Arabidopsis PROTODERMAL FACTOR2 binds lysophosphatidylcholines and transcriptionally regulates phospholipid metabolism.

Plant homeodomain leucine zipper IV (HD-Zip IV) transcription factors (TFs) contain an evolutionarily conserved steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain. While the START domain is required for TF activity, its presumed role as a lipid sensor is not clear. Here we used tandem affinity purification from Arabidopsis cell cultures to demonstrate that PROTODERMAL FACTOR2 (PDF2), a representative member that controls epidermal differentiation, recruits lysophosphatidylcholines (LysoPCs) in a START-dependent manner. Microscale thermophoresis assays confirmed that a missense mutation in a predicted ligand contact site reduces lysophospholipid binding. We additionally found that PDF2 acts as a transcriptional regulator of phospholipid- and phosphate (Pi) starvation-related genes and binds to a palindromic octamer with consensus to a Pi response element. Phospholipid homeostasis and elongation growth were altered in pdf2 mutants according to Pi availability. Cycloheximide chase experiments revealed a role for START in maintaining protein levels, and Pi starvation resulted in enhanced protein destabilization, suggesting a mechanism by which lipid binding controls TF activity. We propose that the START domain serves as a molecular sensor for membrane phospholipid status in the epidermis. Our data provide insights toward understanding how the lipid metabolome integrates Pi availability with gene expression.

Obstetric and anesthetic management in parturients with ventriculoperitoneal shunt: a case series.

Further study is needed to determine the safest mode of delivery and anesthetic management for parturients with ventriculoperitoneal shunts (VP). Prior recommendation for delivery in women with ventriculoperitoneal shunts was cesarean delivery. However, both vaginal delivery and neuraxial anesthesia have been shown to be safe in women with appropriately functioning VP shunts. We present a case series of parturients with VP shunt. Parturients with VP shunts were identified and VP shunt placement indications, neurologic symptoms during pregnancy, delivery mode, anesthetic type, and postpartum complications were reviewed. Forty patients were identified, and fifteen women with twenty deliveries were included. Two women experienced neurological symptoms during pregnancy and one required postpartum shunt revision for blurry vision and ataxia. There were ten cesarean deliveries and ten vaginal deliveries (eight normal spontaneous, one vacuum assisted, and one forceps assisted). Assisted vaginal deliveries were performed to decrease Valsalva including the patient with neurological symptoms related to shunt malfunction. Of the vaginal deliveries, six (60%) had epidural analgesia. Anesthesia for cesarean delivery included neuraxial anesthesia (n = 5) and general anesthesia (n = 5). In our cohort, women with VP shunt received neuraxial blockade without complication. Neuraxial techniques should be offered to women with appropriately functioning VP shunt.

Acute toxicity of the fungicide captan to honey bees and mixed evidence for synergism with the insecticide thiamethoxam.

Honey bees are commonly co-exposed to pesticides during crop pollination, including the fungicide captan and neonicotinoid insecticide thiamethoxam. We assessed the impact of exposure to these two pesticides individually and in combination, at a range of field-realistic doses. In laboratory assays, mortality of larvae treated with captan was 80-90% greater than controls, dose-independent, and similar to mortality from the lowest dose of thiamethoxam. There was evidence of synergism (i.e., a non-additive response) from captan-thiamethoxam co-exposure at the highest dose of thiamethoxam, but not at lower doses. In the field, we exposed whole colonies to the lowest doses used in the laboratory. Exposure to captan and thiamethoxam individually and in combination resulted in minimal impacts on population growth or colony mortality, and there was no evidence of synergism or antagonism. These results suggest captan and thiamethoxam are each acutely toxic to immature honey bees, but whole colonies can potentially compensate for detrimental effects, at least at the low doses used in our field trial, or that methodological differences of the field experiment impacted results (e.g., dilution of treatments with natural pollen). If compensation occurred, further work is needed to assess how it occurred, potentially via increased queen egg laying, and whether short-term compensation leads to long-term costs. Further work is also needed for other crop pollinators that lack the social detoxification capabilities of honey bee colonies and may be less resilient to pesticides.

The Effects of a Guided Mindful Walk on Mental Health in University Students.

College campuses in the United States are experiencing high levels of mental distress without adequate psychological resources to address the need. In addition, the majority of university students do not meet the physical activity guidelines for mental and physical health. Effective and time efficient resources are needed to address poor mental health and low physical activity among university students on college campuses. Mindful walking may be a promising solution. The purpose was to 1) measure change in mental health and 2) estimate physical activity from participation in a guided mindful walk in a diverse student sample. Students participated in a mindful walking route which included seven stops (0.85 miles) during the Spring 2022 semester. Undergraduate students (n = 44) were mean ± SD age 20.9 ± 3.8 years and 68% female. Validated surveys were given pre- and post-participation measuring mental health constructs of state mindfulness (Toronto Mindfulness Scale; TMS), state anxiety (visual analogue scale), and state stress (Short Stress State Questionnaire; SSSQ). Physical activity was estimated via steps on a Yamax pedometer worn at the hip. After the guided mindful walk, total state mindfulness score significantly improved (mean ± SD) (pre: 27.5 ± 8.2, post: 32.8 ± 9.5; p < 0.001); state anxiety significantly decreased (pre: 3.7 ± 2.4, post: 2.4 ± 2; p < 0.0001) and total state stress score was reduced (pre: 66.1 ± 10.7, post: 63.4 ± 8.3; p = 0.03). Physical activity averaged 1,726 ± 159 steps. Completion of a guided mindful walk can reduce anxiety and stress, while increasing mindfulness among university students.

Injury Risk Predictions in Lunar Terrain Vehicle (LTV) Extravehicular Activities (EVAs): A Pilot Study.

Extravehicular activities will play a crucial role in lunar exploration on upcoming Artemis missions and may involve astronauts operating a lunar terrain vehicle (LTV) in a standing posture. This study assessed kinematic response and injury risks using an active muscle human body model (HBM) restrained in an upright posture on the LTV by simulating dynamic acceleration pulses related to lunar surface irregularities. Linear accelerations and rotational displacements of 5 lunar obstacles (3 craters; 2 rocks) over 5 slope inclinations were applied across 25 simulations. All body injury metrics were below NASA's injury tolerance limits, but compressive forces were highest in the lumbar (250-550N lumbar, tolerance: 5300N) and lower extremity (190-700N tibia, tolerance: 1350N) regions. There was a strong association between the magnitudes of body injury metrics and LTV resultant linear acceleration (ρ = 0.70-0.81). There was substantial upper body motion, with maximum forward excursion reaching 375 mm for the head and 260 mm for the chest. Our findings suggest driving a lunar rover in an upright posture for these scenarios is a low severity impact presenting low body injury risks. Injury metrics increased along the load path, from the lower body (highest metrics) to the upper body (lowest metrics). While upper body injury metrics were low, increased body motion could potentially pose a risk of injury from flail and occupant interaction with the surrounding vehicle, suit, and restraint hardware.

The impact of different strategies for modeling associations between medications at low doses and health outcomes: a simulation study and practical application to postpartum opioid use.

Pharmacoepidemiological studies commonly examine the association between drug dose and adverse health outcomes. In situations where no safe dose exists, the choice of modeling strategy can lead to identification of an apparent safe low dose range in the presence of a non-linear relationship or due to the modeling strategy forcing a linear relationship through a dose of 0. We conducted a simulation study to assess the performance of several regression approaches to model the drug dose-response curve at low doses in a setting where no safe range exists, including the use of a (1) linear dose term, (2) categorical dose term, and (3) natural cubic spline terms. Additionally, we introduce and apply an expansion of prior work related to modeling dose-response curves at low and infrequently used doses in the setting of no safe dose ("spike-at-zero" and "slab-and-spline"). Furthermore, we demonstrate and empirically assess the use of these regression strategies in a practical scenario examining the association between the dose of the initial postpartum opioid prescribed after vaginal delivery and the subsequent total dose of opioids prescribed in the entire postpartum period among a cohort of opioid-naïve women with a vaginal delivery enrolled in a State Medicaid program (2007-2014).

Hypertensive Disorders of Pregnancy: Innovative Management Strategies.

Hypertensive disorders of pregnancy (HDP) complicate 13% to 15% of pregnancies in the United States. Historically marginalized communities are at increased risk, with preeclampsia and eclampsia being the leading cause of death in this population. Pregnant individuals with HDP require more frequent and intensive monitoring throughout the antepartum period outside of routine standard of care prenatal visits. Additionally, acute rises in blood pressure often occur 3 to 6 days postpartum and are challenging to identify and treat, as most postpartum individuals are usually scheduled for their first visit 6 weeks after delivery. Thus, a multifaceted approach is necessary to improve recognition and treatment of HDP throughout the peripartum course. There are limited studies investigating interventions for the management of HDP, especially within the United States, where maternal mortality is rising, and in higher-risk groups. We review the state of current management of HDP and innovative strategies such as blood pressure self-monitoring, telemedicine, and community health worker intervention.

African American Preschoolers' Performance on Norm-Referenced Language Assessments: Examining the Effect of Dialect Density and the Use of Scoring Modifications.

PURPOSE: We investigated and compared the outcomes from two standardized, norm-referenced screening assessments of language (i.e., Clinical Evaluation of Language Fundamentals Preschool-Second Edition [CELFP-2], Diagnostic Evaluation of Language Variation-Screening Test [DELV-ST]) with African American preschoolers whose spoken dialect differed from that of General American English (GAE). We (a) described preschoolers' performance on the CELFP-2 Core Language Index (CLI) and its subtests with consideration of degree of dialect variation (DVAR) observed, (b) investigated how the application of dialect-sensitive scoring modifications to the expressive morphology and syntax Word Structure (WS) subtest affected CELFP-2 CLI scores, and (c) evaluated the screening classification agreement rates between the DELV-ST and the CELFP-2 CLI. METHOD: African American preschoolers (N = 284) completed the CELFP-2 CLI subtests (i.e., Sentence Structure, WS, Expressive Vocabulary) and the DELV-ST. Density of spoken dialect use was estimated with the DELV-ST Part I Language Variation Status, and percentage of DVAR was calculated. The CELFP-2 WS subtest was scored with and without dialect-sensitive scoring modifications. RESULTS: Planned comparisons of CELFP-2 CLI performance indicated statistically significant differences in performance based on DELV-ST-determined degree of language variation groupings. Scoring modifications applied to the WS subtest increased subtest scaled scores and CLI composite standard scores. However, preschoolers who demonstrated strong variation from GAE continued to demonstrate significantly lower performance than preschoolers who demonstrated little to no language variation. Affected-status agreement rates between assessments (modified and unmodified CELFP-2 CLI scores and DELV-ST Part II Diagnostic Risk Status) were extremely low. CONCLUSIONS: The application of dialect-specific scoring modifications to standardized, norm-referenced assessments of language must be simultaneously viewed through the lenses of equity, practicality, and psychometry. The results of our multistage study reiterate the need for reliable methods of identifying risk for developmental language disorder within children who speak American English dialects other than GAE. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.26017978.

Improving age-friendly advance care planning in primary care: Outcomes from a Pacific Northwest learning collaborative.

BACKGROUND: Advance care planning (ACP) is the process of having conversations with patients to ensure preferences are known and support patient healthcare goals. ACP and the Age-Friendly Health Systems (AFHS) Initiative's, "What Matters," are synergistic approaches to patient-centered conversations. Implementation and measurement of ACP in primary care (PC) are variables in quality and consistency. We examined whether participation in an ACP learning collaborative (LC) would improve knowledge and ability to conduct ACP discussions and increase the frequency of documented ACP in participating practices. METHODS: The WWAMI (Washington, Wyoming, Alaska, Montana, and Idaho) region Practice and Research Network (WPRN) and the Northwest Geriatrics Workforce Enhancement Center collaboratively organized a 9-month virtual LC. It consisted of 4 synchronous, 1.5-h sessions, technical support, and a panel of ACP experts. A Wilcoxon rank sum test assessed differences in knowledge from a pre-post survey. Documentation of ACP in the EHR was collected after at least one plan-do-study-act cycle. RESULTS: We enrolled 17 participants from 6 PC practices (3 hospital-affiliated; 3 Federally Qualified Health Centers) from the WPRN. Two practices did not complete all LC activities. There was a trend toward increased ACP knowledge and skills overall especially in having discussions patients and families (pre-mean 2.9 [SD = 0.7]/post-mean 4.0[SD = 1.1], p < 0.05). 4/6 practices observed an increase in EHR documentation post-collaborative (median 16.3%, IQR 1.3%-36.9%). CONCLUSIONS: The LC increased PC providers knowledge and skills of ACP and AFHS's What Matters, reported ACP EHR documentation, and contributed to practice change.

Correspondence between the alcohol-P3 event-related potential and alcohol reward phenotypes among young adults.

BACKGROUND: Behavioral economic theory suggests that the value of alcohol depends upon elements of the choice context, such that increasing constraints on alternatives (e.g., price) or increasing the benefits of alcohol (e.g., social context) may result in greater likelihood of heavy drinking. The P3 event-related potential elicited by alcohol-related cues, a proposed marker of incentive salience, may be an electrophysiological parallel for behavioral economic alcohol demand. However, these indices have not been connected in prior research, and studies typically do not disaggregate social influences in the context of alcohol cue reactivity. METHOD: The current study recruited heavy drinking young adults (N = 81) who completed measures of alcohol use and alcohol demand, in addition to a 2 (social/nonsocial) × 2 (alcohol/nonalcohol) visual oddball task to elicit the P3. RESULTS: In multilevel models controlling for demographic characteristics, P3 reactivity was greater to alcohol (p < 0.001) and social (p < 0.001) cues than to nonalcohol and nonsocial cues, but without a significant interaction. Higher alcohol consumption (p = 0.02) and lower elasticity of demand (p = 0.01) were associated with greater P3 response to alcohol than nonalcohol cues. CONCLUSIONS: The results highlight a brain-behavior connection that may be an important marker for alcohol reward across units of analysis and may be sensitive to changes in the economic choice contexts that influence the likelihood of alcohol use.

Early physical rehabilitation dosage in the IntensiveCare Unit predicts hospital outcomes after criticalCOVID-19.

Objective: to examine the relationship between physical rehabilitation parameters including a novel approach to quantifying dosage with hospital outcomes for patients with critical COVID-19. Design: Retrospective practice analysis from March 5, 2020, to April 15, 2021. Setting: Intensive care units (ICU) at four medical institutions. Patients: n = 3,780 adults with ICU admission and diagnosis of COVID-19. Interventions: We measured the physical rehabilitation treatment delivered in ICU and patient outcomes: 1) mortality; 2) discharge disposition; and 3) physical function at hospital discharge measured by the Activity Measure-Post Acute Care (AM-PAC) "6-Clicks" (6-24, 24=greater functional independence). Physical rehabilitation dosage was defined as the average mobility level scores in the first three sessions (a surrogate measure of intensity) multiplied by the rehabilitation frequency (PT + OT frequency in hospital). Measurements and Main Results: The cohort was a mean 64 ± 16 years old, 41% female, mean BMI of 32 ± 9 kg/m2 and 46% (n=1739) required mechanical ventilation. For 2191 patients with complete data, rehabilitation dosage and AM-PAC at discharge were moderately, positively associated (Spearman's rho [r] = 0.484, p < 0.001). Multivariate linear regression (model adjusted R2= 0.68, p <0.001) demonstrates mechanical ventilation (ß = -0.86, p = 0.001), average mobility score in first three sessions (ß = 2.6, p <0.001) and physical rehabilitation dosage (ß = 0.22, p = 0.001) were predictive of AM-PAC scores at discharge when controlling for age, sex, BMI, and ICU LOS. Conclusions: Greater physical rehabilitation exposure early in the ICU is associated with physical function at hospital discharge.

Data Equity as a Building Block for Health Equity: Improving Surveillance Data for People With Disabilities, With Substance Use Disorder, or Experiencing Homelessness, United States.

OBJECTIVES: People with disabilities, people experiencing homelessness, and people who have substance use disorders face unique health challenges. Gaps in public health surveillance data limit the identification of public health needs of these groups and data-driven action. This study aimed to identify current practices, challenges, and opportunities for collecting and reporting COVID-19 surveillance data for these populations. METHODS: We used a rapid qualitative assessment to explore COVID-19 surveillance capacities. From July through October 2021, we virtually interviewed key informants from the Centers for Disease Control and Prevention, state and local health departments, and health care providers across the United States. We thematically analyzed and contextualized interview notes, peer-reviewed articles, and participant documents using a literature review. RESULTS: We identified themes centered on foundational structural and systems issues that hinder actionable surveillance data for these and other populations that are disproportionately affected by multiple health conditions. Qualitative data analysis of 61 interviews elucidated 4 primary challenges: definitions and policies, resources, data systems, and articulation of the purpose of data collection to these groups. Participants noted the use of multisector partnerships, automated data collection and integration, and data scorecards to circumvent challenges. CONCLUSIONS: This study highlights the need for multisector, systematic improvements in surveillance data collection and reporting to advance health equity. Improvements must be buttressed with adequate investment in data infrastructure and promoted through clear communication of how data are used to protect health.

Performance of Phenotype Algorithms for the Identification of Opioid-Exposed Infants.

OBJECTIVE: Observational studies examining outcomes among opioid-exposed infants are limited by phenotype algorithms that may under identify opioid-exposed infants without neonatal opioid withdrawal syndrome (NOWS). We developed and validated the performance of different phenotype algorithms to identify opioid-exposed infants using electronic health record data. METHODS: We developed phenotype algorithms for the identification of opioid-exposed infants among a population of birthing person-infant dyads from an academic health care system (2010-2022). We derived phenotype algorithms from combinations of 6 unique indicators of in utero opioid exposure, including those from the infant record (NOWS or opioid-exposure diagnosis, positive toxicology) and birthing person record (opioid use disorder diagnosis, opioid drug exposure record, opioid listed on medication reconciliation, positive toxicology). We determined the positive predictive value (PPV) and 95% confidence interval for each phenotype algorithm using medical record review as the gold standard. RESULTS: Among 41 047 dyads meeting exclusion criteria, we identified 1558 infants (3.80%) with evidence of at least 1 indicator for opioid exposure and 32 (0.08%) meeting all 6 indicators of the phenotype algorithm. Among the sample of dyads randomly selected for review (n = 600), the PPV for the phenotype requiring only a single indicator was 95.4% (confidence interval: 93.3-96.8) with varying PPVs for the other phenotype algorithms derived from a combination of infant and birthing person indicators (PPV range: 95.4-100.0). CONCLUSIONS: Opioid-exposed infants can be accurately identified using electronic health record data. Our publicly available phenotype algorithms can be used to conduct research examining outcomes among opioid-exposed infants with and without NOWS.

Time to split: biomarker trajectories in pediatric acute respiratory distress syndrome hint at underlying disease.

Pediatric acute respiratory distress syndrome (ARDS) is severe, noncardiac hypoxemic respiratory failure that carries a substantial risk of death. Given the complexity of this clinically defined syndrome and the repeated failure of therapeutic trials, there has been an effort to identify subphenotypes of ARDS that may share targetable mechanisms of disease. In this issue of the JCI, Yehya and colleagues measured 19 plasma biomarkers in 279 children over the first seven days of ARDS. Increases in select tissue injury makers and inflammatory cytokines in peripheral blood were associated with multiple organ dysfunction syndrome and death, but not persistent ARDS. These findings argue that splitting patients by clinical and molecular phenotype may be more informative than lumping them under the umbrella diagnosis of ARDS. However, future studies are needed to determine whether these plasma factors represent targetable pathways in lung injury or are a consequence of systemic organ dysfunction.

Qualitative Study to Explore the Occupational and Reproductive Health Challenges among Women Tobacco Farm Laborers in Mysore District, India.

Tobacco farm laborers are primarily women and children working for very low wages. The aim of this study was to explore occupational and reproductive health challenges faced by women tobacco farm laborers in Mysore District, India. We conducted interviews and six focus group discussions among 41 women tobacco farm laborers. Codes and themes were generated based on deductive and inductive approaches using the socioecological model. Participants reported symptoms of green tobacco sickness including headaches, back pain, gastric problems, weakness, and allergies during menstruation, pre-natal, and post-natal periods. Participants had poor awareness about the health effects of tobacco farming, and there were gender inequalities in wages and the use of personal protective equipment. Participants received support from family and community health workers during their pregnancy and post-natal period. Women reported wanting maternity benefits from the tobacco board, as well as monetary support and nutritional supplements. There is a need for health education about the environmental dangers of tobacco among farm laborers, and more supportive policies for women farmworkers during pregnancy and post-natal periods.

Specific exercise patterns generate an epigenetic molecular memory window that drives long-term memory formation and identifies ACVR1C as a bidirectional regulator of memory in mice.

Exercise has beneficial effects on cognition throughout the lifespan. Here, we demonstrate that specific exercise patterns transform insufficient, subthreshold training into long-term memory in mice. Our findings reveal a potential molecular memory window such that subthreshold training within this window enables long-term memory formation. We performed RNA-seq on dorsal hippocampus and identify genes whose expression correlate with conditions in which exercise enables long-term memory formation. Among these genes we found Acvr1c, a member of the TGF ß family. We find that exercise, in any amount, alleviates epigenetic repression at the Acvr1c promoter during consolidation. Additionally, we find that ACVR1C can bidirectionally regulate synaptic plasticity and long-term memory in mice. Furthermore, Acvr1c expression is impaired in the aging human and mouse brain, as well as in the 5xFAD mouse model, and over-expression of Acvr1c enables learning and facilitates plasticity in mice. These data suggest that promoting ACVR1C may protect against cognitive impairment.

Childhood Maltreatment and Amygdala-Mediated Anxiety and Posttraumatic Stress Following Adult Trauma.

Background: Childhood abuse (physical, emotional, and sexual) is associated with aberrant connectivity of the amygdala, a key threat-processing region. Heightened amygdala activity also predicts adult anxiety and posttraumatic stress disorder (PTSD) symptoms, as do experiences of childhood abuse. The current study explored whether amygdala resting-state functional connectivity may explain the relationship between childhood abuse and anxiety and PTSD symptoms following trauma exposure in adults. Methods: Two weeks posttrauma, adult trauma survivors (n = 152, mean age [SD] = 32.61 [10.35] years; women = 57.2%) completed the Childhood Trauma Questionnaire and underwent resting-state functional magnetic resonance imaging. PTSD and anxiety symptoms were assessed 6 months posttrauma. Seed-to-voxel analyses evaluated the association between childhood abuse and amygdala resting-state functional connectivity. A mediation model evaluated the potential mediating role of amygdala connectivity in the relationship between childhood abuse and posttrauma anxiety and PTSD. Results: Childhood abuse was associated with increased amygdala connectivity with the precuneus while covarying for age, gender, childhood neglect, and baseline PTSD symptoms. Amygdala-precuneus resting-state functional connectivity was a significant mediator of the effect of childhood abuse on anxiety symptoms 6 months posttrauma (B = 0.065; 95% CI, 0.013-0.130; SE = 0.030), but not PTSD. A secondary mediation analysis investigating depression as an outcome was not significant. Conclusions: Amygdala-precuneus connectivity may be an underlying neural mechanism by which childhood abuse increases risk for anxiety following adult trauma. Specifically, this heightened connectivity may reflect attentional vigilance for threat or a tendency toward negative self-referential thoughts. Findings suggest that childhood abuse may contribute to longstanding upregulation of attentional vigilance circuits, which makes one vulnerable to anxiety-related symptoms in adulthood.

Experiences of childhood abuse are related to long-term mental health outcomes, but the mechanisms of this relationship have been unclear. In this study of adult trauma survivors, Harb et al. found that experiences of childhood abuse are related to abnormal connectivity patterns of the amygdala, a key region for fear and threat processing, and precuneus. These connectivity patterns were identified as a mechanism through which experiences of child abuse are related to adult anxiety symptoms posttrauma. These findings advance our understanding of the specific downstream impacts of experiencing childhood abuse and can inform targeted assessment and intervention methods, especially in an adult trauma sample.