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Previous studies have shown mixed results on the relationship between prenatal, birth, and postnatal (“pregnancy-related”) risk factors and attention-deficit/hyperactivity disorder (ADHD). We conducted meta-analyses to identify potentially modifiable pregnancy-related factors associated with ADHD. A comprehensive search of PubMed, Web of Science, and EMBASE in 2014, followed by an updated search in January 2021, identified 69 articles published in English on pregnancy-related risk factors and ADHD for inclusion. Risk factors were included in the meta-analysis if at least three effect sizes with clear pregnancy-related risk factor exposure were identified. Pooled effect sizes were calculated for ADHD overall, ADHD diagnosis, inattention, and hyperactivity/impulsivity. Odds ratios (OR) were calculated for dichotomous measures and correlation coefficients (CC) for continuous measures. Prenatal factors (pre-pregnancy weight, preeclampsia, pregnancy complications, elevated testosterone exposure), and postnatal factors (Apgar score, neonatal illness, no breastfeeding) were positively associated with ADHD overall; the findings for ADHD diagnosis were similar with the exception that there were too few effect sizes available to examine pre-pregnancy weight and lack of breastfeeding. Prenatal testosterone was significantly associated with inattention and hyperactivity/impulsivity. Effect sizes were generally small (range 1.1–1.6 ORs, -0.16–0.11 CCs). Risk factors occurring at the time of birth (perinatal asphyxia, labor complications, mode of delivery) were not significantly associated with ADHD. A better understanding of factors that are consistently associated with ADHD may inform future prevention strategies. The findings reported here suggest that prenatal and postnatal factors may serve as potential targets for preventing or mitigating the symptoms of ADHD.

Background Radiation therapy is integral to effective thoracic cancer treatments, but its application is limited by sensitivity of critical organs such as the heart. The impacts of acute radiation-induced damage and its chronic effects on normal heart cells are highly relevant in radiotherapy with increasing lifespans of patients. Biomarkers for normal tissue damage after radiation exposure, whether accidental or therapeutic, are being studied as indicators of both acute and delayed effects. Recent research has highlighted the potential importance of RNAs, including messenger RNAs (mRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) as biomarkers to assess radiation damage. Understanding changes in mRNA and non-coding RNA expression will elucidate biological pathway changes after radiation. Methods To identify significant expression changes in mRNAs, lncRNAs, and miRNAs, we performed whole transcriptome microarray analysis of mouse heart tissue at 48 h after whole-body irradiation with 1, 2, 4, 8, and 12 Gray (Gy). We also validated changes in specific lncRNAs through RT-qPCR. Ingenuity Pathway Analysis (IPA) was used to identify pathways associated with gene expression changes. Results We observed sustained increases in lncRNAs and mRNAs, across all doses of radiation. Alas2 , Aplnr, and Cxc3r1 were the most significantly downregulated mRNAs across all doses. Among the significantly upregulated mRNAs were cell-cycle arrest biomarkers Gdf15, Cdkn1a, and Ckap2. Additionally, IPA identified significant changes in gene expression relevant to senescence, apoptosis, hemoglobin synthesis, inflammation, and metabolism. LncRNAs Abhd11os, Pvt1, Trp53cor1 , and Dino showed increased expression with increasing doses of radiation. We did not observe any miRNAs with sustained up- or downregulation across all doses, but miR-149-3p, miR-6538, miR-8101, miR-7118-5p, miR-211-3p, and miR-3960 were significantly upregulated after 12 Gy. Conclusions Radiation-induced RNA expression changes may be predictive of normal tissue toxicities and may indicate targetable pathways for radiation countermeasure development and improved radiotherapy treatment plans.

Radiation injury from medical, accidental, or intentional sources can induce acute and long-term hepatic dysregulation, fibrosis, and cancer. This long-term hepatic dysregulation decreases quality of life and may lead to death. Our goal in this study is to determine acute changes in biological pathways and discover potential RNA biomarkers predictive of radiation injury. We performed whole transcriptome microarray analysis of mouse liver tissue (C57BL/6 J) 48 h after whole-body irradiation with 1, 2, 4, 8, and 12 Gray to identify significant expression changes in mRNAs, lncRNAs, and miRNAs, We also validated changes in specific RNAs through qRT-PCR. We used Ingenuity Pathway Analysis (IPA) to identify pathways associated with gene expression changes. We observed significant dysregulation of multiple mRNAs across all doses. In contrast, miRNA dysregulation was observed upwards of 2 Gray. The most significantly upregulated mRNAs function as tumor suppressors: Cdkn1a , Phlda3 , and Eda2r . The most significantly downregulated mRNAs were involved in hemoglobin synthesis, inflammation, and mitochondrial function including multiple members of Hbb and Hba . The most significantly upregulated miRNA included: miR-34a-5p, miR-3102-5p, and miR-3960, while miR-342-3p, miR-142a-3p, and miR-223-3p were most significantly downregulated. IPA predicted activation of cell cycle checkpoint control pathways and inhibition of pathways relevant to inflammation and erythropoietin. Clarifying expression of mRNA, miRNA and lncRNA at a short time point (48 h) offers insight into potential biomarkers, including radiation markers shared across organs and animal models. This information, once validated in human models, can aid in development of bio-dosimetry biomarkers, and furthers our understanding of acute pathway dysregulation.

Gottingen minipigs mirror the physiological radiation response observed in humans and hence make an ideal candidate model for studying radiation biodosimetry for both limited-sized and mass casualty incidents. We examined the whole blood gene expression profiles starting one day after total-body irradiation with increasing doses of gamma-rays. The minipigs were monitored for up to 45 days or time to euthanasia necessitated by radiation effects. We successfully identified dose- and time-agnostic (over a 1–7 day period after radiation), survival-predictive gene expression signatures derived using machine-learning algorithms with high sensitivity and specificity. These survival-predictive signatures fare better than an optimally performing dose-differentiating signature or blood cellular profiles. These findings suggest that prediction of survival is a much more useful parameter for making triage, resource-utilization and treatment decisions in a resource-constrained environment compared to predictions of total dose received. It should hopefully be possible to build such classifiers for humans in the future.

Poor parental mental health and stress have been associated with children’s mental disorders, including attention-deficit/hyperactivity disorder (ADHD), through social, genetic, and neurobiological pathways. To determine the strength of the associations between parental mental health and child ADHD, we conducted a set of meta-analyses to examine the association of parent mental health indicators (e.g., parental depression, antidepressant usage, antisocial personality disorder, and stress and anxiety) with subsequent ADHD outcomes in children. Eligible ADHD outcomes included diagnosis or symptoms. Fifty-eight articles published from 1980 to 2019 were included. We calculated pooled effect sizes, accounting for each study’s conditional variance, separately for test statistics based on ADHD as a dichotomous (e.g., diagnosis or clinical cutoffs) or continuous measurement (e.g., symptoms of ADHD subtypes of inattentiveness and hyperactivity/impulsivity). Parental stress and parental depression were significantly associated with increased risk for ADHD overall and both symptoms and diagnosis. Specifically, maternal stress and anxiety, maternal prenatal stress, maternal depression, maternal post-partum depression, and paternal depression were positively associated with ADHD. In addition, parental depression was associated with symptoms of ADHD inattentive and hyperactive/impulsive subtypes. Parental antisocial personality disorder was also positively associated with ADHD overall and specifically ADHD diagnosis. Prenatal antidepressant usage was associated with ADHD when measured dichotomously only. These findings raise the possibility that prevention strategies promoting parental mental health and addressing parental stress could have the potential for positive long-term impacts on child health, well-being, and behavioral outcomes.

Evacuation and relocation are key actions used to protect the public in response to natural or technological disasters, but there are inherent risks to both. Unfortunately, these risks have not been fully quantified, which limits the ability of emergency managers and the public to effectively balance the risks and benefits of evacuation or relocation. This work provides quantitative data on the risks of health effects from displacement following evacuation or relocation. Researchers performed a literature review and meta-analysis of published studies and quantified risks of 14 different health effects, including both physical and socio-behavioral outcomes, from studies of 9 different disaster types. The findings show statistically significant increases in 9 of the 14 health effects in displaced populations, indicating an increased likelihood of experiencing detrimental health effects compared with nondisplaced populations. A pooled analysis of all negative health effects found an odds ratio of 1.49 (95% confidence interval: 1.24-1.79), which shows a significant relationship between displacement and negative health outcomes. These findings demonstrate that evacuated or relocated populations have an increased risk of experiencing negative health effects associated with displacement. The broad number of disaster types included mean that findings are applicable to any emergency evacuation or relocation.

Although neurobiologic and genetic factors figure prominently in the development of attention deficit/hyperactivity disorder (ADHD), adverse physical health experiences and conditions encountered during childhood may also play a role. Poor health is known to impact the developing brain with potential lifelong implications for behavioral issues. In attempt to better understand the relationship between childhood physical health and the onset and presence of ADHD symptoms, we summarized international peer-reviewed articles documenting relationships between a select group of childhood diseases or health events (e.g., illnesses, injuries, syndromes) and subsequent ADHD outcomes among children ages 0–17 years. Drawing on a larger two-phase systematic review, 57 longitudinal or retrospective observational studies (1978–2021) of childhood allergies, asthma, eczema, head injury, infection, or sleep problems and later ADHD diagnosis or symptomatology were identified and subjected to meta-analysis. Significant associations were documented between childhood head injuries, infections, and sleep problems with both dichotomous and continuous measures of ADHD, and between allergies with dichotomous measures of ADHD. We did not observe significant associations between asthma or eczema with ADHD outcomes. Heterogeneity detected for multiple associations, primarily among continuously measured outcomes, underscores the potential value of future subgroup analyses and individual studies. Collectively, these findings shed light on the importance of physical health in understanding childhood ADHD. Possible etiologic links between physical health factors and ADHD are discussed, as are implications for prevention efforts by providers, systems, and communities.

Push-coring is used to collect Holocene-aged coral sub-fossils, but its applications can be limited by underlying reef geology. Here, we report on a new approach of coring inundated coastal karst formations—i.e., coral holes—to determine the historical context of coral reefs in Guam. Three cores were extracted and processed to recover coral fragments as well as abundances of the photosymbiotic foraminifera Baculogypsina sphaerulata, a proxy for water clarity. Coral fragments, with the oldest dating to a median calibrated age of 221 cal. BP (1729 CE), revealed greater than 100 years of consistent accumulation and composition, suggesting a period of relative stability for macrobenthos. However, we documented a drop in B. sphaerulata abundance from approximately 100 years cal. BP, suggesting a period of environmental decline in Guam. Our results provide the first multi-centennial record of coral assemblages from Guam and provide a proof of concept for future historical investigations.

Background Early diagnosis and treatment of tick-borne diseases (TBDs) is critical for mitigating their adverse health outcomes, but the differential diagnosis of TBDs is challenging because many symptoms are nonspecific and commonly used diagnostic assays have significant shortcomings. Furthermore, although the local incidence of TBDs is recognized as an important factor in diagnosis, tools to help clinicians formally consider surveillance data in their decision-making are not available. To address these gaps, Gryphon Scientific developed a differential diagnosis application (app) for TBDs that calculates a patient’s likelihood of infection with specific TBDs based on their symptoms, risk factors, and state of suspected tick exposure. Methods A differential diagnosis model for TBDs was developed using data on: (1) TBD symptom and risk factor prevalence in TBD patient populations, collected from clinical studies; and (2) human TBD incidence data from notifiable disease surveillance systems and tick infection prevalence data from reports and public databases, which were combined to develop an environmental risk measure. These data were used to build a Bayesian Belief Network (BBN) model that predicts TBD infection probabilities based on a patient’s symptoms, risk factors, and state of suspected tick exposure. Performance of the model was validated using case studies from the biomedical literature. The model was incorporated into an app developed using R-shiny, called TBD-DDx (Figures 1 and 3). Results A pilot application was developed that includes 10 states (AR, CT, MA, ME, MN, MO, NH, RI, VT, and WI) and the 11 TBDs endemic to those states. The differential diagnosis model identified the patient’s true disease as the top-predicted disease in 56% of cases and within the top three predicted TBD in 84% of cases. The inclusion of incidence factors in the model improved performance (Figure 4). Conclusion These results demonstrate that the TBD-DDx app is a promising tool for informing clinical diagnoses of TBDs to guide selection of diagnostic testing and treatment. This study represents the first use of a BBN modeling approach that incorporates an environmental risk measure and could be adapted for differential diagnosis of other diseases with environmental or other exposure risks. Disclosures All authors: No reported disclosures.

Provocative curation can make an exhibition. The opening wall of \"Simply Curious,\" a group show organized by gallery partner Martin Shopland, presented a seemingly abstract oil painting in a muted palette of ochres and dark reds by François Xavier Saint-Pierre, flanked by two bronze sculptures of male slaves on pedestals, their black-patinated bodies writhing and twisting against their shackles and away from the painting. It was a curious but somehow suitable pairing that became even more interesting when one learned that the contemporary painting actually depicted the reflection of a ship's mast in water and that the slaves (ca. late 18th century) were galley slaves modelled after figures found on a monument to Ferdinando II de' Medici in the Tuscan port city of Livorno.