Extreme behavioural and psychological symptoms of dementia: a case study.

BACKGROUND: The seven tiered behavioural and psychological symptoms of dementia (BPSD) model of service delivery has been used by inpatient units. The classification of each tier is broadly defined and not always agreed upon by clinicians. The case study uses novel approach by combining the BPSD classification criteria with clinical presentation to identify the clinical characteristics of the case and match these characteristics against the BPSD classification. This process was enhanced by using case specific measures such as the Neuropsychiatric Inventory (NPI) and Cohen Mansfield Agitation Inventory (CMAI) scales and key clinical data. CASE PRESENTATION: A case study of 76 year old male diagnosed with mixed Alzheimer's and Vascular dementia. The clinical presentation of the symptomatology was deemed to be extreme, thus fitting into the seventh tier (Extreme) of the BPSD model of service delivery. The case is considered to fit into the Extreme BPSD category given the high levels of aggression, which were consistently reflected in high scores on NPI and CMAI, as well as long length of inpatient stay (over 3 years). The average number of Pro re nata (PRN) psychotropics medications per month was 56 and seclusion episodes of 6 times per month, with each episode lasting on average 132 min shows severity of behaviours. His level of aggression had resulted in environmental damage and staff injuries. CONCLUSION: We recommend patient clinical characteristics, relevant hospital data and specific measures should be used to develop consensus around defining and classifying cases into Extreme BPSD.

A Principal Components Analysis and Functional Annotation of Differentially Expressed Genes in Brain Regions of Gray Rats Selected for Tame or Aggressive Behavior.

The process of domestication, despite its short duration as it compared with the time scale of the natural evolutionary process, has caused rapid and substantial changes in the phenotype of domestic animal species. Nonetheless, the genetic mechanisms underlying these changes remain poorly understood. The present study deals with an analysis of the transcriptomes from four brain regions of gray rats (Rattus norvegicus), serving as an experimental model object of domestication. We compared gene expression profiles in the hypothalamus, hippocampus, periaqueductal gray matter, and the midbrain tegmental region between tame domesticated and aggressive gray rats and revealed subdivisions of differentially expressed genes by principal components analysis that explain the main part of differentially gene expression variance. Functional analysis (in the DAVID (Database for Annotation, Visualization and Integrated Discovery) Bioinformatics Resources database) of the differentially expressed genes allowed us to identify and describe the key biological processes that can participate in the formation of the different behavioral patterns seen in the two groups of gray rats. Using the STRING- DB (search tool for recurring instances of neighboring genes) web service, we built a gene association network. The genes engaged in broad network interactions have been identified. Our study offers data on the genes whose expression levels change in response to artificial selection for behavior during animal domestication.

Improved Perception of Aggression Under (un)Related Threat of Shock.

Anxiety shifts visual attention and perceptual mechanisms, preparing oneself to detect potentially threatening information more rapidly. Despite being demonstrated for threat-related social stimuli, such as fearful expressions, it remains unexplored if these effects encompass other social cues of danger, such as aggressive gestures/actions. To this end, we recruited a total of 65 participants and asked them to identify, as quickly and accurately as possible, potentially aggressive actions depicted by an agent. By introducing and manipulating the occurrence of electric shocks, we induced safe and threatening conditions. In addition, the association between electric shocks and aggression was also manipulated. Our result showed that participants have improved sensitivity, with no changes to criterion, when detecting aggressive gestures during threat compared to safe conditions. Furthermore, drift diffusion model analysis showed that under threat participants exhibited faster evidence accumulation toward the correct perceptual decision. Lastly, the relationship between threat source and aggression appeared to not impact any of the effects described above. Overall, our results indicate that the benefits gained from states of anxiety, such as increased sensitivity toward threat and greater evidence accumulation, are transposable to social stimuli capable of signaling danger other than facial expressions.

Animal behavior: A tale of two apes.

A new paper shows that rates of aggression are higher, and rates of coalition formation are lower, among male bonobos than among male chimpanzees. These findings are noteworthy because they challenge the view that female bonobos' preferences for less aggressive males favored a reduction in male aggression and an increase in social tolerance.

Relations Between Perceptions of Parental Messages Supporting Fighting and Nonviolence and Adolescents' Physical Aggression: Beliefs as Mediators.

The purpose of this study was to examine adolescents' beliefs about fighting as mediators of longitudinal relations between perceptions of parental support for fighting and nonviolence and changes in adolescents' physical aggression. Participants were 2,575 middle school students (Mage = 12.20, SD = 1.02; 52% female; 83% African American) from the southeastern U.S. attending schools in communities with high rates of violence. Participants completed four waves of assessments every 3 months (i.e., fall, winter, spring, and summer). Each belief subscale mediated relations between perceptions of parental support for fighting and nonviolence and changes in aggression. Parental support for nonviolence was negatively associated with beliefs supporting reactive aggression and positively associated with beliefs against fighting. Parental support for retaliation was positively associated with beliefs supporting reactive and proactive aggression, and negatively associated with beliefs against fighting. Parental support for fighting as sometimes necessary was positively associated with beliefs supporting reactive aggression and beliefs that fighting is sometimes necessary. Beliefs supporting reactive and proactive aggression and beliefs that fighting is sometimes necessary were positively associated with aggression, whereas beliefs against fighting was negatively associated with aggression. Parents' support for fighting and for nonviolence may directly and indirectly reduce adolescents' physical aggression by influencing beliefs about the appropriateness of using aggression for self-defense and to attain a goal. This highlights the importance of jointly investigating multiple types of parental messages and types of beliefs about fighting.

Estimated Prevalence of Resident-to-Resident Aggression in Assisted Living.

Importance: Resident-to-resident aggression in assisted living facilities can result in physical and psychological harm, but its prevalence is unknown. Objective: To estimate the prevalence of resident-to-resident aggression, including physical, verbal, and sexual, among residents in assisted living facilities. Design, Setting, and Participants: This study used cross-sectional, observational data from a clinical trial, in which residents of assisted living facilities were monitored for events over a 1-month period. All residents of 14 large facilities randomly selected from 2 geographic locations (N = 1067), except those receiving hospice care (n = 11), were invited to participate; 93 died or moved prior to enrollment. There were 33 family and resident refusals; 930 residents were enrolled. Data were collected between May 30, 2018, and August 11, 2022. Main Outcomes and Measures: The data are from a clinical trial testing the effectiveness of an intervention to reduce resident-to-resident aggression. In addition, the study was designed to assess prevalence using the Time 1 (baseline) data, using a probability sample of facilities to allow for this analysis. Resident-to-resident aggression was identified using a mixed-method, case-finding strategy involving 6 sources: (1) cognitively capable resident reports regarding 22 possible events, (2) direct care staff report, (3) staff member reports collected from event-reporting forms, (4) research assistant observation of events in real time, (5) facility accident or incident reports, and (6) resident records. Results: The prevalence of resident-to-resident aggression among the 930 participants (mean [SD] age, 88.0 [7.2] years; 738 women [79.4%]) during the past month was estimated to be 15.2% (141 of 930 residents; 95% CI, 12.1%-18.8%). The most common forms of aggression included verbal (11.2% [104 of 930 residents; 95% CI, 8.8%-14.2%]), physical (41 of 930 residents; 4.4% [95% CI, 3.1%-6.3%]), sexual (0.8% [7 of 930 residents; 95% CI, 0.4%-1.6%]), and other (70 of 930 residents; 7.5% [95% CI, 5.5%-10.2%]). These categories are not mutually exclusive as residents could be involved with more than 1 type of aggressive behavior. Conclusions and Relevance: In this cross-sectional, observational prevalence study, resident-to-resident aggression in assisted living facilities was highly prevalent. Verbal aggression was the most common form, and physical aggression also occurred frequently. The effects of resident-to-resident aggression can be both morbid and mortal; therefore, intervention research is needed to prevent it and to treat it when it occurs.

Risk assessment for aggressive behaviour in schizophrenia.

BACKGROUND: Aggressive or violent behaviour is often associated with people with schizophrenia in common perceptions of the disease. Risk assessment methods have been used to identify and evaluate the behaviour of those individuals who are at the greatest risk of perpetrating aggression or violence or characterise the likelihood to commit acts. Although many different interventions have been developed to decrease aggressive or violent incidences in inpatient care, staff working in inpatient settings seek easy-to-use methods to decrease patient aggressive events. However, many of these are time-consuming, and they require intensive training for staff and patient monitoring. It has also been recognised in clinical practice that if staff monitor patients' behaviour in a structured manner, the monitoring itself may result in a reduction of aggressive/violent behaviour and incidents in psychiatric settings. OBJECTIVES: To assess the effects of structured aggression or violence risk assessment methods for people with schizophrenia or schizophrenia-like illnesses. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, PubMed, ISRCTN registry, ClinicalTrials.gov, and WHO ICTRP, on 10 February 2021. We also inspected references of all identified studies. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing structured risk assessment methods added to standard professional care with standard professional care for the evaluation of aggressive or violent behaviour among people with schizophrenia. DATA COLLECTION AND ANALYSIS: At least two review authors independently inspected citations, selected studies, extracted data, and appraised study quality. For binary outcomes, we calculated a standard estimation of the risk ratio (RR) and its 95% confidence interval (CI). For continuous outcomes, we calculated the mean difference (MD) and its 95% CI. We assessed risk of bias in the included studies and created a summary of findings table using the GRADE approach. MAIN RESULTS: We included four studies in the review. The total number of participants was not identifiable, as some studies provided number of participants included, and some only patient days. The studies compared a package of structured assessment methods with a control group that included routine nursing care and drug therapy or unstructured psychiatric observations/treatment based on clinical judgement. In two studies, information about treatment in control care was not available. One study reported results for our primary outcome, clinically important change in aggressive/violent behaviour, measured by the rate of severe aggression events. There was likely a positive effect favouring structured risk assessment over standard professional care (RR 0.59, 95% CI 0.41 to 0.85; 1 RCT; 1852 participants; corrected for cluster design: RR 0.59, 95% CI 0.37 to 0.93; moderate-certainty evidence). One trial reported data for the use of coercive measures (seclusion room). Compared to standard professional care, structured risk assessment may have little or no effect on use of seclusion room as days (corrected for cluster design: RR 0.92, 95% CI 0.27 to 3.07; N = 20; low-certainty evidence) or use of seclusion room as secluded participants (RR 1.83, 95% CI 0.39 to 8.7; 1 RCT; N = 20; low-certainty evidence). However, seclusion room may be used less frequently in the standard professional care group compared to the structured risk assessment group (incidence) (corrected for cluster design: RR 1.63, 95% CI 0.49 to 5.47; 1 RCT; N = 20; substantial heterogeneity, Chi2 = 0.0; df = 0.0; P = 0.0; I2 = 100%; low-certainty evidence). There was no evidence of a clear effect on adverse events of escape (RR 0.2, 95% CI 0.01 to 4.11; 1 RCT; n = 200; very low-certainty evidence); fall down (RR 0.33, 95% CI 0.04 to 3.15; 1 RCT; n = 200; very low-certainty evidence); or choking (RR 0.2, 95% CI 0.01 to 4.11; 1 RCT; n = 200; very low-certainty evidence) when comparing structured risk assessment to standard professional care. There were no useable data for patient-related outcomes such as global state, acceptance of treatment, satisfaction with treatment, quality of life, service use, or costs. AUTHORS' CONCLUSIONS: Based on the available evidence, it is not possible to conclude that structured aggression or violence risk assessment methods are effective for people with schizophrenia or schizophrenia-like illnesses. Future work should combine the use of interventions and structured risk assessment methods to prevent aggressive incidents in psychiatric inpatient settings.

Violent and prosocial music: Evidence for the impact of lyrics and musical tone on aggressive thoughts, feelings, and behaviors.

Although there is a large research base on the psychological impacts of violent and prosocial visual media, there is little research addressing the impacts of violent and prosocial music, and which facets of the music have the greatest impact. Four experiments tested the impact of lyrics and/or musical tone on aggressive and prosocial behavior, and on underlying psychological processes, using purpose-built songs to avoid the effect of music-related confounds. In study one, where mildly aggressive, overtly aggressive and violent lyrics were compared to neutral lyrics, any level of lyrical aggression caused an increase in behavioral aggression, which plateaued for all three aggression conditions. Violent lyrics were better recalled than other lyrics one week later. In studies two-three no significant effects of lyrics, or of aggressive versus nonaggressive musical tone, were found on aggressive or prosocial behavior. In terms of internal states, violent lyrics increased hostility/hostile cognitions in all studies, and negatively impacted affective state in three studies. Prosocial lyrics decreased hostility/hostile cognitions in three studies, but always in tandem with another factor. Aggressive musical tone increased physiological arousal in two studies and increased negative affect in one. In study four those who listened to violent lyrics drove more aggressively on a simulated drive that included triggers for aggression. Overall, violent lyrics consistently elicited hostility/hostile cognitions and negative affect, but these did not always translate to aggressive behavior. Violent music seems more likely to elicit behavioral aggression when there are aggression triggers and a clear way to aggress. Implications are discussed.

ANK3 rs10994336 and ZNF804A rs7597593 polymorphisms: genetic interaction for emotional and behavioral symptoms of alcohol withdrawal syndrome.

OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a complex condition associated with alcohol use disorder (AUD), characterized by significant variations in symptom severity among patients. The psychological and emotional symptoms accompanying AWS significantly contribute to withdrawal distress and relapse risk. Despite the importance of neural adaptation processes in AWS, limited genetic investigations have been conducted. This study primarily focuses on exploring the single and interaction effects of single-nucleotide polymorphisms in the ANK3 and ZNF804A genes on anxiety and aggression severity manifested in AWS. By examining genetic associations with withdrawal-related psychopathology, we ultimately aim to advance understanding the genetic underpinnings that modulate AWS severity. METHODS: The study involved 449 male patients diagnosed with alcohol use disorder. The Self-Rating Anxiety Scale (SAS) and Buss-Perry Aggression Questionnaire (BPAQ) were used to assess emotional and behavioral symptoms related to AWS. Genomic DNA was extracted from peripheral blood, and genotyping was performed using PCR. RESULTS: Single-gene analysis revealed that naturally occurring allelic variants in ANK3 rs10994336 (CC homozygous vs. T allele carriers) were associated with mood and behavioral symptoms related to AWS. Furthermore, the interaction between ANK3 and ZNF804A was significantly associated with the severity of psychiatric symptoms related to AWS, as indicated by MANOVA. Two-way ANOVA further demonstrated a significant interaction effect between ANK3 rs10994336 and ZNF804A rs7597593 on anxiety, physical aggression, verbal aggression, anger, and hostility. Hierarchical regression analyses confirmed these findings. Additionally, simple effects analysis and multiple comparisons revealed that carriers of the ANK3 rs10994336 T allele experienced more severe AWS, while the ZNF804A rs7597593 T allele appeared to provide protection against the risk associated with the ANK3 rs10994336 mutation. CONCLUSION: This study highlights the gene-gene interaction between ANK3 and ZNF804A, which plays a crucial role in modulating emotional and behavioral symptoms related to AWS. The ANK3 rs10994336 T allele is identified as a risk allele, while the ZNF804A rs7597593 T allele offers protection against the risk associated with the ANK3 rs10994336 mutation. These findings provide initial support for gene-gene interactions as an explanation for psychiatric risk, offering valuable insights into the pathophysiological mechanisms involved in AWS.

Phosphodiesterase 5A regulates the vomeronasal pump in mice.

The vomeronasal organ (VNO) is a specialized chemoreceptive structure in many vertebrates that detects chemical stimuli, mostly pheromones, which often elicit innate behaviors such as mating and aggression. Previous studies in rodents have demonstrated that chemical stimuli are actively transported to the VNO via a blood vessel-based pumping mechanism, and this pumping mechanism is necessary for vomeronasal stimulation in behaving animals. However, the molecular mechanisms that regulate the vomeronasal pump remain mostly unknown. In this study, we observed a high level of expression of phosphodiesterase 5A (PDE5A) in the vomeronasal blood vessel of mice. We provided evidence to support the potential role of PDE5A in vomeronasal pump regulation. Local application of PDE5A inhibitors-sildenafil or tadalafil-to the vomeronasal organ (VNO) reduced stimulus delivery into the VNO, decreased the pheromone-induced activity of vomeronasal sensory neurons, and attenuated male-male aggressive behaviors. PDE5A is well known to play a role in regulating blood vessel tone in several organs. Our study advances our understanding of the molecular regulation of the vomeronasal pump.

The interrelationship between sleep disturbance symptoms and aggression before and after the campus closure of the COVID-19 pandemic: insight from a cross-lagged panel network model.

Background: The COVID-19 pandemic is detrimental to sleep quality and increases aggression among college students. Nevertheless, relevant studies were rare. Hence, we collected longitudinal data during and post-campus closure in the current study to investigate the relationship between sleep disturbance and aggression. Methods: Data from 665 college students (59.2% females, Meanage = 19.01, SD age = 1.25) were collected before (wave 1) and after (wave 2) the campus closure of COVID-19. All participants were asked to fill out the Buss-Perry Aggression Questionnaire and the Youth Self-Rating Insomnia Scale. Two symptom networks and a cross-lagged panel network were formed and tested. Results: Hostility has the highest centrality in the symptom network both in waves 1 and 2, and it bridges sleep disturbance and aggression. "Easily be woken" - "wake up too early" and "wake up with tired" - "function hindrance" are two important symptom associations in networks of waves 1 and 2. All symptoms except "difficulty in falling asleep" and "easily be woken" ameliorated after closure. Moreover, "physical aggression" and "hostility" can trigger other symptoms in wave 2. Conclusion: As the first study about aggression and sleep disturbance in the background of COVID-19, we provide valuable information about the relationship between sleep disturbance and aggression on the symptom dimension.

B7-H3 Expression in Breast Cancer and Brain Metastasis.

Brain metastasis is a significant challenge for some breast cancer patients, marked by its aggressive nature, limited treatment options, and poor clinical outcomes. Immunotherapies have emerged as a promising avenue for brain metastasis treatment. B7-H3 (CD276) is an immune checkpoint molecule involved in T cell suppression, which is associated with poor survival in cancer patients. Given the increasing number of clinical trials using B7-H3 targeting CAR T cell therapies, we examined B7-H3 expression across breast cancer subtypes and in breast cancer brain metastases to assess its potential as an interventional target. B7-H3 expression was investigated using immunohistochemistry on tissue microarrays of three clinical cohorts: (i) unselected primary breast cancers (n = 347); (ii) brain metastatic breast cancers (n = 61) and breast cancer brain metastases (n = 80, including a subset of 53 patient-matched breast and brain metastasis cases); and (iii) mixed brain metastases from a range of primary tumours (n = 137). In primary breast cancers, B7-H3 expression significantly correlated with higher tumour grades and aggressive breast cancer subtypes, as well as poorer 5-year survival outcomes. Subcellular localisation of B7-H3 impacted breast cancer-specific survival, with cytoplasmic staining also correlating with a poorer outcome. Its expression was frequently detected in brain metastases from breast cancers, with up to 90% expressing B7-H3. However, not all brain metastases showed high levels of expression, with those from colorectal and renal tumours showing a low frequency of B7-H3 expression (0/14 and 2/16, respectively). The prevalence of B7-H3 expression in breast cancers and breast cancer brain metastases indicates potential opportunities for B7-H3 targeted therapies in breast cancer management.

The Affective Side of Disruptive Behavior: Toward Better Understanding, Assessment, and Treatment.

Historically, much of the progress made in youth mental health research can be classified as focusing on externalizing problems, characterized by disruptive behavior (e.g. aggression, defiance), or internalizing problems, characterized by intense negative affect (e.g. depression, anxiety). Until recently, however, less attention has been given to topics that lie somewhere in between these domains, topics that we collectively refer to as the affective side of disruptive behavior. Like the far side of the moon, the affective side of disruptive behavior captures facets of the phenomenon that may be less obvious or commonly overlooked, but are nonetheless critical to understand. This affective side clarifies socially disruptive aspects of traditionally "externalizing" behavior by elucidating proximal causation via intense negative affect (traditionally "internalizing"). Such problems include irritability, frustration, anger, temper loss, emotional outbursts, and reactive aggression. Given a recent explosion of research in these areas, efforts toward integration are now needed. This special issue was developed to help address this need. Beyond the present introductory article, this collection includes 4 empirical articles on developmental psychopathology topics, 4 empirical articles on applied treatment/assessment topics, 1 evidence base update review article on measurement, and 2 future directions review articles concerning outbursts, mood, dispositions, and youth psychopathology more broadly. By deliberatively investigating the affective side of disruptive behavior, we hope these articles will help bring about better understanding, assessment, and treatment of these challenging problems, for the benefit of youth and families.

Improving Employee Safety Through a Comprehensive Patient Behavioral Program.

BACKGROUND: Health care workers in the United States are facing increasing rates of exposure to aggressive behavior, resulting in an increase in employee injuries related specifically to patient behavioral events. By leveraging interprofessional collaboration and system-level innovation, we aimed to reduce the rate of employee injuries related to patient behavioral events at a children's hospital by 50% over a 3-year period. METHODS: An interdisciplinary quality improvement team comprising physicians, behavior analysts, nursing, and other key stakeholders developed a comprehensive behavior program in our children's hospital. The team developed 5 key pillars: aggression mitigation tools, clinical resources, advanced training, screening and management, and behavior emergency response. The outcome measure was rate of reported employee safety events related to patient behavioral events. This was tracked via prospective time series analysis statistical process control chart using established rules to detect special cause variation. RESULTS: The average rate of employee injuries resulting from patient behavioral events decreased from 0.96 to 0.39 per 1000 adjusted patient-days, with special cause variation observed on a statistical process control U-chart. This improvement has been sustained for 16 months. Staff members who experienced injuries included nurses and patient technicians, with common antecedents to injuries including medical interventions or patient requests that could not be safely met. CONCLUSIONS: A unified and multimodal system aimed to address pediatric patient behavioral events can reduce employee injuries and foster a culture of employee safety in the pediatric inpatient setting.

Violencia en el lugar de trabajo desde la percepción de profesionales de enfermería en un servicio de emergencia pediátrica / Violence in the workplace from the perception of nursing professionals in a pediatric emergency service

Introducción: Los profesionales de la salud tienen un mayor riesgo de sufrir lesiones físicas, sexuales o psicológicas debido a la violencia en el lugar de trabajo ocupando su rol al brindar cuidados de salud hacia el paciente pediátrico en casos de Emergencia. Los incidentes en los que el profesional es abusado, amenazado o agredido en las circunstancias relacionadas con su trabajo implican un desafío explícito o implícito a su seguridad, bienestar o salud. Objetivo: Explorar la percepción de profesionales de enfermería sobre la violencia laboral en el desempeño y ejecución de actividades orientadas al cuidado de salud de Enfermería en la Emergencia Pediátrica. Método: Investigación cualitativa de diseño fenomenológico, el estudio se realizó en profesionales de Enfermería del servicio de Emergencia Pediátrica con una muestra de 32 participantes, distribuidas en 4 grupos focales. Se diseñó una guía de preguntas semiestructuradas sobre los aspectos percibidos en el ámbito del trabajo del profesional que fueron recopiladas mediante archivos de voz y notas de campo, los resultados fueron analizados identificando las fuentes de la violencia en el lugar de trabajo. Resultados: Con la recopilación de datos de los participantes, la investigadora principal analizará la forma en que se presenta la violencia laboral desde la percepción de profesionales de Enfermería determinando los riesgos presentes para brindar recomendaciones y diseñar un plan de acción que ayuda a prevenir la violencia. (AU)

Introduction: Healthcare professional face a higher risk of experiencing physical, sexual, or psychological injuries due to violence in the workplace fulfilling their role in providing health care to a pediatric patient in emergency cases. Incidents where professionals are abused, threatened, or assaulted in circumstances related to their work pose an explicit or implicit challenge to their safety, well-being, or health.Objective: To explore the perception of nursing professionals regarding workplace violence in the performance and execution of healthcare activities in Pediatric Emergency Nursing. Method: Qualitative research with a phenomenological design. The study was conducted among nursing professionals in the Pediatric Emergency Service, with a sample size of 32 participants divided into 4 focus groups. A semi-structured questions were designed to gather perceptions about various aspects of their work, that were collected through voice recordings and field notes. The results were analyzed to identify the sources of violence in the workplace. Results: Through the data collected from the participants, the lead researcher analyzed the manifestation of workplace violence as perceived by nursing professionals. This analysis determined the existing risks and provided recommendations for designing an action plan to prevent violence. (AU)

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.

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.

Single-cell transcriptome analysis profiling lymphatic invasion-related TME in colorectal cancer.

Lymphatic invasion (LI) is extremely aggressive and induces worse prognosis among patients with colorectal cancer (CRC). Thus, it is critical to characterize the cellular and molecular mechanisms underlying LI in order to establish novel and efficacious therapeutic targets that enhance the prognosis of CRC patients. RNA-seq data, clinical and survival information of colon adenocarcinoma (COAD) patients were obtained from the TCGA database. In addition, three scRNA-seq datasets of CRC patients were acquired from the GEO database. Data analyses were conducted with the R packages. We assessed the tumor microenvironment (TME) differences between LI+ and LI- based scRNA-seq data, LI+ cells exhibited augmented abundance of immunosuppression and invasive subset. Marked extracellular matrix network activation was also observed in LI+ cells within SPP1+ macrophages. We revealed that an immunosuppressive and pro-angiogenic TME strongly enhanced LI, as was evidenced by the CD4+ Tregs, CD8+ GZMK+, SPP1+ macrophages, e-myCAFs, and w-myCAFs subcluster infiltrations. Furthermore, we identified potential LI targets that influenced tumor development, metastasis, and immunotherapeutic response. Finally, a novel LIRS model was established based on the expression of 14 LI-related signatures, and in the two testing cohorts, LIRS was also proved to have accurate prognostic predictive ability. In this report, we provided a valuable resource and extensive insights into the LI of CRC. Our conclusions can potentially benefit the establishment of highly efficacious therapeutic targets as well as diagnostic biomarkers that improve patient outcomes.