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Introducción: Actualmente existe amplia evidencia acerca de la relación entre sucesos vitales (sv) y depresión. No obstante, los sv se han dividido en sv dependientes, aquellos que ocurren debido en parte a las características o comportamientos del individuo; y sv independientes, aquellos que suceden independientemente del comportamiento del sujeto. Esta distinción es importante, dado que ambas clases de sucesos podrían tener un peso diferente en la depresión. Además, y desde un modelo clásico de diátesis-estrés, los sv no tendrían el mismo impacto en todas las personas. Una variable de personalidad que se ha relacionado de forma importante con la depresión y que podría considerarse como un factor de diátesis sería el neuroticismo. Por tanto, el principal objetivo de este estudio fue examinar el posible efecto moderador de la personalidad en la relación entre los sv y los síntomas depresivos en adolescentes. Método: Se evaluaron los síntomas depresivos, los sucesos vitales y la personalidad a una muestra de 776 jóvenes (media de edad = 14,29; DT = 1,575). Resultados: El neuroticismo y los sv presentaban efectos aditivos en los síntomas depresivos. Además, encontramos efectos de moderación significativos entre la personalidad y los sv independientes, sugiriendo una mayor afectación de los sv independientes en personas que puntuaron más alto en la dimensión de neuroticismo. Conclusiones: Nuestros resultados ayudan a entender mejor los factores personales y sociales involucrados en el desarrollo de síntomas depresivos en la adolescencia, y serían de utilidad en el desarrollo de intervenciones psicológicas personalizadas más efectivas. Introduction: Nowadays there is a lot of evidence about the relationship between life events (le) and depression. However, le have been divided into dependent le, those which are in part caused by individual characteristics or behaviors; and independent le, those that happen regardless of the subject’s behavior. This distinction is important, since both of them could have a different weight in the explanation of depressive symptomatology. In addition, and based on the classical diathesis- stress model, le would not have the same impact on everybody. A personality variable that has been significantly related to depression and could be considered as a diathesis factor, would be neuroticism. Therefore, the main objective of this study was to examine the possible moderating effect of personality on the relationship between le and depressive symptoms in adolescents. Method: Depressive symptoms, life events and personality were evaluated in a sample of 776 teenagers (mean age = 14.29; DT = 1.575). Results: Neuroticism and le had additive effects on depressive symptoms. In addition, we found significant moderating effects between personality and independent le, suggesting greater involvement of independent LE in people who scored higher in neuroticism. Conclusions: Our results help to achieve a better understanding of the personal and social factors involved in the development of depressive symptoms in adolescence, and would be useful in the development of more effective personalized psychological interventions.

Developing a simple, fast, and label-free method for discrimination between live cancer cells and normal cells in biological samples still remains a challenge. Here, a system is described that fulfills these features to analyze individual living cells. The system consists of a gold nanohole array biosensor plus a microscope optical design to isolate the spectral response of a single cell. It is demonstrated that differences in the spectral behavior between tumor (colorectal cancer cell lines and primary cells from colorectal cancer tissue) and non-tumor cells (peripheral blood mononuclear cells, skin fibroblasts and colon epithelial cells) are influenced by the actin cortex, which lies within the short penetration depth of the surface plasmon electromagnetic field. The efficacy of this system was assessed by the analysis of about one thousand single cells showing the highest discrimination capacity between normal colon epithelial cells and colorectal cancer cells from surgical specimens, with values of sensitivity and specificity ranging 80-100% and 87-100%, respectively. It is also demonstrated that cell discrimination capacity of the system is highly reduced by disrupting the formation of actin cortex. This plasmonic system may find wide applications in biomedicine and to study key cellular processes that involve the actin cortex, including proliferation, differentiation, and migration. This work was supported by the Instituto de Salud Carlos III through grant DTS18/00141, co-funded by European Regional Development Fund/ European Social Fund “A way to make Europe/Investing in your future” and Instituto de Investigación Valdecilla (IDIVAL) (APG/03).

COVID-19 has affected mental health and well-being. Lifestyles are relevant to understand the impact of psychosocial dysfunctions. The objective was to examine the role of healthy habits in the relations between psychosocial dysfunction and psychological well-being/distress during COVID-19. Participants completed measures of psychosocial dysfunction, healthy habits, life satisfaction, well-being, depression, and anxiety symptoms. Psychosocial dysfunction was associated with distress symptoms, while health habits were associated with well-being. Healthy habits were mediators: greater psychosocial dysfunction was associated with less healthy habits, which in turn were associated with lower overall well-being, and greater depression. Programs addressing healthy habits can be of great utility.

Purpose This mixed-methods study examined the effect of a supports-based intervention on the interactions between John, a 9-year-old minimally speaking autistic student with access to a speech-generating augmentative and alternative communication device, and nonautistic peers in the classroom. Method We used a single-case experimental ABAB design to evaluate the relation between provision of social supports and the frequency of communicative offers between John and one nonautistic peer, Ethan. In addition, we integrated interview data and situated discourse analyses involving a variety of adult and child participants to illustrate the nature of peer interactions both before and during provision of social supports. Results In summary, visual inspection of the single-case data supported a functional relation of moderate effect size between the provision of social support and an increased frequency of communicative offers between John and Ethan. Results from the discourse analysis suggested that social supports led to the (a) emergence of completed turns across peers, (b) flexible use of multimodal communicative resources, and (c) movement toward egalitarian interactions. Conclusions This study is one of the first to provide experimental evidence for a supports-based approach to peer interactions involving a minimally verbal autistic student. Clinical implications focus on encouraging flexible multimodality and adopting a strength-based approach that fosters autistic sociality.

The Mental Health Continuum-Short Form (MHC-SF) is a multidimensional instrument designed to capture emotional, psychological, and social well-being. It is one of the self-report measures of international use in clinical practice and research, although so far it has no validation in Spanish-Speaking adolescents. Therefore, the objective of this study was to analyze the reliability and validity evidence (structure, convergent and criterion), and the temporal and gender invariance of the MHC-SF in Spanish adolescent population.Two assessment moments with a 6-month time interval were used, with an initial sample of 5,479 adolescents and a later sample of 2,129.The CFA showed optimal fit for the bi-factor model, and an adequate fit for correlated three-factor model. The results of the gender and temporal invariance analysis showed optimal fit. Reliability coefficients were all higher than .77. The MHC-SF presented significant positive associations (p.001) with indicators of well-being (r.60) and negative associations with indicators of psychological distress (r-.21).The MHC-SF shows evidence of reliability and validity in Spanish adolescents, being the bi-factor model invariant through time and across gender groups.

There is mounting empirical evidence of the detrimental effects of the coronavirus disease 2019 (COVID-19) outbreak on mental health. Previous research has underscored the effects of similar destabilizing situations such as war, natural disasters or other pandemics on acute stress levels which have been shown to exacerbate current and future psychopathological symptoms.To explore the role of acute stress responses (intrusive, avoidance and hyperarousal) as mediators in the association between fear of COVID-19 and emotional dysfunction-related problems: Depression, agoraphobia, panic, obsessive-compulsive, generalized anxiety, social anxiety and health anxiety symptoms.A sample of 439 participants from a university community in Spain (age: mean ± SD: 36.64 ± 13.37; 73.1% females) completed several measures assessing their fear of COVID-19, acute stress responses and emotional dysfunction syndromes through an online survey. Data collection was carried out from the start of home confinement in Spain until May 4, 2020, coinciding with initial de-escalation measures. Processing of the dataset included descriptive and frequency analyses, Mann-Whitney U Test of intergroup comparisons and path analysis for direct and indirect effects. This is an observational, descriptive-correlational and cross-sectional study.The prevalence of clinical symptoms in our sample, reported since the beginning of the pandemic, reached 31.44%. The female group presented higher scores although the effect size was small. Overall, the participants who exceeded the clinical cut-off points in emotional problems showed higher levels of fear of COVID-19 and of cognitive, motor and psychophysiological responses of acute stress, unlike the group with normative scores. In addition, the results show significant mediated effects of hyperarousal stress among fear of COVID-19 and emotional dysfunction psychopathology. However, the clinical syndromes most related to the consequences of the pandemic (The present study illustrates a clearer picture of the role of acute stress on several forms of psychopathology during the COVID-19 crisis and home confinement.

Background/objective: Research has highlighted the role of neuroticism, rumination, and depression in predicting suicidal thoughts, but studies on how these variables interplay are scarce. The aims of the present study were to test a model in which emotional stability (i.e., low neuroticism) would act as an antecedent and moderator of rumination and depressed mood in the prediction of suicidal ideation (i.e., moderated serial-mediation), and to explore their repli- cability across four countries and sex, among college students as an at-risk-group for suicide. Method: Participants were 3482 undergraduates from U.S, Spain, Argentina, and the Nether- lands. Path analysis and multi-group analysis were conducted. Results: Emotional stability was indirectly linked to suicidal ideation via rumination and depressed mood. Moreover, emotional stability moderated the associations between rumination and depressed mood, and between depressed mood and suicidal ideation. Findings were consistent in males and females, and across countries studied. Discussion: Regardless of sex and country, people with low emotional stability reported higher levels of rumination, which in turn was associated with more depressed mood, and these were associated with higher reports of suicidal thoughts. This cascade of psychological risk factors for suicidal ideation seems to be more harmful in people who endorse low levels of emotional stability.

Pulmonary vascular resistance (PVR) is a marker of pulmonary vascular remodeling. A non-invasive model assessed by cardiovascular magnetic resonance (CMR) has been proposed to estimate PVR. However, its accuracy has not yet been evaluated in patients with heart failure. We prospectively included 108 patients admitted with acute heart failure (AHF), in whom a right heart catheterization (RHC) and CMR were performed at the same day. PVR was estimated by CMR applying the model: PVR = 19.38 − [4.62 × Ln pulmonary artery average velocity (in cm/s)] − [0.08 × right ventricle ejection fraction (in %)], and by RHC using standard formulae. The median age of the cohort was 67 years (interquartile range 58–73), and 34% were females. The median of PVR assessed by RHC and CMR were 2.2 WU (1.5–4) and 5 WU (3.4–7), respectively. We found a weak correlation between invasive PVR and PVR assessed by CMR (Spearman r = 0.21, p = 0.02). The area under the ROC curve for PVR assessed by CMR to detect PVR ≥ 3 WU was 0.57, 95% confidence interval (CI): 0.47–0.68. In patients with AHF, the non-invasive estimation of PVR using CMR shows poor accuracy, as well as a limited capacity to discriminate increased PVR values.

espanolEl impacto psicologico debido a la pandemia por coronavirus (COVID-19) ha sido evidenciado. Algunas de las variables asociadas a este han sido la presencia de problemas financieros previos, ser estudiantes o encontrarse inactivo, todas ellas cuestiones relacionadas con el ambito laboral y academico. En consecuencia, el objetivo principal del trabajo fue analizar el papel mediador que tienen las fortalezas personales para la salud mental frente a la interferencia academica/laboral provocada por el confinamiento debido a la COVID-19 en Espana en funcion del estatus laboral (estudiantes, trabajadores activos e inactivos), controlando a su vez otras variables sociodemograficas (sexo y edad). Para la recogida de datos del presente estudio descriptivo de corte transversal se utilizo una encuesta online, compuesta por instrumentos para valorar el grado de interferencia en las actividades academicas/laborales (ad hoc), las estrategias de afrontamiento desadaptativas (COPE-28), la resiliencia (CD-RISC), la covitalidad (SEHS), los habitos saludables (ad hoc), el bienestar psicologico (WHO-5) y malestar psicologico (PHQ-4). Los resultados mostraron, por un lado, que los colectivos de estudiantes y de inactividad manifestaron peores indicadores de salud mental y recursos personales, mientras que el efecto contrario fue hallado en el grupo de trabajadores activos; y, por otro lado, los modelos de mediacion PROCESS (modelo 4) evidenciaron un efecto amortiguador de los recursos personales entre la interferencia academica/laboral percibida y los indicadores de ajuste psicosocial (bienestar y malestar psicologico), independientemente de la categoria laboral. En conclusion, se destaca la funcion protectora de los recursos personales en el ajuste psicosocial durante el periodo de confinamiento por COVID-19. EnglishThe psychological impact due to the coronavirus pan-demic (COVID-19) has been evidenced. Some of the var-iables associated with this havebeen the presence of pre-vious financial problems, being students or being inactive, all of them issues related to the work and academic scope. Consequently, the main objective of the work was to ana-lyze the mediating role that personal strengths for mentalhealth have in the face of academic/work interference caused by lockdown due to COVID-19 in Spain based on work status(students, workers active and inactive), con-trolling in turn for other sociodemographic variables(sex and age). For the data collectionof this descriptive cross-sectional study, an online survey was used, composed of instruments to assess the degree of interference in aca-demic/work activities(ad hoc), maladaptive coping strat-egies(COPE-28), resilience(CD-RISC), covitality(SEHS), healthy habits(ad hoc), psychological well-being(WHO-5) and psychological distress(PHQ-4). The results showed: on the one hand, that the groups of students and inactivity showed worse mentalhealth indicators and per-sonal resources, while the opposite effect was found in the group of active workers; and, on the other hand, the PROCESS mediation models (model 4) evidenced a damping effect of personal resources between perceived academic/work interference and psychological adjustment indicators (well-beingand psychological distress), regard-less of the work category. In conclusion, the protective role of personal resources in psychological adjustment during lockdown due to COVID-19 is highlighted

BACKGROUND The short form, 17-item version of the Pediatric Symptom Checklist-Youth Self-Report (PSC-17-Y) is a validated measure that assesses psychosocial problems overall (OVR) and in 3 major psychopathological domains (internalizing, externalizing, and attention-deficit/hyperactivity disorder), taking 5-10 min to complete. Prior research has established sound psychometric properties of the PSC-17-Y for English speakers. OBJECTIVE This study extends psychometric evidence for the acceptability of the PSC-17-Y in a large sample of Spanish adolescents, providing proof of its reliability and structure, convergent and discriminant validity, and longitudinal and gender invariance. METHODS Data were collected on 5430 adolescents, aged 12-18 years, who filled out the PSC-17-Y twice during 2018-2019 (7-month interval). We calculated the Cronbach alpha and the McDonald omega coefficients to test reliability, the Pearson correlation for convergent (distress) and criterion validity (well-being, quality of life, and socioemotional skills), confirmatory factor analysis (CFA) for structure validity, and multigroup and longitudinal measurement invariance analysis for longitudinal and gender stability. RESULTS Within structural analysis for the PSC-17-Y, CFA supported a correlated 3-factor solution, which was also invariant longitudinally and across gender. All 3 subscales showed evidence of reliability, with coefficients near or above .70. Moreover, scores of PSC-17-Y subscales were positively related with convergent measures and negatively related with criterion measures. Normative data for the PSC-17-Y are presented in the form of percentiles (75th and 90th). CONCLUSIONS This work provides the first evidence of the reliability and validity of the Spanish version of the PSC-17-Y administered over the internet to assess mental health problems among adolescents, maintaining the same domains as the long version.

Abstract. The aim of this psychometric study was to construct an abridged 50-item form, 10 for each of the five factors of personality, of the Junior Spanish version of the NEO-PI-R (JS NEO-A50). Two separate studies were conducted. In Study 1, 400 high school students completed two personality scales to examine the factor structure (exploratory factor analysis), convergent validity, and reliability of the JS NEO-A50. In Study 2, an independent sample of 385 adolescents completed the JS NEO-A50 and several outcome measures to replicate the factor structure (exploratory structural equation model) and examine criterion validity, respectively. The five-factor structure found in Study 1 was satisfactorily replicated in the second, independent sample. Sources of reliability (internal consistency and test-retest) and validity (convergent) were adequate. Also, the outcome measures assessed in Study 2 were related to personality traits in the expected direction. Life satisfaction was significantly predicted by emotional stability; symptoms of behavioral problems were predicted by low scores in both agreeableness and conscientiousness while internalizing emotional symptoms were mainly predicted by emotional instability; finally, academic performance was mainly predicted by conscientiousness. We conclude that the JS NEO-A50 is a sound inventory to measure the five broad personality domains in Spanish-speaking adolescents.

Very few studies about the psychometric properties of the Anxiety Severity Measures (ASM) proposed in the DSM-5 exist, and none in Spanish-speaking populations. Thus, the aim of the present study was to provide validity and reliability evidence for the Spanish versions of the Agoraphobia, Social Anxiety, Separation Anxiety, Panic, Generalized Anxiety and Specific Phobia Severity measures.Participants included 567 Spaniards (mean age=21.26, SD=3.61; 68.3% women). We performed Exploratory and Confirmatory Factor Analyses to test the structure of the scales, Differential Item Functioning (DIF) by sex, Cronbach's alpha and ordinal omega to test reliability, and the Pearson correlations between the ASM and different outcomes to provide evidence for convergent/discriminant (internalizing/externalizing symptoms) and criterion validity (satisfaction, quality of life and personality).Structural analyses supported a one-factor solution for all of the ASM except for the Specific Phobia scale, which was also the only scale that exhibited DIF. Reliability indices ranked from .82 to .93. All six scales showed stronger associations with internalizing than externalizing measures and were also negatively related to criterion measures.The Spanish version of ASM is suitable for assessing anxiety-related symptoms, except the Specific Phobia Scale, which requires further examination.

[Objectives] The brains of individuals with Down syndrome (DS) present defects in neurogenesis and synaptogenesis during prenatal and early postnatal stages that are partially responsible for their cognitive disabilities. Because oleic and linolenic fatty acids enhance neurogenesis, synaptogenesis, and cognitive abilities in rodents and humans, in this study we evaluated the ability of these compounds to restore these altered phenotypes in the Ts65Dn (TS) mouse model of DS during early postnatal stages., [Methods] TS and euploid mice were treated with oleic or linolenic acid from PD3 to PD15, and the short- and long- term effects of these acids on neurogenesis and synaptogenesis were evaluated. The effects of these treatments on the cognitive abilities of TS mice during early adulthood were also evaluated., [Results] Administration of oleic or linolenic acid did not modify cell proliferation immediately after treatment discontinuation or several weeks later. However, oleic acid increased the total number of DAPI+ cells (+ 26%), the percentage of BrdU+ cells that acquired a neural phenotype (+ 9.1%), the number of pre- (+ 29%) and post-synaptic (+ 32%) terminals and the cognitive abilities of TS mice (+ 18.1%). In contrast, linolenic acid only produced a slight cognitive improvement in TS mice. (+12.1%)., [Discussion] These results suggest that early postnatal administration of oleic acid could palliate the cognitive deficits of DS individuals.

PurposeThe present clinical focus draws on an intrinsic case study to provide a thick description of the communication profile of John, a 9-year-old minimally verbal autistic student.MethodSpecifically, traditional behavioral assessments, classroom video observations, and semistructured interviews were used to gather information regarding John's communication profile and potential sensory–motor differences.ResultsConvergent evidence indicated that John's expressive profile was characterized by single words, emergent word combinations, some conventional gestures, and a low frequency of communicative initiations. Concomitant language comprehension challenges and poor intelligibility associated with motor speech impairment were also indicated. His sensory–motor profile was marked by fine motor impairment, relative strengths in gross motor abilities, and sensory differences across visual, hearing, and tactile modalities.ConclusionDirect implications for supporting minimally verbal autistic students like John include the need to (a) consider sensory–motor influences on social interaction and (b) support flexible use of multimodal communication resources, including augmentative and alternative communication.Supplemental Materialhttps://doi.org/10.23641/asha.12202448

L’adaptació espanyola per a adolescents del NEO PI-R, el JS NEO-S, és un instrument de 150 ítems que avalua el model de cinc factors de la personalitat. No obstant, per la població a la que es dirigeix aquest qüestionari, completar una escala de 150 ítems pot resultar costós. El nostre objectiu és desenvolupar una versió abreviada de 50 ítems del JS NEO-S. El qüestionari es va administrar a una mostra de 400 participants d’entre 12 i 17 anys. Junt al JS NEO-S, també es va administrar un altre instrument de 5 factors, el BFPTSQ, així com el SENA i l’SLSS per avaluar símptomes psicopatològics i benestar subjectiu, respectivament. Finalment, es va dur a terme un retest d’un mes del JS A-50 i es van sol·licitar les notes. Es seleccionaren 50 ítems mitjançant anàlisi factorial exploratòria. Ítems de la majoria de facetes van estar representats en totes les dimensions. Els valors de validesa convergent presentaren correlacions d’entre 0,55 i 0,69 amb el BFPTSQ. Els valors de validesa de criteri també van ser adequats. Els índexs alfa per a les dimensions estigueren entre 0,73 i 0,83. Finalment, també es va trobar una fiabilitat d’estabilitat temporal adequada (d’entre 0,77 i 0,83). Aquests resultats evidencien unes propietats psicomètriques acceptables. Les limitacions principals del nostre treball serien, per una banda, la grandària mostral reduïda, així com la conveniència de replicar l’estudi amb una mostra independent. Futurs estudis haurien de continuar la validació del JS NEO-A50 atenent les limitacions indicades. The Spanish adaptation of the NEO PI-R for adolescents, the JS NEO-S is a 150-item instrument that assesses the Five-Factor Model of personality. However, for the population that this questionnaire is aimed at, completing a 150-item scale can be complicated. Our aim is to develop an abridged, 50- item version of the JS NEO-S. The questionnaire was administered to a sample of 400 participants between the ages of 12 and 17. Along with the JS NEO-S, another 5-factor instrument was administered, the BFPTSQ, as well as the SENA and SLSS to assess psychopathological symptoms and subjective wellbeing, respectively. Finally, a one-month retest was conducted for the JS NEO-A50 and grades were requested. 50 items were selected employing an exploratory factor analysis. Items from the majority of the facets were represented in each of the dimensions. Convergent validity values yielded correlations between 0.55 and 0.69 with the BFPTSQ. Criterion validity values were also adequate. Alpha indices for the domains were between 0.73 and 0.83. Finally, an adequate temporal stability reliability (between 0.77 and 0.83) was found. These results show acceptable psychometric properties. The main limitations of our study were, on the one hand, the small sample size, as well as the need for replication of the study with an independent sample. Future studies should continue to validate the JS NEO-A50 taking the highlighted limitations into account.

Aims The aim of this study was to evaluate the safety profile in terms of changes in renal function after co‐treatment with sacubitril/valsartan and empagliflozin in patients with type 2 diabetes (T2D) and heart failure with reduced ejection fraction (HFrEF). Methods and results This multicentre observational analysis included 108 patients with T2D and HFrEF treated with both agents: baseline sacubitril/valsartan (Group A; n = 43), baseline empagliflozin (Group B; n = 42), or both agents initiated simultaneously (Group C; n = 23). The primary endpoint was estimated glomerular filtration rate (eGFR) dynamics across treatment groups. A binary characterization of worsening renal function (WRF)/improved renal function (IRF) was included in the primary endpoint. WRF and IRF were defined as an increase/decrease in serum creatinine ≥ 0.3 mg/dL or GFR ≥ 20%. Changes in quantitative variables were evaluated using joint modelling of survival and longitudinal data (JM). Rates and their treatment differences were determined by Poisson regression. The mean left ventricle ejection fraction and eGFR were 32 ± 6% and 70 ± 28 mL/min/1.73 m2, respectively. At a median follow‐up of 1.01 years (inter‐quartile range 0.71–1.50), 377 outpatient visits were recorded. Although there were differences in GFR trajectories over time within each treatment, they did not achieve statistical significance (omnibus P = 0.154). However, when these differences were contrasted among groups, there was a significant decrease in GFR in Group A as compared with Group B (P = 0.002). The contrast between Groups C and B was not significant (P = 0.430). These differences were also reflected when the rates for WRF and IRF were contrasted among treatments. Conclusions The co‐administration of sacubitril/valsartan and empagliflozin in patients with HFrEF and concomitant T2D appears to be safe in terms of renal function.

The aim of this study was to develop a 60-item, abridged form of the Junior Spanish version of the NEO-PI-R (JS NEO-A60), consisting of 12 items per dimension. A sample of 399 high school students completed two personality scales to examine the factor structure (Exploratory Structural Equation Model), reliability and convergent validity of the JS NEO-A60. Our sample also completed several consequential life outcome measures in order to examine criterion validity. The five-factor structure, along with representation of the majority of lower-order facets, was satisfactorily covered by the JS NEO-A60. Sources of reliability (internal consistency and test-retest) and validity (convergent) were adequate. The life outcome variables revealed links to personality traits in the expected direction. Namely, internalizing emotional symptoms (anxiety and depression) were mainly predicted by emotional instability. Symptoms of behavioral problems (aggression and antisocial behavior) were predicted by low scores in both agreeableness and conscientiousness. Life satisfaction was significantly predicted by emotional stability. Last, academic performance via students’ grades was predicted by conscientiousness and openness. We conclude that the JS NEO-A60 is a sound inventory to assess the five broad personality domains in Spanish-speaking adolescents.

Background: The cognitive dysfunction in Down syndrome (DS) is partially caused by deficient neurogenesis during fetal stages. Curcumin enhances neurogenesis and learning and memory. Objectives: We aimed to test the ability of curcumin to rescue the neuromorphological and cognitive alterations of the Ts65Dn (TS) mouse model of DS when administered prenatally or during early postnatal stages, and to evaluate whether these effects were maintained several weeks after the treatment. Methods: To evaluate the effects of prenatal curcumin administration, 65 pregnant TS females were subcutaneously treated with curcumin (300 mg/kg) or vehicle from ED (Embryonic Day) 10 to PD (Postnatal Day) 2. All the analyses were performed on their TS and Control (CO) male and female progeny. At PD2, the changes in neurogenesis, cellularity, and brain weight were analyzed in 30 TS and CO pups. The long-term effects of prenatal curcumin were evaluated in another cohort of 44 TS and CO mice between PD30 and PD45. The neuromorphological effects of the early postnatal administration of curcumin were assessed on PD15 in 30 male and female TS and CO pups treated with curcumin (300 mg/kg) or vehicle from PD2 to PD15. The long-term neuromorphological and cognitive effects were assessed from PD60 to PD90 in 45 mice. Data was compared by ANOVAs. Results: Prenatal administration of curcumin increased the brain weight (+45%, P < 0.001), the density of BrdU (bromodeoxyuridine)- (+150%, P < 0.001) and DAPI (4',6-diamidino-2-phenylindole)- (+38%, P = 0.005) positive cells, and produced a long-term improvement of cognition in TS (+35%, P = 0.007) mice with respect to vehicle-treated mice. Postnatal administration of curcumin did not rescue any of the short- or long-term altered phenotypes of TS mice. Conclusion: The beneficial effects of prenatal curcumin administration to TS mice suggest that it could be a therapeutic strategy to treat DS cognitive disabilities. This study was supported by the “Fondazione Generali e Assicurazioni Generali”, Italy; Fundación Tatiana Pérez de Guzmán el Bueno, IDIVAL (NVAL 19/23), and the Spanish Ministry of Economy and Competitiveness (PSI-2016-76194-R, AEI/FEDER, EU).

Background Intravenous ferric carboxymaltose ( FCM ) improves symptoms, functional capacity, and quality of life in heart failure and iron deficiency. The mechanisms underlying these effects are not fully understood. The aim of this study was to examine changes in myocardial iron content after FCM administration in patients with heart failure and iron deficiency using cardiac magnetic resonance. Methods and Results Fifty‐three stable heart failure and iron deficiency patients were randomly assigned 1:1 to receive intravenous FCM or placebo in a multicenter, double‐blind study. T2* and T1 mapping cardiac magnetic resonance sequences, noninvasive surrogates of intramyocardial iron, were evaluated before and 7 and 30 days after randomization using linear mixed regression analysis. Results are presented as least‐square means with 95% CI. The primary end point was the change in T2* and T1 mapping at 7 and 30 days. Median age was 73 (65–78) years, with N‐terminal pro‐B‐type natriuretic peptide, ferritin, and transferrin saturation medians of 1690 pg/mL (1010–2828), 63 ng/mL (22–114), and 15.7% (11.0–19.2), respectively. Baseline T2* and T1 mapping values did not significantly differ across treatment arms. On day 7, both T2* and T1 mapping (ms) were significantly lower in the FCM arm (36.6 [34.6–38.7] versus 40 [38–42.1], P =0.025; 1061 [1051–1072] versus 1085 [1074–1095], P =0.001, respectively). A similar reduction was found at 30 days for T2* (36.3 [34.1–38.5] versus 41.1 [38.9–43.4], P =0.003), but not for T1 mapping (1075 [1065–1085] versus 1079 [1069–1089], P =0.577). Conclusions In patients with heart failure and iron deficiency, FCM administration was associated with changes in the T2* and T1 mapping cardiac magnetic resonance sequences, indicative of myocardial iron repletion. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 03398681.

Down syndrome (DS) is characterized by structural and functional anomalies that are present prenatally and that lead to intellectual disabilities. Later in life, the cognitive abilities of DS individuals progressively deteriorate due to the development of Alzheimer's disease (AD)-associated neuropathology (i.e., β-amyloid (Aβ) plaques, neurofibrillary tangles (NFTs), neurodegeneration, synaptic pathology, neuroinflammation and increased oxidative stress). Increasing evidence has shown that among these pathological processes, neuroinflammation plays a predominant role in AD etiopathology. In AD mouse models, increased neuroinflammation appears earlier than Aβ plaques and NFTs, and in DS and AD models, neuroinflammation exacerbates the levels of soluble and insoluble Aβ species, favoring neurodegeneration. The Ts65Dn (TS) mouse, the most commonly used murine model of DS, recapitulates many alterations present in both DS and AD individuals, including enhanced neuroinflammation. In this study, we observed an altered neuroinflammatory milieu in the hippocampus of the TS mouse model. Pro-inflammatory mediators that were elevated in the hippocampus of this model included pro-inflammatory cytokine IL17A, which has a fundamental role in mediating brain damage in neuroinflammatory processes. Here, we analyzed the ability of an anti-IL17A antibody to reduce the neuropathological alterations that are present in TS mice during early neurodevelopmental stages (i.e., hippocampal neurogenesis and hypocellularity) or that are aggravated in later-life stages (i.e., cognitive abilities, cholinergic neuronal loss and increased cellular senescence, APP expression, Aβ peptide expression and neuroinflammation). Administration of anti-IL17 for 5 months, starting at the age of 7 months, partially improved the cognitive abilities of the TS mice, reduced the expression of several pro-inflammatory cytokines and the density of activated microglia and normalized the APP and Aβ levels in the hippocampi of the TS mice. These results suggest that IL17-mediated neuroinflammation is involved in several AD phenotypes in TS mice and provide a new therapeutic target to reduce these pathological characteristics., This study was supported by the Jerome Lejeune Foundation, Fundación Tatiana Pérez de Guzmán el Bueno, the Spanish Ministry of Economy and Competitiveness (PSI-2016-76194-R, SAF2014-55088-R, SAF2017-82905-R, SAF2016-75195-R, AEI/FEDER, EU) and Luchamos por la Vida Foundation.

Purpose The present clinical focus article describes and illustrates 3 key elements of a supports-based approach to enhancing friendship with autistic students. Method In comparison to the predominant skills-based approach, we highlight 3 key elements of a supports-based approach to social interaction for autistic children and youth. We then offer descriptive details of the activity-based music program as an illustrative example of a program that integrated all 3 elements of a supports-based approach. Specifically, we designed an activity-based music program to enhance social interaction among a 7-year-old autistic student and 4 of his nonautistic peers. Results We focused on 3 key elements of a supports-based approach for enhancing peer interaction: (a) focusing on participation in a shared activity, (b) encouraging flexible use of multiple communicative resources, and (c) supporting egalitarian interaction. Conclusion A supports-based approach presents a theoretically distinct and viable alternative to a skills-based approach in the design of social supports for autistic students and their peers.

Purpose The study examined the nature and potential impact of a relatively novel clinician strategy, behavioral interpretation, on peer interactions involving an autistic child. Method This extended qualitative analysis reviewed 49 instances of a clinician using behavioral interpretation as part of a music education program. The program was designed to facilitate peer interaction across a 7-year-old autistic child. Aaron, and 4 of his nonautistic peers from the same classroom. After reviewing the 21 video-recorded sessions, the research team selected the most salient examples of behavioral interpretation for microanalyses. Findings By focusing on a detailed review of the 6 most clear, concise, and compelling examples, we found that behavioral interpretation took 2 forms aimed at helping explain an unclear behavior: narrating (e.g., “I see you looking at strings”) and offering possible meanings (e.g., “I think he wants you to play guitar”). After limited exposure to behavioral interpretation, peers began displaying similar patterns of interaction that drew attention and speculation regarding Aaron's nonverbal forms of communication. Conclusions Behavioral interpretation, a relatively undocumented strategy in the autism literature, appeared as a feasible and promising strategy for shaping egalitarian peer interaction. Important nuances regarding the implementation and limitations of this strategy are also discussed.

Patients with COVID-19 may present a hypercoagulable state, with an important impact on morbidity and mortality. Because of this situation pulmonary embolism is a frequent complication during the course of infection. We present the case of a patient recently discharged, after admission with confirmed COVID-19, who developed a pulmonary embolism and thrombosis of a biological mitral valve prosthesis, producing valve obstruction and stenosis. After 15 days of anticoagulant treatment, resolution of the thrombus and normalization of prosthetic valve function was observed. This case supports current recommendations of administering full-dose anticoagulation therapy to COVID-19 patients with biological heart valve prosthesis, even after the acute phase of infection., We present the case of a patient who developed a pulmonary embolism and thrombosis of a biological mitral valve prosthesis, during recovery from COVID-19 infection. Our findings supports the recommendation of a prolonged anticoagulation strategy at full therapeutic doses in COVID-19 patients with biological heart valve prosthesis.

Background: The cognitive impairments that characterize Down syndrome (DS) have been attributed to brain hypocellularity due to neurogenesis impairment during fetal stages. Thus, enhancing prenatal neurogenesis in DS could prevent or reduce some of the neuromorphological and cognitive defects found in postnatal stages. Objectives: As fatty acids play a fundamental role in morphogenesis and brain development during fetal stages, in this study, we aimed to enhance neurogenesis and the cognitive abilities of the Ts65Dn (TS) mouse model of DS by administering oleic or linolenic acid. Methods: In total, 85 pregnant TS females were subcutaneously treated from Embryonic Day (ED) 10 until Postnatal Day (PD) 2 with oleic acid (400 mg/kg), linolenic acid (500 mg/kg), or vehicle. All analyses were performed on their TS and Control (CO) male and female progeny. At PD2, we evaluated the short-term effects of the treatments on neurogenesis, cellularity, and brain weight, in 40 TS and CO pups. A total of 69 TS and CO mice were used to test the long-term effects of the prenatal treatments on cognition from PD30 to PD45, and on neurogenesis, cellularity, and synaptic markers, at PD45. Data were compared by ANOVAs. Results: Prenatal administration of oleic or linolenic acid increased the brain weight (+36.7% and +45%, P < 0.01), the density of BrdU (bromodeoxyuridine)- (+80% and +115%; P < 0.01), and DAPI (4',6-diamidino-2-phenylindole)-positive cells (+64% and +22%, P < 0.05) of PD2 TS mice with respect to the vehicle-treated TS mice. Between PD30 and PD45, TS mice prenatally treated with oleic or linolenic acid showed better cognitive abilities (+28% and +25%, P < 0.01) and a higher density of the postsynaptic marker PSD95 (postsynaptic density protein 95) (+65% and +44%, P < 0.05) than the vehicle-treated TS animals. Conclusion: The beneficial cognitive and neuromorphological effects induced by oleic or linolenic acid in TS mice suggest that they could be promising pharmacotherapies for DS-associated cognitive deficits. This study was supported by “Fondazione Generali e Assicurazioni Generali”, Italy; Fundación Tatiana Pérez de Guzmán el Bueno, IDIVAL (NVAL 19/23), and the Spanish Ministry of Economy and Competitiveness (PSI-2016- 76194-R, AEI/FEDER, EU).

Prosthetic valve endocarditis is a major diagnostic challenge in clinical practice, due to the lower sensitivity of the modified Duke criteria and a higher percentage of cases with negative or inconclusive echocardiography results. The delay in establishing medical and surgical treatment increases the morbidity/mortality rate. New imaging techniques and 18F-FDG PET/CT in particular have meant a significant advance in cases of high clinical suspicion and negative or inconclusive echocardiography, increasing the overall sensitivity of the modified Duke criteria.We report the case of a male patient with prosthetic valve endocarditis, where 18F-FDG PET/CT provided the diagnostic key, determining the origin of the endocarditis and avoiding treatment delay. Resumo: A endocardite das próteses valvulares é um desafio diagnóstico real na prática clínica devido à menor sensibilidade dos critérios de Duke modificados e a uma maior percentagem de casos em que o ecocardiograma é negativo ou inconclusivo. O atraso no início do tratamento médico ou cirúrgico aumenta a taxa de morbilidade e mortalidade, de modo que o surgimento de novas técnicas de imagem e, em particular, da 18F-FDG PET/CT tem sido um grande avanço em casos de alta suspeição clínica com ecocardiograma negativo ou duvidoso, o que aumenta a sensibilidade global dos critérios diagnósticos de endocardite.Apresentamos o caso clínico de um homem com endocardite da prótese valvular em quem 18F-FDG PET/CT foi a chave diagnóstica que permitiu diferenciar a origem da endocardite e evitar o atraso do tratamento. Keywords: Prosthetic valve endocarditis, Cardiac imaging, 18F-FDG PET/CT, Modified Duke criteria, Palavras-chave: Endocardite das próteses valvulares, Imagem cardíaca, 18F-FDG PET/CT, Critérios de Duke modificados

Objective We characterized the dynamics of eosinophils in blood and in the infarcted myocardium in patients and in a swine model of reperfused myocardial infarction (MI). The association of eosinophil dynamics with various outcomes was assessed. Methods Serial eosinophil count and pre-discharge cardiac magnetic resonance were carried out in a prospective series of 620 patients with a first ST-elevation MI. In a swine model of reperfused MI, the dynamics of circulating eosinophils and their presence in the infarcted myocardium were determined. In autopsies from chronic MI patients, eosinophils were quantified. Results Patient eosinophil count sharply decreased 12h post-reperfusion compared to arrival. A lower minimum eosinophil count was associated with more extensive edema, microvascular obstruction, and infarct size as measured by cardiac magnetic resonance, and also with a higher rate of cardiac events (death, re-infarction, or heart failure) during follow-up. In the experimental model, eosinophil count boosted during ischemia and dropped back immediately post-reperfusion. Myocardial samples revealed progressive eosinophil migration into the infarcted myocardium, especially areas with microvascular obstruction. Markers of eosinophil maturation and survival (interleukin-5), degranulation (eosinophil cationic protein) and migration (eotoxin-1) were detected in the blood of patients, and in porcine myocardium. Eosinophil infiltration was detected in autopsies from chronic MI patients. Conclusion Eosinopenia post-MI was associated with an impaired cardiac structure and adverse events. The decay in circulating eosinophils soon after reperfusion mirrors their migration into the infarcted myocardium, as reflected by their presence in heart samples from swine and patients. Further studies are needed to understanding this unexplored pathway and its therapeutic implications.