Perspectives of adolescents and young adults on cannabis use during pregnancy.

PURPOSE: Rates of cannabis use during pregnancy are highest for adolescents and young adults (AYAs). This study aims to understand AYA perspectives regarding the medical and legal consequences of prenatal and parental cannabis use. METHODS: This study delivered five open-ended survey questions regarding prenatal cannabis use in May/June 2022 via a text message polling platform to the MyVoice cohort, a cohort of AYA aged 14-24 throughout the United States recruited from social media to target national benchmarks set by the American Community Survey. We used qualitative content analysis to analyze open-ended responses and summarized code frequency and demographic data with descriptive statistics. RESULTS: Of 826 AYAs, 666 responded to at least one question (response rate = 80.6 %) and the mean age of respondents was 19.9 years (SD = 2.3). We identified four themes from responses: (1) AYA believe cannabis is harmful during pregnancy, (2) they are divided on whether prenatal cannabis exposure should be considered child abuse or neglect, (3) they have mixed attitudes about safe parenting and regular cannabis use, and (4) they support counseling from health care professionals about prenatal cannabis use. CONCLUSIONS: AYAs were concerned about potential risks of prenatal cannabis exposure and want clinicians to counsel about cannabis use during pregnancy. More than one in three AYAs surveyed felt prenatal cannabis use should be classified as child abuse or neglect, in contrast to the declining perception of risk among pregnant people.

Association Between Psychosocial Acuity and Glycemic Control in a Pediatric Type 1 Diabetes Clinic.

PURPOSE: The purpose of this study was to describe the frequency of psychosocial risk and its associations with glycemic levels in youth with type 1 diabetes (T1D) seen by social work staff during regular clinical care. METHODS: A retrospective longitudinal analysis of observational clinical data was conducted. Individuals (1-26 years) with known T1D who were seen at a pediatric diabetes clinic in a US academic medical center between 2014 and 2021 were included. Variables included psychosocial acuity, A1C, and demographic characteristics. Chi-square tests, Wilcoxon rank sum tests, and mixed linear regressions were used to examine associations between demographic variables, psychosocial acuity, and A1C. RESULTS: Of 966 patients, 513 (53.1%) were male, 76 (7.9%) were non-Hispanic Black, and 804 (83.2%) were non-Hispanic White. There was a mean of 6.9 annual social work encounters per patient, with 3 psychosocial domains measured at each visit. Results showed that as psychosocial acuity level increased, glycemic control decreased. There were significant differences in A1C according to race/ethnicity, insurance, age, and psychosocial acuity. CONCLUSIONS: In a real-world clinical population, psychosocial acuity was associated with glycemic control. Presenting for psychosocial issues in their diabetes clinic was associated with reduced glycemic control among youth with T1D. There is an opportunity to connect pediatric patients with appropriate mental health services and psychosocial supports.

How a speaker herds the audience: Multi-brain neural convergence over time during naturalistic storytelling.

Storytelling-an ancient way for humans to share individual experiences with others-has been found to induce neural synchronization among listeners. In our exploration of the dynamic fluctuations in listener-listener (LL) coupling throughout stories, we uncover a significant correlation between LL and lag-speaker-listener (lag-SL) couplings over time. Using the analogy of neural pattern (dis)similarity as distances between participants, we term this phenomenon the "herding effect": like a shepherd guiding a group of sheep, the more closely listeners follow the speaker's prior brain activity patterns (higher lag-SL similarity), the more tightly they cluster together (higher LL similarity). This herding effect is particularly pronounced in brain regions where neural synchronization among listeners tracks with behavioral ratings of narrative engagement, highlighting the mediating role of narrative content in the observed multi-brain neural coupling dynamics. By integrating LL and SL neural couplings, this study illustrates how unfolding stories shape a dynamic multi-brain functional network and how the configuration of this network may be associated with moment-by-moment efficacy of communication.

Youth experiences with and perspectives on long covid.

BACKGROUND: Research on the long-term effects of COVID-19 infection is ongoing, and the psychological and physical impacts of Long Covid on youth is poorly understood. To assess these impacts, we surveyed youth regarding their experiences with, and perspectives on, the long-term effects of COVID-19. METHODS: We conducted a nationwide text message survey of youth ages 14-24 years in the United States. The survey asked four open ended questions regarding their experiences and perceptions regarding the long-term effects of COVID-19. Qualitative data was analyzed independently by three investigators using thematic analysis. Prevalence of codes were summarized using descriptive statistics. RESULTS: Among 1150 participants, 991 responded to at least one survey question (response rate 86.1%). The vast majority of our sample had COVID-19 or knew someone who did (75%), and approximately one third (32%) of youth indicated that they knew someone who had experienced symptoms consistent with Long Covid. Many youth (50%) reported worry and concern about Long Covid even if they, or someone they knew, did not have Long Covid. Among youth who were not concerned about Long Covid, the most commonly reported reasons were having received the vaccine (29%) and not having a prior COVID-19 infection (24%). CONCLUSIONS: Our findings suggest that among younger populations, there is significant concern regarding the long-term effects of COVID-19. Vaccination campaigns and youth-centered public health communication about Long Covid may not only reduce COVID-19 transmission, but also alleviate worries and concerns about Long Covid among youth.

Reactive Oxygen Species in Drought-Induced Stomatal Closure: The Potential Roles of NPR1.

Stomatal closure is a vital, adaptive mechanism that plants utilize to minimize water loss and withstand drought conditions. We will briefly review the pathway triggered by drought that governs stomatal closure, with specific focuses on salicylic acid (SA) and reactive oxygen species (ROS). We propose that the non-expressor of PR Gene 1 (NPR1), a protein that protects plants during pathogen infections, also responds to SA during drought to sustain ROS levels and prevent ROS-induced cell death. We will examine the evidence underpinning this hypothesis and discuss potential strategies for its practical implementation.

Integrin ß3 directly inhibits the Gα13-p115RhoGEF interaction to regulate G protein signaling and platelet exocytosis.

The integrins and G protein-coupled receptors are both fundamental in cell biology. The cross talk between these two, however, is unclear. Here we show that ß3 integrins negatively regulate G protein-coupled signaling by directly inhibiting the Gα13-p115RhoGEF interaction. Furthermore, whereas ß3 deficiency or integrin antagonists inhibit integrin-dependent platelet aggregation and exocytosis (granule secretion), they enhance G protein-coupled RhoA activation and integrin-independent secretion. In contrast, a ß3-derived Gα13-binding peptide or Gα13 knockout inhibits G protein-coupled RhoA activation and both integrin-independent and dependent platelet secretion without affecting primary platelet aggregation. In a mouse model of myocardial ischemia/reperfusion injury in vivo, the ß3-derived Gα13-binding peptide inhibits platelet secretion of granule constituents, which exacerbates inflammation and ischemia/reperfusion injury. These data establish crucial integrin-G protein crosstalk, providing a rationale for therapeutic approaches that inhibit exocytosis in platelets and possibly other cells without adverse effects associated with loss of cell adhesion.

Information flow across the cortical timescale hierarchy during narrative construction.

When listening to spoken narratives, we must integrate information over multiple, concurrent timescales, building up from words to sentences to paragraphs to a coherent narrative. Recent evidence suggests that the brain relies on a chain of hierarchically organized areas with increasing temporal receptive windows to process naturalistic narratives. We hypothesized that the structure of this cortical processing hierarchy should result in an observable sequence of response lags between networks comprising the hierarchy during narrative comprehension. This study uses functional MRI to estimate the response lags between functional networks during narrative comprehension. We use intersubject cross-correlation analysis to capture network connectivity driven by the shared stimulus. We found a fixed temporal sequence of response lags-on the scale of several seconds-starting in early auditory areas, followed by language areas, the attention network, and lastly the default mode network. This gradient is consistent across eight distinct stories but absent in data acquired during rest or using a scrambled story stimulus, supporting our hypothesis that narrative construction gives rise to internetwork lags. Finally, we build a simple computational model for the neural dynamics underlying the construction of nested narrative features. Our simulations illustrate how the gradual accumulation of information within the boundaries of nested linguistic events, accompanied by increased activity at each level of the processing hierarchy, can give rise to the observed lag gradient.

Youth Perspectives on Their Medical Team's Role in Screening for and Addressing Social Determinants of Health.

PURPOSE: Little is known about adolescents' and young adults' desires and preferences surrounding healthcare-based social determinants of health (SDOHs) interventions. To assess these preferences, we surveyed youth regarding their perspectives on their medical team's role in addressing SDOHs. METHODS: We conducted a national text message survey of youth aged 14-24 years. The survey asked five open-ended questions about SDOHs and SDOH interventions. Qualitative data were analyzed independently by two investigators using thematic analysis. Prevalence of codes was summarized using descriptive statistics. RESULTS: Among 1,156 participants, 1,038 responded to at least one survey question (response rate = 89.8%). Respondents were 19.2 (standard deviation: 2.4) years old on average, 48.9% male, 62.1% non-Hispanic white, and 38.9% qualified for free or reduced lunch. A large majority of our sample (81%) indicated that they think it is important for their doctor or medical team to ask about SDOHs. The most commonly reported barrier to seeking or receiving SDOH assistance was embarrassment (30%). Youth wanted their providers to help with SDOHs not only by providing information about resources (25%) and referrals (13%) but also by offering general advice (22%) and listening (11%). Approximately half (51%) of our sample preferred to receive information about SDOH assistance in person. DISCUSSION: Most youth believe it is important for their medical teams to ask about and address SDOHs. Implementation of healthcare-based SDOH interventions for youth should optimize opportunities for face-to-face discussions about assistance during clinical encounters.

Gα13 Mediates Transendothelial Migration of Neutrophils by Promoting Integrin-Dependent Motility without Affecting Directionality.

Neutrophil migration requires ß2 integrins and chemoattractant receptor signaling for motility and directionality. G protein subunit Gα13 can facilitate cell migration by mediating RhoA activation induced by G protein-coupled receptors. However, the possible role of Gα13-integrin interaction in migration is unclear. In this study, we show that Gα13 -/- neutrophils are deficient in transendothelial migration and migration on ß2 integrin ligand ICAM-1. However, unlike G protein-coupled receptors and integrin inside-out signaling pathways, Gα13 is important in migration velocity and neutrophil spreading but not in directionality nor cell adhesion. Importantly, neutrophil recruitment in vivo was also inhibited in Gα13 -/- mice, suggesting the importance of Gα13 in transendothelial migration of neutrophils in vitro and in vivo. Furthermore, a synthetic peptide (MB2mP6) derived from the Gα13 binding site of ß2 inhibited Gα13-ß2 interaction and Gα13-mediated transient RhoA inhibition in neutrophils, suggesting that this peptide inhibited integrin outside-in signaling. MB2mP6 inhibited migration of control neutrophils through endothelial cell monolayers or ICAM-1-coated filters, but was without further effect on Gα13 -/- neutrophils. It also inhibited integrin-dependent neutrophil migration velocity without affecting directionality. In vivo, MB2mP6 markedly inhibited neutrophil infiltration into the cardiac tissues induced by ischemia/reperfusion injury. Thus, Gα13-dependent outside-in signaling enables integrin-dependent neutrophil motility without affecting directionality and may be a new therapeutic target for inhibiting neutrophil trafficking but not adhesion.

The "Narratives" fMRI dataset for evaluating models of naturalistic language comprehension.

The "Narratives" collection aggregates a variety of functional MRI datasets collected while human subjects listened to naturalistic spoken stories. The current release includes 345 subjects, 891 functional scans, and 27 diverse stories of varying duration totaling ~4.6 hours of unique stimuli (~43,000 words). This data collection is well-suited for naturalistic neuroimaging analysis, and is intended to serve as a benchmark for models of language and narrative comprehension. We provide standardized MRI data accompanied by rich metadata, preprocessed versions of the data ready for immediate use, and the spoken story stimuli with time-stamped phoneme- and word-level transcripts. All code and data are publicly available with full provenance in keeping with current best practices in transparent and reproducible neuroimaging.

Relating the Past with the Present: Information Integration and Segregation during Ongoing Narrative Processing.

This study examined how the brain dynamically updates event representations by integrating new information over multiple minutes while segregating irrelevant input. A professional writer custom-designed a narrative with two independent storylines, interleaving across minute-long segments (ABAB). In the last (C) part, characters from the two storylines meet and their shared history is revealed. Part C is designed to induce the spontaneous recall of past events, upon the recurrence of narrative motifs from A/B, and to shed new light on them. Our fMRI results showed storyline-specific neural patterns, which were reinstated (i.e., became more active) during storyline transitions. This effect increased along the processing timescale hierarchy, peaking in the default mode network. Similarly, the neural reinstatement of motifs was found during Part C. Furthermore, participants showing stronger motif reinstatement performed better in integrating A/B and C events, demonstrating the role of memory reactivation in information integration over intervening irrelevant events.

High-loading Gα13-binding EXE peptide nanoparticles prevent thrombosis and protect mice from cardiac ischemia/reperfusion injury.

Inefficient delivery is a major obstacle to the development of peptide-based drugs targeting the intracellular compartment. We recently showed that selectively inhibiting integrin outside-in signaling using a peptide (mP6) derived from the Gα13-binding ExE motif within the integrin ß3 cytoplasmic domain had antithrombotic effects. Here, we engineered lipid-stabilized, high-loading peptide nanoparticles (HLPN), in which a redesigned ExE peptide (M3mP6) constituted up to 70% of the total nanoparticle molarity, allowing efficient in vivo delivery. We observed that M3mP6 HLPN inhibited occlusive thrombosis more potently than a clopidogrel/aspirin combination without adverse effects on hemostasis in rodents. Furthermore, M3mP6 HLPN synergized with P2Y12 receptor inhibitors or the clopidogrel/aspirin combination in preventing thrombosis, without exacerbating hemorrhage. M3mP6 HLPN also inhibited intravascular coagulation more potently than the P2Y12 inhibitor cangrelor. Postischemia injection of M3mP6 HLPN protected the heart from myocardial ischemia-reperfusion injury in a mouse model. This study demonstrates an efficient in vivo peptide delivery strategy for a therapeutic that not only efficaciously prevented thrombosis with minimal bleeding risk but also protected from myocardial ischemia-reperfusion injury in mice.

Cortical encoding of linguistic constituent with and without morphosyntactic cues.

This study examined the brain areas involved in combining words into larger units when there are few or no morphosyntactic cues. We manipulated constituent length in word strings of the same length under two conditions: Mandarin sentence, which had sparse morphosyntactic cues, and nominal phrase that had no morphosyntactic cues [e.g., ((honey mustard) (chicken burger))]. Contrasting sentences to word lists revealed a network that largely overlapped with the one reported in languages with rich morphosyntactic cues, including left IFGorb/IFGtri and areas along left STG/STS. Both conditions showed increased activation in left IFGtri/IFGorb in functional ROIs defined based on previous study in sentence processing, while the nominal phrases additionally revealed a constituent length effect in bilateral dorsal IFGtri, left IFGoper, left pMTG/pSTG, left IPL, and several subcortical areas, which might reflect an increased reliance on semantic and pragmatic information. Moreover, in upper left IFGtri/IFGoper and left thalamus/caudate, this effect increased with the participants' tendency to combine nouns into phrases. The absence of syntactic constraints on linguistic composition might highlight individual differences in cognitive control, which helps to integrate non-syntactic information.

Differential brain mechanisms during reading human vs. machine translated fiction and news texts.

Few neuroimaigng studies on reading comprehension have been conducted under natural reading settings. In this study, we showed texts presented in a natural way during functional MRI (fMRI) measurements to reveal brain areas sensitive to reading comprehension. Specifically, this paradigm independently manipulated two holistic features of article style: text genre and translation style, a qualitative index of how typical word choices and arrangements are made in daily use of the language. Specifically, articles from The New York Times (news) and Reader's Digest (fiction) translated from English to Mandarin Chinese either by human experts or machine (Google Translate) were used to investigate the correlation of brain activity across participants during article reading. We found that bi-hemispheric visual cortex, precuneus, and occipito-parietal junction show significantly correlated hemodynamics across participants regardless of translation style and article genre. Compared to machine translation, reading human expert translation elicited more reliable fMRI signals across participants at precuneus, potentially because narrative representations and contents can be coherently presented over tens of seconds. We also found significantly stronger inter-subject correlated fMRI signals at temporal poles and fusiform gyri in fiction reading than in news reading. This may be attributed to more stable empathy processing across participants in fiction reading. The degree of stability of brain responses across subjects at extra-linguistic areas was found correlated with subjective rating on the text fluency. The functional connectivity between these areas was modulated by text genre and translation style. Taken together, our imaging results suggested stable and selective neural substrates associated with comprehending holistic features of written narratives.

Administration, Billing, and Payment for Pharmacy Student-Based Immunizations to Medicare Beneficiaries at Mobile Medicare Clinics.

Training student pharmacists to administer vaccinations requires a substantial investment in vaccines, supplies, and time. Few schools of pharmacy seek out or receive any reimbursement for the provision of vaccines, despite the fact it is a covered service. This study sought to implement, deliver, and demonstrate an innovative, financially sustainable curriculum-based immunization program by trained pharmacy students as part of their experiential learning. Thirty-nine community health clinics targeting Medicare beneficiaries were conducted throughout Northern/Central California during Medicare's fall open enrollment periods between 2014⁻2016. American Pharmacists Association (APhA)-trained student pharmacists (under licensed pharmacist supervision) administered 1777 vaccinations. Vaccines were billed via a secure Health Insurance Portability and Accountability Act of 1996 (HIPAA)-compliant web-based portal. The total net income was $11,905 and $8032 for 2015 and 2016, respectively. Return on investment was greatest for the influenza vaccine > Tdap > pneumococcal. Pharmacy students are already being trained to provide immunizations and can utilize their skills to deliver financially viable public health programs.

Perceived Barriers to Physical Activity Among Low-Income Latina Women at Risk for Type 2 Diabetes.

Purpose The purpose of this study was to examine perceived barriers to physical activity among low-income Latina women who were at risk for type 2 diabetes, as well as the demographic factors that influence these perceived barriers. Methods Recruited in the waiting room of a community health center in a low-income neighborhood (n = 160), Latina women between the ages of 18 and 49 years completed a survey to assess demographic characteristics and perceived barriers to physical inactivity. Descriptive statistics, chi-square tests, and multivariate regression analyses were conducted to identify barriers to physical activity and the associations between demographic factors and perceived barriers. Results The most commonly perceived barriers to physical activity in the study sample were lack of willpower and lack of energy. After adjusting for other characteristics, overweight/obese participants were more likely than women of normal weight to report social influence and fear of injury as important barriers to exercise. In addition, women whose preferred language was Spanish were more likely than women whose preferred language was English to perceive lack of time, and social influence as important barriers. Conclusions The effective encouragement of physical activity among Latina women at risk for type 2 diabetes must address the perceived barriers of lack of willpower and lack of energy. Although all women at risk for type 2 diabetes could benefit from counseling and other strategies to encourage physical activity, these efforts should be targeted toward Spanish-speaking overweight/obese women, who are more likely to perceive barriers to exercise.

The Neural Substrates Underlying the Implementation of Phonological Rule in Lexical Tone Production: An fMRI Study of the Tone 3 Sandhi Phenomenon in Mandarin Chinese.

This study examined the neural substrates underlying the implementation of phonological rule in lexical tone by the Tone 3 sandhi phenomenon in Mandarin Chinese. Tone 3 sandhi is traditionally described as the substitution of Tone 3 with Tone 2 when followed by another Tone 3 (33 →23) during speech production. Tone 3 sandhi enables the examination of tone processing in the phonological level with the least involvement of segments. Using the fMRI technique, we measured brain activations corresponding to the monosyllable and disyllable sequences of the four Chinese lexical tones, while manipulating the requirement on overt oral response. The application of Tone 3 sandhi to disyllable sequence of Tone 3 was confirmed by our behavioral results. Larger brain responses to overtly produced disyllable Tone 3 (33 > 11, 22, and 44) were found in right posterior IFG by both whole-brain and ROI analyses. We suggest that the right IFG was responsible for the processing of Tone 3 sandhi. Intense temporo-frontal interaction is needed in speech production for self-monitoring. The involvement of the right IFG in tone production might result from its interaction with the right auditory cortex, which is known to specialize in pitch. Future studies using tools with better temporal resolutions are needed to illuminate the dynamic interaction between the right inferior frontal regions and the left-lateralized language network in tone languages.

Adaptation of the human visual system to the statistics of letters and line configurations.

By adulthood, literate humans have been exposed to millions of visual scenes and pages of text. Does the human visual system become attuned to the statistics of its inputs? Using functional magnetic resonance imaging, we examined whether the brain responses to line configurations are proportional to their natural-scene frequency. To further distinguish prior cortical competence from adaptation induced by learning to read, we manipulated whether the selected configurations formed letters and whether they were presented on the horizontal meridian, the familiar location where words usually appear, or on the vertical meridian. While no natural-scene frequency effect was observed, we observed letter-status and letter frequency effects on bilateral occipital activation, mainly for horizontal stimuli. The findings suggest a reorganization of the visual pathway resulting from reading acquisition under genetic and connectional constraints. Even early retinotopic areas showed a stronger response to letters than to rotated versions of the same shapes, suggesting an early visual tuning to large visual features such as letters.