Publications by authors named "Patricia Gonzalez"

137 Publications

Use of EHRs in a Tertiary Hospital During COVID-19 Pandemic: A Multi-Purpose Approach Based on Standards.

Stud Health Technol Inform 2021 May;281:28-32

Hospital Universitario 12 de Octubre, Madrid, Spain.

This work aims to describe how EHRs have been used to meet the needs of healthcare providers and researchers in a 1,300-beds tertiary Hospital during COVID-19 pandemic. For this purpose, essential clinical concepts were identified and standardized with LOINC and SNOMED CT. After that, these concepts were implemented in EHR systems and based on them, data tools, such as clinical alerts, dynamic patient lists and a clinical follow-up dashboard, were developed for healthcare support. In addition, these data were incorporated into standardized repositories and COVID-19 databases to improve clinical research on this new disease. In conclusion, standardized EHRs allowed implementation of useful multi- purpose data resources in a major Hospital in the course of the pandemic.
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http://dx.doi.org/10.3233/SHTI210114DOI Listing
May 2021

Extracellular vesicles from recombinant cell factories improve the activity and efficacy of enzymes defective in lysosomal storage disorders.

J Extracell Vesicles 2021 Mar 12;10(5):e12058. Epub 2021 Mar 12.

Drug Delivery & Targeting CIBBIM-Nanomedicine Vall d'Hebron Institute of Research Universitat Autònoma de Barcelona Barcelona Spain.

In the present study the use of extracellular vesicles (EVs) as vehicles for therapeutic enzymes in lysosomal storage disorders was explored. EVs were isolated from mammalian cells overexpressing alpha-galactosidase A (GLA) or N-sulfoglucosamine sulfohydrolase (SGSH) enzymes, defective in Fabry and Sanfilippo A diseases, respectively. Direct purification of EVs from cell supernatants was found to be a simple and efficient method to obtain highly active GLA and SGSH proteins, even after EV lyophilization. Likewise, EVs carrying GLA (EV-GLA) were rapidly uptaken and reached the lysosomes in cellular models of Fabry disease, restoring lysosomal functionality much more efficiently than the recombinant enzyme in clinical use. In vivo, EVs were well tolerated and distributed among all main organs, including the brain. DiR-labelled EVs were localized in brain parenchyma 1 h after intra-arterial (internal carotid artery) or intravenous (tail vein) administrations. Moreover, a single intravenous administration of EV-GLA was able to reduce globotriaosylceramide (Gb3) substrate levels in clinically relevant tissues, such kidneys and brain. Overall, our results demonstrate that EVs from cells overexpressing lysosomal enzymes act as natural protein delivery systems, improving the activity and the efficacy of the recombinant proteins and facilitating their access to organs neglected by conventional enzyme replacement therapies.
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http://dx.doi.org/10.1002/jev2.12058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953474PMC
March 2021

Early Changes in Nitrate Uptake and Assimilation Under Drought in Relation to Transpiration.

Front Plant Sci 2020 23;11:602065. Epub 2020 Dec 23.

Division of Controlled Environment Horticulture, Faculty of Life Sciences, Albrecht Daniel Thaer-Institute of Agricultural and Horticultural Sciences, Humboldt-University of Berlin, Berlin, Germany.

Soil drying combined with nitrogen (N) deficiency poses a grave threat to agricultural crop production. The rate at which nitrate (NO) is taken up depends partly on the uptake and transpiration of water. Rapid changes in nitrate assimilation, in contrast to other N forms, may serve as a component of the plant stress response to drought because nitrate assimilation may lead to changes in xylem pH. The modulation of xylem sap pH may be relevant for stomata regulation the delivery of abscisic acid (ABA) to guard cells. In several factorial experiments, we investigated the interactions between nitrate and water availability on nitrate fate in the plant, as well as their possible implications for the early drought-stress response. We monitored the short-term response (2-6 days) of nitrate in biomass, transport to shoot and reduction in , , , and and correlated this with sap pH and transpiration rates (TRs). Cultivation on inorganic substrate ensured control over nutrient and water supply and prevented nodulation in legume species. NO content in biomass decreased in most of the species under drought indicating significant decline in NO uptake. had the highest NO concentrations in all organs even under drought and low NO treatment. This species can likely respond much better to the combined adverse effects of low NO and water scarcity. Nitrate reductase activity (NRA) was reduced in both roots and leaves of water deficient (WD) plants in all species except , presumably due to its high NO contents. Further, transient reduction in NO availability had no effect on sap pH. Therefore, it seems unlikely that NRA shifts from shoot root leading to the supposed alkalization of sap. We also did not observe any interactive effects of NO and water deficiency on transpiration. Hence, as long as leaf NO content remains stable, NO availability in soil is not linked to short-term modulation of transpiration.
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http://dx.doi.org/10.3389/fpls.2020.602065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793686PMC
December 2020

Consumption of Alcohol, Tobacco and Psychoactive Substances in Adolescents from an Indigenous Territory in the Colombian Amazon.

Rev Colomb Psiquiatr (Engl Ed) 2020 Oct - Dec;49(4):246-254. Epub 2019 Jul 29.

Fundación Universitaria de Ciencias de la Salud (FUCS), Bogotá, Colombia.

Introduction: There are very few studies on the consumption of psychoactive substances (PAS) among young people from indigenous territories and evening or blended learning students. In Inírida, a municipality in the Colombian Amazon, there were concerns about a possible consumption issue that had never been characterised before.

Objective: To characterise the consumption of alcohol, tobacco and PAS in Inírida among teenage evening and blended learning students.

Methods: The Inter-American Uniform Drug Use Data System (SIDUC) survey developed by the Inter-American Drug Abuse Control Commission (CICAD) was adapted to the cultural context and carried out on 95% of 284 evening and blended learning students (262). Descriptive statistics and multiple correspondence analyses were used.

Results: Currently, 59% consume alcohol; 28% tobacco; 21% marijuana; 3% cocaine paste; 1% ecstasy (MDMA); 1% cocaine; and 1% inhalants. Also, 61% believe that drugs are available inside and around the vicinity of their school, and that marijuana (62%) and cocaine paste (35%) are easily acquired. Drugs are most commonly offered in neighbourhoods (56%) and at parties (30%). Those offering the highest quantity of drugs are acquaintances (35%) and friends (29%). And 51% stated that they had participated in preventive activities related to consumption.

Conclusions: The population has a higher consumption of the substances studied in comparison with the national reference, that of Orinoquía and Amazonía, with the exception of cocaine and inhalants. The consumption situation was confirmed, so participatory actions are proposed.
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http://dx.doi.org/10.1016/j.rcp.2019.06.002DOI Listing
July 2019

Tailored Helicobacter pylori eradication therapy in obese patients undergoing bariatric surgery.

Rev Esp Enferm Dig 2021 May;113(5):345-347

Gastroenterología , Sanatorio La Trinidad, Argentina.

Objectives: to compare the efficacy and safety of a tailored quadruple concomitant therapy based on body weight, with the same scheme but with fixed doses in obese patients undergoing bariatric surgery.

Methods: a prospective study was performed of 104 obese patients.

Results: the weight-based therapy group achieved significantly higher eradication rates in the intention-to-treat analysis; 86.3 % (95 % CI: 74.3-93.2) vs 66.1 % (95 % CI: 52.6-77.3), p < 0.05. Relative risk: 1.31 (95 % CI: 1.05-1.63). Discontinuations and adverse events were similar in both groups.

Conclusions: a tailored quadruple concomitant therapy based on body weight seems to be more effective than the standard quadruple concomitant therapy in obese patients.
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http://dx.doi.org/10.17235/reed.2020.7433/2020DOI Listing
May 2021

The problem with implementing fish farms in agricultural regions: A trial in a pampean pond highlights potential risks to both human and fish health.

Chemosphere 2021 Jan 24;262:128408. Epub 2020 Sep 24.

Dirección Centro Regional Entre Ríos, Instituto Nacional de Tecnología Agropecuaria (INTA), Ruta 11, Km. 12.5 (3100), Paraná, Entre Ríos, Argentina.

The safety of creating fish farms in agricultural settings was evaluated by growing Piaractus mesopotamicus in a pond, while crops where cultivated in a nearby field under a pesticide application regime typical of the Pampa region. Atrazine, glyphosate and its metabolite, aminomethylphosphonic acid (AMPA), were detected in the water of the pond at concentrations ranging between 92 and 118 μg/L for atrazine, 12 and 221 μg/L for glyphosate and 21 and 117 μg/L for AMPA. Atrazine and malathion were detected in fish muscles at concentrations ranging between 70 and 105 μg/kg for atrazine and 8.6 and 23.7 μg/kg for malathion. Compared to fish raised in a pisciculture, fish from the agricultural pond presented reduced values of pack cell volume, hemoglobin, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, together with significantly greater cholinesterase activity in both plasma and liver and reduced glutathione-S-transferase activity in the liver. A comet assay also demonstrated that P. mesopotamicus from the agricultural pond presented a significantly greater level of DNA damage in both erythrocytes and gill cells. Overall, the present study demonstrates that pisciculture ponds established in an agricultural setting may receive pesticides applied to nearby cultures and that these pesticides may be taken up by the fish and affect their physiology and health. The accumulation of pesticides residues in fish flesh may also present a risk to human consumers and should be closely controlled.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128408DOI Listing
January 2021

Hepatitis C and HIV combined screening in primary care: A cluster randomized trial.

J Viral Hepat 2021 02 7;28(2):345-352. Epub 2020 Oct 7.

Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.

Hepatitis C virus (HCV) and HIV are major causes of worldwide disease. We aimed to evaluate the effect of a combined screening programme, which included a risk-assessment questionnaire and rapid tests for point-of-care diagnosis, on screening and new diagnosis rates. This prospective, cluster randomized study was carried out in primary care. The intervention arm included a 4-hour educational programme, the use of a risk-assessment questionnaire and rapid tests. In the control centres, only the educational intervention was provided. The main variables compared were the screening coverage and the number and rate of new HCV and HIV diagnoses. Of a total of 7991 participants, 4670 (58.5%) and 2894 (36.2%) presented a risk questionnaire for HIV or HCV, respectively. The younger participants, men and those from Latin America and Eastern Europe, showed the greatest risk of presenting with a positive questionnaire. The overall screening coverage was higher within the intervention arm (OR 17.7; 95% CI 16.2-19.5; P < .001). Only two HIV-positives were identified compared to one in control centres. The rate of HCV diagnoses was higher among intervention centres, with 37 versus seven positive tests (OR 5.2; 95% CI 2.3-11.6; P < .001). Of them, 10 were new diagnoses and 27 had been previously diagnosed, although not linked to care. In conclusion, a simple operational programme can lead to an increase in HCV and HIV screening rates, compared to an exclusively educational programme. The selection of at-risk patients with a self-questionnaire and the use of rapid tests significantly increased the diagnostic rate of HCV infection.
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http://dx.doi.org/10.1111/jvh.13413DOI Listing
February 2021

Factorial invariance of the Marianismo Beliefs Scale among Latinos in the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study.

J Clin Psychol 2021 Jan 21;77(1):312-328. Epub 2020 Jul 21.

Department of Psychology, San Diego State University, San Diego, California, USA.

Objective: The Marianismo Beliefs Scale (MBS) assesses five components of marianismo, a cultural script of Latina gender role expectations. This study evaluated the MBS's psychometric properties across language, sex, and Latino subgroups (Mexican American, Central American, Cuban American, Dominican American, Puerto Rican, and South American).

Method: Study sample was derived from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Sociocultural Ancillary Study which consisted of a community sample of 4879 Latino adults aged 18-64 from four field centers (Miami, FL, USA; San Diego, CA, USA; Bronx, NY, USA; Chicago, IL, USA).

Results: Confirmatory factor analyses supported five factors. English and Spanish versions demonstrated equivalence of factor loadings and error variances across Latino subgroups and sex.

Conclusion: Although the MBS English and Spanish versions are psychometrically sound measures for male and female Latino adults, future research is needed to determine whether direct scale scores are comparable.
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http://dx.doi.org/10.1002/jclp.23031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143788PMC
January 2021

Substance use among Latino international and domestic college students.

J Ethn Subst Abuse 2020 Apr 3:1-23. Epub 2020 Apr 3.

Indiana University Bloomington, Bloomington, Indiana, USA.

While the United States hosts the greatest number of international students in the world, Latino international students remain understudied, especially in regards to substance use. The present study tests differences between Latino international and Latino domestic undergraduates in how they use alcohol, cigarette, and illicit drugs. Participants ( = 786 students, 386 international and 400 domestic, 65% female, mean age = 21.2 years) were a subsample of Latino students surveyed in the 2009 American College Health Association's revised National College Health Assessment (ACHA-NCHA II). Results indicate that Latino international students reported more alcohol use than Latino domestic students, but had similar use of cigarettes and illicit drugs. Among international students, gender, participation in Greek life, cigarette use, marijuana use, and year in school were associated with alcohol use. Similarly, gender, cigarette use, and marijuana use were significantly related to international students' binge drinking. Prevention and research implications are discussed.
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http://dx.doi.org/10.1080/15332640.2020.1747037DOI Listing
April 2020

Cirrhosis Hampers Early and Rapid Normalization of Natural Killer Cell Phenotype and Function in Hepatitis C Patients Undergoing Interferon-Free Therapy.

Front Immunol 2020 25;11:129. Epub 2020 Feb 25.

Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain.

Chronic hepatitis C virus (HCV) infection impairs natural killer (NK) cell phenotype and function. Whether restoration of NK cells occurs after successful interferon (IFN)-free therapies remains a controversial issue. To analyze how HCV-related liver cirrhosis impacts changes in NK cells prior and post-IFN-free therapies. NK cell analysis by multicolor flow cytometry was performed in HCV-infected patients with ( = 17) and without ( = 14) cirrhosis at baseline, week 4 during therapy, and weeks 12 and 48 after the end of therapy (FU12 and FU48, respectively). Non-HCV cirrhotic patients ( = 12) and healthy individuals ( = 12) served as controls. At baseline, HCV cirrhotic patients presented an altered distribution of NK subsets (CD56 and CD56) with higher expression of NKp46, HLA-DR, NKp30, KIR2DL2/L3, NKG2A, and CD85j receptors compared to healthy controls. All frequencies normalized by FU48, except for CD85j cells. Likewise, substantial alterations were detected in NK cell function assessed by (i) signal transducer and activator of transcription 1 (STAT1) and phosphorylated levels of STAT1 and STAT4, (ii) degranulation (CD107a), (iii) cytotoxicity [tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)], and (iv) cytokine production [IFN-γ and tumor necrosis factor-α (TNF-α)]. Of note, NK cell function at FU48 remained partially impaired. In contrast, non-cirrhotics showed normal baseline frequencies of HLA-DR-, NKG2A-, and CD85j-expressing NK cells. Importantly, altered baseline frequencies of NK cell subsets and NKp46 CD56 cells, as well as NK cell function, were rapidly and completely restored. NK cell phenotype alterations persist after HCV eradication in cirrhotic patients, while their function is only partially restored, compromising immune restoration and immunosurveillance.
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http://dx.doi.org/10.3389/fimmu.2020.00129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052355PMC
March 2021

Measurement Properties of Sabogal's Familism Scale: Findings from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Sociocultural Ancillary Study.

J Lat Psychol 2019 Nov 7;7(4):257-272. Epub 2019 Feb 7.

Department of Psychology, San Diego State University.

Familism is a central Hispanic/Latino cultural value that emphasizes close, supportive family relationships and prioritizing family over the self. One of its best-known measures is Sabogal's Familism Scale (Sabogal, Marin, Otero-Sabogal, VanOss Marin, & Perez-Stable, 1987). Although widely used, this scale's measurement properties are not well understood. This study addressed that gap by examining the factor structure, factorial invariance, convergent and discriminant validity, and internal consistency of Sabogal's Familism Scale using data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Sociocultural Ancillary Study. A diverse population-based sample of Hispanics/Latinos ( = 5,313) completed measures that were administered via interview in English or Spanish. Confirmatory factor analyses ( = 5,310) revealed that a three-factor model (, , ; Sabogal's original three factors) fit the data well and did not vary across English and Spanish language groups (i.e., factorial invariance). Convergent and discriminant validities were also established; familism correlated positively with other Hispanic/Latino cultural values (simpatía, fatalism) and correlated negatively with U.S. acculturation. Internal consistency was acceptable. Sabogal's Familism Scale is recommended for continued use in the study of familism in U.S. Hispanics/Latinos.
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http://dx.doi.org/10.1037/lat0000126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918829PMC
November 2019

Zileuton™ loaded in polymer micelles effectively reduce breast cancer circulating tumor cells and intratumoral cancer stem cells.

Nanomedicine 2020 02 27;24:102106. Epub 2019 Oct 27.

Drug Delivery and Targeting Group, Molecular Biology and Biochemistry Research Centre for Nanomedicine (CIBBIM-Nanomedicine), Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain; Networking Research Centre for Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III, Zaragoza, Spain. Electronic address:

Tumor recurrence, metastatic spread and progressive gain of chemo-resistance of advanced cancers are sustained by the presence of cancer stem cells (CSCs) within the tumor. Targeted therapies with the aim to eradicate these cells are thus highly regarded. However, often the use of new anti-cancer therapies is hampered by pharmacokinetic demands. Drug delivery through nanoparticles has great potential to increase efficacy and reduce toxicity and adverse effects. However, its production has to be based on intelligent design. Likewise, we developed polymeric nanoparticles loaded with Zileuton™, a potent inhibitor of cancer stem cells (CSCs), which was chosen based on high throughput screening. Its great potential for CSCs treatment was subsequently demonstrated in in vitro and in in vivo CSC fluorescent models. Encapsulated Zileuton™ reduces amount of CSCs within the tumor and effectively blocks the circulating tumor cells (CTCs) in the blood stream and metastatic spread.
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http://dx.doi.org/10.1016/j.nano.2019.102106DOI Listing
February 2020

Identification and characterization of Cardiac Glycosides as senolytic compounds.

Nat Commun 2019 10 21;10(1):4731. Epub 2019 Oct 21.

Laboratory of Stem Cells in Cancer and Aging, Health Research Institute of Santiago de Compostela (IDIS), Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), E15706, Santiago de Compostela, Spain.

Compounds with specific cytotoxic activity in senescent cells, or senolytics, support the causal involvement of senescence in aging and offer therapeutic interventions. Here we report the identification of Cardiac Glycosides (CGs) as a family of compounds with senolytic activity. CGs, by targeting the Na+/K+ATPase pump, cause a disbalanced electrochemical gradient within the cell causing depolarization and acidification. Senescent cells present a slightly depolarized plasma membrane and higher concentrations of H+, making them more susceptible to the action of CGs. These vulnerabilities can be exploited for therapeutic purposes as evidenced by the in vivo eradication of tumors xenografted in mice after treatment with the combination of a senogenic and a senolytic drug. The senolytic effect of CGs is also effective in the elimination of senescence-induced lung fibrosis. This experimental approach allows the identification of compounds with senolytic activity that could potentially be used to develop effective treatments against age-related diseases.
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http://dx.doi.org/10.1038/s41467-019-12888-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803708PMC
October 2019

Colorectal cancer screening among Hispanics/Latinos in the HCHS/SOL sociocultural ancillary study.

Prev Med Rep 2019 Sep 4;15:100947. Epub 2019 Jul 4.

University of California, San Diego, Moores Cancer Center, La Jolla, CA, United States of America.

Latino adults are more likely to be diagnosed with colorectal cancer (CRC) at later stages compared to white adults which may be explained by disparities in screening rates. The aim of this study was to examine factors associated with three CRC screening indicators [i.e., 1) any CRC screening ever (via, fecal occult blood test (FOBT), sigmoidoscopy, or colonoscopy); 2) FOBT in last year, 3) sigmoidoscopy/colonoscopy in last 10 years) among US Hispanics/Latinos. We analyzed population-based data collected in 2008-2011 from 2265 adults aged 50-75 from San Diego, Bronx, Miami and Chicago from the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study. Based on the Behavioral Model of Health Services Use, the following correlates of CRC screening were examined: predisposing (i.e., age, education, income, acculturation), enabling (i.e., recent physician visit, insurance, recent mammogram), and need (i.e., health-related quality of life and family/personal history of cancer) factors. Separate logistic regression models were analyzed for the three CRC screening indicators. Enabling factors associated with all CRC screening indicators included: health insurance, a recent physician visit, and a mammogram in the last year (women only). For women, being older, more acculturated (i.e., English language or foreign-born but in the US for 10 or more years), and having a personal history of cancer was associated with at least one CRC screening. Findings suggest that improving access and utilization of care among Hispanics/Latinos may be critical for earlier CRC diagnosis and survival.
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http://dx.doi.org/10.1016/j.pmedr.2019.100947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639649PMC
September 2019

Perceived Discrimination and Cardiometabolic Risk Among US Hispanics/Latinos in the HCHS/SOL Sociocultural Ancillary Study.

Int J Behav Med 2019 Aug;26(4):331-342

Department of Psychology, University of Miami, Miami, FL, USA.

Background: Metabolic syndrome (MetS) is a group of cardiovascular risk factors including elevated blood pressure, elevated triglycerides, decreased high-density lipoprotein cholesterol, impaired fasting glucose, and abdominal obesity, which disproportionately affects Hispanics/Latinos. The present study examined associations between perceived discrimination and MetS in Hispanic/Latino adults from various background groups (i.e., Dominican, Central American, Cuban, Mexican, Puerto Rican, South American).

Methods: Data were obtained from 5174 Hispanics/Latinos who participated in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Sociocultural Ancillary Study. MetS components and covariates were measured at a baseline examination, and perceived discrimination was assessed within 9 months of baseline. Path analysis modeled associations of perceived discrimination with MetS prevalence and each of the six components of MetS, controlling for age, sex, income, acculturation, physical activity, diet, smoking, and alcohol use.

Results: Among the full cohort, perceived discrimination was not associated with MetS prevalence in any of the models evaluated. Higher perceived discrimination at work/school was associated with larger waist circumference. When examining background groups separately, higher perceived ethnicity-associated threat was related to increased MetS prevalence only among individuals of Central American background. Differential patterns of association between perceived discrimination and MetS components were found for different background groups.

Conclusions: Overall results suggested that perceived discrimination was not strongly or consistently associated with MetS among Hispanics/Latinos.
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http://dx.doi.org/10.1007/s12529-019-09782-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294575PMC
August 2019

Barriers to an Information Effect on Diagnostic Disparities of Autism Spectrum Disorder in Young Children.

Health Serv Res Manag Epidemiol 2019 Jan-Dec;6:2333392819853058. Epub 2019 Jun 3.

Department of Humanities, University of Costa Rica, Alajuela, Costa Rica.

Objectives: Autism spectrum disorder (ASD) is underdiagnosed in children from minority and low socioeconomic status families, and reports indicate that parental "lack of awareness" of symptoms is a factor, which implicates the adoption of the category globally. However, parental knowledge of ASD has failed to explain emerging clusters of cases. The objective of the present research was to identify and describe barriers to an "information effect" in diagnosis.

Methods: Interviews were conducted with the parents of 54 children with ASD in Costa Rica, many living within clusters that appeared after a genetic study conducted an information campaign for recruitment. The interviews explored factors influencing symptom recognition and help-seeking behaviors. Several barriers were identified that prevent information about ASD or exposure to diagnosed cases from influencing parents' help-seeking behaviors.

Results: Early symptoms in most children gave parents no reason to suspect ASD. Later, parents' understanding of ASD depended on caricatures of the disorder. Parents often received unsolicited advice from strangers, although rarely from family, and it was always seen as critical of their parenting; furthermore, the advice was too late to influence the referral process, which was well underway by the time classical symptoms of ASD appeared, if they did at all. Postdiagnosis, the interviewees occasionally gave advice to other parents, mostly strangers, but none had apparently been diagnosed.

Conclusions: The results implicate efforts to educate parents about symptoms of ASD, where a focus on generic developmental delays and neurodevelopmental disorders in general may be more effective than ASD-specific information.
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http://dx.doi.org/10.1177/2333392819853058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547173PMC
June 2019

College students' barriers to seeking mental health counseling: Scale development and psychometric evaluation.

J Couns Psychol 2019 Oct 30;66(5):626-639. Epub 2019 May 30.

Department of Counseling and Educational Psychology.

This article reports the development and psychometric properties of the 27-item Barriers to Seeking Mental Health Counseling (BMHC) scale, which assesses perceived help-seeking barriers among college-aged students. Across 2 studies involving ethnically diverse samples (e.g., Latinx majority students), the authors provided evidence for this new measure's validity and reliability. Exploratory and confirmatory factor analyses (including a bifactor analysis) provided support for the BMHC scale's multidimensionality reflecting 6 barriers: Negative Perceived Value, Discomfort with Emotions, Ingroup Stigma, Lack of Knowledge, Lack of Access, and Cultural Barriers. Evidence for criterion-related validity was shown through significant but differential correlations with self-stigma, emotional control, and the 4 components of Ajzen's (1991) Theory of Planned Behavior model-attitude, subjective norm of social stigma, perceived behavioral control, and mental health help-seeking intention. Discriminant evidence of validity was established through nonsignificant or small correlations between BMHC subscales and 2 measures of socially desirable responding. The authors also found evidence for incremental validity and measurement invariance across race, and evidence for internal reliability and temporal stability of the BMHC subscales. Findings are discussed in light of the conceptual, methodological, and clinical contributions of the BMHC scale. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/cou0000356DOI Listing
October 2019

Context-Dependent Impact of RAS Oncogene Expression on Cellular Reprogramming to Pluripotency.

Stem Cell Reports 2019 05 2;12(5):1099-1112. Epub 2019 May 2.

Laboratorio de Células Madre en Cáncer y Envejecimiento, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), E15706 Santiago de Compostela, Spain. Electronic address:

Induction of pluripotency in somatic cells with defined genetic factors has been successfully used to investigate the mechanisms of disease initiation and progression. Cellular reprogramming and oncogenic transformation share common features; both involve undergoing a dramatic change in cell identity, and immortalization is a key step for cancer progression that enhances reprogramming. However, there are very few examples of complete successful reprogramming of tumor cells. Here we address the effect of expressing an active oncogene, RAS, on the process of reprogramming and found that, while combined expression with reprogramming factors enhanced dedifferentiation, expression within the context of neoplastic transformation impaired reprogramming. RAS induces expression changes that promote loss of cell identity and acquisition of stemness in a paracrine manner and these changes result in reprogramming when combined with reprogramming factors. When cells carry cooperating oncogenic defects, RAS drives cells into an incompatible cellular fate of malignancy.
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http://dx.doi.org/10.1016/j.stemcr.2019.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524732PMC
May 2019

Cancer fatalism and adherence to national cancer screening guidelines: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Cancer Epidemiol 2019 06 21;60:39-45. Epub 2019 Mar 21.

Department of Psychology and Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, United States. Electronic address:

Background: Sociocultural factors, such as health insurance status, income, education, and acculturation, predict cancer screening among U.S. Hispanics/Latinos. However, these factors can be difficult to modify. More research is needed to identify individual-level modifiable factors that may improve screening and subsequent cancer outcomes in this population. The aim of this study was to examine cancer fatalism (i.e., the belief that there is little or nothing one can do to lower his/her risk of developing cancer) as a determinant of adherence to national screening guidelines for colorectal, breast, prostate, and cervical cancer among Hispanics/Latinos.

Methods: Participants were from the multi-site Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Sociocultural Ancillary Study (N = 5313). The National Cancer Institute (NCI) Health Interview National Trends Survey was used to assess cancer fatalism and receipt of cancer screening. Adherence was defined as following screening guidelines from United States Preventive Services Task Force and the American Cancer Society during the study period.

Results: Adjusting for well-established determinants of cancer screening and covariates (health insurance status, income, education, acculturation, age, Hispanic/Latino background), lower cancer fatalism was marginally associated with greater adherence to screening for colorectal (OR 1.13, 95% CI [.99-1.30], p = .07), breast (OR 1.16, 95% CI [.99-1.36], p = .08) and prostate cancer (OR 1.18, 95% CI [.97-1.43], p = .10), but not cervical cancer.

Conclusions: The associations of cancer fatalism were small and marginal, underlining that sociocultural factors are more robust determinants of cancer screening adherence among Hispanics/Latinos.
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http://dx.doi.org/10.1016/j.canep.2019.03.003DOI Listing
June 2019

Proprioceptive Stabilizer™ training of the abdominal wall muscles in healthy subjects: a quasi-experimental study.

Rev Assoc Med Bras (1992) 2018 Dec;64(12):1134-1138

Physiotherapy Department. Faculty of Health, Exercise, and Sport, European University of Madrid, Villaviciosa de Odón, Madrid, Spain.

Objective: The present quasi-experimental study aimed to assess the transversus abdominis (TrA), internal oblique (IO) and external oblique (EO) thickness in healthy subjects with the proprioceptive Stabilizer™ training in abdominal wall muscles.

Methods: A sample of 41 healthy participants (age: 31.9 ± 4.5 y; height: 1.7 ± 0.1 m; weight: 68.3 ± 13.1 kg; body mass index, BMI: 22.9 ± 2.7 kg/m2) were recruited to participate in this study. Ultrasound images of the EO, IO, TrA, rectus anterior (RA) and interrecti distance (IRD) were measured and analyzed by the ImageJ software. Measurements were made at rest and during the abdominal drawing-maneuver (ADIM) developed by the patients with the Stabilizer™ located in the low back holding 40 mmHg for 10 seconds with a visual stimulus provided by a circular pressure marker.

Results: Ultrasound measurements for the abdominal wall muscles showed statistically significant differences (Π < .05) for a thickness decrease of the EO, IO and a thickness increase of TrA. A proprioceptive Stabilizer™ training produced a thickness increase in TrA muscle and a thickness decrease in EO and IO muscles in healthy subjects.

Conclusions: These findings suggest that a proprioceptive Stabilizer™ training could be useful in individuals with low back pain and lumbopelvic pain.
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http://dx.doi.org/10.1590/1806-9282.64.12.1134DOI Listing
December 2018

Early HCV viral kinetics under DAAs may optimize duration of therapy in patients with compensated cirrhosis.

Liver Int 2019 05 28;39(5):826-834. Epub 2018 Dec 28.

The Program for Experimental & Theoretical Modeling, Division of Hepatology, Loyola University Medical Center, Maywood, Illinois.

Background & Aims: Detailed hepatitis C virus (HCV) kinetics modelling is scarce in patients with advanced liver disease receiving direct-acting antivirals (DAAs). Due to budget restrictions, patients and health systems would benefit from the shortest possible treatment course. We investigated whether modelling very early HCV kinetics in cirrhotic patients under DAAs therapy could be used to individualize care and reduce treatment duration to achieve cure.

Methods: We included 74 patients with HCV-related cirrhosis who received interferon-free treatments for 12-24 weeks. HCV genotype, liver disease stage and treatment regimen were recorded. Viral load was determined prospectively at very frequent intervals until target not detected (TND, <15 IU/mL). A viral kinetic model was used to predict time to cure based on HCV clearance in extracellular body fluid (CL-EF).

Results: Sixty-eight patients (92%) achieved cure. Thirteen (18%) had MELD ≥15, 35 (47%) were Child-Pugh (CTP) ≥7. Median time to reach TND was 2 weeks (IQR: 1-4 weeks). Modelling indicated an average DAAs efficacy in blocking viral production of ε = 99.1%. HCV half-life (t ) was significantly shorter in patients with CTP <7, LSM <21 kPa or MELD <15 (1.5 vs 2.5 hours; P = 0.0057). The overall median CL-EF was 5.6 weeks (4.1-7.8). A CTP >7 and a LSM ≥21 kPa were significantly (P = 0.016) associated with longer CL-EF.

Conclusions: The study provides insights into HCV dynamics during DAAs therapy in patients with compensated and decompensated cirrhosis. Viral kinetics modelling suggests that treatment duration may be optimized in patients with compensated cirrhosis.
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http://dx.doi.org/10.1111/liv.14014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483833PMC
May 2019

Hepatitis C virus intrinsic molecular determinants may contribute to the development of cholestatic hepatitis after liver transplantation.

J Gen Virol 2019 01 19;100(1):63-68. Epub 2018 Nov 19.

1​Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain.

Cholestatic hepatitis C (CHC) is a severe form of hepatitis C virus (HCV) infection recurrence that leads to high graft loss rates early after liver transplantation (LT). To investigate the pathogenic mechanisms of CHC, we analysed HCV quasispecies in CHC patients compared to a control group (mild hepatitis C recurrence) by deep pyrosequencing. At the time of LT, NS5B quasispecies complexity was similar between the two groups but, after LT, it decreased more sharply in CHC patients than in the control group. Interestingly, the major variant before LT propagated efficiently and remained as the dominant sequence after LT in 62 % of CHC patients versus 11 % of controls (P=0.031). Sequence analysis of the complete non-structural region in a limited number of patients revealed a potential 12 aa signature specific to the CHC group. These data suggest that intrinsic molecular determinants in the circulating HCV quasispecies may provide a fitness advantage, contributing to the development of CHC.
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http://dx.doi.org/10.1099/jgv.0.001175DOI Listing
January 2019

Pkd2 deletion during embryo development does not alter mesonephric programmed cell senescence.

Int J Dev Biol 2018 ;62(9-10):637-640

Laboratorio de Células Madre en Cáncer y Envejecimiento, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), XXIS/SERGAS, Santiago de Compostela, Spain.

Programmed cell senescence during embryo development is a recently described process that opens a new perspective to understand the senescence response and that adds a new player whose contribution to development needs to be addressed. Identifying developmental syndromes with a root in deregulated programmed cell senescence will undoubtedly reinforce our view of senescence and could provide a new angle to confront disease. One of the structures that was initially reported to undergo cellular senescence is the mesonephros. During E12.5-E14.5, before regression, mesonephric tubules are positive for the most widely used marker of cell senescence, SAβG, and negative for proliferation marker, Ki67, in a p21Cip1-dependent manner. PKD2 is one of the genes defective in autosomal dominant polycystic kidney disease (ADPKD). Inherited mutations in this gene result in cyst formation in adults after a secondary hit. Polycystin-2 (PC2) protein, the product of PKD2 gene expression, inhibits cell cycle progression by inducing p21Cip1, whereas mutated PKD2 results in increased proliferation and defective differentiation of kidney epithelial cells. Here, we addressed the possibility of defective programmed cell senescence as a consequence of Pkd2 deletion in mice. We analyzed embryos for the expression of the senescence marker SAβG, for the proliferative status of mesonephric tubule cells, and for the expression of p21Cip1, without identifying any noticeable deregulation of cell senescence. Our results exclude defective programmed cell senescence upon Pkd2 ablation as an initial event in ADPKD.
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http://dx.doi.org/10.1387/ijdb.180078mcDOI Listing
May 2019

Loss of PICH Results in Chromosomal Instability, p53 Activation, and Embryonic Lethality.

Cell Rep 2018 09;24(12):3274-3284

Department of Cellular and Molecular Medicine, Center for Chromosome Stability and Center for Healthy Aging, University of Copenhagen, Copenhagen 2200, Denmark. Electronic address:

PICH is a DNA translocase necessary for the resolution of ultrafine anaphase DNA bridges and to ensure the fidelity of chromosomal segregation. Here, we report the generation of an animal model deficient for PICH that allowed us to investigate its physiological relevance. Pich KO mice lose viability during embryonic development due to a global accumulation of DNA damage. However, despite the presence of chromosomal instability, extensive p53 activation, and increased apoptosis throughout the embryo, Pich KO embryos survive until day 12.5 of embryonic development. The absence of p53 failed to improve the viability of the Pich KO embryos, suggesting that the observed developmental defects are not solely due to p53-induced apoptosis. Moreover, Pich-deficient mouse embryonic fibroblasts exhibit chromosomal instability and are resistant to RAS/E1A-induced transformation. Overall, our data indicate that PICH is essential to preserve chromosomal integrity in rapidly proliferating cells and is therefore critical during embryonic development and tumorigenesis.
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http://dx.doi.org/10.1016/j.celrep.2018.08.071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167640PMC
September 2018

Canine adenovirus type 1 (CAdV-1) in free-ranging European brown bear (Ursus arctos arctos): A threat for Cantabrian population?

Transbound Emerg Dis 2018 Dec 20;65(6):2049-2056. Epub 2018 Sep 20.

SERIDA, Servicio Regional de Investigación y Desarrollo Agroalimentario, Centro de Biotecnología Animal, Gijón, Spain.

Canine adenovirus type 1 (CAdV-1) is responsible for infectious canine hepatitis. The disease has been described in captive American black bear (Ursus americanus) and European brown bear (Ursus arctos arctos), with just one recently reported case in a cub of a free-ranging brown bear (Ursus arctos horribilis) from Alaska. The aim of this work is to summarize findings related to presence and associated mortality of CAdV-1 in 21 free-ranging Cantabrian brown bears (Ursus arctos arctos) submitted to necropsy in Asturias and Castilla y León (northwestern Spain) from 1998 to 2018. On the basis of the anatomopathological findings and laboratory results three free-ranging brown bears died due to infectious canine hepatitis, which is to our knowledge the first description of death due to this disease in free-ranging bears in Europe. Gross lesions consisted of petechial haemorrhages and congestion in different internal organs, haemorrhagic fluid in internal cavities, friable and yellowish liver and thickening of gall bladder. Microscopic lesions were observed mainly in liver, kidney and brain and consisted of multifocal necrosis of cells with presence of basophilic intranuclear inclusions. Immunohistochemical (IHC) and real-time polymerase chain reaction (qPCR) techniques were used to assess the presence of CAdV-1 in paraffin-embedded liver samples. Viral antigens were detected by IHC labelling within hepatocytes and Küppfer cells in the three animals. The presence of viral DNA was confirmed by qPCR in one of them. In order to evaluate the circulation of CAdV-1 in brown bears, a retrospective study was performed using both IHC and qPCR techniques in 11 and 12 additional brown bears, respectively. An extra brown bear was found positive by IHC. This study shows that CAdV-1 surveillance of brown bears and sympatric carnivores should be considered as major concern for the monitoring the population evolution throughout time in this endangered species.
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http://dx.doi.org/10.1111/tbed.13013DOI Listing
December 2018

Hepatitis C virus early kinetics and resistance-associated substitution dynamics during antiviral therapy with direct-acting antivirals.

J Viral Hepat 2018 12 4;25(12):1515-1525. Epub 2018 Oct 4.

Liver Unit, Hospital Clínic, IDIBAPS, CIBEREHD, Universitat de Barcelona, Barcelona, Spain.

The emergence of resistance-associated substitutions (RASs) can compromise the high efficacy of direct-acting antivirals (DAAs). Little is known about RASs selection at very early time points during DAA treatment. Therefore, we analyzed the potential emergence of RASs immediately after therapy initiation. Samples of 71 patients treated with different DAAs were collected at baseline, during therapy (hours 4 and 8; days 1-7; weeks 2-4) or until target not detected. HCV-RNA levels were determined by qPCR, and RASs were detected by deep sequencing. Sixty-three (89%) patients achieved a sustained virological response (SVR), 7 (10%) relapsed, and 1 (1%) experienced a breakthrough. Almost all non-SVR (7/8, 88%) showed RASs either at baseline or relapse. High-frequency RASs detected at baseline (Y93H and L159F+C316N) remained detectable at early time points during therapy and reappeared as most prevalent substitutions at relapse. Conversely, emergent RASs at relapse (Q80R, D168E/V, R155K and L31V) were not observed during the first hours-days, before HCV-RNA became undetectable. HCV-RNA decay and genetic evolution of the quasispecies followed a similar pattern during the first hours of therapy in SVR and non-SVR patients. In conclusion, the absence of early RASs selection and the similar dynamics of HCV kinetics and quasispecies in SVR and non-SVR patients after therapy initiation suggest that RASs selection may occur at later stages in the remaining reservoir, where viral populations persist hidden at very low replication levels. Nevertheless, we cannot completely exclude very early selection, when RASs are present below the sensitivity limit of deep sequencing.
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http://dx.doi.org/10.1111/jvh.12986DOI Listing
December 2018

Adult Sox2+ stem cell exhaustion in mice results in cellular senescence and premature aging.

Aging Cell 2018 Oct 20;17(5):e12834. Epub 2018 Aug 20.

Laboratorio de Células Madre en Cáncer y Envejecimiento, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain.

Aging is characterized by a gradual functional decline of tissues with age. Adult stem and progenitor cells are responsible for tissue maintenance, repair, and regeneration, but during aging, this population of cells is decreased or its activity is reduced, compromising tissue integrity and causing pathologies that increase vulnerability, and ultimately lead to death. The causes of stem cell exhaustion during aging are not clear, and whether a reduction in stem cell function is a cause or a consequence of aging remains unresolved. Here, we took advantage of a mouse model of induced adult Sox2+ stem cell depletion to address whether accelerated stem cell depletion can promote premature aging. After a short period of partial repetitive depletion of this adult stem cell population in mice, we observed increased kyphosis and hair graying, and reduced fat mass, all of them signs of premature aging. It is interesting that cellular senescence was identified in kidney after this partial repetitive Sox2+ cell depletion. To confirm these observations, we performed a prolonged protocol of partial repetitive depletion of Sox2+ cells, forcing regeneration from the remaining Sox2+ cells, thereby causing their exhaustion. Senescence specific staining and the analysis of the expression of genetic markers clearly corroborated that adult stem cell exhaustion can lead to cellular senescence induction and premature aging.
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http://dx.doi.org/10.1111/acel.12834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156495PMC
October 2018

NLRP3 Inflammasome and Caspase-1/11 Pathway Orchestrate Different Outcomes in the Host Protection Against Acute Infection.

Front Immunol 2018 3;9:913. Epub 2018 May 3.

Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI - CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.

Infection with protozoan parasite results in activation of nucleotide-binding domain and leucine-rich repeat containing receptors (NLRs). NLR activation leads to inflammasome formation, the activation of caspase-1, and the subsequent cleavage of IL-1β and IL-18. Considering that inflammasome activation and IL-1β induction by macrophages are key players for an appropriate T cell response, we investigated the relevance of NLR pyrin domain-containing 3 (NLRP3) and caspase-1/11 to elucidate their roles in the induction of different T cell phenotypes and the relationship with parasite load and hepatic inflammation during Tulahuen strain acute infection. We demonstrated that infected and C57BL/6 wild type (WT) mice exhibited similar parasitemia and survival, although the parasite load was higher in the livers of mice than in those of WT mice. Increased levels of transaminases and pro-inflammatory cytokines were found in the plasma of WT and mice indicating that NLRP3 is dispensable to control the parasitemia but it is required for a better clearance of parasites in the liver. Importantly, we have found that NLRP3 and caspase-1/11-deficient mice differentially modulate T helper (Th1, Th2, and Th17) and cytotoxic T lymphocyte phenotypes. Strikingly, mice showed the most dramatic reduction in the number of IFN-γ- and IL-17-producing CD4+ and CD8+ T cells associated with higher parasitemia and lower survival. Additionally, mice demonstrated significantly reduced liver inflammation with the lowest alanine aminotransferase (ALT) levels but the highest hepatic parasitic load. These results unequivocally demonstrate that caspase-1/11 pathway plays an important role in the induction of liver adaptive immunity against this parasite infection as well as in hepatic inflammation.
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http://dx.doi.org/10.3389/fimmu.2018.00913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944318PMC
June 2019

Lethal and sublethal responses in the fish, Odontesthes bonariensis, exposed to chlorpyrifos alone or under mixtures with endosulfán and lambda-cyhalothrin.

Ecotoxicology 2018 Sep 9;27(7):968-979. Epub 2018 May 9.

Centro de Investigaciones del Medio Ambiente, Facultad de Ciencias Exactas, Universidad Nacional de la Plata - CONICET, Buenos Aires, Argentina.

Need for ecotoxicological information on local species has been recently highlighted as a priority issue in Latin America. In addition, little information has been found on concentration distances between lethal and sublethal effects, and the effect of mixtures at these two levels of analysis. Chlorpyrifos (CPF) is an organophosphate insecticide broadly used in soybean crops which has dramatically expanded in Latin America and other regions of the world. The aim of the present study was to evaluate lethal and sublethal effects of CPF, singly or in mixtures, on the inland "Pejerrey" (Odontesthes bonariensis) under laboratory conditions. Bioassays were performed using 15-30 d post hatch Pejerrey larvae. Six toxicity tests were run for estimating the average inter-assay dose-response curve of CPF and other six for assessing the effects of mixtures of CPF with endosulfan (EN) or lambda-cyhalothrin (LC), at three toxic units (TU) proportions (25:75, 50:50, 75:25). In addition, four assays were performed to describe the average inter-assay dose-response inhibition curve of acetylcholinesterase (AchE) for CPF alone and two for assessing the mixtures. The estimated 96 h-LC for CPF was 2.26 ± 1.11 µg/L and the incipiency value was 0.048 ± 0.012 µg/L, placing this Neotropical species among the 13% of worldwide fish more sensitive to CPF. In addition, the 96 h-LC for EN and LC were 0.30 ± 0.012 µg/L and 0.043 ± 0.031 µg/L, respectively. Therefore, relative toxicity of the three soybean insecticides for O. bonariensis was LC > EN > CPF. Effects of mixtures with EN and LC were variable, but in general fitted to both, independent action (IA) and concentration addition (CA) models. Slight antagonism was found when CPF TU proportions were above 50%. Therefore, from the regulatory point of view, the use of both mixture models, CA or IA, would be precautionary. Differential sensitivity to CPF was found for AchE inhibition at the head (96 h-IC = 0.065 ± 0.058 µg/L) and the body (96 h-IC = 0.48 ± 0.17 µg/L). In addition, whereas no significant effects induced by mixtures was observed in body AchE activity, antagonism was induced in head AchE inhibition in presence of both, EN and LC in the mixture. The lethal to sublethal ratio was close to 25.2 and 3.4 when comparing the CPF-LC and ICs for head and body AchE activity, respectively. However, considerable overlapping was observed between concentration-response curves, indicating that the use of AchE as biomarker for environmental monitoring would be limited.
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http://dx.doi.org/10.1007/s10646-018-1941-5DOI Listing
September 2018