Linking Cardiac Psychology and Cardiovascular Medicine via Self-Determination Theory and Shared Decision-Making.

Despite considerable progress in recent years, research in cardiac psychology is not widely translated into routine practice by clinical cardiologists or clinical health psychologists. Self-determination theory (SDT), which addresses how basic psychological needs of autonomy, competence, and relatedness contribute to the internalization of motivation, may help bridge this research-practice gap through its application to shared decision-making (SDM). This narrative review discusses the following: (a) brief background information on SDT and SDM, (b) the application of SDT to health behavior change and cardiology interventions, and (c) how SDT and SDM may be merged using a dissemination and implementation (D&I) framework. We address barriers to implementing SDM in cardiology, how SDM and SDT address the need for respect of patient autonomy, and how SDT can enhance D&I of SDM interventions through its focus on autonomy, competence, and relatedness and its consideration of other constructs that facilitate the internalization of motivation.

Resilient together-ALS: leveraging the NDD transdiagnostic framework to develop an early dyadic intervention for people with amyotrophic lateral sclerosis and their informal care-partners.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive weakness and eventual death, usually within 3-5 years. An ALS diagnosis is associated with substantial emotional distress for both the affected person and their family care-partners which impairs the ability to engage in important conversations about long term care planning, negatively impacts ALS symptoms for the patient, and quality of life for both patient and care-partner. Here we 1) discuss published works identified by the authors about psychosocial interventions for the ALS population, 2) identify a lack of early, dyadic interventions to support psychosocial needs of people with ALS and care-partners; 3) describe the Neurodegenerative Diseases (NDD) framework for early dyadic intervention development and 4) propose an adaptation of an evidence-based early dyadic psychosocial intervention, Recovering Together, for the unique needs of people with ALS and their care-partners (Resilient Together-ALS; RT-ALS) using the NDD framework. Future work will use stakeholder feedback to optimize the intervention for subsequent efficacy testing.

A roadmap for early psychosocial support in palliative care for people impacted by ALS-reducing suffering, building resiliency, and setting the stage for delivering timely transdiagnostic psychosocial care.

This commentary describes the current state of psychosocial care for people with amyotrophic lateral sclerosis and their caregivers. We provide recommendations for developing a roadmap for future research based on existing literature and our group's clinical and research experience to inform next steps to expand evidence-based psychosocial care for people with amyotrophic lateral sclerosis and their caregivers, with potential implications for a range of advanced illnesses.

This article talks about psychosocial care for people with amyotrophic lateral sclerosis and the loved ones who take care of them (caregivers). We talk about gaps in current psychosocial care and offer ideas about research to help develop care options for people with amyotrophic lateral sclerosis and their caregivers. It is possible that this work could also guide the development of psychosocial care for people with other advanced illnesses and their caregivers.

Meaning Salience and Meaning in Life Prospectively Predict Lower Distress During the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic is a widespread source of stress with adverse mental health impacts. Meaning in life, both as a trait and as momentary awareness of what is personally meaningful (meaning salience), is associated with positive health outcomes and may buffer against the deleterious effects of stress. PURPOSE: This project examines prospective associations between baseline meaning salience (daily, post-laboratory stressor) and meaning in life with perceived stress during COVID-19. METHODS: A community sample of healthy adults (n = 147) completed a laboratory stress protocol in 2018-2019, where perceived stress, meaning in life, and meaning salience (daily, post-stressor) were assessed. During April and July 2020 (n = 95, and 97, respectively), participants were re-contacted and reported perceived stress. General linear mixed-effects models accounting for repeated measures of stress during COVID-19 were conducted. RESULTS: Partial correlations holding constant baseline perceived stress showed that COVID-19 perceived stress was correlated with daily meaning salience (r = -.28), post-stressor meaning salience (r = -.20), and meaning in life (r = -.22). In mixed-effects models, daily and post-stressor meaning salience and higher meaning in life, respectively, predicted lower perceived stress during COVID-19, controlling for age, gender, and baseline perceived stress. CONCLUSIONS: Individuals more capable of accessing meaning when exposed to laboratory stress reported lower perceived stress during a global health crisis. Despite study limitations concerning generalizability, results support meaning in life and meaning salience as important aspects of psychological functioning that may promote well-being by affecting stress appraisals and available resources for coping.

The COVID-19 pandemic is a widespread source of stress. Having a sense of meaning in life, or that you have goals in life and a sense that the things you do are worthwhile and significant, is an important part of psychological well-being and might help reduce stress. We collected data on 147 healthy adults in 2018­2019 regarding their stress levels, sense of meaning in life, and how often they were aware of their life's meaning on daily basis and after a stress task in the laboratory. We re-contacted these adults in both April and July 2020 to ask about their stress, and 95 adults responded. Adults who had higher meaning in life in 2018­2019 experienced less stress during the early months of the COVID-19 pandemic. Adults who were more aware of their life's meaning each day and immediately after a stress task in the laboratory also experienced less stress during the COVID-19 pandemic. Results from this study provide evidence that having a strong sense of meaning in life overall and being aware of your life's meaning each day and during times of stress, may promote psychological well-being and reduce stress during times when stress is widespread and abundant.

The Recovering Together study protocol: A single-blind RCT to prevent chronic emotional distress in patient-cargiver dyads in the Neuro-ICU.

INTRODUCTION: Patients admitted to the Neuroscience Intensive Care Unit (Neuro-ICU) with acute neurological illnesses (ANI; e.g., stroke, tumor, TBI) and their informal caregivers experience high rates of anxiety, depression, and posttraumatic stress. To address this need, we previously developed the Recovering Together (RT) dyadic intervention to help prevent chronic emotional distress in both patients and caregivers. Currently, we are conducting a fully-powered, single-blind randomized clinical trial (RCT) to evaluate the efficacy of RT versus an attention matched health education control. Here, we describe the protocol and current status of this RCT. METHODS: We aim to recruit 194 at risk patient-caregiver dyads from the Neuro-ICU at MGH. Eligible dyads include patients diagnosed with ANI, cognitively intact, at least one partner endorses emotional distress (on Hospital Anxiety and Depression Scale), English speaking, age 18 or older. Dyads are randomized to the intervention (RT-1) or control condition (RT-2) (both six sessions). RT-1 teaches resiliency (e.g., coping, mindfulness) and interpersonal skills. RT-2 provides education on health-related topics (e.g., stress, self-care, adhering to medical recommendations). Blinded research assistants collect measures at baseline, post-intervention, and three months follow-up. We will conduct mixed linear, mediation, and actor-partner interdependence models to examine changes in dyads' outcomes across time. RESULTS: We have recruited 41 dyads and aim to recruit 194 total. DISCUSSION: If successful, we plan to test RT in a large-scale, multisite hybrid effectiveness-implementation study in Neuro-ICUs across the country. Enhancing psychosocial supports for patients and families could improve health outcomes, healthcare efficiency, and the culture of these units.

Brief report: Meaning in life is mediated by self-efficacy in the prediction of physical activity.

Meaning and purpose in life are related to a reduced risk of mortality and cardiovascular events, and meaning has been established as a correlate of physical activity. However, it is not clear what mechanisms account for the relationship between meaning and physical activity. A cross-sectional analysis (N = 94) indicated that self-efficacy in improving physical fitness is a statistically significant mediator of the relationship between meaning and physical activity.

Long-term follow-up of mind-body medicine practices among medical school graduates.

INTRODUCTION: We sought to determine the long-term use of mind-body medicine (MBM) skills after graduation from medical school. METHODS: An online survey was sent to Georgetown University School of Medicine (GUSOM) graduates who completed at least one semester of a MBM skills training course. Using a quantitative-qualitative mixed-methods approach, we assessed the personal and professional practices of graduates, and identified factors that may influence practice/training after graduation. RESULTS: Current personal practices were positively related to the level of the course completed and amount of home practice during medical school (N = 112). Over half the sample indicated they currently practice MBM and refer patients to MBM. Moreover, physician specialty and awareness of home institution MBM training was associated with MBM patient training and referral. Participants reported a dearth of MBM training at their home institutions, and provided qualitative insights about the personal and professional impact of MBM training as well as barriers to continued MBM practice. CONCLUSIONS: The results provide preliminary evidence that MBM training during medical school may be related over time to physician trainee self-care and patient care. Rigorous tests of these relationships should be conducted in future work.

Complementary and Alternative Medicine Use and Latina Breast Cancer Survivors' Symptoms and Functioning.

Complementary and alternative medicine (CAM) is used widely in cancer populations, particularly among women, and has shown promise for addressing symptom and functioning outcomes. Few studies to date have evaluated CAM use and associations over time with symptoms and function among Latina breast cancer survivors. We administered a baseline (N = 136) and follow-up (n = 58) telephone survey in Spanish or English assessing Latina breast cancer survivor demographics, physical function, anxiety, depression, fatigue, satisfaction with social roles, and both CAM activities and devotional and spiritual practices. About one-third of our sample (35% baseline; 36% follow-up) reported using CAM (yoga, meditation, massage, or herbal/dietary supplements). We assessed devotional and spiritual practices separately from CAM (church attendance, prayer, religious groups, and reading devotional and religious texts); the majority of Latina survivors reported devotional and spiritual practices (80% baseline; 81% follow-up). At baseline, CAM demonstrated a positive association with better physical functioning and lower depression. In contrast, CAM use at the time of follow-up appeared to be related to lower levels of satisfaction with social roles and physical function. In longitudinal analyses, devotional and spiritual practices at baseline significantly predicted lower anxiety, depression, and fatigue at follow-up. Findings suggest CAM plays a complex and not always linear role in symptoms and function outcomes for Latina breast cancer survivors. These findings contribute to the literature on longitudinal CAM use and associations with symptom and functioning outcomes among Latina breast cancer survivors.

Engaging Latina cancer survivors, their caregivers, and community partners in a randomized controlled trial: Nueva Vida intervention.

INTRODUCTION: Few studies have evaluated interventions to improve quality of life (QOL) for Latina breast cancer survivors and caregivers. Following best practices in community-based participatory research (CBPR), we established a multi-level partnership among Latina survivors, caregivers, community-based organizations (CBOs), clinicians, and researchers to evaluate a survivor-caregiver QOL intervention. METHODS: A CBO in the mid-Atlantic region, Nueva Vida, developed a patient-caregiver program called Cuidando a mis Cuidadores (Caring for My Caregivers), to improve outcomes important to Latina cancer survivors and their families. Together with an academic partner, Nueva Vida and three CBOs established a multi-level team of researchers, clinicians, Latina cancer survivors, and caregivers to conduct a national randomized trial to compare the patient-caregiver program to usual care. RESULTS: Incorporating team feedback and programmatic considerations, we adapted the prior patient-caregiver program into an 8-session patient- and caregiver-centered intervention that includes skill-building workshops such as managing stress, communication, self-care, social well-being, and impact of cancer on sexual intimacy. We will measure QOL domains with the patient-reported outcomes measurement information system, dyadic communication between the survivor and caregiver, and survivors' adherence to recommended cancer care. To integrate the intervention within each CBO, we conducted interactive training on the protection of human subjects, qualitative interviewing, and intervention delivery. CONCLUSION: The development and engagement process for our QOL intervention study is innovative because it is both informed by and directly impacts underserved Latina survivors and caregivers. The CBPR-based process demonstrates successful multi-level patient engagement through collaboration among researchers, clinicians, community partners, survivors, and caregivers.

Human YKL-39 is a pseudo-chitinase with retained chitooligosaccharide-binding properties.

The chitinase-like proteins YKL-39 (chitinase 3-like-2) and YKL-40 (chitinase 3-like-1) are highly expressed in a number of human cells independent of their origin (mesenchymal, epithelial or haemapoietic). Elevated serum levels of YKL-40 have been associated with a negative outcome in a number of diseases ranging from cancer to inflammation and asthma. YKL-39 expression has been associated with osteoarthritis. However, despite the reported association with disease, the physiological or pathological role of these proteins is still very poorly understood. Although YKL-39 is homologous to the two family 18 chitinases in the human genome, it has been reported to lack any chitinase activity. In the present study, we show that human YKL-39 possesses a chitinase-like fold, but lacks key active-site residues required for catalysis. A glycan screen identified oligomers of N-acetylglucosamine as preferred binding partners. YKL-39 binds chitooligosaccharides and a newly synthesized derivative of the bisdionin chitinase-inhibitor class with micromolar affinity, through a number of conserved tryptophan residues. Strikingly, the chitinase activity of YKL-39 was recovered by reverting two non-conservative substitutions in the active site to those found in the active enzymes, suggesting that YKL-39 is a pseudo-chitinase with retention of chitinase-like ligand-binding properties.

Bisdionin C-a rationally designed, submicromolar inhibitor of family 18 chitinases.

Chitinases of the GH18 family play important roles in a variety of pathogenic organisms and have also been shown to be involved in human asthma progression, making these enzymes potential drug targets. While a number of potent GH18 chitinase inhibitors have been described, in general, these compounds suffer from limited synthetic accessibility or unfavorable medicinal-chemical properties, making them poor starting points for the development of chitinase-targeted drugs. Exploiting available structural data, we have rationally designed bisdionin C, a submicromolar inhibitor of GH18 enzymes, that possesses desirable druglike properties and tractable chemical synthesis. A crystallographic structure of a chitinase-bisdionin C complex shows the two aromatic systems of the ligand interacting with two conserved tryptophan residues exposed in the active site cleft of the enzyme, while at the same time forming extensive hydrogen-bonding interactions with the catalytic machinery. The observed mode of binding, together with inhibition data, suggests that bisdionin C presents an attractive starting point for the development of specific inhibitors of bacterial-type, but not plant-type, GH 18 chitinases.

Natural product-guided discovery of a fungal chitinase inhibitor.

Natural products are often large, synthetically intractable molecules, yet frequently offer surprising inroads into previously unexplored chemical space for enzyme inhibitors. Argifin is a cyclic pentapeptide that was originally isolated as a fungal natural product. It competitively inhibits family 18 chitinases by mimicking the chitooligosaccharide substrate of these enzymes. Interestingly, argifin is a nanomolar inhibitor of the bacterial-type subfamily of fungal chitinases that possess an extensive chitin-binding groove, but does not inhibit the much smaller, plant-type enzymes from the same family that are involved in fungal cell division and are thought to be potential drug targets. Here we show that a small, highly efficient, argifin-derived, nine-atom fragment is a micromolar inhibitor of the plant-type chitinase ChiA1 from the opportunistic pathogen Aspergillus fumigatus. Evaluation of the binding mode with the first crystal structure of an A. fumigatus plant-type chitinase reveals that the compound binds the catalytic machinery in the same manner as observed for argifin with the bacterial-type chitinases. The structure of the complex was used to guide synthesis of derivatives to explore a pocket near the catalytic machinery. This work provides synthetically tractable plant-type family 18 chitinase inhibitors from the repurposing of a natural product.

Rhombohedral crystals of the human vinculin head domain in complex with a vinculin-binding site of talin.

Intermolecular interactions between the cytoskeletal proteins talin and vinculin are required for outside-in integrin signaling triggered by the formation of focal adhesions. Talin possesses three non-contiguous vinculin-binding sites (VBS); binding of one of these motifs, VBS3, provokes dramatic alterations in the structure of the vinculin's head (Vh) domain and this activates vinculin (Izard et al., 2004). To address the role of talin's other VBSs in vinculin activation, talin VBS1 (human residues 607-636) was crystallized in complex with the Vh (human residues 1-258) domain. Rhombohedral crystals of human Vh-VBS1 were obtained. The crystals belong to space group R32, with unit-cell parameters a = 88.7 A, alpha = 105.5 degrees and diffract to 2.4 A on a third-generation synchrotron source. The packing density for one heterodimer in the asymmetric unit is 3.04 A(3) Da(-1), with a solvent content of 0.59.

Vinculin activation by talin through helical bundle conversion.

Vinculin is a conserved component and an essential regulator of both cell-cell (cadherin-mediated) and cell-matrix (integrin-talin-mediated focal adhesions) junctions, and it anchors these adhesion complexes to the actin cytoskeleton by binding to talin in integrin complexes or to alpha-actinin in cadherin junctions. In its resting state, vinculin is held in a closed conformation through interactions between its head (Vh) and tail (Vt) domains. The binding of vinculin to focal adhesions requires its association with talin. Here we report the crystal structures of human vinculin in its inactive and talin-activated states. Talin binding induces marked conformational changes in Vh, creating a novel helical bundle structure, and this alteration actively displaces Vt from Vh. These results, as well as the ability of alpha-actinin to also bind to Vh and displace Vt from pre-existing Vh-Vt complexes, support a model whereby Vh functions as a domain that undergoes marked structural changes that allow vinculin to direct cytoskeletal assembly in focal adhesions and adherens junctions. Notably, talin's effects on Vh structure establish helical bundle conversion as a signalling mechanism by which proteins direct cellular responses.