Barriers and facilitators to care for agitation and/or aggression among persons living with dementia in long-term care.

BACKGROUND: Agitation and/or aggression affect up to 60% of persons living with dementia in long-term care (LTC). It can be treated via non-pharmacological and pharmacological interventions, but the former are underused in clinical practice. In the literature, there is currently a lack of understanding of the challenges to caring for agitation and/or aggression among persons living with dementia in LTC. This study assesses what barriers and facilitators across the spectrum of care exist for agitation and/or aggression among people with dementia in LTC across stakeholder groups. METHODS: This was a qualitative study that used semi-structured interviews among persons involved in the care and/or planning of care for people with dementia in LTC. Participants were recruited via purposive and snowball sampling, with the assistance of four owner-operator models. Interviews were guided by the Theoretical Domains Framework and transcribed and analyzed using Framework Analysis. RESULTS: Eighteen interviews were conducted across 5 stakeholder groups. Key identified barriers were a lack of agitation and/or aggression diagnostic measures, limited training for managing agitation and/or aggression in LTC, an overuse of physical and chemical restraints, and an underuse of non-pharmacological interventions. Facilitators included using an interdisciplinary team to deliver care and having competent and trained healthcare providers to administer non-pharmacological interventions. CONCLUSIONS: This study advances care for persons living with dementia in LTC by drawing attention to unique and systemic barriers present across local and national Canadian LTC facilities. Findings will support future implementation research endeavours to eliminate these identified barriers across the spectrum of care, thus improving care outcomes among people with dementia in LTC.

Microaggressions in Nursing.

How to address these behaviors to promote health equity and inclusion.

The impact of a hospital-based special care unit on behavioural and psychological symptoms in older people living with dementia.

BACKGROUND: Hospital patients with behavioural and psychological symptoms of dementia (BPSD) are vulnerable to a range of adverse outcomes. Hospital-based Special Care Units (SCUs) are secure dementia-enabling environments providing specialised gerontological care. Due to a scarcity of research, their value remains unconfirmed. OBJECTIVE: To compare hospital based SCU management of BPSD with standard care. DESIGN: Single-case multiple baseline design. SETTING AND PARTICIPANTS: One-hundred admissions to an 8-bed SCU over 2 years in a large Australian public hospital. METHODS: Repeated measures of BPSD severity were undertaken prospectively by specialist dementia nurses for patients admitted to a general ward (standard care) and transferred to the SCU. Demographic and other clinical data, including diagnoses, medication use, and care-related outcomes were obtained from medical records retrospectively. Analysis used multilevel models to regress BPSD scores onto care-setting outcomes, adjusting for time and other factors. RESULTS: When receiving standard care, patients' BPSD severity was 6.8 (95% CI 6.04-7.64) points higher for aggression, 15.6 (95% CI 13.90-17.42) points higher for the neuropsychiatric inventory, and 5.8 (95% CI 5.14-6.50) points higher for non-aggressive agitation compared to SCU. Patients receiving standard care also experienced increased odds for patient-to-nurse violence (OR 2.61, 95% CI 1.67-4.09), security callouts (OR 5.39 95% CI 3.40-8.52), physical restraint (OR 17.20, 95% CI 7.94-37.25) and antipsychotic administration (OR 3.41, 95% CI 1.60-7.24). CONCLUSION: Clinically significant reductions in BPSD and psychotropic administration were associated with SCU care relative to standard ward care. These results suggest more robust investigation of hospital SCUs, and dementia-enabling design are warranted.

Freshwater trematodes differ from marine trematodes in patterns connected with division of labor.

Background: Prior research suggests that trematode rediae, a developmental stage of trematode parasites that reproduce clonally within a snail host, show evidence of division of labor (DOL). Single-species infections often have two morphologically distinct groups: small rediae, the 'soldiers', are active, aggressive, and do not appear to reproduce; large rediae, the 'reproductives', are larger, sluggish, and full of offspring. Most data supporting DOL come from trematodes infecting marine snails, while data from freshwater trematodes are more limited and generally do not supported DOL. The shorter lifespan typical of freshwater snails may partially explain this difference: defending a short-lived host at the expense of reproduction likely provides few advantages. Here, we present data from sixty-one colonies spanning twenty species of freshwater trematode exploring morphological and behavioral patterns commonly reported from marine trematodes believed to have DOL. Methods: Trematode rediae were obtained from sixty-one infected snails collected in central Vermont, USA. A portion of the COI gene was sequenced to make tentative species identifications ('COI species'). Samples of rediae were photographed, observed, and measured to look for DOL-associated patterns including a bimodal size distribution, absence of embryos in small rediae, and pronounced appendages and enlarged pharynges (mouthparts) in small rediae. Additional rediae were used to compare activity levels and likelihood to attack heterospecific trematodes in large vs. small rediae. Results: Many of the tests for DOL-associated patterns showed mixed results, even among colonies of the same COI species. However, we note a few consistent patterns. First, small rediae of most colonies appeared capable of reproduction, and we saw no indication (admittedly based on a small sample size and possibly insufficient attack trial methodology) that small rediae were more active or aggressive. This differs from patterns reported from most marine trematodes. Second, the small rediae of most colonies had larger pharynges relative to their body size than large rediae, consistent with marine trematodes. We also observed that colonies of three sampled COI species appear to produce a group of large rediae that have distinctly large pharynges. Conclusions: We conclude that these freshwater species likely do not have a group of specialized non-reproductive soldiers because small rediae of at least some colonies in almost every species do appear to produce embryos. We cannot rule out the possibility that small rediae act as a temporary soldier caste. We are intrigued by the presence of rediae with enlarged pharynges in some species and propose that they may serve an adaptive role, possibly similar to the defensive role of small 'soldier' rediae of marine trematodes. Large-pharynx rediae have been documented in other species previously, and we encourage future efforts to study these large-pharynx rediae.

The effectiveness of Forensic Outpatient Systemic Therapy in the treatment of juvenile antisocial behavior: A study protocol of a Multiple Case Experimental Design.

BACKGROUND: Juvenile antisocial behavior can have long-lasting and devastating effects for juveniles themselves, victims, and society. Evidence-based treatment is vital. Forensic Outpatient Systemic Therapy (Forensische Ambulante Systeem Therapie; FAST) is a promising treatment for juveniles showing severe antisocial behavior including aggression, (domestic) violence, and delinquent behavior. FAST has a flexible intensity and length, addresses individual and systemic risk and protective factors, and is responsive to the abilities of the client (system), intervention characteristics all considered crucial for effective treatment. The current study will investigate whether FAST is effective in reducing aggression of the juvenile, reaching client formulated subgoals, and improving family functioning. Processes of change will be examined, as well as mediation by reaching client formulated subgoals and improved family functioning. METHODS: A Multiple Case Experimental Design (MCED) with an ABC design will be performed (A = baseline, B = intervention, and C = follow-up). Juveniles with primary aggression and/or anger problems (N = 15) and their caregiver(s) will be recruited. Data collection will consist of self-report questionnaires and case file analysis. Participants fill out frequent short self-report questionnaires (twice a week during phase A, every other week during phase B, and every week during phase C) and two main questionnaires at the start of the intervention and immediately after intervention end, thereby covering a period of 5 to 11 months. Both visual and statistical analyses will be performed. DISCUSSION: This study will generate robust knowledge and inform clinical practice on the effectiveness, processes of change, and mediating mechanisms of FAST, aiming to improve the treatment of future families within youth forensic care. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov on 28/08/2023, protocol ID 60-63600-98-1138a.

Gendered racial microaggressions and stress in PAs who are Black women.

OBJECTIVE: This mixed-methods study explored whether physician associates/assistants (PAs) who are Black women (for brevity, called Black women PAs throughout this article) experience gendered racial microaggressions and whether these experiences correlated with psychologic distress. The phrase Black women encompasses those who identify with the sociocultural roles, behaviors, and expressions of being a Black woman. METHODS: We conducted an online survey of Black women PAs using the Gendered Racial Microaggressions Scale during a 2-month period in 2019. RESULTS: Black women PAs experienced gendered racial microaggressions in clinical settings. Gendered racial microaggressions were correlated with stress, being silenced and marginalized, and assumptions of beauty and sexual objectification. No correlations were found between stress and the angry Black woman and strong Black woman variables. CONCLUSIONS: This study revealed that Black women have interlocking forms of oppression related to their race and gender, which are associated with psychologic distress. Awareness of these occurrences can reduce the unknowing perpetuation of gendered racial microaggressions and create cultural awareness practices.

Borderline personality disorder and aggressive behavior: A study based on the DSM-5 alternative model.

INTRODUCTION: Unplanned reactive aggressive acts are a clinical feature of particular interest in patients with borderline personality disorder (BPD). The early identification of personality traits correlated to aggressive behavior is certainly desirable in BDP populations. This study analyzes a clinical sample of 122 adult outpatients with BPD referred to Adult Mental Health Services of the Department of Mental Health of Bologna, in Italy. METHODS: The study examines the relationship with personality facets of the DSM-5 alternative model for personality disorders (AMPD), Personality Inventory for DSM (PID-5), with respect to the four main components of aggression measured by the Aggression Questionnaire (AQ): hostility, anger, verbal and physical aggression. Using robust regression models, the relationships between PID-5 facets and domains and the aggression components under consideration were identified. RESULTS: Verbal and physical aggression in our sample of BPD outpatients is mainly associated to PID-5 antagonism domain. Physically aggressive behavior is also related to callousness facet. CONCLUSIONS: The traits most consistently associated with aggression were the domain of Antagonism and the facet of Hostility. The study findings highlight the need for clinicians working with individuals with BPD to pay particular attention to traits of hostility, callousness, and hostility to understand aggression.

Green Space and Internalizing or Externalizing Symptoms Among Children.

Importance: Evidence suggests that living near green space supports mental health, but studies examining the association of green space with early mental health symptoms among children are rare. Objective: To evaluate the association between residential green space and early internalizing (eg, anxiety and depression) and externalizing (eg, aggression and rule-breaking) symptoms. Design, Setting, and Participants: Data for this cohort study were drawn from the Environmental Influences on Child Health Outcomes cohort; analysis was conducted from July to October 2023. Children born between 2007 and 2013 with outcome data in early (aged 2-5 years) and/or middle (aged 6-11 years) childhood who resided in 41 states across the US, drawing from clinic, hospital, and community-based cohorts, were included. Cohort sites were eligible if they recruited general population participants and if at least 30 children had outcome and residential address data to measure green space exposure. Nine cohorts with 13 sites met these criteria. Children diagnosed with autism or developmental delay were excluded, and 1 child per family was included. Exposures: Green space exposure was measured using a biannual (ie, summer and winter) Normalized Difference Vegetation Index, a satellite image-based indicator of vegetation density assigned to monthly residential history from birth to outcome assessment. Main Outcome and Measures: Child internalizing and externalizing symptoms were assessed using the Child Behavior Checklist for Ages 1½ to 5 or 6 to 18. The association between green space and internalizing and externalizing symptoms was modeled with multivariable linear regression using generalized estimating equations, adjusting for birthing parent educational level, age at delivery, child sex, prematurity, and neighborhood socioeconomic vulnerability. Models were estimated separately for early and middle childhood samples. Results: Among 2103 children included, 1061 (50.5%) were male; 606 (29.1%) identified as Black, 1094 (52.5%) as White, 248 (11.9%) as multiple races, and 137 (6.6%) as other races. Outcomes were assessed at mean (SD) ages of 4.2 (0.6) years in 1469 children aged 2 to 5 years and 7.8 (1.6) years in 1173 children aged 6 to 11 years. Greater green space exposure was associated with fewer early childhood internalizing symptoms in fully adjusted models (b = -1.29; 95% CI, -1.62 to -0.97). No associations were observed between residential green space and internalizing or externalizing symptoms in middle childhood. Conclusions and Relevance: In this study of residential green space and children's mental health, the association of green space with fewer internalizing symptoms was observed only in early childhood, suggesting a sensitive period for nature exposure. Policies protecting and promoting access to green space may help alleviate early mental health risk.

Child-to-Parent Violence ­ Der Blinde Fleck in der Forschung zur familiären Gewalt? Ein Systematic Review / Child-to-Parent Violence ­The Blind Spot in Research on Family Violence? A Systematic Review.

Child-to-Parent Violence -The Blind Spot in Research on Family Violence? A Systematic Review Child-to-parent violence (CPV) is a phenomenon that has received little attention in the German scientific community. With this paper, the authors present the international state of research in the context of a systematic review. By means of a search a dataset of 317 scientific publications for the period 2012-2022 was identified at August 2022. After applying the inclusion and exclusion criteria, 14 studies were finally defined and analyzed in detail. Based on the analysis, the following variables are highlighted as outcomes: Forms of CPV, prevalence, age and gender of individuals performing CPV, risk and protective factors, the direction of CPV within family constellations as well as external conditioning factors of CPV.The results show that there are some concrete findings in research regarding these variables, particularly in the area of risk and protective factors. An initial systematization of violent behaviour in the context of CPV can also be derived fromthe current state of research. At the same time, however, there are still clear gaps in research, e. g. in terms of prevalence, which is mainly due to very different definitions of "violence". This applies both with regard to the international state of research, but especially with regard to the situation in German-speaking countries.

Neural correlates of aggression outcome expectation and their association with aggression: A voxel-based morphometry study.

BACKGROUND: Aggression outcome expectation is an important cognitive factor of aggression. Discovering the neural mechanism of aggression outcome expectation is conducive to developing aggression research. However, the neural correlates underlying aggression outcome expectation and its effect remain elusive. METHODS: We utilized voxel-based morphometry (VBM) to unravel the neural architecture of aggression outcome expectation measured by the Social Emotional Information Processing Assessment for Adults and its relationship with aggression measured by the Buss Perry Aggression Questionnaire in a sample of 185 university students (114 female; mean age = 19.94 ± 1.62 years; age range: 17-32 years). RESULTS: We found a significantly positive correlation between aggression outcome expectation and the regional gray matter volume (GMV) in the right middle temporal gyrus (MTG) (x = 55.5, y = -58.5, z = 1.5; t = 3.35; cluster sizes = 352, p < 0.05, GRF corrected). Moreover, aggression outcome expectation acted as a mediator underlying the association between the right MTG volume and aggression. CONCLUSIONS: These results revealed the neural correlates of aggression outcome expectation and its effect on aggression for the first time, which may contribute to our understanding of the cognitive neural mechanism of aggression and potentially identifying neurobiological markers for aggression.

Genetic Variation in Male Aggression Is Influenced by Genotype of Prior Social Partners in Drosophila melanogaster.

AbstractSocial behaviors can be influenced by the genotypes of interacting individuals through indirect genetic effects (IGEs) and can also display developmental plasticity. We investigated how developmental IGEs, which describe the effects of a prior social partner's genotype on later behavior, can influence aggression in male Drosophila melanogaster. We predicted that developmental IGEs cannot be estimated by simply extending the effects of contextual IGEs over time and instead have their own unique effects on behavior. On day 1 of the experiment, we measured aggressive behavior in 15 genotypic pairings (n=600 males). On day 2, each of the males was paired with a new opponent, and aggressive behavior was again measured. We found contextual IGEs on day 1 of the experiment and developmental IGEs on day 2 of the experiment: the influence of the day 1 partner's genotype on the focal individual's day 2 behavior depended on the genotypic identity of both the day 1 partner and the focal male. Importantly, the developmental IGEs in our system produced fundamentally different dynamics than the contextual IGEs, as the presence of IGEs was altered over time. These findings represent some of the first empirical evidence demonstrating developmental IGEs, a first step toward incorporating developmental IGEs into our understanding of behavioral evolution.

Effect of CHST11, a novel biomarker, on the biological functionalities of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor, and the role of carbohydrate sulfotransferase 11 (CHST11) in this cancer remains unclear. Here, by using bioinformatics methods, we comprehensively analyzed the relationship between CHST11 and clinical significance, immune infiltration, functional enrichment, m6A methylation, and protein-protein interaction networks. We found that CHST11 expression was significantly higher in ccRCC samples than in normal tissues. Additionally, CHST11 levels correlated with the clinicopathological features of ccRCC patients and functioned as a prognostic factor for patient survival. Functional analysis revealed the involvement of CHST11 in metabolic pathways. Immune infiltration and m6A methylation analysis suggested the association of CHST11 with immune cell abundance in the tumor microenvironment and specific methylation patterns in ccRCC. The in vitro analysis of the clinical samples and ccRCC cell lines demonstrated that the overexpression of CHST11 promotes ccRCC cell proliferation, migration, and invasion, while its suppression has the opposite effect. Thus, CHST11 may play a remarkable role in the occurrence and progression of ccRCC. Functionally, CHST11 promotes the aggressiveness of ccRCC cells. These findings provide insights into the role of CHST11 in ccRCC progression.Registry and the Registration No. of the study/trial: No. 2021K034.

Factors influencing smartphone overdependence among adolescents.

Adolescents are particularly vulnerable to smartphone overdependence. Therefore, we identified the factors influencing smartphone overdependence and risk subgroups among adolescents. The current study is a secondary analysis of nationally representative data from the 2020 Korea Youth Risk Behavior Survey. The survey targeted middle- and high-school students in South Korea aged 12-18 using stratified, clustered, multistage probability sampling, and 53,457 students from 793 schools participated in this study. Complex sample data were analyzed considering the strata, clusters, and weights. Multiple logistic regression analysis revealed age, gender, household economic status, anxiety, loneliness, depressive symptoms, and experience of violent treatment as significant predictors of smartphone overdependence. Adolescents with severe anxiety were at a 3.326 times higher risk of smartphone overdependence than adolescents with minimal anxiety. Decision tree analysis showed that anxiety, gender, loneliness, and depressive symptoms were important in differentiating risk subgroups, with anxiety being the most significant factor. Group 13, comprising girls with severe anxiety, had the highest risk at 52.9%. Thus, early detection and prevention of issues such as anxiety, loneliness, and depressive symptoms, as well as treatment for violence, can prevent smartphone overdependence among adolescents. Additionally, more thorough interventions for anxiety are warranted to prevent smartphone overdependence.

Assessing psychopathic traits with the MMPI-3: Findings from correctional, university, and community samples.

OBJECTIVE: The Minnesota Multiphasic Personality Inventory (MMPI) instruments have a long history with respect to the assessment of psychopathic personality traits. The most recent version, the MMPI-3, should be in a good position to continue this tradition, and the aim of the current research was to evaluate its scales for this purpose. We examined, on the basis of previous research, how well conceptually relevant MMPI-3 scales mapped onto dominant contemporary psychopathy models: the traditional three-factor model and triarchic psychopathy model. HYPOTHESES: We hypothesized that MMPI-3 markers of internalizing would be negatively correlated with boldness, whereas broad and specific markers of externalizing proclivities would be associated with disinhibition and antisociality. We also hypothesized that egocentricity and callousness would be associated with MMPI-3 scales measuring various features of externalizing, interpersonal aggression/antagonism, and grandiosity. METHOD: We used archival samples of male prison inmates (n = 452), community members with externalizing proclivities (n = 205), and university students (n = 645). These participants completed the Expanded Levenson Self-Report Psychopathy Scale and the Triarchic Psychopathy Measure. RESULTS: Zero-order correlation analyses indicated support for many of our hypotheses across samples, with notable exceptions. Regression and dominance analyses yielded information about the most potent MMPI-3 predictors of each psychopathy domain, with consistency across the three samples. Boldness was associated with low scores on Emotional/Internalizing Dysfunction, Low Positive Emotions, Shyness, and Negative Emotionality/Neuroticism and high scores on Self-Importance and Dominance. For meanness and disinhibition, we found substantial overlap with MMPI-3 scales (e.g., Behavioral/Externalizing Dysfunction, Antisocial Behavior). Meanness was indicated by high Aggression, Cynicism, Aggressiveness, and Disaffiliativeness; disinhibition/antisociality was primarily marked by high Antisocial Behavior, Hypomanic Activation, Impulsivity, and Disconstraint; and Anger Proneness, Aggression, and Cynicism were secondary indicators. CONCLUSIONS: These findings provide support for using the MMPI-3 in clinical assessments to corroborate other sources of information regarding psychopathy as well as generate hypotheses for further consideration. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A multisite feasibility randomized clinical trial of mindfulness-based resilience training for aggression, stress, and health in law enforcement officers.

BACKGROUND: Law enforcement officers (LEOs) are exposed to significant stressors that can impact their mental health, increasing risk of posttraumatic stress disorder, burnout, at-risk alcohol use, depression, and suicidality. Compromised LEO health can subsequently lead to aggression and excessive use of force. Mindfulness training is a promising approach for high-stress populations and has been shown to be effective in increasing resilience and improving mental health issues common among LEOs. METHODS: This multi-site, randomized, single-blind clinical feasibility trial was intended to establish optimal protocols and procedures for a future full-scale, multi-site trial assessing effects of mindfulness-based resilience training (MBRT) versus an attention control (stress management education [SME]) and a no-intervention control, on physiological, attentional, and psychological indices of stress and mental health. The current study was designed to enhance efficiency of recruitment, engagement and retention; optimize assessment, intervention training and outcome measures; and ensure fidelity to intervention protocols. Responsiveness to change over time was examined to identify the most responsive potential proximate and longer-term assessments of targeted outcomes. RESULTS: We observed high feasibility of recruitment and retention, acceptability of MBRT, fidelity to assessment and intervention protocols, and responsiveness to change for a variety of putative physiological and self-report mechanism and outcome measures. CONCLUSIONS: Results of this multi-site feasibility trial set the stage for a full-scale, multi-site trial testing the efficacy of MBRT on increasing LEO health and resilience, and on decreasing more distal outcomes of aggression and excessive use of force that would have significant downstream benefits for communities they serve. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03784846 . Registered on December 24th, 2018.

[Research progress on the neural mechanism of the regulation of social isolation on innate behaviors].

Innate behavior is mainly controlled by genetics, but is also regulated by social experiences such as social isolation. Studies in animal models such as Drosophila and mice have found that social isolation can regulate innate behaviors through the changes at the molecular level, such as hormone, neurotransmitter, neuropeptide level, and at the level of neural circuits. In this review, we summarized the research progress on the regulation of social isolation on various animal innate behaviors, such as sleep, reproduction and aggression by altering the expression of conserved neuropeptides and neurotransmitters, hoping to deepen the understanding of the key and conserved signal pathways that regulate innate behavior by social isolation.

Differences in expression of male aggression between wild bonobos and chimpanzees.

Researchers investigating the evolution of human aggression look to our closest living relatives, bonobos (Pan paniscus) and chimpanzees (Pan troglodytes), as valuable sources of comparative data.1,2 Males in the two species exhibit contrasting patterns: male chimpanzees sexually coerce females3,4,5,6,7,8 and sometimes kill conspecifics,9,10,11,12 whereas male bonobos exhibit less sexual coercion13,14 and no reported killing.13 Among the various attempts to explain these species differences, the self-domestication hypothesis proposes negative fitness consequences of male aggression in bonobos.2,15,16 Nonetheless, the extent to which these species differ in overall rates of aggression remains unclear due to insufficiently comparable observation methods.17,18,19,20,21,22,23 We used 14 community-years of focal follow data-the gold standard for observational studies24-to compare rates of male aggression in 3 bonobo communities at the Kokolopori Bonobo Reserve, Democratic Republic of Congo, and 2 chimpanzee communities at Gombe National Park, Tanzania. As expected, given that females commonly outrank males, we found that bonobos exhibited lower rates of male-female aggression and higher rates of female-male aggression than chimpanzees. Surprisingly, we found higher rates of male-male aggression among bonobos than chimpanzees even when limiting analyses to contact aggression. In both species, more aggressive males obtained higher mating success. Although our findings indicate that the frequency of male-male aggression does not parallel species difference in its intensity, they support the view that contrary to male chimpanzees, whose reproductive success depends on strong coalitions, male bonobos have more individualistic reproductive strategies.25.

Exploring the profound link: Breastfeeding's impact on alleviating the burden of breast cancer - A review.

Breastfeeding has emerged as a critical factor in understanding and potentially mitigating the risk of breast cancer among women. This review delves into the intricate relationship between breastfeeding and breast cancer, elucidating the biological mechanisms, protective effects, and broader implications for public health. Epidemiological evidence consistently demonstrates a correlation between breastfeeding and a reduced risk of breast cancer, with longer durations of lactation showing a dose-dependent decrease in risk. The biological nexus between breastfeeding and breast cancer involves hormonal changes and the elimination of potentially damaged cells, influencing breast tissue and potentially mitigating carcinogenesis. Moreover, breastfeeding appears to impact tumor subtypes and aggressiveness, particularly demonstrating associations with lower risks of hormone receptor-negative and certain aggressive breast cancer subtypes. Recognizing the significance of breastfeeding in reducing breast cancer risk has profound public health implications, necessitating comprehensive support, education, and policies to encourage and facilitate breastfeeding.

Combined deletion of MEN1, ATRX and PTEN triggers development of high-grade pancreatic neuroendocrine tumors in mice.

Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of tumors that exhibit an unpredictable and broad spectrum of clinical presentations and biological aggressiveness. Surgical resection is still the only curative therapeutic option for localized PanNET, but the majority of patients are diagnosed at an advanced and metastatic stage with limited therapeutic options. Key factors limiting the development of new therapeutics are the extensive heterogeneity of PanNETs and the lack of appropriate clinically relevant models. In that context, genomic sequencing of human PanNETs revealed recurrent mutations and structural alterations in several tumor suppressors. Here, we demonstrated that combined loss of MEN1, ATRX, and PTEN, tumor suppressors commonly mutated in human PanNETs, triggers the development of high-grade pancreatic neuroendocrine tumors in mice. Histopathological evaluation and gene expression analyses of the developed tumors confirm the presence of PanNET hallmarks and significant overlap in gene expression patterns found in human disease. Thus, we postulate that the presented novel genetically defined mouse model is the first clinically relevant immunocompetent high-grade PanNET mouse model.

Targeting of REST with rationally-designed small molecule compounds exhibits synergetic therapeutic potential in human glioblastoma cells.

BACKGROUND: Glioblastoma (GBM) is an aggressive brain cancer associated with poor prognosis, intrinsic heterogeneity, plasticity, and therapy resistance. In some GBMs, cell proliferation is fueled by a transcriptional regulator, repressor element-1 silencing transcription factor (REST). RESULTS: Using CRISPR/Cas9, we identified GBM cell lines dependent on REST activity. We developed new small molecule inhibitory compounds targeting small C-terminal domain phosphatase 1 (SCP1) to reduce REST protein level and transcriptional activity in glioblastoma cells. Top leads of the series like GR-28 exhibit potent cytotoxicity, reduce REST protein level, and suppress its transcriptional activity. Upon the loss of REST protein, GBM cells can potentially compensate by rewiring fatty acid metabolism, enabling continued proliferation. Combining REST inhibition with the blockade of this compensatory adaptation using long-chain acyl-CoA synthetase inhibitor Triacsin C demonstrated substantial synergetic potential without inducing hepatotoxicity. CONCLUSIONS: Our results highlight the efficacy and selectivity of targeting REST alone or in combination as a therapeutic strategy to combat high-REST GBM.