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Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis and limited treatment options. Bulk genomic characterization of ACC has not yielded obvious therapeutic or immunotherapeutic targets, yet novel therapies are needed. We hypothesized that elucidating the intratumoral cellular heterogeneity by single nuclei RNA sequencing analyses would yield insights into potential therapeutic vulnerabilities of this disease. In addition to characterizing the immune cell and fibroblast landscape, our analyses of single nuclei gene expression profiles identified an adrenal cortex cell cluster exhibiting a program of replication stress and DNA damage response in primary and metastatic ACC. In vitro assessment of replication stress and DNA damage response using an ACC cell line and a series of newly-derived hormonally active patient-derived tumor organoids revealed ATR sensitivity. These findings provide novel mechanistic insight into ACC biology and suggest that an underlying dependency on ATR may be leveraged therapeutically in advanced ACC.

PIK3CA-related overgrowth spectrum (PROS) disorders are caused by somatic mosaic variants that result in constitutive activation of the phosphatidylinositol-3-kinase/AKT/mTOR pathway. Promising responses to molecularly targeted therapy have been reported, although identification of an appropriate agent can be hampered by the mosaic nature and corresponding low variant allele frequency of the causal variant. Moreover, our understanding of the molecular consequences of these variants-for example how they affect gene expression profiles-remains limited. Here we describe in vitro expansion of a human capillary malformation followed by molecular characterization using exome sequencing, single cell gene expression, and targeted long-read single cell RNA-sequencing in a patient with clinical features consistent with Megalencephaly-Capillary Malformation Syndrome (MCAP, a PROS condition). These approaches identified a targetable PIK3CA variant with expression restricted to PAX3+ fibroblast and undifferentiated keratinocyte populations. This study highlights the innovative combination of next-generation single cell sequencing methods to better understand unique transcriptomic profiles and cell types associated with MCAP, revealing molecular intricacies of this genetic syndrome., (© 2024. The Author(s).)

Oppositional defiant problems (ODP) and obsessive-compulsive problems (OCP) may co-occur in children, though the way they interact is not known. The aim of the study was to examine longitudinal associations between executive functions at age 3 and ODP, ODP dimensions, and OCP at age 6. The sample consisted of 622 preschoolers (50% were boys) from the general population. Executive functions were assessed by teachers using the Behavior Rating Inventory of Executive Functioning - Preschool version questionnaire when children were 3 years old, and ODP and OCP were informed by parents and teachers at the age of 6 years. Multiple linear regression analyses indicated that higher Inhibit and Emotional Control and lower Shift deficits were associated with higher ODP reported by teachers, while higher Shift but lower Inhibit deficits were related to higher OCP. Moreover, ODP and OCP shared difficulties on the Flexibility Index, which means that the capacity to modulate emotions and behavior according to contextual and environmental demands is compromised in both disorders. The findings inform etiology and prevention, pointing out not only the executive function specificities related to each problem, but also common cognitive challenges related to Flexibility. Young children could benefit from training and programs designed to improve executive function processes at an early age to prevent later behavioral difficulties.

Somatic mosaicism is a known cause of neurological disorders, including developmental brain malformations and epilepsy. Brain mosaicism is traditionally attributed to post-zygotic genetic alterations arising in fetal development. Here we describe post-zygotic rescue of meiotic errors as an alternate origin of brain mosaicism in patients with focal epilepsy who have mosaic chromosome 1q copy number gains. Genomic analysis showed evidence of an extra parentally derived chromosome 1q allele in the resected brain tissue from five of six patients. This copy number gain is observed only in patient brain tissue, but not in blood or buccal cells, and is strongly enriched in astrocytes. Astrocytes carrying chromosome 1q gains exhibit distinct gene expression signatures and hyaline inclusions, supporting a novel genetic association for astrocytic inclusions in epilepsy. Further, these data demonstrate an alternate mechanism of brain chromosomal mosaicism, with parentally derived copy number gain isolated to brain, reflecting rescue in other tissues during development., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Somatic variants are a major cause of human disease, including neurological disorders like focal epilepsies, but can be challenging to study due to their mosaicism in bulk tissue biopsies. Coupling single-cell genotype and transcriptomic data has potential to provide insight into the role somatic variants play in disease etiology, such as by determining what cell types are affected or how the mutations affect gene expression. Here, we asked whether commonly used single-nucleus 3'- or 5'-RNA-sequencing assays can be used to derive single-nucleus genotype data for a priori known variants that are located near to either end of a transcript. To that end, we compared performance of commercially available single-nuclei 3'- and 5'- gene expression kits using resected brain samples from three pediatric patients with focal epilepsy. We quantified the ability to detect genetic variants in single-nucleus datasets depending on distance from the transcript end. Finally, we demonstrated the ability to identify affected cell types in a patient with a RHEB somatic variant causing an epilepsy-associated cortical malformation. Our results demonstrate that single-nuclei 3' or 5'-RNA-sequencing data can be used to identify known somatic variants in single-nuclei when they are expressed within proximity to a transcript end., (© 2023. The Author(s).)

Rasmussen encephalitis (RE) is a rare childhood neurological disease characterized by progressive unilateral loss of function, hemispheric atrophy and drug-resistant epilepsy. Affected brain tissue shows signs of infiltrating cytotoxic T-cells, microglial activation, and neuronal death, implicating an inflammatory disease process. Recent studies have identified molecular correlates of inflammation in RE, but cell-type-specific mechanisms remain unclear. We used single-nucleus RNA-sequencing (snRNA-seq) to assess gene expression across multiple cell types in brain tissue resected from two children with RE. We found transcriptionally distinct microglial populations enriched in RE compared to two age-matched individuals with unaffected brain tissue and two individuals with Type I focal cortical dysplasia (FCD). Specifically, microglia in RE tissues demonstrated increased expression of genes associated with cytokine signaling, interferon-mediated pathways, and T-cell activation. We extended these findings using spatial proteomic analysis of tissue from four surgical resections to examine expression profiles of microglia within their pathological context. Microglia that were spatially aggregated into nodules had increased expression of dynamic immune regulatory markers (PD-L1, CD14, CD11c), T-cell activation markers (CD40, CD80) and were physically located near distinct CD4+ and CD8+ lymphocyte populations. These findings help elucidate the complex immune microenvironment of RE., (© 2022. The Author(s).)

This work tackles the measurement invariance of the social cognition construct when different observers, age and participant's age are considered. This is a prior question that needs to be answered before attributing discrepancies in information coming from diverse sources just to the varying behavior occurring across setting, and mainly interpret the discrepancies as indicative of cross-contextual variability. The article also studies the link between discrepancies and source-specific information and the validity of that information to predict several outcomes. The measurement invariance across sex, time and informant of a social cognition measure applied to children's parents and teachers was longitudinally tested in a Spanish general population sample, at ages 5 ( N  = 581) and 10 ( N  = 438). Full or partial metric and scalar equivalence were found across sex and over time within informants. Partial scalar invariance was not obtained across informants. Latent class analysis identified 2 classes of difficulties in social cognition for both informants at both ages: low social cognition and high social cognition. Comparison of classes resulting predicting outcomes yielded differential predictions due not only to varying context but also to a different concept of social cognition across informants. In general, significant differences between raters were informant dependent. We conclude that it is important to consider both teachers' and parents' observations to fully understand the construct of social cognition.

This study ascertains how the proposed subtypes and specifiers of oppositional defiant disorder (ODD) based on irritability and prosocial emotions co-develop and describes the clinical characteristics of the resultant classes. A sample of 488 community children was followed up from ages 3 to 12 years and assessed with categorical and dimensional measures answered by parents and teachers. Latent class growth analysis for three parallel processes [defiant/headstrong, irritability, and limited prosocial emotions (LPE)] identified a 4-class model with adequate entropy (.912) and posterior probabilities of class membership (≥ .921). Class 1 (n = 38, 7.9%) was made up of children with defiant/headstrong with chronic irritability and LPE. Class 2 (n = 128, 26.3%) was comprised of children with defiant/headstrong with chronic irritability and typical prosocial emotions. Class 3 (n = 101, 20.7%) clustered children with LPE without defiant/headstrong and without irritability. Class 4 (n = 220, 45.1%) included children with the lowest scores in all the processes. The classes were distinguishable and showed different clinical characteristics through development. These findings support the validity of ICD-11 ODD subtypes based on chronic irritability and may help to guide clinicians' decision-making regarding treating oppositionality in children., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Although irritability, headstrong/defiant behavior, and callous-unemotional traits (CU traits) often co-occur, the prospective associations between them are not well known. A general population sample of 622 children was followed up yearly from ages 3 to 12 years and assessed using dimensional measures of irritability, headstrong/defiant, and CU traits with teacher provided information. A random intercept cross-lagged panel model, accounting for all unmeasured time-invariant confounding using the children as their own controls, revealed cross-lagged reciprocal associations between increased headstrong/defiant and increased CU traits at all ages and a unidirectional association from headstrong/defiant to irritability. The findings are consistent with headstrong/defiant behavior and CU traits mutually influencing each other over time and headstrong/defiant behavior enhancing irritability. School-based intervention and prevention programs should take these findings into consideration. They also suggest that irritability acts as a distinct developmental dimension of headstrong/defiant and callous-unemotional behaviors and needs to be addressed independently., (© 2022. The Author(s).)

This longitudinal study aims to provide meaningful cutoff scores for total score of the teacher-rated Inventory of Callous-Unemotional Traits (ICU) from the preschool age until early adolescence, separately by age and sex. The ICU cutoff scores were determined by using low/high trajectories of oppositional defiant problems (ODP) and conduct problems in a Spanish community sample of 620 children that were followed up between the ages of 3 and 13. Receiver operating characteristic (ROC) curves with the two trajectories as criteria and ICU total score at each age as a predictor were estimated by sex separately, and the area under the ROC curve (AUC) was obtained. Average ICU cutoff scores of 26 for boys and 22 for girls were found to be of moderate utility for the prediction of high trajectories of each of ODP and conduct problems. They identified cases with an average sensitivity of 66% and specificity of 70% for boys and an average sensitivity of 69% and specificity of 72% for girls. The obtained cutoff scores might help clinical practitioners in their decision-making process when identifying low and high-risk groups of children. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Introduction: Necrotizing enterocolitis (NEC) remains a significant surgical emergency in neonates. We have demonstrated the efficacy of Lactobacillus reuteri (Lr) in protecting against experimental NEC when administered as a biofilm by incubation with maltose loaded dextranomer microspheres. Lr possesses antimicrobial and anti-inflammatory properties. We developed mutant strains of Lr to examine the importance of its antimicrobial and anti-inflammatory properties in protecting the intestines from NEC., Methods: Premature rat pups were exposed to hypoxia/hypothermia/hypertonic feeds to induce NEC. To examine the importance of antimicrobial reuterin and anti-inflammatory histamine, pups received either native or mutant forms of Lr, in either its planktonic or biofilm states, prior to induction of NEC. Intestinal histology was examined upon sacrifice., Results: Compared to no treatment, administration of a single dose of Lr in its biofilm state significantly decreased the incidence of NEC (67% vs. 18%, p < 0.0001), whereas Lr in its planktonic state had no significant effect. Administration of reuterin-deficient or histamine-deficient forms of Lr, in either planktonic or biofilm states, resulted in significant loss of efficacy., Conclusion: Antimicrobial and anti-inflammatory effects of Lr contribute to its beneficial effects against NEC. This suggests that both infectious and inflammatory components contribute to the etiology of NEC., Competing Interests: Declaration of Competing Interest Drs. Besner, Goodman and Bailey hold stock options and equity in Scioto Biosciences, Inc., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Little is known about the coexistence of oppositionality and obsessive-compulsive problems (OCP) in community children and how it affects their development until adolescence to prevent possible dysfunctions. The co-development of oppositional defiant dimensions and OCP is studied in 563 children (49.7% female) from ages 6 to 13 years, assessed yearly with measures answered by parents and teachers. A 4-class model based on Latent Class Growth Analysis for three parallel processes (irritability, defiant, and OCP) was selected, which showed adequate fitting indexes. Class 1 (n = 349, 62.0%) children scored low on all the measures. Class 2 (n = 53, 9.4%) contained children with high OCP and low irritability and defiant. Class 3 (n = 108, 19.2%) clustered children with high irritability and defiant and low OCP. Class 4 (n = 53, 9.4%) clustered comorbid irritability, defiant, and OCP characteristics. The classes showed different clinical characteristics through development. The developmental co-occurrence of irritability and defiant plus obsessive-compulsive behaviors is frequent and adds severity through development regarding comorbidity, peer problems, executive functioning difficulties, and daily functioning. The identification of different classes when combining oppositional problems and OCP may be informative to prevent developmental dysfunctions and to promote good adjustment through development., (© 2021. The Author(s).)

Callous Unemotional (CU) traits are associated with different environmental risk factors, such as negative stressful life events (SLE). The most common studied SLE associated with CU trait has been childhood maltreatment, but less is known about how other SLE impact the development of CU traits. Therefore, this work examines risk factors, personal factors (executive functioning), and mental health outcomes associated with the trajectories of Callous Unemotional (CU) traits and Stressful Life Events (SLE) in a community sample of children. A cohort of 377 preschoolers were followed up between ages 3 and 10. Several risk factors and outcomes for three trajectory groups (high CU/SLE; high CU/low SLE; and the reference group with low CU/SLE) were analyzed by using multiple post-hoc comparisons. We hypothesized that children with high CU/SLE would face more contextual risk factors, more executive functioning difficulties and more mental health problems than children with high CU/low SLE or the reference group. At the age of 3, children who showed high CU/SLE faced more early contextual adversity, including socioeconomic difficulties and maternal antisocial behavior than the other groups of children. At the age of 10, children with high CU/SLE presented more peer problems and higher psychopathology symptoms than the reference group, but no differences on mental health outcomes in comparison to the high CU/low SLE group. These results have potential implications for clinical practice and studies attempting to identify different CU subtypes in children.

This longitudinal study aims to define the developmental trajectories of social cognition (SC) in a community sample (N = 378) assessed from preschool (3 years old) to preadolescence (12 years old). Parents and teachers reported on a SC measure at ages 5, 10, and 12. We tested the existence of different trajectories and whether they discriminated outcomes in early adolescence. The data were collected from different sources, the children, the parents, and teachers, by means of different methods. Using Growth Mixture Modeling (GMM), we identified three distinct social cognition trajectories: persistently mild difficulties reported by parents and teachers (7.9% of the children), stable low problems reported by parents and increased difficulties reported by teachers (10.5% of the sample), and stable low problems reported by both informants for most of the participants (81.5%). Comparison of the psychological outcomes between classes using regression models showed that the two trajectories including children with any level of problems differ from the normative one as regards their association with psychological problems, daily functioning, and variables, such as aggressive behavior and callousness. The two non-normative trajectories also differ from each other in terms of the personal characteristics of the adolescents included in them. Adolescents in the increasing problematic class in the school have a tougher and more problematic style of social relating, while children with persistent and non-context-dependent difficulties are more anxious. These results might help to better detect and design specific interventions for children with deficits in SC that might respond to different personal characteristics leading to different outcomes., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Objectives: Although previous studies have proposed a positive influence of resilience on the mental and physical health of health care workers, empirical evidence on its relationship with occupational health remains scarce. This study aimed to analyze the relationship between individual resilience and several occupational health indicators, as well as exploring the moderating role of organizational resilience and sociodemographic attributes on this relationship., Methods: A cross-sectional design was used with a questionnaire applied to a sample of 325 workers from the Spanish health care sector., Results: Individual resilience was significantly associated with the indicators of occupational health. A direct effect of individual resilience on job satisfaction was found. The influence of resilience on the perception of fatigue and suffering from an illness was reverse. Age moderated the impact of resilience on the perception of stress and medical leave. Besides, organizational resilience proved to be an important adjustment variable in job satisfaction and perception of stress., Conclusions: The findings show the relevance to take both individual and organizational resilience into account when applying intervention programs to improve the occupational health of health care workers., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Maternal internalizing symptoms have been linked with child internalizing symptoms, but paternal internalizing difficulties have received little attention. Our aims were to prospectively analyse the simultaneous effect of maternal and paternal internalizing symptoms on child internalizing difficulties, examining gender differences, and to verify the mediating effect of parenting practices and child irritability. The sample included 470 families assessed at child ages 3, 6, 8, and 11. Multi-group structural equation modelling was performed with Mplus8.2. Complete equivalence was found between boys and girls for all paths. Maternal internalizing symptoms at age 3 had an indirect effect on child internalizing symptoms at age 11, via irritability at age 8. Paternal internalizing symptoms at age 3 were not associated with any of the variables under study. Maternal internalizing symptoms and child irritability are targets for intervention in order to prevent child internalizing difficulties., (© 2021 The British Psychological Society.)

The objective of this study was to explore social functioning in schizophrenic patients who have suffered child sexual abuse (CSA) in comparison with those who have not suffered from it in a Spanish sample of 50 patients with schizophrenia or schizoaffective disorder. The Quality of Life (QOL) Scale, the Childhood Trauma Questionnaire (CTQ-SF), and the NEO Five Factor Inventory (NEO-FFI) were administered in this study. We found a CSA prevalence of 22% in our sample. Results showed that QOL global scores reduced by 9.34% at a statistically significant level ( p = .037) in sexually abused patients in comparison with those who did not report experiencing sexual abuse. Regression analysis in the QOL scales showed no differences in intrapsychic foundation scores or in the social relations scale. Scores in the instrumental role scale were reduced by 4.42 points in patients with CSA ( p = .009). Neither neuroticism nor extraversion results differ between the trauma group and those who did not suffer trauma. Clinical implications of these results are discussed.

Background: Clostridium difficile infection is the most common cause of antimicrobial-associated diarrhea. Our aim was to introduce a novel and efficient clinical sickness score (CSS), and to define a detailed histologic injury score (HIS) in a murine model of C. difficile colitis. Methods: Mice received an antibiotic cocktail (kanamycin, gentamicin, colistin, metronidazole, and vancomycin) for 96 h. After 48 h, mice received an intraperitoneal injection of clindamycin, followed by oral C. difficile (1.5 × 10 7 CFU). Signs of sickness were scored using a novel CSS (range 0-12) with scores ≥6 consistent with C. difficile colitis. Intestinal tissue was analyzed utilizing an adapted HIS (range 0-9) with scores ≥4 consistent with C. difficile colitis. Stool was analyzed for C. difficile, and survival evaluated. Results: No control mice showed signs of sickness, whereas 23% of mice receiving antibiotics alone and 65% of mice exposed to antibiotics and subsequently C. difficile demonstrated signs of sickness ( p  = 0.0134). No control mice had histologic injury, whereas 8% of mice receiving antibiotics alone and 75% of mice exposed to antibiotics followed by C. difficile had evidence of histologic injury ( p  = 0.0001). Mice exposed to C. difficile lost more weight, although not significant ( p  = 0.070). Mice that received C. difficile had decreased survival compared to control mice and mice receiving antibiotics only ( p  = 0.03). Conclusions: We have developed a novel clinical scoring system, and detailed histological grading system, that enables the objective evaluation of a murine C. difficile colitis model. This model allows the study of this disease in a host that demonstrates clinical and histologic signs comparable to human C. difficile infection. This will allow for improved study of therapeutics for this disease in the future.

Irritability is a transdiagnostic symptom in oppositional defiant disorder, depression, and anxiety, all highly comorbid disorders but with unknown simultaneous evolution. The aim was to obtain the developmental trajectories of simultaneous irritability and oppositional, depression, and anxiety problems from preschool age to early adolescence. A sample of 493 community children was followed up annually from ages 3-11 years and assessed using categorical and dimensional measures answered by parents and teachers. Latent Class Growth Analysis for four parallel processes was used to identify distinct groups of individual trajectories for irritability and oppositional, depression, and anxiety problems. Outcomes at ages 11 and 12 were compared among trajectories using regression models and multiple comparisons. A 3-class model showed the highest entropy (0.961) and adequate posterior probabilities of class membership (≥0.969). Class 1 (n = 331, 67.1%) was made up of children with stable low scores in all the variables; class 2 (n = 55, 11.2%) of children with high depression, anxiety, and irritability and above the mean stable profiles for oppositional problems; and class 3 (n = 107, 21.7%) of children with medium-high increasing irritability and oppositional problems and on the mean depression and anxiety. The classes with symptomatology and irritability (2 and 3) clearly differed from class 1 (low) at baseline and in outcomes. The course of irritability and oppositional, depression, and anxiety problems from ages 3-11 years differed qualitatively and quantitatively across subgroups of children. The 3 classes identified may help to guide clinicians' decision-making regarding treating irritability and its comorbid disorders., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Spanish children were locked down for 72 days due to COVID-19, causing severe disruption to their normal life. The threat posed by COVID-19 continues and clinicians, administrators, and families need to know the life conditions associated with more psychological problems to modify them and minimize their effect on mental health. The goal was to study the life conditions of adolescents during lockdown and their association with psychological problems. A total of 226 parents of 117 girls and 109 boys (mean age: 13.9; Standard deviation: 0.28) from the community that were participants in a longitudinal study answered an online questionnaire about life conditions during lockdown and the Strengths and Difficulties Questionnaire (SDQ). Stepwise regression analyses controlling by previous reports of SDQ were performed. Conduct, peer, prosocial, and total problems scores increased after lockdown. After adjusting for previous measures of psychopathology, worse adolescents' mental health during COVID-19 lockdown was associated with unhealthy activities, worsening of the relationships with others, and dysfunctional parenting style. It seems important to mitigate psychological stress in a situation of isolation due to a state of emergency by keeping the adolescent active and maintaining their daily habits and routines in a non-conflictive atmosphere and give support to parents.

Lifestyle has a determining influence on the progression of a chronic kidney disease (CKD), which starts with some kidney damage, that can remain and progress by the influence of risk factors and accumulate subsequent injury of kidney damage throughout life. It is more common in adults and frequently remains hidden from routine analysis, but if it can be detected early, treatment and healthy lifestyle can be applied, which would allow stopping or lengthening the progress of kidney damage, in order to avoid the need of a renal transplant or dialysis. The objective of this work was to show the possible lifestyles to apply, such as visits to the doctor, not smoking, have intense to moderate physical activity, consume enough vegetables and fruits, avoid diets high in carbohydrates and lipids. To carry out this review, it was obtained literature from databases between 1980 and 2017, freely accessible, using keywords like “chronic kidney disease (CKD)”, “lifestyle” and “risk factors”, and its equivalents in Spanish., (Copyright: © 2020 Revista Medica del Instituto Mexicano del Seguro Social.)

Background: The Affective Reactivity Index (ARI) is a brief instrument originally designed as a self- and parent report. However, the view of teachers, who can observe social situations that may give rise to irritability, is relevant. The goal is to provide the measurement qualities of the ARI score as reported by teachers., Method: Children formed part of a longitudinal study on behavior problems in Barcelona (Spain) and they were assessed when they were 7 (N = 471) and 11 years old (N = 454) with questionnaires about psychopathology, anger and aggressive behavior, and a diagnostic interview answered by the parents, youths and teachers. Confirmatory factor analysis, measurement invariance, reliability and validity were studied for the ARI answered by teachers., Results: The 6-item, 1-factor model fitted well. Almost full metric invariance and partial scalar invariance was obtained across sex and over age. The ARI scores largely converged with other teacher-reported measures of anger and irritability, and with other measures of psychopathology, aggressive behavior, and callous-unemotional traits at a medium level. The associations with parent's measures were medium to low, and very low for child self-reported measures. The ARI scores significantly differentiated children with and without psychopathology and functional impairment, both cross-sectionally and longitudinally., Limitations: Only one child self-report measure of irritability included. Limited internal consistency of some scale scores. Findings are mostly generalizable to Spanish children., Conclusions: ARI could be a suitable instrument for measuring irritability as reported by teachers. The teacher's view can be useful when planning treatment by helping to identify treatment targets., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The objective was to obtain developmental trajectories combining callous-unemotional traits and the number of stressful life-events between ages 3 and 9 years and to ascertain their association with the polymorphism rs53576 at the Oxytocin Receptor gene (OXTR). A total of 377 children were assessed yearly from ages 3 to 9 years. Latent class growth analysis for parallel processes was used to identify distinct trajectories for callous-unemotional traits (assessed using the Inventory of Callous-Unemotional Traits, ICU) and number of stressful life-events, and then the influence of being an A allele carrier on class membership was included with OXTR genotypes as a binary time-invariant predictor, following a 3-step approach. A 3-class model showed the highest entropy (.859) and adequate posterior probabilities of class membership (≥.884). Class 1 (n = 226, 59.9%) included children with low and stable ICU scores and low and descending stressful life-events; class 2 (n = 127, 33.7%) included children with high and ascending ICU scores and low and slightly descending stressful life-events; and class 3 (n = 24, 6.4%) included children with persistently high profiles both for ICU scores and stressful life-events. Carrying an A allele (genotypes GA/AA) increased the odds of pertaining to class 3 (high and persistent ICU scores and stressful life-events) as opposed to class 2 (OR = 4.27, p = 0.034) or class 1 (OR = 3.81, p = 0.042). The results suggest the importance of considering callous-unemotional traits and stressful life-events in conjunction. In addition, the genetic variability of OXTR (rs53576) may help to understand individual differences in early development.

To study the prevalence of subthreshold oppositional defiant disorder (ST ODD)-less than 4 symptoms, but nonetheless an impairing form of oppositional defiant disorder (ODD)-its coexistence with other homotypic externalizing and heterotypical internalizing problems in children and associated impairment, as well as the long-term effect of this condition. A population-based sample of 622 preschoolers (5.0% boys) was followed up from preschool to preadolescence. Parents were interviewed when the children were 3, 6 and 9 years old with the Diagnostic Interview for Preschoolers/Children and Adolescents versions following DSM-5 and the children's functioning was assessed by trained clinicians. ST ODD diagnosis is highly prevalent (19.4-25.5%), highly comorbid [homo- (1.9-18.4%) and heterotypical (5.8-23.7%)], resulting in functional impairment across child development in a similar way for both genders. ST is also a risk factor condition that predicts the presence of psychological problems and impairment in childhood and preadolescence from preschool age. A broader clinical assessment and intervention similar to that provided full syndrome cases is needed for children presenting subthreshold forms of ODD.

Irritability and parenting are potential targets for transdiagnostic studies to identify the common and core dysfunctional characteristics underlying several diagnostic pictures with the goal of addressing these issues in treatment. Our objective was to investigate the different paths from temperament to child psychopathology (affective, anxiety, and oppositional problems) through irritability and parenting using a prospective design from ages 3 to 7. A sample of 614 3-year-old preschoolers was followed at ages 4, 6, and 7. Parents answered questionnaires about temperament (age 3), irritability (age 4), parenting practices (age 6), and psychopathology (age 7). Statistical analyses were carried out through structural equation modeling (SEM) to test the mediation effect of irritability and parenting practices from temperament (negative affectivity and effortful control) through to affective, anxious, and oppositional problems. The proposed model fit the data well. SEM showed (a) an indirect effect from temperament to affective problems, via irritability and positive parenting; (b) a direct effect from negative affectivity to anxiety, plus an indirect effect from both temperament dimensions, via irritability and autonomy parenting practices; and (c) an indirect effect from temperament to oppositional problems, via irritability and punitive parenting. Irritability and parenting are transdiagnostic mediational variables that should be focused on in intervention programs for affective, anxiety, and oppositional problems., (© 2019 Wiley Periodicals, Inc.)

Introduction: School victimization by peers is an important social problem with serious short- and long-term consequences poorly studied at preschool ages, which can lead to school bullying without timely intervention. Longitudinal data was used to determine the prevalence of warning signs of preschool peer victimization and its individual and family risk factors., Methods: Data was obtained from 577 community preschoolers. School victimization was measured using the Strengths and Difficulties Questionnaire (SDQ) administered to parents and teachers of children at ages 4 and 5. Risk factors for the child (demographics, conduct and emotional problems, aggressiveness) and the family (maternal problems during pregnancy and early development, parenting styles, adaptive functioning and parents' problems) were previously recorded at 3 years old., Results: Combined information from parents and teachers showed that 4.2% of preschoolers presented warning signs of victimization at ages 4 and 5. Low socioeconomic status, poor emotional control, early problems making friends and low level of parenting education in social norms at age 3 predicted later victimization at ages 4 and 5 (AUC = .78)., Conclusion: Peer victimization affects a considerable percentage of preschoolers. Early detection may help to reduce the risk of escalation., Competing Interests: The authors have declared that no competing interests exist.

The similarities between high functioning autism (HFA) and schizotypal-schizoid personality disorder (SSPD) in terms of social cognition and interpersonal deficits may lead to confusion in symptom interpretation, and consequently result in misdiagnosis. Thus, this study aims to investigate differences in mentalizing with particular interest on the socio-cognitive and socio-affective dimensions. Three Advanced Theory of Mind (ToM) tests were applied in 35 patients with HFA, 30 patients with SSPD and 36 healthy controls. Individuals with HFA showed greater impairment and no dissociation between affective and cognitive ToM components. Conversely, SSPD individuals displayed less difficulties but greater impairments on the cognitive component. Beyond the replicability of ToM impairment in HFA individuals, our findings suggest more impaired cognitive ToM in SSPD participants which further support the sequence of mentalizing development build upon different chronological stages.

Chemotherapy-Related Cognitive Impairment (CRCI) can be an adverse effect in women treated for breast cancer. Some longitudinal studies reported deficits in attention, memory, and executive function following treatment, but other studies did not find cognitive changes. It is known that practice effects (PE) on repeated assessments with cognitive tests contribute to the discrepancies in these results, but its influence on scores has not been systematically explored. The present study examines the impact of PE on retest scores in a group of women with breast cancer treated with chemotherapy and evaluated longitudinally., Method: 51 women with breast cancer treated with a combination of 5-fluorouracil, epirubicin, and cyclophosphamide with or without taxanes were assessed after surgery but before chemotherapy (T1), post-chemotherapy (T2), and at one year after T2 (T3). Longitudinal changes on cognitive performance were analyzed twice: when retest scores were not corrected for PE and when correction for PE was applied to T2 and T3 scores., Results: When PE was not corrected, progressive improvement over time in measures of memory and divided attention at T2 and T3 was observed. In contrast, when PE was corrected, worsening was found in measures of memory, fluency, executive function, and attention at T2 and in attention and executive function at T3. Results after correction for PE are in line with previous longitudinal studies that report cognitive impairment after treatment with chemotherapy for breast cancer., Conclusion: Accounting for PE is recommended to identify true change on cognition through treatment with chemotherapy for breast cancer.

Objective: To examine the 1-year first incidence and prevalence of oppositional defiant disorder (ODD), the outcomes on psychopathology and functioning by age of onset and the risk factors of onset of ODD from ages 3 to 9 in children from the Spanish general population., Design: Longitudinal with seven follow-ups and double cohort (ODD and non-ODD children)., Setting: General population of preschool and elementary school children in Barcelona (Spain)., Participants: On a first phase, the parent-rated Strengths and Difficulties Questionnaire conduct problems scale plus ODD Diagnostic and Statistical Manual of Mental Disorders, fourth version, symptoms were used to screen for behavioural problems. The second phase sample size contained 622 cases at age 3 and, at age 9, 418 remained in the study., Results: The probability of the onset of ODD showed increasing values at ages 4 (R=2.7%) and 5 years (R=4.4%). These values decreased until age 7 (R=1.9%) and increased again until age 9 (R=3.6%). Up to 9 years old, the cumulative risk of new cases of ODD was 21.9%. Early onset was associated with a higher risk of depression comorbidity and later onset with higher functional impairment and symptomatology. Subthreshold ODD, high scores in irritability and headstrong dimensions, attention deficit/hyperactivity disorder and other comorbidity, negative affectivity until age 7, difficulties in inhibit and emotional control, punitive parenting and maternal internalising problems were risk factors of a first episode of ODD during this 7-year period., Conclusions: The risk of new cases of ODD in the general population at preschool age and during childhood is high. Preschool age is a target period for preventive interventions. Identified risk factors are objectives for targeted and indicated interventions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

One significant drawback of current probiotic therapy for the prevention of necrotizing enterocolitis (NEC) is the need for at least daily administration because of poor probiotic persistence after enteral administration, increasing the risk of the probiotic bacteria causing bacteremia or sepsis if the intestines are already compromised. We previously showed that the effectiveness of Lactobacillus reuteri ( Lr) in preventing NEC is enhanced when Lr is grown as a biofilm on the surface of dextranomer microspheres (DM). Here we sought to test the efficacy of Lr administration by manipulating the Lr biofilm state with the addition of biofilm-promoting substances (sucrose and maltose) to DM or by mutating the Lr gtfW gene (encoding an enzyme central to biofilm production). Using an animal model of NEC, we determined that Lr adhered to sucrose- or maltose-loaded DM significantly reduced histologic injury, improved host survival, decreased intestinal permeability, reduced intestinal inflammation, and altered the gut microbiome compared with Lr adhered to unloaded DM. These effects were abolished when DM or GtfW were absent from the Lr inoculum. This demonstrates that a single dose of Lr in its biofilm state decreases NEC incidence. Importantly, preloading DM with sucrose or maltose further enhances Lr protection against NEC in a GtfW-dependent fashion, demonstrating the tunability of the approach and the potential to use other cargos to enhance future probiotic formulations. NEW & NOTEWORTHY Previous clinical trials of probiotics to prevent necrotizing enterocolitis have had variable results. In these studies, probiotics were delivered in their planktonic, free-living form. We have developed a novel probiotic delivery system in which Lactobacillus reuteri (Lr) is delivered in its biofilm state. In a model of experimental necrotizing enterocolitis, this formulation significantly reduces intestinal inflammation and permeability, improves survival, and preserves the natural gut microflora compared with the administration of Lr in its free-living form.

Background: Hostile Attributional Bias (HAB) has been related to conduct problems. The common and unique associations between the different dimensions of Oppositional Defiant Disorder (ODD) symptoms, specific components of HAB, sex and types of aggression (overt and relational) in a community sample of 491 7-year-old children are investigated., Method: Teachers rated the children's ODD symptoms and aggression and the children self-reported about HAB. Multiple linear regressions showed that ODD dimensions were directly associated with both types of aggression., Results: Boys were more overtly aggressive and girls more relational. Emotional distress was directly associated with relational aggression. The relational component of HAB uniquely moderated the influence of the oppositional dimension on relational aggressive behaviour., Conclusions: The assessment of social cognition variables is necessary to approach specific interventions in the presence of ODD symptoms, as this may help to identify a subset of children prone to aggressive reactions.

Objective: To obtain joint hypermobility classes in children from the general population and to study their characteristics in relation to anxiety measures., Methods: A total of 336 nine-year-old children from the general population were clinically assessed through 9 items of hypermobility, and their parents reported about the severity of anxiety symptoms. Latent class analysis was estimated to group the children according to the presence of hypermobility symptoms, and the obtained classes were related to anxiety., Results: A 2-class solution, labeled as high hypermobility and low hypermobility, best fitted the data. Children in the high hypermobility group scored higher in separation anxiety, social phobia, physical injury fears, and total anxiety than did those in the low group. When applying the threshold reference scores to the total anxiety score, 7.4% of children in the high hypermobility group versus 6% in the low group were reported to experience clinical elevations on total anxiety., Conclusion: High symptoms of hypermobility are associated with higher scores in anxiety symptoms in children from the general population. Children with frequent symptoms of hypermobility may benefit from screening for anxiety symptoms because a subset of them are experiencing clinical elevations and may need comprehensive physical and psychological treatment.

We provide the first validation data on the Spanish version of the Brief Problem Monitor-Parent form (BPM-P), a recently developed abbreviated version of the 120-item Child Behavior Checklist for Ages 6 to 18 (CBCL/6-18) in young schoolchildren. Parents of a community sample of 521 children aged 6-8 answered the CBCL/6-18 yearly, and the 19 BPM-P items were examined; parents also provided different measures of psychopathology. Confirmatory factor analysis of the expected 3-factor model (attention, externalizing, and internalizing) showed adequate fit (root mean square error of approximation, RMSEA ≤ .057), and measurement invariance across sex and age was observed. Internal consistency for the derived scores was satisfactory (ω ≥ .83). Concurrent validity with the equivalent scale scores of the original full CBCL/6-18 (r ≥ .84) and convergent validity with parents' ratings of the Strengths and Difficulties Questionnaire scores (r ≥ .52) were good. BPM-P scores at age 7 showed good predictive accuracy for discriminating the use of mental health services (OR ≥ 1.12), functional impairment (B ≤ -1.25), and the presence of the corresponding disorders diagnosed with an independent clinical interview, both cross-sectionally at age 7 and longitudinally at age 8 (OR ≥ 1.24). The BPM-P provides reliable and valid scores as a very brief follow-up and screening tool for assessing behavioral and emotional problems in young schoolchildren. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

In the present study, silver nanoparticles (AgNPs) were synthesized in situ on orthodontic elastomeric modules (OEM) using silver nitrate salts as metal-ion precursors and extract of the plant Hetheroteca inuloides ( H. inuloides ) as bioreductant via a simple and eco-friendly method. The synthesized AgNPs were characterized by UV-visible spectroscopy; scanning electron microscopy-energy-dispersive spectroscopy (SEM-EDS) and transmission electron microscopy (TEM). The surface plasmon resonance peak found at 472 nm confirmed the formation of AgNPs. SEM and TEM images reveal that the particles are quasi-spherical. The EDS analysis of the AgNPs confirmed the presence of elemental silver. The antibacterial properties of OEM with AgNPs were evaluated against the clinical isolates Streptococcus mutans , Lactobacillus casei , Staphylococcus aureus and Escherichia coli using agar diffusion tests. The physical properties were evaluated by a universal testing machine. OEM with AgNPs had shown inhibition halos for all microorganisms in comparison with OEM control. Physical properties increased with respect to the control group. The results suggest the potential of the material to combat dental biofilm and in turn decrease the incidence of demineralization in dental enamel, ensuring their performance in patients with orthodontic treatment., Competing Interests: All authors declare that we have no conflict of interest.

Performance of a group of 35 youth and adults with High-Functioning Autism (HFA) was compared with a typical developing (TD) group on three Advanced Theory of Mind tests. The distinction between the social-cognitive and social-perceptual components of Theory of Mind was also explored. The HFA group had more difficulties in all tasks. Performance on the two social-cognitive tests was highly correlated in the HFA group, but these were not related with the social-perceptual component. These results suggest that the youth with HFA have difficulties on all the components of social knowledge but may be using different underlying cognitive abilities depending on the nature of the task.

Purpose: The aim of this study is to elucidate the role of taxanes on cognition when they are administered as a part of the treatment with a fluorouracil, epirubicin and cyclophosphamide (FEC) regimen for breast cancer (BC)., Methods: Two groups of women (n = 51) with a novel diagnostic of BC that were treated with a combination of FEC alone (6 cycles of FEC) or with taxanes (4 cycles of FEC plus 8 cycles of taxanes) were compared at three moments: before chemotherapy, after its completion (short-term evaluation) and at a mean of 74.5 weeks from baseline as a long-term evaluation., Results: Both groups showed worsening in tests of attention and executive functions on the short-term assessment, with the group treated with taxanes showing more number of affected cognitive measures at this time point, including verbal learning and speed measures. At the long-term evaluation, cognitive dysfunction was still found in attention and executive functions in both groups., Conclusion: Our results suggest that chemotherapy for BC with a FEC regimen can have a negative effect on cognition. Acute deficits seem to be larger when taxanes are added, but treatment seems to affect cognition also at long term.

Background: There is debate about whether the difficulties that children with different degrees of oppositionality (ODD) and callous-unemotional traits (CU) have in processing emotions are global or specific. The aim of this study is to identify difficulties in recognizing emotion (happiness, anger, sadness and fear) through a go/no-go task in children with different levels of ODD and CU traits., Method: A total of 320 8-year-old children were assessed through questionnaires filled out by teachers about oppositional defiant symptoms and CU traits and were then distributed into four groups: LowCU-HighODD, HighCU-LowODD, HighCU-HighODD and a comparison group (LowCU-LowODD)., Results: The analyses of variance comparing the 4 groups showed that the two groups with high ODD were less accurate than the control group in recognizing the emotion when the stimuli expressed happiness, fear or neutral emotion. The HighCU-HighODD group differed in the quality of the response (correct/wrong responses) but not in the reaction time in relation to the comparison group. The LowCU-HighODD group was faster to respond to emotions than the comparison group., Implications: The results show that the deficit in emotion processing is not restricted to specific distressing emotions such as fear or sadness, but they point to a global impairment in emotion processing in children scoring high in the constructs studied. The results also suggest that the difficulties that children with combined CU traits and oppositional conduct problems have in processing emotions are more of an emotional rather than an attentional nature., (Copyright © 2017 Elsevier Inc. All rights reserved.)

As with all orally consumed probiotics, the Gram-positive bacterium Lactobacillus reuteri encounters numerous challenges as it transits through the gastrointestinal tract of the host, including low pH, effectors of the host immune system, as well as competition with commensal and pathogenic bacteria, all of which can greatly reduce the availability of live bacteria for therapeutic purposes. Recently we showed that L. reuteri , when adhered in the form of a biofilm to a semi-permeable biocompatible dextranomer microsphere, reduces the incidence of necrotizing enterocolitis by 50% in a well-defined animal model following delivery of a single prophylactic dose. Herein, using the same semi-permeable microspheres, we showed that providing compounds beneficial to L. reuteri as diffusible cargo within the microsphere lumen resulted in further advantageous effects including glucosyltransferase-dependent bacterial adherence to the microsphere surface, resistance of bound bacteria against acidic conditions, enhanced adherence of L. reuteri to human intestinal epithelial cells in vitro , and facilitated production of the antimicrobial compound reuterin and the anti-inflammatory molecule histamine. These data support continued development of this novel probiotic formulation as an adaptable and effective means for targeted delivery of cargo beneficial to the probiotic bacterium.

Periodontal disease exemplifies a chronic and recurrent infection with a necessary biofilm component. Mucosal inflammation is a hallmark response of the host seen in chronic diseases, such as colitis, gingivitis, and periodontitis (and the related disorder peri-implantitis). We have taken advantage of our recently developed rat model of human peri-implantitis that recapitulates osteolysis, the requirement of biofilm formation, and the perpetuation of the bona fide disease state, to test a new therapeutic modality with two novel components. First we used hyperimmune antiserum directed against the DNABII family of proteins, now known to be a critical component of the extracellular matrix of bacterial biofilms. Second we delivered the antiserum as cargo in biodegradable microspheres to the site of the biofilm infection. We demonstrated that delivery of a single dose of anti-DNABII in poly(lactic-co-glycolic acid) (PLGA) microspheres induced significant resolution of experimental peri-implantitis, including marked reduction of inflammation. These data support the continued development of a DNABII protein-targeted therapeutic for peri-implantitis and other chronic inflammatory pathologies of the oral cavity in animals and humans., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background/purpose: Probiotics reduce the incidence of necrotizing enterocolitis (NEC) albeit only when administered at high frequency (at least daily). We have developed a novel probiotic delivery system in which probiotics are grown as a biofilm on microspheres, allowing enhanced efficacy with only a single treatment., Methods: Neonatal rats were subjected to experimental NEC. Pups received a single enteral dose of: (1) vehicle only, (2) unloaded microspheres, (3) MRS (broth)-loaded microspheres, (4) Lactobacillus reuteri, (5) L. reuteri grown on unloaded microspheres, or (6) L. reuteri grown on MRS-loaded microspheres. Intestinal injury was graded histologically and intestinal permeability determined by serum levels of enterally administered fluorescein isothiocyanate-labeled dextran., Results: 69% of untreated pups developed NEC, whereas 32% of pups treated with L. reuteri grown as a biofilm on unloaded microspheres (p=0.009) and 33% of pups treated with L. reuteri grown as a biofilm on MRS-loaded microspheres (p=0.005) developed NEC. No other group had a significant reduction in NEC. Furthermore, pups treated with L. reuteri grown as a biofilm had significantly reduced intestinal permeability., Conclusions: A single dose of Lactobacillus biofilm grown on biocompatible microspheres significantly reduces NEC incidence and severity. This novel probiotic delivery system may be beneficial in the prevention of NEC in the future., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Previous studies on developmental trajectories have used ad hoc definitions of oppositional defiant behaviors (ODB), which makes it difficult to compare results. This article defines developmental trajectories of ODB from ages 3-5 based on five different standard measurements derived from three separate instruments., Method: A sample of 622 three-year-old preschoolers, followed up at ages 4, 5, and 6, was assessed with the five measures of oppositionality answered by parents and teachers. Growth-Mixture-Modeling (GMM) estimated separate developmental trajectories for each ODB measure for ages 3 to 5., Results: The number of classes-trajectories obtained in each GMM depended on the ODB measure, but two clear patterns emerged: four trajectories (persistent low, decreasers, increasers/high increasers, persistent moderate/persistent high) or three trajectories (persistent low, decreasers, increasers/high increasers). Persistent high trajectories accounted for 4.4%-9.5% of the children. The trajectories emerging from the different ODB measures at ages 3 to 5 discriminated disruptive disorders, comorbidity, use of services, and impairment at age 6, and globally showed a similar pattern, summarizing longitudinal information on oppositionality in preschool children in a similar way., Conclusions: Trajectories resulting from standard scales of the questionnaires have predictive validity for identifying relevant clinical outcomes, but are measure-specific. The results contribute to knowledge about the development of ODB in preschool children.

Introduction: Patients suffering from severe mental disorder present a mixed complexity of clinical and social needs which can be reliably evaluated through the Camberwell Assessment of Needs (CAN). In his study, several social, personal and clinical variables will be examined as predictive factors of the detected needs of these patients., Methodology: A sample of 518 patients included in a program of Severe Mental Disorder and treated at two centers in Barcelona was assessed with the CAN. Descriptive statistics and Poisson and negative binomial regression models were applied to identify predictive factors of needs., Results: The average number of needs was 5.1 (4 met and 1.1 unmet needs), figures similar to those found in European cities (Epsilon study). The more often reported needs were symptoms of anxiety or psychological discomfort, psychotic symptoms, problems in the home care, lack of social contact, medical and eating problems. Factors associated to higher number of needs were low socioeconomic class, older age, worse overall performance and presence of psychotic disorder., Conclusions: Needs detected through CAN in patients suffering from severe mental illness, can be predicted by a set of variables including age, socio-economic class, overall performance and presence of psychotic disorder. These findings might be useful to plan the provision of services and strategies to satisfy the needs of patients with serious mental disorder.

Criticism directed by caregivers towards a family member with schizophrenia, both from the perspective of the patient and of the caregiver, predicts relapse, although both perspectives differ. This study aims to verify if the same applies to a Mediterranean sample, where criticism is not the main attitude of high expressed emotion families. The Camberwell Family Interview was applied to assess the family's perspective, and the Perceived Criticism and the Family Emotional Involvement and Criticism Scales were used to assess the patients' perspective, in 21 dyads. The association between both perspectives and psychotic symptoms was also examined. Results replicated those of previous studies in other countries, revealing that the perspectives on Criticism of patients and families do not match. The fact that family members also presented positive attitudes towards the patient did not cushion the patient's perceived criticism. Thus, it seems that families considered to be critical may not be perceived as such by the patients. Furthermore, only the warmth from the family's perspective correlated with the symptoms: positive affect proved to be more relevant than negative affect. Therefore, the patients' subjective assessments and family warmth should be included in clinical and research proposals.

High expressed emotion (EE) as measured by the Camberwell Family Interview (CFI) predicts the course of eating disorders (ED). Despite its important contribution to the field, the CFI has two major limitations; it is time-consuming and it does not consider the patient's perspective. Obtaining the patient's view may help shed light on the dyadic nature of caregiver's EE and the patient's illness course. The objectives of our study of 77 patients with ED were to develop further a brief measure to assess the patients' perceptions of their caregivers' EE, the patient version of the Brief Dyadic Scale of Expressed Emotion (BDSEE), and to evaluate its psychometric properties. Three clearly separate factors were identified: perceived criticism, perceived emotional overinvolvement, and perceived warmth. The BDSEE also demonstrated good levels of reliability and construct validity. The BDSEE subscales are significantly related to other measures of the perceived family emotional climate and to the CFI, the gold standard in the field of EE. The clinical implications of the ED patients' perceptions of their caregivers' EE are discussed. Findings support the utility of the expanded BDSEE for both research and clinical practise in assessing the perspective of patients with ED., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Studies of psychotic-like experiences (PLEs) within community samples of adolescents have explored predominantly positive experiences. There is a paucity of research examining the prevalence and correlates of negative PLEs, and whether particular subtypes of negative PLEs can be identified among the general population of adolescents. This study examined the association of both positive and negative PLEs with depressive symptoms, including detailed analysis of subtypes of positive and negative psychosis dimensions., Method: A community sample of 777 adolescents (50.9% girls: mean age 14.4 years) completed a questionnaire assessing positive and negative PLEs and depressive symptoms., Results: Principal component factor analysis identified four factors of positive symptoms (persecutory ideation, grandiose thinking, first-rank/hallucinatory experiences and self-referential thinking), and three factors of negative symptoms (social withdrawal, affective flattening, and avolition). Depressive symptoms were associated positively with persecutory ideation, first-rank/hallucinatory experiences, social withdrawal, and avolition, whereas grandiose thinking related negatively with depressive symptoms. Neither self-referential thinking nor affective flattening related to self-reported depression., Conclusions: These findings support the view that not all types of positive and negative PLEs in adolescence are associated with depression and, therefore, they may not confer the same vulnerability for psychotic disorders., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

This study examined 'Theory of Mind' (ToM) functioning, its association with psychometric schizotypy and with self-reported psychotic-like experiences (PLEs) and depressive symptoms, in a community sample of adolescents. Seventy-two adolescents (mean age 14.51years) from Barcelona, Spain, completed questionnaires assessing PLEs, depressive symptoms, and schizotypy. A verbal ToM task and a vocabulary test were administered. The effect of symptomatology, vocabulary ability, age, and gender on task performance was explored. Neither total score on schizotypy nor PLEs were associated with ToM performance. A significant effect of vocabulary on adolescent's performance of both ToM and control stories was found. ToM showed significant negative associations with positive schizotypy, and with one cluster of positive PLEs: first-rank experiences. Positive significant associations between ToM and persecutory delusions and the impulsive aspects of schizotypy were found. Depressive symptoms did not affect ToM performance. Positive schizotypal traits and first-rank symptoms are associated with ToM deficits in adolescents. Results support the trait-(versus state-) dependent notion of ToM impairments in schizophrenia. ToM may be a developmental impairment associated with positive schizotypy and PLEs., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

To report a case of nanophthalmos in which the intraocular pressure (IOP) off medication was 45 mm Hg and on dorzolamide hydrochloride once daily was 15 mm Hg for many years. No other medication affected the IOP. A chart review of a patient with nanophthalmos and glaucoma. A case of angle closure glaucoma in a nanophthalmic eye which had an unusually great and prolonged reduction of IOP secondary to the use of dorzolamide once daily, was reported., (Copyright 2010, SLACK Incorporated.)

A coordinated study of water chemistry, sediment mineralogy, and sediment microbial community was conducted on four >73 degrees C springs in the northwestern Great Basin. Despite generally similar chemistry and mineralogy, springs with short residence time (approximately 5-20 min) were rich in reduced chemistry, whereas springs with long residence time (>1 day) accumulated oxygen and oxidized nitrogen species. The presence of oxygen suggested that aerobic metabolisms prevail in the water and surface sediment. However, Gibbs free energy calculations using empirical chemistry data suggested that several inorganic electron donors were similarly favorable. Analysis of 298 bacterial 16S rDNAs identified 36 species-level phylotypes, 14 of which failed to affiliate with cultivated phyla. Highly represented phylotypes included Thermus, Thermotoga, a member of candidate phylum OP1, and two deeply branching Chloroflexi. The 276 archaeal 16S rDNAs represented 28 phylotypes, most of which were Crenarchaeota unrelated to the Thermoprotei. The most abundant archaeal phylotype was closely related to "Candidatus Nitrosocaldus yellowstonii", suggesting a role for ammonia oxidation in primary production; however, few other phylotypes could be linked with energy calculations because phylotypes were either related to chemoorganotrophs or were unrelated to known organisms.

Ephemerally wet playas are conspicuous features of arid landscapes worldwide; however, they have not been well studied as habitats for microorganisms. We tracked the geochemistry and microbial community in Silver Lake playa, California, over one flooding/desiccation cycle following the unusually wet winter of 2004-2005. Over the course of the study, total dissolved solids increased by approximately 10-fold and pH increased by nearly one unit. As the lake contracted and temperatures increased over the summer, a moderately dense planktonic population of approximately 1x10(6) cells ml(-1) of culturable heterotrophs was replaced by a dense population of more than 1x10(9) cells ml(-1), which appears to be the highest concentration of culturable planktonic heterotrophs reported in any natural aquatic ecosystem. This correlated with a dramatic depletion of nitrate as well as changes in the microbial community, as assessed by small subunit ribosomal RNA gene sequencing of bacterial isolates and uncultivated clones. Isolates from the early-phase flooded playa were primarily Actinobacteria, Firmicutes, and Bacteroidetes, yet clone libraries were dominated by Betaproteobacteria and yet uncultivated Actinobacteria. Isolates from the late-flooded phase ecosystem were predominantly Proteobacteria, particularly alkalitolerant isolates of Rhodobaca, Porphyrobacter, Hydrogenophaga, Alishwenella, and relatives of Thauera; however, clone libraries were composed almost entirely of Synechococcus (Cyanobacteria). A sample taken after the playa surface was completely desiccated contained diverse culturable Actinobacteria typically isolated from soils. In total, 205 isolates and 166 clones represented 82 and 44 species-level groups, respectively, including a wide diversity of Proteobacteria, Bacteroidetes, Actinobacteria, Firmicutes, Gemmatimonadetes, Acidobacteria, and Cyanobacteria.