Additive drug-specific and sex-specific risks associated with co-use of marijuana and tobacco during pregnancy: Evidence from 3 recent developmental cohorts (2003-2015).

BACKGROUND: Methodologic challenges related to the concomitant use (co-use) of substances and changes in policy and potency of marijuana contribute to ongoing uncertainty about risks to fetal neurodevelopment associated with prenatal marijuana use. In this study, we examined two biomarkers of fetal neurodevelopmental risk-birth weight and length of gestation-associated with prenatal marijuana use, independent of tobacco (TOB), alcohol (ALC), other drug use (OTH), and socioeconomic risk (SES), in a pooled sample (N = 1191) derived from 3 recent developmental cohorts (2003-2015) with state-of-the-art substance use measures. We examined differential associations by infant sex, and multiplicative effects associated with co-use of MJ and TOB. METHODS: Participants were mother-infant dyads with complete data on all study variables derived from Growing Up Healthy (n = 251), Behavior and Mood in Babies and Mothers (Cohorts 1 and 2; n = 315), and the Early Growth and Development Study (N = 625). We estimated direct effects on birth weight and length of gestation associated with MJ, TOB, and co-use (MJ x TOB), using linear regression analysis in the full sample, and in male (n = 654) and female (n = 537) infants, separately. RESULTS: Mean birth weight and length of gestation were 3277 g (SD = 543) and 37.8 weeks (SD = 2.0), respectively. Rates of prenatal use were as follows: any use, n = 748 (62.8%); MJ use, n = 273 (22.9%); TOB use, n = 608 (51.0%); co-use of MJ and TOB, n = 230 (19.3%); ALC use, n = 464 (39.0%); and OTH use n = 115 (9.7%.) For all infants, unique effects on birth weight were observed for any MJ use [B(SE) = -84.367(38.271), 95% C.I. -159.453 to -9.281, p = .028], any TOB use [B(SE) = -0.99.416(34.418), 95% C.I. -166.942 to -31.889, p = .004], and each cigarette/day in mean TOB use [B(SE) = -12.233(3.427), 95% C.I. -18.995 to -5.510, p \u3c .001]. Additional effects of co-use on birth weight, beyond these drug-specific effects, were not supported. In analyses stratified by sex, while TOB use was associated with lower birth weight in both sexes, MJ use during pregnancy was associated with lower birth weight of male infants [B(SE) = -153.1 (54.20); 95% C.I. -259.5 to -46.7, p = .005], but not female infants [B(SE) = 8.3(53.1), 95% C.I. -96.024 to 112.551, p = .876]. TOB, MJ, and their co-use were not associated with length of gestation. CONCLUSIONS: In this sample, intrauterine co-exposure to MJ and TOB was associated with an estimated 18% reduction in birth weight not attributable to earlier delivery, exposure to ALC or OTH drugs, nor to maternal SES. We found evidence for greater susceptibility of male fetuses to any prenatal MJ exposure. Examination of dose-dependence in relationships found in this study, using continuous measures of exposure, is an important next step. Finally, we underscore the need to consider (a) the potential moderating influence of fetal sex on exposure-related neurodevelopmental risks; and (b) the importance of quantifying expressions of risk through subtle alterations, rather than dichotomous outcomes

Commonality and variation in mental representations of music revealed by a cross-cultural comparison of rhythm priors in 15 countries

Music is present in every known society but varies from place to place. What, if anything, is universal to music cognition? We measured a signature of mental representations of rhythm in 39 participant groups in 15 countries, spanning urban societies and Indigenous populations. Listeners reproduced random 'seed' rhythms; their reproductions were fed back as the stimulus (as in the game of 'telephone'), such that their biases (the prior) could be estimated from the distribution of reproductions. Every tested group showed a sparse prior with peaks at integer-ratio rhythms. However, the importance of different integer ratios varied across groups, often reflecting local musical practices. Our results suggest a common feature of music cognition: discrete rhythm 'categories' at small-integer ratios. These discrete representations plausibly stabilize musical systems in the face of cultural transmission but interact with culture-specific traditions to yield the diversity that is evident when mental representations are probed across many cultures. [Abstract copyright: © 2024. The Author(s).

Identification of Novel MET Exon 14 Skipping Variants in Non-Small Cell Lung Cancer Patients: A Prototype Workflow Involving in Silico Prediction and RT-PCR

Background and aims: The MET exon 14 skipping (METex14) is an oncogenic driver mutation that provides a therapeutic opportunity in non-small cell lung cancer (NSCLCs) patients. This event often results from sequence changes at the MET canonical splicing sites. We characterize two novel non-canonical splicing site variants of MET that produce METex14. Materials and Methods: Two variants were identified in three advanced-stage NSCLC patients in a next-generation sequencing panel. The potential impact on splicing was predicted using in silico tools. METex14 mutation was confirmed using reverse transcription (RT)-PCR and a Sanger sequencing analysis on RNA extracted from stained cytology smears. Results: The interrogated MET (RefSeq ID NM_000245.3) variants include a single nucleotide substitution, c.3028+3A>T, in intron 14 and a deletion mutation, c.3012_3028del, in exon 14. The in silico prediction analysis exhibited reduced splicing strength in both variants compared with the MET normal transcript. The RT-PCR and subsequent Sanger sequencing analyses confirmed METex14 skipping in all three patients carrying these variants. Conclusion: This study reveals two non-canonical MET splice variants that cause exon 14 skipping, concurrently also proposes a clinical workflow for the classification of such non-canonical splicing site variants detected by routine DNA-based NGS test. It shows the usefulness of in silico prediction to identify potential METex14 driver mutation and exemplifies the opportunity of routine cytology slides for RNA-based testing

Parents’ Readiness to Change Affects BMI Reduction Outcomes in Adolescents with Polycystic Ovary Syndrome

Evidence supports the importance of parental involvement for youth’s ability to manage weight. This study utilized the stages of change (SOC) model to assess readiness to change weight control behaviors as well as the predictive value of SOC in determining BMI outcomes in forty adolescent-parent dyads (mean adolescent age = 15 ± 1.84 (13–20), BMI = 37 ± 8.60; 70% white) participating in a weight management intervention for adolescent females with polycystic ovary syndrome (PCOS). Adolescents and parents completed a questionnaire assessing their SOC for the following four weight control domains: increasing dietary portion control, increasing fruit and vegetable consumption, decreasing dietary fat, and increasing usual physical activity. Linear regression analyses indicated that adolescent change in total SOC from baseline to treatment completion was not predictive of adolescent change in BMI from baseline to treatment completion. However, parent change in total SOC from baseline to treatment completion was predictive of adolescent change in BMI, (t(24) = 2.15, p=0.043). Findings support future research which carefully assesses adolescent and parent SOC and potentially develops interventions targeting adolescent and parental readiness to adopt healthy lifestyle goals