Nucleation and growth inhibition of biological minerals by cementum attachment protein-derived peptide (CAP-pi).

Biomineralization is a highly regulated process where proteins/peptides-crystal interactions contribute to the shaping, phasing and aggregation of minerals. We have identified and synthesized a cementum attachment protein-derived peptide (CAP-pi), which corresponds to amino acids 40-53 of the N-terminal CAP domain (MASSDEDGTNGGAS) and its phosphorylated variant (MASpSpDEDGTNGGASp) (CAP-pip). The peptide is composed of polar and negatively charged amino acids, which are disordered, according to in silico analysis. Our results show that CAP-pi inhibits hydroxyapatite (HA) formation and growth. However, it possesses low capacity to inhibit calcium oxalate crystal growth. CAP-pip showed a stronger inhibitory effect on the formation and growth of HA. As well as a high capacity to inhibit calcium oxalate monohydrate growth, mainly due to adsorption on specific growth faces. Small peptides have many advantages over the full-size protein, including low-cost production and modulation characteristics that allow for structural changes. Our findings suggest that CAP-pip-derived peptide could possess therapeutic potential to prevent or treat pathological calcifications such as renal stones and vascular calcification.

[Results of the Program for the Rational Use of Antimicrobials in a Mexican hospital, 2013-2018Resultados de um programa para o uso racional de antimicrobianos num hospital no México, 2013-2018]. / Resultados del Programa de Uso Racional de Antimicrobianos en un hospital de México, 2013-2018.

OBJECTIVE: Describe the results of the Program for the Rational Use of Antimicrobials at Mexico's Juárez Hospital. METHODS: An observational, cross-sectional, retrospective, descriptive study was designed. For the consumption of antimicrobial agents, data from January 2013 to December 2018 were analyzed by calculating the defined daily dose (DDD). For the cost analysis, a traditional costing calculation was used. RESULTS: For the group of carbapenem agents, there was a sizeable reduction in the consumption of imipenem / cilastatin: the DDD declined from 2.3 in 2013 to 0.7 in 2018, a decrease of 70%. By contrast, for the other two agents, increases were observed. The consumption of meropenem increased by 2% (from 2.4 in 2013 to 2.5 in 2018); the consumption of ertapenem increased by 75% (from 1 in 2013 to 1.8 in 2018). The total expenditure on antimicrobial agents was USD 930 556.46 during 2013, compared to USD 856 079.10 during 2018, representing a difference of 8% or USD 74 905.61 of the total expenditure. CONCLUSIONS: Programs for the rational use of antimicrobials need to be evaluated continuously, by monitoring both consumption of agents by patients and related institutional expenditures.

OBJETIVO: Descrever os resultados do Programa para o Uso Racional de Antimicrobianos no Hospital Juárez de México. MÉTODOS: Elaboramos um estudo observacional, transversal, retrospectivo e descritivo. Analisamos o consumo de antimicrobianos de janeiro de 2013 a dezembro de 2018 pelo cálculo da dose diária definida (DDD); para a análise de custos, realizamos um cálculo de custos tradicional. RESULTADOS: No grupo dos carbapenens, a redução do consumo de imipenem/cilastatina foi notável: passou-se de uma DDD de 2,3 em 2013 para 0,7 em 2018, uma redução de 70%. Por outro lado, observou-se um aumento no uso dos dois outros medicamentos: no caso do meropenem, foi registrado um aumento de 2% (de 2,4 em 2013 a 2,5 em 2018); no consumo de ertapenem o aumento foi de 75% (de 1 em 2013 a 1,8 em 2018). No total, as despesas com antimicrobianos foram de USD 930 556,46 em 2013 e de USD 856 079,10 em 2018, uma diferença de 8%, o que equivale a uma redução de USD 74 905,61 nas despesas totais. CONCLUSÕES: É necessário avaliar continuamente os programas para o uso racional de antimicrobianos pelo monitoramento do consumo e das despesas derivadas.

Sources and profiles of toxins in shellfish from the south-central coast of Chile (36°â€’ 43° S).

The study of marine toxins in shellfish is of the utmost importance to ensure people's food safety. Marine toxins in shellfish and microalgae in the water column off the south-central coast of Chile (36°â€’43° S) were studied in a network of 64 stations over a 14-month period. The relative abundance of harmful species Alexandrium catenella, Alexandrium ostenfeldii, Protoceratium reticulatum, Dinophysis acuminata, Dinophysis acuta, Pseudo-nitzschia seriata group and P. delicatissima group was analyzed. The detection and quantification of lipophilic toxins and domoic acid (DA) in shellfish was determined by UHPLC-MS/MS, and for Paralytic Shellfish Toxins (PSTs) by HPLC-FD with post-column oxidation, while for a culture of A. ostenfeldii a Hylic-UHPLC-MS/MS was used. Results showed that DA, gonyautoxin (GTX)-2, GTX-3 and pectenotoxin (PTX)-2 were detected below the permitted limits, while Gymnodimine (GYM)-A and 13-desmethylespirolide C (SPX-1) were below the limit of quantitation. According to the distribution and abundance record of microalgae, DA would be associated to P. seriata and P. delicatissima-groups, PTX-2 to D. acuminata, and GTX-2, GTX-3, GYM-A, and SPX-1 to A. ostenfeldii. However, the toxin analysis of an A. ostenfeldii culture from the Biobío region only showed the presence of the paralytic toxins C2, GTX-2, GTX-3, GTX-5 and saxitoxin, therefore, the source of production of GYM and SPX is still undetermined.

Th17 Cell and Inflammatory Infiltrate Interactions in Cutaneous Leishmaniasis: Unraveling Immunopathogenic Mechanisms.

The inflammatory response during cutaneous leishmaniasis (CL) involves immune and non-immune cell cooperation to contain and eliminate Leishmania parasites. The orchestration of these responses is coordinated primarily by CD4+ T cells; however, the disease outcome depends on the Th cell predominant phenotype. Although Th1 and Th2 phenotypes are the most addressed as steers for the resolution or perpetuation of the disease, Th17 cell activities, especially IL-17 release, are recognized to be vital during CL development. Th17 cells perform vital functions during both acute and chronic phases of CL. Overall, Th17 cells induce the migration of phagocytes (neutrophils, macrophages) to the infection site and CD8+ T cells and NK cell activation. They also provoke granzyme and perforin secretion from CD8+ T cells, macrophage differentiation towards an M2 phenotype, and expansion of B and Treg cells. Likewise, immune cells from the inflammatory infiltrate have modulatory activities over Th17 cells involving their differentiation from naive CD4+ T cells and further expansion by generating a microenvironment rich in optimal cytokines such as IL-1ß, TGF-ß, IL-6, and IL-21. Th17 cell activities and synergies are crucial for the resistance of the infection during the early and acute stages; however, if unchecked, Th17 cells might lead to a chronic stage. This review discusses the synergies between Th17 cells and the inflammatory infiltrate and how these interactions might destine the course of CL.

A Naturalistic Behavioral Intervention to Increase Interaction between Siblings with and without Autism.

Research suggests that including typically developing siblings in interventions for children with autism spectrum disorder (ASD) may be beneficial. However, studies have predominantly involved only participants with mild symptoms of ASD and have not also reported outcomes for the typically developing sibling. The purpose of this study was to address these gaps by replicating and extending an intervention package consisting of structured, interest-based play activities, adult instruction and modeling, and response to child questions. A reversal design across two sibling dyads was used to demonstrate the effects of the intervention on the social interaction behaviors of the child with ASD and typically developing sibling. Social interaction increased for both sibling dyads, results generalized for one dyad, and multiple measures indicated a high level of social validity. Recommendations for practitioners and caregivers working with children with ASD and potential areas of future research are discussed.

Levels of Polychlorinated Dibenzo-p-Dioxins/Furans (PCDD/Fs) and Dioxin-Like Polychlorinated Biphenyls (DL-PCBs) in Human Breast Milk in Chile: A Pilot Study.

Persistent organic pollutants (POPs) are organic compounds that resist biochemical degradation, moving long distances across the atmosphere before deposition occurs. Our goal was to provide up-to-date data on the levels of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in breast milk from Chilean women and to estimate the exposure of infants due to breast milk consumption. In Chile, we conducted a cross-sectional study based on methodologies proposed by the WHO, with a sample of 30 women recruited from three defined areas: 10 from the Arica Region (urban; Arica and Parinacota Region), 10 from Coltauco (rural; O'Higgins Region), and 10 from Molina (40% rural; Maule Region). High-resolution gas chromatography coupled with high-resolution mass spectrometry (HRGC/HRMS) was performed on pooled samples from each area. We calculated equivalent toxic concentrations (WHO-TEQ) based on the current WHO Toxic Equivalency Factors (TEF). The minimum and maximum values of ∑ PCDDs/Fs + DL-PCBs-TEQ were 4.317 pg TEQ/g fat in Coltauco and 6.31 pg TEQ/g fat in Arica. Molina had a total TEQ of 5.50 pg TEQ/g fat. The contribution of PCDD/Fs was approximately five-fold higher than that of DL-PCBs. The Estimated Daily Intake (EDI) of ∑ PCDDs/Fs + DL-PCBs based on the three pooled samples ranged between 6.71 and 26.28 pg TEQ/kg body weight (bw)/day, with a mean intake of 16.11 (±6.71) pg TEQ/kg bw/day in breastfed children from 0 to 24 months old. These levels were lower than those reported in international studies. Despite the fact that the observed levels were low compared to those in most industrialized countries, the detection of a variety of POPs in breast milk from Chilean women indicates the need for follow-up studies to determine whether such exposures during childhood could represent a health risk in adulthood.

Study of the interaction between progesterone and beta-cyclodextrin by electrochemical techniques and steered molecular dynamics.

The interaction of progesterone with beta-cyclodextrin (beta-CD) was studied by differential pulse polarography. The aim of the present work was to study the effect of beta-CD on the electrochemical behavior of progesterone in aqueous solution and also to analyze the molecular interactions involved in formation of the inclusion complex. The complex with stoichiometry of 1:1 was thermodynamically characterized. In addition, steered molecular dynamics (SMD) was used to investigate the energetic properties of formation of the inclusion complex along four different pathways (reaction coordinates), considering two possible orientations. From multiple trajectories along these pathways, the potentials of mean force for formation of the beta-CD progesterone inclusion complex were calculated. The energy analysis was in good agreement with the experimental results. In the beta-CD progesterone inclusion complex, a large portion of the steroid skeleton is included in the beta-CD cavity. The lowest energy was found when the D-ring of the guest molecule is located near the secondary hydroxyls of the beta-CD cavity. In the most probable orientation, one intermolecular hydrogen bond is formed between the O of the C-20 keto group of the progesterone and a secondary hydroxyl of the beta-CD.

Naturalistic Speech-Generating Device Interventions for Children With Complex Communication Needs: A Systematic Review of Single-Subject Studies.

Purpose: This article presents a systematic review that aimed to synthesize single-subject-design studies that have examined naturalistic interventions for teaching the expressive use of speech-generating devices (SGDs) to children with complex communication needs. Specifically, this review describes what intervention strategies are most commonly applied in studies with positive effects and minimal methodological flaws and examines the populations and outcomes for which these strategies have been effective. Method: A systematic approach was used to qualitatively code variables of interest to this review. Results were summarized via both visual analysis and effect size methods, and a certainty of evidence methodology was adopted to describe the quality of the evidence. Results: Thirty-two unique studies met inclusion criteria, with 19 having consistent positive results and meeting minimum requirements for certainty of evidence. Although studies used a variety of titles to describe intervention packages (e.g., milieu teaching, interaction strategies), certain strategies were common across studies. These included (a) creating and capturing communication opportunities via methods such as time delay and questioning; (b) providing feedback via methods such as reinforcement of requests, praise, or expansions; (c) prompting (verbal, physical, gestural); (d) modeling; and (e) training communication partners. Conclusions: Findings regarding these intervention components help to provide practical guidelines for naturalistic SGD intervention. Limitations of the current body of research (e.g., need to include more home-based studies and more intermediate to advanced SGDs, need to critically analyze the most critical intervention components) provide suggestions for future research. Supplemental Material: https://doi.org/10.23641/asha.6615332.

Variables psicosociales en cefalea infantil / Psychosocial variables in child headache

La cefalea es un motivo frecuente de consulta en niños y adolescentes. Los factores psicológicos influyen en la evolución sintomática y han sido abordados desde distintos puntos de vista según los diversos modelos teóricos. Para realizar diagnóstico de cefalea se debe objetivar evolución, frecuencia, intensidad, horario y duración, localización, características del dolor, síntomas asociados, factores desencadenantes, antecedentes familiares y antecedentes personales. El objetivo de este estudio fue evaluar las variables psicológicas y sociales en pacientes que consultan en la Unidad de Cefalea del Servicio de Neurología Infantil del Hospital San Juan de Dios. Los pacientes fueron evaluados mediante una encuesta diseñada por el equipo, que incluyó las variables psicológicas a estudiar: características personales, disfunción y conflictos familiares, violencia intrafamiliar y problemas en el ámbito escolar. Se caracterizó el nivel socioeconómico mediante escala de Graffar. Los pacientes con cefalea evaluados se presentaron con mayor frecuencia en sexo femenino. Se encontró frecuentemente alteración de las variables psicológicas estudiadas. Al plantear el tratamiento, hay diversas modalidades de intervención, así se realizó manejo familiar y/o individual. La inclusión de variables psicosociales, parecen ser útiles tanto en la evaluación como en el posterior diseño de estrategias de intervención que apoyen el tratamiento de estos pacientes.

Headache is a frequent symptom in children and adolescents. Psychological variables affect the clinical evolution and they have been approached from different theoretical models. Headache diagnosis requires specifying course, frequency, intensity, duration, localization, associated symptoms, family and personal history. The aims of this study were to evaluate the psychological and social variables in outpatients consulting the Headache Unit in Neurology Pediatric Service of Hospital San Juan de Dios. The patients were assessed with a structured questionnaire designed for this purpose and socioeconomic status was evaluated with Graffar scale. The patients of our sample were mainly females. The psychological variables were frequently present in all patients. There are different treatments for this kind of pathology; we chose family and/or individual interventions depending on the case. This approach seems to be useful both to proper assessment and treatment strategies for these patients.

Efectos del estimulador de alto voltaje como medio de intervención fisioterapéutica temprana en el aprovechamiento proteico de los pacientes con hipercatabolismo que ingresan a la unidad de cuidados intensivos / Effects of a high voltage stimulator as a means of early physical therapy intervention in the protein exploitation of patients with hypercatabolism in the ICU

El propósito de este resumen consistió en identificar los efectos de Estimulador de Alto Voltaje como un medio para promover una intervención fisioterapéutica temprana en la rehabilitación del paciente en estado critico; ya que debido a los efectos de la inmovilización prolongada por la enfermedad, estos pacientes suelen presentar el bien conocido síndrome de Desacondicionamiento Físico, el cual puede tener consecuencias tan severas o más grandes que la misma patología base. Por tal motivo se buscó la influencia de este tipo de terapia en el aprovechamiento proteico de los pacientes con un estado hipercatabolico, reflejado a través de los niveles de Creatinina (Cr.O) y Nitrógeno (N.U.U) en orina de 24 horas.

Balance de nitrógeno tomados semanalmente y niveles de glicemia en sangre tomados diariamente. El tipo de diseño usado en este estudio fue experimental pre prueba post prueba con grupo estudio y control con un universo total de 30 pacientes, 15 por cada grupo, de los cuales 2 fallecieron. La aplicación de la electroestimulación se realizó una semana en cada paciente del grupo de estudio, con un tiempo de terapia diaria de 1 hora (15 minutos por cada músculo). La asignación a los grupos se hizo de manera aleatoria según el orden de llegada de cada paciente, por lo que se requirió un tiempo máximo de aplicación de dos meses y medio. Adicionalmente para obtener un mayor control sobre las variables los parámetros nutricionales de proteínas y carbohidratos fueron similares para cada uno de los grupos. Una vez se finalizó la aplicación total del estudio, se procedió a realizar un análisis estadístico con la prueba t de student con un intervalo de confianza de 0.05; la cual arrojó diferencias significativas en los grupos, para las glicemias en sangre de los días 6 y 7 del protocolo; y en los balances de nitrógeno ureico en orina respecto al grupo de control, el cual alcanzó a neutralizar sus balances pareciendo indicar que la aplicación de la electroestimulación puede influir sobre el aprovechamiento proteico. Por otra parte para las otras variables estudiadas (Cr.O y N.U.U. 24 hrs) no se presentaron diferencias estadísticamente significativas pero las hipótesis de trabajo tomaron la dirección esperada, siendo esto un buen indicador de un mejor aprovechamiento proteico por este tipo de pacientes.