Interpersonal Risk Factors, Sexual and Gender Minority Status, and Suicidal Ideation: Is BDSM Disclosure Protective?

Suicidal ideation is elevated among individuals who engage in BDSM practices and those with sexual and gender minority (SGM) identities. There is limited research on the intersectionality of these identities and how they relate to suicidal ideation, especially within a theoretical framework of suicide risk, such as the interpersonal theory of suicide. Thus, we tested the indirect relation between BDSM disclosure and suicidal ideation through thwarted belongingness and perceived burdensomeness, as well as the moderating role of SGM identity on these indirect associations. Participants were 125 (Mage = 28.27 years; 64% cisgender men) individuals recruited via online BDSM-related forums who endorsed BDSM involvement and recent suicidal ideation. Results indicated significant moderated mediation, such that BDSM disclosure was indirectly negatively related to suicidal ideation through lower thwarted belongingness, but not perceived burdensomeness, among SGM individuals. This was due to the significant relation between BDSM disclosure and thwarted belongingness. There were no significant moderated mediation or indirect effects related to perceived burdensomeness. We also provide supplemental analyses with positive ideation (i.e., positive thoughts toward life) as the criterion variable. In conclusion, BDSM disclosure appears to be protective against suicidal ideation through thwarted belongingness but only for SGM individuals. This work furthers our understanding of the impact of intersecting marginalized identities on suicide risk and resilience. Implications, limitations, and future directions are further discussed.

The moderating role of pessimism in the association between retrospective relational peer victimization, interpersonal risk factors, and suicide ideation.

Peer victimization (PV) is a serious concern for youth and is associated with subsequent suicide ideation in young adulthood. The interpersonal theory of suicide may provide a framework for understanding suicide ideation in this population. Specifically, thwarted belongingness (TB) and perceived burdensomeness (PB) have been significantly associated with suicide ideation among young adults with a history of peer victimization. Additionally, the personality trait of pessimism is associated with elevated suicide ideation. Thus, this study tested the association between self-reported frequency of retrospective relational (i.e., verbal and indirect) PV in primary and secondary school, thwarted interpersonal needs (TB and PB), and current suicide ideation, as well as how these relations may vary based on current pessimism. Participants were 330 undergraduate students. Nonparametric bootstrap moderated mediation procedures were used to test hypotheses. Results indicated significant indirect effects of frequency of retrospective relational PV and suicide ideation through PB and TB. Contrary to predictions, results did not indicate significant moderated mediation; however, the association between PB and suicide ideation was stronger at lower pessimism levels. We also provide supplemental analysis with optimism as the moderator. These findings suggest that clinicians may consider targeting TB, PB, as well as pessimism and optimism among those with a history of relational PV when assessing and intervening on current suicide ideation. Implications, limitations, and future directions are further discussed.

Personal growth initiative as a buffer against suicide ideation severity in psychotherapy outpatients with depressive symptoms.

OBJECTIVE: Many people who die by suicide experience major depressive disorder (MDD), but most people with MDD do not die by suicide and many do not report thoughts of death or suicide. This cross-sectional study examined the potential of personal growth initiative (PGI) skills to protect against suicide ideation among adult psychotherapy outpatients. METHOD: Adult outpatients (N = 178) completed measures of suicide ideation severity (SI), depressive symptom severity (DEP), and PGI skills (PGI) at intake. RESULTS: Although higher DEP significantly correlated with higher suicide ideation, a significant DEP × PGI interaction, indicated significant positive relations between DEP and SI only when PGI was at or below the mean for this sample. CONCLUSIONS: PGI skills may function as a protective factor against the development of suicide ideation even in the presence of severe depressive symptoms. This suggests that training PGI skills might prevent or reduce suicide ideation among depressed patients.

Short Warwick-Edinburgh Mental Well-being Scale (SWEMWBS): performance in a clinical sample in relation to PHQ-9 and GAD-7.

PURPOSE: This study assesses the construct validity and sensitivity to change of the Short Warwick-Edinburgh Mental Well-being Scale (SWEMWBS) as an outcome measure in the treatment of common mental disorders (CMD) in primary care settings. METHODS: 127 participants attending up to 5 sessions of therapy for CMD in primary care self-rated the SWEMWBS, the Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder (GAD-7) scales. SWEMWBS's construct validity and sensitivity to change was evaluated against the PHQ-9 and GAD-7 across multiple time points in two ways: correlation coefficients were calculated between the measures at each time point; and sensitivity to change over time was assessed using repeated measures ANOVA. RESULTS: Score distributions on SWEMWBS, but not PHQ-9 and GAD-7, met criteria for normality. At baseline, 92.9% (118/127) of participants scored above clinical threshold on either PHQ-9 or GAD-7. Correlations between SWEMWBS and PHQ-9 scores were calculated at each respective time point and ranged from 0.601 to 0.793. Correlations between SWEMWBS and GAD-7 scores were calculated similarly and ranged from 0.630 to 0.743. Significant improvements were seen on all three scales over time. Changes in PHQ-9 and GAD-7 were curvilinear with greatest improvement between sessions 1 and 2. Change in SWEMWBS was linear over the five sessions. CONCLUSIONS: This exploratory study suggests that SWEMWBS is acceptable as a CMD outcome measure in primary care settings, both in terms of construct validity and sensitivity to change. Given patient preference for positively over negatively framed measures and statistical advantages of measures which are normally distributed, SWEMWBS could be used as an alternative to PHQ-9 and GAD-7 in monitoring and evaluating CMD treatment.

Examining the relations between hopelessness, thwarted interpersonal needs, and passive suicide ideation among older adults: does meaning in life matter?

Older adults are at an elevated risk for passive suicide ideation. The interpersonal theory of suicide and the 3-step theory may provide a framework to better understand factors that contribute to passive suicide ideation among older adults. Specifically, this study aimed to test components of prominent suicide theories and examine the role of meaning in life in the associations between hopelessness, thwarted belongingness, perceived burdensomeness and passive suicide ideation among older adults. Participants were 243 adults aged 60 and older recruited from primary care settings in the southwest United States. We hypothesized that high meaning in life would weaken the associations between hopelessness, thwarted belongingness, perceived burdensomeness and passive suicide ideation. Results from moderation analyses indicate that meaning in life was a significant moderator of the associations between hopelessness and passive suicide ideation, thwarted belongingness and passive suicide ideation, and perceived burdensomeness and passive suicide ideation. These findings suggest that when meaning in life is low there are significant negative associations between hopelessness, thwarted belongingness, perceived burdensomeness and passive suicide ideation among older adults. Implications, limitations, and future directions are discussed.

The Intervening Roles of Psychological Inflexibility and Functional Impairment in the Relation between Cancer-related Pain and Psychological Distress.

BACKGROUND: Psychological distress is a significant problem among patients with a diagnosis of cancer and is associated with elevated risk for mortality; however, not all patients with a diagnosis of cancer experience significant psychological distress. Cancer-related pain has been associated with greater psychological distress among patients with a cancer diagnosis (current or previous). The current study aimed to examine potential theoretical mechanisms (i.e., cognitive fusion, experiential avoidance, and functional impairment) as proposed by the psychological flexibility model, for the association between cancer-related pain and psychological distress. We hypothesized that cancer-related pain would be indirectly positively associated with psychological distress among patients with a cancer diagnosis (current or previous) through psychological inflexibility (i.e., cognitive fusion and experiential avoidance) related to pain and functional impairment, in serial. METHOD: Sixty-one adult outpatients diagnosed with cancer completed self-report assessments of cancer-related pain, psychological inflexibility related to pain, pain-related functional impairment, and psychological distress. RESULTS: Cancer-related pain was positively associated with psychological distress indirectly through greater pain-related psychological inflexibility (i.e., cognitive fusion and experiential avoidance) and functional impairment, in serial. Alternative models were explored but unsupported. CONCLUSION: Consistent with the psychological flexibility model, psychological inflexibility and functional impairment may be potential mechanisms underlying the association between cancer-related pain and psychological distress among patients with a cancer diagnosis (current or previous).

Do criminal associates impact psychiatric inpatients' social support and interpersonal needs?

Suicide risk is elevated among psychiatric inpatients; however, research has not examined moderators of the associations between perceived social support and thwarted belongingness (TB) and perceived burdensomeness (PB), such as involvement with criminal associates. Adult psychiatric inpatients (N = 142) completed assessments. Perceived social support was negatively associated with TB and PB; however, associates' criminal involvement did not moderate these associations. A significant interaction indicated a stronger negative association between perceived social support and TB when participants spent more time with associates. Therefore, time spent with associates, regardless of criminal involvement, may be a relevant interpersonal suicide risk factor.

Experiential avoidance, cognitive fusion, and suicide ideation among psychiatric inpatients: The role of thwarted interpersonal needs.

OBJECTIVE: The interpersonal theory of suicide posits the simultaneous presence of thwarted belongingness and perceived burdensomeness (i.e., thwarted interpersonal needs) leads to active suicide ideation. According to the psychological flexibility model, psychological inflexibility is in part a product of cognitive fusion (i.e., becoming entangled or wrapped up in one's thoughts) and experiential avoidance (i.e., avoidance of internal private experiences, which include thoughts and feelings). We hypothesized that thwarted belongingness and perceived burdensomeness, in parallel, would mediate the positive relation between experiential avoidance and suicide ideation and between cognitive fusion and suicide ideation. METHOD: Participants were 118 adult psychiatric inpatients who completed self-report assessments of thwarted interpersonal needs, cognitive fusion, experiential avoidance, and suicide ideation. RESULTS: Using bootstrapped parallel mediation regression procedures, results indicated thwarted belongingness and perceived burdensomeness mediated, in parallel, the positive relation between experiential avoidance and suicide ideation and between cognitive fusion and suicide ideation. Additionally, thwarted belongingness, but not perceived burdensomeness, independently mediated the relation between cognitive fusion and suicide ideation. CONCLUSION: The current findings indicate that psychological inflexibility variables are associated with increased thwarted interpersonal needs and suicide ideation. The findings of this study provide support for the integration of the interpersonal theory of suicide and psychological flexibility model to improve our conceptualization of suicide risk among psychiatric inpatients. Clinical or methodological significance summary: The findings of this study provide support for the integration of the interpersonal theory of suicide and psychological flexibility model to improve our conceptualization of suicide risk among psychiatric inpatients.

Responsiveness of the Short Warwick Edinburgh Mental Well-Being Scale (SWEMWBS): evaluation a clinical sample.

BACKGROUND: SWEMWBS is a popular measure of mental wellbeing, shown to be valid in clinical populations. Responsiveness to change has not yet been formally assessed. METHODS: Analysis of data from a clinical sample of 172 clients undergoing up to 4 sessions of cognitive hypnotherapy. Cohen's D effect size (ES), Standardised response mean (SRM), probability of change statistic (P^) were used to evaluate whether SWEMWBS detected statistically important changes at the group level. Cohen's D effect size (ES) and Standard error of measurement (SEM) and were used to evaluate whether SWEMWBS detected statistically important changes at the individual level. RESULTS: Mean (SD) SWEMWBS scores increased from baseline to therapy 4 from 19.28 (3.921) to 23.32 (4.873). At group level, using Cohen's D effect size, improvement ranges from ES = 0.20-1.41 and using SRM, ranged from 0.30-0.88, increasing with number of therapy sessions. (P^) ranged from 0.65-0.8. At individual level, use of Cohens D ES > 0.5 indicated statistically important improvement in 29.9-86.1% cf. 20.1-80.6% using a standard of 2.77 SEM (2.87 points). The lower threshold of 1 SEM (1.03 points) indicated statistically important improvement in 43.0-81.0%. CONCLUSION: SWEMWBS is responsive to change at individual and group level. At individual level a change of between 1 and 3 points meets thresholds for statisticially important change, depending on standard used. Anchor based studies are necessary to confirm that such change represents minimally important change from the perspective of study participants.

Suicide Risk Among BDSM Practitioners: The Role of Acquired Capability for Suicide.

OBJECTIVE: Bondage and discipline, dominance and submission, and sadomasochism (BDSM) practitioners are at increased risk for suicidal thoughts and behaviors. We hypothesized the association between (a) lifetime frequency of BDSM-related sexual behaviors and (b) BDSM identification and suicide attempt status would be mediated by acquired capability components (i.e., fearlessness about death and pain tolerance). Gender differences were examined. METHOD: Participants were 576 BDSM practitioners (meanage = 28.71; 66.7% male) recruited from online BDSM-related groups, cross-sectionally. RESULTS: Among males, the total indirect effect of acquired capability components in the relation between BDSM-related sexual behaviors and suicide attempt status was significant. The specific indirect effect of perceived pain tolerance in the relation between both BDSM-related sexual behaviors and BDSM identification and suicide attempt status was significant. There were no significant effects for females. Additionally, 12% reported a suicide attempt history. CONCLUSION: Among males, BDSM-related sexual behaviors and BDSM identification were associated with increased acquired capability components, which were positively associated with suicide attempt status.

The clinical application of suicide risk assessment: A theory-driven approach.

The interpersonal theory of suicide posits that thwarted belongingness (TB) and perceived burdensomeness (PB) increase suicide ideation; however, studies have found mixed results regarding this hypothesis among psychiatric inpatients. This study aimed to (a) demonstrate how assessing TB and PB using the Interpersonal Needs Questionnaire (INQ) can provide clinically useful information and (b) investigate how statistical methodology may impact the clinical application of the INQ. Participants were 139 (Sample 1) and 104 (Sample 2) psychiatric inpatients. In both samples, ordinal logistic regression results indicated TB and PB, separately, were significant predictors of suicide ideation-related outcomes; however, when examined as simultaneous predictors, TB was no longer a significant predictor. The interaction between TB and PB was not significant for either sample. Despite this, TB and PB scores provided clinically relevant information about suicide ideation-related outcomes. For example, the highest scores on TB and PB indicated a 93% and 95% chance of having some level of distress due to suicide ideation (Sample 1), a 91% and 92% chance of having some level of desire for death, and a 79% and 84% chance of having some level of desire for suicide, respectively (Sample 2). This study also proposes clinical cutoff scores for the INQ (for TB and PB, respectively, cutoff scores were 22 and 17 for distress due to suicide ideation, 33 and 17 for desire for death, and 31 and 22 for desire for suicide). Although these results indicate that multicollinearity between TB and PB may create interpretational ambiguity for clinicians, TB and PB may each be useful separate predictors of suicide ideation-related outcomes in psychiatric inpatient settings and should be incorporated into suicide risk assessment. KEY PRACTITIONER MESSAGE: The 15-item Interpersonal Needs Questionnaire (an assessment of thwarted belongingness and perceived burdensomeness) should be incorporated into suicide risk assessment. Among psychiatric inpatients, greater thwarted belongingness and perceived burdensomeness, as separate predictors, were associated with increased levels of distress due to suicide ideation, desire for death, and desire for suicide. The highest scores on thwarted belongingness and perceived burdensomeness indicated a 79% to 95% chance of experiencing an elevated level of distress due to suicide ideation, desire for death, or desire for suicide. Recommended clinical cutoff scores were provided. For example, thwarted belongingness cutoff score of 31 and perceived burdensomeness cutoff score of 22 maximized the sensitivity and specificity of the INQ to detect some level of desire for suicide.

Synthesis of a simplified triazole analogue of pateamine A.

Pateamine A is a naturally occurring metabolite extracted from the marine sponge Mycale hentscheli. It exhibits potent cytotoxicity towards cancer cell lines and has been shown to target protein translation initiation via inhibition of the function of eukaryotic initiation factor 4A proteins. We have synthesised a simplified analogue of pateamine A, consisting of the skeletal core of the natural product but with the thiazole heterocycle replaced by a triazole. The convergent design of the synthesis features a base-induced opening of a δ-valerolactone to access the Z,E-dienoate moiety, Julia-Kocienski olefination and copper-catalysed azide-alkyne cycloaddition. Bioactivity testing of the simplified pateamine A analogue (3) indicated a significant reduction in cytotoxicity, compared to natural pateamine A. We propose that this reduced activity is due mainly to the substitution of the thiazole for the triazole heterocycle. This supports the hypothesis that the thiazole of pateamine A is important for binding to its biological target.

Public mental health: an interdisciplinary subject?

The Chief Medical Officer's report for 2013 was the first of its kind to highlight the public's mental rather than physical health and thus represents a very important landmark for public health in the UK. Written primarily from the perspective of psychiatrists, the report has created confusion in public health circles by failing to adequately address the public health perspective. David Foreman's editorial in this issue, calling as it does for more training in public health for psychiatrists, is therefore very welcome and timely.

Research priorities for public mental health in Europe: recommendations of the ROAMER project.

BACKGROUND: The ROAdmap for MEntal health Research in Europe project aimed to create an integrated European roadmap for mental health research. Leading mental health research experts across Europe have formulated consensus-based recommendations for future research within the public mental health field. METHODS: Experts were invited to compile and discuss research priorities in a series of topic-based scientific workshops. In addition, a Delphi process was carried out to reach consensus on the list of research priorities and their rank order. Three web-based surveys were conducted. Nearly 60 experts were involved in the priority setting process. RESULTS: Twenty priorities for public mental health research were identified through the consensus process. The research priorities were divided into summary principles-encompassing overall recommendations for future public mental health research in Europe-and thematic research priorities, including area-specific top priorities on research topics and methods. The priorities represent three overarching goals mirroring societal challenges, that is, to identify causes, risk and protective factors for mental health across the lifespan; to advance the implementation of effective public mental health interventions and to reduce disparities in mental health. CONCLUSIONS: The importance of strengthening research on the implementation and dissemination of promotion, prevention and service delivery interventions in the mental health field needs to be emphasized. The complexity of mental health and its broader conceptualisation requires complementary research approaches and interdisciplinary collaboration to better serve the needs of the European population.

A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells.

Susceptibility to Crohn's disease, a complex inflammatory disease involving the small intestine, is controlled by over 30 loci. One Crohn's disease risk allele is in ATG16L1, a gene homologous to the essential yeast autophagy gene ATG16 (ref. 2). It is not known how ATG16L1 or autophagy contributes to intestinal biology or Crohn's disease pathogenesis. To address these questions, we generated and characterized mice that are hypomorphic for ATG16L1 protein expression, and validated conclusions on the basis of studies in these mice by analysing intestinal tissues that we collected from Crohn's disease patients carrying the Crohn's disease risk allele of ATG16L1. Here we show that ATG16L1 is a bona fide autophagy protein. Within the ileal epithelium, both ATG16L1 and a second essential autophagy protein ATG5 are selectively important for the biology of the Paneth cell, a specialized epithelial cell that functions in part by secretion of granule contents containing antimicrobial peptides and other proteins that alter the intestinal environment. ATG16L1- and ATG5-deficient Paneth cells exhibited notable abnormalities in the granule exocytosis pathway. In addition, transcriptional analysis revealed an unexpected gain of function specific to ATG16L1-deficient Paneth cells including increased expression of genes involved in peroxisome proliferator-activated receptor (PPAR) signalling and lipid metabolism, of acute phase reactants and of two adipocytokines, leptin and adiponectin, known to directly influence intestinal injury responses. Importantly, Crohn's disease patients homozygous for the ATG16L1 Crohn's disease risk allele displayed Paneth cell granule abnormalities similar to those observed in autophagy-protein-deficient mice and expressed increased levels of leptin protein. Thus, ATG16L1, and probably the process of autophagy, have a role within the intestinal epithelium of mice and Crohn's disease patients by selective effects on the cell biology and specialized regulatory properties of Paneth cells.

A Psychometric Evaluation of the Interpersonal Hopelessness Scale Among Individuals With Elevated Suicide Risk.

The interpersonal theory of suicide hypothesizes that suicide ideation (SI) emerges specifically in the context of hopelessness about the immutability of thwarted belongingness (TB) and perceived burdensomeness (PB; i.e., interpersonal hopelessness). The psychometrics of the Interpersonal Hopelessness Scale (IHS), which could be used to test this hypothesis directly, have not been rigorously evaluated. Participants (U.S. adults reporting past-year SI) completed online self-report assessments at Waves 1 (W1; N = 595) and 2 (W2; N = 215), 1 week apart. Confirmatory factor analyses supported a two-factor structure, IHS-TB and IHS-PB. Correlations indicated strong concurrent validity. Hurdle negative binomial regressions indicated that W1 IHS-TB and IHS-PB scores were associated with SI presence and severity at both waves, but this was inconsistent when adjusting for other W1 variables. IHS-TB and IHS-PB demonstrated excellent internal consistency and moderate to good test-retest reliability. The IHS could improve theory testing and suicide risk assessment and management.

A Prospective Examination of Sexual Orientation and Suicidal and Nonsuicidal Self-Injurious Thoughts and Behaviors Among a Diverse Sample of At-risk Young Adult Women.

Minoritized sexual orientation is an established correlate for suicide ideation (SI) and nonsuicidal self-injury (NSSI); however, prospective associations between sexual orientation and SI and NSSI is limited. The current study builds on existing literature by examining sexual orientation as a prospective distal risk factor for SI and NSSI risk among a diverse sample of young women after adjusting for histories of SI and/or NSSI and empirically supported correlates and risk factors. Participants were 135 young adult women (aged 18-24), who were predominately Black with approximately half of the sample experiencing poverty. Participants completed an interview that assessed SI and NSSI at baseline and 6- and 12-month follow-ups. A single item was used to collect participants' self-identified sexual orientation at baseline. Minoritized sexual orientation was strongly associated with NSSI history and future SI and NSSI, adjusting for baseline correlates and predictors of interest. Psychological and physical victimization, race, and poverty were non-significant prospective predictors of SI and NSSI. Race and poverty did not moderate the associations between sexual orientation and follow-up SI and NSSI. These findings suggest young adult women who self-identify as lesbian, gay, bisexual, queer, or questioning (LGBQ) are more likely than those who identify as heterosexual to experience both SI and NSSI in the following year. Sexual orientation should be part of a culturally-informed comprehensive risk assessment. A culturally-informed intersectionality approach may be necessary to identify culturally-specific risk and resiliency factors for SI and NSSI that can guide effective prevention and intervention strategies for LGBQ individuals.

Examining sleep disturbance components as near-term predictors of suicide ideation in daily life.

Suicide ideation emerges and fluctuates over short timeframes (minutes, hours, days); however, near-term predictors of such fluctuations have not been well-elucidated. Sleep disturbance is a distal suicide risk factor, but less work has examined whether daily sleep disturbance predicts near-term changes in suicide ideation. We examined subjective sleep disturbance components as predictors of passive and active suicide ideation at the within-person (i.e., day-to-day changes within individuals relative to their own mean) and between-persons (individual differences relative to the sample mean) levels. A transdiagnostic sample of 102 at-risk young adults ages 18-35 completed a 21-day ecological momentary assessment protocol, during which they reported on sleep and passive and active suicide ideation. At the within-persons level, nightmares, sleep quality, and wake after sleep onset predicted passive suicide ideation, and sleep quality and wake after sleep onset predicted active suicide ideation. At the between-persons level, nightmares, sleep onset latency, and sleep quality were associated with passive suicide ideation, and sleep onset latency was associated with active suicide ideation. In contrast, suicide ideation did not predict subsequent sleep at the within-person level. Specific sleep disturbance components are near-term predictors of intraindividual increases in suicide ideation and may hold promise for suicide prevention and intervention.

Development of a Questionnaire to Measure Public Perceptions of the Role of Community Pharmacy in Public Health (PubPharmQ).

BACKGROUND: Community pharmacies are well placed to provide public-health interventions within primary care settings. This study aimed to establish the general public's perceptions of community pharmacy-based public-health services in the UK by designing a structured questionnaire to assess the barriers and facilitators to optimizing this role. METHODS: A standardized questionnaire was developed informed by the literature, additional semi-structured interviews, and synthesis of key findings with the authors' previous research based on data generated from eight focus groups. The original 42-item questionnaire was distributed online from May to June 2021 via social media platforms to capture the views of non-regular pharmacy users. Following exploratory factor analysis, and Cronbach's alpha analysis, total Likert scale response scores were calculated. RESULTS: Of the 306 responders, 76.8% were female with a mean age of 34.5 years (SD = 15.09). The most prevalent pharmacy use reported was 1-2 times a year (28.1%). Exploratory factor analysis revealed four scales: Expertise, Role in Public Health, Privacy, and Relationship (18 items) with acceptable internal consistency and good face and content validity. Awareness of well-established pharmacy services was high; however, responders demonstrated poor awareness of public-health-related services and low recognition of pharmacy expertise for this role. A lack of an established relationship with community pharmacies and privacy concerns were also perceived barriers. CONCLUSIONS: Based on these findings, considerable effort is needed to increase public awareness and address these concerns if strategic plans to utilize community pharmacy in the delivery of public-health policy are to be successful. The PubPharmQ provides a novel, structured questionnaire to measure the public's perceptions of community pharmacy's role in public health.

Efficient colonic mucosal wound repair requires Trem2 signaling.

The colonic epithelial lining undergoes constant replacement, driven by epithelial stem cells in crypts of Lieberkühn. Stem cells lost because of damage or disease can be replaced by adjacent crypts that undergo fission. The close proximity of an extraordinary number of luminal microbes creates a challenge for this repair process; infection must be prevented while immune system activation and epithelial stem cell genetic damage must be minimized. To understand the factors that modulate crypt/stem cell replacement in the mouse colon, we developed an in vivo acute injury system analogous to punch biopsy of the skin. In contrast to epidermal stem cells, colonic epithelial progenitors did not migrate over the wound bed. Instead, their proliferative expansion was confined to crypts adjacent to wound beds and was delayed to the latter phase of healing. This increased epithelial proliferation was coincident with the infiltration of Trem2 expressing macrophages and increased expression of IL-4 and IL-13 in the wound bed. Interestingly, Trem2(-/-) mice displayed slow and incomplete wound healing of colonic mucosal injuries. We found the latter phase of healing in Trem2(-/-) mice showed a diminished burst of epithelial proliferation, increased expression of IFN-gamma and TNF-alpha, diminished expression of IL-4 and IL-13, and increased markers of classical macrophage activation. Ablation of these cytokines in injured WT and Trem2(-/-) mice demonstrated that their expression ultimately determined the rate and nature of wound healing. These studies show that Trem2 signaling is an important pathway to promote healing of wounds in the colon where stem cell replacement is necessary.