Two Chromatin Remodeling Activities Cooperate during Activation of Hormone Responsive Promoters

Steroid hormones regulate gene expression by interaction of their receptors with hormone responsive elements (HREs) and recruitment of kinases, chromatin remodeling complexes, and coregulators to their target promoters. Here we show that in breast cancer cells the BAF, but not the closely related PBAF complex, is required for progesterone induction of several target genes including MMTV, where it catalyzes localized displacement of histones H2A and H2B and subsequent NF1 binding. PCAF is also needed for induction of progesterone target genes and acetylates histone H3 at K14, an epigenetic mark that interacts with the BAF subunits by anchoring the complex to chromatin. In the absence of PCAF, full loading of target promoters with hormone receptors and BAF is precluded, and induction is compromised. Thus, activation of hormone-responsive promoters requires cooperation of at least two chromatin remodeling activities, BAF and PCAF

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

New Host and Locality Records for the Ixodes Auritulus (Acari: Ixodidae) Species Group, with a Review of Host Relationships and Distribution in the Neotropical Zoogeographic Region

New Neotropical records are presented for ticks belonging to the Ixodes auritulusIxodes auritulus Neumann, 1904, species group, together with a review of hosts and localities from which members of this complex have previously been collected. The range of the I. auritulus species group is now understood to include Colombia, and 15 bird species are listed as new hosts. From Guatemala to southern Argentina and Chile, specimens of the I. auritulus group have been found on birds belonging to the orders Ciconiiformes, Columbiformes, Falconiformes, Galliformes, Passeriformes, Piciformes, Procellariiformes and Tinamiformes. Passeriform birds are probably the principal hosts, sustaining tick populations throughout the Neotropics. Collection data have yielded four areas ? southern South America (from 56 S to 51 S), southern Brazil (25 S?22 S), south-central Peru (14 S?10 S) and Central America (10 N?15 N) ? where the I. auritulus group appears to commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species Peru (14 S?10 S) and Central America (10 N?15 N) ? where the I. auritulus group appears to commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species belonging to the orders Ciconiiformes, Columbiformes, Falconiformes, Galliformes, Passeriformes, Piciformes, Procellariiformes and Tinamiformes. Passeriform birds are probably the principal hosts, sustaining tick populations throughout the Neotropics. Collection data have yielded four areas ? southern South America (from 56 S to 51 S), southern Brazil (25 S?22 S), south-central Peru (14 S?10 S) and Central America (10 N?15 N) ? where the I. auritulus group appears to commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species Peru (14 S?10 S) and Central America (10 N?15 N) ? where the I. auritulus group appears to commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species understood to include Colombia, and 15 bird species are listed as new hosts. From Guatemala to southern Argentina and Chile, specimens of the I. auritulus group have been found on birds belonging to the orders Ciconiiformes, Columbiformes, Falconiformes, Galliformes, Passeriformes, Piciformes, Procellariiformes and Tinamiformes. Passeriform birds are probably the principal hosts, sustaining tick populations throughout the Neotropics. Collection data have yielded four areas ? southern South America (from 56 S to 51 S), southern Brazil (25 S?22 S), south-central Peru (14 S?10 S) and Central America (10 N?15 N) ? where the I. auritulus group appears to commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species Peru (14 S?10 S) and Central America (10 N?15 N) ? where the I. auritulus group appears to commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species belonging to the orders Ciconiiformes, Columbiformes, Falconiformes, Galliformes, Passeriformes, Piciformes, Procellariiformes and Tinamiformes. Passeriform birds are probably the principal hosts, sustaining tick populations throughout the Neotropics. Collection data have yielded four areas ? southern South America (from 56 S to 51 S), southern Brazil (25 S?22 S), south-central Peru (14 S?10 S) and Central America (10 N?15 N) ? where the I. auritulus group appears to commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species Peru (14 S?10 S) and Central America (10 N?15 N) ? where the I. auritulus group appears to commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species I. auritulus species group is now understood to include Colombia, and 15 bird species are listed as new hosts. From Guatemala to southern Argentina and Chile, specimens of the I. auritulus group have been found on birds belonging to the orders Ciconiiformes, Columbiformes, Falconiformes, Galliformes, Passeriformes, Piciformes, Procellariiformes and Tinamiformes. Passeriform birds are probably the principal hosts, sustaining tick populations throughout the Neotropics. Collection data have yielded four areas ? southern South America (from 56 S to 51 S), southern Brazil (25 S?22 S), south-central Peru (14 S?10 S) and Central America (10 N?15 N) ? where the I. auritulus group appears to commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species Peru (14 S?10 S) and Central America (10 N?15 N) ? where the I. auritulus group appears to commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species belonging to the orders Ciconiiformes, Columbiformes, Falconiformes, Galliformes, Passeriformes, Piciformes, Procellariiformes and Tinamiformes. Passeriform birds are probably the principal hosts, sustaining tick populations throughout the Neotropics. Collection data have yielded four areas ? southern South America (from 56 S to 51 S), southern Brazil (25 S?22 S), south-central Peru (14 S?10 S) and Central America (10 N?15 N) ? where the I. auritulus group appears to commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species Peru (14 S?10 S) and Central America (10 N?15 N) ? where the I. auritulus group appears to commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species I. auritulus group have been found on birds belonging to the orders Ciconiiformes, Columbiformes, Falconiformes, Galliformes, Passeriformes, Piciformes, Procellariiformes and Tinamiformes. Passeriform birds are probably the principal hosts, sustaining tick populations throughout the Neotropics. Collection data have yielded four areas ? southern South America (from 56 S to 51 S), southern Brazil (25 S?22 S), south-central Peru (14 S?10 S) and Central America (10 N?15 N) ? where the I. auritulus group appears to commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species Peru (14 S?10 S) and Central America (10 N?15 N) ? where the I. auritulus group appears to commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species S to 51 S), southern Brazil (25 S?22 S), south-central Peru (14 S?10 S) and Central America (10 N?15 N) ? where the I. auritulus group appears to commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species S?10 S) and Central America (10 N?15 N) ? where the I. auritulus group appears to commonly parasitize birds, but additional collections may show that the range of this complex is less discontinuous than currently perceived. Several morphological differences are described for ticks within and among these areas, but it is still unclear whether the I. auritulus group comprises more than one species more than one species I. auritulus group comprises more than one speciesFil: González Acuña, Daniel. Universidad de Concepción; ChileFil: Venzal, José M.. Universidad de la República; UruguayFil: Keirans, James E.. Walter Reed Army Medical Center; Estados UnidosFil: Robbins, Richard G.. Walter Reed Army Medical Center; Estados UnidosFil: Ippi, Silvina Graciela. Universidad Nacional del Comahue; ArgentinaFil: Guglielmone, Alberto Alejandro. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Santa Fe. Estacion Experimental Agropecuaria Rafaela. Agencia de Extension Rural Rafaela.; Argentin

Effects of the pesticide chlorpyrifos on breast cancer disease. Implication of epigenetic mechanisms

Chlorpyrifos (CPF) is an organophosphorus pesticide used for agricultural pest control all over the world. We have previously demonstrated that environmental concentrations of this pesticide alter mammary gland histological structure and hormonal balance in rats chronically exposed. In this work, we analyzed the effects of CPF on mammary tumors development. Our results demonstrated that CPF increases tumor incidence and reduces latency of NMU-induced mammary tumors. Although no changes were observed in tumor growth rate, we found a reduced steroid hormone receptor expression in the tumors of animals exposed to the pesticide. Moreover, we analyzed the role of epigenetic mechanisms in CPF effects. Our results indicated that CPF alters HDAC1 mRNA expression in mammary gland, although no changes were observed in DNA methylation. In summary, we demonstrate that the exposure to CPF promotes mammary tumors development with a reduced steroid receptors expression. It has also been found that CPF affects HDAC1 mRNA levels in mammary tissue pointing that CPF may act as a breast cancer risk factor.Fil: Ventura, Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Zappia, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Lasagna, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Pavicic, Walter Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Richard, Silvina Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Bolzan, Alejandro Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Monczor, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Núñez, M.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Cocca, Claudia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentin