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It has not yet been determined if the commonly reported cannabis–psychosis association is limited to individuals with pre-existing genetic risk for psychotic disorders.
We examined whether the relationship between polygenic risk score for schizophrenia (PRS-Sz) and psychotic-like experiences (PLEs), as measured by the Community Assessment of Psychic Experiences-42 (CAPE-42) questionnaire, is mediated or moderated by lifetime cannabis use at 16 years of age in 1740 of the individuals of the European IMAGEN cohort. Secondary analysis examined the relationships between lifetime cannabis use, PRS-Sz and the various sub-scales of the CAPE-42. Sensitivity analyses including covariates, including a PRS for cannabis use, were conducted and results were replicated using data from 1223 individuals in the Dutch Utrecht cannabis cohort.
PRS-Sz significantly predicted cannabis use (p = 0.027) and PLE (p = 0.004) in the IMAGEN cohort. In the full model, considering PRS-Sz and covariates, cannabis use was also significantly associated with PLE in IMAGEN (p = 0.007). Results remained consistent in the Utrecht cohort and through sensitivity analyses. Nevertheless, there was no evidence of a mediation or moderation effects.
These results suggest that cannabis use remains a risk factor for PLEs, over and above genetic vulnerability for schizophrenia. This research does not support the notion that the cannabis–psychosis link is limited to individuals who are genetically predisposed to psychosis and suggests a need for research focusing on cannabis-related processes in psychosis that cannot be explained by genetic vulnerability.
Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.
The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.
The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.
We investigated the effects of pathogens associated with subclinical intramammary infections on yield, composition and quality indicators of goat milk. By means of a longitudinal study, individual half udder milk samples (n = 132) were collected at different lactation periods and assessed for milk yield and physicochemical composition, somatic cell count (SCC), total bacteria count (TBC) and microbiological culture. Staphylococci species accounted for the great majority of the isolates (96.1%). Intramammary infections significantly reduced fat and total solids in goat milk and increased both SCC and TBC. However, these indicators were significantly higher in udder halves affected by S. aureus compared with other staphylococci species.
Sex-related differences in psychopathology are known phenomena, with externalizing and internalizing symptoms typically more common in boys and girls, respectively. However, the neural correlates of these sex-by-psychopathology interactions are underinvestigated, particularly in adolescence.
Participants were 14 years of age and part of the IMAGEN study, a large (N = 1526) community-based sample. To test for sex-by-psychopathology interactions in structural grey matter volume (GMV), we used whole-brain, voxel-wise neuroimaging analyses based on robust non-parametric methods. Psychopathological symptom data were derived from the Strengths and Difficulties Questionnaire (SDQ).
We found a sex-by-hyperactivity/inattention interaction in four brain clusters: right temporoparietal-opercular region (p < 0.01, Cohen's d = −0.24), bilateral anterior and mid-cingulum (p < 0.05, Cohen's d = −0.18), right cerebellum and fusiform (p < 0.05, Cohen's d = −0.20) and left frontal superior and middle gyri (p < 0.05, Cohen's d = −0.26). Higher symptoms of hyperactivity/inattention were associated with lower GMV in all four brain clusters in boys, and with higher GMV in the temporoparietal-opercular and cerebellar-fusiform clusters in girls.
Using a large, sex-balanced and community-based sample, our study lends support to the idea that externalizing symptoms of hyperactivity/inattention may be associated with different neural structures in male and female adolescents. The brain regions we report have been associated with a myriad of important cognitive functions, in particular, attention, cognitive and motor control, and timing, that are potentially relevant to understand the behavioural manifestations of hyperactive and inattentive symptoms. This study highlights the importance of considering sex in our efforts to uncover mechanisms underlying psychopathology during adolescence.
A cluster of 18 scarlet fever cases and large illness absenteeism (32%, 58/184) in a school prompted concern and further investigation. We conducted telephone interviews with parents to ascertain cases and better comprehend parents' views. We identified 19 cases, of which 13 reported scarlet fever diagnosis by a physician and only seven fulfilled the probable case definition. We concluded that the outbreak was far smaller than suspected and found that communication and reporting could be improved. Accurate information and communication is essential in an outbreak; the school's concern could have been alleviated sooner and response measures better targeted.
Total anomalous pulmonary venous connection is a rare congenital heart defect. We report an infant with a mixed form of supracardiac TAPVC, in whom all pulmonary veins, except the right upper, entered a pulmonary venous confluence that is connected to a vertical vein and drained into the superior vena caval–right atrial junction. Several segmental right upper pulmonary veins entered the superior vena cava, superior to the entry of the vertical vein. Surgical repair consisted of the Warden procedure combined with direct anastomosis of the vertical vein to the left atrium. Separate pulmonary venous drainage pathways decreased the risk of post-operative pulmonary venous obstruction. Our patient had an uneventful post-operative course and encouraging 2-month follow-up echocardiography. Careful follow-up is warranted to detect post-operative complications, including obstruction of the pulmonary venous and cavoatrial anastomoses.
Tobacco smoking remains one of the leading causes of preventable illness and death and is heritable with complex underpinnings. Converging evidence suggests a contribution of the polygenic risk for smoking to the use of tobacco and other substances. Yet, the underlying brain mechanisms between the genetic risk and tobacco smoking remain poorly understood.
Genomic, neuroimaging, and self-report data were acquired from a large cohort of adolescents from the IMAGEN study (a European multicenter study). Polygenic risk scores (PGRS) for smoking were calculated based on a genome-wide association study meta-analysis conducted by the Tobacco and Genetics Consortium. We examined the interrelationships among the genetic risk for smoking initiation, brain structure, and the number of occasions of tobacco use.
A higher smoking PGRS was significantly associated with both an increased number of occasions of tobacco use and smaller cortical volume of the right orbitofrontal cortex (OFC). Furthermore, reduced cortical volume within this cluster correlated with greater tobacco use. A subsequent path analysis suggested that the cortical volume within this cluster partially mediated the association between the genetic risk for smoking and the number of occasions of tobacco use.
Our data provide the first evidence for the involvement of the OFC in the relationship between smoking PGRS and tobacco use. Future studies of the molecular mechanisms underlying tobacco smoking should consider the mediation effect of the related neural structure.
Working consistently through one's early 60s is key to retirement security. However, workers without access to retirement plans and health insurance will likely struggle to achieve such security. This paper uses the Health and Retirement Study to identify nontraditional jobs – which lack these benefits – and applies sequence analysis to explore how workers aged 50–62 use them. The results suggest that most nontraditional jobs are used by workers consistently, and that fewer workers use these jobs briefly or as a bridge to retirement. Workers consistently in nontraditional jobs end up with less retirement income and are more likely to be depressed.
La schizophrénie reste une pathologie invalidante malgré une prise en charge médicamenteuse efficace. Il importe de développer d’autres stratégies adjuvantes efficaces sur les symptômes de la maladie en limitant les effets secondaires des traitements pharmacologiques. L’efficacité des activités physiques dans le traitement de la schizophrénie n’est pas démontrée mais des travaux soulignent des bénéfices sur les symptômes négatifs et dépressifs [1,2].
Nous souhaitons évaluer l’impact clinique d’un programme d’activité physique sur une population de sujets atteints de schizophrénie.
Un programme d’activités physiques supervisé par deux moniteurs a été élaboré. Il comprend une heure de multi-activités, 2 fois par semaine, pendant 12 semaines. L’intensité minimale de chaque séance était fixée à 50 % de la fréquence cardiaque de réserve. Des mesures comprenant les échelles PANSS, SANS, SAPS, CDSS, S-QoL, un bilan anthropométrique et biologique ont été réalisés à S 0, S 6, S 12 et S 16.
Deux groupes de 5 patients (n = 10) ont réalisé le programme. Une amélioration clinique est retrouvée sur l’ensemble des échelles utilisées entre S 0 et S 16. Les changements observés ne sont pas en faveur d’une amélioration du syndrome métabolique et nous notons une prise de poids des sujets sur la période de l’étude. Le traitement statistique des données présente des résultats non significatifs (p > 0,05).
La couverture médiatique d’un fait suicidaire influence le taux de suicide par le biais d’un effet d’incitation, aussi nommé « effet Werther » (EW) ou d’un potentiel rôle préventif via « l’effet Papageno » (EP) . L’objectif du programme national français Papageno est d’améliorer les propriétés qualitatives du contenu médiatique dont dépendent principalement l’EW et l’EP, via l’application des recommandations de l’Organisation mondiale de la Santé (OMS) pour un traitement journalistique plus responsable du suicide. L’évaluation de l’efficacité du programme est donc un enjeu de prévention qui nécessite un outil d’analyse fidèle à ces recommandations.
Élaborer et valider une grille d’analyse qualitative permettant, pour chaque article de presse traitant du suicide, de mesurer le degré de compliance aux recommandations de l’OMS et de quantifier le risque d’EW et le potentiel EP.
La grille d’évaluation PReSS (Print media Reporting on Suicide Scale) combine 10 items descriptifs et 19 items qualitatifs issus de l’opérationnalisation des 11 recommandations de l’OMS. La validation de la fiabilité interjuges a été obtenue par séries de double cotation-correction de 25 articles traitant du suicide. Les critères de satisfaction des items ont été affinés après chaque série jusqu’à obtention d’un coefficient de kappa ≥ 0.7 pour chacun. À titre d’illustration, le traitement médiatique du supposé suicide du pilote d’avion A. Lubitz en mars 2015 a été analysé grâce à la PReSS.
Trois séries de cotation-correction ont été nécessaires pour valider la grille. L’analyse de la couverture du suicide présumé d’A. Lubitz montre un compliance faible aux recommandations, un score Papageno bas et un score Werther élevé.
La grille d’évaluation PReSS est un outil fiable et utile pour mesurer la compliance aux recommandations de l’OMS concernant la couverture médiatique du suicide.
L’accès aux soins des personnes à risque constitue un pilier essentiel de la prévention du suicide. Cependant, les idées reçues véhiculées autour des conduites suicidaires y opposent un obstacle significatif. Afin de cibler au mieux les campagnes d’information qui dissiperaient ces mythes, et pour en évaluer l’efficacité, les connaissances sur le suicide devraient pouvoir être quantifiées de façon fiable. À ce jour, seules quelques études anglo-saxonnes dédiées ont été validées. La limite décisive à leur interprétation tient cependant à ce qu’elles ne permettent pas d’approche normative. En effet, l’exactitude de leurs propositions n’est validée par aucun étalon officiel, alors même que certaines relèvent plus de l’expérience clinique que de connaissances issues de la littérature. Notre objectif consiste à palier cette limite en proposant une échelle dont la cotation est adaptée à l’évaluation d’un savoir normé. Le Questionnaire d’Évaluation des Connaissances sur le Suicide (QECS) est un auto-questionnaire qui explore, en 35 items, les principales connaissances relatives à l’épidémiologie et aux mythes communs concernant le suicide. Les réponses y sont recueillies par échelle visuelle analogique. La cotation finale se fait en confrontant ces réponses à celles d’un panel de référence constitué de spécialistes en suicidologie (n = 47). Nous présentons ici les résultats de ce panel, ainsi qu’une illustration des potentialités d’interprétation du QECS, via l’évaluation des connaissances d’un échantillon test d’étudiants en journalisme (n = 111). Les réponses du panel de référence étaient significativement différentes de « ni accord, ni désaccord » pour 27 des 29 items dédiés aux mythes. Pour 25 de ces items, une différence significative était retrouvée entre l’échantillon test et le panel de référence. Ainsi attestée, l’existence d’un avis expertal spécifique a servi d’étalon pour 2 modes de cotation des réponses de l’échantillon test : un score de véracité et un score de concordance aux experts.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Off-target movement of dicamba and 2,4-D may injure and reduce the yield of many fruit and vegetable crops, impacting specialty crop producers and herbicide applicators alike. Two field experiments were established, using plant growth regulator–resistant soybean herbicide technologies, to evaluate drift and carryover risks to horseradish production. The drift experiment was conducted in 2015 and 2016 to evaluate impact of dicamba and 2,4-D simulated drift on horseradish production with a mid-POST application in soybean. Simulated drift rates were 1/10,000X, 1/1,000X, and 1/100X, with 1/2X, 1X, and 2X of standard application rates. Injury and yield loss was greater following application of 2,4-D than with dicamba. Yield reductions were observed beginning at the 1/1,000X rate of 2,4-D, with complete crop loss occurring when rates exceed 1/2X. In comparison, dicamba only reduced yields when applied at the 1X and 2X rates. Only horseradish roots from plants treated with dicamba at the 2X rate had greater dicamba residue than the nontreated control, and the amount detected, 0.32 parts per billion (ppb), was lower than the EPA tolerance of 100 ppb in root crops. There was little to no harvestable tissue for 2,4-D residue analysis for plants treated with 2,4-D at rates above 1/2X. The carryover experiment was a 2-yr rotational evaluation conducted in 2014, 2015, and 2016 to assess dicamba carryover to horseradish following application to dicamba-resistant soybean the previous season. Observations taken at 4, 6, and 8 wk after planting indicated no significant horseradish injury, nor was height, stand, or root weight reduced. These results suggest that horseradish growers should have few concerns about injury from dicamba drift or carryover. While 2,4-D applicators may need to be cautious when making applications near horseradish fields, 2,4-D may be an effective tool for controlling volunteer horseradish in 2,4-D–resistant soybean.
Little is known about health-related quality of life in young children undergoing staged palliation for single-ventricle CHD. The aim of this study was to assess the impact of CHD on daily life in pre-schoolers with single-ventricle CHD and to identify determinants of health-related quality of life.
Prospective two-centre cohort study assessing health-related quality of life using the Preschool Paediatric Cardiac Quality of Life Inventory in 46 children at a mean age of 38 months and 3 weeks. Children with genetic anomalies were excluded. Scores were compared with reference data of children with biventricular CHD. Multiple linear regression analysis was used to identify determinants of health-related quality of life.
Health-related quality of life in pre-schoolers with single-ventricle CHD was comparable to children with biventricular CHD. Preterm birth and perioperative variables were significant predictors of low health-related quality of life. Notably, pre-Fontan brain MRI findings and neurodevelopmental status were not associated with health-related quality of life. Overall, perioperative variables explained 24% of the variability of the total health-related quality of life score.
Despite substantial health-related burden, pre-schoolers with single-ventricle CHD showed good health-related quality of life. Less-modifiable treatment-related risk factors and preterm birth had the highest impact on health-related quality of life. Long-term follow-up assessment of self-reported health-related quality of life is needed to identify patients with poorer health-related quality of life and to initiate supportive care.
Abnormalities in reward circuit function are considered a core feature of addiction. Yet, it is still largely unknown whether these abnormalities stem from chronic drug use, a genetic predisposition, or both.
In the present study, we investigated this issue using a large sample of adolescent children by applying structural equation modeling to examine the effects of several dopaminergic polymorphisms of the D1 and D2 receptor type on the reward function of the ventral striatum (VS) and orbital frontal cortex (OFC), and whether this relationship predicted the propensity to engage in early alcohol misuse behaviors at 14 years of age and again at 16 years of age.
The results demonstrated a regional specificity with which the functional polymorphism rs686 of the D1 dopamine receptor (DRD1) gene and Taq1A of the ANKK1 gene influenced medial and lateral OFC activation during reward anticipation, respectively. Importantly, our path model revealed a significant indirect relationship between the rs686 of the DRD1 gene and early onset of alcohol misuse through a medial OFC × VS interaction.
These findings highlight the role of D1 and D2 in adjusting reward-related activations within the mesocorticolimbic circuitry, as well as in the susceptibility to early onset of alcohol misuse.
OBJECTIVES/SPECIFIC AIMS: We sought to investigate the role of the host microbiome during severe, acute respiratory infection (ARI) to understand the drivers of both acute clinical pathogenesis. METHODS/STUDY POPULATION: Nasopharyngeal swabs comprised of mixed cell populations at the active site of infection were collected from 192 hospitalized pediatric patients with ARI. We combined comprehensive respiratory virus detection and virus genome sequencing with 16S rRNA gene sequencing to evaluate the microbial content of the airway during ARI. This data was coupled with 11 clinical parameters, which were compiled to create a clinical severity score. The microbiome profiles were assessed to determine if clinical severity of infection, and/or specific virus was associated with increased clinical severity. RESULTS/ANTICIPATED RESULTS: We identified 8 major microbiome profiles classified by dominant bacterial genus, Moraxella, Corynebacterium, Staphylococcus, Haemophilus, Streptococcus, Alloiococcus, Schlegelella, and Diverse. Increased clinical severity was significantly associated with microbiome profiles dominated by Haemophilus, Streptococcus, and Schlegelella, whereas Corynebacterium and Alloiococcus were more prevalent in children with less severe disease. Independent of the microbial community, more than 60% of patients with the highest clinical severity were infected with either respiratory syncytial virus or rhinovirus. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results indicate that individually and in combination, both virus and microbial composition may drive clinical severity during acute respiratory viral infections. It is still unclear how the complex interplay between virus, bacterial community, and the host response influence long-term respiratory impacts, such as the development of asthma. Nonetheless, during ARIs therapeutic interventions such as antibiotics and probiotics may be warranted in a subset of patients that are identified to have both a virus and microbiome profile that is associated with increased pathogenesis to limit both acute and long-term phenotypes.