[Ten years of the prefrontal symptoms inventory (PSI). A systematic review]. / Diez años del inventario de síntomas prefrontales (ISP). Una revisión sistemática.

INTRODUCTION: Ten years ago, Revista de Neurologia published the validation of a new free tool: the Prefrontal Symptoms Inventory (PSI), from which an abbreviated version (PSI-20) was subsequently extracted. Over this decade, authors have demonstrated its excellent psychometric properties and clinical usefulness. This systematic review, conducted in accordance with the PRISMA statement, aims to analyse the body of research that has used the PSI or PSI-20 in order to assess its relevance in other research teams, other clinical populations and even other cultures. MATERIALS AND METHODS: A search was conducted to find articles written in Spanish, English, French and Portuguese that have used the inventory to carry out empirical research. Finally, 56 articles were selected. RESULTS: The results show that the PSI and the PSI-20 have been widely used in Spain as well as in other Spanish-speaking countries (Argentina, Chile, Colombia, Cuba, Ecuador or Venezuela) and employed to a moderate extent in non-Spanish-speaking countries (Belgium, Brazil, Sweden or Switzerland). The clinical populations in which they have been used range from acquired brain injury and degenerative dementias to chronic pain, fibromyalgia, addictive behaviours or personality disorders. Given their versatility, they have also been used with the general population, including prison inmates, women in rural areas, university students or to study cognitive reserve. CONCLUSIONS: The PSI and PSI-20 are useful instruments for research and clinical use, and the next challenge is to validate an English version, which is currently being worked on.

TITLE: Diez años del inventario de síntomas prefrontales (ISP). Una revisión sistemática.Introducción. Hace 10 años, Revista de Neurología publicaba la validación de una nueva herramienta gratuita: el inventario de síntomas prefrontales (ISP), de la que posteriormente se extrajo su versión abreviada (ISP-20). Durante esta década, los autores han acreditado sus excelentes propiedades psicométricas y su utilidad clínica. La presente revisión sistemática, sometida a la declaración PRISMA, tiene el objetivo de analizar el corpus de investigación que ha utilizado el ISP o el ISP-20, para valorar su trascendencia en otros equipos de investigación, en otras poblaciones clínicas e incluso en otras culturas. Materiales y métodos. Se buscaron artículos que hayan utilizado el inventario para realizar trabajos empíricos, en español, inglés, francés y portugués. Finalmente, se seleccionaron 56 trabajos. Resultados. Los resultados muestran que el ISP y el ISP-20 han tenido un uso elevado en España, así como en otros países de habla hispana (Argentina, Chile, Colombia, Cuba, Ecuador o Venezuela), y un uso moderado en países de habla no hispana (Bélgica, Brasil, Suecia o Suiza). Las poblaciones clínicas en las que se han utilizado abarcan desde el daño cerebral adquirido y las demencias degenerativas hasta el dolor crónico, la fibromialgia, las conductas adictivas o los trastornos de la personalidad. Dada su versatilidad, también se han usado con población general, incluyendo población reclusa, mujeres en entorno rural, estudiantes universitarios o para el estudio de la reserva cognitiva. Conclusiones. El ISP y el ISP-20 son instrumentos útiles para la investigación y la clínica, cuyo siguiente desafío es la validación de una versión en inglés, en la que se está trabajando.

Self-collected versus clinician-collected cervical samples for the detection of HPV infections by 14-type DNA and 7-type mRNA tests.

BACKGROUND: HPV self-sampling has been widely supported by the scientific community following a strong body of literature on the subject. Self-sampling is important in cervical cancer screening as it has been shown to improve participation. It is well documented that HPV-testing has proven superior to cytology with regards to sensitivity in detection of CIN and cancer. The value of self-collected samples is reliant on the quality of the molecular testing performed, as well as the patients' preference in sampling procedure and compliance to follow up on positive test results. Due to the incompatibility of self-samples and cytology, triage of HPV-DNA positives by testing for molecular biomarkers is highly warranted. METHODS: Our objective was to compare the detection rate of genital Human Papillomavirus (HPV) infection in self- and clinician-collected samples by a 14-type HPV-DNA test and a 7-type mRNA E6/E7 test. RESULTS: Five hundred five women were recruited. Each study participant had two sample collection procedures performed upon the same visit, alternating order in execution of the self-collection or the clinician-taken procedure first or second, 1010 samples in total. HPV-DNA prevalence was 22.8% in self-collected versus 19.2% in clinician-collected samples (P = 0.19). Overexpression of mRNA E6/E7 from 7 HPV types was 7.1 and 6.3%, respectively (P = 0.71). The difference between HPV-DNA and HPV-mRNA positivity rates were statistically significant in both self-collected (22.8% versus 7.1%, P < 0.001) and clinician-collected samples (19.2% versus 6.3%, P < 0.001). Overall agreement between the two collection methods was fair, with a concordance rate of 78.2% (390/505), k = 0.34 (95% CI: 0.25-0.44), P < 0.001, for the HPV-DNA test and 92.5% (467/505), k = 0.40 (95% CI, 0.25-0.56), P < 0.001, for the mRNA test, respectively. 96.8% of the participants reported they felt confident carrying out the self-collection themselves, and 88.8% reported no discomfort at all performing the procedure. CONCLUSIONS: This comparative study of two sampling methods reports fair agreement of HPV positivity rates between the self-collected and clinician-collected specimens using Abbott hrHPV and PreTect HPV-Proofer'7 tests. Only one third of HPV-DNA positive women had overexpression of mRNA E6/E7. TRIAL REGISTRATION: ISRCTN77337300 .

Nonparametric analysis of casein complex genes' epistasis and their effects on phenotypic expression of milk yield and composition in Murciano-Granadina goats.

Improving knowledge on the causative polymorphisms or genes regulating the expression of milk quantitative and qualitative traits and their interconnections plays a major role in dairy goat breeding programs and genomic research. This information enables optimization of predictive and selective tools, to obtain better-performing animals to help satisfy market demands more efficiently. Goat milk casein proteins (αS1, αS2, ß, and κ) are encoded by 4 loci (CSN1S1, CSN1S2, CSN2, and CSN3) clustered within 250 kb on chromosome 6. Among the statistical methods used to identify epistatic interactions in genome-wide qualitative association studies (GWAS), gene-based methods have recently grown in popularity due to their better statistical power and biological interpretability. However, most of these methods make strong assumptions about the magnitude of the relationships between SNP and phenotype, limiting statistical power. Thus, the aims of this study were to quantify the epistatic relationships among 48 SNP in the casein complex on the expression of milk yield and components (fat, protein, dry matter, lactose, and somatic cells) in Murciano-Granadina goats, to explain the qualitative nature of the SNP used to quantify the genotypes produced as a result. Categorical principal component analysis (CATPCA) was used to delimit and group the number of SNP studied depending on their implications in the explanation of milk yield and components variability. Afterward, nonlinear canonical correlation analysis was used to identify relationships among and within the SNP groups detected by CATPCA. Our results suggest that 79.65% of variability in the traits evaluated may be ascribed to the epistatic relationships across and within 7 SNP groups. Two partially overlapping groups of epistatically interrelated SNP were detected: one group of 21 SNP, explaining 57.56% of variability, and another group of 20 SNP, explaining 42.43% (multiple fit ≥ 0.1). Additionally, SNP18, 32, and 36 (CSN1S2, CSN1S1, and CSN2 loci, respectively) were the most significant SNP to explain intragroup epistatic variability (component loading > |0.5|). Conclusively, milk yield and quality may not only depend on the specific casein gene pool of individuals, but may also be relevantly conditioned by the relationships set across and within such genes. Hence, studying epistasis in isolation may be crucial to optimize selective practices for economically important dairy traits.

Short-Term Hemodynamic and Electrophysiological Effects of Cardiac Resynchronization by Left Ventricular Septal Pacing.

BACKGROUND: Cardiac resynchronization therapy (CRT) is usually performed by biventricular (BiV) pacing. Previously, feasibility of transvenous implantation of a lead at the left ventricular (LV) endocardial side of the interventricular septum, referred to as LV septal (LVs) pacing, was demonstrated. OBJECTIVES: The authors sought to compare the acute electrophysiological and hemodynamic effects of LVs with BiV and His bundle (HB) pacing in CRT patients. METHODS: Temporary LVs pacing (transaortic approach) alone or in combination with right ventricular (RV) (LVs+RV), BiV, and HB pacing was performed in 27 patients undergoing CRT implantation. Electrophysiological changes were assessed using electrocardiography (QRS duration), vectorcardiography (QRS area), and multielectrode body surface mapping (standard deviation of activation times [SDAT]). Hemodynamic changes were assessed as the first derivative of LV pressure (LVdP/dtmax). RESULTS: As compared with baseline, LVs pacing resulted in a larger reduction in QRS area (to 73 ± 22 µVs) and SDAT (to 26 ± 7 ms) than BiV (to 93 ± 26 µVs and 31 ± 7 ms; both p < 0.05) and LVs+RV pacing (to 108 ± 37 µVs; p < 0.05; and 29 ± 8 ms; p = 0.05). The increase in LVdP/dtmax was similar during LVs and BiV pacing (17 ± 10% vs. 17 ± 9%, respectively) and larger than during LVs+RV pacing (11 ± 9%; p < 0.05). There were no significant differences between basal, mid-, or apical LVs levels in LVdP/dtmax and SDAT. In a subgroup of 16 patients, changes in QRS area, SDAT, and LVdP/dtmax were comparable between LVs and HB pacing. CONCLUSIONS: LVs pacing provides short-term hemodynamic improvement and electrical resynchronization that is at least as good as during BiV and possibly HB pacing. These results indicate that LVs pacing may serve as a valuable alternative for CRT.

[The role of the cognitive reserve in the cognitive recovery of patients who have suffered a severe addiction to substances]. / Papel de la reserva cognitiva en la recuperacion cognitiva de pacientes que han sufrido una adiccion grave a sustancias.

INTRODUCTION: Cognitive reserve has been shown to be a prognostic variable in cognitive recovery after brain damage. Few studies have addressed its role in the cognitive status after a sustained period of substance addiction. AIM: To analyse the modulating role of cognitive reserve in the relation between withdrawal time and the cognitive status of patients with severe substance addiction. PATIENTS AND METHODS: A total of 26 patients recovering from severe substance addiction were assessed using a neuropsychological assessment protocol and cognitive reserve questionnaires. Exploratory factor analysis is used to define the variables and linear regression analysis is employed to view the predictive relations. RESULTS: Three cognitive functioning factors are obtained: processing integrity, inhibitory control and verbal memory, as well as an overall reserve factor. In the regression models, predictive relations are found only in a model of a direct relation between withdrawal and verbal memory, and in a model of an independent relation between cognitive reserve and withdrawal time and verbal memory, but not in the modulation relationship or in other relations in the rest of the factors. CONCLUSION: The article discusses the role of the cognitive reserve as a mediator in the cognitive status of patients in a period of withdrawal after a serious addiction to substances. A relationship with memory is shown, but no modulation of the role of withdrawal time on that cognitive status is detected.

TITLE: Papel de la reserva cognitiva en la recuperacion cognitiva de pacientes que han sufrido una adiccion grave a sustancias.Introduccion. La reserva cognitiva resulta ser una variable de pronostico en la recuperacion cognitiva tras un daño cerebral. Pocos estudios han abordado su papel en el estado cognitivo tras un periodo sostenido de adiccion a sustancias. Objetivo. Analizar el papel modulador de la reserva cognitiva sobre la relacion entre el tiempo de abstinencia y el estado cognitivo de los pacientes con adiccion grave a sustancias. Pacientes y metodos. Se valora a un total de 26 pacientes en recuperacion tras una adiccion grave a sustancias con un protocolo de evaluacion neuropsicologica y cuestionarios de reserva cognitiva. Se emplea el analisis factorial exploratorio para conformar las variables y el analisis de regresion lineal para ver las relaciones predictivas. Resultados. Se obtienen tres factores de funcionamiento cognitivo: integridad de procesamiento, control inhibitorio y memoria verbal, asi como un factor global de reserva. En los modelos de regresion, solo se encuentran relaciones predictivas en un modelo de relacion directa entre la abstinencia y la memoria verbal, y en un modelo de relacion independiente entre la reserva cognitiva y el tiempo de abstinencia con la memoria verbal, pero no en la relacion de modulacion, ni en otras relaciones en el resto de los factores. Conclusion. Se debate el papel de la reserva cognitiva como mediadora en el estado cognitivo en los pacientes en periodo de abstinencia tras una adiccion grave a sustancias: muestra una relacion con la memoria, pero no una modulacion del papel del tiempo de abstinencia sobre ese estado cognitivo.

Modelling for the inheritance of multiple births and fertility in endangered equids: Determining risk factors and genetic parameters in donkeys (Equus asinus).

Multiple births or twinning in equids are dangerous, undesirable situations that compromise the life of the dam and resulting offspring. However, embryo vitrification and freezing techniques take advantage of individuals whose multiple ovulations allow flushing more fertilised embryos from the oviduct to be collected, increasing the productivity and profitability of reproductive techniques. Embryo preservation is especially important in highly endangered populations such as certain donkey (Equus asinus) breeds; for which conventional reproductive techniques have previously been deemed inefficient. For instance, becoming an effective alternative to artificial insemination with frozen semen to preserve the individuals' genetic material. The objective of this study was to examine the historical foaling records of Andalusian donkeys to estimate prevalence, risk factors, phenotypic and genetic parameters for multiple births, assessing the cumulative foal number born per animal, maximum foal number per birth and multiple birth number per animal. We designed a Bayesian General Animal Mixed Model with single records considering the 'fixed' effects of birth year, birth season, birth month, sex, farm, location, and husbandry system. Age was considered and included as a linear and quadratic covariate. Gibbs sampling reported heritability estimates ranging from 0.18 ±â€¯0.101 to 0.24 ±â€¯0.078. Genetic and phenotypic correlations ranged from 0.496 ±â€¯0.298 to 0.846 ±â€¯0.152 and 0.206 ±â€¯0.063 to 0.607 ±â€¯0.054, respectively. Predicted breeding values obtained enable the potential selection against/for these traits, offering a new perspective for donkey breeding and conservation.

Prefrontal symptomatology in People with Amyotrophic lateral Sclerosis: Clinical Utility and Psychometric Properties of Prefrontal Symptoms Inventory (PSI)

The Amyotrophic Lateral Sclerosis (ALS) is a multisystemic disorder. It is considered a neuromuscular disease but also involves cognitive (executive functions, social cognition, attention, memory and language), emotional or behavior changes in over 50% of the reported cases and to of frontotemporal diagnosis lobar degeneration of behavioral variant in up to 15% of the cases. For this reason, the presence of cognitive and motivational problems was analysed in a Spanish sample of ALS patients through the prefrontal symptoms inventory (PSI) to determine applicability in this disease STI. A sample of 31 patients with a potential ALS or definitive diagnostic criteria according to El Escorial was used. Obtained results ISP were compared with a sample of 31 healthy people in the same proportions of gender, age and education level. Obtained results showed a not significant difference between the two populations in the motivational factor problems, related to the depression symptomatology frequently associated with ALS. A significant positive correlation between age at diagnosis and the scale of the motivational problems was observed, with a not significant trend related to problems in the executive control and in social the behavior control and with the age at diagnosis, in the same sense with age at diagnosis. Therefore, it can be concluded that, despite the results obtained, emotional and behavioral deficits in ALS patients and symptoms related to frontotemporal dementia (among others, anosognosia or lack of consciousness symptoms) could have interfered in patient perception about their symptomatology

[Prefrontal symptoms in daily life: normalization and standardization of the Prefrontal Symptoms Inventory in the Spanish population]. / Sintomas prefrontales en la vida diaria: normalizacion y estandarizacion del inventario de sintomas prefrontales abreviado en poblacion española.

INTRODUCTION: The short Prefrontal Symptoms Inventory (PSI-20) is a questionnaire that investigates symptoms of prefrontal malfunctioning in daily life. It has been shown to have good psychometric properties and has been applied in the general population and clinical samples from Spain and other Spanish-speaking countries. AIMS: To normalise and standardise the PSI-20 in a broad sample of subjects of all ages in a Spanish population. SUBJECTS AND METHODS: The PSI-20 was administered to 4704 subjects: in one sample made up of 2474 subjects from the Spanish general population, over 18 years of age, and in another consisting of 2230 school-age subjects (15-17 years old), representative of the population of Madrid. RESULTS: The effect of the interaction of sex, age and level of education on the scores was observed, although the effect of level of education was low. As expected, the adolescents, still undergoing their process of maturation, obtained higher scores on all the subscales and the questionnaire as a whole. Females scored significantly higher on symptoms of poor emotional control, and males achieved higher scores on symptoms of poor control over social behaviour. Tables were developed differentiated by sex and for those above and below 18 years of age. CONCLUSION: The data presented allow us to interpret the scores obtained in the PSI-20 in the Spanish population, including subjects under 18 and adults.

TITLE: Sintomas prefrontales en la vida diaria: normalizacion y estandarizacion del inventario de sintomas prefrontales abreviado en poblacion española.Introduccion. El inventario de sintomas prefrontales abreviado (ISP-20) es un cuestionario que investiga sintomas de mal funcionamiento prefrontal en la vida diaria. Ha mostrado buenas propiedades psicometricas y se ha aplicado en poblacion general y muestras clinicas de España y otros paises de habla hispana. Objetivo. Normalizar y estandarizar el ISP-20 en una muestra amplia de sujetos de todas las edades en poblacion española. Sujetos y metodos. Se administro el ISP-20 a 4.704 sujetos: una muestra de 2.474 sujetos de poblacion general española, mayores de edad, y otra de 2.230 menores de edad escolarizados (15-17 años), representativa de la poblacion de Madrid. Resultados. Se observo el efecto de interaccion del sexo, la edad y el nivel educativo sobre las puntuaciones, aunque el nivel de estudios presenta un efecto bajo. Los adolescentes, como era de esperar por encontrarse en pleno proceso madurativo, obtuvieron mayores puntuaciones en todas las subescalas y el cuestionario en su conjunto. Las mujeres puntuaron significativamente mas en sintomas de mal control emocional, y los varones lo hicieron mas en sintomas de mal control de la conducta social. Se configuraron tablas diferenciadas por sexo y para menores y mayores de edad. Conclusion. Los datos presentados permiten interpretar las puntuaciones obtenidas en el ISP-20 en poblacion española, incluyendo los menores de edad y los adultos.

Effect of different olive oil-derived antioxidants (hydroxytyrosol and 3,4-dihydroxyphenylglycol) on the quality of frozen-thawed ram sperm.

The aim of the present study was to evaluate the effect of the addition of different concentrations of two olive oil-derived antioxidants, hydroxytyrosol (3,4-dihydroxyphenylethanol, HT) and 3,4-dihydroxyphenylglycol (DHPG), on ovine semen during the freezing-thawing process. Sperm was collected, pooled and diluted with commercial extenders and then divided into aliquots supplemented with different concentrations (10 µg/ml, 30 µg/ml, 50 µg/ml and 70 µg/ml) of HT, DHPG and a mixture (MIX) of both antioxidants. A control group, without antioxidant, was also prepared. Sperm motility, viability, acrosome integrity, mitochondrial membrane potential and lipid peroxidation (LPO) were assessed. The results showed that frozen-thawed ram spermatozoa exhibited lower values for motility, membrane integrity, acrosome and mitochondrial membrane potential than fresh samples (P ≤ 0.01). However, when antioxidants were added, thawed spermatozoa exhibited relatively low LPO, recording values similar to fresh spermatozoa; by contrast, the control group of frozen-thawed spermatozoa without antioxidants exhibited significantly higher LPO (P ≤ 0.01). The addition of a HT+DHPG mixture (MIX) had a negative impact on sperm membrane and acrosome integrity, suggesting that a pure antioxidant supplementation has the potential to offer superior results. In conclusion, HT and DHPG exhibited a positive effect on the frozen-thawed spermatozoa inasmuch as they reduced the LPO. These olive oil-derived antioxidants have the potential to improve frozen-thawed sperm quality, although further studies should be carried out to analyse the antioxidant effect at different times after thawing.

A model to infer the demographic structure evolution of endangered donkey populations.

Stemming from The Worldwide Donkey Breeds Project, an initiative aiming at connecting international researchers and entities working with the donkey species, molecularly tested pedigree analyses were carried out to study the genetic diversity, structure and historical evolution of the Andalusian donkey breed since the 1980s to infer a model to study the situation of international endangered donkey breeds under the remarkably frequent unknown genetical background status behind them. Demographic and genetic variability parameters were evaluated using ENDOG (v4.8). Pedigree completeness and generation length were quantified for the four gametic pathways. Despite mean inbreeding was low, highly inbred animals were present in the pedigree. Average coancestry, relatedness, and non-random mating degree trends were computed. The effective population size based on individual inbreeding rate was about half when based on individual coancestry rate. Nei's distances and equivalent subpopulations number indicated differentiated farms in a highly structured population. Although genetic diversity loss since the founder generations could be considered small, intraherd breeding policies and the excessive contribution of few ancestors to the gene pool could lead to narrower pedigree bottlenecks. Long average generation intervals could be considered when reducing inbreeding. Wright's fixation statistics indicated slight inbreeding between farms. Pedigree shallowness suggested applying new breeding strategies to reliably estimate descriptive parameters and control the negative effects of inbreeding, which could indeed, mean the key to preserve such valuable animal resources avoiding the extinction they potentially head towards, making the present model become an international referent when assessing endangered donkey populations.

[Prefrontal Symptoms Inventory (PSI): ecological validity and convergence with neuropsychological measures]. / Inventario de sintomas prefrontales (ISP): validez ecologica y convergencia con medidas neuropsicologicas.

INTRODUCTION: The Prefrontal Symptoms Inventory (PSI) is a self-reported questionnaire, created in Spain, which asks about cognitive, emotional and behavioural alterations in activities of daily living and which can be applied in both the general population and in multiple clinical populations. There is a shorter 20-item version (PSI-20) with excellent psychomotor properties for screening. AIM: To study the convergent and divergent validity of the PSI and PSI-20, by analysing how their scales reflect the day-to-day consequences of real deficits found in neurological assessment performed by means of performance tests. PATIENTS AND METHODS: A sample of 52 persons undergoing treatment for substance addiction (31 males and 21 females) were administered the PSI together with an abbreviated neuropsychological examination battery focused on describing attentional, mnemonic and executive processes. RESULTS: Both versions of the PSI present optimal psychometric properties (0.78 > alpha > 0.94 for the complete 46-item version and 0.7 > alpha > 0.89 for the abbreviated 20-item version). The results confirm the hypotheses regarding their validity: the performance problems scale is related with the capacity to resolve tests that supposedly rate the executive functions of a prefrontal origin (convergent validity), whereas the scales of problems in emotional control and problems with social behaviour are not related with those cognitive capabilities (discriminant validity). CONCLUSIONS: The PSI is a test that is clinically useful, psychometrically valid and applicable in multiple clinical populations.

TITLE: Inventario de sintomas prefrontales (ISP): validez ecologica y convergencia con medidas neuropsicologicas.Introduccion. El inventario de sintomas prefrontales (ISP) es un cuestionario autoinformado creado en España que interroga sobre alteraciones cognitivas, emocionales y comportamentales en las actividades de la vida diaria y que resulta aplicable tanto en poblacion general como en multiples poblaciones clinicas. Existe una version abreviada de 20 items (ISP-20) con excelentes propiedades psicometricas para el cribado. Objetivo. Estudiar la validez convergente y divergente del ISP e ISP-20, analizando como sus escalas reflejan las consecuencias cotidianas de deficits reales hallados en evaluacion neuropsicologica mediante pruebas de ejecucion. Pacientes y metodos. Se estudiaron 52 personas con adiccion a sustancias en tratamiento (31 varones y 21 mujeres) a las que se administro el ISP junto con una bateria de exploracion neuropsicologica abreviada centrada en describir procesos atencionales, mnemicos y ejecutivos. Resultados. Ambas versiones del ISP presentan optimas propiedades psicometricas (0,78 > alfa > 0,94 para la version completa de 46 items y 0,7 > alfa > 0,89 para la version abreviada de 20 items). Los resultados confirman las hipotesis sobre su validez: la escala de problemas en la ejecucion se relaciona con la capacidad para resolver tests que presumiblemente valoran funciones ejecutivas de origen prefrontal (validez convergente), mientras que las escalas de problemas en el control emocional y problemas en la conducta social no se relacionan con dichas capacidades cognitivas (validez discriminante). Conclusiones. El ISP es una prueba clinicamente util, psicometricamente valida y aplicable en multiples poblaciones clinicas.

Green chemistry synthesis of nano-cuprous oxide.

Green chemistry and a central composite design, to evaluate the effect of reducing agent, temperature and pH of the reaction, were employed to produce controlled cuprous oxide (Cu2O) nanoparticles. Response surface method of the ultraviolet-visible spectroscopy is allowed to determine the most relevant factors for the size distribution of the nanoCu2O. X-ray diffraction reflections correspond to a cubic structure, with sizes from 31.9 to 104.3 nm. High-resolution transmission electron microscopy reveals that the different shapes depend strongly on the conditions of the green synthesis.

Deformability properties of timolol-loaded transfersomes based on the extrusion mechanism. Statistical optimization of the process.

The purpose of this work was to analyze the deformability properties of different timolol maleate (TM)-loaded transfersomes by extrusion. This was performed because elastic liposomes may contribute to the elevation of amount and rate of drug permeation through the corneal membrane. This paper describes the optimization of a transfersome formulation by use of Taguchi orthogonal experimental design and two different statistical analysis approaches were utilized. The amount of cholesterol (F1), the amount of edge-activator (F2), the distribution of the drug into the vesicle (F3), the addition of stearylamine (F4) and the type of edge-activator (F5) were selected as causal factors. The deformability index, the phosphorous recovery, the vesicle size, the polydispersity index, the zeta potential and percentage of drug entrapped were fixed as the dependent variables and these responses were evaluated for each formulation. Two different statistical analysis approaches were applied. The better statistical approach was determined by comparing their prediction errors, where regression analysis provided better optimized responses than marginal means. From the study, an optimized formulation of TM-loaded transfersomes was prepared and obtained for the proposed ophthalmic delivery for the treatment of open angle glaucoma. It was found that the lipid to surfactant ratio and type of surfactant are the main key factors for determining the flexibility of the bilayer of transfersomes. From in vitro permeation studies, we can conclude that TM-loaded transfersomes may enhance the corneal transmittance and improve the bioavailability of conventional TM delivery.

Loss of the tumor suppressor spinophilin (PPP1R9B) increases the cancer stem cell population in breast tumors.

The spinophilin (Spn, PPP1R9B) gene is located at 17q21.33, a region frequently associated with microsatellite instability and loss of heterozygosity, especially in breast tumors. Spn is a regulatory subunit of phosphatase1a (PP1), which targets the catalytic subunit to distinct subcellular locations. Spn downregulation reduces PPP1CA activity against the retinoblastoma protein, pRb, thereby maintaining higher levels of phosphorylated pRb. This effect contributes to an increase in the tumorigenic properties of cells in certain contexts. Here, we explored the mechanism of how Spn downregulation contributes to the malignant phenotype and poor prognosis in breast tumors and found an increase in the stemness phenotype. Analysis of human breast tumors showed that Spn mRNA and protein are reduced or lost in 15% of carcinomas, correlating with a worse prognosis, a more aggressive tumor phenotype and triple-negative tumors, whereas luminal tumors showed high Spn levels. Downregulation of Spn by shRNA increased the stemness properties along with the expression of stem-related genes (Sox2, KLF4, Nanog and OCT4), whereas ectopic overexpression of Spn cDNA reduced these properties. Breast tumor stem cells appeared to have low levels of Spn mRNA, and Spn loss correlated with increased stem-like cell appearance in breast tumors as indicated by an increase in CD44+/CD24- cells. A reduction of the levels of PPP1CA mimicked the cancer stem-like cell phenotype of Spn downregulation, suggesting that the mechanism of Spn involves PP1a. These increased cancer stem cell-like properties with reduced Spn might account for the malignant phenotype observed in Spn-loss tumors and may contribute to a worse patient prognosis.

Genetic parameters of traits associated with the growth curve in Segureña sheep.

This paper studies the genetic importance of growth curve parameters and their relevance as selection criteria in breeding programmes of Segureño sheep. Logistic and Verhulst growth functions were chosen for their best fit to BW/age in this breed; the first showed the best general fit and the second the best individual fit. Live weights of 41 330 individuals from the historical archives of the National Association of Segureña Sheep Breeders were used in the analysis. The progeny of 1464 rams and 27 048 ewes were used to study the genetic and phenotypic parameters of growth curve parameters and derived traits. Reproductive management in the population consists in controlled natural mating inside every herd, with a minimum of 15% of the females fertilized by artificial insemination with fresh semen; with the purpose being the herd genetic connections, all herd genealogies are screened with DNA markers. Estimates of growth curve parameters from birth to 80 days were obtained for each individual and each function by the non-linear regression procedure using IBM SPSS statistics (version 21) with the Levenberg-Marquart estimation method. (Co)variance components and genetic parameters were estimated by using the REML/Animal model methodology. The heritability of mature weight was estimated as 0.41±0.042 and 0.38±0.021 with the logistic and Verhulst models, respectively, and the heritability of other parameters ranged from 0.41 to 0.62 and 0.37 to 0.61, with the models, respectively. A negative genetic correlation between mature weight and rate of maturing was found.

Characterization of commercial and biological growth curves in the Segureña sheep breed.

Non-linear models were analysed to describe both the biological and commercial growth curves of the Segureña sheep, one of the most important Spanish breeds. We evaluated Brody, von Bertalanffy, Verhulst, logistic and Gompertz models, using historical data from the National Association of Segureña Sheep Breeders (ANCOS). These records were collected between 2000 and 2013, from a total of 129 610 weight observations ranging from birth to adulthood. The aim of this research was to establish the mathematical behaviour of body development throughout this breed's commercial life (birth to slaughter) and biological life (birth to adulthood); comparison between both slopes gives important information regarding the best time for slaughter, informs dietary advice according to animals' needs, permits economical predictions of productions and, by using the curve parameters as selection criteria, enables improvements in growth characteristics of the breed. Models were fitted according to the non-linear regression procedure of statistical package SPSS version19. Model parameters were estimated using the Levenberg-Marquardt algorithm. Candidate models were compared using the determinative coefficient, mean square error, number of iterations, Akaike information coefficient and biological coherence of the estimated parameters. The von Bertalanffy and logistic models were found to be best suited to the biological and commercial growth curves, respectively, for both sexes. The Brody equation was found to be unsuitable for studying the commercial growth curve. Differences between the parameters in both sexes indicate a strong impact of sexual dimorphism on growth. This can emphasize the value of the highest growth rate for females, indicating that they reach maturity earlier.

[Neurocognitive screening in substance addicts: the Montreal Cognitive Assessment]. / Cribado neurocognitivo en adictos a sustancias: la evaluacion cognitiva de Montreal.

INTRODUCTION: The detection of neurocognitive disorders in addicts would allow subjects with functional impairment to be assigned to cognitive rehabilitation programmes. The Montreal Cognitive Assessment (MoCA) is a screening test that can be a valuable aid with this kind of patient. AIMS: To use the MoCA with a sample of subjects with addictions who are receiving treatment and to compare the results with the criteria proposed for the general population, mild cognitive impairment and early dementias. It also intends to examine the concurrent validity with global execution tests and the relationship with socio-demographic variables and others related to addiction. PATIENTS AND METHODS: The MoCA and the Allen Cognitive Level Screen-5 (ACLS-5) test were administered to a sample of 79 patients with addiction who were beginning treatment in a specific centre. RESULTS: Only 29.1% of the participants presented normal performance in terms of the criteria proposed by the authors. The others achieved scores below the cut-off point, many of them displaying an alarmingly low score, even when compared with criteria for mild cognitive impairment and early dementias. The MoCA showed concurrent validity with the ACLS-5 and correlation with academic level, but not with variables related to addiction. CONCLUSIONS: The MoCA is a test that is quick and simple to administer and correct. It allows the detection of subjects with extremely low cognitive performance that require neuropsychological and occupational interventions for cognitive rehabilitation, which increases treatment compliance and the benefits to be gained from other interventions with important cognitive demands, such as relapse prevention psychotherapy.

Effects of non-pharmacological therapy on normal ageing and on cognitive decline: reflections on treatment objectives.

INTRODUCTION: Non-pharmacological therapies for normal ageing and dementia are a set of treatment programmes intended to improve the performance of cognitive processes, improve emotional well-being, promote independence in daily life activities, and ultimately increase patients' quality of life. METHODS: We applied a battery of tests assessing four major domains (general mental state, emotional well-being, quality of life, and daily life activities) to a sample of 317 adults older than 64 (240 with normal ageing and 77 with cognitive impairment). They were then assigned either to non-pharmacological therapy groups according to their abilities or to other non-specific activities. Progress was assessed 9 months later using the same test battery. RESULTS: The results show a general improvement in mental state in the group with normal ageing and absence of disease progression in the group with pathological ageing. In both groups, emotional well-being (anxiety and depression) and self-identified quality of life both benefited from non-pharmacological therapy. However, other aspects commonly included among the therapeutic targets did not seem to improve, including independence in daily life activities. CONCLUSIONS: This study provides evidence that non-pharmacological therapy in ageing patients can produce positive results. It must be stressed that benefits are greater in individuals with cognitive impairment, although generalising use of this therapy could prove to be an excellent primary programme for preventing cognitive and emotional disorders.