Caregiver Experiences With an Internet-Delivered Insomnia Intervention: SHUTi-CARE Trial Primary Qualitative Analysis.

BACKGROUND: Digital health interventions show potential to increase caregivers' access to psychosocial care; however, it is unclear to what extent existing interventions may need to be tailored to meet caregivers' unique needs. PURPOSE: This study aimed to determine whether-and if so, how-an efficacious Internet-delivered insomnia program should be modified for caregivers. The generalizability of these findings beyond the tested program was also examined. METHODS: Higher-intensity family caregivers (N = 100; age M = 52.82 [SD = 13.10], 75% non-Hispanic White, 66% ≥college degree) received access to an Internet-based cognitive-behavioral therapy for insomnia (CBT-I) program. Participants who completed one or more intervention "Cores" provided open-ended feedback on their experience; nonusers (completed no Cores) shared their barriers. RESULTS: Most caregivers who used the program (n = 82, 82%) found it feasible, citing its user-friendly, fully automated online format. Many reported that CBT-I strategies were helpful, although some faced challenges in implementing these strategies due to the unpredictability of their caregiving responsibilities. Opinions were divided on the utility of tailoring the program for caregivers. Nonusers (n = 18, 18%) primarily cited concerns about time burden and lifestyle compatibility as usage barriers. CONCLUSIONS: Delivering fully automated behavioral interventions through the Internet appears suitable for many caregivers. Extensive tailoring may not be required for most caregivers to benefit from an existing online CBT-I program, although additional guidance on integrating CBT-I strategies in the context of challenging sleep schedules and environments may help a subset of caregivers. Future research should explore how such tailoring may enhance digital health intervention uptake and effectiveness for caregivers.

This study examined family caregivers' experiences using an online cognitive-behavioral therapy for insomnia program. The aim was to determine if the program needed changes to better fit caregivers' needs. Researchers gave 100 caregivers with insomnia access to Sleep Healthy Using the Internet (SHUTi), an online insomnia program that had no caregiver-specific tailoring. Of the 82 caregivers who used the program, most found the program easy to use and helpful, although some struggled with behavioral strategies because of their unpredictable caregiving duties. There was no clear consensus among caregivers on whether tailoring would be helpful. The 18 caregivers who did not use the program most commonly said that they did not have enough time to use the program or that they felt it would not work well with their lifestyle. Overall, findings suggest that providing interventions via the Internet is a good fit for many caregivers. Many caregivers benefitted from an online insomnia program without being tailored specifically for caregivers, although some additional guidance on how to follow behavioral strategies may be helpful to some caregivers.

A broadly-neutralizing antibody against Ebolavirus glycoprotein that potentiates the breadth and neutralization potency of other antibodies.

Ebolavirus disease (EVD) is caused by multiple species of Ebolavirus. Monoclonal antibodies (mAbs) against the virus glycoprotein (GP) are the only class of therapeutic approved for treatment of EVD caused by Zaire ebolavirus (EBOV). Therefore, mAbs targeting multiple Ebolavirus species may represent the next generation of EVD therapeutics. Broadly reactive anti-GP mAbs were produced; among these, mAbs 11886 and 11883 were broadly neutralizing in vitro. A 3.0 Å cryo-electron microscopy structure of EBOV GP bound to both mAbs shows that 11886 binds a novel epitope bridging the glycan cap (GC), 310 pocket and GP2 N-terminus, whereas 11883 binds the receptor binding region (RBR) and GC. In vitro, 11886 synergized with a range of mAbs with epitope specificities spanning the RBR/GC, including 11883. Notably, 11886 increased the breadth of neutralization by partner mAbs against different Ebolavirus species. These data provide a strategic route to design improved mAb-based next-generation EVD therapeutics.

Family Cancer Caregiver Use of and Benefit from an Internet-delivered Insomnia Intervention: Results from a Single-Group Feasibility Trial.

Background: Cancer caregivers are more likely to report clinically significant symptoms of insomnia than cancer patients and the general population, yet research has been limited regarding cognitive-behavioral therapy for insomnia (CBT-I) among this population. Methods: To better understand cancer caregivers' engagement with and benefit from CBT-I, cancer caregivers were enrolled in a nonrandomized pilot feasibility trial of an evidence-based Internet-delivered insomnia program. Thirteen caregivers completed mixed-methods assessments prior to receiving the insomnia program and after the nine-week intervention period. Results: Compared to the five caregivers who did not complete any intervention Cores, the eight caregivers who completed at least one of the intervention Cores tended to report more sleep impairment (insomnia symptom severity; minutes of sleep onset latency and wake after sleep onset), less physical and emotional strain from caregiving, and less maladaptive sleep beliefs at the baseline assessment. These caregivers who used the program also showed large improvements in their insomnia symptoms. Caregivers' qualitative feedback about their experience with the program identified potential areas that might be modified to improve caregivers' engagement with and benefit from Internet-delivered insomnia programs. Conclusions: Findings suggest that family cancer caregivers can use and benefit from a fully-automated Internet-delivered CBT-I program, even without caregiving-specific tailoring. Further rigorous research is needed to better understand whether and how program modifications may allow more caregivers to initiate and engage with this program.

Caregivers' Internet-Delivered Insomnia Intervention Engagement and Benefit: SHUTi-CARE Trial Primary Quantitative Analysis.

BACKGROUND: Delivering insomnia treatment by the Internet holds promise for increasing care access to family caregivers, but their ability to adhere to and benefit from such fully-automated programs has not been rigorously tested. PURPOSE: This fully-powered, single-group trial tested whether characteristics of the caregiving context influence high-intensity caregivers' engagement with and benefit from an empirically validated Internet intervention for insomnia. METHODS: At baseline, caregivers providing unpaid time- and responsibility-intensive care who reported insomnia (N = 100; age M = 52.82 [SD = 13.10], 75% non-Hispanic white, 66% ≥college degree) completed questionnaires about caregiving context and sleep, then 10 prospectively-collected online daily sleep diaries. Caregivers then received access to SHUTi (Sleep Healthy Using the Internet), which has no caregiver-specific content, for 9 weeks, followed by post-assessment (questionnaires, diaries). Engagement was tracked by the SHUTi delivery system. RESULTS: Sixty caregivers completed SHUTi, 22 initiated but did not complete SHUTi, and 18 did not initiate SHUTi. Caregivers were more likely to use SHUTi (than not use SHUTi) when their care recipient (CR) had worse functioning, and were more likely to complete SHUTi when supporting more CR activities of daily living (ADL; ps < .03). Higher caregiver guilt, more CR problem behaviors, and being bedpartners with the CR related to more improved sleep outcomes, whereas supporting more CR instrumental ADL related to less improvement (ps < .05). CONCLUSIONS: Factors associated with greater caregiving burden, including greater CR impairment and caregiving guilt, were generally associated with better engagement and outcomes. Caregivers with substantial burdens can adhere to and benefit from a fully automated insomnia program without caregiver-specific tailoring.

This study examined how family caregivers, who often have trouble sleeping due to their responsibilities, used an online insomnia treatment program. The goal was to determine if certain aspects of caregiving would influence how caregivers engage with or benefit from the program. Researchers surveyed 100 caregivers with insomnia about their caregiving situation and sleep, and caregivers also kept online sleep diaries for 10 days. Afterward, caregivers used an online insomnia program with no caregiver-specific content called Sleep Healthy Using the Internet (SHUTi) for 9 weeks. Caregivers' usage was monitored, and they repeated measures of sleep outcomes and 10 online sleep diaries. Sixty caregivers completed SHUTi, 22 partially completed the program, and 18 did not initiate the program. Caregivers who cared for individuals with more severe functional limitations were more likely to use and complete SHUTi. Additionally, caregivers experiencing more guilt and those who managed more challenging behaviors from the person they cared for tended to report greater improvements in their sleep. This study suggests that caregivers, even those with significant care responsibilities, can use and benefit from an online insomnia treatment program like SHUTi, even when it has not been specifically tailored for caregivers.

Presentation, management, and outcomes of norovirus in adult and pediatric solid organ and hematopoietic stem cell transplant recipients: A multicenter, retrospective study.

BACKGROUND: Norovirus (NoV) can cause chronic relapsing and remitting diarrhea in immunocompromised patients.  Few multicenter studies have described the clinical course, outcomes, and complications of chronic NoV in transplant recipients. METHODS: A multicenter retrospective study of adult and pediatric SOT and HSCT recipients diagnosed with NoV between November 1, 2017, and February 28, 2021. Data were obtained from electronic medical records (EMR) and entered into a central REDCap database. Descriptive statistics were calculated. RESULTS: A total of 280 NoV+ patients were identified across eight sites. The majority were adults (74.1%) and SOT recipients (91.4%). Initial diagnosis of NoV occurred a median of 36 months post-Tx (IQR [15.0, 90.0]). Most NoV cases had >3 diarrheal episodes daily (66.0%), nausea and vomiting (60.1%). Duration of diarrhea varied greatly (median = 10 days, mean = 85.9 days, range (1, 2100)). 71.3% were hospitalized. Adjustment of immunosuppression, including reduction and discontinuation of mToR inhibitor, CNI, and/or MMF, was the most common management intervention for NoV. Other therapies resulted only in temporary improvement. Four patients died within 30 days and three others died by 180 days postdiagnosis. Clinically significant renal dysfunction was observed in 12.5% by 30 days and 21.4% by 180 days post-NoV diagnosis. CONCLUSION: In HSCT and SOT patients, NoV frequently resulted in severe symptoms, prolonged diarrhea (30% persistent with diarrhea for >30 days), and clinically significant renal dysfunction (up to 21% of patients). Utilized therapies did not reliably result in the resolution of infection demonstrating the need for more effective treatment.

Sleep and Caregiver Burden Among Caregivers of Persons Living With Dementia: A Scoping Review.

Background and Objectives: Caregivers of persons with dementia report worse sleep when compared to the general population. The objective of this review was to synthesize evidence regarding the link between caregiver burden and dementia caregivers' sleep. Research Design and Methods: We conducted a scoping review using a systematic search for pertinent literature in PubMed, CINAHL, and Web of Science through March 2022. Keywords included content areas of dementia, caregiver burden, and sleep. Inclusion criteria were informal caregivers of persons living with dementia, a measured relationship between informal dementia caregiver sleep and subjective caregiver burden variables, and original research. Non-English studies were excluded. Extracted data were organized in tables, compared, and synthesized. Results: The search yielded 540 nonduplicate articles screened by title and abstract; 118 full-text articles were reviewed; 24 were included. Most studies were cross-sectional, with variable sample sizes. Dementia caregivers had significantly poorer overall perceived sleep than noncaregivers across 4 studies that examined self-reported sleep measures. Eighteen studies investigated the association between caregiver burden and self-reported sleep quality, with 14 reporting a significant positive association between caregiver burden and self-reported sleep quality, and 4 finding null results. Only 2 of the 4 studies reporting the association between caregiver burden and objective sleep parameters (ie, actigraphy and polysomnography) reported a significant positive association for at least one sleep subdomain. Discussion and Implications: Although subjective sleep quality is commonly affected by dementia caregiving burden, there is a lack of corresponding evidence on the relationship between burden and objective sleep metrics. Healthcare providers should consider the dementia caregiver burden's impact on sleep and regularly assess caregivers' sleep difficulties. Future studies should focus on consistently measuring caregiver burden and sleep to promote dementia caregiver health and well-being.

A randomized controlled trial of a distress screening, consultation, and targeted referral system for family caregivers in oncologic care.

OBJECTIVE: Distress screening is standard practice among oncology patients, yet few routine distress screening programs exist for cancer caregivers. The objective of this study was to demonstrate the feasibility, acceptability, and preliminary efficacy of Cancer Support Source-CaregiverTM (CSS-CG, 33-item), an electronic distress screening and automated referral program with a consultation (S + C) to improve caregiver unmet needs, quality of life, anxiety, depression, and distress relative to Enhanced Usual Care (EUC; access to educational materials). METHOD: 150 caregivers of patients with varying sites/stages of cancer were randomized to S + C or EUC and completed assessments at baseline, 3-months post-baseline, and 6-months post-baseline. A subset of participants (n = 10) completed in-depth qualitative interviews. RESULTS: S + C was feasible: among 75 caregivers randomized to S + C, 66 (88%) completed CSS-CG and consultation. Top concerns reported were: (1) patient's pain and/or physical discomfort; (2) patient's cancer progressing/recurring; and (3) feeling nervous or afraid. Differences between groups in improvements on outcomes by T2 and T3 were modest (ds < 0.53) in favor of S + C. Qualitative data underscored the helpfulness of S + C in connecting caregivers to support and helping them feel cared for and integrated into cancer care. CONCLUSIONS: S + C is feasible, acceptable, and yields more positive impact on emotional well-being than usual care. Future studies will examine programmatic impact among caregivers experiencing higher acuity of needs, and benefits of earlier integration of S + C on caregiver, patient, and healthcare system outcomes.

Effects of Caregiver Sleep Disturbances on Relationship Quality With Their Care Recipient.

OBJECTIVES: Sleep problems are highly prevalent and disruptive for caregivers. Although the connection between caregivers' sleep and outcomes like caregiver burden and quality of life is well established, the potential influence of caregivers' sleep on their reported relationship quality with the care recipient is not known. The current study sought to address this gap. METHODS: We analyzed data from the 2017 National Health and Aging Trends Study and linked it with data from the 2017 National Study of Caregiving. Our dependent variable was caregiver-reported relationship quality, and our predictor variable of interest was caregiver sleep problems. We also included several covariates related to the caregiver and care recipient. We used a generalized linear model to examine the relationship between caregiver sleep problems and relationship quality, controlling for other potentially influential factors. RESULTS: Sleep problems were significantly related to relationship quality. Compared to caregivers who reported no sleep problems, those who reported at least one sleep problem (ß: -0.23, 95% CI: -0.46 to -0.01) had lower relationship quality with the care recipient. Other factors that remained related to relationship quality in the generalized linear model were negative aspects of caregiving, emotional difficulties, caregiver race, relationship type, care recipient depressive symptoms, and care recipient sex. DISCUSSION: Sleep problems are influential health behaviors that are related to relationship quality for caregivers. Therefore, it is critical that sleep is more systematically assessed and addressed in caregiving populations.

Mobile sensing to advance tumor modeling in cancer patients: A conceptual framework.

As mobile and wearable devices continue to grow in popularity, there is strong yet unrealized potential to harness people's mobile sensing data to improve our understanding of their cellular and biologically-based diseases. Breakthrough technical innovations in tumor modeling, such as the three dimensional tumor microenvironment system (TMES), allow researchers to study the behavior of tumor cells in a controlled environment that closely mimics the human body. Although patients' health behaviors are known to impact their tumor growth through circulating hormones (cortisol, melatonin), capturing this process is a challenge to rendering realistic tumor models in the TMES or similar tumor modeling systems. The goal of this paper is to propose a conceptual framework that unifies researchers from digital health, data science, oncology, and cellular signaling, in a common cause to improve cancer patients' treatment outcomes through mobile sensing. In support of our framework, existing studies indicate that it is feasible to use people's mobile sensing data to approximate their underlying hormone levels. Further, it was found that when cortisol is cycled through the TMES based on actual patients' cortisol levels, there is a significant increase in pancreatic tumor cell growth compared to when cortisol levels are at normal healthy levels. Taken together, findings from these studies indicate that continuous monitoring of people's hormone levels through mobile sensing may improve experimentation in the TMES, by informing how hormones should be introduced. We hope our framework inspires digital health researchers in the psychosocial sciences to consider how their expertise can be applied to advancing outcomes across levels of inquiry, from behavioral to cellular.

Correlates of posttraumatic stress in cancer patients and their family caregivers across two years following diagnosis.

OBJECTIVE: To examine risk-factors of cancer-related PTSS in the 2-years post-diagnosis in adult colorectal cancer patients and caregivers. METHODS: Patients with colorectal cancer and their caregivers (N = 130 dyads) self-reported sociodemographic, psychosocial, and medical factors at diagnosis/treatment initiation (T1), at 1- (T2), and 2-year (T3) post-diagnosis. Cancer-related PTSS were assessed, and path analysis examined associations between proposed correlates and PTSS. RESULTS: Among patients, higher neuroticism and greater physical symptom distress were concurrently associated with higher PTSS (Bs ≥ 0.10, ps ≤ 0.02); greater physical symptom distress at T1 and greater social support at T2 were associated with higher PTSS at T3 (Bs ≥ 0.37, ps ≤ 0.04). Among caregivers, female gender, higher neuroticism (Bs ≥ 0.12, ps < 0.01), and lower social support (Bs  ≤ -0.24, ps ≤ 0.02) were associated with higher concurrent PTSS; lower patient physical symptom distress and social support at T1 (Bs  ≤ -0.27, ps ≤ 0.03) and longer hours spent caregiving at T2 (B = 0.03, p = 0.05) were associated with higher PTSS at T3. CONCLUSIONS: Findings identify cancer-specific risk factors (physical symptoms, hours caregiving), in addition to established risk factors (female, neuroticism, social support) in non-medical populations. The identified subgroups should receive ongoing screening and psychosocial referral for cancer-related PTSS.

Associations between context and affect within the daily lives of cancer caregivers.

PURPOSE: This study used ecological momentary assessment (EMA) to test the association between activity, location, and social company contexts with cancer caregivers' in-the-moment affect to identify precisely when and where to deliver psychological interventions for caregivers. METHODS: Current cancer caregivers (N = 25) received 8 EMA prompts per day for 7 consecutive days. At each prompt, caregivers reported their current positive affect and negative affect, as well as what they were doing, where they were located, and who they were with. Multilevel logistic regressions tested the associations between caregivers' contexts with their own person-mean-centered state (concurrent momentary level) and trait (overall weekly average) positive or negative affect. RESULTS: Caregivers reported lower state negative affect, as well as higher state positive affect, when socializing (ps < .001), when at a public location (ps < .03), and when around their friends, family, spouse/partner, or care recipient (i.e., person with cancer, ps < .02), relative to when not endorsing the context. Caregivers also reported lower state negative affect when eating/drinking or engaging in leisure (ps < .01; but no parallel effects for state positive affect). Caregivers reported higher state negative affect while working, when at their workplace, or when around work colleagues (ps < .001) and lower state positive affect when at home or alone (ps < .03). CONCLUSIONS: Results suggest the pertinence of a behavioral activation framework to mitigate the emotional strain of caregiving. Interventions that facilitate caregivers' ability to socialize with a range of friends and family, including their loved one with cancer, outside of the home may have the strongest positive emotional impact.

Developing a Healthy Lifestyle Program for Recent Kidney Transplant Recipients.

INTRODUCTION: Many kidney transplant recipients experience weight gain in the first year after transplantation. RESEARCH QUESTION: The objective of this research study was to assess the desires of recent kidney transplant patients about the design features of a healthy lifestyle program to counter unnecessary weight gain. DESIGN: In this descriptive study, recent recipients at 2 transplant centers were invited to participate in an online survey. Survey items included sociodemographic information, current medications, health conditions, weight change posttransplant, diet behaviors, physical activity participation, and desired features of a lifestyle program. RESULTS: Fifty-three participants, mean age 60.5 (11.2) years, primarily males, completed surveys. Forty percent gained weight posttransplantation with many indicating struggling with their diet. Physical activity levels stayed the same (17%) or decreased (40%) posttransplantation. Eighty-seven percent of participants indicated they would participate in an online lifestyle program and 76% wanted online physical activity and nutrition sessions to meet at least once weekly. Suggestions about the type of information and activities, included eating strategies (eg, how to eat healthfully at restaurants, grocery shopping tips, and recipes), resources for at-home physical activities, access to cooking classes, and apps to track both activity and food intake. CONCLUSION: Recent kidney transplant recipients would benefit from and desired to join a lifestyle program featuring tailored nutrition education and physical activity coaching. Gathered information will be used to inform and tailor a lifestyle program. Identifying features for the prevention of unnecessary weight gain with patients' input is essential for promoting and sustaining healthy behaviors.

Online sleep diaries: considerations for system development and recommendations for data management.

STUDY OBJECTIVES: To present development considerations for online sleep diary systems that result in robust, interpretable, and reliable data; furthermore, to describe data management procedures to address common data entry errors that occur despite those considerations. METHODS: The online sleep diary capture component of the Sleep Healthy Using the Internet (SHUTi) intervention has been designed to promote data integrity. Features include diary entry restrictions to limit retrospective bias, reminder prompts and data visualizations to support user engagement, and data validation checks to reduce data entry errors. Despite these features, data entry errors still occur. Data management procedures relying largely on programming syntax to minimize researcher effort and maximize reliability and replicability. Presumed data entry errors are identified where users are believed to have incorrectly selected a date or AM versus PM on the 12-hour clock. Following these corrections, diaries are identified that have unresolvable errors, like negative total sleep time. RESULTS: Using the example of one of our fully-powered, U.S. national SHUTi randomized controlled trials, we demonstrate the application of these procedures: of 45,598 total submitted diaries, 487 diaries (0.01%) required modification due to date and/or AM/PM errors and 27 diaries (<0.001%) were eliminated due to unresolvable errors. CONCLUSION: To secure the most complete and valid data from online sleep diary systems, it is critical to consider the design of the data collection system and to develop replicable processes to manage data. CLINICAL TRIAL REGISTRATION: Sleep Healthy Using The Internet for Older Adult Sufferers of Insomnia and Sleeplessness (SHUTiOASIS); https://clinicaltrials.gov/ct2/show/NCT03213132; ClinicalTrials.gov ID: NCT03213132.

Digital health and telehealth in cancer care: a scoping review of reviews.

The COVID-19 pandemic necessitated remote cancer care delivery via the internet and telephone, rapidly accelerating an already growing care delivery model and associated research. This scoping review of reviews characterised the peer-reviewed literature reviews on digital health and telehealth interventions in cancer published from database inception up to May 1, 2022, from PubMed, Cumulated Index to Nursing and Allied Health Literature, PsycINFO, Cochrane Reviews, and Web of Science. Eligible reviews conducted a systematic literature search. Data were extracted in duplicate via a pre-defined online survey. Following screening, 134 reviews met the eligibility criteria. 77 of those reviews were published since 2020. 128 reviews summarised interventions intended for patients, 18 addressed family caregivers, and five addressed health-care providers. 56 reviews did not target a specific phase of the cancer continuum, whereas 48 reviews tended to address the active treatment phase. 29 reviews included a meta-analysis, with results showing positive effects on quality of life, psychological outcomes, and screening behaviours. 83 reviews did not report intervention implementation outcomes but when reported, 36 reported acceptability, 32 feasibility, and 29 fidelity outcomes. Several notable gaps were identified in these literature reviews on digital health and telehealth in cancer care. No reviews specifically addressed older adults, bereavement, or sustainability of interventions and only two reviews focused on comparing telehealth to in-person interventions. Addressing these gaps with rigorous systematic reviews might help guide continued innovation in remote cancer care, particularly for older adults and bereaved families, and integrate and sustain these interventions within oncology.

Structure of the Inmazeb cocktail and resistance to Ebola virus escape.

Monoclonal antibodies can provide important pre- or post-exposure protection against infectious disease for those not yet vaccinated or in individuals that fail to mount a protective immune response after vaccination. Inmazeb (REGN-EB3), a three-antibody cocktail against Ebola virus, lessened disease and improved survival in a controlled trial. Here, we present the cryo-EM structure at 3.1 Å of the Ebola virus glycoprotein, determined without symmetry averaging, in a simultaneous complex with the antibodies in the Inmazeb cocktail. This structure allows the modeling of previously disordered portions of the glycoprotein glycan cap, maps the non-overlapping epitopes of Inmazeb, and illuminates the basis for complementary activities and residues critical for resistance to escape by these and other clinically relevant antibodies. We further provide direct evidence that Inmazeb protects against the rapid emergence of escape mutants, whereas monotherapies even against conserved epitopes do not, supporting the benefit of a cocktail versus a monotherapy approach.

Dyadic digital health interventions: Their rationale and implementation.

While most psychosocial and behavioral digital health interventions have been designed to be consumed by an individual, intervening at the level of a dyad - two interdependent individuals - can more comprehensively address the needs of both individuals and their relationship. The clinical utility of the dyadic digital health intervention approach, as well as the practical implementation of this design, will be demonstrated via three examples: eSCCIP, FAMS, and OurRelationship.

MTCH2 is a mitochondrial outer membrane protein insertase.

In the mitochondrial outer membrane, α-helical transmembrane proteins play critical roles in cytoplasmic-mitochondrial communication. Using genome-wide CRISPR screens, we identified mitochondrial carrier homolog 2 (MTCH2), and its paralog MTCH1, and showed that it is required for insertion of biophysically diverse tail-anchored (TA), signal-anchored, and multipass proteins, but not outer membrane ß-barrel proteins. Purified MTCH2 was sufficient to mediate insertion into reconstituted proteoliposomes. Functional and mutational studies suggested that MTCH2 has evolved from a solute carrier transporter. MTCH2 uses membrane-embedded hydrophilic residues to function as a gatekeeper for the outer membrane, controlling mislocalization of TAs into the endoplasmic reticulum and modulating the sensitivity of leukemia cells to apoptosis. Our identification of MTCH2 as an insertase provides a mechanistic explanation for the diverse phenotypes and disease states associated with MTCH2 dysfunction.

Development and feasibility of a communication training to assist caregivers with advanced care planning.

OBJECTIVE: Caregivers are critical in advanced care planning (ACP) discussions, which are difficult but necessary to carry out patients' goals of care. We developed and evaluated the feasibility and acceptability of a communication training to equip caregivers of patients with malignant brain tumors with skills to navigate ACP conversations. METHOD: Caregivers completed a 2-h virtual training addressing ACP Discussions with Your Loved One and ACP Discussions with the Medical Team. A pre-training assessment was completed at baseline and a training evaluation was completed one day post-training. A subset of participants completed semi-structured interviews 2 months post-training. RESULTS: Of 15 caregivers recruited, 9 attended the training and 4 completed qualitative interviews. Post-training, 40% felt confident in discussing ACP with loved ones and 67% felt confident doing so with healthcare professionals; 100% reported feeling confident in using skills learned in the training to facilitate these conversations. Data from qualitative interviews highlighted additional benefits of the training in empathic communication skills and fostering social support. SIGNIFICANCE OF RESULTS: Our communication skills training shows promise in supporting caregivers' skills and confidence in engaging in ACP discussions with patients and healthcare providers. A future randomized controlled trial with a larger and more diverse caregiving sample is needed to determine training efficacy.

Glycan shield of the ebolavirus envelope glycoprotein GP.

The envelope glycoprotein GP of the ebolaviruses is essential for host cell entry and the primary target of the host antibody response. GP is heavily glycosylated with up to 17 N-linked sites, numerous O-linked glycans in its disordered mucin-like domain (MLD), and three predicted C-linked mannosylation sites. Glycosylation is important for host cell attachment, GP stability and fusion activity, and shielding from neutralization by serum antibodies. Here, we use glycoproteomics to profile the site-specific glycosylation patterns of ebolavirus GP. We detect up to 16 unique O-linked glycosylation sites in the MLD, and two O-linked sites in the receptor-binding GP1 subunit. Multiple O-linked glycans are observed within N-linked glycosylation sequons, suggesting crosstalk between the two types of modifications. We confirmed C-mannosylation of W288 in full-length trimeric GP. We find complex glycosylation at the majority of N-linked sites, while the conserved sites N257 and especially N563 are enriched in unprocessed glycans, suggesting a role in host-cell attachment via DC-SIGN/L-SIGN. Our findings illustrate how N-, O-, and C-linked glycans together build the heterogeneous glycan shield of GP, guiding future immunological studies and functional interpretation of ebolavirus GP-antibody interactions.

Effects of an internet-delivered insomnia intervention for older adults: A secondary analysis on symptoms of depression and anxiety.

OBJECTIVE: To test whether an Internet-delivered cognitive behavioral therapy for insomnia (CBT-I) program for older adults attenuates symptoms of depression and anxiety. METHODS: Adults aged ≥ 55 with insomnia were randomized to SHUTi-OASIS (Sleep Healthy Using the Internet for Older Adult Sufferers of Insomnia and Sleeplessness; N = 207) or Patient Education (PE; N = 104). Depression and anxiety were assessed (HADS-D and HADS-A, respectively) at baseline, post-assessment, and 6- and 12-month follow-ups. RESULTS: Multilevel modeling of HADS-D showed a condition by time interaction (F[3,779] = 3.23, p = .02): SHUTi-OASIS participants reported lower symptoms than PE at post-assessment. There was no such interaction effect for HADS-A (F[3,779] = 2.12, p = .10). Generalized linear modeling showed no moderation of effects by baseline symptom severity. CONCLUSIONS: Participants randomized to Internet-delivered CBT-I showed stable depression and anxiety across time, while control participants' depressive symptoms briefly increased. CBT-I may help prevent development or worsening of psychological distress among older adults with insomnia. TRIAL REGISTRATION: [Registered at ClinicalTrials.gov; identifier removed for anonymity].