Humoral and cellular immune memory to four COVID-19 vaccines.

Multiple COVID-19 vaccines, representing diverse vaccine platforms, successfully protect against symptomatic COVID-19 cases and deaths. Head-to-head comparisons of T cell, B cell, and antibody responses to diverse vaccines in humans are likely to be informative for understanding protective immunity against COVID-19, with particular interest in immune memory. Here, SARS-CoV-2-spike-specific immune responses to Moderna mRNA-1273, Pfizer/BioNTech BNT162b2, Janssen Ad26.COV2.S, and Novavax NVX-CoV2373 were examined longitudinally for 6 months 100% of individuals made memory CD4+ T cells, with cTfh and CD4-CTL highly represented after mRNA or NVX-CoV2373 vaccination. mRNA vaccines and Ad26.COV2.S induced comparable CD8+ T cell frequencies, though only detectable in 60-67% of subjects at 6 months. A differentiating feature of Ad26.COV2.S immunization was a high frequency of CXCR3+ memory B cells. mRNA vaccinees had substantial declines in antibodies, while memory T and B cells were comparatively stable. These results may also be relevant for insights against other pathogens.

A Molecular Calcium Integrator Reveals a Striatal Cell Type Driving Aversion.

The ability to record transient cellular events in the DNA or RNA of cells would enable precise, large-scale analysis, selection, and reprogramming of heterogeneous cell populations. Here, we report a molecular technology for stable genetic tagging of cells that exhibit activity-related increases in intracellular calcium concentration (FLiCRE). We used FLiCRE to transcriptionally label activated neural ensembles in the nucleus accumbens of the mouse brain during brief stimulation of aversive inputs. Using single-cell RNA sequencing, we detected FLiCRE transcripts among the endogenous transcriptome, providing simultaneous readout of both cell-type and calcium activation history. We identified a cell type in the nucleus accumbens activated downstream of long-range excitatory projections. Taking advantage of FLiCRE's modular design, we expressed an optogenetic channel selectively in this cell type and showed that direct recruitment of this otherwise genetically inaccessible population elicits behavioral aversion. The specificity and minute resolution of FLiCRE enables molecularly informed characterization, manipulation, and reprogramming of activated cellular ensembles.

Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity.

Limited knowledge is available on the relationship between antigen-specific immune responses and COVID-19 disease severity. We completed a combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4+ and CD8+ T cell and neutralizing antibody responses in acute and convalescent subjects. SARS-CoV-2-specific CD4+ and CD8+ T cells were each associated with milder disease. Coordinated SARS-CoV-2-specific adaptive immune responses were associated with milder disease, suggesting roles for both CD4+ and CD8+ T cells in protective immunity in COVID-19. Notably, coordination of SARS-CoV-2 antigen-specific responses was disrupted in individuals ≥ 65 years old. Scarcity of naive T cells was also associated with aging and poor disease outcomes. A parsimonious explanation is that coordinated CD4+ T cell, CD8+ T cell, and antibody responses are protective, but uncoordinated responses frequently fail to control disease, with a connection between aging and impaired adaptive immune responses to SARS-CoV-2.

Molecular and Circuit-Dynamical Identification of Top-Down Neural Mechanisms for Restraint of Reward Seeking.

Reward-seeking behavior is fundamental to survival, but suppression of this behavior can be essential as well, even for rewards of high value. In humans and rodents, the medial prefrontal cortex (mPFC) has been implicated in suppressing reward seeking; however, despite vital significance in health and disease, the neural circuitry through which mPFC regulates reward seeking remains incompletely understood. Here, we show that a specific subset of superficial mPFC projections to a subfield of nucleus accumbens (NAc) neurons naturally encodes the decision to initiate or suppress reward seeking when faced with risk of punishment. A highly resolved subpopulation of these top-down projecting neurons, identified by 2-photon Ca2+ imaging and activity-dependent labeling to recruit the relevant neurons, was found capable of suppressing reward seeking. This natural activity-resolved mPFC-to-NAc projection displayed unique molecular-genetic and microcircuit-level features concordant with a conserved role in the regulation of reward-seeking behavior, providing cellular and anatomical identifiers of behavioral and possible therapeutic significance.

Engineered allostery in light-regulated LOV-Turbo enables precise spatiotemporal control of proximity labeling in living cells.

The incorporation of light-responsive domains into engineered proteins has enabled control of protein localization, interactions and function with light. We integrated optogenetic control into proximity labeling, a cornerstone technique for high-resolution proteomic mapping of organelles and interactomes in living cells. Through structure-guided screening and directed evolution, we installed the light-sensitive LOV domain into the proximity labeling enzyme TurboID to rapidly and reversibly control its labeling activity with low-power blue light. 'LOV-Turbo' works in multiple contexts and dramatically reduces background in biotin-rich environments such as neurons. We used LOV-Turbo for pulse-chase labeling to discover proteins that traffic between endoplasmic reticulum, nuclear and mitochondrial compartments under cellular stress. We also showed that instead of external light, LOV-Turbo can be activated by bioluminescence resonance energy transfer from luciferase, enabling interaction-dependent proximity labeling. Overall, LOV-Turbo increases the spatial and temporal precision of proximity labeling, expanding the scope of experimental questions that can be addressed with proximity labeling.

Interacting neural ensembles in orbitofrontal cortex for social and feeding behaviour.

Categorically distinct basic drives (for example, for social versus feeding behaviour1-3) can exert potent influences on each other; such interactions are likely to have important adaptive consequences (such as appropriate regulation of feeding in the context of social hierarchies) and can become maladaptive (such as in clinical settings involving anorexia). It is known that neural systems regulating natural and adaptive caloric intake, and those regulating social behaviours, involve related circuitry4-7, but the causal circuit mechanisms of these drive adjudications are not clear. Here we investigate the causal role in behaviour of cellular-resolution experience-specific neuronal populations in the orbitofrontal cortex, a major reward-processing hub that contains diverse activity-specific neuronal populations that respond differentially to various aspects of caloric intake8-13 and social stimuli14,15. We coupled genetically encoded activity imaging with the development and application of methods for optogenetic control of multiple individually defined cells, to both optically monitor and manipulate the activity of many orbitofrontal cortex neurons at the single-cell level in real time during rewarding experiences (caloric consumption and social interaction). We identified distinct populations within the orbitofrontal cortex that selectively responded to either caloric rewards or social stimuli, and found that activity of individually specified naturally feeding-responsive neurons was causally linked to increased feeding behaviour; this effect was selective as, by contrast, single-cell resolution activation of naturally social-responsive neurons inhibited feeding, and activation of neurons responsive to neither feeding nor social stimuli did not alter feeding behaviour. These results reveal the presence of potent cellular-level subnetworks within the orbitofrontal cortex that can be precisely engaged to bidirectionally control feeding behaviours subject to, for example, social influences.

Province-Wide Ascertainment of Lynch Syndrome in Manitoba.

BACKGROUND & AIMS: We describe the experience of Lynch syndrome (LS) diagnosis in the province of Manitoba, Canada, over the past 20 years. METHODS: We performed a retrospective review of charts from the provincial Genetics Clinic from January 1, 2000, to May 31, 2023. We extracted data on individuals identified to carry a germline pathogenic or likely pathogenic LS gene variant, the mode of ascertainment, family history, and cascade genetic testing (CGT). Data were stratified and compared before and after the year of implementation (October 2013) of the provincial LS screening program (LSSP) and ascertainment by the LSSP vs clinic referrals (CRs). RESULTS: Between 2014 and 2021, 50 of 101 (49.5%) index cases were identified by the LSSP compared with 51 of 101 (50.5%) from CRs. The proportion of PMS2 variants was 34% (17 of 50) for LSSP index cases compared with 21.6% (11 of 51) for CRs from 2014 to 2021 (P < .001). Among CRs from 2014 to 2021, 24 of 51 (47.1%) families met the Amsterdam criteria, compared with 11 of 50 (22.0%) for the LSSP (P = .01). CGT occurred among 46.8% (95 of 203; average, 1.9 relatives/index) of first-degree relatives of CR index cases vs 36.5% (84 of 230; average, 1.7 relatives/index) of first-degree relatives of LSSP index cases (P = .03). Daughters were most likely to undergo CGT. CONCLUSIONS: A tumor screening program is more effective at detecting individuals with lower penetrant gene variants and families who do not meet traditional family history-based criteria. Cascade genetic testing is higher among clinic referrals compared with the screening program. These findings suggest a complementary role of these 2 ascertainment methods for Lynch syndrome.

Promoting toddlers' self-regulation and healthy eating habits among families living in poverty: A randomized controlled trial of Recipe 4 Success.

The Recipe 4 Success preventive intervention targeted multiple factors critical to the health and well-being of toddlers living in poverty. This randomized controlled trial, which was embedded within Early Head Start home visits for 12 weeks, included 242 racially and ethnically diverse families (51% girls; toddler mean age = 2.58 years; data collected 2016-2019). Compared to parents in usual practice home visits, parents in Recipe 4 Success displayed greater sensitive scaffolding of toddlers' learning and more responsive food parenting practices (Cohen's d = .21-.30). Toddlers in Recipe 4 Success exhibited greater self-regulation and had healthier eating habits (Cohen's d = |.16-.35|). Results highlight the value of Recipe 4 Success in promoting parent and toddler behavior change that could have life-long benefits.

The effects of parent-child dysfunctional interactions on early childhood weight: A serial mediation model through emotional feeding and child appetite traits.

Parent-child dysfunctional interactions (PCDI) are known to contribute to children's weight status. However, the underlying mechanisms in how dysfunctional interactions between parent and child influence child weight are not clear. This study investigates the impact of PCDI on toddlers' weight, focusing on the potential serial mediation by maternal emotional feeding and child appetite traits. We conducted a secondary analysis of longitudinal data from a larger intervention trial to prevent childhood obesity in low-income Hispanic families. A total of 241 mother-child dyads were included in these analyses. Measurements were taken at various stages: PCDI at child age 19 months, maternal emotional feeding at 28 months, and both child appetite traits and weight-for-age z-score (WFAz) at 36 months. Serial mediation analyses revealed a significant indirect effect of early PCDI on later child WFAz through maternal emotional feeding and two child food approach traits (food responsiveness, emotional overeating) out of the eight child appetite traits assessed. PCDI at 19 months was associated with increased use of emotional feeding in mothers at 28 months, which was associated with heightened food responsiveness and emotional overeating in children at 36 months, which in turn was linked to greater child WFAz at 36 months. The findings of this study expand the understanding of the mechanisms underlying PCDI and child weight, emphasizing the interplay between maternal feeding practices and child appetite in the context of adverse parent-child interactions during early childhood.

Cigarette smoking cessation, duration of smoking abstinence, and head and neck squamous cell carcinoma prognosis.

BACKGROUND: Tobacco use is a major risk factor for developing head and neck squamous cell carcinoma (HNSCC). However, the prognostic associations with smoking cessation are limited. The authors assessed whether smoking cessation and increased duration of abstinence were associated with improved overall (OS) and HNSCC-specific survival. METHODS: Clinicodemographic and smoking data from patients with HNSCC at Princess Margaret Cancer Center (2006-2019) were prospectively collected. Multivariable Cox and Fine and Gray competing-risk models were used to assess the impact of smoking cessation and duration of abstinence on overall mortality and HNSCC-specific/noncancer mortality, respectively. RESULTS: Among 2482 patients who had HNSCC, former smokers (adjusted hazard ratio [aHR], 0.71; 95% CI, 0.58-0.87; p = .001; N = 841) had a reduced risk of overall mortality compared with current smokers (N = 931). Compared with current smokers, former smokers who quit >10 years before diagnosis (long-term abstinence; n = 615) had the most improved OS (aHR, 0.72; 95% CI, 0.56-0.93; p = .001). The 5-year actuarial rates of HNSCC-specific and noncancer deaths were 16.8% and 9.4%, respectively. Former smokers (aHR, 0.71; 95% CI, 0.54-0.95; p = .019) had reduced HNSCC-specific mortality compared with current smokers, but there was no difference in noncancer mortality. Abstinence for >10 years was associated with decreased HNSCC-specific death compared with current smoking (aHR, 0.64; 95% CI, 0.46-0.91; p = .012). Smoking cessation with a longer duration of quitting was significantly associated with reduced overall and HNSCC-specific mortality in patients who received primary radiation. CONCLUSIONS: Smoking cessation before the time of diagnosis reduced overall mortality and cancer-specific mortality among patients with HNSCC, but no difference was observed in noncancer mortality. Long-term abstinence (>10 pack-years) had a significant OS and HNSCC-specific survival benefit.

A Canadian Provincial Screening Program for Lynch Syndrome.

INTRODUCTION: Manitoba implemented the first Canadian provincial program of reflex screening through mismatch repair immunohistochemistry (MMR-IHC) for all colorectal cancers diagnosed at age 70 years or younger in December 2017. We evaluated compliance to universal reflex testing and for referrals to Genetics for individuals with MMR-deficient tumors. METHODS: We searched the provincial pathology database with "adenocarcinoma" in the colorectal specimen pathology reports between March 2018 and December 2020. We cross-referenced with paper and electronic records in the Program of Genetics and Metabolism to determine whether patients with MMR-deficient tumors had been referred for Genetic assessment and what proportion of patients and first-degree relatives accepted an appointment and genetic testing. We performed logistic regression analysis to identify predictors of testing. RESULTS: We identified 3,146 colorectal adenocarcinoma specimens (biopsies and surgical resections) from 1,692 unique individuals (mean age 68.66 years, male 57%). Of those aged 70 years or younger (n = 936), 89.4% received MMR-IHC screening. Individual pathologists (categorized by the highest, average, and lowest screening rates) were the biggest predictors of MMR-IHC screening on multivariable analysis (highest vs lowest: odds ratio 17.5, 95% confidence interval 6.05-50.67). While only 53.4% (n = 31) of 58 screen-positive cases were referred by pathologists for genetic assessment, other clinicians referred an additional 22.4% (n = 13), resulting in 75.8% overall referral rate of screen-positive cases. Thirteen (1.4%) patients (1.1%, aged 70 years or younger) were confirmed to experience Lynch syndrome through germline testing, and 8 first-degree relatives (an average of 1.6 per patient) underwent cascade genetic testing. DISCUSSION: The first Canadian Lynch syndrome screening program has achieved high rates of reflex testing.

Disparities in melanoma-specific mortality by race/ethnicity, socioeconomic status, and health care systems.

BACKGROUND: Despite encouraging trends in survival, sociodemographic inequalities persist among patients with melanoma. OBJECTIVE: We sought to quantify the effect of race/ethnicity, socioeconomic status, and health care systems on melanoma-specific mortality within an insured population of patients. METHODS: Using a retrospective cohort study, we identified insured adults diagnosed with Stage I to IV melanoma from January 1, 2009, to December 31, 2014, followed through 2017, from the California Cancer Registry. We compared melanoma-specific mortality between insured patients diagnosed within the largest vertically integrated health care system in California, Kaiser Permanente Southern California, and insured patients with other private insurance (OPI). RESULTS: Our cohort included 14,614 adults diagnosed with melanoma. Multivariable analyses demonstrated that race/ethnicity was not associated with survival disparities, while socioeconomic status was a strong predictor of melanoma-specific mortality, particularly for those with OPI. For example, hazard ratios demonstrate that the poorest patients with OPI have a 70% increased risk of dying from their melanoma compared to their wealthiest counterparts, while the poorest patients in Kaiser Permanente Southern California have no increased risk. LIMITATIONS: Our main limitation includes inadequate data for certain racial/ethnic groups, such as Native Americans. CONCLUSIONS: Our findings underscore the persistence of socioeconomic disparities within an insured population, specifically among those in non-integrated health care systems.

Rabies screen reveals GPe control of cocaine-triggered plasticity.

Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the increase in GPe labelling. Inhibition of GPe activity revealed that it contributes to two forms of cocaine-triggered behavioural plasticity, at least in part by disinhibiting dopamine neurons in the ventral tegmental area. These results suggest that rabies-based unbiased screening of changes in input populations can identify previously unappreciated circuit elements that critically support behavioural adaptations.

The impact of early palliative care on the quality of life of patients with advanced pancreatic cancer: The IMPERATIVE case-crossover study.

PURPOSE: Pancreatic cancer is a lethal disease. Many patients experience a heavy burden of cancer-associated symptoms and poor quality of life (QOL). Early palliative care alongside standard oncologic care results in improved QOL and survival in some cancer types. The benefit in advanced pancreatic cancer (APC) is not fully quantified. METHODS: In this prospective case-crossover study, patients ≥ 18 years old with APC were recruited from ambulatory clinics at a tertiary cancer center. Patients underwent a palliative care consultation within 2 weeks of registration, with follow up visits every 2 weeks for the first month, then every 4 weeks until week 16, then as needed. The primary outcome was change in QOL between baseline (BL) and week 16, measured by Functional Assessment of Cancer Therapy - hepatobiliary (FACT-Hep). Secondary outcomes included symptom control (ESAS-r), depression, and anxiety (HADS, PHQ-9) at week 16. RESULTS: Of 40 patients, 25 (63%) were male, 28 (70%) had metastatic disease, 31 (78%) had ECOG performance status 0-1, 31 (78%) received chemotherapy. Median age was 70. Mean FACT-hep score at BL was 118.8, compared to 125.7 at week 16 (mean change 6.89, [95%CI (-1.69-15.6); p = 0.11]). On multivariable analysis, metastatic disease (mean change 15.3 [95%CI (5.3-25.2); p = 0.004]) and age < 70 (mean change 12.9 [95%CI (0.5-25.4); p = 0.04]) were associated with improved QOL. Patients with metastatic disease had significant improvement in symptom burden (mean change -7.4 [95%CI (-13.4 to -1.4); p = 0.02]). There was no difference in depression or anxiety from BL to week 16. CONCLUSION: Palliative care should be integrated early in the journey for patients with APC, as it can improve QOL and symptom burden. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03837132.

Heterogeneous Effects of Depression on Parenting Competence and Child Behavior Among Families Living in Poverty.

This study examined how depression and psychosocial protective factors, such as self-efficacy and conscientiousness, were related to parenting competence and child behavior among families living in poverty. The sample included 238 families (37% White, 25% Black, 19% Latinx, 17% Multiracial, and 2% Asian; 42% of parents reporting clinically significant symptoms of depression) with young children (mean age = 31 months, 51% female). Latent profile analysis identified five distinct subgroups of parents who differed on levels of depression and psychosocial protective factors. A small group of parents who had high levels of depression and low levels of protective factors displayed the least parenting competence and had children with lower levels of adjustment. At the same time, parents in two other profiles had high levels of depression, but moderate or high levels of protective factors, and displayed average parenting competence and had children who displayed average or above average levels of adjustment. In this study, depression appeared less predictive of parenting competence and child behavior than the psychosocial protective factors. This study suggests that many parents, despite having depression and living in poverty, exhibit psychosocial protective factors that are associated with high levels of parenting competence and rear children who are doing well.

Integration of optogenetics with complementary methodologies in systems neuroscience.

Modern optogenetics can be tuned to evoke activity that corresponds to naturally occurring local or global activity in timing, magnitude or individual-cell patterning. This outcome has been facilitated not only by the development of core features of optogenetics over the past 10 years (microbial-opsin variants, opsin-targeting strategies and light-targeting devices) but also by the recent integration of optogenetics with complementary technologies, spanning electrophysiology, activity imaging and anatomical methods for structural and molecular analysis. This integrated approach now supports optogenetic identification of the native, necessary and sufficient causal underpinnings of physiology and behaviour on acute or chronic timescales and across cellular, circuit-level or brain-wide spatial scales.

YAP Mediates Hair Cell Regeneration in Balance Organs of Chickens, But LATS Kinases Suppress Its Activity in Mice.

Loss of sensory hair cells causes permanent hearing and balance deficits in humans and other mammals, but for nonmammals such deficits are temporary. Nonmammals recover hearing and balance sensitivity after supporting cells proliferate and differentiate into replacement hair cells. Evidence of mechanical differences between those sensory epithelia and their supporting cells prompted us to investigate whether the capacity to activate YAP, an effector in the mechanosensitive Hippo pathway, correlates with regenerative capacity in acceleration-sensing utricles of chickens and mice of both sexes. After hair cell ablation, YAP accumulated in supporting cell nuclei in chicken utricles and promoted regenerative proliferation, but YAP remained cytoplasmic and little proliferation occurred in mouse utricles. YAP localization in supporting cells was also more sensitive to shape change and inhibition of MST1/2 in chicken utricles than in mouse utricles. Genetic manipulations showed that in vivo expression of the YAP-S127A variant caused robust proliferation of neonatal mouse supporting cells, which produced progeny that expressed hair cell markers, but proliferative responses declined postnatally. Expression of YAP-5SA, which more effectively evades inhibitory phosphorylation, resulted in TEAD-dependent proliferation of striolar supporting cells, even in adult utricles. Conditional deletion of LATS1/2 kinases abolished the inhibitory phosphorylation of endogenous YAP and led to striolar proliferation in adult mouse utricles. The findings suggest that damage overcomes inhibitory Hippo signaling and facilitates regenerative proliferation in nonmammalian utricles, whereas constitutive LATS1/2 kinase activity suppresses YAP-TEAD signaling in mammalian utricles and contributes to maintaining the proliferative quiescence that appears to underlie the permanence of sensory deficits.SIGNIFICANCE STATEMENT Loud sounds, ototoxic drugs, infections, and aging kill sensory hair cells in the ear, causing irreversible hearing loss and balance deficits for millions. In nonmammals, damage evokes shape changes in supporting cells, which can divide and regenerate hair cells. Such shape changes are limited in mammalian ears, where supporting cells develop E-cadherin-rich apical junctions reinforced by robust F-actin bands, and the cells fail to divide. Here, we find that damage readily activates YAP in supporting cells within balance epithelia of chickens, but not mice. Deleting LATS kinases or expressing YAP variants that evade LATS-mediated inhibitory phosphorylation induces proliferation in supporting cells of adult mice. YAP signaling eventually may be harnessed to overcome proliferative quiescence that limits regeneration in mammalian ears.

Molecular tools for imaging and recording neuronal activity.

To understand how the brain relates to behavior, it is essential to record neural activity in awake, behaving animals. To achieve this goal, a large variety of genetically encoded sensors have been developed to monitor and record the series of events following neuronal firing, including action potentials, intracellular calcium rise, neurotransmitter release and immediate early gene expression. In this Review, we discuss the existing genetically encoded tools for detecting and integrating neuronal activity in animals and highlight the remaining challenges and future opportunities for molecular biologists.

Projections from neocortex mediate top-down control of memory retrieval.

Top-down prefrontal cortex inputs to the hippocampus have been hypothesized to be important in memory consolidation, retrieval, and the pathophysiology of major psychiatric diseases; however, no such direct projections have been identified and functionally described. Here we report the discovery of a monosynaptic prefrontal cortex (predominantly anterior cingulate) to hippocampus (CA3 to CA1 region) projection in mice, and find that optogenetic manipulation of this projection (here termed AC-CA) is capable of eliciting contextual memory retrieval. To explore the network mechanisms of this process, we developed and applied tools to observe cellular-resolution neural activity in the hippocampus while stimulating AC-CA projections during memory retrieval in mice behaving in virtual-reality environments. Using this approach, we found that learning drives the emergence of a sparse class of neurons in CA2/CA3 that are highly correlated with the local network and that lead synchronous population activity events; these neurons are then preferentially recruited by the AC-CA projection during memory retrieval. These findings reveal a sparsely implemented memory retrieval mechanism in the hippocampus that operates via direct top-down prefrontal input, with implications for the patterning and storage of salient memory representations.

Parents' Self-Reported Psychological Impacts of COVID-19: Associations With Parental Burnout, Child Behavior, and Income.

OBJECTIVE: The current study investigates associations between parents' perceived coronavirus disease 2019 (COVID-19) psychological impacts and experiences of parental burnout, children's behaviors, and income. METHODS: Data were collected during an online survey of parents' (N = 1000) pandemic experiences in April 2020. Parents (M = 36.5 years old, SD = 6.0; 82.1% White) with at least one child 12 years or younger reported on measures of mental health, perceived COVID-19 impacts, parental burnout, and perceived increases in children's stress and positive behaviors. RESULTS: Path model analyses revealed that parents who perceived increased psychological impacts from COVID-19 reported higher levels of parental burnout, greater increases in children's stress behaviors, and less positive behavior in children. Additionally, there were significant indirect effects of parental burnout on the link between COVID-19 psychological impacts and children's behaviors. Finally, family income moderated associations between psychological impacts and children's stress behaviors, such that the association was stronger for families with lower income. CONCLUSIONS: These results suggest parents' perceptions of how the COVID-19 pandemic has impacted their mental health has implications for parent and child well-being, with stronger associations for low-income families. Given the potential for spillover effects between parents and children, promoting family well-being through practice and policy initiatives is crucial, including providing financial and caregiving relief for parents, and mental and behavioral health support for families.