Reliability and Construct Validity of a Mobile Application for the Finger Tapping Test Evaluation in People with Multiple Sclerosis.

The finger tapping test (FTT) is a tool to evaluate the motor performance of the hand and fingers and eye-hand coordination with applicability in people with multiple sclerosis (pwMS). The aim of this study was to evaluate the intra- and inter-rater reliability of the TappingPro® mobile app and the construct validity between this app and validated clinical scales for motor performance in healthy subjects and pwMS. 42 healthy subjects (mean age 25.05) and 13 pwMS (mean age 51.69, EDSS between 3 and 7.5E) participated. FTT was performed with the TappingPro® mobile app. All participants were examined twice, with a one-week interval between the two appointments. For the analysis of construct validity, the Jamar® hydraulic hand dynamometer, Box and Blocks Test (BBT), and Nine Hole Peg Test (NHPT) were used. The intra-rater reliability showed a good correlation (Intraclass Correlation Coefficient, ICC > 0.787) for both upper limbs and both times of FTT for healthy subjects, and an excellent correlation (ICC > 0.956) for upper limbs and both times of FTT for pwMS. The ICC for the inter-rater reliability was good (ICC = 0.869) for the non-dominant upper limb in the FTT 10 s of the healthy subjects, and excellent (ICC > 0.904) for all the other measurements of the healthy subjects and pwMS. However, the Bland-Altman plots showed disagreement between observers and measurements that should be considered in the interpretation of clinical evaluations. The correlation analysis for healthy subjects showed poor associations between all variables, except for the association between hand grip strength and the FTT 60 s in the non-dominant upper limb, which had a moderate coefficient. For pwMS, there were moderate to excellent associations between BBT and the NHPT and FTT for both upper limbs. The correlations between hand grip strength and FFT were poor. This mobile app could be a useful and low-cost assessment tool in pwMS, allowing a simple evaluation and follow-up that has excellent correlation with clinical scales validated in this pathology.

Flow Behavior through Porous Media and Displacement Performance of a SILICA/PAM Nanohybrid: Experimental and Numerical Simulation Study.

Nanoparticles (NPs) have been proposed as additives to improve the rheological properties of polymer solutions and reduce mechanical degradation. This study presents the results of the retention experiment and the numerical simulation of the displacement efficiency of a SiO2/hydrolyzed polyacrylamide (HPAM) nanohybrid (CSNH-AC). The CSNH-AC was obtained from SiO2 NPs (synthesized by the Stöber method) chemically modified with HPAM chains. Attenuated total reflection-Fourier transform infrared spectroscopy, field emission gun-scanning electron microscopy, X-ray diffraction, and thermogravimetric analysis were used to characterize the nanohybrid. The injectivity and dynamic retention tests were performed at 56 °C in a sandstone core with a porosity of ∼26% and a permeability of 117 and 287 mD. A history matching of the dynamic retention test was performed to determine the maximum and residual adsorption, IPV, and residual resistance factor (RRF). A laboratory-scale model was used to evaluate the displacement efficiency of CSNH-AC and HPAM through numerical simulation. According to the results, the nanohybrid exhibits better rheological behavior than the HPAM solution at a lower concentration. The nanopolymer sol adsorption and IPV (29,7 µg/grock, 14,5) are greater than those of the HPAM solution (9,2 µg/grock, 10), which was attributed to the difference between the rock permeabilities used in the laboratory tests (HPAM: 287 mD and CSNH-AC: 117 mD). The RF of both samples gradually increases with the increase in shear rate, while the RRF slightly decreases and tends to balance. However, the nanopolymer sol exhibits greater RF and RRF values than that of the polymer solution due to the strong flow resistance of the nanohybrid (higher retention in the porous media). According to the field-scale simulation, the incremental oil production could be 295,505 and 174,465 barrels for the nanopolymer sol and the HPAM solution, respectively (compared to waterflooding). This will represent an incremental recovery factor of 11.3% for the nanopolymer sol and 6.7% for the HPAM solution.

Dysregulation of the endogenous cannabinoid system following opioid exposure.

Rates of opioid-related deaths and overdoses in the United States are at record-high levels. Thus, novel neurobiological targets for the treatment of OUD are greatly needed. Given the close interaction between the endogenous opioid system and the endocannabinoid system (ECS), targeting the ECS may have therapeutic potential in OUD. The various components of the ECS, including cannabinoid receptors, their lipid-derived endogenous ligands (endocannabinoids [eCBs]), and the related enzymes, present potential targets for developing new medications in OUD treatment. The purpose of this paper is to review the clinical and preclinical literature on the dysregulation of the ECS after exposure to opioids. We review the evidence of ECS dysregulation across various study types, exposure protocols, and measurement protocols and summarize the evidence for dysregulation of ECS components at specific brain regions. Preclinical research has shown that opioids disrupt various ECS components that are region-specific. However, the results in the literature are highly heterogenous and sometimes contradictory, possibly due to variety of different methods used. Further research is needed before a confident conclusion could be made on how exposure to opioids can affect ECS components in various brain regions.

Emerging issues on Staphylococcus aureus endocarditis and the role in therapy of daptomycin plus fosfomycin.

INTRODUCTION: Methicillin-resistant and -susceptible Staphylococcus aureus (MRSA/MSSA) infections are a major global health-care problem. Bacteremia with S. aureus exhibits high rates of morbidity and mortality and can cause complicated infections such as infective endocarditis (IE). The emerging resistance profile of S. aureus is worrisome, and several international agencies have appealed for new treatment approaches to be developed. AREAS COVERED: Daptomycin presents a rapid bactericidal effect against MRSA and has been considered at least as effective as vancomycin in treating MRSA bacteremia. However, therapy failure is often related to deep-seated infections, e.g. endocarditis, with high bacterial inocula and daptomycin regimens <10 mg/kg/day. Current antibiotic options for treating invasive S. aureus infections have limitations in monotherapy. Daptomycin in combination with other antibiotics, e.g. fosfomycin, may be effective in improving clinical outcomes in patients with MRSA IE. EXPERT OPINION: Exploring therapeutic combinations has shown fosfomycin to have a unique mechanism of action and to be the most effective option in preventing the onset of resistance to and optimizing the efficacy of daptomycin, suggesting the synergistic combination of fosfomycin with daptomycin is a useful alternative treatment option for MSSA or MRSA IE.

Thienopyrimidine Derivatives as GPR55 Receptor Antagonists: Insight into Structure-Activity Relationship.

GPR55 is an orphan G-protein coupled receptor involved in various pathophysiological conditions. However, there are only a few noncannabinoid GPR55 ligands reported so far. The lack of potent and selective GPR55 ligands precludes a deep exploration of this receptor. The studies presented here focused on a thienopyrimidine scaffold based on the GPR55 antagonist ML192, previously discovered by high-throughput screening. The GPR55 activities of the new synthesized compounds were assessed using ß-arrestin recruitment assays in Chinese hamster ovary cells overexpressing human GPR55. Some derivatives were identified as GPR55 antagonists with functional efficacy and selectivity versus CB1 and CB2 cannabinoid receptors.

Poison cassette exon splicing of SRSF6 regulates nuclear speckle dispersal and the response to hypoxia.

Hypoxia induces massive changes in alternative splicing (AS) to adapt cells to the lack of oxygen. Here, we identify the splicing factor SRSF6 as a key factor in the AS response to hypoxia. The SRSF6 level is strongly reduced in acute hypoxia, which serves a dual purpose: it allows for exon skipping and triggers the dispersal of nuclear speckles. Our data suggest that cells use dispersal of nuclear speckles to reprogram their gene expression during hypoxic adaptation and that SRSF6 plays an important role in cohesion of nuclear speckles. Down-regulation of SRSF6 is achieved through inclusion of a poison cassette exon (PCE) promoted by SRSF4. Removing the PCE 3' splice site using CRISPR/Cas9 abolishes SRSF6 reduction in hypoxia. Aberrantly high SRSF6 levels in hypoxia attenuate hypoxia-mediated AS and impair dispersal of nuclear speckles. As a consequence, proliferation and genomic instability are increased, while the stress response is suppressed. The SRSF4-PCE-SRSF6 hypoxia axis is active in different cancer types, and high SRSF6 expression in hypoxic tumors correlates with a poor prognosis. We propose that the ultra-conserved PCE of SRSF6 acts as a tumor suppressor and that its inclusion in hypoxia is crucial to reduce SRSF6 levels. This may prevent tumor cells from entering the metastatic route of hypoxia adaptation.

Endocannabinoid-Binding Receptors as Drug Targets.

Cannabis plant has been used from ancient times with therapeutic purposes for treating human pathologies, but the identification of the cellular and molecular mechanisms underlying the therapeutic properties of the phytocannabinoids, the active compounds in this plant, occurred in the last years of the past century. In the late 1980s and early 1990s, seminal studies demonstrated the existence of cannabinoid receptors and other elements of the so-called endocannabinoid system. These G protein-coupled receptors (GPCRs) are a key element in the functions assigned to endocannabinoids and appear to serve as promising pharmacological targets. They include CB1, CB2, and GPR55, but also non-GPCRs can be activated by endocannabinoids, like ionotropic receptor TRPV1 and even nuclear receptors of the PPAR family. Their activation, inhibition, or simply modulation have been associated with numerous physiological effects at both central and peripheral levels, which may have therapeutic value in different human pathologies, then providing a solid experimental explanation for both the ancient medicinal uses of Cannabis plant and the recent advances in the development of cannabinoid-based specific therapies. This chapter will review the scientific knowledge generated in the last years around the research on the different endocannabinoid-binding receptors and their signaling mechanisms. Our intention is that this knowledge may help readers to understand the relevance of these receptors in health and disease conditions, as well as it may serve as the theoretical basis for the different experimental protocols to investigate these receptors and their signaling mechanisms that will be described in the following chapters.

Estimulación temprana en el hogar de infantes que asisten a un centro infantil / Home-based early stimulation for infants attending a daycare center

Introducción: En el ambiente del hogar se propician estilos de crianza, aprendizajes, actividades, experiencias y estímulos que modulan la estimulación del niño(a). Objetivo: Identificar el grado de estimulación temprana y su relación con variables de tipología familiar y participación en el cuidado de niños(as) entre 1 y 4 años de un centro de desarrollo infantil en Pereira, Colombia, en 2019. Métodos: Estudio transversal. Se realizó un muestreo tipo censo que incluyó a todos los niños y cuidadores, que cumplían con los criterios de selección (niños sin antecedente de patologías neurológicas, consentimiento informado de cuidadores). Se midieron variables sociodemográficas y de tipología familiar. Se empleó el Inventario de estimulación temprana en el hogar HOME45 (Home Observation for Measurement of the Environment). Se realizó análisis univariado y bivariado. Para la asociación entre predictores y el puntaje global de estimulación temprana (desenlace: alta/media/baja) se efectuó una regresión logística ordinal. Resultados: Participaron 76 diadas madre-hijo. La mediana de edad de los niños fue 36 meses (RIQ=11, 12-48). El cuidado diario fue brindado en un 67% por la madre. Se evidenció una alta estimulación en el 50% de las diadas. Los predictores que redujeron la probabilidad de estimulación alta fueron (p<0,05): hábito de lectura (No, RP=0,29 (0,09-0,87)), participación en fiestas infantiles (No, RP=0,24 (0,07­0,79)), edad del cuidador (mayor a 36 años, RP=0,95 (0,92-1,00)), estrategia de corrección (castigo verbal o físico, RP=0,16 (0,03-0,98)). Conclusión: Corregir al niño mediante diálogo, incentivar la lectura y participar de fiestas infantiles, además de tener un cuidador menor de 35 años, fueron variables que incrementaron la probabilidad de presentar una alta estimulación.

Introduction: Home environment fosters parenting styles, learning, activities, experiences, and stimuli modulating children's stimulation. Objective: To identify the degree of home-based early stimulation and its relationship with family variables and participation in the care of children aged 1 to 4 years attending a daycare center in Pereira, Colombia in 2019. Materials and Methods: A cross-sectional study was conducted by means of a census sampling including all children and caregivers who met the selection criteria (children with no history of neurological disorders and caregiver informed consent.) Sociodemographic and family variables were also measured. The Early Childhood HOME45 (Home Observation for Measurement of the Environment) inventory was administered. Univariate and bivariate analyses were carried out. Ordinal logistic regression was performed for associating predictors and total early stimulation score (high/medium/low). Results: The average age of children was 36 months (RIQ=11, 12-48). 67% of mothers gave children daily care. High stimulation was observed for 50% of the dyads. Predictors that reduced the probability of high stimulation (p<0.05) were reading habit (No, PR=0.29 (0.09-0.87)), participation in children's parties (No, PR=0.24 (0.07-0.79)), caregiver age (older than 36 years old, PR=0.95 (0.92-1.00)), child discipline strategy applied (verbal or physical abuse) (PR=0.16 (0.03-0.98)). Conclusions: Educating children through dialogue, encouraging reading and participating in children's parties, as well as having a caregiver under 35 years of age, were variables that increased the probability of high stimulation in children.

Introdução: O ambiente familiar fomenta estilos de criação, aprendizagem, atividades, experiências e estímulos que modulam a estimulação das crianças. Objetivo: Identificar o grau de estimulação precoce e sua relação com variáveis de tipologia familiar e participação no cuidado de crianças entre 1 e 4 anos de idade em um centro de desenvolvimento infantil em Pereira, Colômbia, em 2019. Métodos: Estudo de corte transversal. Foi realizada uma amostragem tipo censo que incluiu todas as crianças e cuidadores que preenchiam os critérios de seleção (crianças sem histórico de patologias neurológicas, consentimento informado dos cuidadores). As variáveis sociodemográficas e de tipologia familiar foram medidas. O inventário de estimulação precoce HOME45 (Home Observation for Measurement of the Environment) foi utilizado. Foram realizadas análises univariadas e bivariadas. Para a associação entre os preditores e a pontuação global de estimulação precoce (resultado: alto/médio/baixo), foi realizada uma regressão logística ordinal. Resultados: Setenta e seis díades mãe-filho participaram. A idade média das crianças era de 36 meses (RIQ=11, 12-48). O cuidado diário era de 67% fornecido pela mãe. A alta estimulação era evidente em 50% das díades. Os preditores que reduziram a probabilidade de alta estimulação foram (p<0,05): hábito de leitura (Não, PR=0,29 (0,09-0,87)), participação em festas infantis (Não, PR=0,24 (0,07-0,79)), idade do cuidador (mais de 36 anos, PR=0,95 (0,92-1,00)), estratégia de correção (castigo verbal ou físico, PR=0,16 (0,03-0,98)). Conclusão. Corrigir a criança através do diálogo, incentivar a leitura e a participação em festas infantis, assim como ter um cuidador com menos de 35 anos de idade, foram variáveis que aumentaram a probabilidade de apresentar um alto nível de estimulação.

The Incredible Years Parenting and Child Treatment Programs: A Randomized Controlled Trial in a Child Welfare Setting in Spain

Incredible Years (IY) is a well-established multicomponent group-based program designed to promote young children’s emotional and social competence, to prevent and treat child behavioral and emotional problems, and to improve parenting practices and the parent-child relationship. This study presents the first randomized controlled trial carried out in Spain to test the effectiveness of the Incredible Years Basic Parenting and Small Group Dinosaur Programs in a sample of families involved in child welfare due to substantiated or risk for child maltreatment. One hundred and eleven families with 4- to 8-year-old children were randomly allocated to IY or to a control group who received standard services. Baseline, post-intervention, and 12-month follow-up assessments were compared. Results showed that compared to the control group, the IY intervention made a significant positive difference in parents’ observed and reported use of praise, and a significant reduction in reported use of inconsistent discipline, parenting stress, depressive symptomatology, and perception of child behavior problems. A full serial mediation effect was found between participation in IY, changes in parenting practices, subsequent parenting stress reduction, and both final child abuse potential reduction and perception of child behavior problems. No moderating influence on IY effects was found. Findings provide evidence that transporting the IY Basic Parenting and the Small Group Dinosaur Programs with fidelity is feasible in Child Welfare Services in Spain. (AU)

Incredible Years (IY) es un programa de intervención grupal multicomponente con base empírica sólida diseñado para promover la competencia emocional y social de los niños y niñas, prevenir y tratar problemas emocionales y comportamentales y mejorar las prácticas parentales y la relación paterno-filial. Este estudio presenta el primer ensayo controlado aleatorizado llevado a cabo en España para probar la eficacia de los subprogramas dirigidos a padres y madres y a niños y niñas en familias atendidas en los Servicios Sociales de Infancia debido a la existencia o riesgo de maltrato infantil. Ciento once familias con niños y niñas de 4 a 8 años fueron asignadas al azar a IY o a un grupo control que recibió los servicios de apoyo habituales. Se llevaron a cabo evaluaciones preintervención, post-intervención (6 meses) y de seguimiento (12 meses). Los resultados mostraron que, en comparación con el grupo control, los padres y madres del grupo IY informaron de más cambios positivos significativos en el uso de elogios e incentivos y una reducción significativa en el uso de disciplina inconsistente, estrés parental, sintomatología depresiva y percepción de problemas de conducta en sus hijos e hijas. Se encontró un efecto de mediación serial entre la participación en IY, cambios en las prácticas parentales, la posterior reducción del estrés parental y la reducción final del potencial de maltrato y de la percepción de problemas de conducta en los hijos e hijas. No se identificó ninguna variable moderadora en los efectos de IY. Los resultados proporcionan evidencia de que es factible aplicar el programa IY con fidelidad en los Servicios Sociales de Infancia en España. (AU)

Correlation of TP53 (rs1625895), TP73 (rs3765730), MMP9 (rs17576), and MTHFR (rs868014) polymorphisms with low ovarian reserve.

OBJECTIVE: To investigate the influence of the Single Nucleotide Polymorphisms (SNPs) TP53 rs1625895, TP73 rs3765730, MMP9 rs17576, and MTHFR rs868014 on ovarian reserve (OR) in infertile patients. STUDY DESIGN: A prospective cross-sectional study was carried out in 145 infertile women. The patients were divided into two groups according to ovarian reserve, characterized by association between AMH levels and AFC:After patient distribution, both groups were compared (LOR X NOR) regarding the genotypes of the SNPs TP53 T/C rs1625895, TP73 G/A rs3765730, MMP9 Gln/Arg rs17576, and MTHFR A/G rs868014. RESULT(S): The frequency of the TP53-T/T genotype was greater in the LOR and the TP53-C/C genotype was more frequent in patients with NOR. This association was confirmed by the frequency of alleles, where the presence of the T allele was significantly higher in patients who exhibited LOR (P = 0.0003). The frequency of the TP73-G/G genotype and of the G allele was higher in the LOR group (P = 0.01). Considering the MMP9 gene, the frequency of the Gln/Gln genotype was higher in the LOR group. However, the Gln/Arg genotype and the Arg allele prevailed in the NOR group (P = 0.006). The frequency of the MTHFR-A/A genotype was higher in the LOR group, whereas that of the MTHFR-GG genotype was higher in the NOR group. The presence of allele A was significantly higher in the LOR group (P = 0.002). The regression analysis shows that patients who present the TP53-T/T, TP73-G/G, MMP9-Gln/Gln, and MTHFR-A/A genotypes are 3.6X, 3.1X, 3.2X, and 3.7X more likely of having LOR, respectively. In addition, the association of the TP53/TT + TP73/GG genotypes increased the chance of women being included in the LOR group in 5.7-fold. CONCLUSION(S): The genotypes TP53-T/T, TP73-G/G, MMP9-Gln/Gln, and MTHFR-A/A increase the chance of women to exhibit LOR. These polymorphisms could be useful as genetic markers of low ovarian reserve in infertile patients.

The Incredible Years Parenting and Child Treatment Programs: A Randomized Controlled Trial in a Child Welfare Setting in Spain.

Incredible Years (IY) is a well-established multicomponent group-based program designed to promote young children's emotional and social competence, to prevent and treat child behavioral and emotional problems, and to improve parenting practices and the parent-child relationship. This study presents the first randomized controlled trial carried out in Spain to test the effectiveness of the Incredible Years Basic Parenting and Small Group Dinosaur Programs in a sample of families involved in child welfare due to substantiated or risk for child maltreatment. One hundred and eleven families with 4- to 8-year-old children were randomly allocated to IY or to a control group who received standard services. Baseline, post-intervention, and 12-month follow-up assessments were compared. Results showed that compared to the control group, the IY intervention made a significant positive difference in parents' observed and reported use of praise, and a significant reduction in reported use of inconsistent discipline, parenting stress, depressive symptomatology, and perception of child behavior problems. A full serial mediation effect was found between participation in IY, changes in parenting practices, subsequent parenting stress reduction, and both final child abuse potential reduction and perception of child behavior problems. No moderating influence on IY effects was found. Findings provide evidence that transporting the IY Basic Parenting and the Small Group Dinosaur Programs with fidelity is feasible in Child Welfare Services in Spain.

Incredible Years (IY) es un programa de intervención grupal multicomponente con base empírica sólida diseñado para promover la competencia emocional y social de los niños y niñas, prevenir y tratar problemas emocionales y comportamentales y mejorar las prácticas parentales y la relación paterno-filial. Este estudio presenta el primer ensayo controlado aleatorizado llevado a cabo en España para probar la eficacia de los subprogramas dirigidos a padres y madres y a niños y niñas en familias atendidas en los Servicios Sociales de Infancia debido a la existencia o riesgo de maltrato infantil. Ciento once familias con niños y niñas de 4 a 8 años fueron asignadas al azar a IY o a un grupo control que recibió los servicios de apoyo habituales. Se llevaron a cabo evaluaciones preintervención, post-intervención (6 meses) y de seguimiento (12 meses). Los resultados mostraron que, en comparación con el grupo control, los padres y madres del grupo IY informaron de más cambios positivos significativos en el uso de elogios e incentivos y una reducción significativa en el uso de disciplina inconsistente, estrés parental, sintomatología depresiva y percepción de problemas de conducta en sus hijos e hijas. Se encontró un efecto de mediación serial entre la participación en IY, cambios en las prácticas parentales, la posterior reducción del estrés parental y la reducción final del potencial de maltrato y de la percepción de problemas de conducta en los hijos e hijas. No se identificó ninguna variable moderadora en los efectos de IY. Los resultados proporcionan evidencia de que es factible aplicar el programa IY con fidelidad en los Servicios Sociales de Infancia en España.

Preclinical Investigation in Neuroprotective Effects of the GPR55 Ligand VCE-006.1 in Experimental Models of Parkinson's Disease and Amyotrophic Lateral Sclerosis.

Cannabinoids act as pleiotropic compounds exerting, among others, a broad-spectrum of neuroprotective effects. These effects have been investigated in the last years in different preclinical models of neurodegeneration, with the cannabinoid type-1 (CB1) and type-2 (CB2) receptors concentrating an important part of this research. However, the issue has also been extended to additional targets that are also active for cannabinoids, such as the orphan G-protein receptor 55 (GPR55). In the present study, we investigated the neuroprotective potential of VCE-006.1, a chromenopyrazole derivative with biased orthosteric and positive allosteric modulator activity at GPR55, in murine models of two neurodegenerative diseases. First, we proved that VCE-006.1 alone could induce ERK1/2 activation and calcium mobilization, as well as increase cAMP response but only in the presence of lysophosphatidyl inositol. Next, we investigated this compound administered chronically in two neurotoxin-based models of Parkinson's disease (PD), as well as in some cell-based models. VCE-006.1 was active in reversing the motor defects caused by 6-hydroxydopamine (6-OHDA) in the pole and the cylinder rearing tests, as well as the losses in tyrosine hydroxylase-containing neurons and the elevated glial reactivity detected in the substantia nigra. Similar cytoprotective effects were found in vitro in SH-SY5Y cells exposed to 6-OHDA. We also investigated VCE-006.1 in LPS-lesioned mice with similar beneficial effects, except against glial reactivity and associated inflammatory events, which remained unaltered, a fact confirmed in BV2 cells treated with LPS and VCE-006.1. We also analyzed GPR55 in these in vivo models with no changes in its gene expression, although GPR55 was down-regulated in BV2 cells treated with LPS, which may explain the lack of efficacy of VCE-006.1 in such an assay. Furthermore, we investigated VCE-006.1 in two genetic models of amyotrophic lateral sclerosis (ALS), mutant SOD1, or TDP-43 transgenic mice. Neither the neurological decline nor the deteriorated rotarod performance were prevented with this compound, and the same happened with the elevated microglial and astroglial reactivities, albeit modest spinal motor neuron preservation was achieved in both models. We also analyzed GPR55 in these in vivo models and found no changes in both TDP-43 transgenic and mSOD1 mice. Therefore, our findings support the view that targeting the GPR55 may afford neuroprotection in experimental PD, but not in ALS, thus stressing the specificities for the development of cannabinoid-based therapies in the different neurodegenerative disorders.

Estrategias lúdicas para mejorar la higiene bucal en una población con síndrome de Down / Playful strategies to improve oral health hygiene in a population with down síndrome / Estratégias lúdicas para melhorar a higiene bucal em um povoado com síndrome de Down

Resumen Objetivos: el objetivo de la investigación fue implementar estrategias lúdicas para mejorar la higiene oral de la población con Síndrome de Down en la Fundación CINDES de la ciudad de Pereira en el periodo 2017-2. Métodos: la investigación adoptó un enfoque cualitativo analizando el mundo social de acuerdo con su propia realidad y experiencia de las 12 personas diagnosticadas con SD y sus padres o cuidadores observándolos en su entorno natural y analizando sus habilidades previas acerca de las técnicas de higiene oral. El método de investigación fue la investigación acción y se usaron estrategias lúdicas, la observación y diarios de campo como técnicas de investigación. Resultados: se evidenció en la mayoría de la población con SD y sus padres o cuidadores que el nivel de conocimiento inicial era regular por el tiempo insuficiente durante el cepillado, falta de uso de la seda dental y mal comportamiento durante el cepillado; con la aplicación de estrategias lúdicas se logró que las personas con síndrome de Down aprendieran a identificar las estructuras de la cavidad oral, los implementos de higiene oral y los riesgos de no realizar un cuidado bucal adecuado, además, mejoraron la ejecución de la técnica de cepillado y se generó cierta autonomía. Conclusiones: se logró mostrar la efectividad de la implementación de estrategias lúdicas como herramienta crucial para lograr un aprendizaje significativo.

Abstract Objectives: The objective of this research was to implement playful strategies to improve the oral hygiene of the population with Down Syndrome (DS) in the CINDES Foundation in the city of Pereira during the 2017-2 period. Method: The research adopted a qualitative approach analyzing the social world according to the own reality and experience of 12 people diagnosed with DS and their parents or caregivers, observing them in their natural environment and analyzing their previous skills regarding oral hygiene techniques. The method applied was action research and playful strategies. Observation and field diaries were used as research techniques. Results: In the majority of the population with DS and their parents or caregivers, it was evidenced that their initial level of knowledge was mediocre due to insufficient time during brushing, lack of use of dental floss and bad behavior during brushing. With the application of playful strategies, it was possible for people with Down Syndrome to learn to identify the structures of the oral cavity, of oral hygiene implements and the risks of not performing adequate oral care. In addition, they improved the execution of the brushing technique and some autonomy was generated. Conclusions: It was possible to show the effectiveness of the implementation of playful strategies as an crucial tool to achieve meaningful learning.

Resumo Objetivos: o objetivo da pesquisa foi realizar estratégias lúdicas para melhorar a higiene oral num grupo com Síndrome de Down na Fundação CINDES da cidade de Pereira no período 2017-2. Métodos: a pesquisa adoptou um enfoque qualitativo analisando o mundo social de acordo com sua própria realidade e experiência das 12 pessoas diagnosticadas com SD e seus pais ou cuidadores observando-os em seu ambiente natural e analisando suas habilidades previas acerca das técnicas de higiene oral. O método de pesquisa foi a pesquisa ação e se usaram estratégias lúdicas, a observação e diários de campo como técnicas de pesquisa. Resultados: evidenciou-se na maioria deste grupo com SD e seus pais ou cuidadores que no nível de conhecimento inicial era regular pelo tempo insuficiente durante o escovado, falta de uso do fio dental e mal comportamento durante a escovação; com a aplicação de estratégias lúdicas se conseguiu que as pessoas com síndrome de Down aprenderam a identificar as estruturas da cavidade oral, o kit de higiene oral e os riscos de não realizar um cuidado bucal adequado, além disso melhora a execução da técnica de escovação e se gerou certa autonomia. Conclusões: conseguiu-se amostrar a efetividade da implementação de estratégias lúdicas como ferramenta crucial para lograr uma aprendizagem significativa.

Development of High-Level Daptomycin Resistance in Abiotrophia and Granulicatella Species Isolates from Patients with Infective Endocarditis.

Abiotrophia and Granulicatella species are fastidious organisms, representing the causative agents of ∼1% to 3% of cases of infective endocarditis (IE). Little is known about the optimal antibiotic treatment for these species, and daptomycin has been suggested as a therapeutic option. We describe the antimicrobial profiles of Abiotrophia and Granulicatella IE isolates, investigate high-level daptomycin resistance (HLDR) development, and evaluate daptomycin activity in combination therapy. In vitro studies with 16 IE strains (6 Abiotrophia defectiva strains, 9 Granulicatella adiacens strains, and 1 G. elegans strain) were performed using microdilution to determine MICs and time-kill methodology to evaluate combination therapy. Daptomycin nonsusceptibility (DNS) (MIC ≥ 2 mg/liter) and HLDR (MIC ≥ 256 mg/liter) were based on existing Clinical and Laboratory Standards Institute (CLSI) breakpoints for viridans group streptococci. All isolates were susceptible to vancomycin: G. adiacens was more susceptible to penicillin and ampicillin than A. defectiva (22% versus 0% and 67% versus 33%) but less susceptible to ceftriaxone and daptomycin (56% versus 83% and 11% versus 50%). HLDR developed in both A. defectiva (33%) and G. adiacens (78%) after 24 h of exposure to daptomycin. Combination therapy did not prevent the development of daptomycin resistance with ampicillin (2/3 strains), gentamicin (2/3 strains), ceftriaxone (2/3 strains), or ceftaroline (2/3 strains). Once developed, HLDR was stable for a prolonged time (>3 weeks) in G. adiacens, whereas in A. defectiva, HLDR reversed to the baseline MIC at day 10. This study is the first to demonstrate rapid HLDR development in Abiotrophia and Granulicatella species in vitro. Resistance was stable, and most combination therapies did not prevent it.

Neuroprotection with the Cannabidiol Quinone Derivative VCE-004.8 (EHP-101) against 6-Hydroxydopamine in Cell and Murine Models of Parkinson's Disease.

The 3-hydroxyquinone derivative of the non-psychotrophic phytocannabinoid cannabigerol, so-called VCE-003.2, and some other derivatives have been recently investigated for neuroprotective properties in experimental models of Parkinson's disease (PD) in mice. The pharmacological effects in those models were related to the activity on the peroxisome proliferator-activated receptor-γ (PPAR-γ) and possibly other pathways. In the present study, we investigated VCE-004.8 (formulated as EHP-101 for oral administration), the 3-hydroxyquinone derivative of cannabidiol (CBD), with agonist activity at the cannabinoid receptor type-2 (CB2) receptor in addition to its activity at the PPAR-γ receptor. Studies were conducted in both in vivo (lesioned-mice) and in vitro (SH-SY5Y cells) models using the classic parkinsonian neurotoxin 6-hydroxydopamine (6-OHDA). Our data confirmed that the treatment with VCE-004.8 partially reduced the loss of tyrosine hydroxylase (TH)-positive neurons measured in the substantia nigra of 6-OHDA-lesioned mice, in parallel with an almost complete reversal of the astroglial (GFAP) and microglial (CD68) reactivity occurring in this structure. Such neuroprotective effects attenuated the motor deficiencies shown by 6-OHDA-lesioned mice in the cylinder rearing test, but not in the pole test. Next, we explored the mechanism involved in the beneficial effect of VCE-004.8 in vivo, by analyzing cell survival in cultured SH-SY5Y cells exposed to 6-OHDA. We found an important cytoprotective effect of VCE-004.8 at a concentration of 10 µM, which was completely reversed by the addition of antagonists, T0070907 and SR144528, aimed at blocking PPAR-γ and CB2 receptors, respectively. The treatment with T0070907 alone only caused a partial reversal, whereas SR144528 alone had no effect, indicating a major contribution of PPAR-γ receptors in the cytoprotective effect of VCE-004.8 at 10 µM. In summary, our data confirmed the neuroprotective potential of VCE-004.8 in 6-OHDA-lesioned mice, and in vitro studies confirmed a greater relevance for PPAR-γ receptors rather than CB2 receptors in these effects.

(+)-trans-Cannabidiol-2-hydroxy pentyl is a dual CB1R antagonist/CB2R agonist that prevents diabetic nephropathy in mice.

Natural cannabidiol ((-)-CBD) and its derivatives have increased interest for medicinal applications due to their broad biological activity spectrum, including targeting of the cannabinoid receptors type 1 (CB1R) and type 2 (CB2R). Herein, we synthesized the (+)-enantiomer of CBD and its derivative (+)-CBD hydroxypentylester ((+)-CBD-HPE) that showed enhanced CB1R and CB2R binding and functional activities compared to their respective (-) enantiomers. (+)-CBD-HPE Ki values for CB1R and CB2R were 3.1 ± 1.1 and 0.8 ± 0.1 nM respectively acting as CB1R antagonist and CB2R agonist. We further tested the capacity of (+)-CBD-HPE to prevent hyperglycemia and its complications in a mouse model. (+)-CBD-HPE significantly reduced streptozotocin (STZ)-induced hyperglycemia and glucose intolerance by preserving pancreatic beta cell mass. (+)-CBD-HPE significantly reduced activation of NF-κB by phosphorylation by 15% compared to STZ-vehicle mice, and CD3+ T cell infiltration into the islets was avoided. Consequently, (+)-CBD-HPE prevented STZ-induced apoptosis in islets. STZ induced inflammation and kidney damage, visualized by a significant increase in plasma proinflammatory cytokines, creatinine, and BUN. Treatment with (+)-CBD-HPE significantly reduced 2.5-fold plasma IFN-γ and increased 3-fold IL-5 levels compared to STZ-treated mice, without altering IL-18. (+)-CBD-HPE also significantly reduced creatinine and BUN levels to those comparable to healthy controls. At the macroscopy level, (+)-CBD-HPE prevented STZ-induced lesions in the kidney and voided renal fibrosis and CD3+ T cell infiltration. Thus, (+)-enantiomers of CBD, particularly (+)-CBD-HPE, have a promising potential due to their pharmacological profile and synthesis, potentially to be used for metabolic and immune-related disorders.

Dyadic Parent-Child Interaction Coding System (DPICS): Factorial Structure and Concurrent Validity.

BACKGROUND: Comprehensive family assessments in Child Protection Services should include instruments with suitable psychometric characteristics. The present study aims to provide initial evidence of the factorial structure and other psychometric properties of the Dyadic Parent-Child Interaction Coding System (DPICS). METHOD: Participants were 80 mother-child dyads with children aged 4-8 who received family support from Child Protection Services in Spain. RESULTS: Confirmatory factor analysis showed good fit for a four-factor solution (Praise, Questions, Clear commands and Negative talk) with 15 items. Inter-rater reliability indices were optimal. Evidence of concurrent validity found that DPICS factors were related to self-reported parenting and teacher-informed child behavior problems. CONCLUSIONS: This study provides preliminary evidence of the DPICS's psychometric properties for assessing mother-child interaction within Child Protection Services. Further research with larger samples of mother-child and father-child dyads is still needed to confirm the four-factor solution.

Analogues of cannabinoids as multitarget drugs in the treatment of Alzheimer's disease.

Given that neuronal degeneration in Alzheimer's disease (AD) is caused by the combination of multiple neurotoxic insults, current directions in the research of novel therapies to treat this disease attempts to design multitarget strategies that could be more effective than the simply use of acetylcholinesterase inhibitors; currently, the most used therapy for AD. One option, explored recently, is the synthesis of new analogues of cannabinoids that could competitively inhibit the acetylcholinesterase (AChE) enzyme and showing the classic neuroprotective profile of cannabinoid compounds. In this work, molecular docking has been used to design some cannabinoid analogues with such multitarget properties, based on the similarities of donepezil and Δ9-tetrahydrocannabinol. The analogues synthesized, compounds 1 and 2, demonstrated to have two interesting characteristics in different in vitro assays: competitive inhibition of AChE and competitive antagonism at the CB1/CB2 receptors. They are highly lipophilic, highlighting that they could easily reach the CNS, and apparently presented a low toxicity. These results open the door to the synthesis of new compounds for a more effective treatment of AD.