Proton transfer and regulation across chemical interfaces by small-molecule assemblies.

We report on measurements and control of proton gradient across interfaces of water and dichloroethane. Such interfaces are interesting as mimics of biological membranes. We use impedance spectroscopy to quantify interfacial proton gradient and identify proton transfer modes. We quantify proton movement using reciprocal of time constant (τ-1 ) acquired from electrochemical impedance modeling. We show that proton gradient across interfaces of water/dichloroethane and τ-1 correlate with the aqueous phase pH, changing from ca. 1 s-1 at pH 1 to 0.2 s-1 at pH 7. τ-1 changes in the presence of proton shuttling fat-soluble molecules. Dinitrophenol acts as a pH activated proton coupler which is active at around neutral pH and inert at pH <4. However, quinone type cofactors change the interfacial proton transport when activated by redox reactions with ferrocene type molecules, such as decamethyl ferrocence (DMFc). Quinone type cofactors show distinct features in their impedance response assigned to a proton coupled electron transfer (PCET) process, different from the uncoupled proton transfer activity of dinitrophenol. The observed PCET reaction significantly changes τ-1 . We use τ-1 as a proton transport descriptor. In particular, CoQ10 -DMFc shows a τ-1 of 3.5 s-1 at pH 7, indicating how small-molecule assemblies change proton availability.

Unraveling reproductive and maternal health challenges of women living with HIV/AIDS in Vietnam: a qualitative study.

BACKGROUND: Human Immunodeficiency Virus (HIV) remains a significant public health concern worldwide. Women living with HIV/AIDS (WLHA) have the additional and unique need to seek sexual and reproductive health services. WLHA's maternal health journeys can be shaped by the cultural norms and resources that exist in their society. This study sought to understand if and how WLHA's family planning, pregnancy, and motherhood experiences could be influenced by the patriarchal culture, gender roles, and HIV stigma in Vietnam, specifically. METHODS: Between December 2021 and March 2022, 30 WLHA with diverse socioeconomic backgrounds and childbirth experiences were interviewed in Hanoi, Vietnam. These semi-structured interviews covered topics including HIV stigma, gender norms, pregnancy experiences, and child-rearing challenges. Interviews were audio recorded, transcribed, and analysed using ATLAS.ti. RESULTS: Qualitative analyses of participant quotes revealed how limited information on one's health prospects and reproductive options posed a significant challenge to family planning. Societal and familial expectations as well as economic circumstances also influenced reproductive decision-making. WLHA often encountered substandard healthcare during pregnancy, labor, and delivery. Stigma and lack of provider attentiveness resulted in cases where women were denied pain relief and other medical services. Communication breakdowns resulted in failure to administer antiretroviral therapy for newborns. Motherhood for WLHA was shadowed by concerns for not only their own health, but also the wellbeing of their children, as HIV stigma affected their children at school and in society as well. Many WLHA highlighted the constructive or destructive role that family members could play in their childbirth decision-making and care-giving experiences. CONCLUSIONS: Overall, this study underscores the complex ways that cultural expectations, family support, and stigma in healthcare impact WLHA. Efforts to educate and engage families and healthcare providers are warranted to better understand and address the needs of WLHA, ultimately improving their reproductive and maternal health.

HIV-related stigma and discrimination have consequential impacts on health and quality of life for women living with HIV (WLHA). WLHA in Vietnam must navigate the additional challenges of a traditionally patriarchal and hierarchical society. Women typically face less educational and occupational opportunities and are often expected to defer to expectations of family and virtue. Stigma among family members, friends, employers, and healthcare providers poses a significant challenge to WLHA autonomy, especially as it relates to their reproductive health decision-making and maternal health experiences. This study aims to better understand the experiences of WLHA throughout family planning, pregnancy, and motherhood. The findings will hopefully shed light on strategies to empower WLHA and to combat HIV- and gender-based stigma not only in Vietnam, but also globally.

Navigating cultural and gender aspects of stigma among women living with HIV in Vietnam.

Women living with HIV often face intersecting challenges of stigma and gender inequality. In Vietnam, this issue is potentially exacerbated by the patriarchal culture. From December 2021 to March 2022, we conducted in-depth interviews with 30 women living with HIV in Hanoi to better understand their experiences and the coping mechanisms to navigate HIV stigma, cultural beliefs and gender norms. The interviews explored various topics including women's social and family roles in Vietnam, HIV-related beliefs, stigma and its impact on one's health and coping strategies. Participants reported stereotypes that assumed that women living with HIV had either engaged in sex work or behaved promiscuously. These stereotypes render them vulnerable to judgement and discrimination owing to widespread expectations of female virtue. As a result, women living with HIV often enacted non-disclosure and self-isolation to avoid stigma. This self-stigmatisation negatively impacted their healthcare-seeking, employment opportunities and ability to fulfil traditional family-caring roles. Conversely, many participants exhibited resilience with the support of family and peers. Overall, the complex interplay between gender, culture and HIV stigma underscores the importance of developing culturally appropriate, multifaceted approaches to engaging family and peers, modifying gender-based discriminatory social practices and enhancing women's self-efficacy and empowerment in Vietnam.

A meta-analysis on the uncinate fasciculus in depression.

Aberrant microstructure of the uncinate fasciculus (UNC), a white matter (WM) tract implicated in emotion regulation, has been hypothesized as a neurobiological mechanism of depression. However, studies testing this hypothesis have yielded inconsistent results. The present meta-analysis consolidates evidence from 44 studies comparing fractional anisotropy (FA) and radial diffusivity (RD), two metrics characterizing WM microstructure, of the UNC in individuals with depression (n = 5016) to healthy individuals (n = 18 425). We conduct meta-regressions to identify demographic and clinical characteristics that contribute to cross-study heterogeneity in UNC findings. UNC FA was reduced in individuals with depression compared to healthy individuals. UNC RD was comparable between individuals with depression and healthy individuals. Comorbid anxiety explained inter-study heterogeneity in UNC findings. Depression is associated with perturbations in UNC microstructure, specifically with respect to UNC FA and not UNC RD. The association between depression and UNC microstructure appears to be moderated by anxiety. Future work should unravel the cellular mechanisms contributing to aberrant UNC microstructure in depression; clarify the relationship between UNC microstructure, depression, and anxiety; and link UNC microstructure to psychological processes, such as emotion regulation.

Canopy parkour: movement ecology of post-hatch dispersal in a gliding nymphal stick insect, Extatosoma tiaratum.

For flightless arboreal arthropods, moving from the understory into tree canopies is cognitively and energetically challenging because vegetational structures present complex three-dimensional landscapes with substantial gaps. Predation risk and wind-induced perturbations in the canopy may further impede the movement process. In the Australian stick insect Extatosoma tiaratum, first-instar nymphs hatch on the forest floor and disperse toward tree canopies in the daytime. Here, we addressed how their tactic responses to environmental cues and movement strategies are adapted to the canopy environment. Newly hatched nymphs ascend with high endurance, travelling >100 m within 60 min. Navigation toward open canopies is underpinned by negative gravitaxis, positive phototaxis and visual responses to vertically oriented contrast patterns. Nymphal E. tiaratum also use directed jumping to cross gaps, and respond to tactile stimulation and potential threat with a self-dropping reflex, resulting in aerial descent. Post-hatch dispersal in E. tiaratum thus consists of visually mediated displacement both on vegetational structures and in the air; within the latter context, gliding is then an effective mechanism enabling recovery after predator- and perturbation-induced descent. These results further support the importance of a diurnal niche, in addition to the arboreal spatial niche, in the evolution of gliding in wingless arboreal invertebrates.

Novel Peptidomic Approach for Identification of Low and High Molecular Weight Tauopathy Peptides Following Calpain Digestion, and Primary Culture Neurotoxic Challenges.

Tauopathy is a class of a neurodegenerative disorder linked with tau hyperphosphorylation, proteolysis, and aggregation. Tau can be subjected to proteolysis upon calpain activation in Alzheimer disease (AD), and traumatic brain injury (TBI). We and others have extensively researched calpain-mediated tau breakdown products (Tau-BDP; 45K, 35K, and 17K). Tau proteolysis might also generate low molecular weight (LMW ≤10K) proteolytic peptides after neurodegenerative damage. In this study, we have subjected purified tau protein (phospho and non-phospho) and mouse brain lysate to calpain-1 digestion to characterize the LMW generated by nano-liquid chromatography coupled to electrospray ionization to tandem mass spectrometry (nano-LC-ESI-MS/MS). We have also challenged differentiated primary cerebrocortical neuronal cultures (CTX) with neurotoxic agents (calcium ionophore calcimycin (A23187), staurosporine (STS), N-methyl-D-aspartate (NMDA), and Maitotoxin (MTX)) that mimic neurodegeneration to investigate the peptidome released into the conditioned cell media. We used a simple workflow in which we fractionate LMW calpain-mediated tau peptides by ultrafiltration (molecular weight cut-off value (MWCO) of 10K) and subject filtrate fractions to nano-LC-MS/MS analysis. The high molecular weight (HMW) peptides and intact proteins retained on the filter were analyzed separately by western blotting using total and phospho-specific tau antibodies. We have identified several novel proteolytic tau peptides (phosphorylated and non-phosphorylated) that are only present in samples treated with calpain or cell-based calpain activation model (particularly N- and C-terminal peptides). Our findings can help in developing future research strategies emphasizing on the suppression of tau proteolysis as a target.

Higher Order Oligomerization of the Licensing ORC4 Protein Is Required for Polar Body Extrusion in Murine Meiosis.

We have previously shown that the DNA replication licensing factor ORC4 forms a cage around the chromosomes that are extruded in both polar bodies during murine oogenesis, but not around the chromosomes that are retained in the oocyte or around the sperm chromatin. We termed this structure the ORC4 cage. Here, we tested whether the formation of the ORC4 cage is necessary for polar body extrusion (PBE). We first experimentally forced oocytes to extrude sperm chromatin as a pseudo-polar body and found that under these conditions the sperm chromatin did become enclosed in an ORC4 cage. Next, we attempted to prevent the formation of the ORC4 cage by injecting peptides that contained sequences of different domains of the ORC4 protein into metaphase II (MII) oocytes just before the cage normally forms. Our rationale was that the ORC4 peptides would block protein-protein interactions required for cage formation. Two out of six tested peptides prevented the ORC4 cage formation and simultaneously inhibited PBE, resulting in the formation of two pronuclei (2 PN) that were retained in the oocyte. Together, these data demonstrate that ORC4 oligomerization is required to form the ORC4 cage and that it is required for PBE. J. Cell. Biochem. 118: 2941-2949, 2017. © 2017 Wiley Periodicals, Inc.

Comparison of Patch Testing Results of White and Black Patients.

Patch testing is the standard diagnostic test used for patients presenting with symptoms of allergic contact dermatitis. The grading of patch test results classically varies from 1 to 3. The assessment of these results begins with a visual inspection of the presence of erythema, vesiculation, and induration. This leads to a subjectivity in visual evaluation of a patch test. Positive patch testing results can present differently in patients with darker skin tones. A greater variety of images of allergic contact dermatitis in patients with darker skin phototypes can better guide the diagnosis of this condition in skin of color. People with darker phototypes are historically underrepresented in dermatologic images and texts; thus, identifying erythema in darker phototypes may be more difficult for dermatologists, whether or not they were trained in areas of decreased phototype diversity. In this article, we present positive patch testing findings on several different phototypes, with the intention of contributing to images of phototypes underrepresented in dermatology literature.

Associations Between Neighborhood Resources and Youths' Response to Reward Omission in a Task Modeling Negatively Biased Environments.

OBJECTIVE: Neighborhoods provide essential resources (eg, education, safe housing, green space) that influence neurodevelopment and mental health. However, we need a clearer understanding of the mechanisms mediating these relationships. Limited access to neighborhood resources may hinder youths from achieving their goals and, over time, shape their behavioral and neurobiological response to negatively biased environments blocking goals and rewards. METHOD: To test this hypothesis, 211 youths (aged ∼13.0 years, 48% boys, 62% identifying as White, 75% with a psychiatric disorder diagnosis) performed a task during functional magnetic resonance imaging. Initially, rewards depended on performance (unbiased condition); but later, rewards were randomly withheld under the pretense that youths did not perform adequately (negatively biased condition), a manipulation that elicits frustration, sadness, and a broad response in neural networks. We investigated associations between the Childhood Opportunity Index (COI), which quantifies access to youth-relevant neighborhood features in 1 metric, and the multimodal response to the negatively biased condition, controlling for age, sex, medication, and psychopathology. RESULTS: Youths from less-resourced neighborhoods responded with less anger (p < .001, marginal R2 = 0.42) and more sadness (p < .001, marginal R2 = 0.46) to the negatively biased condition than youths from well-resourced neighborhoods. On the neurobiological level, lower COI scores were associated with a more localized processing mode (p = .039, marginal R2 = 0.076), reduced connectivity between the somatic-motor-salience and the control network (p = .041, marginal R2 = 0.040), and fewer provincial hubs in the somatic-motor-salience, control, and default mode networks (all pFWE < .05). CONCLUSION: The present study adds to a growing literature documenting how inequity may affect the brain and emotions in youths. Future work should test whether findings generalize to more diverse samples and should explore effects on neurodevelopmental trajectories and emerging mood disorders during adolescence. DIVERSITY & INCLUSION STATEMENT: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group.

A Quality Improvement Initiative to Improve Health Care Transition Planning at Adolescent Well Visits.

OBJECTIVE: Health care transition (HCT) planning supports adolescents as they move from pediatric to adult health care and is recommended for all youth. HCT planning uptake remains low, with little known about HCT in the adolescent well child check (WCC) setting. We sought to increase rates of HCT planning at WCCs by adapting best practices for HCT from specialty and chronic care. METHODS: This quality improvement initiative at 12 to 17-year-old WCCs at four Internal Medicine-Pediatrics primary care clinics, was based on the first three of the "Six Core Elements" of HCT framework and integrated into the electronic health record. Two uptake measures were assessed via chart review after three plan-do-study-act (PDSA) cycles, with two provider surveys and an implementation science analysis further informing interpretation. RESULTS: By the final PDSA cycle, the percentage of 14 to 17-year-old WCCs at which HCT planning was discussed and a screening tool completed increased from 5% to 31%, and the percentage of 12 to 13-year-old WCCs at which the HCT policy was discussed increased from 6% to 47%. Provider survey results revealed endorsement of HCT goals, but time and technological barriers, which were further elucidated in the implementation science analysis. CONCLUSIONS: This quality improvement initiative increased rates of HCT planning during adolescent WCCs. While limited to three Core Elements and Internal Medicine-Pediatrics clinics, strengths include measures capturing all WCCs, contextualized by provider surveys and an implementation science framework. Lessons from this effort can inform future tailored HCT initiatives at adolescent WCCs.

Associations between social media use, fitness- and weight-related online content, and use of legal appearance- and performance-enhancing drugs and substances.

Prior research has documented the connection between social media use and engaging with fitspiration with body dissatisfaction, disordered eating behaviors, and various health risk behaviors (e.g., substance use). However, gaps remain in the knowledge base on whether social media use and engaging with fitness- and weight-related online content are associated with the use of legal appearance- and performance-enhancing drugs and substances (APEDS; e.g., whey protein), which was the aim of this study. Data from participants ages 16-30 years in Canadian Study of Adolescent Health Behaviors (N = 2731) were analyzed. Multiple modified Poisson regression analyses were conducted to determine the associations between hours per day of social media use and any engagement with fitness- and weight-related online content in the past 30 days and use of 10 different legal APEDS in the past 30 days. Greater time on social media was significantly associated with use of energy drinks and pre-workout drinks or powders in the past 30 days. Engaging with fitness- and weight-related online content was significantly associated with the use of caffeine, creatine monohydrate, pre-workout drinks or powders, probiotics, protein bars, and whey protein powders or shakes in the past 30 days. These findings expand prior research on the correlates of social media use and engagement with fitness- and weight-related online content among young people and have important implications for healthcare and public health professionals, as well as technology companies.

The scope of antimicrobial resistance in residential aged care facilities determined through analysis of Escherichia coli and the total wastewater resistome.

IMPORTANCE: Antimicrobial resistance (AMR) is a global threat that imposes a heavy burden on our health and economy. Residential aged care facilities (RACFs), where frequent inappropriate antibiotic use creates a selective environment that promotes the development of bacterial resistance, significantly contribute to this problem. We used wastewater-based epidemiology to provide a holistic whole-facility assessment and comparison of antimicrobial resistance in two RACFs and a retirement village. Resistant Escherichia coli, a common and oftentimes problematic pathogen within RACFs, was isolated from the wastewater, and the phenotypic and genotypic AMR was determined for all isolates. We observed a high prevalence of an international high-risk clone, carrying an extended-spectrum beta-lactamase in one facility. Analysis of the entire resistome also revealed a greater number of mobile resistance genes in this facility. Finally, both facilities displayed high fluoroquinolone resistance rates-a worrying trend seen globally despite measures in place aimed at limiting their use.

"Eat more protein, build more muscle": A grounded theory study of muscle-building behaviors among Canadian adolescents and young adults.

Unique risk factors for the development of muscle dissatisfaction and engagement in muscle-building behaviors have been described by theoretical frameworks and supported by empirical research. What remains unknown are the unique processes, including catalysts and facilitators, which underpin engagement in muscle-building behaviors. Therefore, this study used a grounded theory methodology to elucidate the process of engagement in muscle-building behaviors. Thirty-three individual semi-structured interviews with Canadian adolescents and young adults ages 16-30 years were conducted. Transcripts were analyzed using initial and focused coding to identify themes that explained the grounded theory. The core theme underpinning the grounded theory was balancing aesthetic, health, and functional goals in relation to participants' engagement in muscle-building behaviors. Participants described experiences that encompassed several unique phases of muscle-building engagement, including the initiation phase, beginner phase, preservation phase, and intensification phase. Participants also described unique methods of gathering information on muscle-building behaviors, and their own analysis and decision-making processes driving their behaviors. Findings from this study extend prior theory and research by conceptualizing a novel process theory of engagement in muscle-building behaviors among adolescent and young adults, resulting in important implications for research and practice.

Neurobiochemical, Peptidomic, and Bioinformatic Approaches to Characterize Tauopathy Peptidome Biomarker Candidates in Experimental Mouse Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a multidimensional damage, and currently, no FDA-approved medicine is available. Multiple pathways in the cell are triggered through a head injury (e.g., calpain and caspase activation), which truncate tau and generate variable fragment sizes (MW 400-45,000 K). In this study, we used an open-head TBI mouse model generated by controlled cortical impact (CCI) and collected ipsilateral (IC) and contralateral (CC) mice htau brain cortices at one (D1) three (D3), and seven (D7) days post-injury. We implemented immunological (antibody-based detection) and peptidomic approaches (nano-reversed-phase liquid chromatography/tandem mass spectrometry) to investigate proteolytic tau peptidome (low molecular weight (LMW) < 10 K)) and pathological phosphorylation sites (high-molecular-weight (HMW); > 10 K) derived from CCI-TBI animal models. Our immunoblotting analysis verified tau hyperphosphorylation, HMW, and HMW breakdown products (HMW-BDP) formation of tau (e.g., pSer202, pThr181, pThr231, pSer396, and pSer404), following CCI-TBI. Peptidomic data revealed unique sequences of injury-dependent proteolytic peptides generated from human tau protein. Among the N-terminal tau peptides, EIPEGTTAEEAGIGDTPSLEDEAAGHVTQA (a.a. 96-125) and AQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARM (a.a. 91-127). Examples of tau C-terminal peptides identified include NVSSTGSIDMVDSPQLATLADEVSASLAKQGL (a.a. 410-441) and QLATLADEVSASLAKQGL (a.a. 424-441). Our peptidomic bioinformatic tools showed the association of proteases, such as CAPN1, CAPN2, and CTSL; CASP1, MMP7, and MMP9; and ELANE, GZMA, and MEP1A, in CCI-TBI tau peptidome. In clinical trials for novel TBI treatments, it might be useful to monitor a subset of tau peptidome as targets for biomarker utility and use them for a "theranostic" approach.

A wastewater-based evaluation of the effectiveness of codeine control measures in Australia.

BACKGROUND AND AIM: From 1 February 2018, codeine was rescheduled from an over-the-counter (OTC) to a prescription-only medicine in Australia. We used wastewater-based epidemiology to measure changes in population codeine consumption before and after rescheduling. METHODS: We analysed 3703 wastewater samples from 48 wastewater treatment plants, taken between August 2016 and August 2019. Our samples represented 10.6 million people, 45% of the Australian population in state capitals and regional areas in each state or territory. Codeine concentrations were determined by liquid chromatography-tandem mass spectrometry and converted to per-capita consumption estimates using the site daily wastewater volume, catchment populations and codeine excretion kinetics. RESULTS: Average per-capita consumption of codeine decreased by 37% nationally immediately after the rescheduling in February 2018 [95% confidence interval (CI) = 35.3-39.4%] and substantially in all states between 24 and 51% (95% CI = 22.4-27.0% and 41.8-59.4%). The decrease was sustained at the lower level to August 2019. Locations with least pharmacy access decreased by 51% (95% CI = 41.7-61.7%), a greater decrease than 37% observed for those with greater pharmacy access (95% CI = 35.1-39.4%). Regional areas decreased by a smaller margin to cities (32 versus 38%, 95% CI = 30.2-34.1% versus 34.9-40.4%, respectively) from a base per-capita usage approximately 40% higher than cities. CONCLUSION: Wastewater analysis shows that codeine consumption in Australia decreased by approximately 37% following its rescheduling as a prescription-only medicine in 2018. Wastewater-based epidemiology can be used to evaluate changes in population pharmaceutical consumption in responses to changes in drug scheduling.

Clinical Response to Upfront Targeted Tyrosine Kinase Inhibitors among Patients with Myeloid/Lymphoid Neoplasms with Eosinophilia and Tyrosine Kinase Gene Fusion.

INTRODUCTION: Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusion (MLN-TK) is an entity encompassed of a heterogeneous group of rare hematopoietic neoplasms that are driven by gene fusion involving PDGDRA/B, FGFR1, JAK2, FLT3 or ETV6::ABL1. Though patients presenting with chronic phase MLN-TK with PDGFRA fusion display a favorable outcome in response to upfront TK inhibitor (TKI) therapy, the outcomes of MLNs driven by other TK fusions are not well described. In this study, we aimed to critically analyze the treatment outcomes of patients with MLN-TK, focusing on the role of upfront TKIs in both chronic- and blast-phase diseases. METHODS: The retrospective study included patients with confirmed MLN-TK from 3 centers and assessed demographic and clinical variables, treatment, and outcomes. RESULTS: Forty-two patients with confirmed MLN-TK [PDGFRA (n = 22), PDGFRB (n = 4), FGFR1(n = 10), JAK2 (n = 2); and FLT3 (n = 3)] were included. Fifteen of 25 (60%) chronic-phased patients received upfront TKI therapy had a long-term remission. Nine of 16 (60%) blast-phase patients with upfront TKIs also achieved complete remission and remained alive at a median follow-up of 20 months. All 3 patients with blast phase disease who received upfront chemotherapy without positive response did not respond to subsequent TKI therapy, emphasizing the importance of initiating TKI therapy early. Upfront TKI therapy was associated with longer overall survival in univariate analyses (HR, 0.054 [95% CI, 0.007-0.42]) and multivariate analyses (HR, 0.03 [95% CI, 0.002-0.47]). CONCLUSION: The outcomes of upfront TKI therapy are excellent for MLN-TK in both chronic and blast phases, regardless of gene abnormalities.

Persistent Frustration-Induced Reconfigurations of Brain Networks Predict Individual Differences in Irritability.

OBJECTIVE: Aberrant responses to frustration are central mechanisms of pediatric irritability, which is a common reason for psychiatric consultation and a risk factor for affective disorders and suicidality. This pilot study aimed to characterize brain network configuration during and after frustration and test whether characteristics of networks formed during or after frustration relate to irritability. METHOD: During functional magnetic resonance imaging, a transdiagnostic sample enriched for irritability (N = 66, mean age = 14.0 years, 50% female participants) completed a frustration-induction task flanked by pretask and posttask resting-state scans. We first tested whether and how the organization of brain regions (ie, nodes) into networks (ie, modules) changes during and after frustration. Then, using a train/test/held-out procedure, we aimed to predict past-week irritability from global efficiency (Eglob) (ie, capacity for parallel information processing) of these modules. RESULTS: Two modules present in the baseline pretask resting-state scan (one encompassing anterior default mode and temporolimbic regions and one consisting of frontoparietal regions) contributed most to brain circuit reorganization during and after frustration. Only Eglob of modules in the posttask resting-state scans (ie, after frustration) predicted irritability symptoms. Self-reported irritability was predicted by Eglob of a frontotemporal-limbic module. Parent-reported irritability was predicted by Eglob of ventral-prefrontal-subcortical and somatomotor-parietal modules. CONCLUSION: These pilot results suggest the importance of the postfrustration recovery period in the pathophysiology of irritability. Eglob in 3 specific posttask modules, involved in emotion processing, reward processing, or motor function, predicted irritability. These findings, if replicated, could represent specific intervention targets for irritability.

Maternal treatment with P7C3-A20 protects from impaired maternal care after chronic gestational stress.

Chronic stress during pregnancy harms both the mother and developing child, and there is an urgent unmet need to understand this process in order to develop protective treatments. Here, we report that chronic gestational stress (CGS) causes aberrant maternal care behavior in the form of increased licking and grooming, decreased nursing, and increased time spent nest building. Treatment of CGS-exposed dams with the NAD+-stabilizing agent P7C3-A20 during pregnancy and postpartum, however, preserved normal maternal care behavior. CGS also caused abnormally low weight gain during gestation and postpartum, which was partially ameliorated by maternal treatment with P7C3-A20. Dams also displayed hyperactive locomotion after CGS, which was not affected by P7C3-A20. Although dams did not display a classic depressive-like phenotype after CGS, some changes in anxiety- and depressive-like behaviors were observed. Our results highlight the need for further characterization of the effects of chronic gestational stress on maternal care behavior and provide clues to possible protective mechanisms.