The Link between Deployment-Related Injuries and Suicidal Thinking in the Army National Guard: Examining the Role of Perceived Burdensomeness and Hopelessness.

OBJECTIVE: In 2020, Army National Guard members demonstrated greater risk of suicide than their military and civilian counterparts. Though literature on deployment-related experiences and suicidal ideation (SI) is mixed, investigations of specific deployment-related experiences (e.g., injuries) may further elucidate the relationship between deployment and suicide risk. Deployment-related injuries, including pain severity and functional impairment, have been linked to increased risk of SI, and correlates like perceived burdensomeness (PB) and hopelessness. The current study sought to examine the cross-sectional relationship between deployment-related injuries, including pain severity and functional impairment, and severity of SI through PB and hopelessness. METHOD: Immediately post-deployment, Army National Guard members (N = 2,261) completed validated self-report measures on past-week SI, PB, hopelessness, and single items regarding injury sustained during deployment and associated functional impairment and pain severity. RESULTS: Indirect effect analyses revealed that experience of deployment-related injury was related to SI through PB and hopelessness (R2 = .1993), functional impairment was related to SI through PB, and pain severity was related to SI through PB. Contrary to hypotheses, hopelessness was not associated with SI when PB was simultaneously considered. CONCLUSIONS: Army National Guard members who develop a sense of PB related to their injury and functional impairment of that injury may be at increased risk for suicidal ideation. Military suicide-prevention efforts may be potentiated through targeting distorted cognitions such as PB and hopelessness, especially in service members who have been injured.

Four-dimensional microED of conformational dynamics in protein microcrystals on the femto-to-microsecond timescales.

As structural determination of protein complexes approaches atomic resolution, there is an increasing focus on conformational dynamics. Here we conceptualize the combination of two techniques which have become established in recent years: microcrystal electron diffraction and ultrafast electron microscopy. We show that the extremely low dose of pulsed photoemission still enables microED due to the strength of the electron bunching from diffraction of the protein crystals. Indeed, ultrafast electron diffraction experiments on protein crystals have already been demonstrated to be effective in measuring intermolecular forces in protein microcrystals. We discuss difficulties that may arise in the acquisition and processing of data and the overall feasibility of the experiment, paying specific attention to dose and signal-to-noise ratio. In doing so, we outline a detailed workflow that may be effective in minimizing the dose on the specimen. A series of model systems that would be good candidates for initial experiments is provided.

Structures of LRP2 reveal a molecular machine for endocytosis.

The low-density lipoprotein (LDL) receptor-related protein 2 (LRP2 or megalin) is representative of the phylogenetically conserved subfamily of giant LDL receptor-related proteins, which function in endocytosis and are implicated in diseases of the kidney and brain. Here, we report high-resolution cryoelectron microscopy structures of LRP2 isolated from mouse kidney, at extracellular and endosomal pH. The structures reveal LRP2 to be a molecular machine that adopts a conformation for ligand binding at the cell surface and for ligand shedding in the endosome. LRP2 forms a homodimer, the conformational transformation of which is governed by pH-sensitive sites at both homodimer and intra-protomer interfaces. A subset of LRP2 deleterious missense variants in humans appears to impair homodimer assembly. These observations lay the foundation for further understanding the function and mechanism of LDL receptors and implicate homodimerization as a conserved feature of the LRP receptor subfamily.

Design of an ultrafast pulsed ponderomotive phase plate for cryo-electron tomography.

Ponderomotive phase plates have shown that temporally consistent phase contrast is possible within electron microscopes via high-fluence static laser modes resonating in Fabry-Perot cavities. Here, we explore using pulsed laser beams as an alternative method of generating high fluences. We find through forward-stepping finite element models that picosecond or shorter interactions are required for meaningful fluences and phase shifts, with higher pulse energies and smaller beam waists leading to predicted higher fluences. An additional model based on quasi-classical assumptions is used to discover the shape of the phase plate by incorporating the oscillatory nature of the electric field. From these results, we find the transient nature of the laser pulses removes the influence of Kapitza-Dirac diffraction patterns that appear in the static resonator cases. We conclude by predicting that a total laser pulse energy of 8.7 µJ is enough to induce the required π/2 phase shift for Zernike-like phase microscopy.

Postdeployment Treatment Gap: Symptoms and Treatment Utilization Among Returning National Guard Soldiers.

This study evaluated rates of psychiatric symptoms and mental health treatment utilization among National Guard service members during the post-deployment period. National Guard service members (n=311) completed surveys assessing demographics, beliefs about mental health treatment, emotion regulation strategies, and psychiatric symptoms. Mental health treatment utilization was assessed at 6-month follow-up. Post-deployment, 41.2% of the sample had psychiatric symptoms above the clinical cut-off for at least one symptom measure. This proportion increased at follow-up (53.5%). Alcohol use disorder (AUD) symptoms showed the largest increase (d=0.66), although symptoms of depression and posttraumatic stress disorder (PTSD) also showed small magnitude increases. Among those with elevated symptoms post-deployment (n=128), only 27.8% received mental health treatment at follow-up. Severity of depression, anxiety, and PTSD were higher among those who utilized treatment. The post-deployment period is a vulnerable one. Continued efforts to understand and address barriers to treatment for this population are warranted.

Homotypic fibrillization of TMEM106B across diverse neurodegenerative diseases.

Misfolding and aggregation of disease-specific proteins, resulting in the formation of filamentous cellular inclusions, is a hallmark of neurodegenerative disease with characteristic filament structures, or conformers, defining each proteinopathy. Here we show that a previously unsolved amyloid fibril composed of a 135 amino acid C-terminal fragment of TMEM106B is a common finding in distinct human neurodegenerative diseases, including cases characterized by abnormal aggregation of TDP-43, tau, or α-synuclein protein. A combination of cryoelectron microscopy and mass spectrometry was used to solve the structures of TMEM106B fibrils at a resolution of 2.7 Å from postmortem human brain tissue afflicted with frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP, n = 8), progressive supranuclear palsy (PSP, n = 2), or dementia with Lewy bodies (DLB, n = 1). The commonality of abundant amyloid fibrils composed of TMEM106B, a lysosomal/endosomal protein, to a broad range of debilitating human disorders indicates a shared fibrillization pathway that may initiate or accelerate neurodegeneration.

Stakeholder perspectives on sustainment of Housing First in a VA permanent supportive housing program.

OBJECTIVE: To evaluate the sustainment of Housing First (HF) implementation in a permanent supportive housing program for homeless-experienced veterans, 5 years after practice implementation. STUDY SETTING: From 2016 to 2017, primary data were collected from providers and veterans in the Department of Housing and Urban Development-VA Supportive Housing (HUD-VASH) program at Los Angeles. STUDY DESIGN: Guided by the integrated sustainability framework, we performed a mixed-methods study to evaluate the sustainment of HF, an evidence-based practice implemented to improve housing outcomes. To assess sustainment, we measured fidelity to HF in six of seven HUD-VASH teams. These data were integrated with qualitative interviews with providers and veterans who described perceived sustainment to HF and contextual factors that supported or impeded sustainment. DATA COLLECTION: Fidelity to HF at 5 years after practice implementation, as a proxy for sustainment, was quantified via surveys with HUD-VASH teams. HUD-VASH providers (n = 51) and 31 veterans participated in semi-structured interviews. Team-based template analyses were used to develop an emergent understanding of stakeholder perspectives on HF sustainment. PRINCIPAL FINDINGS: Overall, HUD-VASH teams reported HF sustainment. The lowest fidelity scores were found in the domains of client-to-staff ratios, frequency of client-provider contact, and time to housing. Qualitative findings indicated that outer contextual factors (e.g., housing scarcity) and organizational factors (e.g., staff turnover) impacted HF sustainment. Providers identified changes in leadership and unmet resource needs as impediments to practice sustainment. All stakeholders identified positively with the HF practice and believed that the approach benefited veterans. CONCLUSIONS: This snapshot of HF sustainment demonstrates that this practice can be sustained over time. However, strong leadership, organizational resources, and community partnerships are needed. Adaptations to HF in response to outer contextual factors and organizational capacity may result in practice sustainment while allowing for flexibility in service provision.

The AD tau core spontaneously self-assembles and recruits full-length tau to filaments.

Tau accumulation is a major pathological hallmark of Alzheimer's disease (AD) and other tauopathies, but the mechanism(s) of tau aggregation remains unclear. Taking advantage of the identification of tau filament cores by cryoelectron microscopy, we demonstrate that the AD tau core possesses the intrinsic ability to spontaneously aggregate in the absence of an inducer, with antibodies generated against AD tau core filaments detecting AD tau pathology. The AD tau core also drives aggregation of full-length wild-type tau, increases seeding potential, and templates abnormal forms of tau present in brain homogenates and antemortem cerebrospinal fluid (CSF) from patients with AD in an ultrasensitive real-time quaking-induced conversion (QuIC) assay. Finally, we show that the filament cores in corticobasal degeneration (CBD) and Pick's disease (PiD) similarly assemble into filaments under physiological conditions. These results document an approach to modeling tau aggregation and have significant implications for in vivo investigation of tau transmission and biomarker development.

Computerized Conjoint Analysis of the Weight Treatment Preferences of Individuals With Schizophrenia.

OBJECTIVE: Innovative approaches are needed for assessing treatment preferences of individuals with schizophrenia. Conjoint analysis methods may help to identify preferences, but the usability and validity of these methods for individuals with schizophrenia remain unclear. This study examined computerized conjoint analysis for persons with schizophrenia and whether preferences for weight management programs predict service use. METHODS: A computerized, patient-facing conjoint analysis system was developed through iterative consultation with 35 individuals with schizophrenia enrolled at a community mental health clinic. An additional 35 overweight participants with schizophrenia then used the system to choose among psychosocial weight management programs varying in four attributes: location (community or clinic), delivery mode (Internet or in person), leader (clinician or layperson), and training mode (individual or group). A multilevel logit model with partial preference data determined contributions of each attribute to groupwide preferences. Associations were studied between preferences and use of a psychosocial weight management group. RESULTS: Conjoint analysis system usability was rated highly. Groupwide preferences were significantly influenced by location (p<0.001; clinic was preferred), leader (p=0.02; clinician was preferred), and training mode (p<0.001; group was preferred) but not delivery mode (p=0.68). Preferences did not correlate with age, gender, body mass index, illness severity, or subsequent program use. Participants described barriers to program attendance, including transportation, scheduling, privacy, psychiatric illness, and lack of motivation. CONCLUSIONS: Computerized conjoint analysis can produce valid assessments of treatment preferences of persons with schizophrenia and inform treatment development and implementation. Although preferences may affect treatment use, they are one of multiple factors.

When the political is professional: Civil disobedience in psychology.

Activists use civil disobedience as a means of putting social justice into practice. Psychologists can engage in civil disobedience to enact psychology's ethical principles, support marginalized communities, promote social welfare, and contest injustice. Drawing from the work of minoritized scholars within and outside of psychology, the American Psychological Association (APA) Ethics Code, social constructionism, intersectionality, and social justice movements, our article aims to empower psychologists to understand and use civil disobedience and advocates for expanding civil disobedience in the profession. Because psychologists' identities and contexts will inform their own civil disobedience, we utilize a social justice issue germane to our own work supporting transgender people as an exemplar where our ethical principles would conflict with law; thus, warranting civil disobedience. This example concerns Ohio House Bill 658, which, if enacted, would have mandated that psychologists "immediately notify, in writing, each of [a] child's parents if the child shows symptoms of gender dysphoria or otherwise demonstrates a desire to be treated in a manner opposite of the child's biological sex." We return to Ohio HB 658 and explore other contemporary social justice issues throughout to reveal how psychologists can conceptualize and enact civil disobedience in pursuit of transformative change. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Insurance- and medical provider-related barriers and facilitators to staying on PrEP: results from a qualitative study.

Pre-exposure prophylaxis (PrEP) is a highly effective biobehavioral strategy for preventing HIV acquisition. Although PrEP uptake has increased steadily, discontinuation rates are high among members of key populations like gay and bisexual men (GBM). Understanding the challenges that arise for PrEP users is key to better PrEP implementation and sustained use over time. We report on barriers that arose for PrEP-using GBM, as well as facilitating factors that aided PrEP persistence, with the goal of informing PrEP implementation efforts. In 2015-2016, 103 PrEP-using GBM in NYC completed qualitative interviews about their engagement with PrEP, including their experiences navigating PrEP-related medical care. Interviews were transcribed verbatim, coded, and analyzed thematically. Over half of participants (53%) received their PrEP-related care from their primary care provider (PCP), one-third (33%) from a community-based health clinic, and 13% from multiple medical providers. Emergent themes regarding the barriers and facilitators to PrEP persistence fell into two categories: insurance- and medical appointment-related barriers and facilitators to continued PrEP use. The experiences of PrEP-using GBM can provide useful insights for providers, program developers, and policymakers aiming to improve the implementation of PrEP. To support PrEP persistence, reliable insurance coverage, cost-assistance, and easy appointment scheduling are key to maintenance. Removing insurance- and appointment-related barriers to persistence may prove essential for sustaining use among GBM.

Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains.

Tau aggregation into insoluble filaments is the defining pathological hallmark of tauopathies. However, it is not known what controls the formation and templated seeding of strain-specific structures associated with individual tauopathies. Here, we use cryo-electron microscopy (cryo-EM) to determine the structures of tau filaments from corticobasal degeneration (CBD) human brain tissue. Cryo-EM and mass spectrometry of tau filaments from CBD reveal that this conformer is heavily decorated with posttranslational modifications (PTMs), enabling us to map PTMs directly onto the structures. By comparing the structures and PTMs of tau filaments from CBD and Alzheimer's disease, it is found that ubiquitination of tau can mediate inter-protofilament interfaces. We propose a structure-based model in which cross-talk between PTMs influences tau filament structure, contributing to the structural diversity of tauopathy strains. Our approach establishes a framework for further elucidating the relationship between the structures of polymorphic fibrils, including their PTMs, and neurodegenerative disease.

Sexual minority men want provider behavior consistent with attitudes and norms during patient-provider interactions regarding HIV prevention.

HIV is a health problem for sexual minority men in the United States. One factor among many that contributes to this HIV disparity is poor patient-provider interactions. We focused on specific provider behavior preferred by sexual minority men during patient-provider interactions about HIV prevention. We interviewed 20 HIV-negative sexual minority men who endorsed 1+ psychosocial HIV risk factor. We used follow up interviews and conventional content analysis. Among our sample, 55% identified as White; 50% as bisexual, (Mage = 28.45). Findings suggested even some providers knowledgeable about sexual minority health provided unhelpful care to sexual minority men (knowledge-behavior discrepancy). Some knowledgeable providers engaged in affirmative, tailored treatment (knowledge-behavior consistency). Specific behaviors of preferred patient-provider interactions regarding HIV prevention are reported. Our recommendations are based on patient perceptions, which is a limit and strength. We identified an important type of unhelpful patient-provider interaction for HIV-negative sexual minority men beyond discriminatory experiences. Patient-provider interaction efforts need to go beyond education to help providers practice skills. With increased focus on cultural competency for sexual minority patients, more providers may advertise their practice as affirmative, yet interactions will likely vary, may require lifelong practice of cultural humility, and impact HIV prevention.

Bottom-up structural proteomics: cryoEM of protein complexes enriched from the cellular milieu.

X-ray crystallography often requires non-native constructs involving mutations or truncations, and is challenged by membrane proteins and large multicomponent complexes. We present here a bottom-up endogenous structural proteomics approach whereby near-atomic-resolution cryo electron microscopy (cryoEM) maps are reconstructed ab initio from unidentified protein complexes enriched directly from the endogenous cellular milieu, followed by identification and atomic modeling of the proteins. The proteins in each complex are identified using cryoID, a program we developed to identify proteins in ab initio cryoEM maps. As a proof of principle, we applied this approach to the malaria-causing parasite Plasmodium falciparum, an organism that has resisted conventional structural-biology approaches, to obtain atomic models of multiple protein complexes implicated in intraerythrocytic survival of the parasite. Our approach is broadly applicable for determining structures of undiscovered protein complexes enriched directly from endogenous sources.

Gay and Bisexual Men's Strategies to Maintain Daily Adherence to Their HIV Pre-exposure Prophylaxis (PrEP) Medication: Results from a Qualitative Study.

Since FDA approval in 2012, HIV pre-exposure prophylaxis (PrEP) has been adopted by key populations, including gay and bisexual men (GBM), to reduce their HIV transmission risk. Given that PrEP is optimally effective when taken as prescribed, it is critical to understand the adherence strategies GBM use. We conducted one-on-one, semi-structured interviews with GBM taking PrEP in 2015-2016 (n = 103). Using thematic analysis, we identified six adherence strategies, with most participants (84.3%) utilizing multiple strategies to maintain adequate adherence: (1) integrating PrEP into part of a daily routine, (2) using a pillbox, (3) cognitive strategies/visual cues, (4) setting recurring smartphone alarms or reminders, (5) keeping medication on oneself at all times, and (6) partner or peer support for reminders and/or pill sharing. Overall, participants reported high PrEP adherence (M = 1.6 missed doses in the prior 30 days), though nearly all described missing at least one dose unintentionally in the past. Participants credited their high levels of adherence in part to the strategies they adopted. Providers working with GBM prescribed PrEP, especially patients reporting difficulties with adherence, might consider recommending any or all of the six strategies described in this study.

What motivates gay and bisexual men to participate in PrEP-related research?

Pre-Exposure Prophylaxis (PrEP) has been demonstrated effective at preventing HIV among key populations like gay and bisexual men (GBM). Yet, there remains a continued need to engage GBM in PrEP behavioral and clinical research (e.g., to monitor adherence and retention in the PrEP treatment cascade). We report on the factors motivating GBM to participate in a PrEP behavioral study, with the aim of our results to inform future recruitment efforts for future PrEP research. In 2015-2016, 103 PrEP-using GBM in NYC completed qualitative interviews about their experiences on PrEP. Participants were also asked about factors that motivated them to join the study. Thematic analysis was used analyze the data. We identified five salient themes as rationale for joining the study: 58.3% cited altruistic reasons, 32% reported intellectual curiosity in the subject matter, 30.1% indicated that remuneration inspired them, 18.4% indicated that familiarity or referral to the research institute influenced their decision. Researchers attempting to enroll PrEP-using GBM may benefit from attending to the altruistic and intellectually curious nature of this population. Further, researchers may benefit from establishing familiarity among diverse communities of GBM. This in turn may contribute to the successful engagement of GBM for PrEP research.

How Do Gay and Bisexual Men Make Up for Missed PrEP Doses, and What Impact Does Missing a Dose Have on Their Subsequent Sexual Behavior?

HIV pre-exposure prophylaxis (PrEP) is being adopted by members of key populations, such as gay and bisexual men (GBM). Since adherence to a daily PrEP regimen ensures a maximum protection, it is critical to understand GBM's behavioral responses to having missed PrEP doses. We report on qualitative interviews with GBM taking PrEP. We identified three behavioral responses: (1) 59% continued with their next scheduled dose; (2) 49% described "making up" for a missed dose by taking medication as soon as possible; and (3) 11% reported "doubling" the next PrEP dose. Participants provided potentially contradictory narratives about their sexual behavior after a missed dose: (1) 54% described making no changes; (2) 49% described adjusting their sexual behavior to reduce HIV risk; and (3) 10% said their decision would be contingent upon how many doses were missed. For PrEP prescribers, our data provide a useful lens to understand patients' lived experiences with PrEP.

A clustered controlled trial of the implementation and effectiveness of a medical home to improve health care of people with serious mental illness: study protocol.

BACKGROUND: People with serious mental illness (SMI) die many years prematurely, with rates of premature mortality two to three times greater than the general population. Most premature deaths are due to "natural causes," especially cardiovascular disease and cancer. Often, people with SMI are not well engaged in primary care treatment and do not receive high-value preventative and medical services. There have been numerous efforts to improve this care, and few controlled trials, with inconsistent results. While people with SMI often do poorly with usual primary care arrangements, research suggests that integrated care and medical care management may improve treatment and outcomes, and reduce treatment costs. METHODS: This hybrid implementation-effectiveness study is a prospective, cluster controlled trial of a medical home, the SMI Patient-Aligned Care Team (SMI PACT), to improve the healthcare of patients with SMI enrolled with the Veterans Health Administration. The SMI PACT team includes proactive medical nurse care management, and integrated mental health treatment through regular psychiatry consultation and a collaborative care model. Patients are recruited to receive primary care through SMI PACT based on having a serious mental illness that is manageable with treatment, and elevated risk for hospitalization or death. In a site-level prospective controlled trial, this project studies the effect, relative to usual care, of SMI PACT on provision of appropriate preventive and medical treatments, health-related quality of life, satisfaction with care, and medical and mental health treatment utilization and costs. Research includes mixed-methods formative evaluation of usual care and SMI PACT implementation to strengthen the intervention and assess barriers and facilitators. Investigators examine relationships among organizational context, intervention factors, and patient and clinician outcomes, and identify patient factors related to successful patient outcomes. DISCUSSION: This will be one of the first controlled trials of the implementation and effectiveness of a patient centered medical home for people with serious mental illness. It will provide information regarding the value of this strategy, and processes and tools for implementing this model in community healthcare settings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01668355 . Registered August 20, 2012.