Dehumanization and the Association With Nonsuicidal Self-Injury and Suicidal Ideation in an Incarcerated Population.

Background: Self-injurious and suicidal thoughts create critical concerns for incarcerated populations, yet relatively little is known about how they are formed and perpetuated within US jails. Dehumanization has been presented as a potentially novel risk factor toward aspects of self-harm; thus, this study assessed the perception of dehumanization from officers by those currently incarcerated. Methods: Across two jail settings (n = 410), self-report surveys were administered asking questions relating to perception of officer dehumanization alongside aspects of nonsuicidal self-injury (NSSI) and suicidal ideation. Results: The findings indicate that perceived officer dehumanization is associated with NSSI thoughts, actively seeking NSSI, and suicidal ideation in jail, but not with NSSI in jail. Limitations: These data are cross-sectional, thus future work should examine the temporal order of these relationships. Conclusions: Perceptions of officer dehumanization appear to be clinically relevant in jail settings; therefore, future research should longitudinally determine how dehumanization imparts suicide risk.

Development and validation of a self-report measure of perceived dehumanization from officers.

PURPOSE: Emerging evidence indicates that incarcerated populations' perceptions of dehumanization by officers are prevalent, yet measures of it are few, and to our knowledge, no self-report measure of dehumanization from officers exists. To fill this gap, we have developed the Perceived Dehumanization from Officers Scale (PDOS), which is designed as a brief measure to assess perception of officer treatment as dehumanizing. METHODS: In this article, we provide preliminary evidence from two studies examining the reliability and validity of the PDOS. In study 1, a jail sample (n = 411), we analyzed the exploratory factor structure, internal consistency, and discriminant validity (in relation to procedural justice [PJ]) of the PDOS. Additionally, using a cross-sectional ordinary least squares (OLS) regression analysis, we related independent variables with the PDOS, the dependent variable. In Study 2, a prison sample (n = 2993), we confirmed the findings from study 1. RESULTS: The PDOS appears to be a psychometrically sound measure of perceived dehumanization from officers with strong association between perceptions of PJ and perceived dehumanization from officers. CONCLUSIONS: The PDOS provides opportunity for future research, intervention through rehumanization efforts, and signals the important officer treatment. Importantly We close by discussing implications of these studies, limitations, and future research directions to further develop and test the PDOS.

Adverse childhood experiences and early initiation of substance use: A survival analysis.

OBJECTIVE: Early adversity, such as adverse childhood experiences (ACEs), is a risk factor for the development of substance use disorder (SUD). ACEs are associated with earlier initiation of substance use. This study examined the relationship between ACEs and age of initiation of substance use using survival analysis. It is hypothesized that individuals with higher ACEs will have an earlier age of initiation. METHOD: Participants were recruited from the University of Kentucky's Laboratory for Human Behavioral Pharmacology. Participants were 18 years or older, English speaking, and actively engaged in substance use. Participants were not in substance abuse treatment nor were they seeking treatment. ACE scores were calculated, and age of substance use initiation was recorded. A Cox proportional hazard model was used to examine the effect of ACE score on age of substance use initiation. RESULTS: A total of 107 participants completed the study. An average number of 2.3 ACEs (SD = 2.2) were endorsed with 24% of participants reporting 4 or more ACEs. Higher ACE scores were associated with cigarette smoking and non-medical prescription opioid use onset ( hazard ratio (HR) = 1.14, 95% CI=1.02-1.28, p = 0.02, and HR=1.19, 95% CI = 1.04-1.37, p = 0.01, respectively. CONCLUSIONS: A significant association was found between higher ACE scores and earlier initiation of cigarette and non-medical prescription opioid use, consistent with prior research. Primary prevention of ACEs, screening for ACEs during childhood, and interventions for ACEs if detected, may help to reduce the risk of substance use/SUD in adulthood.

Sleep-specific outcomes attributable to digitally delivered cognitive behavioral therapy for insomnia in adults with insomnia and depressive symptoms.

OBJECTIVE: Randomized controlled trials (RCTs) of digitally delivered Cognitive Behavioral Therapy for insomnia (CBT-I) have demonstrated reductions in insomnia severity, depression symptoms, anxiety symptoms, and suicidal ideation. The present study aimed to evaluate the effectiveness of self-guided, digital CBT-I to improve sleep-specific outcomes. METHOD: An RCT of Australian adults with insomnia and depressive symptoms (N = 1149) compared SHUTi, a digital CBT-I intervention, with HealthWatch, an attention-matched control internet program, at baseline, posttest (9 weeks) and at 6-, 12-, and 18-month follow-ups. Online sleep diaries were used to derive measures of sleep-onset latency (SOL), wake after sleep onset (WASO), sleep efficiency (SE), number of awakenings, sleep quality, and total sleep time (TST). RESULTS: Participants in the SHUTi condition had greater improvements at posttest compared with control for: SOL, WASO, SE, number of awakenings, and sleep quality. These improvements were sustained at every follow-up (p < .02 for all outcomes except TST, in which statistically significant increases were observed only at 12- and 18-months). CONCLUSIONS: Digitally delivered CBT-I produced lasting improvements in sleep outcomes among adults with insomnia and depressive symptoms. Findings provide further evidence of long-term improvements associated with a digital therapeutic for insomnia, compared to an attention-control condition.

µMap Photoproximity Labeling Enables Small Molecule Binding Site Mapping.

The characterization of ligand binding modes is a crucial step in the drug discovery process and is especially important in campaigns arising from phenotypic screening, where the protein target and binding mode are unknown at the outset. Elucidation of target binding regions is typically achieved by X-ray crystallography or photoaffinity labeling (PAL) approaches; yet, these methods present significant challenges. X-ray crystallography is a mainstay technique that has revolutionized drug discovery, but in many cases structural characterization is challenging or impossible. PAL has also enabled binding site mapping with peptide- and amino-acid-level resolution; however, the stoichiometric activation mode can lead to poor signal and coverage of the resident binding pocket. Additionally, each PAL probe can have its own fragmentation pattern, complicating the analysis by mass spectrometry. Here, we establish a robust and general photocatalytic approach toward the mapping of protein binding sites, which we define as identification of residues proximal to the ligand binding pocket. By utilizing a catalytic mode of activation, we obtain sets of labeled amino acids in the proximity of the target protein binding site. We use this methodology to map, in vitro, the binding sites of six protein targets, including several kinases and molecular glue targets, and furthermore to investigate the binding site of the STAT3 inhibitor MM-206, a ligand with no known crystal structure. Finally, we demonstrate the successful mapping of drug binding sites in live cells. These results establish µMap as a powerful method for the generation of amino-acid- and peptide-level target engagement data.

Lifetime and Jail-Specific Suicidal Ideation: Prevalence and Correlates in a Sample of People in Jail in the United States.

Despite high suicide mortality in U.S. jails, there is limited research into precursors for suicide in this population, such as suicidal ideation. The current study examined the prevalence and correlates of lifetime and jail-specific suicidal ideation among a sample of 196 individuals (137 men) in custody in a U.S. jail. Nearly half the sample had reported lifetime suicidal ideation (45%), whereas 30% had reported jail-specific suicidal ideation. Adjusted correlates of lifetime suicidal ideation included a history of mental illness (OR = 2.79) and drug use (OR = 2.70). Adjusted correlates of jail-specific suicidal ideation included a history of mental illness (OR = 2.74), drug use (OR = 3.16), and a dehumanizing custodial environment (OR = 3.74). Some theoretically and empirically relevant factors were not significantly associated with suicidal ideation. Both expected and unexpected findings are discussed within the context of suicide theory and research, and practical implications are explored.

People in Custody With a Suicidal History: An Ideation-to-Action Perspective Involving Individuals Incarcerated in Two U.S. Jails.

OBJECTIVE: Despite high suicide mortality in U.S. jails, little is known about the cognitive (ideation) and behavioral (attempt) spectrum of suicide risk in this population. Identifying factors associated with the development of suicidal ideation, as well as the translation of thoughts to acts of suicide, is important for suicide prevention. METHOD: Using data from a cross-sectional study conducted in 2018-2019, we investigated suicidal ideation and attempt among 548 individuals incarcerated in jail in the United States. Specifically, we compared those with suicidal ideation (n = 212) to those without suicidal ideation (n = 336), as well as compared those who had experienced suicidal ideation and attempted suicide (n = 114) to those who thought about suicide without making an attempt (n = 98), on a range of sociodemographic and clinical factors. RESULTS: Over one-third (38.7%) of participants had a history of suicidal ideation, whereas 23.3% had attempted suicide. In the adjusted analyses, a family history of suicide (OR = 2.09), drug use (OR = 2.26), social support (OR = 0.61), and self-harm (OR = 24.93) were linked to suicidal ideation. No wish to live (OR = 5.26) and interpersonal violence while intoxicated (OR = 2.41) were associated with the progression from suicidal ideation to a suicide attempt. CONCLUSIONS: Consistent with extant theoretical and empirical work, findings suggest that factors linked to the development of suicidal cognitions differ from those underlying the progression from suicidal ideation to a (non-lethal) suicide attempt.HIGHLIGHTSSuicidal risk is particularly high among individuals who are incarcerated in jail.Factors linked to suicidal ideation differ from those underlying acts of suicide.Ideators and attempters possess a different set of targets for intervention.

Real-World Evaluation of Clinical Response and Long-Term Healthcare Resource Utilization Patterns Following Treatment with a Digital Therapeutic for Chronic Insomnia.

Background and Objectives: This analysis evaluated insomnia severity and long-term impact on healthcare resource utilization (HCRU) and costs after treatment with Somryst® (previously called SHUTi), a digital therapeutic delivering cognitive behavioral therapy for insomnia (CBT-I). Methods: Change from baseline in insomnia severity index (ISI) score was assessed using last observed ISI score. A pre/post analysis of claims data was conducted, comparing HCRU in patients with self-identified sleep problems who successfully initiated the therapeutic (index date) between June 1, 2016 and December 31, 2018. Results: A total of 248 patients were analyzed (median age 56.5 years, 57.3% female, mean ISI score 19.13, 52.4% treated with sleep aid medications pre-index). After 9 weeks, mean ISI score declined by 37.2% from baseline (19.1 vs 12.0), 58.8% of patients achieved ISI responder status (ISI score improved by =>7; NNT: 1.7), and 26.6% of patients achieved insomnia remission (ISI score <8; NNT for remission: 3.8). After two-year follow-up, post-index events were reduced (compared to 2 years pre-index) for emergency department visits (-53%; IRR: 0.47; 95% CI 0.27, 0.82; P=0.008), hospiatizations (-21%; IRR: 0.79; 95% CI 0.46, 1.35; P=0.389) and hospital outpatient visits (-13%; IRR: 0.87; 95% CI 0.66, 1.14; P=0.315). Slightly increased rates were observed for ambulatory surgical center visits (2%; IRR: 1.02; 95% CI 0.73, 1.44; P=0.903) and office visits (2%; IRR: 1.02; 95% CI 0.92, 1.14; P=0.672). The number of patients treated with sleep aid medications dropped 18.5% (52.4% pre-index vs 42.7% post-index). Average number of prescriptions decreased from 3.98 pre-index to 3.73 post-index (P= 0.552). Total two-year cost reduction post-index vs pre-index was $510,678, or -$2059 per patient. Conclusion: In a real-world cohort of patients with chronic insomnia, treatment with a digital therapeutic delivering CBT-I was associated with reductions in insomnia severity, emergency department visits, and net costs.

Small molecule photocatalysis enables drug target identification via energy transfer.

Over half of new therapeutic approaches fail in clinical trials due to a lack of target validation. As such, the development of new methods to improve and accelerate the identification of cellular targets, broadly known as target ID, remains a fundamental goal in drug discovery. While advances in sequencing and mass spectrometry technologies have revolutionized drug target ID in recent decades, the corresponding chemical-based approaches have not changed in over 50 y. Consigned to outdated stoichiometric activation modes, modern target ID campaigns are regularly confounded by poor signal-to-noise resulting from limited receptor occupancy and low crosslinking yields, especially when targeting low abundance membrane proteins or multiple protein target engagement. Here, we describe a broadly general platform for photocatalytic small molecule target ID, which is founded upon the catalytic amplification of target-tag crosslinking through the continuous generation of high-energy carbene intermediates via visible light-mediated Dexter energy transfer. By decoupling the reactive warhead tag from the small molecule ligand, catalytic signal amplification results in unprecedented levels of target enrichment, enabling the quantitative target and off target ID of several drugs including (+)-JQ1, paclitaxel (Taxol), dasatinib (Sprycel), as well as two G-protein-coupled receptors-ADORA2A and GPR40.

Changes in sleep following internet-delivered cognitive-behavioral therapy for insomnia in women treated for breast cancer: A 3-year follow-up assessment.

BACKGROUND: Sleep disturbances are common in women treated for breast cancer. We have previously shown that internet-delivered cognitive-behavioral therapy for insomnia (e-CBT-I) is an efficacious, low-cost treatment approach. Furthermore, research has shown that e-CBT-I can result in sustained improvements at 12 months post-treatment. However, given the complexity and long duration of post-treatment symptomatology in breast cancer patients, as well as the recommended use of antihormonal therapy for up to 10 years, it is relevant to investigate long-term (>12 months) changes in sleep following e-CBT-I in this population. In the present study, we report data from a 3-year long-term follow-up assessment after e-CBT-I. METHODS: Women treated for breast cancer with sleep disturbances (Pittsburg Sleep Quality Index [PSQI] global score >5) who had previously been enrolled in a randomized-controlled trial investigating the efficacy of e-CBT-I (n = 255), were invited to participate in a 3-year follow-up study. All women in the initial control group had also been granted access to e-CBT-I. Assessment included self-reported sleep quality (PSQI), insomnia severity (Insomnia Severity Index, ISI), cancer-related fatigue and symptoms of depression. Within-group changes in these outcomes from baseline to the 3-year long-term follow-up assessment were analyzed. RESULTS: A total of 131 women (51%) participated in the 3-year follow-up study of which 77 (59%) were from the initial intervention group and 54 (41%) from the initial control group. For the pooled sample, within-group improvements from baseline to the 3-year follow-up assessment corresponding to large effect sizes were observed in sleep quality (Cohen's d = 1.0 95% CI [0.78, 1.21]) and insomnia severity (Cohen's d = 1.36 CI 95% [1.12, 1.59]). Similar changes were observed in cancer-related fatigue (Cohen's d = 0.48 CI 95% [0.30, 0.66]) and symptoms of depression (Cohen's d = 0.80 CI 95%. [0.60, 0.99]). The proportion of patients with scores above established cut-offs on the PSQI and the ISI were 56.1% and 29.8%, respectively. Within the initial intervention group, 15.6% evidenced relapse at the 3-year assessment. CONCLUSION: Overall, these results indicate that long-term sleep quality and insomnia severity following the use of e-CBT-in women treated for breast cancer is significantly lower than the pre-treatment levels. However, a substantial proportion of participants still evidence sleep disturbances.

Futurelessness and Commitment to Institutional Rules Among People in Jail.

The current study builds on prior work examining the association between futurelessness and commitment institutional rules among correctional populations. Using cross-sectional data from a sample of 413 people incarcerated in United States jails from 2018 to 2019, this study employs Ordinary Least Squares regression to examine the association between futurelessness and commitment to institutional rules controlling for various importation and deprivation factors previously linked with institutional misconduct. Results provide support for the importance of futurelessness for commitment to institutional rules, suggesting that this finding is consistent across correctional environments. In addition, findings suggest that an index measure of futurelessness is a stronger construct for testing futurelessness than single-item measures used in prior studies. Consistent with prior literature on futurelessness, our findings suggest that among people incarcerated in jail futurelessness is linked to a weaker commitment to institutional rules.

µMap-Red: Proximity Labeling by Red Light Photocatalysis.

Modern proximity labeling techniques have enabled significant advances in understanding biomolecular interactions. However, current tools primarily utilize activation modes that are incompatible with complex biological environments, limiting our ability to interrogate cell- and tissue-level microenvironments in animal models. Here, we report µMap-Red, a proximity labeling platform that uses a red-light-excited SnIV chlorin e6 catalyst to activate a phenyl azide biotin probe. We validate µMap-Red by demonstrating photonically controlled protein labeling in vitro through several layers of tissue, and we then apply our platform in cellulo to label EGFR microenvironments and validate performance with STED microscopy and quantitative proteomics. Finally, to demonstrate labeling in a complex biological sample, we deploy µMap-Red in whole mouse blood to profile erythrocyte cell-surface proteins. This work represents a significant methodological advance toward light-based proximity labeling in complex tissue environments and animal models.

Chemically Modified Bacterial Sacculi as a Vaccine Microparticle Scaffold.

Vaccine scaffolds and carrier proteins increase the immunogenicity of subunit vaccines. Here, we developed, characterized, and demonstrated the efficacy of a novel microparticle vaccine scaffold comprised of bacterial peptidoglycan (PGN), isolated as an entire sacculi. The PGN microparticles contain bio-orthogonal chemical handles allowing for site-specific attachment of immunogens. We first evaluated the purification, integrity, and immunogenicity of PGN microparticles derived from a variety of bacterial species. We then optimized PGN microparticle modification conditions; Staphylococcus aureus PGN microparticles containing azido-d-alanine yielded robust conjugation to immunogens. We then demonstrated that this vaccine scaffold elicits comparable immunostimulation to the conventional carrier protein, keyhole limpet hemocyanin (KLH). We further modified the S. aureus PGN microparticle to contain the SARS-CoV-2 receptor-binding domain (RBD)─this conjugate vaccine elicited neutralizing antibody titers comparable to those elicited by the KLH-conjugated RBD. Collectively, these findings suggest that chemically modified bacterial PGN microparticles are a conjugatable and biodegradable microparticle scaffold capable of eliciting a robust immune response toward an antigen of interest.

Real-world evidence from users of a behavioral digital therapeutic for chronic insomnia.

BACKGROUND: There have been many research trials of various digital therapeutics, but few real world evaluations of their efficacy. This type of data, however, can provide a more rounded understanding of their impact, utility, reach, and adoption. Findings presented here focus on outcome and patient engagement data of SHUTi (Sleep Health Using the Internet), a digital therapeutic delivering Cognitive Behavioral Therapy for insomnia (CBT-I), in a large real-world dataset of adults with insomnia. METHODS: 7216 adults who purchased access to SHUTi between December 2015 and February 2019 are included in the analysis. The Insomnia Severity Index (ISI) was administered at the beginning of each of six treatment Cores of the intervention. Users entered sleep diaries between Cores to track changes in sleep over time and obtain tailored sleep recommendations. Number of Cores completed and sleep diaries entered indicate program usage. RESULTS: Users showed a reduction in mean ISI scores and a corresponding increase in effect size at the start of each subsequent Core (compared to Core 1) (range: d = 0.3-1.9). Effect sizes at the last Core relative to the first were moderate-to-large for diary-derived sleep onset latency and wake after sleep onset. A reduction in number of medicated nights was also found, with those with severe insomnia showing the largest reduction from last-to-first week of treatment (d = 0.3). At the last Core, 61% met criteria for meaningful treatment response (reduction of >7 points on ISI) and 40% met criteria for remission (ISI<8). Engagement was comparable to SHUTi research trials. CONCLUSION: Consistent with controlled trials, real-world data suggest that digital therapeutics can result in relatively high levels of engagement and clinically meaningful sleep improvements.

mySmartCheck, a Digital Intervention to Promote Skin Self-examination Among Individuals Diagnosed With or at Risk for Melanoma: A Randomized Clinical Trial.

BACKGROUND: Regular skin self-examination (SSE) reduces melanoma mortality but is not often conducted. PURPOSE: To promote SSE performance in individuals at increased risk for melanoma. METHODS: One hundred sixteen individuals at heightened risk for development of melanoma (i.e., personal/family history of melanoma, high-risk mole phenotype) who did not conduct a thorough SSE during in the prior 3 months were randomly assigned to receive either an automated internet-based intervention (mySmartCheck) or usual care (UC). One hundred sixteen participants completed surveys before random assignment and 99 completed the follow-up survey 13-weeks afterward. The primary outcome was participant self-reported examination (SSE) of all 15 parts of the body in the last 3 months. Secondary outcomes were SSE of any part of the body in the last 3 months and number of body parts examined during the last SSE. RESULTS: More mySmartCheck participants examined all 15 body parts (32.6% vs. 7.1%, p = .001). More individuals in mySmartCheck reported conducting SSE on any body part than those in UC (81.4% vs. 62.5%, p = .04). Effect sizes were large (d = 1.19 all 15 body parts) to moderate (d = 0.55 for any body part). mySmartCheck participants examined more body areas than UC participants (12.7 vs. 10.3, p = 0.003) during the last SSE. Participants in mySmartCheck reported higher levels of knowledge of suspicious lesions, SSE benefits, SSE self-efficacy, and planning for SSE, and lower SSE barriers, than those assigned to UC. CONCLUSIONS: mySmartCheck had a significant positive impact on SSE performance and behaviors. Additional research with a larger sample size, a longer follow-up, and more varied clinical settings is needed. TRIAL REGISTRATION: ClinicalTrials.gov registration # NCT03725449 (https://clinicaltrials.gov/ct2/show/NCT03725449).

Enhancing Response to Foodborne Disease Outbreaks: Findings of the Foodborne Diseases Centers for Outbreak Response Enhancement (FoodCORE), 2010-2019.

CONTEXT: Each year, foodborne diseases cause an estimated 48 million illnesses resulting in 128000 hospitalizations and 3000 deaths in the United States. Fast and effective outbreak investigations are needed to identify and remove contaminated food from the market to reduce the number of additional illnesses that occur. Many state and local health departments have insufficient resources to identify, respond to, and control the increasing burden of foodborne illnesses. PROGRAM: The Centers for Disease Control and Prevention (CDC) Foodborne Diseases Centers for Outbreak Response Enhancement (FoodCORE) program provides targeted resources to state and local health departments to improve completeness and timeliness of laboratory, epidemiology, and environmental health activities for foodborne disease surveillance and outbreak response. IMPLEMENTATION: In 2009, pilot FoodCORE centers were selected through a competitive application process and then implemented work plans to achieve faster and more complete surveillance and outbreak response activities in their jurisdiction. By 2019, 10 centers participated in FoodCORE: Colorado, Connecticut, Minnesota, New York City, Ohio, Oregon, South Carolina, Tennessee, Utah, and Wisconsin. EVALUATION: CDC and FoodCORE centers collaboratively developed performance metrics to evaluate the impact and effectiveness of FoodCORE activities. Centers used performance metrics to document successes, identify gaps, and set goals for their jurisdiction. CDC used performance metrics to evaluate the implementation of FoodCORE priorities and identify successful strategies to develop replicable model practices. This report provides a description of implementing the FoodCORE program during year 1 (October 2010 to September 2011) through year 9 (January 2019 to December 2019). DISCUSSION: FoodCORE centers address gaps in foodborne disease response through enhanced capacity to improve timeliness and completeness of surveillance and outbreak response activities. Strategies resulting in faster, more complete surveillance and response are documented as model practices and are shared with state and local foodborne disease programs across the country.

Unifying Catalysis Framework to Dissect Proteasomal Degradation Paradigms.

Diverging from traditional target inhibition, proteasomal protein degradation approaches have emerged as novel therapeutic modalities that embody distinct pharmacological profiles and can access previously undrugged targets. Small molecule degraders have the potential to catalytically destroy target proteins at substoichiometric concentrations, thus lowering administered doses and extending pharmacological effects. With this mechanistic premise, research efforts have advanced the development of small molecule degraders that benefit from stable and increased affinity ternary complexes. However, a holistic framework that evaluates different degradation modes from a catalytic perspective, including focusing on kinetically favored degradation mechanisms, is lacking. In this Outlook, we introduce the concept of an induced cooperativity spectrum as a unifying framework to mechanistically understand catalytic degradation profiles. This framework is bolstered by key examples of published molecular degraders extending from molecular glues to bivalent degraders. Critically, we discuss remaining challenges and future opportunities in drug discovery to rationally design and phenotypically screen for efficient degraders.