 days. An additive-by-additive epistatic interaction was observed between CAPN4751 and markers on the CAST gene. In conclusion, these markers should be considered for use in breeding programs.

Comparison of different models to estimate genetic parameters for carcass traits in a commercial broiler line

The effect of genetic and non-genetic factors for carcass, breast meat and leg weights, and yields of a commercial broiler line were investigated using the restricted maximum likelihood method, considering four different animal models, including or excluding maternal genetic effect with covariance between direct and maternal genetic effects, and maternal permanent environmental effect. The likelihood ratio test was used to determine the most adequate model for each trait. For carcass, breast, and leg weight, and for carcass and breast yield, maternal genetic and permanent environmental effects as well as the covariance between direct and maternal genetic effects were significant. The estimates of direct and maternal heritability were 0.17 and 0.04 for carcass weight, 0.26 and 0.06 for breast weight, 0.22 and 0.02 for leg weight, 0.32 and 0.02 for carcass yield, and 0.52 and 0.04 for breast yield, respectively. For leg yield, maternal permanent environmental effect was important, in addition to direct genetic effects. For that trait, direct heritability and maternal permanent environmental variance as a proportion of the phenotypic variance were 0.43 and 0.02, respectively. The results indicate that ignoring maternal effects in the models, even though they were of small magnitude (0.02 to 0.06), tended to overestimate direct genetic variance and heritability for all traits.

H(2) infrared line emission from the ionized region of planetary nebulae

Context. The analysis and interpretation of the H(2) line emission from planetary nebulae have been done in the literature by assuming that the molecule survives only in regions where the hydrogen is neutral, as in photodissociation, neutral clumps, or shocked regions. However, there is strong observational and theoretical evidence that at least part of the H(2) emission is produced inside the ionized region of these objects. Aims. The aim of the present work is to calculate and analyze the infrared line emission of H(2) produced inside the ionized region of planetary nebulae using a one-dimensional photoionization code. Methods. The photoionization code Aangaba was improved in order to calculate the statistical population of the H(2) energy levels, as well as the intensity of the H(2) infrared emission lines in the physical conditions typical of planetary nebulae. A grid of models was obtained and the results then analyzed and compared with the observational data. Results. We show that the contribution of the ionized region to the H(2) line emission can be important, particularly in the case of nebulae with high-temperature central stars. This result explains why H(2) emission is more frequently observed in bipolar planetary nebulae (Gatley's rule), since this kind of object typically has hotter stars. Collisional excitation plays an important role in populating the rovibrational levels of the electronic ground state of H(2) molecules. Radiative mechanisms are also important, particularly for the upper vibrational levels. Formation pumping can have minor effects on the line intensities produced by de-excitation from very high rotational levels, especially in dense and dusty environments. We included the effect of the H(2) molecule on the thermal equilibrium of the gas, concluding that, in the ionized region, H(2) only contributes to the thermal equilibrium in the case of a very high temperature of the central star or a high dust-to-gas ratio, mainly through collisional de-excitation.

Effects of Aflatoxin B(1) and Fumonisin B(1) on the Viability and Induction of Apoptosis in Rat Primary Hepatocytes

The present study evaluated the effect of aflatoxin B(1) (AFB(1)) and fumonisin B(1) (FB(1)) either alone, or in association, on rat primary hepatocyte cultures. Cell viability was assessed by flow cytometry after propidium iodine intercalation. DNA fragmentation and apoptosis were assessed by agarose gel electrophoresis and acridine orange and ethidium bromide staining. At the concentrations of AFB(1) and FB(1) used, the toxins did not decrease cell viability, but did induce apoptosis in a concentration and time-dependent manner.

Association of Trypanosoma vivax in extracellular sites with central nervous system lesions and changes in cerebrospinal fluid in experimentally infected goats

Changes in cerebrospinal fluid (CSF) and anatomical and histopathological central nervous system (CNS) lesions were evaluated, and the presence of Trypanosoma vivax in CNS tissues was investigated through PCR. Twelve adult male goats were divided into three groups (G): G1, infected with T. vivax and evaluated during the acute phase; G2, infected goats evaluated during the chronic phase; and G3, consisting of non-infected goats. Each goat from G1 and G2 was infected with 1.25 x 10(5) trypomastigotes. Cerebrospinal fluid (CSF) analysis and investigation of T. vivax was performed at the 15(th) day post-infection (dpi) in G1 goats and on the fifth day after the manifestation of nervous system infection signs in G2 goats. All goats were necropsied, and CNS fragments from G1 and G2 goats were evaluated by PCR for the determination of T. vivax. Hyperthermia, anemia and parasitemia were observed from the fifth dpi for G1 and G2, with the highest parasitemia peak between the seventh and 21(st) dpi. Nervous system infection signs were observed in three G2 goats between the 30(th) and 35(th) dpi. CSF analysis revealed the presence of T. vivax for G2. Meningitis and meningoencephalitis were diagnosed in G2. PCR were positive for T. vivax in all the samples tested. In conclusion, T. vivax may reach the nervous tissue resulting in immune response from the host, which is the cause of progressive clinical and pathological manifestations of the CNS in experimentally infected goats.

Single-nucleotide polymorphism, linkage disequilibrium and geographic structure in the malaria parasite Plasmodium vivax: prospects for genome-wide association studies

Background: The ideal malaria parasite populations for initial mapping of genomic regions contributing to phenotypes such as drug resistance and virulence, through genome-wide association studies, are those with high genetic diversity, allowing for numerous informative markers, and rare meiotic recombination, allowing for strong linkage disequilibrium (LD) between markers and phenotype-determining loci. However, levels of genetic diversity and LD in field populations of the major human malaria parasite P. vivax remain little characterized. Results: We examined single-nucleotide polymorphisms (SNPs) and LD patterns across a 100-kb chromosome segment of P. vivax in 238 field isolates from areas of low to moderate malaria endemicity in South America and Asia, where LD tends to be more extensive than in holoendemic populations, and in two monkey-adapted strains (Salvador-I, from El Salvador, and Belem, from Brazil). We found varying levels of SNP diversity and LD across populations, with the highest diversity and strongest LD in the area of lowest malaria transmission. We found several clusters of contiguous markers with rare meiotic recombination and characterized a relatively conserved haplotype structure among populations, suggesting the existence of recombination hotspots in the genome region analyzed. Both silent and nonsynonymous SNPs revealed substantial between-population differentiation, which accounted for similar to 40% of the overall genetic diversity observed. Although parasites clustered according to their continental origin, we found evidence for substructure within the Brazilian population of P. vivax. We also explored between-population differentiation patterns revealed by loci putatively affected by natural selection and found marked geographic variation in frequencies of nucleotide substitutions at the pvmdr-1 locus, putatively associated with drug resistance. Conclusion: These findings support the feasibility of genome-wide association studies in carefully selected populations of P. vivax, using relatively low densities of markers, but underscore the risk of false positives caused by population structure at both local and regional levels.

Cloud condensation nuclei in pristine tropical rainforest air of Amazonia: size-resolved measurements and modeling of atmospheric aerosol composition and CCN activity

Atmospheric aerosol particles serving as cloud condensation nuclei (CCN) are key elements of the hydrological cycle and climate. We have measured and characterized CCN at water vapor supersaturations in the range of S=0.10-0.82% in pristine tropical rainforest air during the AMAZE-08 campaign in central Amazonia. The effective hygroscopicity parameters describing the influence of chemical composition on the CCN activity of aerosol particles varied in the range of kappa approximate to 0.1-0.4 (0.16+/-0.06 arithmetic mean and standard deviation). The overall median value of kappa approximate to 0.15 was by a factor of two lower than the values typically observed for continental aerosols in other regions of the world. Aitken mode particles were less hygroscopic than accumulation mode particles (kappa approximate to 0.1 at D approximate to 50 nm; kappa approximate to 0.2 at D approximate to 200 nm), which is in agreement with earlier hygroscopicity tandem differential mobility analyzer (H-TDMA) studies. The CCN measurement results are consistent with aerosol mass spectrometry (AMS) data, showing that the organic mass fraction (f(org)) was on average as high as similar to 90% in the Aitken mode (D <= 100 nm) and decreased with increasing particle diameter in the accumulation mode (similar to 80% at D approximate to 200 nm). The kappa values exhibited a negative linear correlation with f(org) (R(2)=0.81), and extrapolation yielded the following effective hygroscopicity parameters for organic and inorganic particle components: kappa(org)approximate to 0.1 which can be regarded as the effective hygroscopicity of biogenic secondary organic aerosol (SOA) and kappa(inorg)approximate to 0.6 which is characteristic for ammonium sulfate and related salts. Both the size dependence and the temporal variability of effective particle hygroscopicity could be parameterized as a function of AMS-based organic and inorganic mass fractions (kappa(p)=kappa(org) x f(org)+kappa(inorg) x f(inorg)). The CCN number concentrations predicted with kappa(p) were in fair agreement with the measurement results (similar to 20% average deviation). The median CCN number concentrations at S=0.1-0.82% ranged from N(CCN,0.10)approximate to 35 cm(-3) to N(CCN,0.82)approximate to 160 cm(-3), the median concentration of aerosol particles larger than 30 nm was N(CN,30)approximate to 200 cm(-3), and the corresponding integral CCN efficiencies were in the range of N(CCN,0.10/NCN,30)approximate to 0.1 to N(CCN,0.82/NCN,30)approximate to 0.8. Although the number concentrations and hygroscopicity parameters were much lower in pristine rainforest air, the integral CCN efficiencies observed were similar to those in highly polluted megacity air. Moreover, model calculations of N(CCN,S) assuming an approximate global average value of kappa approximate to 0.3 for continental aerosols led to systematic overpredictions, but the average deviations exceeded similar to 50% only at low water vapor supersaturation (0.1%) and low particle number concentrations (<= 100 cm(-3)). Model calculations assuming aconstant aerosol size distribution led to higher average deviations at all investigated levels of supersaturation: similar to 60% for the campaign average distribution and similar to 1600% for a generic remote continental size distribution. These findings confirm earlier studies suggesting that aerosol particle number and size are the major predictors for the variability of the CCN concentration in continental boundary layer air, followed by particle composition and hygroscopicity as relatively minor modulators. Depending on the required and applicable level of detail, the information and parameterizations presented in this paper should enable efficient description of the CCN properties of pristine tropical rainforest aerosols of Amazonia in detailed process models as well as in large-scale atmospheric and climate models.