Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood.

The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) included the central nucleus of the amygdala, hippocampal dentate gyrus, and medial prefrontal cortex (mPFC). Genes and exons within the mPFC carried most disease signals replicated across two independent cohorts. Pathways pointed to immune function, neuronal and synaptic regulation, and stress hormones. Multiomic factor and gene network analyses provided the underlying genomic structure. Single nucleus RNA sequencing in dorsolateral PFC revealed dysregulated (stress-related) signals in neuronal and non-neuronal cell types. Analyses of brain-blood intersections in >50,000 UK Biobank participants were conducted along with fine-mapping of the results of PTSD and MDD genome-wide association studies to distinguish risk from disease processes. Our data suggest shared and distinct molecular pathology in both disorders and propose potential therapeutic targets and biomarkers.

Lymphangitic Melanomatosis: Case Report of Intralymphatic Spread of Melanoma in a 66-year-old Man.

ABSTRACT: Melanoma with lymphatic invasion has been associated with increased risk of metastasis, but the mechanisms and clinical implications are poorly understood. Although current reports have documented angiotropic spread of melanoma and suggest lymphatic spread of melanoma to increase the likelihood of metastasis, to our knowledge, lymphangitic metastatic melanoma resembling cutaneous carcinomatosis or presenting with facial hyperpigmentation has not been described. In this case report, we describe extensive cutaneous intralymphatic spread of melanoma, or lymphangitic melanomatosis, producing macular skin pigmentation in a 66-year-old man.

FOXP1 Haploinsufficiency Contributes to the Development of Congenital Diaphragmatic Hernia.

FOXP1 encodes a transcription factor involved in tissue regulation and cell-type-specific functions. Haploinsufficiency of FOXP1 is associated with a neurodevelopmental disorder: autosomal dominant mental retardation with language impairment with or without autistic features. More recently, heterozygous FOXP1 variants have also been shown to cause a variety of structural birth defects including central nervous system (CNS) anomalies, congenital heart defects, congenital anomalies of the kidney and urinary tract, cryptorchidism, and hypospadias. In this report, we present a previously unpublished case of an individual with congenital diaphragmatic hernia (CDH) who carries an approximately 3.8 Mb deletion. Based on this deletion, and deletions previously reported in two other individuals with CDH, we define a CDH critical region on chromosome 3p13 that includes FOXP1 and four other protein-coding genes. We also provide detailed clinical descriptions of two previously reported individuals with CDH who carry de novo, pathogenic variants in FOXP1 that are predicted to trigger nonsense-mediated mRNA decay. A subset of individuals with putatively deleterious FOXP4 variants has also been shown to develop CDH. Since FOXP proteins function as homo- or heterodimers and the homologs of FOXP1 and FOXP4 are expressed at the same time points in the embryonic mouse diaphragm, they may function together as a dimer, or in parallel as homodimers, to regulate gene expression during diaphragm development. Not all individuals with heterozygous, loss-of-function changes in FOXP1 develop CDH. Hence, we conclude that FOXP1 acts as a susceptibility factor that contributes to the development of CDH in conjunction with other genetic, epigenetic, environmental, and/or stochastic factors.

Real-World Outcomes of Patients with Advanced Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer in Canada Using Data Extracted by Large Language Model-Based Artificial Intelligence.

Real-world evidence for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC) in Canada is limited. This study's objective was to use previously validated DARWENTM artificial intelligence (AI) to extract data from electronic heath records of patients with non-squamous NSCLC at University Health Network (UHN) to describe EGFR mutation prevalence, treatment patterns, and outcomes. Of 2154 patients with NSCLC, 613 had advanced disease. Of these, 136 (22%) had common sensitizing EGFR mutations (cEGFRm; ex19del, L858R), 8 (1%) had exon 20 insertions (ex20ins), and 338 (55%) had EGFR wild type. One-year overall survival (OS) (95% CI) for patients with cEGFRm, ex20ins, and EGFR wild type tumours was 88% (83, 94), 100% (100, 100), and 59% (53, 65), respectively. In total, 38% patients with ex20ins received experimental ex20ins targeting treatment as their first-line therapy. A total of 57 patients (36%) with cEGFRm received osimertinib as their first-line treatment, and 61 (39%) received it as their second-line treatment. One-year OS (95% CI) following the discontinuation of osimertinib was 35% (17, 75) post-first-line and 20% (9, 44) post-second-line. In this real-world AI-generated dataset, survival post-osimertinib was poor in patients with cEGFR mutations. Patients with ex20ins in this cohort had improved outcomes, possibly due to ex20ins targeting treatment, highlighting the need for more effective treatments for patients with advanced EGFRm NSCLC.

Methylphenidate-Induced Non-ischemic Heart Failure With Reduced Ejection Fraction and Mild Pulmonary Hypertension.

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that is commonly diagnosed during childhood. Patients present with hyperactive-impulsive behavior and/or inappropriate inattention which may persist through adulthood. Central nervous system stimulants have been used to manage patients with ADHD. Methylphenidate which is used as a first-line therapy has been shown to have adverse cardiovascular effects in these patients. This is a case of a young male with a history of ADHD since childhood on methylphenidate who was diagnosed with acute non-ischemic heart failure with an ejection fraction of 15-20%. Methylphenidate-induced heart failure is the rare adverse effect seen in ADHD patients who are on this medication. Our patient was started on goal-directed medical therapy for heart failure and was discharged with an implantable cardioverter defibrillator (LifeVest®, ZOLL, Pittsburgh, PA) because of his persistently low left ventricular ejection fraction. It is important for physicians to always consider heart failure as a possible cardiovascular adverse effect when starting patients on methylphenidate for the management of ADHD.

The effects of physical activity on sleep architecture and mood in naturalistic environments.

Physical activity has been found to alter sleep architecture, but these effects have been studied predominantly in the laboratory and the generalizability of these findings to naturalistic environments and longer time intervals, as well as their psychological effects, have not been evaluated. Recent technological advancements in wearable devices have made it possible to capture detailed measures of sleep outside the lab, including timing of specific sleep stages. In the current study, we utilized photoplethysmography coupled with accelerometers and smartphone ambulatory assessment to collect daily measurements of sleep, physical activity and mood in a sample of N = 82 over multi-month data collection intervals. We found a robust inverse relationship between sedentary behavior and physical activity and sleep architecture: both low-intensity and moderate-to-vigorous physical activity were associated with increased NREM sleep and decreased REM sleep, as well as a longer REM latency, while higher levels of sedentary behavior showed the opposite pattern. A decreased REM/NREM ratio and increased REM latency were in turn associated with improved wellbeing, including increased energy, reduced stress and enhanced perceived restfulness of sleep. Our results suggest that physical activity and sleep account for unique variance in a person's mood, suggesting that these effects are at least partially independent.

Summary of Research: Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC.

This is a summary of the original article ?Overall survival with osimertinib in resected EGFR-mutated NSCLC.Ë® Osimertinib blocks the activity of the epidermal growth factor receptor (EGFR) on cancer cells, causing cancer cell death and tumor shrinkage, and is an effective treatment for EGFR-mutated non-small cell lung cancer (NSCLC). The ADAURA study assessed the effects of osimertinib versus placebo in patients with EGFR-mutated (exon 19 deletion or L858R) early stage (IB-IIIA) NSCLC removed by surgery (resected). Previous results from ADAURA demonstrated that patients treated with osimertinib stayed alive and cancer-free (disease-free survival) significantly longer than patients who received placebo. Recent data showed the overall length of time patients were alive after starting treatment (overall survival). In both the primary stage II-IIIA and overall stage IB-IIIA populations, patients in the osimertinib group had a significant 51% reduction in the risk of death compared with the placebo group. The data demonstrated that osimertinib after surgery significantly improved overall survival in patients with resected, EGFR-mutated, stage IB-IIIA NSCLC.

Effects of colour-coded compartmentalised syringe trays on anaesthetic drug error detection under cognitive load.

BACKGROUND: Anaesthetic drug administration is complex, and typical clinical environments can entail significant cognitive load. Colour-coded anaesthetic drug trays have shown promising results for error identification and reducing cognitive load. METHODS: We used experimental psychology methods to test the potential benefits of colour-coded compartmentalised trays compared with conventional trays in a simulated visual search task. Effects of cognitive load were also explored through an accompanying working memory-based task. We hypothesised that colour-coded compartmentalised trays would improve drug-detection error, reduce search time, and reduce cognitive load. This comprised a cognitive load memory task presented alongside a visual search task to detect drug errors. RESULTS: All 53 participants completed 36 trials, which were counterbalanced across the two tray types and 18 different vignettes. There were 16 error-present and 20 error-absent trials, with 18 trials presented for each preloaded tray type. Syringe errors were detected more often in the colour-coded trays than in the conventional trays (91% vs 83%, respectively; P=0.006). In signal detection analysis, colour-coded trays resulted in more sensitivity to the error signal (2.28 vs 1.50, respectively; P<0.001). Confidence in response accuracy correlated more strongly with task performance for the colour-coded tray condition, indicating improved metacognitive sensitivity to task performance (r=0.696 vs r=0.447). CONCLUSIONS: Colour coding and compartmentalisation enhanced visual search efficacy of drug trays. This is further evidence that introducing standardised colour-coded trays into operating theatres and procedural suites would add an additional layer of safety for anaesthetic procedures.

Associations of residential green space with internalizing and externalizing behavior in early childhood.

BACKGROUND: Green space exposures may promote child mental health and well-being across multiple domains and stages of development. The aim of this study was to investigate associations between residential green space exposures and child mental and behavioral health at age 4-6 years. METHODS: Children's internalizing and externalizing behaviors in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) cohort in Shelby County, Tennessee, were parent-reported on the Child Behavior Checklist (CBCL). We examined three exposures-residential surrounding greenness calculated as the Normalized Difference Vegetation Index (NDVI), tree cover, and park proximity-averaged across the residential history for the year prior to outcome assessment. Linear regression models were adjusted for individual, household, and neighborhood-level confounders across multiple domains. Effect modification by neighborhood socioeconomic conditions was explored using multiplicative interaction terms. RESULTS: Children were on average 4.2 years (range 3.8-6.0) at outcome assessment. Among CANDLE mothers, 65% self-identified as Black, 29% as White, and 6% as another or multiple races; 41% had at least a college degree. Higher residential surrounding greenness was associated with lower internalizing behavior scores (-0.66 per 0.1 unit higher NDVI; 95% CI: -1.26, -0.07) in fully-adjusted models. The association between tree cover and internalizing behavior was in the hypothesized direction but confidence intervals included the null (-0.29 per 10% higher tree cover; 95% CI: -0.62, 0.04). No associations were observed between park proximity and internalizing behavior. We did not find any associations with externalizing behaviors or the attention problems subscale. Estimates were larger in neighborhoods with lower socioeconomic opportunity, but interaction terms were not statistically significant. CONCLUSIONS: Our findings add to the accumulating evidence of the importance of residential green space for the prevention of internalizing problems among young children. This research suggests the prioritization of urban green spaces as a resource for child mental health.

Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial.

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance-which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment-and developing effective therapies to overcome them, remains an unmet need. Here the phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure of anti-PD-(L)1-containing immunotherapy and platinum-doublet therapy. A total of 268 patients received durvalumab (anti-PD-L1 monoclonal antibody)-ceralasertib (ATR kinase inhibitor), durvalumab-olaparib (PARP inhibitor), durvalumab-danvatirsen (STAT3 antisense oligonucleotide) or durvalumab-oleclumab (anti-CD73 monoclonal antibody). Greatest clinical benefit was observed with durvalumab-ceralasertib; objective response rate (primary outcome) was 13.9% (11/79) versus 2.6% (5/189) with other regimens, pooled, median progression-free survival (secondary outcome) was 5.8 (80% confidence interval 4.6-7.4) versus 2.7 (1.8-2.8) months, and median overall survival (secondary outcome) was 17.4 (14.1-20.3) versus 9.4 (7.5-10.6) months. Benefit with durvalumab-ceralasertib was consistent across known immunotherapy-refractory subgroups. In ATM-altered patients hypothesized to harbor vulnerability to ATR inhibition, objective response rate was 26.1% (6/23) and median progression-free survival/median overall survival were 8.4/22.8 months. Durvalumab-ceralasertib safety/tolerability profile was manageable. Biomarker analyses suggested that anti-PD-L1/ATR inhibition induced immune changes that reinvigorated antitumor immunity. Durvalumab-ceralasertib is under further investigation in immunotherapy-refractory NSCLC.ClinicalTrials.gov identifier: NCT03334617.

Associations of Organophosphate Ester Flame Retardant Exposures during Pregnancy with Gestational Duration and Fetal Growth: The Environmental influences on Child Health Outcomes (ECHO) Program.

BACKGROUND: Widespread exposure to organophosphate ester (OPE) flame retardants with potential reproductive toxicity raises concern regarding the impacts of gestational exposure on birth outcomes. Previous studies of prenatal OPE exposure and birth outcomes had limited sample sizes, with inconclusive results. OBJECTIVES: We conducted a collaborative analysis of associations between gestational OPE exposures and adverse birth outcomes and tested whether associations were modified by sex. METHODS: We included 6,646 pregnant participants from 16 cohorts in the Environmental influences on Child Health Outcomes (ECHO) Program. Nine OPE biomarkers were quantified in maternal urine samples collected primarily during the second and third trimester and modeled as log2-transformed continuous, categorized (high/low/nondetect), or dichotomous (detect/nondetect) variables depending on detection frequency. We used covariate-adjusted linear, logistic, and multinomial regression with generalized estimating equations, accounting for cohort-level clustering, to estimate associations of OPE biomarkers with gestational length and birth weight outcomes. Secondarily, we assessed effect modification by sex. RESULTS: Three OPE biomarkers [diphenyl phosphate (DPHP), a composite of dibutyl phosphate and di-isobutyl phosphate (DBUP/DIBP), and bis(1,3-dichloro-2-propyl) phosphate] were detected in >85% of participants. In adjusted models, DBUP/DIBP [odds ratio (OR) per doubling=1.07; 95% confidence interval (CI): 1.02, 1.12] and bis(butoxyethyl) phosphate (OR for high vs. nondetect=1.25; 95% CI: 1.06, 1.46), but not other OPE biomarkers, were associated with higher odds of preterm birth. We observed effect modification by sex for associations of DPHP and high bis(2-chloroethyl) phosphate with completed gestational weeks and odds of preterm birth, with adverse associations among females. In addition, newborns of mothers with detectable bis(1-chloro-2-propyl) phosphate, bis(2-methylphenyl) phosphate, and dipropyl phosphate had higher birth weight-for-gestational-age z-scores (ß for detect vs. nondetect=0.04-0.07); other chemicals showed null associations. DISCUSSION: In the largest study to date, we find gestational exposures to several OPEs are associated with earlier timing of birth, especially among female neonates, or with greater fetal growth. https://doi.org/10.1289/EHP13182.

CNS Efficacy of Osimertinib With or Without Chemotherapy in Epidermal Growth Factor Receptor-Mutated Advanced Non-Small-Cell Lung Cancer.

PURPOSE: We report CNS efficacy of first-line osimertinib plus chemotherapy versus osimertinib monotherapy in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) from the phase III FLAURA2 study according to baseline CNS metastasis status. METHODS: Patients were randomly assigned to osimertinib plus platinum-pemetrexed (combination) or osimertinib monotherapy until disease progression or discontinuation. Brain scans were performed in all patients at baseline and progression and at scheduled assessments until progression for patients with baseline CNS metastases; scans were assessed by neuroradiologist CNS blinded independent central review (BICR). RESULTS: On the basis of baseline CNS BICR, 118 of 279 (combination) and 104 of 278 (monotherapy) randomly assigned patients had ≥one measurable and/or nonmeasurable CNS lesion and were included in the CNS full analysis set (cFAS); 40 of 118 and 38 of 104 had ≥one measurable target CNS lesion and were included in the post hoc CNS evaluable-for-response set (cEFR). In the cFAS, the hazard ratio (HR) for CNS progression or death was 0.58 (95% CI, 0.33 to 1.01). In patients without baseline CNS metastases, the HR for CNS progression or death was 0.67 (95% CI, 0.43 to 1.04). In the cFAS, CNS objective response rates (ORRs; 95% CI) were 73% (combination; 64 to 81) versus 69% (monotherapy; 59 to 78); 59% versus 43% had CNS complete response (CR). In the cEFR, CNS ORRs (95% CI) were 88% (73 to 96) versus 87% (72 to 96); 48% versus 16% had CNS CR. CONCLUSION: Osimertinib plus platinum-pemetrexed demonstrated improved CNS efficacy compared with osimertinib monotherapy, including delaying CNS progression, irrespective of baseline CNS metastasis status. These data support this combination as a new first-line treatment for patients with EGFR-mutated advanced NSCLC, including those with CNS metastases.

Unidirectional mating-type switching is underpinned by a conserved MAT1 locus architecture.

Unidirectional mating-type switching is a form of homothallic reproduction known only in a small number of filamentous ascomycetes. Their ascospores can give rise to either self-sterile isolates that require compatible partners for subsequent sexual reproduction, or self-fertile individuals capable of completing this process in isolation. The limited studies previously conducted in these fungi suggest that the differences in mating specificity are determined by the architecture of the MAT1 locus. In self-fertile isolates that have not undergone unidirectional mating-type switching, the locus contains both MAT1-1 and MAT1-2 mating-type genes, typical of primary homothallism. In the self-sterile isolates produced after a switching event, the MAT1-2 genes are lacking from the locus, likely due to a recombination-mediated deletion of the MAT1-2 gene information. To determine whether these arrangements of the MAT1 locus support unidirectional mating-type switching in the Ceratocystidaceae, the largest known fungal assemblage capable of this reproduction strategy, a combination of genetic and genomic approaches were used. The MAT1 locus was annotated in representative species of Ceratocystis, Endoconidiophora, and Davidsoniella. In all cases, MAT1-2 genes interrupted the MAT1-1-1 gene in self-fertile isolates. The MAT1-2 genes were flanked by two copies of a direct repeat that accurately predicted the boundaries of the deletion event that would yield the MAT1 locus of self-sterile isolates. Although the relative position of the MAT1-2 gene region differed among species, it always disrupted the MAT1-1-1 gene and/or its expression in the self-fertile MAT1 locus. Following switching, this gene and/or its expression was restored in the self-sterile arrangement of the locus. This mirrors what has been reported in other species capable of unidirectional mating-type switching, providing the strongest support for a conserved MAT1 locus structure that is associated with this process. This study contributes to our understanding of the evolution of unidirectional mating-type switching.

Serum Titanium Levels Remain Elevated But Urine Titanium is Undetectable in Children With Early Onset Scoliosis Undergoing Growth-Friendly Surgical Treatment: A Prospective Study.

BACKGROUND: Elevated serum titanium levels have been found in patients with early onset scoliosis (EOS) treated with traditional growing rods (TGR), magnetically controlled growing rods (MCGR), and vertical expandable prosthetic titanium rib (VEPTR). No studies have investigated whether serum titanium remains persistently elevated and if titanium is excreted. Our purpose was to compare serum titanium levels in patients with EOS with growth-friendly instrumentation to age-matched controls and evaluate urine titanium and serial serum titanium levels in patients with EOS. METHODS: This was a prospective case-control study. Patients with EOS with TGR, MCGR, or VEPTR underwent urine titanium and serial serum titanium collection at a minimum 6-month interval. Control patients did not have a history of metal implant insertion and underwent serum titanium collection before fracture fixation. RESULTS: Twenty patients with EOS (6 TGR, 8 MCGR, and 6 VEPTR) and 12 controls were analyzed. The control group had no detectable serum titanium (0 ng/mL), whereas the patients with EOS had a median serum titanium of 4.0 ng/mL ( P < 0.001). Analysis of variance showed significantly higher median serum titanium levels in the MCGR and VEPTR groups than the TGR group at time point 1 (5.5 vs 6.0 vs 2.0 ng/mL, P = 0.01) and time point 2 (6.5 vs 7.5 vs 2.0 ng/mL, P < 0.001). Binary comparisons showed a significant difference in serum titanium level between TGR and MCGR (time point 1: P = 0.026, time point 2: P = 0.011) and TGR and VEPTR (time point 1: P = 0.035, time point 2: P = 0.003). However, there was no difference between MCGR and VEPTR (time point 1: P = 0.399, time point 2: P = 0.492) even though the VEPTR group had a longer duration of follow-up ( P = 0.001) and a greater number of lengthenings per patient at the first serum collection ( P = 0.016). No patients with EOS had detectable urine titanium. CONCLUSIONS: Patients with EOS treated with titanium alloy growth-friendly instrumentation had elevated serum titanium levels compared with age-matched controls that persisted over time with no evidence of renal excretion. Additional studies are necessary to assess for local and systemic accumulation of titanium and the significance of long-term exposure to titanium in growing children. LEVEL OF EVIDENCE: Level III, therapeutic.

Presentation and outcomes of KRASG12C mutant non-small cell lung cancer patients with stage IV disease at diagnosis (de novo) versus at recurrence.

Close monitoring after diagnosis of patients with stage I-III non-small cell lung cancer (NSCLC) may result in fitter patients with lower disease burden at the time of metastatic recurrence or progression compared to patients diagnosed initially as stage IV (de novo). We compared the presentation, treatments, and outcomes of patients with KRASG12C-mutated NSCLC with de novo versus recurrent stage IV disease. Of 109 patients, 94% had a smoking history. When compared to patients with KRASG12C-mutated NSCLC who developed stage IV disease at recurrence (n = 38), de novo stage IV patients (n = 71) had worse ECOG performance status (p = 0.007), greater numbers of extra-thoracic metastatic sites (p = 0.001), and were less likely to receive 2nd/3rd line systemic therapy (p = 0.05, p = 0.002) or targeted therapy (p = 0.001). De novo metastatic patients had shorter overall survival than metastatic patients at recurrence (9.1 versus 24.2 months; adjusted-hazard-ratio=1.94 (95% CI: 1.14-3.28; p = 0.01)). There is a critical need for well-tolerated targeted therapies in the first-line setting for metastatic patients with de novo, high-burden, stage IV KRASG12C-mutated NSCLCs.

Postnatal maternal care moderates the effects of prenatal bisphenol exposure on offspring neurodevelopmental, behavioral, and transcriptomic outcomes.

Bisphenols (BPs), including BPA and "BPA-free" structural analogs, are commonly used plasticizers that are present in many plastics and are known endocrine disrupting chemicals. Prenatal exposure to BPA has been associated with negative neurodevelopmental and behavioral outcomes in children and rodent models. Prenatal BPA exposure has also been shown to impair postnatal maternal care provisioning, which can also affect offspring neurodevelopment and behavior. However, there is limited knowledge regarding the biological effects of prenatal exposure to bisphenols other than BPA and the interplay between prenatal BP exposure and postnatal maternal care on adult behavior. The purpose of the current study was to determine the interactive impact of prenatal BP exposure and postnatal maternal care on neurodevelopment and behavior. Our findings suggest that the effects of prenatal BP exposure on eye-opening, adult attentional set shifting and anxiety-like behavior in the open field are dependent on maternal care in the first five days of life. Interestingly, maternal care might also attenuate the effects of prenatal BP exposure on eye opening and adult attentional set shifting. Finally, transcriptomic profiles in male and female medial prefrontal cortex and amygdala suggest that the interactive effects of prenatal BP exposure and postnatal maternal care converge on estrogen receptor signaling and are involved in biological processes related to gene expression and protein translation and synthesis. Overall, these findings indicate that postnatal maternal care plays a critical role in the expression of the effects of prenatal BP exposure on neurodevelopment and adult behavior. Understanding the underlying biological mechanisms involved might allow us to identify potential avenues to mitigate the adverse effects of prenatal BP exposure and improve health and well-being in human populations.

Shaping the development of complex social behavior.

Early life experiences can have an enduring impact on the brain and behavior, with implications for stress reactivity, cognition, and social behavior. In particular, the neural systems that contribute to the expression of social behavior are altered by early life social environments. However, paradigms that have been used to alter the social environment during development have typically focused on exposure to stress, adversity, and deprivation of species-typical social stimulation. Here, we explore whether complex social environments can shape the development of complex social behavior. We describe lab-based paradigms for studying early life social complexity in rodents that are generally focused on enriching the social and sensory experiences of the neonatal and juvenile periods of development. The impact of these experiences on social behavior and neuroplasticity is highlighted. Finally, we discuss the degree to which our current approaches for studying social behavior outcomes give insight into "complex" social behavior and how social complexity can be better integrated into lab-based methodologies.

Personality traits predict attitudes toward individuals with intellectual disability.

Background: Explaining individual differences in people's attitudes toward individuals with intellectual disability (ID) is important for increasing social inclusion of people with ID. The aim of the current study was to replicate and extend past research by formulating a single model of attitudes toward individuals with ID with several predictors: personality traits, quality and quantity of contact, perceived knowledge of ID, social desirability, and demographics. Methods: A sample of 221 undergraduate students in the United States completed several surveys in a lab setting: the Mental Retardation Attitude Inventory-Revised, the Big Five Inventory, McManus et al.'s measures of contact with and perceived knowledge of ID, and the Marlowe-Crowne Social Desirability Scale. Results: Results replicated previous findings by showing quality of contact was the strongest predictor of attitudes. Additionally, we found openness to experience and agreeableness remained significant predictors after holding all other variables constant. A follow-up mediation analysis demonstrated that quality of contact mediated the relations from openness and agreeableness to attitudes. Conclusions: Findings suggest personality factors can influence attitudes toward individuals with ID, and further emphasize the importance of quality of contact. Implications for the social inclusion of individuals with ID are discussed.