Dynamic YAP expression in the non-parenchymal liver cell compartment controls heterologous cell communication.

INTRODUCTION: The Hippo pathway and its transcriptional effectors yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are targets for cancer therapy. It is important to determine if the activation of one factor compensates for the inhibition of the other. Moreover, it is unknown if YAP/TAZ-directed perturbation affects cell-cell communication of non-malignant liver cells. MATERIALS AND METHODS: To investigate liver-specific phenotypes caused by YAP and TAZ inactivation, we generated mice with hepatocyte (HC) and biliary epithelial cell (BEC)-specific deletions for both factors (YAPKO, TAZKO and double knock-out (DKO)). Immunohistochemistry, single-cell sequencing, and proteomics were used to analyze liver tissues and serum. RESULTS: The loss of BECs, liver fibrosis, and necrosis characterized livers from YAPKO and DKO mice. This phenotype was weakened in DKO tissues compared to specimens from YAPKO animals. After depletion of YAP in HCs and BECs, YAP expression was induced in non-parenchymal cells (NPCs) in a cholestasis-independent manner. YAP positivity was detected in subgroups of Kupffer cells (KCs) and endothelial cells (ECs). The secretion of pro-inflammatory chemokines and cytokines such as C-X-C motif chemokine ligand 11 (CXCL11), fms-related receptor tyrosine kinase 3 ligand (FLT3L), and soluble intercellular adhesion molecule-1 (ICAM1) was increased in the serum of YAPKO animals. YAP activation in NPCs could contribute to inflammation via TEA domain transcription factor (TEAD)-dependent transcriptional regulation of secreted factors. CONCLUSION: YAP inactivation in HCs and BECs causes liver damage, and concomitant TAZ deletion does not enhance but reduces this phenotype. Additionally, we present a new mechanism by which YAP contributes to cell-cell communication originating from NPCs.

Eyes Fixed on Heaven's Gate: An Empirical Examination of Blink Rate and Suicide.

Anecdotal and theoretical work suggests blink rate as an indicator of imminent suicide risk. We sought to empirically examine whether suicide decedents displayed a reduced blink rate in goodbye videos filmed before death, compared to several control groups. Independent raters coded blink rates from videos of 34 suicide decedents and four comparison groups: "mundane" product review, non-suicidal arousal, non-suicidal depression, and non-imminent risk of suicidal ideation. Mean blink rate was lower in the suicide decedent group relative to all comparison groups (ps < .001), except the depressed (p = .976) and suicidal ideation (p = .393) groups. Findings indicate blink rate may be reduced among individuals at imminent risk for suicide, exhibiting clinically-significant depressive symptoms, or experiencing suicidal ideation.

Spatial modeling reveals nuclear phosphorylation and subcellular shuttling of YAP upon drug-induced liver injury.

The Hippo signaling pathway controls cell proliferation and tissue regeneration via its transcriptional effectors yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). The canonical pathway topology is characterized by sequential phosphorylation of kinases in the cytoplasm that defines the subcellular localization of YAP and TAZ. However, the molecular mechanisms controlling the nuclear/cytoplasmic shuttling dynamics of both factors under physiological and tissue-damaging conditions are poorly understood. By implementing experimental in vitro data, partial differential equation modeling, as well as automated image analysis, we demonstrate that nuclear phosphorylation contributes to differences between YAP and TAZ localization in the nucleus and cytoplasm. Treatment of hepatocyte-derived cells with hepatotoxic acetaminophen (APAP) induces a biphasic protein phosphorylation eventually leading to nuclear protein enrichment of YAP but not TAZ. APAP-dependent regulation of nuclear/cytoplasmic YAP shuttling is not an unspecific cellular response but relies on the sequential induction of reactive oxygen species (ROS), RAC-alpha serine/threonine-protein kinase (AKT, synonym: protein kinase B), as well as elevated nuclear interaction between YAP and AKT. Mouse experiments confirm this sequence of events illustrated by the expression of ROS-, AKT-, and YAP-specific gene signatures upon APAP administration. In summary, our data illustrate the importance of nuclear processes in the regulation of Hippo pathway activity. YAP and TAZ exhibit different shuttling dynamics, which explains distinct cellular responses of both factors under physiological and tissue-damaging conditions.

Environmental impacts of eco-nutrition swine feeding programs in spatially explicit geographic regions of the United States.

This study was conducted to determine greenhouse gas (GHG) emissions, water consumption, land use, as well as nitrogen (N), phosphorus (P), and carbon (C) balance of five diet formulation strategies and feeding programs for growing-finishing pigs (25-130 kg body weight) in the three spatially explicit geographic regions where the majority of U.S. pork production occurs. Feeding programs evaluated consisted of 1) standard corn-soybean meal (CSBM) diets, 2) CSBM containing 15% corn distillers dried grains with solubles (DDGS), 3) CSBM with 8.6% thermally processed supermarket food waste (FW), 4) low crude protein CSBM diets supplemented with synthetic amino acids (SAA), and 5) CSBM with phytase enzyme (PHY) added at 600 FTU (phytase units)/kg of diet. An attributional Life Cycle Assessment approach using a highly specialized, spatially explicit Food System Supply-Chain Sustainability (FoodS3) model was used to quantify GHG emissions, water consumption, and land use of corn, soybean meal, and DDGS based on county level sourcing. The DDGS, FW, and SAA feeding programs had less estimated N and P intake and excretion than CSBM, and the PHY feeding program provided the greatest reduction in P excretion. The FW feeding program had the least overall GHG emissions (319.9 vs. 324.6 to 354.1 kg CO2 equiv./market hog), land use (331.5 vs. 346.5 to 385.2 m2/market hog), and water consumption (7.64 vs. 7.70 to 8.30 m3/market hog) among the alternatives. The DDGS feeding program had the greatest GHG emissions (354.1 kg CO2 equiv./market hog) among all programs but had less impacts on water consumption (7.70 m3) and land use (346.5 m2) per market hog than CSBM and PHY. The SAA feeding program provided a 6.5-7.4% reduction in land use impacts compared with CSBM and PHY, respectively. Regardless of feeding program, the Midwest had the least contributions to GHG emissions and land use attributed to feed and manure among regions. Water consumption per market hog associated with feeding programs was much greater in the Southwest (59.66-63.58 m3) than in the Midwest (4.45-4.88 m3) and Mid-Atlantic (1.85-2.14 m3) regions. Results show that diet composition and U.S. geographic region significantly affect GHG emissions, water consumption, and land use of pork production systems, and the potential use of thermally processed supermarket food waste at relatively low diet inclusion rates (<10%) can reduce environmental impacts compared with other common feeding strategies.

Very few studies have been conducted to determine the differences in environmental impacts based on the diet composition of growing-finishing swine feeding programs across major pork production regions in the United States. Therefore, the objective of this study was to determine and compare greenhouse gas (GHG) emissions, water consumption, land use, as well as nitrogen (N), phosphorus (P), and carbon (C) balance of five diet formulation strategies and feeding programs for growing-finishing pigs (25­130 kg body weight) in the three spatially explicit U.S. pork production regions. The corn dried distillers grains with solubles (DDGS), food waste (FW), and low protein-synthetic amino acid (SAA) diets had less estimated N and P excretion compared with corn-soybean meal (CSBM) diets, and the addition of phytase (PHY) to CSBM diets resulted in the greatest reduction in P excretion among feeding programs. Adding FW to diets resulted in the least overall greenhouse gas emissions, water consumption, and land use compared with all other feeding programs, and land use was less for the DDGS and SAA feeding programs than CSBM and PHY feeding programs. The Midwest had the least GHG emissions and land use impact compared with other regions, while the Southwest region had the greatest water consumption associated with feeding programs.

Global Registries in Congenital Hyperinsulinism.

Congenital hyperinsulinism (HI) is the most frequent cause of severe, persistent hypoglycemia in newborn babies and children. There are many areas of need for HI research. Some of the most critical needs include describing the natural history of the disease, research leading to new and better treatments, and identifying and managing hypoglycemia before it is prolonged and causes brain damage or death. Patient-reported data provides a basis for understanding the day-to-day experience of living with HI. Commonly identified goals of registries include performing natural history studies, establishing a network for future product and treatment studies, and supporting patients and families to offer more successful and coordinated care. Congenital Hyperinsulinism International (CHI) created the HI Global Registry (HIGR) in October 2018 as the first global patient-powered hyperinsulinism registry. The registry consists of thirteen surveys made up of questions about the patient's experience with HI over their lifetime. An international team of HI experts, including family members of children with HI, advocates, clinicians, and researchers, developed the survey questions. HIGR is managed by CHI and advised by internationally recognized HI patient advocates and experts. This paper aims to characterize HI through the experience of individuals who live with it. This paper includes descriptive statistics on the birthing experience, hospitalizations, medication management, feeding challenges, experiences with glucose monitoring devices, and the overall disease burden to provide insights into the current data in HIGR and demonstrate the potential areas of future research. As of January 2022, 344 respondents from 37 countries consented to participate in HIGR. Parents or guardians of individuals living with HI represented 83.9% of the respondents, 15.3% were individuals living with HI. Data from HIGR has already provided insight into access challenges, patients' and caregivers' quality of life, and to inform clinical trial research programs. Data is also available to researchers seeking to study the pathophysiology of HI retrospectively or to design prospective trials related to improving HI patient outcomes. Understanding the natural history of the disease can also guide standards of care. The data generated through HIGR provides an opportunity to improve the lives of all those affected by HI.

Congenital Hyperinsulinism International: A Community Focused on Improving the Lives of People Living With Congenital Hyperinsulinism.

Congenital hyperinsulinism (HI) is a rare disease affecting newborns. HI causes severe hypoglycemia due to the overproduction of insulin. The signs and symptoms of hypoglycemia in HI babies is often not discovered until brain damage has already occurred. Prolonged hypoglycemia from HI can even lead to death. Disease management is often complex with a high burden on caregivers. Treatment options are extremely limited and often require long hospital stays to devise. Cascading from suboptimal treatments and diagnostic practices are a host of other problems and challenges that many with HI and their families experience including continued fear of hypoglycemia and feeding problems. The aim of this paper is (1) to describe the current challenges of living with HI including diagnosis and disease management told from the perspective of people who live with the condition (2), to provide family stories of life with HI, and (3) to share how a rare disease patient organization, Congenital Hyperinsulinism International (CHI) is working to improve the lives of HI patients and their families. CHI is a United States based nonprofit organization with a global focus. The paper communicates the programs the patient advocacy organization has put into place to support HI families through its virtual and in-person gatherings. The organization also helps individuals access diagnostics, medical experts, and treatments. CHI also raises awareness of HI to improve patient outcomes with information about HI and prolonged hypoglycemia in twenty-three languages. CHI drives innovation for new and better treatments by funding research pilot grants, conducting research through the HI Global Registry, and providing patient experience expertise to researchers developing new treatments. The organization is also the sponsor of the CHI Collaborative Research Network which brings medical and scientific experts together for the development of a patient-focused prioritized research agenda.

Acquired Resistance to Antiangiogenic Therapies in Hepatocellular Carcinoma Is Mediated by Yes-Associated Protein 1 Activation and Transient Expansion of Stem-Like Cancer Cells.

Induction of neoangiogenesis is a hallmark feature during disease progression of hepatocellular carcinoma (HCC). Antiangiogenetic compounds represent a mainstay of therapeutic approaches; however, development of chemoresistance is observed in the majority of patients. Recent findings suggest that tumor-initiating cells (TICs) may play a key role in acquisition of resistance, but the exact relevance for HCC in this process remains to be defined. Primary and established hepatoma cell lines were exposed to long-term sorafenib treatment to model acquisition of resistance. Treatment effects on TICs were estimated by sphere-forming capacity in vitro, tumorigenicity in vivo, and flow cytometry. Adaptive molecular changes were assessed by whole transcriptome analyses. Compensatory mechanisms of resistance were identified and directly evaluated. Sustained antiproliferative effect following sorafenib treatment was observed in three of six HCC cell lines and was followed by rapid regrowth, thereby mimicking responses observed in patients. Resistant cells showed induction in sphere forming in vitro and tumor-initiating capacity in vivo as well as increased number of side population and epithelial cell adhesion molecule-positive cells. Conversely, sensitive cell lines showed consistent reduction of TIC properties. Gene sets associated with resistance and poor prognosis, including Hippo/yes-associated protein (YAP), were identified. Western blot and immunohistochemistry confirmed increased levels of YAP. Combined treatment of sorafenib and specific YAP inhibitor consistently revealed synergistic antioncogenic effects in resistant cell lines. Conclusion: Resistance to antiangiogenic therapy might be driven by transient expansion of TICs and activation of compensatory pro-oncogenic signaling pathways, including YAP. Specific targeting of TICs might be an effective therapeutic strategy to overcome resistance in HCC.

Co-expression of YAP and TAZ associates with chromosomal instability in human cholangiocarcinoma.

BACKGROUND: Activation of the oncogene yes-associated protein (YAP) is frequently detected in intrahepatic cholangiocarcinoma (iCCA); however, the expression pattern and the functional impact of its paralogue WW domain-containing transcription regulator 1 (WWTR1; synonym: TAZ) are not well described in different CCA subtypes. METHODS: Immunohistochemical analysis of YAP and TAZ in iCCA and extrahepatic CCA (eCCA) cohorts was performed. YAP/TAZ shuttling and their functional impact on CCA cell lines were investigated. Target genes expression after combined YAP/TAZ inhibition was analyzed. RESULTS: Immunohistochemical analysis of iCCA and eCCA revealed YAP or TAZ positivity in up to 49.2%; however, oncogene co-expression was less frequent (up to 23%). In contrast, both proteins were jointly detectable in most CCA cell lines and showed nuclear/cytoplasmic shuttling in a cell density-dependent manner. Next to the pro-proliferative function of YAP/TAZ, both transcriptional co-activators cooperated in the regulation of a gene signature that indicated the presence of chromosomal instability (CIN). A correlation between YAP and the CIN marker phospho-H2A histone family member X (pH2AX) was particularly observed in tissues from iCCA and distal CCA (dCCA). The presence of the CIN genes in about 25% of iCCA was statistically associated with worse prognosis. CONCLUSIONS: YAP and TAZ activation is not uncoupled from cell density in CCA cells and both factors cooperatively contribute to proliferation and expression of CIN-associated genes. The corresponding group of CCA patients is characterized by CIN and may benefit from YAP/TAZ-directed therapies.

Military Suicide Research Consortium common data elements: Bifactor analysis and longitudinal predictive ability of suicidal ideation and suicide attempts within a clinical sample.

To enhance and standardize the assessment of suicidal self-directed violence (SDV) in military populations, the Military Suicide Research Consortium developed the Common Data Elements (CDEs). Previous research supported the CDEs as assessing a higher-order factor of suicidal SDV in military populations. The present study had two aims: 1) confirm the bifactor structure of the CDEs in a high-risk sample, and 2) assess the ability of the factorially derived suicidal SDV factor to predict suicide attempts and return to care for suicidal ideation over 3-month follow-up. Utilizing a sample of service members referred for a psychiatric evaluation (N = 1,044), the CDE structure was assessed with confirmatory bifactor modeling. Logistic regressions and receiver operating characteristic (ROC) analyses were used to assess the suicidal SDV risk factor's prediction of suicide attempts and return to care for suicidal ideation during follow-up (n = 758). Bifactor modeling suggested adequate fit for the overarching suicidal SDV risk factor. Logistic regressions supported the overarching suicidal SDV risk factor as a predictor of suicide attempts (OR = 4.07, p < .001) and return to care for suicidal ideation (OR = 2.81, p < .001) over follow-up. However, ROC analyses suggested that the model including the suicidal SDV risk factor was only significantly better at classifying suicide attempts over follow-up (not return to care for suicidal ideation) than the model that did not include it (AUC difference = 0.15, p < .001). Findings suggest that the shared variance assessed across CDEs better predicts future suicide attempts beyond any individual suicide-related constructs. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Prospective Implementation and Evaluation of a Decision-Tree Algorithm for Route of Hysterectomy.

OBJECTIVE: To evaluate the rate of vaginal hysterectomy and outcomes after initiation of a prospective decision-tree algorithm to determine the optimal surgical route of hysterectomy. METHODS: A prospective algorithm to determine optimal route of hysterectomy was developed, which uses the following factors: history of laparotomy, uterine size, and vaginal access. The algorithm was implemented at our institution from November 24, 2015, to December 31, 2017, for patients requiring hysterectomy for benign indications. Expected route of hysterectomy was assigned by the algorithm and was compared with the actual route performed to identify compliance compared with deviation. Surgical outcomes were analyzed. RESULTS: Of 365 patients who met inclusion criteria, 202 (55.3%) were expected to have a total vaginal hysterectomy, 57 (15.6%) were expected to have an examination under anesthesia followed by total vaginal hysterectomy, 52 (14.2%) were expected to have an examination under anesthesia followed by robotic-assisted total laparoscopic hysterectomy, and 54 (14.8%) were expected to have an abdominal or robotic-laparoscopic route of hysterectomy. Forty-six procedures (12.6%) deviated from the algorithm to a more invasive route (44 robotic, two abdominal). Seven patients had total vaginal hysterectomy when robotic-assisted total laparoscopic hysterectomy or abdominal hysterectomy was expected by the algorithm. Overall, 71% of patients were expected to have a vaginal route of hysterectomy per the algorithm, of whom 81.5% had a total vaginal hysterectomy performed; more than 99% of the total vaginal hysterectomies attempted were successfully completed. CONCLUSION: Vaginal surgery is feasible, carries a low complication rate with excellent outcomes, and should have a place in gynecologic surgery. National use of this prospective algorithm may increase the rate of total vaginal hysterectomy and decrease health care costs.

Reducing anticipated non-suicidal self-injury by improving body esteem in individuals with weight suppression: A proof of concept study.

OBJECTIVE: Research suggests that weight suppression (WS) is linked to non-suicidal self-injury (NSSI) and that drive for thinness and depression may explain this association. We conducted a proof-of-concept study using a randomized control trial design to determine if improving body esteem and reducing depressive symptoms reduced NSSI in individuals with WS. METHOD: Weight suppressed participants (N = 60) who engaged in NSSI were recruited from the community and randomly assigned to an on-line intervention or control condition. The on-line intervention was adapted from a cognitive-dissonance intervention originally designed to reduce thin-ideal internalization in females to an intervention to reduce internalization of unhealthy body ideals in both genders. Participants' weight/shape concerns, depressive symptoms, and NSSI were assessed at pre- and post-intervention, or at baseline and 2-week follow-up for controls. RESULTS: Compared to controls, participants in the treatment condition reported greater decreases in likelihood of future NSSI [Cohen's d (95% CI) = -0.38 (-0.90-0.15)], weight/shape concerns [-1.19 (-1.75 to -0.62)], depressive symptoms [-1.00 (-1.56 to -0.45)], and significant improvements in appearance [1.27 (0.70-1.84)] and weight esteem [1.38 (0.80-1.96)]. DISCUSSION: Future work could test this intervention in a larger trial with an active alternative treatment condition.

Outcomes of Vaginal Hysterectomy With and Without Perceived Contraindications to Vaginal Surgery.

OBJECTIVE: The aim of this study was to compare outcomes of vaginal hysterectomy between patients with and without the following perceived contraindications to vaginal surgery: uterine weight greater than 280 g, prior cesarean delivery, no vaginal parity, and obesity. METHODS: Retrospective cohort of benign vaginal hysterectomies between 2009 and 2013 was obtained. Outcomes included uterine debulking, transfusion, intraoperative complications, length of stay, and Accordion grade 2+ postoperative complications. For each outcome, the association between the presence of each contraindication and the outcome was evaluated using univariate and multivariate logistic regression models. RESULTS: Among 692 vaginal hysterectomies, 11% (76/691) had a uterine weight greater than 280 g, 11.3% (78/690) had no vaginal parity, 14.9% (103/690) had a history of cesarean delivery, and 37.7% (248/657) had a body mass index of 30 kg/m or greater; 110 (15.9%) had 2 or more contraindications. Uterine debulking occurred in 146 women (21.1%), and both uterine weight greater 280 g (adjusted odds ratio, 39.2; 95% confidence interval, 18.4-83.5) and prior cesarean delivery (adjusted odds ratio, 2.1; 95% confidence interval, 1.2-3.7) were significantly associated with an increased likelihood of uterine debulking after adjusting for age, hematologic disease, and preoperative diagnosis. None of the contraindications were significantly associated with need for a blood transfusion, presence of an intraoperative complication, length of stay greater than 2 days, or presence of an Accordion grade 2+ postoperative complication, which occurred in 2.7%, 2.5%, 14.0%, and 6.9% of all women, respectively. CONCLUSIONS: Vaginal hysterectomy can be safely performed with favorable outcomes, even in women with a uterus greater than 280 g, prior cesarean delivery, no vaginal parity, and obesity. Our findings challenge several perceived contraindications to vaginal hysterectomy.

The Military Suicide Research Consortium Common Data Elements: An Examination of Measurement Invariance Across Current Service Members and Veterans.

Suicide rates within the U.S. military are elevated, necessitating greater efforts to identify those at increased risk. This study utilized a multigroup confirmatory factor analysis to examine measurement invariance of the Military Suicide Research Consortium Common Data Elements (CDEs) across current service members (n = 2,015), younger veterans (<35 years; n = 377), and older veterans (≥35 years; n = 1,001). Strong factorial invariance was supported with adequate model fit observed for current service members, younger veterans, and older veterans. The structures of all models were generally comparable with few exceptions. The Military Suicide Research Consortium CDEs demonstrate at least adequate model fit for current military service members and veterans, regardless of age. Thus, the CDEs can be validly used across military and veteran populations. Given similar latent structures, research findings in one group may inform clinical and policy decision making for the other.

Exercise dependence: Associations with capability for suicide and past suicidal behavior.

OBJECTIVE: Exercise dependence has been linked to capability for suicide and suicidal behavior; however, less understood are which facets of exercise dependence confer risk for suicidal behavior and the potential mechanisms of this association. This study examined relationships between exercise dependence, capability for suicide, and past suicidal behavior. METHODS: A sample of 540 individuals recruited via MTurk completed online measures of their exercise dependence, capability for suicide, and history of suicidal behavior. RESULTS: Suicide attempters reported higher levels of continuance in exercise despite physical or psychological consequences, lack of control over exercise, and reductions in other activities due to exercise than nonattempters. Capability for suicide accounted for the relationship between continuance in exercise despite adverse consequences and lifetime number of suicide attempts. CONCLUSIONS: When exercise becomes pathological in the form of exercise dependence, steps should be taken to reduce such engagement due to its observed association with suicidal behavior.

Urinary Tract Infection After Hysterectomy for Benign Gynecologic Conditions or Pelvic Reconstructive Surgery.

OBJECTIVE: To report rates and identify risk factors for urinary tract infection (UTI) after hysterectomy for benign conditions or combined with pelvic reconstructive surgery. METHODS: This is a cohort study that included women who underwent hysterectomy either for benign gynecologic conditions or hysterectomy combined with pelvic reconstructive surgery from January 1, 2012, through June 30, 2014, at a single institution. The primary outcome was UTI within 8 weeks of surgery. Logistic regression modeling was used to develop a model for predicting UTI after surgery. RESULTS: Of 1,156 women included in the study, 136 (11.8%, 95% CI 10.0-13.8) developed UTI within 8 weeks. Women who underwent hysterectomy for a benign gynecologic condition that was not combined with pelvic reconstructive surgery had an overall UTI rate of 7.3% (95% CI 5.6-9.3) vs 21.7% (95% CI 17.6-26.4) after hysterectomy combined with pelvic reconstructive surgery. After adjusting for hormone therapy use, the following were independent variables associated with postoperative UTI: premenopausal status with an adjusted odds ratio (OR) of 1.80 (95% CI 1.11-2.99), anterior vaginal wall prolapse with an adjusted OR of 4.39 (95% CI 2.77-6.97), and postvoid residual greater than 150 mL with an adjusted OR of 2.38 (95% CI 1.12-4.36). Using this model, postoperative UTI rates ranged from 4.3% to 59.4% with high postvoid residual and presence of anterior prolapse having the strongest association. CONCLUSION: There are wide variations in the rate of UTI after hysterectomy for begin disease including pelvic reconstructive surgery. These variations can be explained with a model based on available preoperative data.

Examining the link between weight suppression and non-suicidal self-injurious behaviors.

BACKGROUND: Given the negative consequences of excess weight, a large portion of the US population is seeking to obtain and maintain weight loss. Weight Suppression (WS) represents the difference between previous highest adult weight and current weight and may have negative psychological consequences. The current study examined the link between WS and lifetime non-suicidal self-injurious (NSSI) behavior and explored indirect effects in this link using survey data in two large samples. METHODS: Sample 1 included 1011 college students (67% female, mean age = 19 years); Sample 2 included 2461 participants from an epidemiological study (68% female, mean age = 34 years). Models of direct and indirect effects were tested in MPlus using bootstrapping. RESULTS: As hypothesized, greater WS was associated with increased likelihood of lifetime NSSI in both samples (OR = 1.05 and 1.02). In both samples, significant indirect effects of drive for thinness (Total R2 = 0.06 and 0.09) and depressive symptoms (Total R2 = 0.13 and 0.29) accounted for this association. Alternative models in which the indirect effect of WS was tested in associations between drive for thinness or depressive symptoms and NSSI were not supported. CONCLUSION: Results suggest that the link between WS and lifetime NSSI may be accounted for by eating or mood-related pathology. Future research should test whether addressing associated eating and mood problems would eliminate the link between WS and NSSI as a means for reducing suicide risk.

Problematic alcohol use and suicidal ideation among firefighters: A multi-study investigation of the explanatory roles of perceived burdensomeness and thwarted belongingness.

BACKGROUND: Firefighters are at increased risk for both problematic alcohol use and suicidality. Research has found that problematic alcohol use is related to suicidality among this population; however, limited data exist regarding what might account for this association. The present two-study investigation (1) examined the association between suicidality and problematic alcohol use among two large samples of firefighters and (2) tested whether interpersonal theory of suicide constructs-perceived burdensomeness (PB) and thwarted belongingness (TB)-serve as indirect indicators of this relationship. METHODS: Participants in Study 1 were 944 U.S. firefighters (12.5% female); participants in Study 2 were 241 U.S. women firefighters. Participants completed the Interpersonal Needs Questionnaire, Alcohol Use Disorders Identification Test, and the Depressive Symptom Inventory-Suicidality Subscale (Study 1) or the Self-Injurious Thoughts and Behaviors Interview-Short Form (Study 2). Bias-corrected bootstrap indirect effects path analyses were utilized. RESULTS: In Study 1, more problematic alcohol use was significantly associated with more severe career suicidal ideation via PB but not TB. In Study 2, problematic alcohol use was associated with career suicidal ideation via both PB and TB. PB seems to account for the relationship between problematic alcohol use and career suicidal ideation among male and female firefighters. LIMITATIONS: Limitations include use of a cross-sectional design, use of retrospective measures of suicidal ideation, and our findings derived from subsamples of two existing datasets. CONCLUSIONS: Findings suggest that PB and TB may explain the relationship between problematic alcohol use and suicidal ideation, but that this effect is discrepant based on gender.