ABSTRACT
Intestinal stromal cells (SCs), which synthesize the extracellular matrix that gives the mucosa its structure, are newly appreciated to play a role in mucosal inflammation. Here, we show that human intestinal vimentin+CD90+smooth muscle actin- SCs synthesize retinoic acid (RA) at levels equivalent to intestinal epithelial cells, a function in the human intestine previously attributed exclusively to epithelial cells. Crohn's disease SCs (Crohn's SCs), however, synthesized markedly less RA than SCs from healthy intestine (normal SCs). We also show that microbe-stimulated Crohn's SCs, which are more inflammatory than stimulated normal SCs, induced less RA-regulated differentiation of mucosal dendritic cells (DCs) (circulating pre-DCs and monocyte-derived DCs), leading to the generation of more potent inflammatory interferon-γhi/interleukin-17hi T cells than normal SCs. Explaining these results, Crohn's SCs expressed more DHRS3, a retinaldehyde reductase that inhibits retinol conversion to retinal and, thus, synthesized less RA than normal SCs. These findings uncover a microbe-SC-DC crosstalk in which luminal microbes induce Crohn's disease SCs to initiate and perpetuate inflammation through impaired synthesis of RA.
ABSTRACT
Moral judgments are often viewed as the outcome of affective and deliberative processes that could be impacted by social factors and individual characteristics. The purpose of this study was to examine the interaction between gender and social context on moral judgment. Participants included 315 undergraduate students (67.3% female). The participants completed the Moral Decision-Making Task while seated at row tables facing the front of the room or round tables facing other participants. The results indicated that males responded in a more utilitarian manner (harm one to save five) than females for moral impersonal (MI) and moral personal (MP) dilemmas regardless of seating arrangements. When seated at round tables, all participants were more likely to respond deontologically (cause no harm) to the moral impersonal dilemmas. In addition, we calculated a moral reasoning difference score for each participant as the difference between the MI and MP scores to represent additional reactivity due to the idea of taking direct action. The moral reasoning difference score was consistent for females but indicated a more deontological response from males at round tables and a more utilitarian response from males at row tables. These results suggest that males are more utilitarian than females and are more likely to be influenced by social context when responding to moral dilemmas. More broadly, the current results indicate that moral judgments are affected by social context particularly in males in ways that have not been incorporated in many models of moral decision making.
ABSTRACT
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.
Subject(s)
Adolescent Behavior , Aggression , Parent-Child Relations , Violence , Humans , Adolescent , Female , Aggression/psychology , Male , Adolescent Behavior/psychology , Child , Violence/psychology , Parenting/psychology , Parents/psychology , Longitudinal StudiesABSTRACT
Violence disproportionately impacts Black American youth, representing a major health disparity. Addressing the possible root causes of structural inequities to reduce violence may increase the impact of prevention strategies. However, efforts to evaluate the impact of such interventions pose numerous methodological challenges, particularly around selecting an effective evaluation design to detect change at the community level, with adequate power and sampling, and appropriate constructs and measurement strategies. We propose a multiple baseline experimental design to evaluate the impact of a community-level youth violence and suicidality prevention strategy. A multiple baseline experimental design with multiple community units balances the need for scientific rigor with practical and values-based considerations. It includes randomization and plausible counterfactuals without requiring large samples or placing some communities in the position of not receiving the intervention. Considerations related to the conceptualization of the logic model, mechanisms of change, and health disparity outcomes informed the development of the measurement strategy. The strengths and weaknesses of a multiple baseline experimental design are discussed in comparison to versions of randomized clinical trials. Future health disparity intervention evaluation research will benefit from (1) building a shared sense of urgent public need to promote health; (2) respecting the validity of values- and partnership-based decision-making; and (3) promoting community-based and systems-level partnerships in scientific grant funding. The described study has been registered prospectively at clinicaltrials.gov, Protocol Record 21-454.
Subject(s)
Violence , Humans , Adolescent , Violence/prevention & control , Black or African American , Program Evaluation , Research DesignABSTRACT
Firearm-related injury and mortality prevention strategies are often incompatible with and potentially ineffective for the very populations at risk. Such incompatibility is reflective of a cultural disconnect between investigators and prevention specialists and those who own and use firearms. The current paper describes Project GRIP, a research study that was guided by the principles of Participatory Action Research (PAR). We present the project as a case-example and demonstration of how PAR principles can inform an approach to partner with firearm owners in injury prevention research. Though PAR is a general approach and not a set of techniques, we describe the strategies we used in the hopes that they may be useful for investigators using PAR with firearm owners. We discuss the project and our approach across different stages of the process, including entering into PAR with firearm owners, building partnerships, developing a shared vision, mutual understanding, and co-learning, building and maintaining positive relationships, and executing the project tasks. The PAR approach and the intentional emphasis on partnership is, in our opinion, vital to ensuring that the perspectives of firearm owners are incorporated into the research literature so that more ecologically valid and potentially effective injury and mortality prevention strategies can be developed and disseminated.
ABSTRACT
This mixed methods study had two aims: (1) to examine the effectiveness of a jail diversion program in reducing recidivism and promoting educational and employment outcomes; and (2) to qualitatively explore mechanisms through which the program was effective. Participants were 17 individuals arrested for drug offenses who participated in an intensive, law enforcement-based jail diversion program, and 17 individuals in a comparison group. Arrests were extracted from police records, and education and employment were extracted from program data. Four intervention participants completed qualitative interviews. Arrest rates in the intervention group decreased significantly postintervention, and arrest rates in the intervention group were numerically lower than those in the comparison group. Participants experienced significant increases in employment and driver's license status. Participants also identified mechanisms through which the program was effective. This jail diversion program shows promise in reducing recidivism and promoting adaptive functioning. Jail diversion programs that include mentorship, peer support, and removal of barriers to success may be particularly effective.
Subject(s)
Jails , Recidivism , Humans , Law Enforcement/methodsABSTRACT
BACKGROUND: While symptoms related to lower urinary tract dysfunction (LUTD) are common in individuals with Alzheimer's disease (AD), pathophysiological links between AD and LUTD remain unclear. OBJECTIVE: This study aimed to investigate whether AD neuropathology would cause autonomic dysfunction along the spinal cord-bladder axis, which could result in alterations in bladder muscle kinetics. METHODS: We utilized APPNL-G-F/NL-G-F knock-in (APP KI) and APPwt/wt (wild-type) mice at two different ages, 4- and 10-month-old, to investigate how AD impacts bladder tissue function by immunohistochemistry, western blotting, and pharmacomyography. RESULTS: We showed that the mucosal layer partially separated from the detrusor in 10-month-old APP KI mouse bladders. Although there was no detectable amyloid deposition in the APP KI bladder, we found amyloid plaques in APP KI lumbar spinal cord. Further immunoblot analysis revealed that tyrosine hydroxylase protein levels were significantly reduced in both 4- and 10-month-old bladder tissues, suggesting reduction of norepinephrine synthesis in APP KI mouse bladders. In contrast, the level of ß2 adrenergic receptor was increased in 4-month-old but not 10-month-old APP KI bladders. In bladder strips, the adrenergic agonist isoproterenol induced increased relaxation in 4- but not 10-month-old APP KI bladders. With 10âHz electrical field stimulation, 10-month-old APP KI bladder strips were more responsive than wild-type controls, with no differences observed in 4-month-old APP KI bladders. CONCLUSIONS: APP KI mice exhibit LUTD, which is likely arising from amyloid pathology in the spinal cord, and results in maturational declines in presynaptic activity combined with compensatory postsynaptic upregulation.
Subject(s)
Alzheimer Disease , Mice , Animals , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Urinary Bladder/metabolism , Urinary Bladder/pathology , Disease Models, Animal , Mice, Transgenic , Plaque, Amyloid/pathologyABSTRACT
E-cycling is a growing area of cycling appealing to competitive cyclists and fitness enthusiasts. Zwift is the most popular e-cycling platform, with approx. 1 million subscribers and is a virtual environment that hosts regular races, including the UCI e-cycling world championships. The popularity of Zwift has given rise to cases of cheating and hacking the system to gain an advantage in e-racing. As a result, some high-profile professional riders have faced bans. We set out to understand the thoughts and concerns e-cyclists have about cheating, hacking, and doping in e-cycling. A total of 337 females and 1130 males were recruited over a 7-week period via social networking sites to complete an online survey. Forty-four per cent had experienced cheating during e-racing, which made them feel angry, annoyed, disappointed, and cheated. However, 15% of those who experienced cheating said they did not care, possibly because many see e-racing as a game or training tool rather than a competitive event. Eighty-seven per cent of participants were in favour of enforcing a ban on cheaters in e-cycling, while 34% wanted cheaters to be banned during in-person cycling events too. Results indicate that many e-cyclists have experienced cheating and would like clearer rules and bans for cheaters during e-races.
ABSTRACT
BACKGROUND: Increasing HIV testing and treatment coverage among people living with HIV (PLHIV) is essential for achieving global AIDS epidemic control. However, compared to women, cis-gender heterosexual men living with HIV are significantly less likely to know their HIV status, initiate anti-retroviral therapy (ART) and achieve viral suppression. This is particularly true in South Africa, where men are also at increased risk of mortality resulting from AIDS-related illnesses. While there is growing knowledge of Treatment as Prevention or the concept Undetectable=Untransmittable (U=U) among PLHIV in Western and high-income countries, the reach and penetration of the U=U message in sub-Saharan Africa remains limited, and few studies have evaluated the impact of accessible and relatable U=U messages on ART initiation and adherence. To address these gaps, rigorous evaluations of interventions that incorporate U=U messages are needed, especially among men in high prevalence settings. METHODS: Building on our U=U messages that we previously developed for men using behavioral economics insights and a human-centered design, we will conduct two sequential hybrid type 1 effectiveness-implementation trials to evaluate the impact of U=U messages on men's uptake of community-based HIV testing and ART initiation (Trial 1), and retention in care and achievement of viral suppression (Trial 2). A cluster randomized trial will be implemented for Trial 1, with HIV testing service site-days randomized to U=U or standard-of-care (SoC) messages inviting men to test for HIV. An individual-level randomized control trial will be implemented for Trial 2, with men initiating ART at six government clinics randomized to receive U=U counselling or SoC treatment adherence messaging. We will incorporate a multi-method evaluation to inform future implementation of U=U messaging interventions. The study will be conducted in the Buffalo City Metro Health District of the Eastern Cape Province and in the Cape Town Metro Health District in the Western Cape Province in South Africa. DISCUSSION: These trials are the first to rigorously evaluate the impact of U=U messaging on HIV testing uptake, ART initiation and achievement of viral suppression among African men. If effective, these messaging interventions can shape global HIV testing, treatment and adherence counselling guidelines and practices.
ABSTRACT
The role of aberrant glycosylation in pancreatic ductal adenocarcinoma (PDAC) remains an under-investigated area of research. In this study, we determined that ST6 ß-galactoside α2,6 sialyltransferase 1 (ST6GAL1), which adds α2,6-linked sialic acids to N-glycosylated proteins, was upregulated in patients with early-stage PDAC and was further increased in advanced disease. A tumor-promoting function for ST6GAL1 was elucidated using tumor xenograft experiments with human PDAC cells. Additionally, we developed a genetically engineered mouse (GEM) model with transgenic expression of ST6GAL1 in the pancreas and found that mice with dual expression of ST6GAL1 and oncogenic KRASG12D had greatly accelerated PDAC progression compared with mice expressing KRASG12D alone. As ST6GAL1 imparts progenitor-like characteristics, we interrogated ST6GAL1's role in acinar to ductal metaplasia (ADM), a process that fosters neoplasia by reprogramming acinar cells into ductal, progenitor-like cells. We verified ST6GAL1 promotes ADM using multiple models including the 266-6 cell line, GEM-derived organoids and tissues, and an in vivo model of inflammation-induced ADM. EGFR is a key driver of ADM and is known to be activated by ST6GAL1-mediated sialylation. Importantly, EGFR activation was dramatically increased in acinar cells and organoids from mice with transgenic ST6GAL1 expression. These collective results highlight a glycosylation-dependent mechanism involved in early stages of pancreatic neoplasia.
Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Mice , Animals , Pancreatic Neoplasms/pathology , Pancreas/pathology , Carcinoma, Pancreatic Ductal/pathology , ErbB Receptors/genetics , Metaplasia/pathology , Sialyltransferases/genetics , beta-D-Galactoside alpha 2-6-Sialyltransferase , Antigens, CDABSTRACT
OBJECTIVE: The purpose of this integrative review was to explore, appraise and synthesize the current literature on correlates of suicide risk in nurses. DESIGN: Integrative literature review. DATA SOURCES: Cumulative Index to Nursing and Allied Health Literature (CINAHL), Joanna Briggs Institute, PubMed, PsycInfo and Scopus electronic databases were searched for abstracts published between 2005 and 2020. Reference lists were hand searched. REVIEW METHODS: The integrative review was based on the Whittemore and Knafl review methodology. Primary qualitative and quantitative studies about suicidal behaviour in nurses published in peer-reviewed journals were included. The methodological quality of included articles was assessed using the Mixed Methods Assessment Tool. RESULTS: Separate correlates of risk and protective factors were identified for suicidal ideation, suicide attempt and death by suicide in nurses. IMPLICATIONS: Due to a number of factors at the individual, interpersonal and work levels, nurses are uniquely positioned to be at risk of dying by suicide. The ideation-to-action framework provides a theoretical guide to understand the interplay between correlates and the effect it has on increasing a nurses' capability for suicide. CONCLUSIONS: This review integrates the empirical literature to elucidate the concept of suicidal behaviour as it applies to nurses.
Subject(s)
Suicidal Ideation , Suicide, Attempted , HumansABSTRACT
AIMS: The Working Group (WG), initiated by the International Continence Society (ICS) Standardisation Steering Committee and supported by the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction, has revised the ICS Standard for pressure-flow studies of 1997. METHODS: Based on the ICS standard for developing evidence-based standards, the WG developed this new ICS standard in the period from May 2020 to December 2022. A draft was posted on the ICS website in December 2022 to facilitate public discussion and the comments received have been incorporated into this final release. RESULTS: The WG has recommended analysis principles for the diagnosis of voiding dysfunction for adult men and women without relevant neurological abnormalities. New standard terms and parameters for objective and continuous grading of urethral resistance (UR), bladder outflow obstruction (BOO) and detrusor voiding contraction (DVC) are introduced in this part 2 of the standard. The WG has summarized the theory and recommendations for the practice of pressure-flow study (PFS) for patients in part 1. A pressure-flow plot is recommended for the diagnosis of every patient, in addition to time-based graphs. Voided percentage and post void residual volume should always be included in PFS analysis and diagnosis. Only parameters that represent the ratio or subtraction of pressure and synchronous flow are recommended to quantify UR and only parameters that combine pressure and flow in a product or sum are recommended to quantify DVC. The ICS BOO index and the ICS detrusor contraction index are introduced in this part 2 as the standard. The WG has suggested clinical PFS dysfunction classes for male and female patients. A pressure-flow scatter graph including every patient's pdet at maximum flow (pdetQmax ) with maximum flow rate (Qmax ) point should be included in all scientific reports considering voiding dysfunction. CONCLUSION: PFS is the gold standard used to objectively assess voiding function. Quantifying the dysfunction and grading of abnormalities are standardized for adult males and females.
Subject(s)
Urinary Bladder Neck Obstruction , Adult , Humans , Male , Female , Urination , Urodynamics , Societies , Repressor ProteinsABSTRACT
AIMS: The working group (WG) initiated by the International Continence Society Standardization Steering Committee and supported by the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction has revised the (1997) ICS Standard for pressure flow studies. METHODS: Based on the ICS standard for developing evidence-based standards, the WG developed this new ICS standard in the period from May 2020 to December 2022. A draft was posted on the ICS website in January 2023 to facilitate public discussion and the comments received have been incorporated into this final release. RESULTS: The WG summarizes the theory and recommends the practice and the terms used for the diagnosis of voiding dysfunction for adult female and male patients without relevant neurological abnormalities, in part 1 of this standard. The WG has also recommended standard principles and parameters for objective and continuous grading of urethral resistance and detrusor voiding contraction on the basis of pressure flow studies in part 2. The recommendations for practice in this part have also the aim to increase the understanding of the physiology as well as the psychology of voiding. The potential effects of the laboratory situation of the test on the voiding as well as the role of the urodynamicist in this regard are discussed. The WG has recommended to use for diagnosis only the voidings that are considered representative by the patient. CONCLUSION: A pressure flow study is the gold standard to assess voiding function and to quantify dysfunction. This part of the standard explains the clinical background, gives recommendations for the execution of a pressure flow study and lists relevant terms, parameters, and units of measurements.
Subject(s)
Urinary Bladder Diseases , Urination , Adult , Humans , Male , Female , Urination/physiology , Urinary Bladder , Societies , Urodynamics/physiology , Repressor ProteinsABSTRACT
The purpose of this proof-of-concept study was to examine the outcomes and acceptability of a spiritual intervention for moral injury led by veteran peers in a Veteran Service Organization (VSO), called "Heroes to Heroes." From baseline to 1-year follow-up, 101 veterans who participated in the intervention completed the evaluation surveys at four time points assessing psychological outcomes (moral injury, posttraumatic stress disorder [PTSD] symptoms, and life satisfaction), spiritual outcomes (spiritual struggles and spiritual transcendence), and their perceived helpfulness of the program. In addition, we conducted four focus groups with six to eight alumni to more fully understand veterans' views and experiences of the program. Focusing on the longitudinal surveys, latent growth modeling analyses revealed veterans generally improved across the psychological and spiritual outcomes in the study. Specifically, veterans reported steady decreases in moral injury outcomes, PTSD symptoms, and spiritual struggles along with increased life satisfaction and spiritual transcendence over the 1-year period. An inductive content analysis of veterans' responses to open-ended items in the surveys and focus group interviews revealed four possible mechanisms or facilitators of these outcomes: (a) social connectivity and belonging (e.g., shared vulnerability and camaraderie); (b) behavioral engagement in core aspects of their spirituality (e.g., sacred practices and visiting sacred places); (c) spiritual transformation and growth (e.g., closeness with God and divine forgiveness); and (d) appreciation for diversity (e.g., religious and military). Overall, these findings affirm the potential effectiveness and acceptability of the VSO's peer-led spiritual intervention for promoting the holistic healing among veterans who are contending with emotional and spiritual wounds of war. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
ABSTRACT
Background: Social disconnection is associated with all-cause mortality and suicide. Measures of social disconnection with reliable cut-off scores are needed to aid in the assessment of clinically significant change. Aims: The current study sought to identify reliable clinical cut-off scores for the 15-item Interpersonal Needs Questionnaire (INQ-15), which assesses two indices of social disconnection associated with suicide ideation - thwarted belonging (TB) and perceived burden (PB) on others. Methods: The INQ-15 and measures of suicide ideation were administered to psychiatric outpatients (Nsample1 = 493; Nsample2 = 213) and psychiatric inpatients (Nsample3 = 79; Nsample4 = 87). Results: Reliable cut-off scores discriminating between the presence and absence of suicide ideation were identified across samples (TB ≥ 36 for psychiatric outpatients and ≥ 32 for inpatients; PB ≥ 12 for both psychiatric outpatients and inpatients). Limitations: Data are cross-sectional; thus, conclusions cannot be made about the predictive utility of INQ scores for future suicide ideation, attempts, or death. Conclusions: The INQ-15 yields scores with reliable cut-off scores for both TB and PB that represent clinically significant levels of social disconnection. These cut-off scores can be used in treatment trials and clinical practice to assess clinical improvement (or decline) in belonging and perceived burden.
Subject(s)
Inpatients , Interpersonal Relations , Humans , Cross-Sectional Studies , Psychometrics , Surveys and Questionnaires , Inpatients/psychology , Suicidal Ideation , Psychological Theory , Risk FactorsABSTRACT
A common pitfall of existing Science, Technology, Engineering, and Math (STEM) outreach programs is that they preferentially engage youth with a preexisting interest in STEM. Biomechanics has the unique potential to broaden access to STEM enrichment due to its direct applicability to sports and human performance. In this study we examine whether biomechanics within youth sports can be used as a venue for STEM outreach, and whether recruiting participants through youth sports programs could broaden access to the STEM pipeline. We created a four-hour sports science clinic that was performed as part of National Biomechanics Day and invited two groups of student participants: youth recruited through local high school sports programs ("Sports Cohort", N = 80) and youth recruited through existing STEM enrichment programs ("STEM Cohort", N = 31). We evaluated interest in STEM, Sports Science, and Sports using a pre-post survey. Somewhat expectedly, youth recruited through sports programs (Sports Cohort) had a lower baseline interest in STEM and a higher baseline interest in sports, compared to those recruited through STEM programs (STEM Cohort). The Sports Cohort exhibited a statistically significant increase in STEM interest following participation in the clinic, while youth in the STEM Cohort maintained their high baseline of STEM interest. These findings provide evidence that youth sports programs can serve as an attractive partner for biomechanists engaged in STEM outreach, and that situating STEM within sports through biomechanical analysis has potential to introduce STEM interest to a wider audience and to broaden access to the STEM fields among diverse youth.
Subject(s)
Sports , Youth Sports , Adolescent , Humans , Biomechanical Phenomena , Engineering , TechnologyABSTRACT
Genomic architecture appears to play crucial roles in health and a variety of diseases. How nuclear structures reorganize over different timescales is elusive, partly because the tools needed to probe and perturb them are not as advanced as needed by the field. To fill this gap, the National Institutes of Health Common Fund started a program in 2015, called the 4D Nucleome (4DN), with the goal of developing and ultimately applying technologies to interrogate the structure and function of nuclear organization in space and time.
Subject(s)
Cell Nucleus , Genome , United States , Cell Nucleus/genetics , GenomicsABSTRACT
Understanding individual differences in theory of mind (ToM; the ability to attribute mental states to others) in middle childhood and adolescence hinges on the availability of robust and scalable measures. Open-ended response tasks yield valid indicators of ToM but are labor intensive and difficult to compare across studies. We examined the reliability and validity of new machine learning and deep learning neural network automated scoring systems for measuring ToM in children and adolescents. Two large samples of British children and adolescents aged between 7 and 13 years (Sample 1: N = 1,135, Mage = 10.22 years, SD = 1.45; Sample 2: N = 1,020, Mage = 10.36 years, SD = 1.27) completed the silent film and strange stories tasks. Teachers rated Sample 2 children's social competence with peers. A single latent-factor explained variation in performance on both the silent film and strange stories task (in Sample 1 and 2) and test performance was sensitive to age-related differences and individual differences within each age-group. A deep learning neural network automated scoring system trained on Sample 1 exhibited interrater reliability and measurement invariance with manual ratings in Sample 2. Validity of ratings from the automated scoring system was supported by unique positive associations between ToM and teacher-rated social competence. The results demonstrate that reliable and valid measures of ToM can be obtained using the new freely available deep learning neural network automated scoring system to rate open-ended text responses. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Subject(s)
Deep Learning , Theory of Mind , Humans , Child , Adolescent , Theory of Mind/physiology , Reproducibility of Results , Motion Pictures , Social SkillsABSTRACT
Volume hyposensitivity resulting from impaired sympathetic detrusor relaxation during bladder filling contributes to detrusor underactivity (DU) associated with aging. Detrusor tension regulation provides an adaptive sensory input of bladder volume to the brainstem and is challenged by physiological stressors superimposed upon biological aging. We recently showed that HCN channels have a stabilizing role in detrusor sympathetic relaxation. While mature mice maintain homeostasis in the face of stressors, old mice are not always capable. In old mice, there is a dichotomous phenotype, in which resilient mice adapt and maintain homeostasis, while non-resilient mice fail to maintain physiologic homeostasis. In this DU model, we used cystometry as a stressor to categorize mice as old-responders (old-R, develop a filling/voiding cycle) or old-non-responders (old-NR, fail to develop a filling/voiding cycle; fluctuating high pressures and continuous leaking), while also assessing functional and molecular differences. Lamotrigine (HCN activator)-induced bladder relaxation is diminished in old-NR mice following HCN-blockade. Relaxation responses to NS 1619 were reduced in old-NR mice, with the effect lost following HCN-blockade. However, RNA-sequencing revealed no differences in HCN gene expression and electrophysiology studies showed similar percentage of detrusor myocytes expressing HCN (Ih) current between old-R and old-NR mice. Our murine model of DU further defines a role for HCN, with failure of adaptive recalibration of HCN participation and intensity of HCN-mediated stabilization, while genomic studies show upregulated myofibroblast and fibrosis pathways and downregulated neurotransmitter-degradation pathways in old-NR mice. Thus, the DU phenotype is multifactorial and represents the accumulation of age-associated loss in homeostatic mechanisms.
Subject(s)
Urinary Bladder, Underactive , Mice , Animals , Urinary Bladder , Aging/physiologyABSTRACT
OBJECTIVE: Increased demands during the transition into college can negatively impact students' physical and mental wellness, and increase risk of suicide. A supportive campus culture that promotes social connectedness and meaningful engagement may amplify wellness and prevent suicide. This study explored whether involvement in extracurricular activities was associated with wellness and suicide ideation and non-fatal suicidal behavior through perceived social support and meaningfulness. METHOD: Undergraduate students (N = 583) recruited from a southeastern university completed a survey of self-report measures. Two parallel mediation models were tested utilizing Hayes PROCESS macro for SPSS. RESULTS: Perceived social support fully mediated the relationship between extracurricular activity involvement and wellness, ß = 0.06, 95%CI [0.03, 0.10], but not suicide ideation and non-fatal suicidal behavior. Meaningfulness was not associated with wellness or suicide ideation and non-fatal suicidal behavior. CONCLUSION: Increased stress is a natural and expected component of university life. ECA involvement may impact college wellness by promoting social support.