Cross-Sectional Associations between Prenatal Per- and Poly-Fluoroalkyl Substances and Bioactive Lipids in Three Environmental Influences on Child Health Outcomes (ECHO) Cohorts.

Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipids─metabolic and inflammation pathway indicators. We estimated associations between prenatal PFAS exposure and bioactive lipids, measuring 12 serum PFAS and 50 plasma bioactive lipids in 414 pregnant women (median 17.4 weeks' gestation) from three Environmental influences on Child Health Outcomes Program cohorts. Pairwise association estimates across cohorts were obtained through linear mixed models and meta-analysis, adjusting the former for false discovery rates. Associations between the PFAS mixture and bioactive lipids were estimated using quantile g-computation. Pairwise analyses revealed bioactive lipid levels associated with PFDeA, PFNA, PFOA, and PFUdA (p < 0.05) across three enzymatic pathways (cyclooxygenase, cytochrome p450, lipoxygenase) in at least one combined cohort analysis, and PFOA and PFUdA (q < 0.2) in one linear mixed model. The strongest signature revealed doubling in PFOA corresponding with PGD2 (cyclooxygenase pathway; +24.3%, 95% CI: 7.3-43.9%) in the combined cohort. Mixture analysis revealed nine positive associations across all pathways with the PFAS mixture, the strongest signature indicating a quartile increase in the PFAS mixture associated with PGD2 (+34%, 95% CI: 8-66%), primarily driven by PFOS. Bioactive lipids emerged as prenatal PFAS exposure biomarkers, deepening insights into PFAS' influence on pregnancy outcomes.

Examining the relationship of acetaminophen use during pregnancy with early language development in children.

BACKGROUND: Acetaminophen is the only analgesic considered safe for use throughout pregnancy. Recent studies suggest that use during pregnancy may be associated with poorer neurodevelopmental outcomes in children, but few have examined language development. METHODS: The Illinois Kids Development Study is a prospective birth cohort in east-central Illinois. Between December 2013 and March 2020, 532 newborns were enrolled and had exposure data available. Participants reported the number of times they took acetaminophen six times across pregnancy. Language data were collected at 26.5-28.5 months using the MacArthur-Bates Communicative Development Inventories (CDI; n = 298), and 36-38 months using the Speech and Language Assessment Scale (SLAS; n = 254). RESULTS: Taking more acetaminophen during the second or third trimester was associated with marginally smaller vocabularies and shorter utterance length (M3L) at 26.5-28.5 months. More acetaminophen use during the third trimester was also associated with increased odds of M3L scores ≤25th percentile in male children. More use during the second or third trimester was associated with lower SLAS scores at 36-38 months. Third trimester use was specifically related to lower SLAS scores in male children. CONCLUSIONS: Higher prenatal acetaminophen use during pregnancy may be associated with poorer early language development. IMPACT: Taking more acetaminophen during pregnancy, particularly during the second and third trimesters, was associated with poorer scores on measures of language development when children were 26.5-28.5 and 36-38 months of age. Only male children had lower scores in analyses stratified by child sex. To our knowledge, this is the first study that has used a standardized measure of language development to assess the potential impact of prenatal exposure to acetaminophen on language development. This study adds to the growing body of literature suggesting that the potential impact of acetaminophen use during pregnancy on fetal neurodevelopment should be carefully evaluated.

Cross-sectional associations between prenatal maternal per- and poly-fluoroalkyl substances and bioactive lipids in three Environmental influences on Child Health Outcomes (ECHO) cohorts.

Background: Per- and poly-fluoroalkyl substances (PFAS) exposure can occur through ingestion of contaminated food and water, and inhalation of indoor air contaminated with these chemicals from consumer and industrial products. Prenatal PFAS exposures may confer risk for pregnancy-related outcomes such as hypertensive and metabolic disorders, preterm birth, and impaired fetal development through intermediate metabolic and inflammation pathways. Objective: Estimate associations between maternal pregnancy PFAS exposure (individually and as a mixture) and bioactive lipids. Methods: Our study included pregnant women in the Environmental influences on Child Health Outcomes Program: Chemicals in our Bodies cohort (CiOB, n=73), Illinois Kids Developmental Study (IKIDS, n=287), and the ECHO-PROTECT cohort (n=54). We measured twelve PFAS in serum and 50 plasma bioactive lipids (parent fatty acids and eicosanoids derived from cytochrome p450, lipoxygenase, and cyclooxygenase) during pregnancy (median 17 gestational weeks). Pairwise associations across cohorts were estimated using linear mixed models and meta-analysis. Associations between the PFAS mixture and individual bioactive lipids were estimated using quantile g-computation. Results: PFDeA, PFOA, and PFUdA were associated (p<0.05) with changes in bioactive lipid levels in all three enzymatic pathways (cyclooxygenase [n=6 signatures]; cytochrome p450 [n=5 signatures]; lipoxygenase [n=7 signatures]) in at least one combined cohort analysis. The strongest signature indicated that a doubling in PFOA corresponded with a 24.3% increase (95% CI [7.3%, 43.9%]) in PGD2 (cyclooxygenase pathway) in the combined cohort. In the mixtures analysis, we observed nine positive signals across all pathways associated with the PFAS mixture. The strongest signature indicated that a quartile increase in the PFAS mixture was associated with a 34% increase in PGD2 (95% CI [8%, 66%]), with PFOS contributing most to the increase. Conclusions: Bioactive lipids were revealed as biomarkers of PFAS exposure and could provide mechanistic insights into PFAS' influence on pregnancy outcomes, informing more precise risk estimation and prevention strategies.

The Effects of Sustained Literacy Engagement on Cognition and Sentence Processing Among Older Adults.

Considerable evidence suggests that language processing depends on memory processes, which are vulnerable to declines with aging. Yet little is known about the effects of language processing in the form of sustained literacy engagement on memory and other aspects of cognition. In the current study, adults (60-79 years of age) were randomly assigned to an 8-week program of leisure reading (n = 38) or to an active puzzle control (n = 38). Relative to the control, the experimental group showed differential improvement in verbal working memory and episodic memory. The experimental group also showed evidence of enhanced conceptual integration in sentence processing. These effects did not vary as a function of personality characteristics (e.g., openness) hypothesized to be compatible with literacy engagement. These findings support the idea that the exercise of cognitive capacities in the context of everyday life may offset age-related impairment in areas of cognition engaged by the activity, regardless of dispositional fit.

Talker-specific predictions during language processing.

Language comprehension is shaped by world knowledge. After hearing about "a farm animal," meanings of typical ("cow") versus atypical exemplars ("ox") are more accessible, as evidenced by N400 responses. Moreover, atypical exemplars elicit a larger post-N400 frontal positivity than typical and incongruous ("ivy") exemplars, indexing the integration of unexpected information. Do listeners adapt this category knowledge to specific talkers? We first replicated typicality effects in the auditory modality. Then, we extended the design to a two-talker context: talkers alternated cueing (Bob: "Susan, name a farm animal") and answering (Susan: "cow"). Critically, participants first heard interviews in which one talker revealed strong associations with atypical exemplars (Susan works on an ox farm). We observed increased frontal positivity to a typical exemplar ("cow") said by Susan compared to Bob, indicating participants appreciated that the typical exemplar was atypical for Susan. These results suggest that comprehenders can tailor their expectations to the talker.

How struggling adult readers use contextual information when comprehending speech: Evidence from event-related potentials.

We investigated how struggling adult readers make use of sentence context to facilitate word processing when comprehending spoken language, conditions under which print decoding is not a barrier to comprehension. Stimuli were strongly and weakly constraining sentences (as measured by cloze probability), which ended with the most expected word based on those constraints or an unexpected but plausible word. Community-dwelling adults with varying literacy skills listened to continuous speech while their EEG was recorded. Participants, regardless of literacy level, showed N400 effects yoked to the cloze probability of the targets, with larger N400 amplitudes for less expected than more expected words. However, literacy-related differences emerged in an earlier time window of 170-300 ms: higher literacy adults produced a reduced negativity for strongly predictable targets over anterior channels, similar to previously reported effects on the Phonological Mapping Negativity (PMN), whereas low-literacy adults did not. Collectively, these findings suggest that in auditory sentence processing literacy may not notably affect the incremental activation of semantic features, but that comprehenders with underdeveloped literacy skills may be less likely to engage predictive processing. Thus, basic mechanisms of comprehension may be recruited differently as a function of literacy development-even in spoken language.

The effects of context on processing words during sentence reading among adults varying in age and literacy skill.

The facilitation of word processing by sentence context reflects the interaction between the build-up of message-level semantics and lexical processing. Yet, little is known about how this effect varies through adulthood as a function of reading skill. In this study, Participants 18-64 years old with a range of literacy competence read simple sentences as their eye movements were monitored. We manipulated the predictability of a sentence-final target word, operationalized as cloze probability. First fixation durations showed an interaction between age and literacy skill, decreasing with age among more skilled readers but increasing among less skilled readers. This pattern suggests that age-related slowing may impact reading when not buffered by skill, but with continued practice, automatization of reading can continue to develop in adulthood. In absolute terms, readers were sensitive to predictability, regardless of age or literacy, in both early and later measures. Older readers showed differential contextual sensitivity in regression patterns, effects not moderated by literacy skill. Finally, comprehension performance increased with age and literacy skill, but performance among less skilled readers was especially reduced when predictability was low, suggesting that low-literacy adults (regardless of age) struggle when creating mental representations under weaker semantic constraints. Collectively, these findings suggest that aging readers (regardless of reading skill) are more sensitive to context for meaning-integration processes; that less skilled adult readers (regardless of age) depend more on a constrained semantic representation for comprehension; and that the capacity for literacy engagement enables continued development of efficient lexical processing in adult reading development. (PsycINFO Database Record

The fox and the cabra: an ERP analysis of reading code switched nouns and verbs in bilingual short stories.

Comprehending a language (or code) switch within a sentence context triggers 2 electrophysiological signatures: an early left anterior negativity post code switch onset - a LAN - followed by a Late Positive Component (LPC). Word class and word position modulate lexico-semantic processes in the monolingual brain, e.g., larger N400 amplitude for nouns than verbs and for earlier than later words in the sentence. Here we test whether the bilingual brain is affected by word class and word position when code switching, or if the cost of switching overrides these lexico-semantic and sentence context factors. Adult bilinguals read short stories in English containing 8 target words. Targets were nouns or verbs, occurred early or late in a story and were presented alternately in English (non-switch) or Spanish (switch) across different story versions. Overall, switched words elicited larger LAN and LPC amplitude than non-switched words. The N400 amplitude was larger for nouns than verbs, more focal for switches than non-switches, and for early than late nouns but not for early than late verbs. Moreover, an early LPC effect was observed only for switched nouns, but not verbs. Together, this indicates that referential elements (nouns) may be harder to process and integrate than relational elements (verbs) in discourse, and when switched, nouns incur higher integration cost. Word position did not modulate the code switching effects, implying that switching between languages may invoke discourse independent processes.

Meaning first: a case for language-independent access to word meaning in the bilingual brain.

This study aimed to determine how deeply a word is processed in the bilingual brain before the word's language membership plays a role in lexical selection. In two ERP experiments, balanced Spanish-English bilinguals read lists of words and pseudowords in Spanish and English, and performed in each language (1) a language-specific lexical decision task, e.g., respond to real words in Spanish, and (2) a language-specific category decision tasks, e.g., respond to Spanish words that refer to a person. In Experiment 1, infrequent words elicited larger negativity between 350 and 650 ms post-stimulus onset for both target and non-target languages. This indicates that language membership did not block lexical access of non-target words, contrary to previous findings. In Experiment 2, we measured the onset of the target-category P300 as a way of determining if words from the non-target language were temporarily treated as targets. When Spanish was the target language, the ERP waveforms diverged early based on semantic category (people versus non-people), indicating that non-target 'English people' words were briefly treated as potential targets. This finding indicates that meaning was accessed prior to using language membership for lexical selection. However, when English was the target language, the waveforms diverged first based on language (Spanish versus English) then semantic category. We argue that the order in which meaning or language membership are accessed may be based on the frequency of use of a bilingual's languages: the more frequently a language is used (English was more frequently used herein), the faster the words are identified as members of the language, and the greater interference it causes when it is not the target language. In brief, these findings make the case for a moment in processing when language membership matters less than meaning.