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Objectives: A range of psychiatric symptoms and cognitive deficits occur in Parkinson disease (PD), and symptom overlap and comorbidity complicate the classification of nonmotor symptoms. The objective of this study was to use analytic-based approaches to classify psychiatric and cognitive symptoms in PD.Design: Cross-sectional evaluation of a convenience sample of patients in specialty care.Setting: Two outpatient movement disorders centers at the University of Pennsylvania and Philadelphia Veterans Affairs Medical Center.Participants: One hundred seventy-seven patients with mild-moderate idiopathic PD and without significant global cognitive impairment.Measurements: Subjects were assessed with an extensive psychiatric, neuropsychological, and neurological battery. Latent class analysis (LCA) was used to statistically delineate group-level symptom profiles across measures of psychiatric and cognitive functioning. Predictors of class membership were also examined.Results: Results from the LCA indicated that a four-class solution best fit the data. The 32.3% of the sample had good psychiatric and normal cognitive functioning, 17.5% had significant psychiatric comorbidity but normal cognition, 26.0% had few psychiatric symptoms but had poorer cognitive functioning across a range of cognitive domains, and 24.3% had both significant psychiatric comorbidity and poorer cognitive functioning. Age, disease severity, and medication use predicted class membership.Conclusions: LCA delineates four classes of patients in mild-moderate PD, three of which experience significant nonmotor impairments and comprise over two thirds of patients. Neuropsychiatric symptoms and cognitive deficits follow distinct patterns in PD, and further study is needed to determine whether these classes are generalizable, stable, predict function, quality of life, and long-term outcomes and are amenable to treatment at a class level. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To examine Montreal Cognitive Assessment (MoCA) performance in patients with Parkinson's disease (PD) with 'normal' global cognition according to Mini-Mental State Examination (MMSE) score. DESIGN: A cross-sectional comparison of the MoCA and the MMSE. SETTING: Two movement disorders centers at the University of Pennsylvania and the Philadelphia Veterans Affairs Medical Center. PARTICIPANTS: A convenience sample of 131 patients with idiopathic PD who were screened for cognitive and psychiatric complications. MEASUREMENTS: Subjects were administered the MoCA and MMSE, and only subjects defined as having a normal age- and education-adjusted MMSE score were included in the analyses (N=100). As previously recommended in patients without PD, a MoCA score less than 26 was used to indicate the presence of at least mild cognitive impairment (MCI). RESULTS: Mean MMSE and MoCA scores+/-standard deviation were 28.8+/-1.1 and 24.9+/-3.1, respectively. More than half (52.0%) of subjects with normal MMSE scores had cognitive impairment according to their MoCA score. Impairments were seen in numerous cognitive domains, including memory, visuospatial and executive abilities, attention, and language. Predictors of cognitive impairment on the MoCA using univariate analyses were male sex, older age, lower educational level, and greater disease severity; older age was the only predictor in a multivariate model. CONCLUSION: Approximately half of patients with PD with a normal MMSE score have cognitive impairment based on the recommended MoCA cutoff score. These results suggest that MCI is common in PD and that the MoCA is a more sensitive instrument than the MMSE for its detection. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii (T. gondii) infects central nervous tissue and is kept in relative dormancy by a healthy immune system. Sleep disturbances have been found to precipitate mental illness, suicidal behavior and car accidents, which have been previously linked to T. gondii as well. We speculated that if sleep disruption, particularly insomnia, would mediate, at least partly, the link between T. gondii infection and related behavioral dysregulation, then we would be able to identify significant associations between sleep disruption and T. gondii. The mechanisms for such an association may involve dopamine (DA) production by T. gondii, or collateral effects of immune activation necessary to keep T. gondii in check. Sleep questionnaires from 2031 Old Order Amish were analyzed in relationship to T. gondii-IgG antibodies measured by enzyme-linked immunosorbent assay (ELISA). Toxoplasma gondii seropositivity and serointensity were not associated with any of the sleep latency variables or Epworth Sleepiness Scale (ESS). A secondary analysis identified, after adjustment for age group, a statistical trend toward shorter sleep duration in seropositive men (p=0.07). In conclusion, it is unlikely that sleep disruption mediates links between T. gondii and mental illness or behavioral dysregulation. Trending gender differences in associations between T. gondii and shorter sleep need further investigation.

Improving public health approaches to suicide prevention requires scalable evidence-based interventions that can be easily disseminated. Given empirical data supporting the association between insomnia and suicide risk, internet-delivered insomnia interventions are promising candidates to meet this need. The purpose of this study was to examine whether an unguided internet-delivered cognitive-behavioral therapy for insomnia (iCBT-I) improved insomnia severity, suicidal ideation (SI), and suicide risk correlates (depression, post-traumatic stress disorder, anxiety, hostility, belongingness, hopelessness, agitation, irritability, concentration) in a sample of veterans. Secondary data analysis of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn veterans (n = 50) with clinically significant insomnia and elevated SI drawn from a larger randomized controlled trial (RCT) of an iCBT-I, Sleep Healthy Using the Internet (SHUTi). Two-sample t-tests or Wilcoxon rank sum tests were used to evaluate between-group differences (SHUTi vs. Insomnia Education Website control) in symptom improvement from baseline to post-intervention. SHUTi participants experienced a significant improvement in insomnia severity (P < .001; d = -1.08) and a non-significant with small (subthreshold medium) effect size reduction of SI (P = .17, d = 0.40), compared to control participants. Significant improvement in hopelessness was observed (medium effect size), with non-significant small to medium effect size reductions in most remaining suicide risk correlates. Self-administered iCBT-I was associated with improvements in insomnia severity in veterans at elevated risk for suicide. These preliminary findings suggest that SI and suicide risk correlates may improve following an iCBT-I intervention, demonstrating the need for future well-powered iCBT-I RCTs targeted for populations at elevated suicide risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Behavioral Medicine.)

Cancer stem cells (CSCs) are one of the cell types that account for cancer heterogeneity. The cancer cells arrest in G0 and generate non-CSC progeny through self-renewal and pluripotency, resulting in tumor recurrence, metastasis, and resistance to chemotherapy. They can stimulate tumor relapse and re-grow a metastatic tumor. So, CSCs is a promising target for eradicating tumors, and developing an anti-CSCs therapy has been considered. In recent years competing endogenous RNA (ceRNA) has emerged as a significant class of post-transcriptional regulators that affect gene expression via competition for microRNA (miRNA) binding. Furthermore, aberrant ceRNA expression is associated with tumor progression. Recent findings show that ceRNA network can cause tumor progression through the effect on CSCs. To overcome therapeutic resistance due to CSCs, we need to improve our current understanding of the mechanisms by which ceRNAs are implicated in CSC-related relapse. Thus, this review was designed to discuss the role of ceRNAs in CSCs' function. Targeting ceRNAs may open the path for new cancer therapeutic targets and can be used in clinical research., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Despite a growing evidence base that internet-delivered cognitive behavioral therapy for insomnia (iCBT-I) is associated with decreased insomnia severity, its efficacy has been minimally examined in veterans., Objective: The objective of this study was to evaluate the efficacy of an unguided iCBT-I (Sleep Healthy Using the Internet [SHUTi]) among veterans., Methods: We conducted a single-blind, randomized controlled trial in Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn veterans eligible for Veterans Health Administration care. Participants were randomly assigned (1:1) to receive SHUTi (a self-guided and interactive program) or an Insomnia Education Website (IEW) that provided nontailored and fixed insomnia information. Web-based assessments were administered at baseline, postintervention, 6 months postintervention, and 1 year postintervention. The primary outcome was self-reported insomnia severity (Insomnia Severity Index [ISI]). Secondary outcomes were self-reported mental and physical health functioning (Veterans RAND 36-item Health Survey). Exploratory outcomes comprised sleep diary parameters., Results: Of the 231 randomized participants (mean age 39.3, SD 7.8 years; 170/231, 73.5% male sex; 26/231, 11.3% Black; 172/231, 74.5% White; 10/231, 4.3% multiracial; and 17/231, 7.4% other; 36/231, 15.6% Hispanic) randomized between April 2018 and January 2019, a total of 116 (50.2%) were randomly assigned to SHUTi and 115 (49.8%) to the IEW. In intent-to-treat analyses, SHUTi participants experienced significantly larger ISI decreases compared with IEW participants at all time points (generalized η 2 values of 0.13, 0.12, and 0.10, respectively; all P<.0001). These corresponded to estimated larger differences in changes of -3.47 (95% CI -4.78 to -2.16), -3.80 (95% CI -5.34 to -2.27), and -3.42 (95% CI -4.97 to 1.88) points on the ISI for the SHUTi group. SHUTi participants experienced significant improvements in physical (6-month generalized η 2 =0.04; P=.004) and mental health functioning (6-month and 1-year generalized η 2 =0.04; P=.009 and P=.005, respectively). Significant sleep parameter improvements were noted for SHUTi (all P<.05), though the pattern and magnitude of these reductions varied by parameter. No adverse events were reported., Conclusions: Self-administered iCBT-I was associated with immediate and long-term improvements in insomnia severity. Findings suggest that leveraging technology to meet insomnia treatment demands among veterans may be a promising approach., Trial Registration: ClinicalTrials.gov NCT03366870; https://clinicaltrials.gov/ct2/show/NCT03366870., (©Sarra Nazem, Sean M Barnes, Jeri E Forster, Trisha A Hostetter, Lindsey L Monteith, Emily B Kramer, Laurel A Gaeddert, Lisa A Brenner. Originally published in JMIR Mental Health (https://mental.jmir.org), 24.11.2023.)

Background: Although research continues to elucidate the molecular mechanism underlying pituitary tumor pathogenesis, limited information is available on the potential role and expression profile of β-catenin in functional and non-functional pituitary neuroendocrine tumors (PitNETs)., Methods and Results: In the current study, 104 pituitary samples (tumors and cadaveric healthy pituitary tissues) were included and the gene and protein expression levels of β-catenin were assessed by Real-Time PCR and immunohistochemistry, respectively. The correlation between expression level of β-catenin and tumor invasive feature and size as well as patient age, gender, and hormonal level was measured. The data showed that PitNET samples expressed higher levels of the β-catenin gene and protein compared to healthy pituitary tissues. Although there was no difference in β-catenin expression level between non-functioning (NF-PitNETs) and growth hormone-producing tumors (GH-PitNETs), both tumor types showed significantly elevated β-catenin levels compared to healthy pituitary tissues. The high level of β-catenin in the invasive functional and non-functional tumors is indicative of the association of β-catenin with PitNETs invasion. The expression pattern of the β-catenin gene and protein was consistently and significantly associated with these tumor types. The correlation between β-catenin and insulin-like growth factor 1 (IGF-1) in GH-PitNETs indicates the potential relevance of β-catenin and IGF-1 for GH-PitNETs., Conclusions: The simultaneous increase in the expression of β-catenin gene and protein level in PitNET tissues and their relationship to the tumor severity indicates the possible contributing role of β-catenin and its underlying signaling mediators in PitNET pathogenesis., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Although sleep disruption has emerged as a theoretically consistent and empirically supported suicide risk factor, the mechanistic pathways underlying the sleep-suicide link are less understood. This paper describes the methodology of a study intended to examine longitudinal mechanisms driving the link between sleep and suicide in Veterans at elevated suicide risk. Participants will be 140 Veterans hospitalized for suicide attempt or ideation with plan and intent or those identified through the Suicide Prevention Coordinator (SPC) office as being at acute risk. After study enrollment, actigraphy and ecological momentary assessment (EMA) data will be collected for 8 weeks, with follow-up assessments occurring at 2, 4, 6, 8, and 26 weeks. Participants respond to EMA questionnaires, derived from psychometrically validated assessments targeting emotional reactivity, emotion regulation, impulsivity, suicide risk, and sleep timing constructs, five times a day. First and last daily EMA target sleep parameters including sleep quantity, quality, timing, nightmares, and nocturnal awakenings. During follow-up assessments, participants will complete self-report assessments and interviews consistent with EMA constructs and the Iowa Gambling Task. The primary outcome for aim 1 is suicide ideation severity and for the primary outcome for aim 2 is suicide behavior. Findings from this study will improve our understanding of the dynamic interactions among sleep disturbance, emotion reactivity/regulation, and impulsivity to inform conceptual Veteran sleep-suicide mechanistic models. Improved models will be critical to optimizing the precision of suicide prevention efforts that aim to intervene and mitigate risk in Veteran populations, especially during a period of acute risk., Competing Interests: None declared. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. Neither the funders nor Ambulatory Monitoring Inc. or Illumivu were involved in the decision to conduct the study or study procedures., (Published by Oxford University Press on behalf of Sleep Research Society 2023.)

Objective: Examine the association between insomnia symptom severity and suicidal ideation (SI), after adjusting for clinical comorbidity in veterans meeting diagnostic criteria for insomnia disorder., Methods: Secondary data analyses of psychometrically validated baseline assessments of depression, posttraumatic stress disorder (PTSD), and anxiety symptoms from two online insomnia intervention randomized clinical trials (n = 232; n = 80) were conducted. Multiple linear regression was used to determine the association between insomnia symptom severity and SI, after controlling for clinical comorbidity and demographics., Results: Insomnia symptom severity was significantly correlated with comorbid depression, PTSD, and anxiety symptoms in both cohorts and significantly correlated with SI in one. After controlling for demographics and clinical comorbidity, insomnia symptom severity was not significantly associated with SI in linear regression models., Conclusion: Findings extend insomnia-suicide research by providing evidence that insomnia symptom severity may not confer a unique risk for SI above comorbid mental health symptoms in veterans meeting diagnostic criteria for insomnia disorder., (© 2023 Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Understanding the molecular mechanism underlying the pathophysiology of primary skeletal tumors is crucial due to the tumor-related complications, incidence at a young age, and tumor recurrence., Methods and Results: The local expression pattern of MMP-9 as an active matrix-degrading protease was detected in 180 bone tissues, including 90 tumors and 90 noncancerous tissues, utilizing real-time qRT-PCR at the mRNA level and immunohistochemistry at the protein level. The correlation of the MMP-9 expression level with the patient's clinical pathological characteristics and the aggressiveness of the tumor was evaluated. The diagnostic significance of MMP-9 and the model of association of variables and MMP-9 expression and their predictive values were determined. Mean mRNA expression was higher in all types of primary bone tumors than their paired non-cancerous tissues. Osteosarcoma and Ewing's sarcoma expressed higher levels of MMP-9 compared to benign giant cell tumors, and the MMP-9 expression level was significantly correlated with the size, metastasis, and recurrence of the malignant tumor. A consistent expression pattern was demonstrated for MMP-9 protein levels in tissues. In addition, the MMP-9 gene and protein levels significantly discriminate between bone tumors and normal tissue, as well as benign and malignant tumors, and could predict potentially malignant traits such as tumor grade and metastasis., Conclusions: The data propose that MMP-9 may be involved in the proliferation and invasion of primary bone tumors and has the potential to monitor and treat the progression of malignant tumors., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Toll-like receptor 4 (TLR4) is actively involved in many health-related problems, including transplantation rejection and autoimmune diseases. Therefore, it is important to identify an antagonist to inhibit the TLR4-induced immune cell activation. In our previous study, 10-hydroxy-2-decanoic acid (10-HDA) was introduced as a potential antagonist for TLR4; however, possible interaction between 10-HDA and TLR4 needed to be detected. Due to the ability of surface plasmon resonance (SPR) biosensor to confirm the specific interactions between receptors and ligands, a new configuration of SPR biosensor proposed to detect the possible interaction between 10-HDA and TLR4. Hence, 10-HDA was immobilized using the (3-aminopropyl) triethoxysilane (APTES) polymer as a crosslinking agent on the Ag-MgF 2 surface. Besides, genetically modified HEK293T cells with high TLR4 expression were used to study the possible interaction between 10-HDA and TLR4. Surprisingly, the SPR angle was significantly reduced in the presence of HEK cells expressing TLR4, while HEK cells without TLR4 did not affect the SPR angle. So, the proposed SPR biosensor successfully detected the interaction betweenTLR4 and 10-HDA. The sensitivity and detection limit of the biosensor were achieved at 0.05 and 0.5 million cells expressing TLR4, respectively, with a two-fold dynamic range., (Copyright © 2022 Elsevier B.V. All rights reserved.)

ATP and other nucleoside phosphates have specific receptors named purinergic receptors. Purinergic receptors and ectonucleotidases regulate various signaling pathways that play a role in physiological and pathological processes. Extracellular ATP in the tumor microenvironment (TME) has a higher level than in normal tissues and plays a role in cancer cell growth, survival, angiogenesis, metastasis, and drug resistance. In this review, we investigated the role of purinergic receptors in the development of resistance to therapy through changes in tumor cell metabolism. When a cell transforms to neoplasia, its metabolic processes change. The metabolic reprogramming modified metabolic feature of the TME, that can cause impeding immune surveillance and promote cancer growth. The purinergic receptors contribute to therapy resistance by modifying cancer cells' glucose, lipid, and amino acid metabolism. Limiting the energy supply of cancer cells is one approach to overcoming resistance. Glycolysis inhibitors which reduce intracellular ATP levels may make cancer cells more susceptible to anti-cancer therapies. The loss of the P2X7R through glucose intolerance and decreased fatty acid metabolism reduces therapeutic resistance. Potential metabolic blockers that can be employed in combination with other therapies will aid in the discovery of new anti-cancer immunotherapy to overcome therapy resistance. Therefore, therapeutic interventions that are considered to inhibit cancer cell metabolism and purinergic receptors simultaneously can potentially reduce resistance to treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Aria, Rezaei, Nazem, Daraei, Nikfar, Mansoori, Bahmanyar, Tavassoli, Vakil and Mansoori.)

This study is aimed to unravel the status of local and circulating β-catenin in different primary bone tumors and its relevance to tumor types, severity, and chemotherapy. The β-catenin mRNA expression level and the expression of the protein (intensity level) were evaluated in tumor tissue and peripheral blood mononuclear cells of 150 patients with different types of primary bone tumors (78 malignant and 72 benign tumors) using Real-Time PCR and immunohistochemistry. The β-catenin mRNA expression level and the expression of the protein were increased in bone tumors which was positively correlated with the tumor malignancy. Amongst osteosarcoma, Ewing's Sarcoma, chondrosarcoma, osteochondroma, Giant Cell Tumor, and exostosis tumors, the osteosarcoma, and Giant Cell Tumor groups showed the highest level of β-catenin expression. The β-catenin expression in malignant bone tumors was significantly correlated with tumor grade, size, metastasis, tumor recurrent, and the level of response to chemotherapy. A similar pattern of β-catenin gene expression and its association with tumor characteristics was detected in the patient's peripheral blood cells. The simultaneous increase in the expression of the β-catenin gene and protein in tumor tissue and in circulating blood cells and its relationship with tumor severity indicates the possible promoting role of β-catenin in primary bone tumor pathogenesis., (© 2022. The Author(s).)

Background: Pituitary adenomas impose a burden of morbidity on patients and characterizing the molecular mechanisms underlying its pathogenesis received remarkable attention. Despite the appealing role of necroptosis as an alternative cell death pathway in cancer pathogenesis, its relevance to pituitary adenoma pathogenesis has yet to be determined that is perused in the current study., Methods: The total number of 109 specimens including pituitary adenomas and cadaveric healthy pituitary tissues were enrolled in the current study. Tumor and healthy pituitary tissues were subjected to RNA extraction and gene analysis using Real-Time PCR. The expression levels of necroptosis markers (RIP1K, RIP3K and, MLKL) and their association with the patient's demographic features were evaluated, also the protein level of MLKL was assessed using immunohistochemistry in tissues., Results: Based on our data, the remarkable reduction in RIP3K and MLKL expression were detected in nonfunctional and GH-secreting pituitary tumors compared to pituitary normal tissues. Invasive tumors revealed lower expression of RIP3K and MLKL compared to non-invasive tumors, also the attenuated level of MLKL was associated with the tumor size in invasive NFPA. The simultaneous down-regulation of MLKL protein in pituitary adenoma tissues was observed which was in line with its gene expression. While, RIP1K over-expressed significantly in both types of pituitary tumors which showed no significant correlation with patient's age, gender and tumor size in GHPPA and NFPA group. Notably, MLKL and RIP3K gene expression was significantly correlated in the GHPPA group., Conclusions: According to our data, the reduced expression of necroptosis mediators (RIP3K, MLKL) in pituitary adenoma reinforces the hypothesis that the necroptosis pathway can be effective in regulating the proliferation and growth of pituitary tumor cells and tumor recurrence., (© 2021. The Author(s).)

Therapeutic management of risk for other-directed violence (ODV) involves screening, assessment, and clinically appropriate intervention. In this 5-part series, effective screening and assessment for ODV have been described as a combination of clinical interviewing and the use of structured tools to inform clinical impressions of both acute and chronic risk for violence. Once risk of violence is identified, therapeutic management of the risk throughout the course of treatment is best achieved by determining the function of the violent ideation and behavior. This can be achieved through the use of functional chain analysis. Chain analysis not only serves the purpose of providing insight into the contingencies of violent behavior but also helps to identify target areas of intervention where other skills, strategies, and means to access resources for support can be applied. In this fifth and final column of the series, we describe an intervention with all of these outcomes as its goals. A safety plan for ODV assists both clients and mental health professionals in disrupting patterns of violent ideation or behavior that would otherwise continue causing not only harm to others but prolonged negative consequences for those engaging in such behaviors., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Violence risk assessment is a requisite component of mental health treatment. Adhering to standards of care and ethical and legal requirements necessitates a cogent process for conducting, and then documenting, other-directed violence (ODV) risk screening, assessment, and management. In this 5-part series, we describe a model for achieving therapeutic risk management of the potentially violent patient, with essential elements involving: clinical interview augmented by structured screening or assessment tools; risk stratification in terms of temporality and severity; chain analysis to intervene on the functions of ODV ideation and behavior; and a personalized safety plan to mitigate/manage risk. In this fourth column of the series, we describe chain analysis as a critical tool for assessing and intervening on ODV ideation and behavior. We identify the pathways of reinforcement that can cause ODV to persist, and how to navigate potential barriers to completing ODV chains. Using a case example, we demonstrate how to apply chain analysis to ODV ideation and behavior and offer interventional strategies that can be used to disrupt the chain and ultimately reduce the risk for violence., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The current study aimed to (a) assess basic nonsuicidal self-injury (NSSI) characteristics using a validated clinical interview among a sample of veterans not recruited for specific diagnostic or environmental criteria and (b) examine the relation between NSSI and medical severity of prior suicide attempts (SAs) among veterans., Design: We conducted secondary data analyses among a combined sample of veterans (N = 165) from two parent studies conducted at a large VA Medical Center that implemented identical recruitment protocols. No psychiatric criteria were utilized for inclusion or exclusion purposes., Results: Approximately 16% of participants reported NSSI history and almost 21% reported SA history. NSSI history was associated with probability of prior SA but not the medical severity of prior SA., Conclusions: NSSI is a prevalent concern among veterans and is associated with probability of SA. It remains unclear whether prior NSSI is associated with more medically serious SA in this population., (© 2020 Wiley Periodicals LLC.)

Violence risk assessment is a requisite component of mental health treatment. Adhering to standards of care and ethical and legal requirements necessitates a cogent process for conducting, and then documenting, other-directed violence risk screening, assessment, and management. In this 5-part series, we describe a model for achieving therapeutic risk management of the potentially violent patient, with essential elements involving: clinical interview augmented by structured screening or assessment tools; risk stratification in terms of temporality and severity; chain analysis to intervene on the functions of violent ideation and behavior; and personalized safety plans to mitigate/manage risk. This third column in the series describes other-directed violence risk stratification in terms of both severity and temporality, as well an approach for characterizing (ie, predatory/planned or impulsive/reactive) the violence risk posed by an individual.

Violence risk assessment is a requisite component of mental health treatment. Adhering to standards of care and ethical and legal requirements necessitates a cogent process for conducting, and then documenting, other-directed violence risk screening, assessment, and management. In this 5-part series, we describe a model for achieving therapeutic risk management of the potentially violent patient, with essential elements involving: clinical interview augmented by structured screening or assessment tools; risk stratification in terms of temporality and severity; chain analysis to intervene on the functions of violent ideation and behavior; and a personalized safety plan to mitigate/manage risk. This second column in the series describes the advantages of, and offers suggestions for, incorporating structured tools into violence risk assessment.

Violence risk assessment is a requisite component of mental health treatment. Adhering to standards of care and ethical and legal requirements necessitates a cogent process for conducting (and documenting) screening, assessment, and management of other-directed violence risk. In this 5-part series, we describe a model for achieving therapeutic risk management of the potentially violent patient, with essential elements involving a clinical interview augmented by structured screening or assessment tools; risk stratification in terms of temporality and severity; chain analysis to intervene on the functions of violent ideation and behavior; and development of a personalized safety plan. This first column of the series focuses on essential aspects of the clinical interview.

When considering critical elements involved in suicide prevention, dialogs are often dominated by suicide assessment, management, and intervention themes. Proactive consideration on what to do if a patient dies by suicide is often overlooked, which can be especially detrimental to our practice and those we serve. In this article, we extend the philosophy of the therapeutic risk management model to consider ways in which we can take good care of the extended community of suicide loss survivors, including providers. We begin by briefly describing the widespread impact of suicide loss and the lack of suicide postvention education and awareness. Given the increased likelihood that providers will be touched by suicide loss, we then provide recommendations and resources to assist the provider in developing and/or enhancing suicide postvention practices.

Background: Military personnel and Veterans are at increased risk for suicide. Theoretical and conceptual arguments have suggested that elevated levels of acquired capability (AC) could be an explanatory factor accounting for this increased risk. However, empirical research utilizing the Acquired Capability for Suicide Scale (ACSS) in military populations has yielded mixed findings., Methods: To better ascertain what factors are associated with AC, and whether methodological limitations may be contributing to mixed findings, a systematic review was conducted., Results: A total of 31 articles utilized the ACSS to examine factors associated with AC, including combat history, in United States (U.S.) military personnel and Veterans. Nearly all studies (96.8%) were rated high risk of bias. Use of the ACSS varied, with seven different iterations utilized. Nearly all studies examined correlations between the ACSS and sample characteristics, mental health and clinical factors, Interpersonal Theory of Suicide constructs, and/or suicide-specific variables. Results of higher-level analyses, dominated by cross-sectional designs, often contradicted correlational findings, with inconsistent findings across studies., Limitations: Included studies were non-representative of all U.S. military and Veteran populations and may only generalize to these populations., Conclusions: Due to the high risk of bias, inconsistent use of the ACSS, lack of sample heterogeneity, and variability in factors examined, interpretation of current ACSS empirical data is cautioned. Suggestions for future research, contextualized by these limitations, are discussed., Competing Interests: Declaration of Competing Interest All authors declare that there are no conflicts of interest to report., (Copyright © 2020. Published by Elsevier B.V.)

Study Objectives: Suicide is a top public health priority, and U.S. Veterans are recognized to be at particularly elevated risk. Sleep disturbances are an independent risk factor for suicide; recent empirical data suggest that nocturnal wakefulness may be a key mechanism underlying this association. Given higher rates of sleep disturbances among U.S. Veterans compared with civilians, we examined associations between nocturnal wakefulness and timing of death by suicide in U.S. Veterans and civilians to determine whether temporal suicide patterns differed., Methods: The American Time Use Survey and the National Violent Death Reporting System were analyzed (2006-2015) to determine whether sleep and temporal suicide patterns differed between age-stratified groups (18-39, 40-64, and ≥65) of U.S. Veterans and civilians. Observed temporal suicide patterns were reported and standardized incidence ratios (SIRs) calculated to compare the percentage of suicides observed with those expected, given the proportion of the population awake, across clock hours., Results: The raw proportion of Veteran suicides peaks between the hours of 1000-1200; however, the peak prevalence of suicide after accounting for the population awake is between 0000 and 0300 hr (p < .00001, ϕ = .88). The highest SIR was at midnight; U.S. Veterans were eight times more likely to die by suicide than expected given the population awake (SIR = 8.17; 95% CI = 7.45-8.94)., Conclusions: Nocturnal wakefulness is associated with increased risk for suicide in U.S. Veterans. Overall patterns of observed suicides by clock hour were similar between U.S. Veterans and civilians. However, Veteran-specific SIRs suggest differences in magnitude of risk by clock hour across age groups. Future research examining female and Post-9/11 U.S. Veterans is warranted., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The limitations of self-report confine clinicians' ability to accurately predict suicides and suicide attempts (SAs). Behavioral assessments (e.g., Death Implicit Association Test [IAT]) may be a means of supplementing self-report and clinician prediction., Objective: The authors aimed to build and test a predictive model of SAs that included established risk factors and measures of suicide risk, and Death IAT scores. The authors also sought to test the predictive validity of the SA model among subgroups of Veterans with and without PTSD., Method: Participants included 166 psychiatrically hospitalized Veterans., Results: A model that included patient prediction, age, and Death IAT scores improved upon clinician prediction of SAs during the six-month follow-up (C-statistic for clinician prediction = 73.6, 95% CI [62.9, 84.4] and C-statistic for model = 82.8, 95% CI [74.6, 91.0]). The model was tested in subgroups of Veterans with and without PTSD. Among Veterans without PTSD, the Death IAT and patient prediction predicted SAs above and beyond clinician prediction, while these variables did not significantly improve prediction among Veterans with PTSD (C-statistic for no-PTSD = 91.3, 95% CI [80.6, 1.00]; C-statistic for PTSD = 86.8, 95% CI [76.8, 96.8]). Building a separate model for Veterans with PTSD did not improve upon clinician prediction., Conclusions: Findings indicate that predictive models may bolster clinician prediction of SAs and that predictors may differ for Veterans with PTSD., (Published 2018. This article is a U.S. Government work and is in the public domain in the USA.)

This study evaluated whether a history of traumatic brain injury (TBI) was associated with increased risk for recent suicidal ideation (SI) after accounting for demographics, depression, posttraumatic stress disorder (PTSD), and sleep quality. In terms of increased risk, we hypothesized that a history of lifetime TBI would be associated with increased recent SI when compared with no history of TBI; multiple injuries were also evaluated. The sample included Iraq and Afghanistan war-era veterans (n = 838) who served in the United States military since 9/2001 and completed a structured TBI interview. Approximately 50% reported a lifetime history of at least 1 TBI, and 17.9% met criteria for current major depressive disorder (MDD). SI over the past week per the Beck Scale for Suicide Ideation was the primary outcome. Demographics, current MDD and posttraumatic stress disorder (PTSD) per Structured Clinical Interview of DSM-IV Axis I Disorders, sleep quality per Pittsburgh Sleep Quality Index, and TBI history per structured interview were included in all statistical models. Current depression and poor sleep quality were consistently associated with recent SI. A history of any TBI history across the life span was not associated with increased recent SI (OR = 1.35, 95% CI [0.83, 2.19]). However, a history of multiple TBIs compared with no history of TBI was associated with increased recent SI (OR = 1.76, 95% CI [1.01, 3.06]). Results support the assertion than an accumulation of injuries amplifies risk. Severity of injury and deployment injuries were not significant factors. Among those with a history of 1 TBI, sleep, and depression, which may also be injury sequelae, may be salient treatment targets. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Suicide research remains fraught with ethical and methodological issues, including researchers' reservations about conducting intensive suicide research protocols due to potential iatrogenic effects and liability concerns. Such issues significantly impede scientific inquiry related to suicide. To date, no research has explored potential iatrogenic effects of intensive, nontreatment suicide research among Veterans. This study aimed to fill this gap. It was hypothesized that participation in suicide-specific protocols would not significantly increase risk among Veterans. Veterans completed self-reports, structured interviews, and rigorous suicide-specific tasks (Study A, N = 34; Study B, N = 18; Study C, N = 119). Findings indicated there were no significant differences in pre- and postassessment suicide risk variables (all ps > .05). Estimated mean change for "urge to harm self" was -0.24 (95% confidence interval [CI]: -0.60, 0.13), -0.28 (CI: -0.56, 0.01), and -0.01 (CI: -0.09, 0.07) and "intent to harm self" was -0.18 (95% CI: -0.45, 0.10), 0 (CI: -0.17, 0.17), and 0.01 (CI: -0.04, 0.06) for Studies A, B, and C, respectively. Results indicated the respective protocols did not produce iatrogenic effects. The current findings are discussed with attention to safety-monitoring techniques that may reduce iatrogenic effects and considerations for future researchers., (© 2018 The American Association of Suicidology.)

Structural approaches to suicide risk assessment (eg, evaluating the frequency and intensity of suicidal ideation and classifying types of suicidal behavior) often fall short of providing an idiographic and dynamic analysis of the factors driving and maintaining an individual's suicide risk. Structural approaches can be bolstered through chain analysis which facilitates an exploration of the factors maintaining suicidal ideation and behavior based on positive and negative reinforcement. By uncovering the factors causing suicidal ideation and behavior to persist, efficient intervention strategies can be selected to target these pathways. In this column, the authors delineate the use of chain analysis to guide suicide risk assessment and inform treatment planning.

The clinical and scientific challenges inherent in treating and investigating suicide warrant novel approaches to this public health issue of paramount importance. The implementation of suicide-specific diagnoses has been proposed as one possible way to address this problem and was described in the first column of this special 2-part series. This second column explores potential unintended consequences related to such proposed diagnoses and alternative solutions that might afford greater benefits. The idea of suicide-specific diagnoses represents a novel approach, and one worthy of further discussion and consideration; the debate featured in this series represents a joint effort to advance the dialogue about suicide and to promote innovation.

Fibronectin type III domain-containing 5 protein (Fndc5) is a glycosylated protein with elevated expression in high energy demanded tissues as heart, brain, and muscle. It has been shown that upregulation of Fndc5 is regulated by peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1α), which is known as a master regulator of mitochondrial function and biogenesis. Also, our group indicated that Fndc5 expression increases gradually during cardiac differentiation of mouse embryonic stem cells (mESCs). In this paper, to clarify the importance of Fndc5 in cardiac differentiation, we south to knock down Fndc5 expression by generation a stably transduced mESC line that derives the expression of a short hairpin RNA (shRNA) against Fndc5 gene following doxycycline (Dox) induction. Knock-down of Fndc5 demonstrated a considerable decrease in expression of cardiac progenitor and cardiomyocyte markers. Considering the fact that mitochondria play a crucial role in cardiac differentiation of ESCs, we investigated the role of Fndc5, as a downstream target of PGC1-α, on mitochondrial indices. Results showed that expression of nuclear encoded mitochondrial genes including PGC1-α, Atp5b, Ndufb5, and SOD2 significantly decreased. Moreover, mitochondrial membrane potential (ΔΨm) and relative ATP content of cardiomyocytes decreased markedly with relative ROS level increase. Together, our results suggest that Fndc5 attenuates process of cardiac differentiation of mESCs which is associated with modulation of mitochondrial function and gene expression., (© 2017 Wiley Periodicals, Inc.)

A better understanding of factors that differentiate those who only experience suicidal ideation from those who engage in self-directed violence (SDV) is critical for suicide prevention efforts (Klonsky & May, 2014; May & Klonsky, 2016). To identify who is at greatest risk for death by suicide, it is imperative that new innovative assessment tools be created to facilitate behavioral measurement of key constructs associated with increased risk for SDV. The aim of the current study was to develop and validate a set of suicide-specific images, called the Self-Directed Violence Picture System (SDVPS), to help meet this need. A sample of 119 U.S. military veterans provided valence, arousal, and dominance ratings on the SDVPS. These ratings were compared to International Affective Picture System (IAPS) negative, neutral, and positive images. SDVPS images were rated with significantly greater negative valence and elicited decreased feelings of being in control than did IAPS positive (p < .001, p < .001), IAPS negative (p = .03, p = .001), and IAPS neutral (p < .001, p < .001) images. SDVPS images were also rated with significantly greater arousal than were IAPS neutral images (p < .001). Initial validation data support that the SDVPS images functioned as intended. Although continued validation of the SDVPS in other populations is necessary, the SDVPS may become a new tool by which researchers can begin to systematically and reliably examine reactions to suicide-related content using behavioral and/or experimental paradigms. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Both public awareness of suicide and professional efforts directed at suicide prevention have increased considerably in recent years. Unfortunately, rates of death by suicide have remained relatively stable over the past decade despite these enhanced efforts. Some have argued that "suicide risk assessment doesn't work" and have called into question the utility of devoting clinical time and energy to risk assessment. In this column, the authors first present an overview of the argument against suicide risk assessment and the data supporting that argument, followed by an alternate argument as to why suicide risk assessment still matters. When properly performed in concert with patient-centered mental health care, suicide risk assessment and management may add to the therapeutic and recovery-oriented benefits of care, independent of the ability to predict death by suicide.

Background: The interpersonal theory of suicide suggests three proximal risk factors for suicide: perceived burdensomeness, thwarted belongingness, and acquired capability. Previous literature indicates that repetitive exposure to painful and provocative events is related to increased acquired capability for suicide. Despite this, research related to the assessment of painful and provocative events has been insufficient. Research has inconsistently administered the Painful and Provocative Events Scale (PPES; a painful and provocative events assessment), and no study has examined the factor structure of the English PPES. This study explored the factor structure of the PPES and the relation between factors and fearlessness about death., Methods: The sample was a cross-sectional, self-report study comprised of 119 Veterans (Mage = 46.5, SD = 13.5)., Results: Findings from an exploratory factor analysis indicated a four-factor solution for the PPES; however, no factor from the PPES significantly related to fearlessness about death (measured by the Acquired Capability for Suicide Scale - Fearlessness About Death Scale; all p >.21)., Limitations: Cross-sectional, small Veteran sample., Conclusions: Findings suggest that the PPES lacks the psychometric properties necessary to reliably investigate painful and provocative factors. Consequently, this measure may not reliably capture and explain how painful and provocative events relate to fearlessness about death, which is a barrier to improving suicide risk assessment and prediction. Recommendations for the construction of a new PPES are offered., (Published by Elsevier B.V.)

Objective: To examine the discrepancy between sleep diary and actigraphic measures of sleep in Veterans with moderate-severe post-acute traumatic brain injury (TBI) and to explore whether these discrepancies vary according to participant characteristics., Setting: VA Medical Center in the Rocky Mountain United States., Participants: Nineteen males with moderate-severe post-acute TBI and insomnia symptoms as measured by the Insomnia Severity Index., Design: Descriptive, cross-sectional., Main Measures: Sleep diary, wrist actigraphy, Ohio State University TBI-Identification Method, Insomnia Severity Index, and Hospital Anxiety and Depression Scale., Results: There was poor agreement between actigraphic and sleep diary measurements of (1) total sleep time, (2) wake after sleep onset, and (3) sleep onset latency. On average, actigraphy measured greater duration of all 3 sleep parameters. Discrepancies were not found to be associated with specific TBI characteristics or mood-related symptoms., Conclusion: When measuring sleep-related outcomes among Veterans with moderate-severe post-acute TBI, notable mismatches were found between actigraphic and self-reported sleep diary data. Knowledge regarding measure-related limitations is important for both clinical and research practices among those with moderate-severe post-acute TBI.

Background: Although rates of anxiety tend to decrease across late life, rates of anxiety increase among a subset of older adults, those with mild cognitive impairment (MCI) or dementia. Our understanding of anxiety in dementia is limited, in part, by a lack of anxiety measures designed for use with this population. This study sought to address limitations of the literature by developing a new measure of anxiety for cognitively impaired individuals, the anxiety in cognitive impairment and dementia (ACID) Scales, which includes both proxy (ACID-PR) and self-report (ACID-SR) versions., Methods: The ACID-SR and ACID-PR were administered to 45 residents, aged 60 years and older, of three long-term care (LTC) facilities, and 38 professional caregivers at these facilities. Other measures of anxiety, and measures of depression, functional ability, cognition, and general physical and mental health were also administered., Results: Initial evaluation of its psychometric properties revealed adequate to good internal consistency for the ACID-PR and ACID-SR. Evidence for convergent validity of measures obtained with the ACID-SR and ACID-PR was demonstrated by moderate-to-strong associations with measures of worry, depressive symptoms, and general mental health. Discriminant validity of measures obtained with the ACID-SR and ACID-PR was demonstrated by weak correlations with measures of cognition, functional ability, and general physical well-being., Conclusions: The preliminary results suggest that the ACID-SR and ACID-PR can obtain reliable and valid measures of anxiety among individuals with cognitive impairment. Given the subjective nature of anxiety, it may be prudent to collect self-report of anxiety symptoms even among those with moderate cognitive impairment.

This study examined relationships among risk/protective factors and suicidal ideation (SI) in deployed and non-deployed National Guard members, particularly examining for possible differential effects of deployment on SI. A total of 3,098 Florida National Guard members completed an anonymous online survey that assessed variables associated with SI including demographics, current psychiatric diagnoses, and pre-, during, and post-deployment experiences. Those deployed had significantly higher rates of SI (5.5%) than those not deployed (3.0%; p < .001). In multivariate analyses, among those not deployed, SI was significantly associated with major depressive disorder (p < .001), posttraumatic stress disorder (PTSD) (p < .001), prior psychological trauma (p < .01), and heavy/hazardous alcohol consumption (p < .05). In contrast, in the deployed, only PTSD (p < .001) and deployment-related mild traumatic brain injury (p < .05) were independently associated with SI. Risk and protective factors differed by deployment status in National Guard members suggesting the possible need for cohort-specific treatment targets to minimize SI.

Study Objectives: The purpose of the study was to examine whether insomnia symptoms and nightmares mediated the relation between alcohol use and suicide risk. Further, we examined whether this mediation was moderated by gender., Design: The study consisted of questionnaires administered online examining insomnia symptoms, nightmares, alcohol use, and suicide risk., Setting: University., Patients or Participants: 375 undergraduate students at a large, public university in the southeastern United States., Interventions: N/A., Measurements and Results: Results indicated that insomnia symptoms significantly mediated the relation between alcohol use and suicide risk; however, this mediation was moderated by gender. For women, there was both a direct effect of alcohol use on suicide risk as well as an indirect effect of alcohol use through insomnia symptoms increasing suicide risk. For men, there was no direct effect of alcohol use on suicide risk, but there was a significant indirect effect of alcohol use increasing suicide risk through insomnia symptoms. Nightmares were not related to alcohol use, and the association between nightmares and suicide risk was found to be independent of alcohol use., Conclusions: Insomnia symptoms are an important factor in explaining the mechanism by which alcohol use increases suicide risk., (© 2014 American Academy of Sleep Medicine.)