Language learning in the context of a global pandemic: proximal and distal factors matter.

BACKGROUND: Public health measures implemented during the COVID-19 pandemic fundamentally altered the socioecological context in which children were developing. METHODS: Using Bronfenbrenner's socioecological theory, we investigate language acquisition among 2-year-old children (n = 4037) born during the pandemic. We focus on "late talkers", defined as children below the 10th percentile on the MacArthur-Bates Communicative Development Inventories-III. RESULTS: Overall, the proportion of late talkers declined as a function of pandemic wave, with 13.0% of those born during the first wave classified as late talkers compared to 10.4% born in wave two, and 8.0% born during wave three. In sex-based analysis, we observed a 15.9% prevalence of late talking among female toddlers, which was significantly different from the norming sample. In contrast, the prevalence of late talking among male toddlers was 9.1%. Using hierarchical logistic regression to identify both proximal and distal factors associated with being a late talker, we found that male sex, lower socioeconomic status, greater screen time, receiving childcare at home, disruptions to childcare, and experiencing greater exposure to public health restrictions were associated with increased odds for being a late talker. CONCLUSION: We interpret the findings in relation to the need to consider the special needs of young children in disaster preparation and response. IMPACT: Two-year-old children acquiring language in the context of the COVID-19 pandemic have vocabulary size similar to historical norms. A higher-than-expected prevalence of late talkers (below the 10th percentile) was observed among females and children born during the first wave of the pandemic. Motivated by Bronfenbrenner's socioecological theory, we show that both proximal and distal environmental factors are associated with vocabulary size. Infants exposed to stricter public measures had reduced vocabulary size. The findings suggest a need to recognize the developmental needs of children as part of the public health response to emergencies.

Access to Online Formative Assessments in Lower-Division Undergraduate Biology Courses: Investigating Barriers to Student Engagement.

Instructors use a variety of online formative assessment (FA) activities to support learning outside class. Previous studies have revealed barriers for students in online courses, but little is known about the barriers students experience when completing online FA assignments. Understanding these barriers to access is critical to fostering more inclusive learning for all students. Using a framework from previous work in online learning, we examined student perceptions of online FA access with respect to five barrier categories: technical resources, instructor organization, social interactions, personal engagement, and learning environment. We developed and administered a survey to more than 1200 undergraduate biology students at 2-year and 4-year institutions. Students responded to statements using Likert scales and open-ended prompts. Statistical models indicated differences in access across the barrier categories and revealed that demographic characteristics were associated with certain barrier categories. Furthermore, technical resources, instructor organization, and personal engagement barriers were associated with lower course performance. In open-ended responses, students most frequently suggested that changes to scheduling logistics, course delivery, and FA format would improve their online FA experience. We discuss how these findings and student suggestions can inform instruction, particularly how instructors can alter their FA characteristics to better suit their student populations.

Revisiting Clickers: In-Class Questions Followed by At-Home Reflections Are Associated with Higher Student Performance on Related Exam Questions.

Clicker questions are a commonly used active learning technique that stimulates student interactions to help advance understanding of key concepts. Clicker questions are often administered with an initial vote, peer discussion, and a second vote, followed by broader classroom explanation. While clickers can promote learning, some studies have questioned whether students maintain this performance on later exams, highlighting the need to further understand how student answer patterns relate to their understanding of the material and to identify ways for clickers to benefit a broader range of students. Systematic requizzing of concepts during at-home assignments represents a promising mechanism to improve student learning. Thus, we paired clicker questions with at-home follow-up reflections to help students articulate and synthesize their understandings. This pairing of clickers with homework allowed us to decipher how student answer patterns related to their underlying conceptions and to determine if revisiting concepts provided additional benefits. We found that students answering both clicker votes correctly performed better on isomorphic exam questions and that students who corrected their answers after the first vote did not show better homework or exam performance than students who maintained an incorrect answer across both votes. Furthermore, completing the follow-up homework assignment modestly boosted exam question performance. Our data suggest that longer-term benefits of clickers and associated homework may stem from students having repeated opportunities to retrieve, refine, and reinforce emerging conceptions.

Prenatal Maternal Distress During the COVID-19 Pandemic and Associations With Infant Brain Connectivity.

BACKGROUND: The COVID-19 pandemic has caused substantially elevated distress in pregnant individuals, which has the potential to affect the developing infant brain. Our main objective was to understand how prenatal distress was related to infant brain structure and function and whether social support moderated the associations. METHODS: The Pregnancy during the COVID-19 Pandemic (PdP) cohort study collected Patient-Reported Outcomes Measurement Information System Anxiety scale, Edinburgh Postnatal Depression Scale, and Social Support Effectiveness Questionnaire data from a population-based sample of pregnant individuals living in Canada (N = 8602). For a subsample of participants, their infants (n = 75) underwent magnetic resonance imaging at 3 months of age to examine whether prenatal maternal distress was associated with infant brain architecture, including the role of social support as a potential protective factor. RESULTS: Overall, 33.4% of participants demonstrated clinically elevated depression symptoms and 47.1% of participants demonstrated clinically elevated anxiety symptoms. We identified lower social support as a significant predictor of clinically elevated prenatal maternal distress (t8598 = -22.3, p < .001). Fifty-eight diffusion image datasets (20 female/38 male, 92 ± 14 days old) and 41 functional datasets (13 female/28 male, 92 ± 14 days old) were included in our analysis after removal of poor-quality images and infants without postpartum maternal distress scores. We found significant relationships between prenatal maternal distress and infant amygdala-prefrontal microstructural and functional connectivity measures, and we demonstrate for the first time that social support moderates these relationships. CONCLUSIONS: Our findings suggest a potentially long-lasting impact of the COVID-19 pandemic on children and show that social support acts as a possible mediator not just for pregnant individuals but also developing infants. These findings provide timely evidence to inform clinical practice and policy surrounding the care of pregnant individuals and highlight the importance of social support.

Vaccination of BALB/c mice with Escherichia coli-expressed vaccinia virus proteins A27L, B5R, and D8L protects mice from lethal vaccinia virus challenge.

The potential threat of smallpox use in a bioterrorist attack has heightened the need to develop an effective smallpox vaccine for immunization of the general public. Vaccination with the current smallpox vaccine, Dryvax, produces protective immunity but may result in adverse reactions for some vaccinees. A subunit vaccine composed of protective vaccinia virus proteins should avoid the complications arising from live-virus vaccination and thus provide a safer alternative smallpox vaccine. In this study, we assessed the protective efficacy and immunogenicity of a multisubunit vaccine composed of the A27L and D8L proteins from the intracellular mature virus (IMV) form and the B5R protein from the extracellular enveloped virus (EEV) form of vaccinia virus. BALB/c mice were immunized with Escherichia coli-produced A27L, D8L, and B5R proteins in an adjuvant consisting of monophosphoryl lipid A and trehalose dicorynomycolate or in TiterMax Gold adjuvant. Following immunization, mice were either sacrificed for analysis of immune responses or lethally challenged by intranasal inoculation with vaccinia virus strain Western Reserve. We observed that three immunizations either with A27L, D8L, and B5R or with the A27L and B5R proteins alone induced potent neutralizing antibody responses and provided complete protection against lethal vaccinia virus challenge. Several linear B-cell epitopes within the three proteins were recognized by sera from the immunized mice. In addition, protein-specific cellular responses were detected in spleens of immunized mice by a gamma interferon enzyme-linked immunospot assay using peptides derived from each protein. Our data suggest that a subunit vaccine incorporating bacterially expressed IMV- and EEV-specific proteins can be effective in stimulating anti-vaccinia virus immune responses and providing protection against lethal virus challenge.

Immune responses to the smallpox vaccine given in combination with ST-246, a small-molecule inhibitor of poxvirus dissemination.

The re-emerging threat of smallpox and the emerging threat of monkeypox highlight the need for effective poxvirus countermeasures. Currently approved smallpox vaccines have unacceptable safety profiles and, consequently, the general populace is no longer vaccinated, leading to an increasingly susceptible population. ST-246, a small-molecule inhibitor of poxvirus dissemination, has been demonstrated in various animal models to be safe and effective in preventing poxviral disease. This suggests that it may also be used to improve the safety of the traditional smallpox vaccine provided that it does not inhibit vaccine-induced protective immunity. In this study, we compared the immune responses elicited by the smallpox vaccine alone or in combination with ST-246 in mice. Normal lesion formation following dermal scarification with the attenuated New York City Board of Health strain (Dryvax), commonly referred to as a vaccine "take", was not inhibited although severe lesions and systemic disease due to vaccination with the virulent Western Reserve (VV-WR) strain were prevented. The vaccine given with ST-246 did not affect cellular immune responses or neutralizing antibody titers although anti-vaccinia ELISA titers were slightly reduced. Vaccination in combination with ST-246 provided equivalent short- and long-term protection against lethal intranasal challenge with VV-WR when compared to vaccine alone. These results suggest that ST-246 does not compromise protective immunity elicited by the vaccine and provide the basis for future studies examining the efficacy of ST-246 in preventing or treating adverse events due to vaccination.

Identification and characterization of potent small molecule inhibitor of hemorrhagic fever New World arenaviruses.

Category A arenaviruses as defined by the National Institute of Allergy and Infectious Diseases (NIAID) are human pathogens that could be weaponized by bioterrorists. Many of these deadly viruses require biosafety level-4 (BSL-4) containment for all laboratory work, which limits traditional laboratory high-throughput screening (HTS) for identification of small molecule inhibitors. For those reasons, a related BSL-2 New World arenavirus, Tacaribe virus, 67-78% identical to Junín virus at the amino acid level, was used in a HTS campaign where approximately 400,000 small molecule compounds were screened in a Tacaribe virus-induced cytopathic effect (CPE) assay. Compounds identified in this screen showed antiviral activity and specificity against not only Tacaribe virus, but also the Category A New World arenaviruses (Junín, Machupo, and Guanarito). Drug resistant variants were isolated, suggesting that these compounds act through inhibition of a viral protein, the viral glycoprotein (GP2), and not through cellular toxicity mechanisms. A lead compound, ST-294, has been chosen for drug development. This potent and selective compound, with good bioavailability, demonstrated protective anti-viral efficacy in a Tacaribe mouse challenge model. This series of compounds represent a new class of inhibitors that may warrant further development for potential inclusion in a strategic stockpile.

Listeria monocytogenes 10403S HtrA is necessary for resistance to cellular stress and virulence.

The HtrA serine protease has been shown to be essential for bacterial virulence and for survival after exposure to many types of environmental and cellular stresses. A Listeria monocytogenes 10403S htrA mutant was found to be sensitive to oxidative and puromycin-induced stress at high temperatures, showed a reduced ability to form biofilms, and was attenuated for virulence in mice.