Efficacy of Web-Based Interventions on Depression and Anxiety in Cancer Caregivers: A Systematic Review and Meta-Analysis.

OBJECTIVE: This study aimed to evaluate the effectiveness of web-based interventions in depression and anxiety among informal caregivers of patients with cancer. METHODS: Databases such as PubMed, Cochrane, Web of Science, Embase, CINAHL, and PsycINFO were systematically searched from inception to April 15, 2024. Eligible studies encompassed randomized controlled trials (RCTs) focusing on web-based interventions tailored to informal caregivers of patients with cancer. The effect size was calculated as the standardized mean difference (SMD) with a 95% confidence interval (CI) utilizing a random effects model. The risk of bias was assessed independently utilizing Cochrane's Risk of Bias Tool (version 2.0) for RCTs. RESULTS: A total of 12 RCTs were incorporated into this meta-analysis. Web-based interventions demonstrated a significant effect in ameliorating depression among informal caregivers of patients with cancer compared to the control group (SMD = -0.21, 95% CI = -0.36 to -0.05, p < 0.01, I2 = 15%). Additionally, a significant effect was also observed in alleviating anxiety (SMD = -0.20, 95% CI = -0.36 to -0.05, p = 0.77, I2 = 0%). CONCLUSIONS: Web-based interventions might be effective in reducing depression and anxiety among informal caregivers of patients with cancer. Nevertheless, several studies with an overall high risk of bias were included. As a result of the limited number and heterogeneity of the studies included in the subgroup analysis, deriving definitive conclusions on the most effective intervention components was challenging. Therefore, further studies incorporating high-quality research are warranted.

Material, Psychological, and Behavioral Financial Hardship Among Lesbian, Gay, and Bisexual Cancer Survivors in the United States.

PURPOSE: Driven by anti-LGBTQ+ stigma, emerging literature suggests that lesbian, gay, and bisexual (LGB) cancer survivors experience financial hardship (FH) more frequently than heterosexual survivors. However, few studies have used nationally representative samples to estimate this inequity. METHODS: National Health Interview Survey data from 2019 to 2022 were pooled and weighted. Outcomes included material, psychological, and behavioral FH. The behavioral domain was further broken down into subdomains including medical care, prescription medications, and mental health care. Multivariable logit models controlling for a variety of factors were used to generate LGB and heterosexual predicted probabilities and differential effects for each FH outcome. Stratified estimates were generated by sex and age groups. RESULTS: A total of N = 374 LGB and N = 12,757 heterosexual cancer survivors were included in this analysis. In adjusted analyses, LGB cancer survivors had significantly higher material (19%, 95% CI, 15 to 24 v 12%, 95% CI, 11 to 13; P = .004), psychological (44%, 95% CI, 38 to 51 v 37%, 95% CI, 36 to 38; P = .035), and behavioral (23%, 95% CI, 18 to 28 v 13%, 95% CI, 13 to 14; P < .0001) FH than heterosexual survivors. LGB cancer survivors also had higher medical behavioral (11%, 95% CI, 7 to 15 v 7%, 95% CI, 6 to 7; P = .030), prescription medication behavioral (14%, 95% CI, 10 to 19 v 10%, 95% CI, 9 to 10; P = .032), and mental health behavioral (9%, 95% CI, 6 to 13 v 3%, 95% CI, 3 to 4; P < .0001) FH than heterosexual survivors. Stratified estimates revealed young LGB cancer survivors had the highest probability of each outcome (material: 31%, 95% CI, 23 to 40; psychological: 58%, 95% CI, 50 to 66; behavioral: 45%, 95% CI, 36 to 53). CONCLUSION: In this nationally representative analysis, LGB cancer survivors experience substantial inequities in all FH outcomes. It is crucial that future FH interventional work should prioritize populations at the highest risk of FH, such as LGB cancer survivors.

Chronic Health Conditions, Disability, and Physical and Cognitive Limitations Among LGBTQ+ Cancer Survivors.

BACKGROUND: Cancer survivors are at high risk for chronic health conditions and physical and cognitive limitations. However, few studies have explored these outcomes among LGBTQ+ survivors. METHODS: We used pooled, weighted Behavioral Risk Factor Surveillance System data from 23 states that completed two specific modules from 2020-2022. We calculated age-adjusted prevalence for heart disease, asthma, COPD, depressive disorders, myocardial infarction, kidney disease, stroke, diabetes, hearing disability, vision disability, cognitive limitations, and difficulty walking, dressing, and running errands in LGBTQ+, lesbian, gay, or bisexual (LGB), transgender or gender non-conforming (TGNC), and non-LGBTQ+ cancer survivors. Four multivariable logistic regression models controlling for different factors were run for each outcome. RESULTS: Of 40,990 cancer survivors, 1,715 were LGBTQ+. LGBTQ+ survivors had significantly higher age-adjusted prevalence of all outcomes. The prevalence of all outcomes was highest among TGNC survivors except for depressive disorders and cognitive limitations. LGBTQ+ survivors had higher odds of reporting asthma (aOR: 1.5, 95%CI:1.2-1.9), depressive disorders (aOR: 1.9, 95%CI:1.6-2.4), kidney disease (aOR: 1.5, 95%CI:1.1-2.1), stroke (aOR: 1.7, 95%CI:1.3-2.3), diabetes (aOR: 1.3, 95%CI:1.0-1.6), vision disability (aOR: 1.6, 95%CI:1.2-2.2), cognitive limitations (aOR: 2.3, 95%CI:1.8-2.9), difficulty walking (aOR: 1.7, 95%CI:1.3-2.0), dressing (aOR: 2.0, 95%CI:1.5-2.7), and running errands (aOR: 1.6, 95%CI:1.3-2.1). In TGNC models, TGNC cancer survivors had increased odds of most outcomes. CONCLUSIONS: LGBTQ+ cancer survivors have an elevated burden of all chronic health conditions, disabilities, and limitations assessed. TGNC cancer survivors experience even higher burden of the same outcomes. IMPACT: Findings highlight substantial disparities regarding the health of LGBTQ+ cancer survivors.

"A strong reason why I enjoy coming to work": Clinician acceptability of a palliative and supportive care intervention (PACT) for older adults with acute myeloid leukemia and their care partners.

INTRODUCTION: Studies about clinician acceptability of integrative palliative care interventions in the inpatient and outpatient cancer settings are limited. In this study, we examined clinician acceptability of a NIH-funded interdisciplinary PAlliative and Supportive Care inTervention (PACT) for older adults with acute myeloid leukemia (AML) and their care partners that transcends both inpatient and outpatient settings. MATERIALS AND METHODS: Data was collected using semi-structured interviews with clinicians who were directly involved in PACT. The domains of the Theoretical Framework of Acceptability were used to guide the qualitative analysis. RESULTS: The clinicians consisted of occupational therapists (37%), physical therapists (25%), registered nurses (25%), and a clinical rehabilitation manager (13%). Five themes were identified in the thematic analysis: (1) Emotions and affect towards the intervention, (2) Intervention coherence and self-efficacy, (3) Barriers, burden, and opportunity costs of delivering the intervention, (4) Usefulness and effectiveness of the intervention, and (5) Recommendations to improve intervention delivery. DISCUSSION: All clinicians found the PACT intervention highly acceptable and expressed the positive impact of the intervention on job fulfillment and satisfaction. Our findings provide evidence to inform the delivery and implementation of future large scale integrative palliative care intervention trials.

Positive emotions co-experienced with strangers and acquaintances predict COVID-19 vaccination intentions through prosocial tendencies.

BACKGROUND: The efficacy of vaccination depends on its widespread adoption, making vaccine uptake not just a personal health behavior but also a prosocial one. Previous research has shown that everyday moments of co-experienced positive emotions (positivity resonance) are associated with higher prosocial tendencies, and these moments, in turn, prospectively predict people's pandemic hygiene behaviors. Yet, limited research has explored how moments of positivity resonance may have predicted greater COVID-19 vaccine intentions during the early months of the pandemic. METHODS: We longitudinally surveyed a national U.S. sample across four weeks during the fall of 2020. We tested the hypothesis that positivity resonance with strangers and acquaintances indirectly predicts COVID-19 vaccine intentions, as statistically mediated by prosocial tendencies. We also aimed to replicate the indirect effects of positivity resonance on hygiene behaviors (such as mask wearing and hand washing), effects that have been demonstrated in previous research. RESULTS: In a pre-registered structural equation model, we found that perceived positivity resonance experienced with strangers and acquaintances prospectively predicted prosocial tendencies, which in turn amplified people's COVID-19 vaccine intentions (ß = 0.053) and hygiene behaviors - i.e., social distancing (ß = 0.032), mask wearing (ß = 0.027), hand washing (ß = 0.049). CONCLUSIONS: Understanding the effects of high-quality social interactions with strangers and acquaintances on vaccine intentions and hygiene behaviors is critical, particularly given the likelihood of emerging pandemics and novel vaccines. We discuss theoretical and practical implications related to perceived positivity resonance, prosocial tendencies, and vaccination uptake for novel vaccines.

Expanding Leadership and Professional Development Opportunities for Oncology Nurse Practitioners.

Nurse practitioner (NP) involvement in professional organizations improves clinical practice, patient outcomes, and health care policy. Results of a survey for a local professional nursing organization showed a need for more NP-level education and NP mentorship and leadership training. Findings were applied to develop a leadership initiative through an NP-led continuing education program. At the conclusion of the program, NP presenters completed a survey. The NP presenters agreed that participating in this program and the mentoring that was provided helped them prepare for their sessions, improve their leadership skills, and prepare for additional speaking engagements. Additionally, each session's attendees completed evaluation surveys. Results from program attendees indicated a high level of agreement about meeting learning objectives in sessions and the effectiveness of the NP presenters. This innovative program may be modeled across a variety of nursing specialties, settings, and organizations to enhance NP professional development and support nursing-led continuing education. [J Contin Educ Nurs. 2024;55(2):94-100.].

Caring for Children in Relation to Financial Hardship, Advance Care Planning, and Genetic Testing Among Adolescent and Young Adults with Cancer.

Purpose: When a cancer diagnosis coincides with caring for children, it may influence the financial impacts of cancer and decisions to pursue advance care planning (ACP) or genetic testing. We examined associations between caring for children and financial hardship, ACP, and genetic testing among female adolescent and young adult (AYA) cancer survivors in North Carolina and California. Methods: Participants were diagnosed at ages 15-39 years with breast, melanoma, gynecologic, lymphoma, or thyroid cancer during 2004-2016. We estimated adjusted prevalence differences (aPDs) and ratios (aPRs) for each outcome by child caring status using marginal structural binomial regression models. Results: Among 1595 women ages 19-54 years at survey (median = 7 years since diagnosis), 819 (51.3%) reported that they were caring for children at diagnosis. Women caring for children had a higher prevalence of material financial hardship (e.g., medical debt; 30% vs. 21.9%; aPD = 9%, 95% confidence interval [CI]: 3 to 14; aPR = 1.39, 95% CI: 1.12 to 1.72) but similar levels of psychological financial hardship compared to noncaregivers. Women caring for children were more likely to complete ACPs (42.2% vs. 30.7%; aPD = 9%, 95% CI: 3 to 16; aPR = 1.30, 95% CI: 1.08 to 1.57). Among the 723 survivors of breast, endometrial, and ovarian cancer, the prevalence of genetic testing was higher among women caring for children (89%) than noncaregivers (81%); this difference was not statistically significant. Conclusion: Women caring for children at diagnosis may be at elevated risk for adverse financial outcomes and may benefit from additional financial navigation support. Childcare responsibilities may further complicate health decision-making for AYAs diagnosed with cancer.

Inequities Among Cancer Caregivers with Diverse Identities: A Review of the Literature and Future Directions.

PURPOSE OF REVIEW: The number of older adults with cancer relying on support from caregivers continues to increase. Health disparities in older adults with cancer often extend to their caregivers. This review aims to assess the state of cancer caregiving research in historically underrepresented diverse populations and provide recommendations for future research and policy. RECENT FINDINGS: Research on caregivers of older adults with cancer from diverse backgrounds has primarily been descriptive. Health disparities for historically underrepresented caregivers (LGBTQ + , BIPOC, rural, young adults, youth) exist across several dimensions (e.g., financial, mental, and physical health, and access to caregiver support). Few published studies have closely examined the unique experiences of these caregivers nor provided culturally appropriate tailored interventions. Health equity research within caregiving populations is in its infancy. Priorities for future work should focus on identifying modifiable targets for intervention, changing systems-level processes in acknowledging and supporting caregivers, and creating policies that reduce financial inequities of caregiving.

Piloting HealthScore: Feasibility and acceptability of a clinically integrated health coaching program for people living with cancer.

BACKGROUND: Cancer supportive care interventions often have limited generalizability, goal misalignment, and high costs. We developed and piloted a health coaching intervention, UNC HealthScore, in patients undergoing cancer treatment (ClinicalTrials.gov identifier NCT04923997). We present feasibility, acceptability, and preliminary outcome data. METHODS: HealthScore is a six-month, theory-based, multicomponent intervention delivered through participant-driven coaching sessions. For the pilot study, participants were provided a Fitbit, responded to weekly symptom and physical function digital surveys, and met with a health coach weekly to develop and monitor goals. Coaching notes were discussed in weekly interdisciplinary team meetings and provided back to the treating oncology team. Symptom alerts were monitored and triaged through a study resource nurse to relevant supportive care services. Feasibility was determined based on intervention enrollment and completion. Acceptability was based on satisfaction with coaching and Fitbit-wearing and was informed by semistructured exit interviews. Outcomes evaluated for signs of improvement included several PROMIS (Patient-Reported Outcomes Measurement Information System) measures, including the primary intervention target, physical function. RESULTS: From May 2020 to March 2022, 50 participants completed the single-arm pilot. Feasibility was high: 66% enrolled and 71% completed the full intervention. Participants reported an average of 4.8 and 4.7 (out of 5) on the acceptability of coaching calls and using the Fitbit, respectively. Physical function scores rose 3.1 points (SE = 1.1) from baseline to 3 months, and 4.3 (SE = 1.0) from baseline to 6 months, above established minimal clinically important difference (MCID). Improvements above MCID were also evident in anxiety and depression, and smaller improvements were demonstrated for emotional support, social isolation, cognitive function, symptom burden, and self-efficacy. DISCUSSION: HealthScore shows feasibility, acceptability, and promising preliminary outcomes. Randomized studies are underway to determine the efficacy of preserving physical function in patients with advanced cancer.

Perspectives of caregivers of older adults with acute myeloid leukemia during initial hypomethylating agents and venetoclax chemotherapy.

BACKGROUND: Older adults with AML commonly receive a hypomethylating agent (HMA) as first-line therapy. The addition of venetoclax (VEN) to HMAs has been shown to improve remission rates and overall survival. The use of combination therapy (HMA + VEN) requires frequent follow-up, results in longer infusion times, and likely increases caregiver responsibility at home. We describe experiences of informal caregivers (family/friends) providing care to older adults with AML receiving HMA + VEN. METHODS: Fourteen caregivers of older adults with AML receiving HMA + VEN (September 2020 to September 2021) were recruited as part of a control group of an ongoing NIH-funded clinical trial. Semi-structured interviews were conducted to gain initial insight into caregiver experiences at the start of HMA + VEN treatment. Two researchers analyzed the data using thematic content analysis. Data saturation occurred when no new themes were found in subsequent interviews, but all interviews were coded and synthesized. RESULTS: Of the 14 caregivers interviewed, the majority were spouses (n = 10), female (n = 13), and aged 45 to 83 (median age 65). We identified five themes: (1) the impact of an AML diagnosis in older adulthood, (2) care recipient condition changes, (3) perspectives of caregiving roles and tasks, (4) factors influencing caregiving experiences, and (5) support system roles. CONCLUSIONS AND IMPLICATIONS: Caregivers for older adults with AML report a range of experiences navigating health systems, caregiving responsibilities, and resource needs. The risk for caregiver burden and unmet needs should be addressed to improve caregivers' abilities to provide care.

Psychological processing among caregivers of allogeneic bone marrow transplant recipients: Qualitative findings from a longitudinal study.

PURPOSE: To describe caregiver psychological processing during the 12 weeks after transplant and the potential role of positive emotions in caregiving experiences. METHODS: We conducted a longitudinal qualitative descriptive study and interviewed 11 BMT caregivers monthly for 12-weeks post-transplant about their experiences and psychological processing. We analyzed 38 interviews using directed content analysis based on guiding theories and inductive in vivo coding to develop themes. RESULTS: The majority of participants appraised caregiving as a challenge that needed to be met. Caregivers described feeling positive emotions throughout the time after transplant (gratitude, interest, and hope). We identified two new themes: mirroring (caregiver feelings reflecting patient status) and emotion regulation (hiding negative emotions and displaying positive emotions when with the patient). IMPLICATIONS: Findings provide further evidence that interventions focused on emotion regulation and positive emotion experiences during caregiving to reduce the negative effects of caregiving related stress may be promising.

A Visual Case-Oriented Analysis of Stress-Related Symptoms in Caregivers of Allogeneic Bone Marrow Transplantation Recipients.

OBJECTIVES: To describe trends in caregiver stress and stress-related symptoms (anxiety, depression, fatigue, and sleep disturbance) across 12 weeks post-transplantation. SAMPLE & SETTING: 11 caregivers were recruited from a National Cancer Institute-designated comprehensive cancer center's bone marrow transplantation (BMT) outpatient clinic in the southeastern United States. METHODS & VARIABLES: A visual case-oriented analysis was conducted on data from 11 caregivers' weekly self-reported data to identify trends after allogeneic BMT. RESULTS: The authors identified three primary trends as follows: U-shaped (highest symptoms at start of transplantation and end of study; n = 3), negatively sloped (highest symptoms at beginning of transplantation and decreasing over time; n = 2), and V-shaped predischarge (highest symptoms at start of transplantation and right before discharge home; n = 4). Two caregivers did not have postdischarge data because of patient death prior to study completion. IMPLICATIONS FOR NURSING: Caregivers may benefit from additional support to manage their stress-related symptoms at the start of transplantation and just before discharge.

Exploring Experiences of Bereaved Caregivers of Older Adult Patients With Acute Myeloid Leukemia.

Caregivers of older adults with acute myeloid leukemia (AML) are requiring more support now that novel, nonintensive therapies, such as hypomethylating agents and venetoclax, are shifting the burden of care to the outpatient setting. Early findings from a larger study describe supportive care needs from the perspective of bereaved caregivers that align with existing research, informing the development of best practices for oncology nurses who support caregivers of older adults with AML.

Identification of Sclareol As a Natural Neuroprotective Cav 1.3-Antagonist Using Synthetic Parkinson-Mimetic Gene Circuits and Computer-Aided Drug Discovery.

Parkinson's disease (PD) results from selective loss of substantia nigra dopaminergic (SNc DA) neurons, and is primarily caused by excessive activity-related Ca2+ oscillations. Although L-type voltage-gated calcium channel blockers (CCBs) selectively inhibiting Cav 1.3 are considered promising candidates for PD treatment, drug discovery is hampered by the lack of high-throughput screening technologies permitting isoform-specific assessment of Cav-antagonistic activities. Here, a synthetic-biology-inspired drug-discovery platform enables identification of PD-relevant drug candidates. By deflecting Cav-dependent activation of nuclear factor of activated T-cells (NFAT)-signaling to repression of reporter gene translation, they engineered a cell-based assay where reporter gene expression is activated by putative CCBs. By using this platform in combination with in silico virtual screening and a trained deep-learning neural network, sclareol is identified from a essential oils library as a structurally distinctive compound that can be used for PD pharmacotherapy. In vitro studies, biochemical assays and whole-cell patch-clamp recordings confirmed that sclareol inhibits Cav 1.3 more strongly than Cav 1.2 and decreases firing responses of SNc DA neurons. In a mouse model of PD, sclareol treatment reduced DA neuronal loss and protected striatal network dynamics as well as motor performance. Thus, sclareol appears to be a promising drug candidate for neuroprotection in PD patients.

Comparable Impairment of Vascular Endothelial Function by a Wide Range of Electronic Nicotine Delivery Devices.

INTRODUCTION: Electronic nicotine delivery systems (ENDS; ie, vaping devices) such as e-cigarettes, heated tobacco products, and newer coil-less ultrasonic vaping devices are promoted as less harmful alternatives to combustible cigarettes. However, their cardiovascular effects are understudied. We investigated whether exposure to aerosol from a wide range of ENDS devices, including a new ultrasonic vaping device, impairs endothelial function. AIMS AND METHODS: We measured arterial flow-mediated dilation (FMD) in rats (n = 8/group) exposed to single session of 10 cycles of pulsatile 5-second exposure over 5 minutes to aerosol from e-liquids with and without nicotine generated from a USONICIG ultrasonic vaping device, previous generation e-cigarettes, 5% nicotine JUUL pods (Virginia Tobacco, Mango, Menthol), and an IQOS heated tobacco product; with Marlboro Red cigarette smoke and clean air as controls. We evaluated nicotine absorption and serum nitric oxide levels after exposure, and effects of different nicotine acidifiers on platelet aggregation. RESULTS: Aerosol/smoke from all conditions except air significantly impaired FMD. Serum nicotine varied widely from highest in the IQOS group to lowest in USONICIG and previous generation e-cig groups. Nitric oxide levels were not affected by exposure. Exposure to JUUL and similarly acidified nicotine salt e-liquids did not affect platelet aggregation rate. Despite lack of heating coil, the USONICIG under airflow conditions heated e-liquid to ~77°C. CONCLUSIONS: A wide range of ENDS, including multiple types of e-cigarettes with and without nicotine, a heated tobacco product, and an ultrasonic vaping device devoid of heating coil, all impair FMD after a single vaping session comparably to combusted cigarettes. IMPLICATIONS: The need to understand the cardiovascular effects of various ENDS is of timely importance, as we have seen a dramatic increase in the use of these products in recent years, along with the growing assumption among its users that these devices are relatively benign. Our conclusion that a single exposure to aerosol from a wide range of ENDS impairs endothelial function comparably to cigarettes indicates that vaping can cause similar acute vascular functional impairment to smoking and is not a harmless activity.

Mesenchymal stromal cell-derived extracellular vesicles reduce lung inflammation and damage in nonclinical acute lung injury: Implications for COVID-19.

Mesenchymal stem cell derived extracellular vesicles (MSC-EVs) are bioactive particles that evoke beneficial responses in recipient cells. We identified a role for MSC-EV in immune modulation and cellular salvage in a model of SARS-CoV-2 induced acute lung injury (ALI) using pulmonary epithelial cells and exposure to cytokines or the SARS-CoV-2 receptor binding domain (RBD). Whereas RBD or cytokine exposure caused a pro-inflammatory cellular environment and injurious signaling, impairing alveolar-capillary barrier function, and inducing cell death, MSC-EVs reduced inflammation and reestablished target cell health. Importantly, MSC-EV treatment increased active ACE2 surface protein compared to RBD injury, identifying a previously unknown role for MSC-EV treatment in COVID-19 signaling and pathogenesis. The beneficial effect of MSC-EV treatment was confirmed in an LPS-induced rat model of ALI wherein MSC-EVs reduced pro-inflammatory cytokine secretion and respiratory dysfunction associated with disease. MSC-EV administration was dose-responsive, demonstrating a large effective dose range for clinical translation. These data provide direct evidence of an MSC-EV-mediated improvement in ALI and contribute new insights into the therapeutic potential of MSC-EVs in COVID-19 or similar pathologies of respiratory distress.

Healthy Lifestyle Behaviors: Nursing Considerations for Social Determinants of Health.

BACKGROUND: Nurses develop meaningful and deep connections with patients, making them particularly skilled to consider how social determinants of health (SDOH) affect patients. SDOH include one's neighborhood and built environment, health and health care, social and community context, education, and economic stability. Consideration of SDOH, in addition to individual factors, allows nurses to better support patient engagement in health behaviors. OBJECTIVES: This article aims to explore how nurses consider SDOH when talking about health behaviors with patients and to provide case exemplars of how incorporation of the SDOH can be increased in holistic, patient-centered nursing care. METHODS: A secondary data analysis was conducted to identify how practicing oncology nurses (N = 75) take SDOH into account when talking about physical activity with patients. FINDINGS: Of the 124 considerations that nurses made when talking about physical activity with patients, most did not relate to SDOH.

Zona incerta subpopulations differentially encode and modulate anxiety.

Despite recent clinical observations linking the zona incerta (ZI) to anxiety, little is known about whether and how the ZI processes anxiety. Here, we subject mice to anxious experiences and observe an increase in ZI c-fos­labeled neurons and single-cell calcium activity as well as an efficient effect of ZI infusion of diazepam, a classical anxiolytic drug. We further identify that somatostatin (SOM)­, calretinin (CR)­, and vesicular glutamate transporter-2 (Vglut2)­expressing cells display unique electrophysiological profiles; however, they similarly respond to anxiety-provoking stimuli and to diazepam. Optogenetic manipulations reveal that each of these ZI neuronal populations triggers specific anxiety-related behavioral phenotypes. Activation of SOM-expressing neurons induced anxiety, while photoactivation of CR-positive cells and photoinhibition of Vglut2-expressing neurons produce anxiolysis. Furthermore, activation of CR- and Vglut2-positive cells provokes rearing and jumps, respectively. Our findings provide the first experimental evidence that ZI subpopulations encode and modulate different components of anxiety.

Release of stem cells from quiescence reveals gliogenic domains in the adult mouse brain.

Quiescent neural stem cells (NSCs) in the adult mouse ventricular-subventricular zone (V-SVZ) undergo activation to generate neurons and some glia. Here we show that platelet-derived growth factor receptor beta (PDGFRß) is expressed by adult V-SVZ NSCs that generate olfactory bulb interneurons and glia. Selective deletion of PDGFRß in adult V-SVZ NSCs leads to their release from quiescence, uncovering gliogenic domains for different glial cell types. These domains are also recruited upon injury. We identify an intraventricular oligodendrocyte progenitor derived from NSCs inside the brain ventricles that contacts supraependymal axons. Together, our findings reveal that the adult V-SVZ contains spatial domains for gliogenesis, in addition to those for neurogenesis. These gliogenic NSC domains tend to be quiescent under homeostasis and may contribute to brain plasticity.

GREB1: An evolutionarily conserved protein with a glycosyltransferase domain links ERα glycosylation and stability to cancer.

What covalent modifications control the temporal ubiquitination of ERα and hence the duration of its transcriptional activity remain poorly understood. We show that GREB1, an ERα-inducible enzyme, catalyzes O-GlcNAcylation of ERα at residues T553/S554, which stabilizes ERα protein by inhibiting association with the ubiquitin ligase ZNF598. Loss of GREB1-mediated glycosylation of ERα results in reduced cellular ERα levels and insensitivity to estrogen. Higher GREB1 expression in ERα+ve breast cancer is associated with greater survival in response to tamoxifen, an ERα agonist. Mice lacking Greb1 exhibit growth and fertility defects reminiscent of phenotypes in ERα-null mice. In summary, this study identifies GREB1, a protein with an evolutionarily conserved domain related to DNA-modifying glycosyltransferases of bacteriophages and kinetoplastids, as the first inducible and the only other (apart from OGT) O-GlcNAc glycosyltransferase in mammalian cytoplasm and ERα as its first substrate.