COVID-19 and Adolescent Outpatient Mental Health Service Utilization.

OBJECTIVE: The COVID-19 pandemic created challenges in accessing mental health (MH) services when adolescent well-being declined. Still, little is known about how the COVID-19 pandemic affected outpatient MH service utilization for adolescents. METHODS: Retrospective data were collected from electronic medical records of adolescents aged 12-17 years at Kaiser Permanente Mid-Atlantic States, an integrated health care system from January 2019 to December 2021. MH diagnoses included anxiety, mood disorder/depression, anxiety and mood disorder/depression, attention-deficit/hyperactivity disorder, or psychosis. We used interrupted time series analysis to compare MH visits and psychopharmaceutical prescribing before and after the COVID-19 onset. Analyses were stratified by demographics and visit modality. RESULTS: The study population of 8121 adolescents with MH visits resulted in a total of 61,971 (28.1%) of the 220,271 outpatient visits associated with an MH diagnosis. During 15,771 (7.2%) adolescent outpatient visits psychotropic medications were prescribed. The increasing rate of MH visits prior to COVID-19 was unaffected by COVID-19 onset; however, in-person visits declined by 230.5 visits per week (P < .001) from 274.5 visits per week coupled with a rise in virtual modalities. Rates of MH visits during the COVID-19 pandemic differed by sex, mental health diagnosis, and racial and ethnic identity. Psychopharmaceutical prescribing during MH visits declined beyond expected values by a mean of 32.8 visits per week (P < .001) at the start of the COVID-19 pandemic. CONCLUSIONS: A sustained switch to virtual visits highlights a new paradigm in care modalities for adolescents. Psychopharmaceutical prescribing declined requiring further qualitative assessments to improve the quality of access for adolescent MH.

Family Structure and Adolescent Mental Health Service Utilization During the COVID-19 Pandemic.

PURPOSE: This study evaluated the relationship between sociodemographic factors including family structure and mental health service (MHS) utilization before and during the COVID-19 pandemic. We also investigated the moderation effects of the COVID-19 pandemic on MHS utilization. METHODS: Our retrospective cohort study analyzed adolescents aged 12-17 years with a mental health diagnosis as identified in the electronic medical record enrolled in Kaiser Permanente Mid-Atlantic States in Maryland and Virginia, a comprehensive integrated health system. We used logistic regression models with an interaction term for the COVID-19 pandemic year to determine the relationship between family structure and adolescent MHS utilization ≥ one outpatient behavioral health visit within the measurement year, while adjusting for age, chronic medical condition (= physical illness lasting > 12 months), mental health condition, race, sex, and state of residence. RESULTS: Among 5,420 adolescents, only those in two-parent households significantly increased MHS utilization during COVID-19 compared to the prepandemic year (McNemar's χ2 = 9.24, p < .01); however, family structure was not a significant predictor. Overall, the odds of adolescents using MHS were associated with a 12% increase during COVID-19 (odds ratio 1.12, 95% confidence interval [CI]: 1.02-1.22, p < .01). Higher odds of using MHS was associated with chronic medical condition (adjusted odds ratio = 1.15; 95% CI: 1.05-1.26, p < .01) and with White adolescents compared to all racial/ethnic minorities. The odds ratio of females using MHS compared to their male counterparts increased by 63% (ratio of adjusted odds ratio = 1.63; 95% CI: 1.39-1.91, p < .01) during the COVID-19 pandemic. DISCUSSION: Individual-level demographic factors served as predictors of MHS utilization with effects moderated by COVID-19.

Non-enzymatic primer extension with strand displacement.

Non-enzymatic RNA self-replication is integral to the emergence of the 'RNA World'. Despite considerable progress in non-enzymatic template copying, demonstrating a full replication cycle remains challenging due to the difficulty of separating the strands of the product duplex. Here, we report a prebiotically plausible approach to strand displacement synthesis in which short 'invader' oligonucleotides unwind an RNA duplex through a toehold/branch migration mechanism, allowing non-enzymatic primer extension on a template that was previously occupied by its complementary strand. Kinetic studies of single-step reactions suggest that following invader binding, branch migration results in a 2:3 partition of the template between open and closed states. Finally, we demonstrate continued primer extension with strand displacement by employing activated 3'-aminonucleotides, a more reactive proxy for ribonucleotides. Our study suggests that complete cycles of non-enzymatic replication of the primordial genetic material may have been facilitated by short RNA oligonucleotides.

Control of DEMETER DNA demethylase gene transcription in male and female gamete companion cells in Arabidopsis thaliana.

The DEMETER (DME) DNA glycosylase initiates active DNA demethylation via the base-excision repair pathway and is vital for reproduction in Arabidopsis thaliana DME-mediated DNA demethylation is preferentially targeted to small, AT-rich, and nucleosome-depleted euchromatic transposable elements, influencing expression of adjacent genes and leading to imprinting in the endosperm. In the female gametophyte, DME expression and subsequent genome-wide DNA demethylation are confined to the companion cell of the egg, the central cell. Here, we show that, in the male gametophyte, DME expression is limited to the companion cell of sperm, the vegetative cell, and to a narrow window of time: immediately after separation of the companion cell lineage from the germline. We define transcriptional regulatory elements of DME using reporter genes, showing that a small region, which surprisingly lies within the DME gene, controls its expression in male and female companion cells. DME expression from this minimal promoter is sufficient to rescue seed abortion and the aberrant DNA methylome associated with the null dme-2 mutation. Within this minimal promoter, we found short, conserved enhancer sequences necessary for the transcriptional activities of DME and combined predicted binding motifs with published transcription factor binding coordinates to produce a list of candidate upstream pathway members in the genetic circuitry controlling DNA demethylation in gamete companion cells. These data show how DNA demethylation is regulated to facilitate endosperm gene imprinting and potential transgenerational epigenetic regulation, without subjecting the germline to potentially deleterious transposable element demethylation.