Parvalbumin interneuron mGlu5 receptors govern sex differences in prefrontal cortex physiology and binge drinking.

Despite established sex differences in the prevalence and presentation of psychiatric disorders, little is known about the cellular and synaptic mechanisms that guide these differences under basal conditions. The proper function of the prefrontal cortex (PFC) is essential for the top-down regulation of motivated behaviors. The activity of the PFC is tightly controlled by parvalbumin-expressing interneurons (PV-INs), a key subpopulation of fast-spiking GABAergic cells that regulate cortical excitability through direct innervations onto the perisomatic regions of nearby pyramidal cells. Recent rodent studies have identified notable sex differences in PV-IN activity and adaptations to experiences such as binge drinking. Here, we investigated the cellular and molecular mechanisms that underlie sex-specific regulation of PFC PV-IN function. Using whole-cell patch-clamp electrophysiology and selective pharmacology, we report that PV-INs from female mice are more excitable than those from males. Moreover, we find that mGlu1 and mGlu5 metabotropic glutamate receptors regulate cell excitability, excitatory drive, and endocannabinoid signaling at PFC PV-INs in a sex-dependent manner. Genetic deletion of mGlu5 receptors from PV-expressing cells abrogates all sex differences observed in PV-IN membrane and synaptic physiology. Lastly, we report that female, but not male, PV-mGlu5-/- mice exhibit decreased voluntary drinking on an intermittent access schedule, which could be related to changes in ethanol's stimulant properties. Importantly, these studies identify mGlu1 and mGlu5 receptors as candidate signaling molecules involved in sex differences in PV-IN activity and behaviors relevant to alcohol use.

Should I stay or should I go? Coral bleaching from the symbionts' perspective.

Coral bleaching, the stress-induced breakdown of coral-algal symbiosis, threatens reefs globally. Paradoxically, despite adverse fitness effects, corals bleach annually, even outside of abnormal temperatures. This generally occurs shortly after the once-per-year mass coral spawning. Here, we propose a hypothesis linking annual coral bleaching and the transmission of symbionts to the next generation of coral hosts. We developed a dynamic model with two symbiont growth strategies, and found that high sexual recruitment and low adult coral survivorship and growth favour bleaching susceptibility, while the reverse promotes bleaching resilience. Otherwise, unexplained trends in the Indo-Pacific align with our hypothesis, where reefs and coral taxa exhibiting higher recruitment are more bleaching susceptible. The results from our model caution against interpreting potential shifts towards more bleaching-resistant symbionts as evidence of climate adaptation-we predict such a shift could also occur in declining systems experiencing low recruitment rates, a common scenario on today's reefs.

Peer perspectives on friendships among peers with and without intellectual and developmental disabilities: A pilot mixed methods study.

BACKGROUND: The benefits of friendships among peers with and without intellectual and developmental disabilities are well supported by research. However, little is known about the nature of these inclusive friendships in inclusive college courses. METHOD: We explored the perspectives of peers on the development of authentic friendships among peers with and without intellectual and developmental disabilities in inclusive college courses in the United States. We used a sequential, explanatory, transformative mixed methods-grounded theory research design. We integrated quantitative (N = 44) and qualitative (N = 8) findings using blended analysis to inform a preliminary grounded theory of inclusive and reciprocal friendships. RESULTS: Quantitative findings suggest two relationships and one predictor of peers' perceived social engagement. Qualitative findings resulted in five themes that promote friendships. CONCLUSIONS: We propose that the context for developing inclusive friendships could be fostered using the preparation and actions stages of the grounded theory model.

A spatial proteomic study of platinum refractory HGSOC implicates dual AKT and WNT activity linked to an immunosuppressive tumor microenvironment.

OBJECTIVE: Advanced-stage high-grade serous ovarian cancer (HGSOC) remains a deadly gynecologic malignancy with high rates of disease recurrence and limited, effective therapeutic options for patients. There is a significant need to better stratify HGSOC patients into platinum refractory (PRF) vs. sensitive (PS) cohorts at baseline to improve therapeutic responses and survival outcomes for PRF HGSOC. METHODS: We performed NanoString for GeoMx Digital Spatial Profile (G-DSP) multiplex protein analysis on PRF and PS tissue microarrays (TMAs) to study the bidirectional communication of cancer cells with immune cells in the tumor microenvironment (TME) of HGSOC. We demonstrate robust stratification of PRF and PS tumors at baseline using multiplex spatial proteomic biomarkers with implications for tailoring subsequent therapy. RESULTS: PS patients had elevated apoptotic and anti-tumor immune profiles, while PRF patients had dual AKT1 and WNT signaling with immunosuppressive profiles. We found that dual activity of AKT1 and WNT signaling supported the exclusion of immune cells, specifically tumor infiltrating lymphocytes (TILs), from the TME in PRF tumors, and this was not observed in PS tumors. The exclusion of immune cells from the TME of PRF tumors corresponded to abnormal endothelial cell structure in tumors with dual AKT1 and WNT signaling activity. CONCLUSIONS: We believe our findings provide improved understanding of tumor-immune crosstalk in HGSOC TME highlighting the importance of the relationship between AKT and WNT pathways, immune cell function, and platinum response in HGSOC.

Mixed Patterns of Intergenerational DNA Methylation Inheritance in Acropora.

For sessile organisms at high risk from climate change, phenotypic plasticity can be critical to rapid acclimation. Epigenetic markers like DNA methylation are hypothesized as mediators of plasticity; methylation is associated with the regulation of gene expression, can change in response to ecological cues, and is a proposed basis for the inheritance of acquired traits. Within reef-building corals, gene-body methylation (gbM) can change in response to ecological stressors. If coral DNA methylation is transmissible across generations, this could potentially facilitate rapid acclimation to environmental change. We investigated methylation heritability in Acropora, a stony reef-building coral. Two Acropora millepora and two Acropora selago adults were crossed, producing eight offspring crosses (four hybrid, two of each species). We used whole-genome bisulfite sequencing to identify methylated loci and allele-specific alignments to quantify per-locus inheritance. If methylation is heritable, differential methylation (DM) between the parents should equal DM between paired offspring alleles at a given locus. We found a mixture of heritable and nonheritable loci, with heritable portions ranging from 44% to 90% among crosses. gBM was more heritable than intergenic methylation, and most loci had a consistent degree of heritability between crosses (i.e. the deviation between parental and offspring DM were of similar magnitude and direction). Our results provide evidence that coral methylation can be inherited but that heritability is heterogenous throughout the genome. Future investigations into this heterogeneity and its phenotypic implications will be important to understanding the potential capability of intergenerational environmental acclimation in reef building corals.

Parvalbumin interneuron mGlu5 receptors govern sex differences in prefrontal cortex physiology and binge drinking.

Despite established sex differences in the prevalence and presentation of psychiatric disorders, little is known about the cellular and synaptic mechanisms that guide these differences under basal conditions. Proper function of the prefrontal cortex (PFC) is essential for the top-down regulation of motivated behaviors. Activity of the PFC is tightly controlled by parvalbumin-expressing interneurons (PV-INs), a key subpopulation of fast-spiking GABAergic cells that regulate cortical excitability through direct innervations onto the perisomatic regions of nearby pyramidal cells. Recent rodent studies have identified notable sex differences in PV-IN activity and adaptations to experiences such as binge drinking. Here, we investigated the cellular and molecular mechanisms that underlie sex-specific regulation of PFC PV-IN function. Using whole-cell patch clamp electrophysiology and selective pharmacology, we report that PV-INs from female mice are more excitable than those from males. Moreover, we find that mGlu1 and mGlu5 metabotropic glutamate receptors regulate cell excitability, excitatory drive, and endocannabinoid signaling at PFC PV-INs in a sex-dependent manner. Genetic deletion of mGlu5 receptors from PV-expressing cells abrogates all sex differences observed in PV-IN membrane and synaptic physiology. Lastly, we report that female, but not male, PV-mGlu5-/- mice exhibit decreased voluntary drinking on an intermittent access schedule, which could be related to changes in ethanol's stimulant properties. Importantly, these studies identify mGlu1 and mGlu5 receptors as candidate signaling molecules involved in sex differences in PV-IN activity and behaviors relevant for alcohol use.

Characterization of the Cynomolgus Macaque Model of Marburg Virus Disease and Assessment of Timing for Therapeutic Treatment Testing.

Marburg virus (MARV) causes severe disease and high mortality in humans. The objective of this study was to characterize disease manifestations and pathogenesis in cynomolgus macaques exposed to MARV. The results of this natural history study may be used to identify features of MARV disease useful in defining the ideal treatment initiation time for subsequent evaluations of investigational therapeutics using this model. Twelve cynomolgus macaques were exposed to a target dose of 1000 plaque-forming units MARV by the intramuscular route, and six control animals were mock-exposed. The primary endpoint of this study was survival to Day 28 post-inoculation (PI). Anesthesia events were minimized with the use of central venous catheters for periodic blood collection, and temperature and activity were continuously monitored by telemetry. All mock-exposed animals remained healthy for the duration of the study. All 12 MARV-exposed animals (100%) became infected, developed illness, and succumbed on Days 8-10 PI. On Day 4 PI, 11 of the 12 MARV-exposed animals had statistically significant temperature elevations over baseline. Clinically observable signs of MARV disease first appeared on Day 5 PI, when 6 of the 12 animals exhibited reduced responsiveness. Ultimately, systemic inflammation, coagulopathy, and direct cytopathic effects of MARV all contributed to multiorgan dysfunction, organ failure, and death or euthanasia of all MARV-exposed animals. Manifestations of MARV disease, including fever, systemic viremia, lymphocytolysis, coagulopathy, and hepatocellular damage, could be used as triggers for initiation of treatment in future therapeutic efficacy studies.

Acute alcohol and chronic drinking bidirectionally regulate the excitability of prefrontal cortex vasoactive intestinal peptide interneurons.

The prefrontal cortex (PFC) regulates drinking behaviors and affective changes following chronic alcohol use. PFC activity is dynamically modulated by local inhibitory interneurons (INs), which can be divided into non-overlapping groups with distinct functional roles. Within deeper layers of neocortex, INs that express either parvalbumin or somatostatin directly inhibit pyramidal cells. By contrast, the plurality of all remaining INs express vasoactive intestinal peptide (VIP), reside within superficial layers, and preferentially target other types of INs. While recent studies have described adaptations to PFC parvalbumin-INs and somatostatin-INs in alcohol use models, whether ethanol or drinking affect the physiology of PFC VIP-INs has not been reported. To address this gap, we used genetically engineered female and male mice to target VIP-INs in layers 1-3 of prelimbic PFC for whole-cell patch-clamp electrophysiology. We found that ethanol (20 mM, ∼0.09 BEC/90 mg/dL) application to PFC brain slices enhances VIP-IN excitability. We next examined effects following chronic drinking by providing mice with 4 weeks of intermittent access (IA) ethanol two-bottle choice in the home cage. In these studies, VIP-INs from female and male IA ethanol mice displayed reduced excitability relative to cells from water-only controls. Finally, we assessed whether these effects continue into abstinence. After 7-13 days without ethanol, the hypo-excitability of VIP-INs from male IA ethanol mice persisted, whereas cells from female IA ethanol mice were not different from their controls. Together, these findings illustrate that acute ethanol enhances VIP-IN excitability and suggest these cells undergo pronounced homeostatic changes following long-term drinking.

Listeriosis Risk Model for Cancer Patients Who Consume Ready-to-Eat Salad.

The foodborne pathogen Listeria monocytogenes generally infects immunocompromised individuals, such as cancer patients, more frequently and with higher morbidity and mortality than the general population. Because of the anticipated risk associated with L. monocytogenes and other pathogens in produce, immunocompromised individuals are often placed on neutropenic diets that exclude fresh produce, though these risks have not been quantified. Therefore, this study developed a data-driven risk model for listeriosis in cancer patients who consume ready-to-eat (RTE) salads, consisting of leafy greens, cucumbers, and tomatoes, as influenced by kitchen-scale treatments and storage practices. Monte Carlo simulations were used to model the risk of invasive listeriosis during one chemotherapy cycle. Refrigerating all salad components decreased the median risk by approximately one-half log. For refrigerated salads with no treatment, the predicted median risk was ≤ 4.3 × 10-08. When salad ingredients were surface blanched with greens rinsed, the predicted risk decreased to 5.4 × 10-10. Predicted risk was lowest (1.4 × 10-13) for a blanched "salad" consisting of solely cucumbers and tomatoes. Interestingly, rinsing, as recommended by FDA, only decreased the median risk by 1 log. A sensitivity analysis revealed that the highly variable dose-response parameter k strongly influenced risk, indicating that reducing uncertainty in this variable may improve model accuracy. Overall, this study demonstrates that kitchen-scale pathogen reduction approaches have high risk reduction efficacy and could be considered as an alternative to diets that exclude produce when making risk management decisions.

Sex differences and hormonal regulation of metabotropic glutamate receptor synaptic plasticity.

Striking sex differences exist in presentation and incidence of several psychiatric disorders. For example, major depressive disorder is more prevalent in women than men, and women who develop alcohol use disorder progress through drinking milestones more rapidly than men. With regards to psychiatric treatment responses, women respond more favorably to selective serotonin reuptake inhibitors than men, whereas men have better outcomes when prescribed tricyclic antidepressants. Despite such well-documented biases in incidence, presentation, and treatment response, sex as a biological variable has long been neglected in preclinical and clinical research. An emerging family of druggable targets for psychiatric diseases, metabotropic glutamate (mGlu) receptors are G-protein coupled receptors broadly distributed throughout the central nervous system. mGlu receptors confer diverse neuromodulatory actions of glutamate at the levels of synaptic plasticity, neuronal excitability, and gene transcription. In this chapter, we summarize the current preclinical and clinical evidence for sex differences in mGlu receptor function. We first highlight basal sex differences in mGlu receptor expression and function and proceed to describe how gonadal hormones, notably estradiol, regulate mGlu receptor signaling. We then describe sex-specific mechanisms by which mGlu receptors differentially modulate synaptic plasticity and behavior in basal states and models relevant for disease. Finally, we discuss human research findings and highlight areas in need of further research. Taken together, this review emphasizes how mGlu receptor function and expression can differ across sex. Gaining a more complete understanding of how sex differences in mGlu receptor function contribute to psychiatric diseases will be critical in the development of novel therapeutics that are effective in all individuals.

Honoring What We Say We Do: Developing Real-World Tools for Routine Family Caregiver Assessment and Support in Outpatient Palliative Care.

Background: Family caregivers are essential to the care of patients with serious illness and supporting caregivers alongside patients is a core tenet of palliative care. While there is increasing recognition of the need to support family caregivers, there are limited resources to assess and support their needs in a systematic way in outpatient palliative care practice. Objectives: The aim of this study is to develop an approach to conducting assessments of routine needs and support of family caregivers in outpatient palliative care practice using a quality improvement framework. Setting: Seven, interdisciplinary, outpatient palliative care teams in California collaborated in this study. Measurements: Family caregivers were surveyed about levels of distress and support using a 10-point scale and asked about specific areas of need for support. Usefulness of a supportive caregiver resource was also measured on a 10-point scale, in addition to qualitative assessment of clinician satisfaction and feasibility of routine caregiver assessment and support. Results: Seven hundred thirty-six caregiver needs assessments were conducted and 44 supportive tool kits were distributed. A majority of family caregivers reported moderate or severe distress related to caregiving (score ≥4 on a 10-point scale). The most common sources of distress included emotional distress, worry caregiving was negatively impacting their own health, and planning for the future. Most caregivers reported feeling moderately or very well supported, most commonly by family, friends, and faith/spirituality. Caregivers rated the supportive tool kit an 8.4 on a 10-point usefulness scale and 92% would recommend it to others. Conclusions: We successfully developed and piloted practical clinical tools for routine family caregiver screening and support.

Evaluation of Services for the Commercial Sexual Exploitation of Children and Youth: A Scoping Review.

Commercial sexual exploitation (CSE) of youth is a public health issue with multiple negative consequences. Despite the complexities and comprehensiveness of service needs for youth experiencing CSE, the evidence base of effective services and programs lags far behind. This scoping review seeks to identify the most up-to-date evidence on programs for youth experiencing CSE that have been evaluated and found to be effective. We conducted a scoping review of current literature, including peer-reviewed articles as well as gray literature using a scientific approach to identify programs and service provisions specifically focused on youth experiencing CSE and examine empirical evidence for their effectiveness. A comprehensive search of five databases was completed in September 2020 then updated in April 2021 to identify relevant publications from January 1, 2000 to present. Additional program mining was conducted on evaluations of programs mentioned in the search results. A total of 3,597 citations from the database searches were screened for title and abstract and 190 citations were included for full-text review. The search process yielded 11 eligible articles with one additional report found through program mining. Identified programs targeted youth, providers, and consumers of CSE. While scientific rigor was not high, all included studies reported positive outcomes. Evidence base for effective services and programs is sparse. While more programs and services are being developed, studies should use rigorous research designs to test the effectiveness of these programs and services. Implications for practice and policy are discussed.

The long-term collateral consequences of juvenile justice involvement for females.

Introduction: Females are the fastest growing justice involved population in the United States, yet there is relatively little empirical research on the collateral consequences of juvenile justice involvement specifically for females. A growing body of empirical research underscores linkages between juvenile justice involvement and negative health and psychosocial outcomes, both in the short and long term. Method: The current study describes the long-term collateral consequences of juvenile justice involvement for females previously involved in the juvenile justice system, drawing from a longitudinal dataset of 166 women who were initially recruited in adolescence due to chronic and severe justice system involvement. Participants were 15 years-old on average at study enrollment and 35 years-old on average at the current assessment. This paper describes the adolescent and adult experiences of the sample, therefore depicting the developmental trajectories of risk and protective factors for females involved with juvenile justice. Results: As adults, 73% of the sample experienced arrest and 36% experienced incarceration. High rates of mental and physical health problems were reported, including that 50% of the sample met diagnostic criteria for posttraumatic stress disorder. Over 400 children were born to the sample, with high rates of documented intergenerational child welfare involvement. Discussion: Study findings are discussed in the context of best practices for supporting adolescent girls involved with the juvenile justice system.

Evolution of focal choroidal excavation in ABCA4-related retinopathy.

Purpose: To report long-term evolution of unilateral focal choroidal excavation in a patient with ABCA4-related retinopathy. Observations: A 51-year-old female with ABCA4-related retinopathy developed a small juxtafoveal defect in Bruch's membrane in a region of macular atrophy in her left eye. In follow-up, the defect widened and subsequently developed into a focal choroidal excavation. Over the next 8 years, serial optical coherence tomography imaging illustrated the conversion of the focal choroidal excavation from conforming subtype into non-conforming subtype with eventual macular hole formation. Conclusions and importance: The long-term follow-up of a patient with serial imaging highlights the potential dynamic nature of focal choroidal excavation in ABCA4-related retinopathy. Progressive retinal degeneration may influence focal choroidal excavation morphology and may promote macular hole formation.

Millennia-old coral holobiont DNA provides insight into future adaptive trajectories.

Ancient DNA (aDNA) has been applied to evolutionary questions across a wide variety of taxa. Here, for the first time, we utilized aDNA from millennia-old fossil coral fragments to gain new insights into a rapidly declining western Atlantic reef ecosystem. We sampled four Acropora palmata fragments (dated 4215 BCE to 1099 CE) obtained from two Florida Keys reef cores. From these samples, we established that it is possible both to sequence aDNA from reef cores and place the data in the context of modern-day genetic variation. We recovered varying amounts of nuclear DNA exhibiting the characteristic signatures of aDNA from the A. palmata fragments. To describe the holobiont sensu lato, which plays a crucial role in reef health, we utilized metagenome-assembled genomes as a reference to identify a large additional proportion of ancient microbial DNA from the samples. The samples shared many common microbes with modern-day coral holobionts from the same region, suggesting remarkable holobiont stability over time. Despite efforts, we were unable to recover ancient Symbiodiniaceae reads from the samples. Comparing the ancient A. palmata data to whole-genome sequencing data from living acroporids, we found that while slightly distinct, ancient samples were most closely related to individuals of their own species. Together, these results provide a proof-of-principle showing that it is possible to carry out direct analysis of coral holobiont change over time, which lays a foundation for studying the impacts of environmental stress and evolutionary constraints.

Evaluating and Validating the Classification Accuracy of a Screening Instrument to Assess Risk for Commercial Sexual Exploitation of Child Welfare-Involved Children and Adolescents.

OBJECTIVES: Identifying children and adolescents within child welfare at risk for commercial sexual exploitation (CSE) can ensure referrals to appropriate services. However, screening measures to understand the prevalence of CSE are missing in child welfare. We evaluated the classification accuracy of a screener developed for the purpose of this study, guided by the Sexual Exploitation among Youth (SEY) risk assessment framework used in practice with child welfare-involved young people, (1) to identify young people at high versus low risk for experiencing CSE and (2) to estimate the prevalence of CSE risk for child welfare-involved children and adolescents. METHODS: We used extant data from the National Survey of Child and Adolescent Well-being study with a nationally representative sample of children and adolescents aged 11-17 years (n = 1054) investigated by child welfare from February 2008 to April 2009. The 26-item screener showed acceptable reliability (α = .73) and test-criterion validity evidence using a CSE proxy outcome (ie, narrowly defined as being paid for sexual relations). We used the receiver-operating curve to classify risk and calculate the optimal cutoff score. RESULTS: Higher scores on the SEY screener (range, 0-20 points) increased the odds of experiencing CSE by 34%. The screener was good at discriminating CSE risk at the 6-point cutoff, with 26.7% of child welfare-involved young people identified as being at high risk for CSE. CONCLUSIONS: Given the absence of accurate prevalence rates of CSE risk in the population, a theoretical cutoff index using an established method can provide an objective decision on how to distinguish risk levels. Prevalence estimates for CSE risk highlight the need for systematic screening in child welfare to identify and provide services for young people at risk.

Diabetes Education and Support Tele-Visit Needs Differ in Duration, Content, and Satisfaction in Older Versus Younger Adults.

Background: Diabetes education and support are critical components of diabetes care. During the COVID-19 pandemic, when telemedicine took the place of in-person visits, remote Certified Diabetes Care and Education Specialist (CDCES) services were offered to address diabetes education and support. Specific needs for older adults, including the time required to provide education and support remotely, have not been previously reported. Methods: Adults with diabetes (primarily insulin-requiring) were referred to remote CDCESs. Utilization was individualized based on patient needs and preferences. Topics discussed, patient satisfaction, and time spent in each tele-visit were evaluated by diabetes type, age, sex, insurance type, glycosylated hemoglobin (HbA1c), pump, and continuous glucose monitor (CGM) usage. t-Tests, one-way analysis of variance, and Pearson correlations were employed as appropriate. Results: Adults (n = 982; mean age 48.4 years, 41.0% age ≥55 years) with type 1 diabetes (n = 846) and type 2 diabetes mellitus (n = 136, 86.0% insulin-treated), 50.8% female; 19.0% Medicaid, 29.1% Medicare, 48.9% private insurance; mean HbA1c 8.4% (standard deviation 1.9); and 46.6% pump and 64.5% CGM users had 2203 tele-visits with remote CDCESs over 5 months. Of those referred, 272 (21.7%) could not be reached or did not receive education/support. Older age (≥55 years), compared with 36-54 year olds and 18-35 year olds, respectively, was associated with more tele-visits (mean 2.6 vs. 2.2 and 1.8) and more time/tele-visits (mean 20.4 min vs. 16.5 min and 14.8 min; p < 0.001) as was coverage with Medicare (mean 2.8 visits) versus private insurance (mean 2.0 visits; p < 0.001) and lower participant satisfaction. The total mean time spent with remote CDCESs was 53.1, 37.4, and 26.2 min for participants aged ≥55, 36-54, and 18-35 years, respectively. During remote tele-visits, the most frequently discussed topics per participant were CGM and insulin pump use (73.4% and 49.7%). After adjustment for sex and diabetes type, older age was associated with lack of access to a computer, tablet, smartphone, or internet (p < 0.001), and need for more education related to CGM (p < 0.001), medications (p = 0.015), hypoglycemia (p = 0.044), and hyperglycemia (p = 0.048). Discussion: Most remote CDCES tele-visits were successfully completed. Older adults/those with Medicare required more time to fulfill educational needs. Although 85.7% of individual sessions lasted <30 min, which does not meet current Medicare requirements for reimbursement, multiple visits were common with a total time of >50 min for most older participants. This suggests that new reimbursement models are needed. Education/support needs of insulin-treated older adults should be a focus of future studies.

Examining Housing Instability Among Females Who Are System-Involved: Comparing Females With and Without Histories of Commercial Sexual Exploitation.

Females involved in child welfare (CW) or juvenile justice (JJ) systems are at-risk for commercial sexual exploitation (CSE). This study used administrative data from CW and JJ agencies in Los Angeles County to examine out-of-home care experiences and identify the types of homes that were associated with housing instability for females who experienced CSE. Demographic and case characteristics of females with a history of CSE and a matched sample without a reported history of CSE were compared using χ2 analyses and t-tests. Females with a history of CSE experienced significantly more housing instability compared to their matched counterparts. Housing instability was associated with leaving care without permission (LCWOP), and females were most likely to move because of LCWOP from group homes. These findings highlight the extremely unstable living situations for females with histories of CSE. Recommendations align with new federal policy, which aims to reduce reliance on group homes.

High-intermediate risk endometrial cancer: moving toward a molecularly based risk assessment profile.

In the USA, endometrial cancer (EMCA) incidence is increasing as the risk factors of obesity, diabetes, and hypertension become more prevalent. Although most EMCA is detected at an early stage and surgical intervention is curative, a subset of patients termed 'high-intermediate risk' (H-IR) experience an increased rate of recurrence. Unfortunately, adjuvant therapies in patients with H-IR EMCA have yet to increase overall survival. Historically, stratification of these patients from their low-risk counterparts incorporated clinical and pathologic findings. However, due to developments in molecular testing and genomic sequencing, tumor biomarkers are now being incorporated into the risk-assessment criteria in the hope of finding molecular profile(s) that could highlight treatment regimens that will increase patient survival. Since modern research aims to accurately identify patients with a higher risk of recurrence and develop effective interventions to improve patient survival, these molecular-based analyses could allow for an enhanced understanding of a patient's true risk of recurrence to facilitate the rise of personalized medicine. This review summarizes key clinical trials and recent advances in molecular and genomic profiles that have influenced current treatment regimens for patients with H-IR EMCA and laid the foundation for subsequent research.