Patient stratification using plasma cytokines and their regulators in sepsis: relationship to outcomes, treatment effect and leucocyte transcriptomic subphenotypes.

RATIONALE: Heterogeneity of the host response within sepsis, acute respiratory distress syndrome (ARDS) and more widely critical illness, limits discovery and targeting of immunomodulatory therapies. Clustering approaches using clinical and circulating biomarkers have defined hyper-inflammatory and hypo-inflammatory subphenotypes in ARDS associated with differential treatment response. It is unknown if similar subphenotypes exist in sepsis populations where leucocyte transcriptomic-defined subphenotypes have been reported. OBJECTIVES: We investigated whether inflammatory clusters based on cytokine protein abundance were seen in sepsis, and the relationships with previously described transcriptomic subphenotypes. METHODS: Hierarchical cluster and latent class analysis were applied to an observational study (UK Genomic Advances in Sepsis (GAinS)) (n=124 patients) and two clinical trial datasets (VANISH, n=155 and LeoPARDS, n=484) in which the plasma protein abundance of 65, 21, 11 circulating cytokines, cytokine receptors and regulators were quantified. Clinical features, outcomes, response to trial treatments and assignment to transcriptomic subphenotypes were compared between inflammatory clusters. MEASUREMENTS AND MAIN RESULTS: We identified two (UK GAinS, VANISH) or three (LeoPARDS) inflammatory clusters. A group with high levels of pro-inflammatory and anti-inflammatory cytokines was seen that was associated with worse organ dysfunction and survival. No interaction between inflammatory clusters and trial treatment response was found. We found variable overlap of inflammatory clusters and leucocyte transcriptomic subphenotypes. CONCLUSIONS: These findings demonstrate that differences in response at the level of cytokine biology show clustering related to severity, but not treatment response, and may provide complementary information to transcriptomic sepsis subphenotypes. TRIAL REGISTRATION NUMBER: ISRCTN20769191, ISRCTN12776039.

Utilization of the web index in the measurement of web creep after syndactyly surgery.

The aim of this study was to explore the feasibility of using a web index to measure web creep after syndactyly surgery. A total of 19 hands in nine children (six preoperatively and 13 immediately postoperatively) underwent measurement of their web position. A preliminary study confirmed that the web index measured on the child's hand at the time of surgery was similar to that measured on photographs taken at the same time. Subsequently, an intra- and inter-observer error rate found excellent agreement among four observers measuring the web index using photographs. Of 13 postoperative webs using a winged central rectangular web flap without skin grafting, 12 were re-measured using photographs at an average of 88 months (range 78 to 96) after surgery. There was evidence of minor web creep in one web only. Our study demonstrates the efficacy of web index calculation on photographs to measure web position in children after syndactyly surgery. The study also demonstrates the effectiveness of the graftless winged central rectangular web flap technique in avoiding web creep.Level of evidence: IV.

The influence of telehealth-based cancer rehabilitation interventions on disability: a systematic review.

PURPOSE: To characterize delivery features and explore effectiveness of telehealth-based cancer rehabilitation interventions that address disability in adult cancer survivors. METHODS: A systematic review of electronic databases (CINAHL Plus, Cochrane Library: Database of Systematic Reviews, Embase, National Health Service's Health Technology Assessment, PubMed, Scopus, Web of Science) was conducted in December 2019 and updated in April 2021. RESULTS: Searches identified 3,499 unique studies. Sixty-eight studies met inclusion criteria. There were 81 unique interventions across included studies. Interventions were primarily delivered post-treatment and lasted an average of 16.5 weeks (SD = 13.1). They were most frequently delivered using telephone calls (59%), administered delivered by nursing professionals (35%), and delivered in a one-on-one format (88%). Risk of bias of included studies was primarily moderate to high. Included studies captured 55 measures of disability. Only 54% of reported outcomes had data that allowed calculation of effect sizes ranging -3.58 to 15.66. CONCLUSIONS: The analyses suggest small effects of telehealth-based cancer interventions on disability, though the heterogeneity seen in the measurement of disability makes it hard to draw firm conclusions. Further research using more diverse samples, common measures of disability, and pragmatic study designs is needed to advance telehealth in cancer rehabilitation. IMPLICATIONS FOR CANCER SURVIVORS: Telehealth-based cancer rehabilitation interventions have the potential to increase access to care designed to reduce disability across the cancer care continuum.

The effect of self-reported balance confidence on community integration after brain injury: an observational study.

OBJECTIVE: To evaluate the correlation between self-reported balance confidence and community integration related to home management for community-dwelling adults with acquired brain injury (ABI). METHODS: This is a study of 141 participants over the age of 18 with a history of ABI, living in the community, who completed an online survey. The survey included a series of demographic questions followed by the Activities-Specific Balance Confidence Scale (ABC) and the Home Integration subscale of the Community Integration Questionnaire (CIQ-H). RESULTS: Data from 119 completed surveys were included in the analysis. Significant positive correlations were found between the ABC and the CIQ-H total scores (rs = 0.241, p = 0.008). There was no significant difference between CIQ-H total scores in individuals by injury type (traumatic vs non-traumatic) or by level of severity (mild, moderate, severe) (p > 0.05). There was no significant difference between ABC total scores by injury type (p > 0.05). CONCLUSIONS: Higher levels of balance confidence may be associated with improved community integration related to home management for individuals with traumatic and non-traumatic BI. This study's results support future research to evaluate the integration of strategies to improve balance confidence as a component of interdisciplinary assessment and rehabilitation to maximize community integration in community-dwelling adults with ABI.

Exercise, Diet, and Weight Management During Cancer Treatment: ASCO Guideline.

PURPOSE: To provide guidance on exercise, diet, and weight management during active cancer treatment in adults. METHODS: A systematic review of the literature identified systematic reviews and randomized controlled trials evaluating the impact of aerobic and resistance exercise, specific diets and foods, and intentional weight loss and avoidance of weight gain in adults during cancer treatment, on quality of life, treatment toxicity, and cancer control. PubMed and the Cochrane Library were searched from January 2000 to May 2021. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS: The evidence base consisted of 52 systematic reviews (42 for exercise, nine for diet, and one for weight management), and an additional 23 randomized controlled trials. The most commonly studied types of cancer were breast, prostate, lung, and colorectal. Exercise during cancer treatment led to improvements in cardiorespiratory fitness, strength, fatigue, and other patient-reported outcomes. Preoperative exercise in patients with lung cancer led to a reduction in postoperative length of hospital stay and complications. Neutropenic diets did not decrease risk of infection during cancer treatment. RECOMMENDATIONS: Oncology providers should recommend regular aerobic and resistance exercise during active treatment with curative intent and may recommend preoperative exercise for patients undergoing surgery for lung cancer. Neutropenic diets are not recommended to prevent infection in patients with cancer during active treatment. Evidence for other dietary and weight loss interventions during cancer treatment was very limited. The guideline discusses special considerations, such as exercise in individuals with advanced cancer, and highlights the critical need for more research in this area, particularly regarding diet and weight loss interventions during cancer treatment.Additional information is available at www.asco.org/supportive-care-guidelines.

Systematic Review of Functional Outcomes in Cancer Rehabilitation.

OBJECTIVE: To systematically review the evidence regarding rehabilitation interventions targeting optimal physical or cognitive function in adults with a history of cancer and describe the breadth of evidence as well as strengths and limitations across a range of functional domains. DATA SOURCES: PubMed, Cumulative Index to Nursing and Allied Health Plus, Scopus, Web of Science, and Embase. The time scope was January 2008 to April 2019. STUDY SELECTION: Prospective, controlled trials including single- and multiarm cohorts investigating rehabilitative interventions for cancer survivors at any point in the continuum of care were included, if studies included a primary functional outcome measure. Secondary data analyses and pilot/feasibility studies were excluded. Full-text review identified 362 studies for inclusion. DATA EXTRACTION: Extraction was performed by coauthor teams and quality and bias assessed using the American Academy of Neurology (AAN) Classification of Evidence Scheme (class I-IV). DATA SYNTHESIS: Studies for which the functional primary endpoint achieved significance were categorized into 9 functional areas foundational to cancer rehabilitation: (1) quality of life (109 studies), (2) activities of daily living (61 studies), (3) fatigue (59 studies), (4) functional mobility (55 studies), (5) exercise behavior (37 studies), (6) cognition (20 studies), (7) communication (10 studies), (8) sexual function (6 studies), and (9) return to work (5 studies). Most studies were categorized as class III in quality/bias. Averaging results found within each of the functional domains, 71% of studies reported statistically significant results after cancer rehabilitation intervention(s) for at least 1 functional outcome. CONCLUSIONS: These findings provide evidence supporting the efficacy of rehabilitative interventions for individuals with a cancer history. The findings should be balanced with the understanding that many studies had moderate risk of bias and/or limitations in study quality by AAN criteria. These results may provide a foundation for future work to establish clinical practice guidelines for rehabilitative interventions across cancer disease types.

Evidence-Based Treatments in Community Mental Health Settings: Use and Congruence With Children's Primary Diagnosis and Comorbidity.

Many evidence-based treatments (EBTs) have been identified for specific child mental health disorders, but there is limited research on the use of EBTs in community-based settings. This study used administrative data from a statewide system of care to examine 1) the extent to which EBTs were provided congruent with the child's primary diagnosis, 2) whether there were differences in effectiveness of EBTs that were congruent or incongruent with the child's primary diagnosis, and 3) whether comorbidity moderated the effectiveness of EBTs for children based on congruence with their primary diagnosis. The sample consisted of 23,895 children ages 3-17 with at least one of the most common diagnoses (attention-deficit/hyperactivity disorder, conduct problems, depressive disorders, anxiety disorders, and post-traumatic stress disorder) who received outpatient psychotherapy. Data were collected as part of routine care, including child demographic characteristics, diagnosis, treatment type, and problem severity. Forty-two percent of children received an EBT congruent with their diagnosis, and these children showed greater improvement than the 35% of children who received no EBT (ES = 0.14-0.16) or the 23% who received an EBT incongruent with their diagnosis (ES = 0.06-0.15). For children with comorbid diagnoses, the use of EBTs congruent with the primary diagnosis was also associated with the greatest improvement, especially when compared to no EBT (ES = 0.22-0.24). Results of the current study support the use of EBTs in community-based settings, and suggest that clinicians should select EBTs that match the child's primary diagnosis to optimize treatment outcomes, especially for children with comorbidity.

Impact of the COVID-19 Pandemic on Child and Adolescent Mental Health Policy and Practice Implementation.

BACKGROUND: The impact of the 2019 coronavirus pandemic on the mental health of millions worldwide has been well documented, but its impact on prevention and treatment of mental and behavioral health conditions is less clear. The COVID-19 pandemic also created numerous challenges and opportunities to implement health care policies and programs under conditions that are fundamentally different from what has been considered to be usual care. Methods: We conducted a qualitative study to determine the impact of the COVID-19 pandemic on implementation of evidence-based policy and practice by State Mental Health Authorities (SMHA) for prevention and treatment of mental health problems in children and adolescents. Semi-structured interviews were conducted with 29 SMHA representatives of 21 randomly selected states stratified by coronavirus positivity rate and rate of unmet services need. Data analysis with SMHA stakeholders used procedures embedded in the Rapid Assessment Procedure-Informed Community Ethnography methodology. Results: The need for services increased during the pandemic due primarily to family stress and separation from peers. States reporting an increase in demand had high coronavirus positivity and high unmet services need. The greatest impacts were reduced out-of-home services and increased use of telehealth. Barriers to telehealth services included limited access to internet and technology, family preference for face-to-face services, lack of privacy, difficulty using with young children and youth in need of substance use treatment, finding a Health Insurance Portability and Accountability Act (HIPAA)-compliant platform, training providers and clients, and reimbursement challenges. Policy changes to enable reimbursement, internet access, training, and provider licensing resulted in substantially fewer appointment cancellations or no-shows, greater family engagement, reduction in travel time, increased access for people living in remote locations, and increased provider communication and collaboration. States with high rates of coronavirus positivity and high rates of unmet need were most likely to continue use of telehealth post-pandemic. Despite these challenges, states reported successful implementation of policies designed to facilitate virtual services delivery with likely long-term changes in practice. Conclusions: Policy implementation during the pandemic provided important lessons for planning and preparedness for future public health emergencies. Successful policy implementation requires ongoing collaboration among policy makers and with providers.

Development of the Exercise in Cancer Evaluation and Decision Support (EXCEEDS) algorithm.

PURPOSE: Participation in exercise or rehabilitation services is recommended to optimize health, functioning, and well-being across the cancer continuum of care. However, limited knowledge of individual needs and complex decision-making are barriers to connect the right survivor to the right exercise/rehabilitation service at the right time. In this article, we define the levels of exercise/rehabilitation services, provide a conceptual model to improve understanding of individual needs, and describe the development of the Exercise in Cancer Evaluation and Decision Support (EXCEEDS) algorithm. METHODS: From literature review, we synthesized defining characteristics of exercise/rehabilitation services and individual characteristics associated with safety and efficacy for each service. We developed a visual model to conceptualize the need for each level of specialized care, then organized individual characteristics into a risk-stratified algorithm. Iterative review with a multidisciplinary expert panel was conducted until consensus was reached on algorithm content and format. RESULTS: We identified eight defining features of the four levels of exercise/rehabilitation services and provide a conceptual model of to guide individualized navigation for each service across the continuum of care. The EXCEEDS algorithm includes a risk-stratified series of eleven dichotomous questions, organized in two sections and ten domains. CONCLUSIONS: The EXCEEDS algorithm is an evidence-based decision support tool that provides a common language to describe exercise/rehabilitation services, a practical model to understand individualized needs, and step-by-step decision support guidance. The EXCEEDS algorithm is designed to be used at point of care or point of need by multidisciplinary users, including survivors. Thus, implementation may improve care coordination for cancer exercise/rehabilitation services.

Clinician training, then what? Randomized clinical trial of child STEPs psychotherapy using lower-cost implementation supports with versus without expert consultation.

OBJECTIVE: Implementation of evidence-based treatments in funded trials is often supported by expert case consultation for clinicians; this may be financially and logistically difficult in clinical practice. Might less costly implementation support produce acceptable treatment fidelity and clinical outcomes? METHOD: To find out, we trained 42 community clinicians from four community clinics in Modular Approach to Therapy for Children (MATCH), then randomly assigned them to receive multiple lower-cost implementation supports (LC) or expert MATCH consultation plus lower-cost supports (CLC). Clinically referred youths (N = 200; ages 7-15 years, M = 10.73; 53.5% male; 32.5% White, 27.5% Black, 24.0% Latinx, 1.0% Asian, 13.5% multiracial, 1.5% other) were randomly assigned to LC (n = 101) or CLC (n = 99) clinicians, and groups were compared on MATCH adherence and competence, as well as on multiple clinical outcomes using standardized measures (e.g., Child Behavior Checklist, Youth Self-Report) and idiographic problem ratings (Top Problems Assessment). RESULTS: Coding of therapy sessions revealed substantial therapist adherence to MATCH in both conditions, with significantly stronger adherence in CLC; however, LC and CLC did not differ significantly in MATCH competence. Trajectories of change on all outcome measures were steep, positive, and highly similar for LC and CLC youths, with no significant differences; a supplemental analysis of posttreatment outcomes also showed similar LC and CLC posttreatment scores, with most LC-CLC differences nonsignificant. CONCLUSIONS: The findings suggest that effective implementation of a complex intervention in clinical practice may be supported by procedures that are less costly and logistically challenging than expert consultation. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The Feasibility of Community-Based, Supervised Exercise Programs to Engage and Monitor Patients in a Postrehabilitation Setting.

Objective. To evaluate the feasibility of disease-specific, community-based supervised exercise programs (CSEPs) to improve biometric and functional outcomes among persons with a variety of chronic medical conditions. Design. Feasibility, cohort study. Subjects were recruited through community placed flyers and provider offices. Exercise programs consisted of aerobic and resistance training that adhered to American College of Sports Medicine guidelines. A Wilcoxon signed rank test was used to assess program outcomes. Setting. Ten, community-based, medical fitness centers. Subjects. A total of 382 total participants. The number of participants in each CSEP ranged from 38 to 119. Individuals were 18 years of age or older and treated for various chronic medical conditions. Results. Varied by cohort, but generally consisted of (a) favorable changes in body composition ( P < .05), (b) significant improvements in submaximal exercise tolerance and functional outcome measures ( P < .05), and (3) significant increase in self-reported exercise behaviors ( P < .05). Conclusion. CSEPs improve outcomes in patients with chronic medical conditions and may be relevant within the continuum of care in outpatient rehabilitation medicine, particularly among bundled or value-based payment models. Further research is needed to evaluate outcomes from CSEPs versus controls.

Comparison of Disease Phenotypes and Clinical Characteristics Among South Asian and White Patients with Inflammatory Bowel Disease at a Tertiary Referral Center.

BACKGROUND: The prevalence and clinical features of inflammatory bowel disease (IBD) vary among different racial and ethnic groups. The aim of this study was to compare the clinical and phenotypic features of Crohn's disease (CD) and ulcerative colitis (UC) in South Asian patients living in the United States with those of a white cohort. METHODS: The demographic, clinical, and phenotypic characteristics of 73 South Asian patients (31 CD and 42 UC) who presented initially to our tertiary referral center from 2012 to 2016 and had subsequent follow-up were retrospectively compared with those of 408 consecutive white patients (245 CD and 163 UC). RESULTS: South Asian IBD patients were significantly more likely to have UC (58.0% vs 40.0%; P = 0.005) than white patients. South Asians with CD were less likely to have a family history of IBD (9.7% vs 26.9%; P = 0.037) and required fewer CD-related surgeries (22.5% vs 46.1; P = 0.012). South Asians were also less likely to be active or former smokers in both the CD (P = 0.004) and UC (P = 0.020) groups. South Asians with UC had a higher incidence of Clostridium difficile infection compared with white patients (19.0% vs 8.6%; P = 0.050). CONCLUSIONS: A cohort of South Asian patients with IBD were more likely to have UC and had differing family and tobacco risk factors, requirements for surgery, and Clostridium difficile infection rates as compared with white patients.

Consensus-Building efforts to identify best tools for screening and assessment for supportive services in oncology.

Purpose: To build consensus around an optimal patient-reported outcome measure of cancer symptoms and patient needs to facilitate patient-provider communication and trigger referrals to supportive services.Methods and materials: The Grid-Enabled Measures platform was used to crowdsource and facilitate collaboration to achieve consensus. Respondents were invited to nominate and independently rate the usefulness of measures that: (1) have been actively used at a healthcare institution, (2) have a multiple choice or yes/no type format, (3) are applicable to adults with cancer, (4) are patient-reported, and 5) have psychometric data if possible. Discussion boards within the GEM workspace allowed respondents to identify barriers to implementing patient assessment and referral systems.Results: 166 individuals from various disciplines from 25 organizations participated. Six instruments were nominated, and 553 rating surveys were submitted. The three most highly-rated overall instruments were the Distress Thermometer, the James Supportive Case Screening, and the Functional Assessment of Cancer Therapy-General. Participants noted that wide-scale implementation of this process requires both identifying problems and providing clinicians with algorithms to facilitate appropriate referrals.Conclusions: Consensus reported three most highly-related measures as optimal for comprehensive screening and identification for referral by assessing multiple domains of functioning and quality of life.Implications for RehabilitationGaining consensus on the best patient reported outcome measures is an important step towards improving access to cancer rehabilitation services.A consensus agreed on several measures to use for cancer rehabilitation screening. Functional Assessment of Cancer Therapy-General, National Comprehensive Cancer. Network Distress Thermometer and the James Instrument.The selected measures do not put undue burden on clinicians and patients.

Neurotoxicity Associated with Traumatic Brain Injury, Blast, Chemical, Heavy Metal and Quinoline Drug Exposure.

Chronic, excessive exposure, and accumulation of neurotoxic agents such as heavy metals (lead, mercury, cadmium), mefloquine (Lariam), and food additives such as monosodium glutamate and aspartame cause neurotoxicity and brain damage. This chemical-induced brain damage closely resembles the pathophysiology of classical traumatic brain injury with decreased cognitive function, neurodegeneration, and increased psychiatric manifestations (depression, anxiety, sleep disturbances, and irritability). Current evidence supports a strong causal relationship between military-related exposure to specific neurotoxins, and the development of serious medical conditions and higher rates of suicide among service members. To address this current deficit in military health care, it is recommended that efficacious, nontoxic, neuroprotective, and neuroregenerative agents such as highly bioavailable magnesium, nutritional lithium, zinc, selenium, boron, ascorbate, tocopherols, heavy metal chelators, and glutathione precursors such as N-acetyl-cysteine be immediately used as a "protective shield" and to support critical healing processes in the brain and nervous system.

Executive function in the classroom: Cognitive flexibility supports reading fluency for typical readers and teacher-identified low-achieving readers.

BACKGROUND: Dominant explanations of reading fluency indicate automatic phonological decoding frees mental resources for processing meaning. However, decoding automaticity does not guarantee attention to meaning. Recent neurocognitive work suggests executive functioning (EF) may contribute to fluency beyond decoding automaticity. AIMS: Two studies examined contributions of an understudied EF, cognitive flexibility, to fluent reading and tested a teacher-administered EF intervention to improve fluency in teacher-identified low-achieving (LA) readers. METHODS AND PROCEDURES: Study 1 assessed word reading fluency, automatic decoding, reading comprehension, verbal and nonverbal ability, and reading-specific and domain-general cognitive flexibility in 50 1st and 2nd grade typically-developing (TD) readers. Study 2 compared TD and LA readers' cognitive flexibility and examined effectiveness of cognitive flexibility intervention for improving fluency in 33 LA 2nd and 3rd graders. OUTCOMES AND RESULTS: Reading-specific flexibility contributed to fluency beyond automatic decoding and all other control variables in TD readers who had significantly higher cognitive flexibility than LA readers. Teacher-administered EF intervention improved reading fluency for LA readers. CONCLUSIONS AND IMPLICATIONS: These findings expand understanding of the neurocognitive basis of reading fluency and add to the growing body of evidence that EF underlies learning differences and serves as a useful target of intervention for LA students.

The immediate effects of knee flexion range of motion following manual therapy or self-stretching/active range of motion following a total knee arthroplasty: a case report.

[Purpose] The purposes of this case study are to: (1) report the immediate effects of knee flexion range of motion following manual therapy (MT) and self-stretching/AROM following a total knee arthroplasty (TKA). (2) contribute empirical evidence to the literature through reports within this case study. [Participant and Methods] For 6 days, the authors utilized a different MT technique and 1 day of self-stretching and active range of motion for an 85-year-old male who was 3 days status post right TKA. [Results] The greatest gains for AROM/PROM for knee flexion were achieved while performing typical arthrokinematic motion joint mobilizations, for AROM and PROM, resulting in a gain of 10 degrees and 10 degrees, respectfully. [Conclusion] We theorize that performing typical arthrokinematic motion joint mobilizations stimulates a greater response from the mechanoreceptors and therefore a greater stimulation response to the central and peripheral nervous systems. This greater stimulation may explain the greatest immediate gain in knee flexion range of motion being performed by typical arthrokinematic motion joint mobilizations. The outcomes of this study demonstrate the start of some empirical evidence while exploring the immediate effects of knee flexion range of motion following manual therapy and self-stretching/AROM following a TKA.

Follow the trail: Using insights from the growth of palliative care to propose a roadmap for cancer rehabilitation.

Despite research explicating the benefits of cancer rehabilitation interventions to optimize physical, social, emotional, and vocational functioning, many reports document low rates of referral to and uptake of rehabilitation in oncology. Cancer rehabilitation clinicians, researchers, and policy makers could learn from the multidisciplinary specialty of palliative care, which has benefited from a growth strategy and has garnered national recognition as an important and necessary aspect of oncology care. The purpose of this article is to explore the actions that have increased the uptake and integration of palliative care to yield insights and multimodal strategies for the development and growth of cancer rehabilitation. After examining the history of palliative care and its growth, the authors highlight 5 key strategies that may benefit the field of cancer rehabilitation: 1) stimulating the science in specific gap areas; 2) creating clinical practice guidelines; 3) building clinical capacity; 4) ascertaining and responding to public opinion; and 5) advocating for public policy change. Coordinated and simultaneous advances on these 5 strategies may catalyze the growth, utilization, and effectiveness of patient screening, timely referrals, and delivery of appropriate cancer rehabilitation care that reduces disability and improves quality of life for cancer survivors who need these services.

Grief and Avoidant Death Attitudes Combine to Predict the Fading Affect Bias.

The fading affect bias (FAB) occurs when unpleasant affect fades faster than pleasant affect. To detect mechanisms that influence the FAB in the context of death, we measured neuroticism, depression, anxiety, negative religious coping, death attitudes, and complicated grief as potential predictors of FAB for unpleasant/death and pleasant events at 2 points in time. The FAB was robust across older and newer events, which supported the mobilization-minimization hypothesis. Unexpectedly, complicated grief positively predicted FAB, and death avoidant attitudes moderated this relation, such that the Initial Event Affect by Grief interaction was only significant at the highest 3 quintiles of death avoidant attitudes. These results were likely due to moderate grief ratings, which were, along with avoidant death attitudes, related to healthy outcomes in past research. These results implicate complicated grief and death avoidant attitudes as resiliency mechanisms that are mobilized during bereavement to minimize its unpleasant effects.

Suppressor of IKKepsilon forms direct interactions with cytoskeletal proteins, tubulin and α-actinin, linking innate immunity to the cytoskeleton.

Suppressor of IKKepsilon (SIKE) is associated with the type I interferon response of the innate immune system through TANK-binding kinase 1 (TBK1). Originally characterized as an endogenous inhibitor of TBK1 when overexpressed in viral infection and pathological cardiac hypertrophic models, a mechanistic study revealed that SIKE acts as a high-affinity substrate of TBK1, but its function remains unknown. In this work, we report that scratch assay analysis of parental and SIKE CRISPR/Cas9 knockout HAP1 cells showed an ~ 20% decrease in cell migration. Investigation of the SIKE interaction network through affinity purification/mass spectrometry showed that SIKE formed interactions with cytoskeletal proteins. In immunofluorescence assays, endogenous SIKE localized to cytosolic puncta in both epithelial and myeloid cells and to nuclear puncta in myeloid cells, while in epithelial cells additional staining occurred in stress fiber-like structures and adjacent to the plasma membrane. Using cellular markers, co-occurrence of SIKE fluorescence with actin, α-actinin, and ezrin was detected. Reciprocal immunoprecipitation revealed a SIKE:tubulin interaction sensitive to the phosphorylation state of SIKE, but a SIKE:α-actinin interaction was unchanged by SIKE phosphorylation. In vitro precipitation assays confirmed a direct SIKE interaction with tubulin and α-actinin. These results indicate that SIKE may promote cell migration by directly associating with the cytoskeleton. In this role, SIKE may mediate cytoskeletal rearrangement necessary in innate immunity, but also link a key catalytic hub, TBK1, to the cytoskeleton. DATABASE: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [1] partner repository with the dataset identifier PXD007262.