Excessive Cell Growth Causes Cytoplasm Dilution And Contributes to Senescence.

Cell size varies greatly between cell types, yet within a specific cell type and growth condition, cell size is narrowly distributed. Why maintenance of a cell-type specific cell size is important remains poorly understood. Here we show that growing budding yeast and primary mammalian cells beyond a certain size impairs gene induction, cell-cycle progression, and cell signaling. These defects are due to the inability of large cells to scale nucleic acid and protein biosynthesis in accordance with cell volume increase, which effectively leads to cytoplasm dilution. We further show that loss of scaling beyond a certain critical size is due to DNA becoming limiting. Based on the observation that senescent cells are large and exhibit many of the phenotypes of large cells, we propose that the range of DNA:cytoplasm ratio that supports optimal cell function is limited and that ratios outside these bounds contribute to aging.

Deregulation of the G1/S-phase transition is the proximal cause of mortality in old yeast mother cells.

Budding yeast cells produce a finite number of daughter cells before they die. Why old yeast cells stop dividing and die is unclear. We found that age-induced accumulation of the G1/S-phase inhibitor Whi5 and defects in G1/S cyclin transcription cause cell cycle delays and genomic instability that result in cell death. We further identified extrachromosomal rDNA (ribosomal DNA) circles (ERCs) to cause the G1/S cyclin expression defect in old cells. Spontaneous segregation of Whi5 and ERCs into daughter cells rejuvenates old mothers, but daughters that inherit these aging factors die rapidly. Our results identify deregulation of the G1/S-phase transition as the proximal cause of age-induced proliferation decline and cell death in budding yeast.

Disparities in preconception health indicators in U.S. women: a cross-sectional analysis of the behavioral risk factor surveillance system 2019.

OBJECTIVES: Optimized preconception care improves birth outcomes and women's health. Yet, little research exists identifying inequities impacting preconception health. This study identifies age, race/ethnicity, education, urbanicity, and income inequities in preconception health. METHODS: We performed a cross-sectional analysis of the Center for Disease Control and Prevention's (CDC) 2019 Behavioral Risk Factor Surveillance System (BRFSS). This study included women aged 18-49 years who (1) reported they were not using any type of contraceptive measure during their last sexual encounter (usage of condoms, birth control, etc.) and (2) reported wanting to become pregnant from the BRFSS Family Planning module. Sociodemographic variables included age, race/ethnicity, education, urbanicity, and annual household income. Preconception health indicators were subdivided into three categories of Physical/Mental Health, Healthcare Access, and Behavioral Health. Chi-squared statistical analysis was utilized to identify sociodemographic inequities in preconception health indicators. RESULTS: Within the Physical/Mental Health category, we found statistically significant differences among depressive disorder, obesity, high blood pressure, and diabetes. In the Healthcare Access category, we found statistically significant differences in health insurance status, having a primary care doctor, and being able to afford a medical visit. Within the Behavioral Health category, we found statistically significant differences in smoking tobacco, consuming alcohol, exercising in the past 30 days, and fruit and vegetable consumption. CONCLUSIONS: Maternal mortality and poor maternal health outcomes are influenced by many factors. Further research efforts to identify contributing factors will improve the implementation of targeted preventative measures in directly affected populations to alleviate the current maternal health crisis.

Disparities in osteoarthritis diagnosis and symptoms between English- and Spanish-speaking Latinas over 40 years of age in the United States: a analysis of the Behavioral Risk Factor Surveillance System.

OBJECTIVE: Osteoarthritis (OA) is a prominent musculoskeletal disorder that affects approximately 303 million people worldwide. The challenges that language barriers present to the Latina population in regard to the diagnosis and treatment of OA remain largely unknown. The objective of this study was to examine disparities in the diagnosis and treatment of arthritic conditions in English- and Spanish-speaking Latinas over 40 years of age. DESIGN: We analyzed data from the CDC's Behavioral Risk Screening and Surveillance System (BRFSS), combining the 2017-2020 cycles using sampling weights provided by BRFSS, adjusted for multiple cycles. Determination of English- or Spanish-speaking groups was based on the language of the survey submitted. We calculated population estimates for arthritis diagnosis, physical limitations, and mean joint pain among language groups and by age (40-64 and 65+) and determined associations via odds ratios. RESULTS: Rates of arthritis diagnosis between groups were similar; however we found that Spanish-speaking Latinas 65+ were statistically more likely to report being limited by pain (AOR: 1.55; 95% CI: 1.14-2.09), and among both age groups Spanish-speaking Latinas reported higher pain scores than the English-speaking group (40-64 age group: Coef: 0.74, SE = 0.14, P < .001; 65 + age group: Coef: 1.05, SE = 0.2, P < .001). CONCLUSION: Results from this study show that while there were no significant differences in rates of diagnosis, Spanish-speaking Latinas were more likely to be limited by joint pain and report higher pain scores.

A systematic review and thematic synthesis of qualitative literature on personal recovery and voice hearing.

BACKGROUND: Personal recovery literature has been influential in the conceptualization of emotional distress and service provision. While personal recovery in psychosis has been well-studied, voice hearing literature has not been reviewed to elucidate recovery processes. METHOD: Five databases were systematically searched to identify relevant qualitative recovery literature. Twelve eligible studies were included in this review, and an appraisal tool was applied to assess quality. Thematic synthesis was used to examine the results. RESULTS: Three superordinate themes were found relating to 'Recovery Phases', 'Recovery Facilitators' and 'Barriers to Recovery'. Papers included descriptions of finding voices distressing initially yet moving towards integrating and accepting voices. Searching for meaning versus seeking distance from voices were pivotal processes to recovery pathways. Enabling and disrupting recovery experiences are discussed within a proposed model. CONCLUSIONS: Recovery in voice hearing is an individual and potentially ongoing process. Future research should seek to examine recovery factors in voice hearing longitudinally and add further evidence to the supportive role services can play in recovery and voice hearing.

High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease.

BACKGROUND: Differentiating infiltrating myeloid cells from resident microglia in neuroinflammatory disease is challenging, because bone marrow-derived inflammatory monocytes infiltrating the inflamed brain adopt a 'microglia-like' phenotype. This precludes the accurate identification of either cell type without genetic manipulation, which is important to understand their temporal contribution to disease and inform effective intervention in its pathogenesis. During West Nile virus (WNV) encephalitis, widespread neuronal infection drives substantial CNS infiltration of inflammatory monocytes, causing severe immunopathology and/or death, but the role of microglia in this remains unclear. METHODS: Using high-parameter cytometry and dimensionality-reduction, we devised a simple, novel gating strategy to identify microglia and infiltrating myeloid cells during WNV-infection. Validating our strategy, we (1) blocked the entry of infiltrating myeloid populations from peripheral blood using monoclonal blocking antibodies, (2) adoptively transferred BM-derived monocytes and tracked their phenotypic changes after infiltration and (3) labelled peripheral leukocytes that infiltrate into the brain with an intravenous dye. We demonstrated that myeloid immigrants populated only the identified macrophage gates, while PLX5622 depletion reduced all 4 subsets defined by the microglial gates. RESULTS: Using this gating approach, we identified four consistent microglia subsets in the homeostatic and WNV-infected brain. These were P2RY12hi CD86-, P2RY12hi CD86+ and P2RY12lo CD86- P2RY12lo CD86+. During infection, 2 further populations were identified as 'inflammatory' and 'microglia-like' macrophages, recruited from the bone marrow. Detailed kinetic analysis showed significant increases in the proportions of both P2RY12lo microglia subsets in all anatomical areas, largely at the expense of the P2RY12hi CD86- subset, with the latter undergoing compensatory proliferation, suggesting replenishment of, and differentiation from this subset in response to infection. Microglia altered their morphology early in infection, with all cells adopting temporal and regional disease-specific phenotypes. Late in disease, microglia produced IL-12, downregulated CX3CR1, F4/80 and TMEM119 and underwent apoptosis. Infiltrating macrophages expressed both TMEM119 and P2RY12 de novo, with the microglia-like subset notably exhibiting the highest proportional myeloid population death. CONCLUSIONS: Our approach enables detailed kinetic analysis of resident vs infiltrating myeloid cells in a wide range of neuroinflammatory models without non-physiological manipulation. This will more clearly inform potential therapeutic approaches that specifically modulate these cells.

After the Study Ends: A Qualitative Study of Factors Influencing Intervention Sustainability.

Sustaining evidence-based practices after initial training and support has ended is necessary to ensure lasting improvements in youth mental health services. This study examined factors impacting community clinicians' decisions to sustain a transdiagnostic youth intervention following participation in a study. The aim of the study was to identify potentially mutable factors impacting sustainability to inform future implementation efforts. Thirteen clinicians (85% women, 92% Caucasian, M age = 35.6) completed interviews after participating in an open trial of an evidence-based intervention for depression, anxiety, and conduct disorders. Interviews were analyzed using thematic analysis methods. All (100%) clinicians reported current use of the intervention. Four themes emerged related to sustainability. Clinicians (100%) reported that making modifications, alignment with prior training, and relative advantage influenced their current intervention use. Clinicians (100%) reported that knowledge transfer from treatment developers was vital to sustainability. They (92%) noted a number of logistical, inner-organizational, and client-level barriers to sustainability. Lastly, clinicians (92%) identified factors related to scaling up the intervention. A variety of personal, organizational, logistical, and client variables influence the sustainment of new interventions, and could be leveraged in future implementation efforts.

Exploring the Role of Social Support in Promoting Community Integration: An Integrated Literature Review.

Community integration has emerged as a priority area among mental health advocates, policy makers, and researchers (Townley, Miller, & Kloos, 2013; Ware, Hopper, Tugenberg, Dickey, & Fisher, 2007). Past research suggests that social support influences community integration for individuals with serious mental illnesses (Davidson, Haglund, Stayner, Rakfeldt, Chinman, & Tebes, 2001; Davidson, Stayner, Nickou, Styron, Rowe, & Chinman, 2001; Wong & Solomon, 2002), but there has not yet been a systematic review on this topic. Therefore, the purpose of this paper was to explore the influence of social support on community integration through a review of the existing literature. An extensive literature search was conducted, resulting in 32 articles that met the search criteria. These articles were organized into three categories: defining community integration, supportive relationships, and mental health services. The search results are analyzed according to the types of support being provided. Article strengths, limitations, implications, and future directions are also addressed. Overall, the findings of this review suggest that social support, which may be provided by a variety of individuals and services, plays an important role in promoting community integration for individuals with serious mental illnesses. Therefore, as community mental health research and practice continues to promote community integration for individuals with serious mental illnesses, the mental health field should emphasize the importance of social support as a key factor influencing community integration.

The influence of sense of community on the relationship between community participation and mental health for individuals with serious mental illnesses.

The goal of the current study is to better understand the association between community participation and mental health by investigating sense of community as a potential mediating factor between community participation, psychological distress, and mental health functioning. A survey was administered to 300 adults with serious mental illnesses using community mental health services in the United States in a cross-sectional design. Hayes PROCESS macro (model 4, version 2.16; Hayes, 2013) was employed to test all of the hypotheses. Results indicate that sense of community partially mediated the association between community participation and psychological distress, as well as mental health functioning. Implications include contributing to the current knowledge base about the influence of community factors on mental health and informing future interventions aimed at promoting community participation of adults with serious mental illnesses.

Highlighting the Way Forward: A Review of Community Mental Health Research and Practice Published in AJCP and JCP.

Articles published in the two most prominent journals of community psychology in North America, the American Journal of Community Psychology (AJCP) and Journal of Community Psychology (JCP), provide a clear indicator of trends in community research and practice. An examination of community psychology's history and scholarship suggests that the field has reduced its emphasis on promoting mental health, well-being, and liberation of individuals with serious mental illnesses over the past several decades. To further investigate this claim, the current review presents an analysis of articles relevant to community mental health (N = 307) published in the American Journal of Community Psychology (AJCP) and Journal of Community Psychology (JCP) from 1973 to 2015. The review focuses on article characteristics (e.g., type of article and methods employed), author characteristics, topic areas, and theoretical frameworks. Results document a downward trend in published articles from the mid-1980s to mid-2000s, with a substantial increase in published work between 2006 and 2015. A majority of articles were empirical and employed quantitative methods. The most frequent topic area was community mental health centers and services (n = 49), but the past three decades demonstrate a clear shift away from mental health service provision to address pressing social issues that impact community mental health, particularly homelessness (n = 42) and community integration of adults with serious mental illnesses (n = 40). Findings reflect both the past and present state of community psychology and suggest promising directions for re-engaging with community mental health and fostering well-being, inclusion, and liberation of adults experiencing serious mental health challenges.

Trends and forecasted rates of adverse childhood experiences among adults in the United States: an analysis of the Behavioral Risk Factor Surveillance System.

CONTEXT: Many studies have shown increases in negative social aspects in the United States that may increase the likelihood of a child experiencing adversity. These rising trends include household dysfunction, poor mental health and substance use, crime rates, and incarceration. Additionally, the pathway of adverse childhood experiences (ACEs) may also perpetuate intergenerational trauma. OBJECTIVES: Given these increased trends, our objective was to determine the mean ACEs reported among adults by year of birth to assess trends of ACEs over time. METHODS: To assess ACEs trends in the United States, we utilized data from the 2020 Behavioral Risk Factor Surveillance System (BRFSS), a nationally representative survey. We summed individuals' reported ACEs and then calculated the mean ACE score within age cohorts (in 1-year increments) by year of birth. We utilized an auto-regressive integrated moving average (ARIMA) model to forecast mean ACEs through 2030. RESULTS: Respondents to the ACEs module (n=116,378) represented 63,076,717 adults in the United States, with an average age cohort of 1715 individuals. The mean reported ACEs among individuals 80 years or older (born in or before 1940) was 0.79, while the highest mean ACEs (2.74) were reported among the cohort born in 1998-an average increase of 0.022 ACEs per year. The ARIMA model forecasted that individuals born in 2018 will, on average, surpass a cumulative of three ACEs. CONCLUSIONS: Given the connection of ACEs to poor health outcomes and quality of life, this trend is alarming and provides evidence for the necessity of child maltreatment prevention. Multigenerational trauma-informed care and education are warranted for individuals with ACEs and may even prevent the cycle from recurring.

Adverse childhood experience categories and subjective cognitive decline in adulthood: an analysis of the Behavioral Risk Factor Surveillance System.

CONTEXT: Adverse childhood experiences (ACEs) negatively impact health outcomes later in life, in a dose-dependent relationship; however, little is known about the impact of the individual ACE categories and subjective cognitive decline (SCD) later in life. OBJECTIVES: The aim of this study was to determine the associations among the eight ACEs and SCD. METHODS: We analyzed data from two cycles of the Behavioral Risk Factor Surveillance System (BRFSS; 2019-2020). We assessed the accumulation of ACEs and their association with SCD, and among individuals reporting only one ACE, we utilized logistic regression to compare the likelihood of reporting SCD and symptomology among the eight categories of adversity. RESULTS: Among included respondents, 10.14% reported experiencing SCD. More ACEs were reported among those with SCD (mean, 2.61; SD, 2.56) compared to those without SCD (mean, 1.44; SD, 1.91). Those with higher ACE scores were significantly less likely to have spoken with a healthcare provider about their cognitive decline. Individuals reporting one ACE of either family mental illness, family substance abuse, family incarceration, emotional abuse, or physical abuse had significantly greater odds of reporting memory loss compared to individuals with no ACEs. CONCLUSIONS: Having multiple ACEs was significantly associated with higher odds of SCD and associated limitation of social activity and was inversely associated with getting help when it is needed. Further, many ACE categories were associated with SCD - a novel addition to the literature and the methodology utilized herein. Interventions focused on improving cognitive health and preventing cognitive decline should consider the potential role of ACEs among affected populations.

"We Deal Here With Grey": Exploring Professional Boundary Development in a Forensic Inpatient Service.

BACKGROUND: Maintaining appropriate professional boundaries with clients in mental health settings can be complex, particularly for forensic inpatient nurses and healthcare workers. The literature in this area has mainly focused on boundary violations, with little research on how staff members develop and maintain boundaries in forensic inpatient units, despite safe working relationships being beneficial for staff experience and client recovery. METHOD: Interviews with 11 nurses and healthcare workers from forensic inpatient wards were analyzed using a constructivist grounded theory methodology. RESULTS: A cyclical model of boundary development was developed in which staff initially acclimatize to the forensic environment before entering a calibration phase of constantly assessing and addressing professional boundary issues in daily working life. Staff members use this experience alongside reflection, social learning, and clinical supervision to undergo individual learning and team development. In the fourth phase, they use this learning to recalibrate their views on boundaries, themselves, and how they work with clients. This recalibration impacts on staff members' further management of daily boundaries, providing more materials for learning, which leads to further recalibration. CONCLUSIONS: This study echoes previous literature suggesting the importance of supervision and reflective spaces in professional boundary understanding. The model is comparable with existing learning theory and reflects a clinical drive toward safe uncertainty. The importance of social and experiential learning is highlighted and has important implications for forensic nurses.

Associations Between Physical Health Limitations and Community Participation Among People With and Without Serious Mental Illnesses.

OBJECTIVE: Research has suggested that individuals with serious mental illnesses are not as physically healthy as the general population and are more likely to experience physical illnesses such as diabetes, obesity, and cardiovascular and respiratory diseases. Less is known about how physical health may be related to community participation among individuals with serious mental illnesses, although research with adults in the general population has suggested strong negative associations between health impairments and engagement in a variety of activity domains. METHODS: In this study, the authors drew from two national data sets to examine the relationship between physical health impairments and community participation among 300 participants with serious mental illnesses and 300 participants without serious mental illnesses. RESULTS: For participants in both groups, physical health concerns and use of mobility aids were associated with lower reported rates of community participation. CONCLUSIONS: Findings shed light on the complex association between physical health impairments and community participation while also suggesting the need to focus on other potential barriers to participation among individuals with serious mental illnesses.

Oncology disease management.

Oncologic conditions are ubiquitous medical illnesses that present a particular challenge for medical management programs designed to address quality and cost issues in patient populations. Disease management strategies represent a reasonable and effective approach for employers and health plans in their arsenal of health management strategies. Multiple reasons exist for the development of specialized disease management programs that deal with cancer patients, some unique to this group of individuals. Health plans and/or employers have solid justification for addressing these issues directly through programs developed specifically to work with cancer patients. Whether developed within a health plan, or "carved out" to an external vendor, proper evaluation of outcomes is essential.

Orexin in Rostral Hotspot of Nucleus Accumbens Enhances Sucrose 'Liking' and Intake but Scopolamine in Caudal Shell Shifts 'Liking' Toward 'Disgust' and 'Fear'.

The nucleus accumbens (NAc) contains a hedonic hotspot in the rostral half of medial shell, where opioid agonist microinjections are known to enhance positive hedonic orofacial reactions to the taste of sucrose ('liking' reactions). Within NAc shell, orexin/hypocretin also has been reported to stimulate food intake and is implicated in reward, whereas blockade of muscarinic acetylcholine receptors by scopolamine suppresses intake and may have anti-reward effects. Here, we show that NAc microinjection of orexin-A in medial shell amplifies the hedonic impact of sucrose taste, but only within the same anatomically rostral site, identical to the opioid hotspot. By comparison, at all sites throughout medial shell, orexin microinjections stimulated 'wanting' to eat, as reflected by increases in intake of palatable sweet chocolates. At NAc shell sites outside the hotspot, orexin selectively enhanced 'wanting' to eat without enhancing sweetness 'liking' reactions. In contrast, microinjections of the antagonist scopolamine at all sites in NAc shell suppressed sucrose 'liking' reactions as well as suppressing intake of palatable food. Conversely, scopolamine increased aversive 'disgust' reactions elicited by bitter quinine at all NAc shell sites. Finally, scopolamine microinjections localized to the caudal half of medial shell additionally generated a fear-related anti-predator reaction of defensive treading and burying directed toward the corners of the transparent chamber. Together, these results confirm a rostral hotspot in NAc medial shell as a unique site for orexin induction of hedonic 'liking' enhancement, similar to opioid enhancement. They also reveal distinct roles for orexin and acetylcholine signals in NAc shell for hedonic reactions and motivated behaviors.

Parenting challenges in the setting of terminal illness: a family-focused perspective.

PURPOSE OF REVIEW: In the advanced stages of illness, families with dependent children experience disruption across all dimensions of family life. The need for family support during palliative care is well recognized, yet little is understood about how parents and their children navigate these difficult circumstances. This review summarizes the current body of research on parenting challenges in advanced cancer. RECENT FINDINGS: To date, the study of parental cancer has focused predominantly on the early stages of disease and its impact on children and adolescents. Less is known about how families with minor children prepare for parental loss. Evidence suggests that having dependent children influences parents' treatment decisions at the end of life, and that a central concern for children and parents is optimizing time spent together. Parents may feel an urgency to engage in accelerated parenting, and maintaining normalcy remains a consistent theme for the ill and healthy parent alike. There is a growing evidence base affirming the importance of responsive communication prior to death. SUMMARY: Advancing knowledge about the parenting experience at the end of life is critical for ensuring effective support to the entire family, as it accommodates and prepares for the loss of a vital member.