Focus ion beam/scanning electron microscopy characterization of osteoclastic resorption of calcium phosphate substrates

This article presents the application of dual focused ion beam/scanning electron microscopy (FIB-SEM) imaging for preclinical testing of calcium phosphates with osteoclast precursor cells and how this high-resolution imaging technique is able to reveal microstructural changes at a level of detail previously not possible. Calcium phosphate substrates, having similar compositions but different microstructures, were produced using low- and high-temperature processes (biomimetic calcium-deficient hydroxyapatite [CDHA] and stoichiometric sintered hydroxyapatite, respectively). Human osteoclast precursor cells were cultured for 21 days before evaluating their resorptive potential on varying microstructural features. Alternative to classical morphological evaluation of osteoclasts (OC), FIB-SEM was used to observe the subjacent microstructure by transversally sectioning cells and observing both the cells and the substrates. Resorption pits, indicating OC activity, were visible on the smoother surface of high-temperature sintered hydroxyapatite. FIB-SEM analysis revealed signs of acidic degradation on the grain surface under the cells, as well as intergranular dissolution. No resorption pits were evident on the surface of the rough CDHA substrates. However, whereas no degradation was detected by FIB sections in the material underlying some of the cells, early stages of OC-mediated acidic degradation were observed under cells with more spread morphology. Collectively, these results highlight the potential of FIB to evaluate the resorptive activity of OC, even in rough, irregular, or coarse surfaces where degradation pits are otherwise difficult to visualize.Peer ReviewedPostprint (author's final draft

The impact of attention-deficit/hyperactivity disorder and specific learning disorders on academic performance in Spanish children from a low-middle- and a high-income population

IntroductionPast research has demonstrated that attention-deficit/hyperactivity disorder (ADHD), specific learning disorders (SLD), and socioeconomic status (SES) affect a host of educational outcomes. However, there are no studies examining whether SES moderates the association between these neurodevelopmental disorders (ND) and the academic achievement of children and adolescents. The present investigation examined the impact of ADHD and SLD on academic performance in 1,287 Spanish students aged 5–17 from a low-middle (LM)- and a high-income population, when adjusted for comorbidity and demographic factors that may influence educational functioning.MethodsParents completed a questionnaire regarding demographic data along with the Strengths and Difficulties Questionnaire. Additionally, teachers provided information on learning difficulties trough the Protocol for Detection and Management of Dyslexia. Teacher’s Version. Academic performance across multiple domains (i.e., first language, foreign language, mathematics) was obtained from school records. ND were determined using standardized diagnostic methods based on the Diagnostic and Statistical Manual of Mental Disorders criteria. To examine the effects of ADHD and SLD on academic achievement and the potential moderating role of SES, a series of ordinal logistic regressions were conducted.ResultsEmotional/behavioral problems, learning difficulties, and ND were more frequent among individuals from the LM-income population. After controlling for gender, age, parental divorce/separation, grade retention, frequency of screen use, and daily meals, both ADHD and SLD were associated with worse educational outcomes. Lower SES also increased the risk for academic impairment, although the interactions with ADHD or SLD were not significant.ConclusionThese findings indicate that ADHD and SLD exert a pervasive impact on academic performance across different socioeconomic backgrounds. Therefore, early detection and effective intervention strategies aimed at students with these ND are crucial to improve their educational functioning and mitigate the negative consequences related to academic problems

The impact of psychopathology on academic performance in school-age children and adolescents

Anxiety; Depression; Psychiatric disordersAnsiedad; Depresión; Desórdenes psiquiátricosAnsietat; Depressió; Trastorns psiquiàtricsPsychiatric symptoms have consistently been associated with negative educational outcomes. However, possible confounding variables, such as comorbid mental and environmental conditions, have not been well addressed. This study examined whether mental health problems were significantly linked to academic performance in a Spanish school-based sample, after adjustment for co-occurring psychiatric symptoms and multiple contextual factors. Parents completed a questionnaire regarding child’s sociodemographic characteristics (i.e., gender, age, type of school, socioeconomic status, ethnicity), stressful events (i.e., adoption, parental divorce/separation, grade retention) and lifestyle (i.e., diet, sleep, screen time), along with the Child Behavior Checklist (CBCL). Academic performance was obtained from school records. The sample comprised 7036 students aged 5–17 with full data on the CBCL. Mixed-effects ordinal logistic regression analyses were conducted to investigate the association between psychopathology and academic achievement, controlling for potential confounders. When examined separately, higher scores on the CBCL scales were related to lower grades, regardless of sociodemographic factors. However, after controlling for the presence of other psychiatric symptoms, we found that students who reported more anxious/depressed and thought problems were less likely to perform poorly, while those with increased levels of attention problems and delinquent behavior had higher risk for academic underachievement. These associations remained mainly the same once stressful events and lifestyle were taken into account. This investigation demonstrates that anxious/depressed symptoms, thought problems, attention problems, and delinquent behavior are independently associated with academic performance, which emphasize the need for preventive and treatment interventions targeted at students’ mental health to improve their psychological well-being and functioning at school.This work was funded by “la Caixa” Banking Foundation, Diputació de Barcelona, Diputació de Lleida, and Ministry of Health of Generalitat de Catalunya

Effect of moisture on the reactivity of alpha-tricalcium phosphate

The ability of the high-temperature polymorph of tricalcium phosphate, a-TCP, to hydrolyse to calcium-deficient hydroxyapatite underlies many developments in the field of synthetic bone grafts, including calcium phosphate cements, foams, and self-setting inks. The objective of the present work was to investigate the effect of humidity on a-TCP powder reactivity. The results showed that a 3-week incubation at high relative humidity (80%) had no impact on reactivity, but, as the incubation was prolonged, the powder started to hydrolyse. This reactivity was associated to the presence of defects and to an amorphous phase induced during powder milling. Moisture studies performed under static/dynamic conditions gave comparable water adsorption percentages. The dynamic studies further proved irreversible water sorption, indicating that some water molecules reacted with the powder after short incubation times. Taken together, these results demonstrate that, although a-TCP powder adsorbs water from moisture immediately, the impact on reactivity appears only after several weeks of storage.Peer ReviewedPostprint (published version

The impact of attention-deficit/hyperactivity disorder and specific learning disorders on academic performance in Spanish children from a low-middle- and a high-income population

Past research has demonstrated that attention-deficit/hyperactivity disorder (ADHD), specific learning disorders (SLD), and socioeconomic status (SES) affect a host of educational outcomes. However, there are no studies examining whether SES moderates the association between these neurodevelopmental disorders (ND) and the academic achievement of children and adolescents. The present investigation examined the impact of ADHD and SLD on academic performance in 1,287 Spanish students aged 5-17 from a low-middle (LM)- and a high-income population, when adjusted for comorbidity and demographic factors that may influence educational functioning. Parents completed a questionnaire regarding demographic data along with the Strengths and Difficulties Questionnaire. Additionally, teachers provided information on learning difficulties trough the Protocol for Detection and Management of Dyslexia. Teacher's Version. Academic performance across multiple domains (i.e., first language, foreign language, mathematics) was obtained from school records. ND were determined using standardized diagnostic methods based on the Diagnostic and Statistical Manual of Mental Disorders criteria. To examine the effects of ADHD and SLD on academic achievement and the potential moderating role of SES, a series of ordinal logistic regressions were conducted. Emotional/behavioral problems, learning difficulties, and ND were more frequent among individuals from the LM-income population. After controlling for gender, age, parental divorce/separation, grade retention, frequency of screen use, and daily meals, both ADHD and SLD were associated with worse educational outcomes. Lower SES also increased the risk for academic impairment, although the interactions with ADHD or SLD were not significant. These findings indicate that ADHD and SLD exert a pervasive impact on academic performance across different socioeconomic backgrounds. Therefore, early detection and effective intervention strategies aimed at students with these ND are crucial to improve their educational functioning and mitigate the negative consequences related to academic problems

Effect of calcium phosphate heparinization on the in vitro inflammatory response and osteoclastogenesis of human blood precursor cells

The immobilization of natural molecules on synthetic bone grafts stands as a strategy to enhance their biological interactions. During the early stages of healing, immune cells and osteoclasts (OC) modulate the inflammatory response and resorb the biomaterial, respectively. In this study, heparin, a naturally occurring molecule in the bone extracellular matrix, was covalently immobilized on biomimetic calcium-deficient hydroxyapatite (CDHA). The effect of heparin-functionalized CDHA on inflammation and osteoclastogenesis was investigated using primary human cells and compared with pristine CDHA and beta-tricalcium phosphate (ß-TCP). Biomimetic substrates led to lower oxidative stresses by neutrophils and monocytes than sintered ß-TCP, even though no further reduction was induced by the presence of heparin. In contrast, heparinized CDHA fostered osteoclastogenesis. Optical images of stained TRAP positive cells showed an earlier and higher presence of multinucleated cells, compatible with OC at 14 days, while pristine CDHA and ß-TCP present OC at 21–28 days. Although no statistically significant differences were found in the OC activity, microscopy images evidenced early stages of degradation on heparinized CDHA, compatible with osteoclastic resorption. Overall, the results suggest that the functionalization with heparin fostered the formation and activity of OC, thus offering a promising strategy to integrate biomaterials in the bone remodelling cycle by increasing their OC-mediated resorption.Peer ReviewedPostprint (author's final draft

Functioning assessment short test (FAST): validity and reliability in adults with Autism Spectrum Disorder

Quocient de l'espectre de l'autisme; Anàlisi factorial; FiabilitatCociente del espectro autista; Análisis factorial; FiabilidadAutism Spectrum quotient; Factor analysis; ReliabilityBackground The assessment of functional impairment is crucial both for the diagnosis and the therapeutic approach to autism spectrum disorder (ASD). The purpose of the present study was to evaluate whether the FAST is a reliable and valid tool to assess functional impairment in adults with Level 1 ASD and to study the differences in psychosocial functioning between younger and older adults with ASD. Methods A case–control study was carried out in a sample of 150 participants, 71 adults with Level 1 ASD, and 79 adults without psychiatric history records. Results Results showed good psychometric properties in terms of validity and reliability. Cronbach’s alpha for the total scale was .91 and the area under the curve was .98. The study also showed that adults with ASD present different profiles of functional impairment depending on their age: while younger patients present greater impairment in autonomy, older patients show more difficulties in interpersonal relationships. Conclusions Our results support the use of the FAST in the evaluation of adaptive functioning in adults with Level 1 ASD.The author ISR is currently funded by the Pla estratègic de recerca i innovació en salut (PERIS) 2016–2020 (SLT006/17/00287) and Instituto de Salud Carlos III (PI18/01788). The funders played no part in study design, collection, management, and interpretation of the data; writing the report; or the decision to submit the report for publication

Functioning assessment short test (FAST) : validity and reliability in adults with Autism Spectrum Disorder

Altres ajuts: PERIS, SLT006/17/00287The assessment of functional impairment is crucial both for the diagnosis and the therapeutic approach to autism spectrum disorder (ASD). The purpose of the present study was to evaluate whether the FAST is a reliable and valid tool to assess functional impairment in adults with Level 1 ASD and to study the differences in psychosocial functioning between younger and older adults with ASD. A case-control study was carried out in a sample of 150 participants, 71 adults with Level 1 ASD, and 79 adults without psychiatric history records. Results showed good psychometric properties in terms of validity and reliability. Cronbach's alpha for the total scale was.91 and the area under the curve was.98. The study also showed that adults with ASD present different profiles of functional impairment depending on their age: while younger patients present greater impairment in autonomy, older patients show more difficulties in interpersonal relationships. Our results support the use of the FAST in the evaluation of adaptive functioning in adults with Level 1 AS

The impact of psychopathology on academic performance in school-age children and adolescents

Psychiatric symptoms have consistently been associated with negative educational outcomes. However, possible confounding variables, such as comorbid mental and environmental conditions, have not been well addressed. This study examined whether mental health problems were significantly linked to academic performance in a Spanish school-based sample, after adjustment for co-occurring psychiatric symptoms and multiple contextual factors. Parents completed a questionnaire regarding child's sociodemographic characteristics (i.e., gender, age, type of school, socioeconomic status, ethnicity), stressful events (i.e., adoption, parental divorce/separation, grade retention) and lifestyle (i.e., diet, sleep, screen time), along with the Child Behavior Checklist (CBCL). Academic performance was obtained from school records. The sample comprised 7036 students aged 5-17 with full data on the CBCL. Mixed-effects ordinal logistic regression analyses were conducted to investigate the association between psychopathology and academic achievement, controlling for potential confounders. When examined separately, higher scores on the CBCL scales were related to lower grades, regardless of sociodemographic factors. However, after controlling for the presence of other psychiatric symptoms, we found that students who reported more anxious/depressed and thought problems were less likely to perform poorly, while those with increased levels of attention problems and delinquent behavior had higher risk for academic underachievement. These associations remained mainly the same once stressful events and lifestyle were taken into account. This investigation demonstrates that anxious/depressed symptoms, thought problems, attention problems, and delinquent behavior are independently associated with academic performance, which emphasize the need for preventive and treatment interventions targeted at students' mental health to improve their psychological well-being and functioning at schoo

Genetic association study of childhood aggression across raters, instruments, and age

Genòmica; Comportament humàGenómica; Comportamiento humanoGenomics; Human behaviourChildhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E–06), PCDH7 (P = 2.0E–06), and IPO13 (P = 2.5E–06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg = 0.46 between self- and teacher-assessment to rg = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range |rg|: 0.19–1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg = ~−0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |rg|: 0.46–0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.We very warmly thank all participants, their parents, and teachers for making this study possible. The project was supported by the “Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies” project (ACTION). ACTION received funding from the European Union Seventh Framework Program (FP7/2007-2013) under grant agreement no 602768. Cohort-specific acknowledgements and funding information may be found in the Supplementary text