Peripubertal exposure of atrazine cause decrease in exploratory activity, deficits in sociability and few alterations on brain monoaminergic systems of rats.

Atrazine is a pesticide used to control weeds in both in pre- and post-emergence crops. The chronic exposure to atrazine can lead to severe damage in animals, especially in the endocrine and reproduction systems, leading to the inclusion of this pesticide into the endocrine disrupting chemicals group. Studies with rats showed that atrazine exposure during lactation in dams caused changes in the juvenile offspring, however; there is still limited information regarding the effects of atrazine during puberty. Thus, the aim of this study is to evaluate the effects of peripubertal exposure of atrazine in rats, assessing motor activity, social behavior and neurochemical alterations. Juvenile rats were treated with different doses of atrazine (0, 10, 30 or 100 mg/kg) by gavage from postnatal day 22 to 41. Behavioral tests were conducted for the evaluation of motor activity and social behavior, and neurochemical evaluation was done in order to assess monoamine levels. Atrazine caused behavioral alterations, evidenced by decrease in the exploratory activity (p values variation between 0.05 and 0.0001) and deficits in the social behavior of both male and females as adults (p values variation between 0.01 and 0.0001). As for the monoaminergic neurotransmission, atrazine led to very few alterations on the dopamine and serotonin systems that were limited to the females (p < 0.05). Altogether, the results suggests that peripubertal exposure of atrazine cause behavioral and neurochemical alterations. More studies need to be conducted to fully understand the differences in atrazine's effects and its use should be considered carefully.

Post-Partum Depression Lactating Rat Model for Evaluating Ketamine's Safety as a Pharmacotherapeutic Treatment: Roles in Cardiac and Urinary Function.

Depression is one of the world's most common and mentally disabling illnesses. Post-partum depression is a subtype of depression that affects one in seven women worldwide. Successful pharmacological treatment must consider the consequences for both, since the mother-child bond is fundamental for the well-being of both mother and infant as well as the general development of the newborn. Changes in maternal physiology and/or behavior can significantly influence the development of breastfed infants. Ketamine has been extensively studied for use as an antidepressant due to its mixed mechanisms of action. Safety and efficacy studies in the cardiovascular and urinary systems of a lactating postpartum depression animal model are essential for contributing toward ketamine's clinical use in the respective patient population. Thus, this project aimed to study the implications of postpartum maternal exposure to ketamine during lactation on the cardiovascular system of female rats submitted to the depression induction model by maternal separation. This model promotes depressive effects through stress caused by the interruption of mother-infant bond early in the offspring's life. To achieve depression, each dam was separated from her offspring for 3 h per day, from post-natal day 2 (PND2) to PND12. Experimental groups received daily treatment with either 5, 10, or 20 mg/kg of ketamine intraperitoneally during the lactation period, from PND2 to PND21. Behavioral tests consisted of the maternal and aggressive maternal behavior tests, the olfactory preference test, and the forced swim test. A technique for the detection of catecholamines and indoleamines in the heart muscle was developed for the experimental model groups. The histopathological evaluation was performed on these animals' cardiac muscles and urinary bladders. Our findings suggest that ketamine is safe for use in postpartum depression and does not induce cardiovascular and/or urinary systems toxicity.

Development, Optimization, and Validation of Forensic Analytical Method for Quantification of Anticholinesterase Pesticides in Biological Matrices from Suspected Cases of Animal Poisoning.

Anticholinesterase pesticides are a main cause of the intentional or accidental poisoning of animals. Anticholinesterases include several substances that cause the overstimulation of both central and peripheral acetylcholine-dependent neurotransmission. Forensic analyses of poisoning cases require high levels of expertise, are costly, and often do not provide reliable quantitative information for unambiguous conclusions. The purpose of the present study was to develop and validate a method of high-performance liquid chromatography with diode array detector (HPLC−DAD) for the identification and quantitation of n-methyl carbamates, organophosphates and respective metabolites from biological samples of animals that were suspected of poisoning. HPLC−DAD is reliable, fast, simplistic and cost-effective. The method was validated for biological samples obtained from stomach contents, liver, vitreous humor and blood from four different animal species. The validation of the method was achieved using the following analytical parameters: linearity, precision, accuracy, selectivity, recovery, and matrix effect. The method showed linearity at the range of 25−500 µg/mL, and the correlation coefficient (r2) values were >0.99 for all matrices. Precision and accuracy were determined by the (a) coefficient of variation (CV), (b) relative standard deviation low-quality control (LQC), (c) medium-quality control (QCM), and (d) high-quality control (QCA). The indicated parameters were all less than 15%. The recovery of analytes ranged from 31 to 71%. The analysis of results showed no significant interfering peaks due to common xenobiotics or matrix effects. The abovementioned method was used to positively identify pesticide analytes in 44 of the 51 animal samples that were suspected of poisoning, demonstrating its usefulness as a forensic tool.

Mortality in civilian trauma patients and massive blood transfusion treated with high vs low plasma: red blood cell ratio. Systematic review and meta-analysis / Mortalidad en pacientes con trauma civil y transfusion masiva tratados con una relación alta de plasma: globulos rojos versus una relacion baja. Revision sistemática y metaanálisis

Abstract Introduction: Massive bleeding in civilian trauma patients leads to dilutional coagulopathy. Transfusion with high plasma:red blood cell (RBC) ratio has been effective in reducing mortality in war trauma patients. However, in civilian trauma the evidence is controversial. Objective: To assess the impact on mortality of high vs low plasma:RBC ratio transfusion, in civilian trauma patients with massive bleeding. Methods: A systematic review and meta-analysis, including observational studies and clinical trials, was conducted. Data bases were systemically searched for relevant studies between January 2007 and June 2019. The main outcome was early (24-hours) and late (30-day) mortality. Fixed and random effects models were used. Results: Out of 1295 studies identified, 33 were selected: 2 clinical trials and 31 observational studies. The analysis of observational trials showed both decreased early mortality (odds ratio [OR] 0.67; 95% confidence interval [CI], 0.60-0.75) and late mortality (OR 0.79; 95% CI, 0.71-0.87) with the use of high plasma:RBC ratio transfusion, but there were no differences when clinical trials were evaluated (OR 0.89; 95% CI, 0.64-1.26). The exclusion of patients who died within the first 24 hours was a source of heterogeneity. The Injury Severity Score (ISS) altered the association between high plasma:RBC ratio and mortality, with a reduced protective effect when the ISS was high. Conclusion: The use of high vs low plasma: RBC ratio transfusion, in patients with massive bleeding due to civil trauma, has a protective effect on early and late mortality in observational studies. The exclusion of patients who died within the first 24 hours was a source of heterogeneity.

Resumen Introducción: El sangrado masivo en los pacientes con trauma civil propicia el desarrollo de coagulopatía dilucional. La transfusión de plasma y glóbulos rojos con una relación alta ha sido efectiva para disminuir la mortalidad en pacientes con trauma de guerra; sin embargo, su evidencia en trauma civil es controversial. Objetivo: Evaluar el efecto sobre la mortalidad de la transfusión de plasma: glóbulos rojos con relación alta (TPGR-RA) versus baja, en pacientes con sangrado masivo por trauma civil. Métodos: Se realizó una revisión sistemática y metaanálisis de estudios observacionales y experimentos clínicos publicados en el periodo de enero de 2007 a junio de 2019. El desenlace principal fue mortalidad temprana (24 horas) y tardía (30 días), utilizando el modelo de efectos fijos y aleatorios. Resultados: De 1.295 estudios identificados se incluyeron 33: dos experimentos clínicos y 31 estudios observacionales. El uso de TPGR-RA mostró una disminución de la mortalidad temprana (OR 0,67; IC 95 %, 0,60-0,75) y tardía (OR 0,79; IC 95 %, 0,71-0,87) cuando se analizaron los estudios observacionales, pero no hubo diferencias cuando se evaluaron los experimentos clínicos (OR 0,89; IC 95 %, 0,64-1,26). La exclusión de pacientes que fallecieron en las primeras 24 horas fue una fuente de heterogeneidad. La gravedad del trauma, ISS (por las iniciales en inglés de injury severity score)modificó la asociación entre la TPGR-RA y mortalidad, siendo menor el efecto protector cuando el ISS era alto. Conclusiones: El uso de TPGR-RA en pacientes con trauma civil y transfusión masiva (TM) tiene efecto protector sobre la mortalidad en los estudios observacionales. La exclusión de pacientes fallecidos en las primeras 24 horas fue causa de heterogeneidad.

Addressing Severe Mental Illness Rehabilitation in Colombia, Costa Rica, and Peru.

Many Latin American countries face the challenge of caring for a growing number of people with severe mental illnesses while promoting deinstitutionalization and community-based care. This article presents an overview of current policies that aim to reform the mental health care system and advance the employment of people with disabilities in Colombia, Costa Rica, and Peru. The authors conducted a thematic analysis by using public records and semistructured interviews with stakeholders. The authors found evidence of supported employment programs for vulnerable populations, including people with disabilities, but found that the programs did not include people with severe mental illnesses. Five relevant themes were found to hamper progress in psychiatric vocational rehabilitation services: rigid labor markets, insufficient advocacy, public subsidies that create conflicting incentives, lack of deinstitutionalized models, and lack of reimbursement for evidence-based psychiatric rehabilitation interventions. Policy reforms in these countries have promoted the use of medical interventions to treat people with severe mental illnesses but not the use of evidence-based rehabilitation programs to facilitate community integration and functional recovery. Because these countries have other supported employment programs for people with nonpsychiatric disabilities, they are well positioned to pilot individual placement and support to accelerate full community integration among individuals with severe mental illnesses.

Insights into BRCA1/2 Genetic Counseling from Ethnically Diverse Latina Breast Cancer Survivors.

Despite the disproportionate underuse of genetic counseling and testing for BRCA1/2 (BRCA)-associated hereditary breast and ovarian cancer (HBOC) risk among Latinas, little is known about the associated barriers and facilitators. We conducted in-depth qualitative interviews with 20 at-risk Latina women from diverse backgrounds. Eligible women were diagnosed with breast cancer <50 years, with or without a family history of breast and/or ovarian cancer (>1 first-degree relative diagnosed <50 years). All interviews were conducted in Spanish, audio recorded, transcribed, and translated into English. Two bilingual coders used thematic analyses to identify 7 main themes. Results revealed very low levels of awareness and knowledge about HBOC and BRCA genetic counseling. Interestingly, for most Latinas, competing life demands and cultural concerns (fatalismo and destino) did not strongly influence personal beliefs about genetic counseling. In addition, older women were equally as interested in education, cancer prevention, and BRCA genetic counseling as younger women. These findings suggest that Latinas, regardless of age, increasingly acknowledge and prioritize their own health. Women reported their main motivator to undergo counseling was concern about family members' cancer risks. Main barriers included financial and insurance concerns, and lack of awareness about genetic services. Investigating the beliefs and attitudes of diverse populations of Latinas at risk for HBOC reveals logistical barriers to BRCA genetic counseling uptake within this under-represented community. Efforts are needed to provide at-risk Latina breast cancer survivors' knowledge of and access to genetic counseling and testing based on risk status and Latinas' increasing responsiveness and uptake of these services.

An ex vivo approach to botanical-drug interactions: a proof of concept study.

ETHNOPHARMACOLOGICAL RELEVANCE: Botanical medicines are frequently used in combination with therapeutic drugs, imposing a risk for harmful botanical-drug interactions (BDIs). Among the existing BDI evaluation methods, clinical studies are the most desirable, but due to their expense and protracted time-line for completion, conventional in vitro methodologies remain the most frequently used BDI assessment tools. However, many predictions generated from in vitro studies are inconsistent with clinical findings. Accordingly, the present study aimed to develop a novel ex vivo approach for BDI assessment and expand the safety evaluation methodology in applied ethnopharmacological research. MATERIALS AND METHODS: This approach differs from conventional in vitro methods in that rather than botanical extracts or individual phytochemicals being prepared in artificial buffers, human plasma/serum collected from a limited number of subjects administered botanical supplements was utilized to assess BDIs. To validate the methodology, human plasma/serum samples collected from healthy subjects administered either milk thistle or goldenseal extracts were utilized in incubation studies to determine their potential inhibitory effects on CYP2C9 and CYP3A4/5, respectively. Silybin A and B, two principal milk thistle phytochemicals, and hydrastine and berberine, the purported active constituents in goldenseal, were evaluated in both phosphate buffer and human plasma based in vitro incubation systems. RESULTS: Ex vivo study results were consistent with formal clinical study findings for the effect of milk thistle on the disposition of tolbutamide, a CYP2C9 substrate, and for goldenseal׳s influence on the pharmacokinetics of midazolam, a widely accepted CYP3A4/5 substrate. Compared to conventional in vitro BDI methodologies of assessment, the introduction of human plasma into the in vitro study model changed the observed inhibitory effect of silybin A, silybin B and hydrastine and berberine on CYP2C9 and CYP3A4/5, respectively, results which more closely mirrored those generated in clinical study. CONCLUSIONS: Data from conventional buffer-based in vitro studies were less predictive than the ex vivo assessments. Thus, this novel ex vivo approach may be more effective at predicting clinically relevant BDIs than conventional in vitro methods.

Engaging Latina cancer survivors, their caregivers, and community partners in a randomized controlled trial: Nueva Vida intervention.

INTRODUCTION: Few studies have evaluated interventions to improve quality of life (QOL) for Latina breast cancer survivors and caregivers. Following best practices in community-based participatory research (CBPR), we established a multi-level partnership among Latina survivors, caregivers, community-based organizations (CBOs), clinicians, and researchers to evaluate a survivor-caregiver QOL intervention. METHODS: A CBO in the mid-Atlantic region, Nueva Vida, developed a patient-caregiver program called Cuidando a mis Cuidadores (Caring for My Caregivers), to improve outcomes important to Latina cancer survivors and their families. Together with an academic partner, Nueva Vida and three CBOs established a multi-level team of researchers, clinicians, Latina cancer survivors, and caregivers to conduct a national randomized trial to compare the patient-caregiver program to usual care. RESULTS: Incorporating team feedback and programmatic considerations, we adapted the prior patient-caregiver program into an 8-session patient- and caregiver-centered intervention that includes skill-building workshops such as managing stress, communication, self-care, social well-being, and impact of cancer on sexual intimacy. We will measure QOL domains with the patient-reported outcomes measurement information system, dyadic communication between the survivor and caregiver, and survivors' adherence to recommended cancer care. To integrate the intervention within each CBO, we conducted interactive training on the protection of human subjects, qualitative interviewing, and intervention delivery. CONCLUSION: The development and engagement process for our QOL intervention study is innovative because it is both informed by and directly impacts underserved Latina survivors and caregivers. The CBPR-based process demonstrates successful multi-level patient engagement through collaboration among researchers, clinicians, community partners, survivors, and caregivers.

Caracterización del gen de a-Amilasade la cepa nativa Bacillussp. BBM1 / Characterization of the a-Amylase gene from Bacillus sp. BBM1

Las enzimas degradadoras del almidón representan cerca del 30% del mercado mundial de enzimas y son utilizadas en la producción de glucosa, maltosa y oligosacáridos; los cuales pueden ser transformados posteriormente en jarabes de fructosa y dextrosa. La glucosa también puede ser utilizada en la producción de etanol, aminoácidos y ácidos orgánicos. La alpha-amilasa también puede ser utilizada como una alternativa a la adición de malta en la industria de la cerveza, el mejoramiento de harinas y la remoción de almidón en la industria papelera y textil y como aditivo de detergentes. En este trabajo reportamos la secuenciación completa del gen codificante para la alpha-amilasa BBM1 producida por la cepa nativa Bacillus sp. BBM1, incluyendo sus regiones reguladoras 3' y 5'. La secuencia de aminoácidos corresponde a una proteína de 659 residuos que, luego de ser secretada y procesada post-traduccionalmente, da origen a una enzima madura de 618 a.a con un peso de 68 kDa. La amilasa BBM1 es transcrita como un mRNA monocistrónico, tal como lo sugiere la presencia de estructuras terminadoras de la transcripción. Su expresión está regulada por el factor CcpA cuya secuencia operadora corresponde al alelo AmyR1. A diferencia de la mayoría de las amilasas estudiadas, BBM1 parece poseer dos dominios adicionales de unión a carbohidratos, lo cual indica que esta enzima puede ser más eficiente en la degradación de almidón granular. Finalmente, se presenta un modelo por homología para esta enzima que indica las posibles interacciones con iones de calcio y el sustrato.

Aislamiento de lactobacillus plantarum LPBM10 y caracterización parcial de su bacteriocina / Isolation of lactobacillus plantarum LPBM10 and partial characterization of its bacteriocin

Las bacterias acidolácticas (BAL) son un grupo de microorganismos Gram positivos utilizados ampliamente en la preservación de alimentos debido a sus propiedades probióticas y su capacidad para producir bacteriocinas. Las bacteriocinas son compuestos antimicrobianos de naturaleza peptídica y han recibido gran atención por la industria de alimentos debido a su uso potencial como sustitutos de aditivos químicos.En este trabajo reportamos el aislamiento y caracterización de la cepa de Lactobacillus plantarum LPBM10.Esta bacteria fue aislada a partir de leche fermentada, presenta propiedades probióticas y es productora de bacteriocinas. El extracto libre de células de LPBM10 presenta actividad antimicrobiana frente a bacterias Gram positivas y Gram negativas. La bacteriocina LPBM10 es altamente termoestable, presenta mayor actividad a pH ácido y su actividad no se ve afectada por la presencia de proteinasa K, agentes quelantes y detergentes. El compuesto antibacteriano LPBM10 fue purificado mediante diálisis y cromatografía de exclusión. El análisis por espectroscopía ultravioleta e infrarroja sugiere que la bacteriocina LPBM10 es de naturaleza peptídica con presencia de tirosina y cisteína. Pruebas sobre el extracto crudo dializado mediante cromatografía de intercambio iónico indican la presencia de un compuesto aniónico antagonista del compuesto LPBM10.