Explore the vast range of titles available.

Selective serotonin reuptake inhibitors (SSRIs) for treatment of prenatal maternal depression have been associated with neonatal neurobehavioral disturbances, though the molecular mechanisms remain poorly understood.  In utero exposure to SSRIs may affect DNA methylation (DNAme) in the human placenta, an epigenetic mark that is established during development and is associated with gene expression. Chorionic villus samples from 64 human placentas were profiled with the Illumina MethylationEPIC BeadChip; clinical assessments of maternal mood and SSRI treatment records were collected at multiple time points during pregnancy. Case distribution was 20 SSRI-exposed cases and 44 SSRI non-exposed cases. Maternal depression was defined using a mean maternal Hamilton Depression score > 8 to indicate symptomatic depressed mood (“maternally-depressed”), and we further classified cases into SSRI-exposed, maternally-depressed (n = 14); SSRI-exposed, not maternally-depressed (n = 6); SSRI non-exposed, maternally-depressed (n = 20); and SSRI non-exposed, not maternally-depressed (n = 24). For replication, Illumina 450K DNAme profiles were obtained from 34 additional cases from an independent cohort (n = 17 SSRI-exposed, n = 17 SSRI non-exposed). No CpGs were differentially methylated at FDR < 0.05 comparing SSRI-exposed to non-exposed placentas, in a model adjusted for mean maternal Hamilton Depression score, or in a model restricted to maternally-depressed cases with and without SSRI exposure. However, at a relaxed threshold of FDR < 0.25, five CpGs were differentially methylated (|Δβ| > 0.03) by SSRI exposure status. Four were covered by the replication cohort measured by the 450K array, but none replicated. No CpGs were differentially methylated (FDR < 0.25) comparing maternally depressed to not depressed cases. In sex-stratified analyses for SSRI-exposed versus non-exposed cases (females n = 31; males n = 33), three additional CpGs in females, but none in males, were differentially methylated at the relaxed FDR < 0.25 cut-off. We did not observe large-scale alterations of DNAme in placentas exposed to maternal SSRI treatment, as compared to placentas with no SSRI exposure. We also found no evidence for altered DNAme in maternal depression-exposed versus depression non-exposed placentas. This novel work in a prospectively-recruited cohort with clinician-ascertained SSRI exposure and mood assessments would benefit from future replication.

Background Prenatal alcohol exposure is the leading preventable cause of behavioral and cognitive deficits, which may affect between 2 and 5 % of children in North America. While the underlying mechanisms of alcohol’s effects on development remain relatively unknown, emerging evidence implicates epigenetic mechanisms in mediating the range of symptoms observed in children with fetal alcohol spectrum disorder (FASD). Thus, we investigated the effects of prenatal alcohol exposure on genome-wide DNA methylation in the NeuroDevNet FASD cohort, the largest cohort of human FASD samples to date. Methods Genome-wide DNA methylation patterns of buccal epithelial cells (BECs) were analyzed using the Illumina HumanMethylation450 array in a Canadian cohort of 206 children (110 FASD and 96 controls). Genotyping was performed in parallel using the Infinium HumanOmni2.5-Quad v1.0 BeadChip. Results After correcting for the effects of genetic background, we found 658 significantly differentially methylated sites between FASD cases and controls, with 41 displaying differences in percent methylation change >5 %. Furthermore, 101 differentially methylated regions containing two or more CpGs were also identified, overlapping with 95 different genes. The majority of differentially methylated genes were highly expressed at the level of mRNA in brain samples from the Allen Brain Atlas, and independent DNA methylation data from cortical brain samples showed high correlations with BEC DNA methylation patterns. Finally, overrepresentation analysis of genes with up-methylated CpGs revealed a significant enrichment for neurodevelopmental processes and diseases, such as anxiety, epilepsy, and autism spectrum disorders. Conclusions These findings suggested that prenatal alcohol exposure is associated with distinct DNA methylation patterns in children and adolescents, raising the possibility of an epigenetic biomarker of FASD.

ObjectiveTo assess the association between time of birth and mortality among preterm infants.Study designPopulation-based study of infants born 22–36 weeks gestation (GA) in Canada from 2010 to 2015 (n = 173 789). Multivariable logistic regression models assessed associations between timing of birth and mortality.ResultAmong infants 22–27 weeks GA, evening birth was associated with higher mortality than daytime birth (adjusted odds ratio [AOR] 1.14, 95% CI 1.01–1.29). Among infants 28–32 weeks GA and 33–36 weeks GA, night birth was associated with lower mortality than daytime birth (AOR 0.75, 95% CI 0.59–0.95; AOR 0.78, 95% CI 0.62–0.99, respectively). Sensitivity analysis excluding infants with major congenital anomaly revealed that associations between hour of birth and mortality among infants born 28–32 and 33–36 weeks GA decreased or were not statistically significant.ConclusionHigher mortality among extremely preterm infants during off-peak hours may suggest variations in available resources based on time of day.

Research on complex health conditions such as neurodevelopmental disorders increasingly relies on large-scale research and clinical studies that would benefit from data sharing initiatives. Organizations that share data stand to maximize the efficiency of invested research dollars, expedite research findings, minimize the burden on the patient community, and increase citation rates of publications associated with the data. This study examined ethics and governance information on websites of databases involving neurodevelopmental disorders to determine the availability of information on key factors crucial for comprehension of, and trust and participation in such initiatives. We identified relevant databases identified using online keyword searches. Two researchers reviewed each of the websites and identified thematic content using principles from grounded theory. The content for each organization was interrogated using the gap analysis method. Sixteen websites from data sharing organizations met our inclusion criteria. Information about types of data and tissues stored, data access requirements and procedures, and protections for confidentiality were significantly addressed by data sharing organizations. However, special considerations for minors (absent from 63%), controls to check if data and tissues are being submitted (absent from 81%), disaster recovery plans (absent from 81%), and discussions of incidental findings (absent from 88%) emerged as major gaps in thematic website content. When present, content pertaining to special considerations for youth, along with other ethics guidelines and requirements, were scattered throughout the websites or available only from associated documents accessed through live links. The complexities of sharing data acquired from children and adolescents will only increase with advances in genomic and neuro science. Our findings suggest that there is a need to improve the consistency, depth and accessibility of governance and policies on which these collaborations can lean specifically for vulnerable young populations.

Background:Risk identification and communication tools have the potential to improve health care by supporting clinician-patient or family discussion of treatment risks and benefits and helping patients make more informed decisions; however, they have yet to be tailored to pediatric surgery. User-centered design principles can help to ensure the successful development and uptake of health care tools.Objective:We aimed to develop and evaluate the usability of an easy-to-use tool to communicate a child’s risk of postoperative pain to improve informed and collaborative preoperative decision-making between clinicians and families.Methods:With research ethics board approval, we conducted web-based co-design sessions with clinicians and family participants (people with lived surgical experience and parents of children who had recently undergone a surgical or medical procedure) at a tertiary pediatric hospital. Qualitative data from these sessions were analyzed thematically using NVivo (Lumivero) to identify design requirements to inform the iterative redesign of an existing prototype. We then evaluated the usability of our final prototype in one-to-one sessions with a new group of participants, in which we measured mental workload with the National Aeronautics and Space Administration (NASA) Task Load Index (TLX) and user satisfaction with the Post-Study System Usability Questionnaire (PSSUQ).Results:A total of 12 participants (8 clinicians and 4 family participants) attended 5 co-design sessions. The 5 requirements were identified: (A) present risk severity descriptively and visually; (B) ensure appearance and navigation are user-friendly; (C) frame risk identification and mitigation strategies in positive terms; (D) categorize and describe risks clearly; and (E) emphasize collaboration and effective communication. A total of 12 new participants (7 clinicians and 5 family participants) completed a usability evaluation. Tasks were completed quickly (range 5-17 s) and accurately (range 11/12, 92% to 12/12, 100%), needing only 2 requests for assistance. The median (IQR) NASA TLX performance score of 78 (66-89) indicated that participants felt able to perform the required tasks, and an overall PSSUQ score of 2.1 (IQR 1.5-2.7) suggested acceptable user satisfaction with the tool.Conclusions:The key design requirements were identified, and that guided the prototype redesign, which was positively evaluated during usability testing. Implementing a personalized risk communication tool into pediatric surgery can enhance the care process and improve informed and collaborative presurgical preparation and decision-making between clinicians and families of pediatric patients.

Background. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has impacted healthcare services and outcomes. We aimed to investigate healthcare resource utilization and early health outcomes of infants born to mothers with perinatal SARS-CoV-2 infection. Methods. The study included all infants born alive between February 1, 2020, and April 30, 2021, in British Columbia. We used linked provincial population-based databases including data on COVID-19 testing, birth, and health information for up to one year from birth. Perinatal COVID-19 exposure for infants was defined being born to mothers with a positive test for SARS-CoV-2 infection during pregnancy or at delivery. Cases of COVID-19-exposed infants were matched with up to four non‐exposed infants by birth month, sex, birthplace, and gestational age in weeks. Outcomes included hospitalizations, emergency department visits, and in-/outpatient diagnoses. Outcomes were compared between groups using conditional logistic regression and linear mixed effects models including effect modification by maternal residence. Results. Among 52,711 live births, 484 infants had perinatal exposure to SARS-CoV-2, an incidence rate of 9.18 per 1000 live births. Exposed infants (54.6% male) had a mean gestational age of 38.5 weeks, and 99% were born in hospital. Proportions of infants requiring at least one hospitalization (8.1% vs. 5.1%) and at least one emergency department visit (16.9% vs. 12.9%) were higher among the exposed vs. unexposed infants, respectively. Among infants from the urban area, those with exposure were more likely to have respiratory infectious diseases (odds ratio: 1.74; 95% confidence intervals: 1.07, 2.84), compared with those without exposure. Interpretation. In our cohort, infants born to mothers with SARS-CoV-2 infection have increased healthcare demands in their early infancy, which warrants further investigation.

Background: Pediatric surgery is associated with a risk of postoperative pain that can impact the family’s quality of life. Although some risk factors for postoperative pain are known, these are often not consistently communicated to families. In addition, although tools for risk communication exist in other domains, none are tailored to pediatric surgery. Objective: As part of a larger project to develop pain risk prediction tools, we aimed to design an easy-to-use tool to effectively communicate a child’s risk of postoperative pain to both clinicians and family members. Methods: With research ethics board approval, we conducted virtual focus groups (~1 hour each) comprising clinicians and family members (people with lived surgical experience and parents of children who had recently undergone surgery/medical procedures) at a tertiary pediatric hospital to understand and evaluate potential design approaches and strategies for effectively communicating and visualizing postoperative pain risk. Data were analyzed thematically to generate design requirements and to inform iterative prototype development. Results: In total, 19 participants (clinicians: n=10, 53%; family members: n=9, 47%) attended 6 focus group sessions. Participants indicated that risk was typically communicated verbally by clinicians to patients and their families, with severity indicated using a descriptive or a numerical representation or both, which would only occasionally be contextualized. Participants indicated that risk communication tools were seldom used but that families would benefit from risk information, time to reflect on the information, and follow-up with questions. In addition, 9 key design requirements and feature considerations for effective risk communication were identified: (1) present risk information clearly and with contextualization, (2) quantify the risk and contextualize it, (3) include checklists for preoperative family preparation, (4) provide risk information digitally to facilitate recall and sharing, (5) query the family’s understanding to ensure comprehension of risk, (6) present the risk score using multimodal formats, (7) use color coding that is nonthreatening and avoids limitations with color blindness, (8) present the most significant factors contributing to the risk prediction, and (9) provide risk mitigation strategies to potentially decrease the patient’s level of risk. Conclusions: Key design requirements for a pediatric postoperative pain risk visualization tool were established and guided the development of an initial prototype. Implementing a risk communication tool into clinical practice has the potential to bridge existing gaps in the accessibility, utilization, and comprehension of personalized risk information between health care professionals and family members. Future iterative codesign and clinical evaluation of this risk communication tool are needed to confirm its utility in practice.

Background To understand biological processes and diseases, it is crucial to unravel the concerted interplay of transcription factors (TFs), microRNAs (miRNAs) and their targets within regulatory networks and fundamental sub-networks. An integrative computational resource generating a comprehensive view of these regulatory molecular interactions at a genome-wide scale would be of great interest to biologists, but is not available to date. Results To identify and analyze molecular interaction networks, we developed MIR@NT@N, an integrative approach based on a meta-regulation network model and a large-scale database. MIR@NT@N uses a graph-based approach to predict novel molecular actors across multiple regulatory processes (i.e. TFs acting on protein-coding or miRNA genes, or miRNAs acting on messenger RNAs). Exploiting these predictions, the user can generate networks and further analyze them to identify sub-networks, including motifs such as feedback and feedforward loops (FBL and FFL). In addition, networks can be built from lists of molecular actors with an a priori role in a given biological process to predict novel and unanticipated interactions. Analyses can be contextualized and filtered by integrating additional information such as microarray expression data. All results, including generated graphs, can be visualized, saved and exported into various formats. MIR@NT@N performances have been evaluated using published data and then applied to the regulatory program underlying epithelium to mesenchyme transition (EMT), an evolutionary-conserved process which is implicated in embryonic development and disease. Conclusions MIR@NT@N is an effective computational approach to identify novel molecular regulations and to predict gene regulatory networks and sub-networks including conserved motifs within a given biological context. Taking advantage of the M@IA environment, MIR@NT@N is a user-friendly web resource freely available at http://mironton.uni.lu which will be updated on a regular basis.

The Pleiades Promoter Project integrates genomewide bioinformatics with large-scale knockin mouse production and histological examination of expression patterns to develop MiniPromoters and related tools designed to study and treat the brain by directed gene expression. Genes with brain expression patterns of interest are subjected to bioinformatic analysis to delineate candidate regulatory regions, which are then incorporated into a panel of compact human MiniPromoters to drive expression to brain regions and cell types of interest. Using single-copy, homologous-recombination \"knockins\" in embryonic stem cells, each MiniPromoter reporter is integrated immediately 5' of the Hprt locus in the mouse genome. MiniPromoter expression profiles are characterized in differentiation assays of the transgenic cells or in mouse brains following transgenic mouse production. Histological examination of adult brains, eyes, and spinal cords for reporter gene activity is coupled to costaining with cell-type-specific markers to define expression. The publicly available Pleiades MiniPromoter Project is a key resource to facilitate research on brain development and therapies.

Background: The perioperative period is a data-rich environment with potential for innovation through digital health tools and predictive analytics to optimize patients’ health with targeted prehabilitation. Although some risk factors for postoperative pain following pediatric surgery are already known, the systematic use of preoperative information to guide personalized interventions is not yet widespread in clinical practice. Objective: Our long-term goal is to reduce the incidence of persistent postsurgical pain (PPSP) and long-term opioid use in children by developing personalized pain risk prediction models that can guide clinicians and families to identify targeted prehabilitation strategies. To develop such a system, our first objective was to identify risk factors, outcomes, and relevant experience measures, as well as data collection tools, for a future data collection and risk modeling study. Methods: This study used a patient-oriented research methodology, leveraging parental/caregiver and clinician expertise. We conducted virtual focus groups with participants recruited at a tertiary pediatric hospital; each session lasted approximately 1 hour and was composed of clinicians or family members (people with lived surgical experience and parents of children who had recently undergone a procedure requiring general anesthesia) or both. Data were analyzed thematically to identify potential risk factors for pain, as well as relevant patient-reported experience and outcome measures (PREMs and PROMs, respectively) that can be used to evaluate the progress of postoperative recovery at home. This guidance was combined with a targeted literature review to select tools to collect risk factor and outcome information for implementation in a future study. Results: In total, 22 participants (n=12, 55%, clinicians and n=10, 45%, family members) attended 10 focus group sessions; participants included 12 (55%) of 22 persons identifying as female, and 12 (55%) were under 50 years of age. Thematic analysis identified 5 key domains: (1) demographic risk factors, including both child and family characteristics; (2) psychosocial risk factors, including anxiety, depression, and medical phobias; (3) clinical risk factors, including length of hospital stay, procedure type, medications, and pre-existing conditions; (4) PREMs, including patient and family satisfaction with care; and (5) PROMs, including nausea and vomiting, functional recovery, and return to normal activities of daily living. Participants further suggested desirable functional requirements, including use of standardized and validated tools, and longitudinal data collection, as well as delivery modes, including electronic, parent proxy, and self-reporting, that can be used to capture these metrics, both in the hospital and following discharge. Established PREM/PROM questionnaires, pain-catastrophizing scales (PCSs), and substance use questionnaires for adolescents were subsequently selected for our proposed data collection platform. Conclusions: This study established 5 key data domains for identifying pain risk factors and evaluating postoperative recovery at home, as well as the functional requirements and delivery modes of selected tools with which to capture these metrics both in the hospital and after discharge. These tools have been implemented to generate data for the development of personalized pain risk prediction models.