Pain in your day? Get sleep treatment anyway! The role of pain in insomnia treatment efficacy in women veterans.

Insomnia and pain disorders are among the most common conditions affecting United States adults and veterans, and their comorbidity can cause detrimental effects to quality of life among other factors. Cognitive behavioural therapy for insomnia and related behavioural therapies are recommended treatments for insomnia, but chronic pain may hinder treatment benefit. Prior research has not addressed how pain impacts the effects of behavioural insomnia treatment in United States women veterans. Using data from a comparative effectiveness clinical trial of two insomnia behavioural treatments (both including sleep restriction, stimulus control, and sleep hygiene education), we examined the impact of pain severity and pain interference on sleep improvements from baseline to post-treatment and 3-month follow-up. We found no significant moderation effects of pain severity or interference in the relationship between treatment phase and sleep outcomes. Findings highlight opportunities for using behavioural sleep interventions in patients, particularly women veterans, with comorbid pain and insomnia, and highlight areas for future research.

Identifying gaps in clinical evaluation and treatment of sleep-disordered breathing in women veterans.

PURPOSE: Sleep-disordered breathing (SDB) is a common sleep disorder in veterans; however, limited research exists in women veterans. We sought to estimate patterns of care in terms of evaluation, diagnosis, and treatment among women veterans with factors associated with elevated SDB risk. METHODS: Within one VA healthcare system, women identified through electronic health record data as having one or more factors (e.g., age >50 years, hypertension) associated with SDB, completed telephone screening in preparation for an SDB treatment study and answered questions about prior care related to SDB diagnosis and treatment. RESULTS: Of 319 women, 111 (35%) reported having completed a diagnostic sleep study in the past, of whom 48 (43%) were diagnosed with SDB. Women who completed a diagnostic study were more likely to have hypertension or obesity. Those who were diagnosed with SDB based on the sleep study were more likely to have hypertension, diabetes, or be ≥50 years old. Of the 40 women who received treatment, 37 (93%) received positive airway pressure therapy. Only 9 (24%) had used positive airway pressure therapy in the prior week. Few women received other treatments such as oral appliances or surgery. CONCLUSIONS: Findings support the need for increased attention to identification and management of SDB in women veterans, especially those with conditions associated with elevated SDB risk.

Veterans' Experiences of Support in Managing Comorbid Sleep Apnea and Type 2 Diabetes.

BACKGROUND: Obstructive sleep apnea (OSA) is highly prevalent in patients with Type 2 diabetes, more so in veterans compared with nonveterans. Positive airway pressure is the recommended first-line treatment for OSA. However, adherence to both positive airway pressure and diabetes management regimens can be challenging for older adults. Support from family or friends may improve glucose control or sleep-apnea-related symptoms, yet the evidence is limited when both conditions coexist. OBJECTIVES: This study aimed to describe veterans' experiences of support from family and friends with managing comorbid sleep apnea and Type 2 diabetes. METHODS: We conducted a postal survey of older veterans with OSA and Type 2 diabetes from one healthcare system. Questions include demographic and health-related information, information about sleep apnea and diabetes treatment and education received, related support from family or a friend, perceived benefits of regular positive airway pressure device use on improving sleep health, and perceived benefits of education for family or a friend on sleep apnea and diabetes. Descriptive and bivariate analyses were performed. RESULTS: Of 145 respondents (mean age = 72 years), 43% reported receiving help for Type 2 diabetes from family or a friend. Almost two thirds of the respondents were currently using a positive airway pressure device, of whom 27% received support with device use from family or friends. About one third of veterans perceived family and friends receiving education on treating sleep apnea and diabetes to be very or extremely helpful. Such perceived benefit was higher among those who were married or identified as non-White. Veterans using a positive airway pressure device had lower hemoglobin A1c levels than nonusers. DISCUSSION: Veterans perceived that additional education for the individuals providing support would be beneficial. Future studies could address interventions to increase sleep apnea and Type 2 diabetes knowledge among families and friends of veterans with these comorbid conditions. In addition, patients' adherence to positive airway pressure may be enhanced by support from family and friends.

Values Expressed by Women Veterans Receiving Treatment for Chronic Insomnia Disorder.

OBJECTIVES: Insomnia may contribute to fewer value-consistent choices and less engagement in meaningful life activities. We sought to identify values commonly expressed by women veterans engaged in a trial testing psychological treatment of insomnia disorder. METHODS: Seventy-four women veterans (mean age = 48.3 [±13] years), meeting DSM-5 diagnostic criteria for insomnia disorder received an acceptance-based behavioral treatment for insomnia. In the first session, participants responded to questions regarding personal values and the impact of insomnia on those values. Responses were categorized into values domains informed by the Bull's Eye Values survey (level 1 categories) and the Valued Living Questionnaire (level 2 categories). RESULTS: Raters reached 100% agreement after independent coding and adjudication. Level 1 value categories in frequency order were: relationships (n = 68), personal care/health (n = 51), work/education (n = 46), pets (n = 12), and leisure (n = 5). The most frequently reported level 2 value categories were: family (other than marriage/parenting; n = 50), parenting (n = 31), work (n = 31), physical health (n = 30), and spirituality (n = 19). The level 1 value categories impacted by insomnia in frequency order were: personal care/health (n = 65), relationships (n = 58), work/education (n = 46), pets (n = 12), and leisure (n = 5). CONCLUSIONS: Women veterans undergoing insomnia treatment highly value relationships and personal care/health, which should be considered patient-centered outcomes of insomnia treatments. CLINICAL TRIALS REGISTRATION: NCT02076165.

Expression, purification and characterization of the suppressor of copper sensitivity (Scs) B membrane protein from Proteus mirabilis.

Suppressor of copper sensitivity (Scs) proteins play a role in the bacterial response to copper stress in many Gram-negative bacteria, including in the human pathogen Proteus mirabilis. Recently, the ScsC protein from P. mirabilis (PmScsC) was characterized as a trimeric protein with isomerase activity that contributes to the ability of the bacterium to swarm in the presence of copper. The CXXC motif catalytic cysteines of PmScsC are maintained in their active reduced state by the action of its membrane-bound partner protein, the Proteus mirabilis ScsB (PmScsB). Thus, PmScsC and PmScsB form a redox relay in vivo. The predicted domain arrangement of PmScsB comprises a central transmembrane ß-domain and two soluble, periplasmic domains, the N-terminal α-domain and C-terminal γ-domain. Here, we provide a procedure for the recombinant expression and purification of the full-length PmScsB protein. Using Lemo21 (DE3) cells we expressed PmScsB and, after extraction and purification, we were able to achieve a yield of 3 mg of purified protein per 8 L of bacterial culture. Furthermore, using two orthogonal methods - AMS labelling of free thiols and a scrambled RNase A activity assay - PmScsB is shown to catalyze the reduction of PmScsC. Our results demonstrate that the PmScsC and PmScsB redox relay can be reconstituted in vitro using recombinant full-length PmScsB membrane protein. This finding provides a promising starting point for the in vitro biochemical and structural characterization of the P. mirabilis ScsC and ScsB interaction.

Circadian rest-activity misalignment in critically ill medical intensive care unit patients.

Circadian alignment of rest-activity rhythms is an essential biological process that may be vulnerable to misalignment in critically ill patients. We evaluated circadian rest-activity rhythms in critically ill patients and their association with baseline (e.g. age) and clinical (e.g. mechanical ventilation status) variables, along with intensive care unit light-dark cycles. Using wrist actigraphy, we collected 48-hr activity and light exposure data from critically ill patients in a tertiary care medical intensive care unit. We evaluated circadian rest-activity rhythms using COSINOR and non-parametric circadian rhythm analysis models, and stratified these data across baseline and clinical variables. We used linear regression to evaluate the association of circadian rest-activity and light-dark exposure rhythms. In COSINOR and non-parametric circadian rhythm analysis analyses, the 34 medical intensive care unit patients completing 48-hr actigraphy recordings exhibited mean MESOR (mean activity levels of a fitted curve) and amplitudes of 0.50 ± 0.32 and 0.20 ± 0.19 movements per 30-s epoch, with high interdaily variability. Patients who were older, mechanically ventilated, sedated, restrained and with higher organ failure scores tended to exhibit greater circadian rest-activity misalignment, with three of 34 (9%) patients exhibiting no circadian rhythmicity. Circadian light-dark exposure misalignment was observed as well and was associated with rest-activity misalignment (p = 0.03). Critically ill patients in our MICU experienced profound circadian rest-activity misalignment, with mostly weak or absent rhythms, along with circadian light-dark exposure misalignment. Potentially modifiable factors contributing to rest-activity misalignment (i.e. mechanical ventilation, restraints, low daytime light levels) highlight possible targets for future improvement efforts.

Change in Dysfunctional Sleep-Related Beliefs is Associated with Changes in Sleep and Other Health Outcomes Among Older Veterans With Insomnia: Findings From a Randomized Controlled Trial.

BACKGROUND: Cognitive behavioral therapy for insomnia (CBTI) targets changing dysfunctional sleep-related beliefs. The impact of these changes on daytime functioning in older adults is unknown. PURPOSE: We examined whether changes in sleep-related beliefs from pre- to post-CBTI predicted changes in sleep and other outcomes in older adults. METHOD: Data included 144 older veterans with insomnia from a randomized controlled trial testing CBTI. Sleep-related beliefs were assessed with the Dysfunctional Beliefs and Attitudes about Sleep-16 (DBAS-16, subscales: Consequences, Worry/Helplessness, Sleep Expectations, Medication). Outcomes included sleep diary variables, actigraphy-measured sleep efficiency, Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Flinders Fatigue Scale (FFS), Patient Health Questionnaire-9, and health-related quality of life. Analyses compared slope of change in DBAS subscales from baseline to posttreatment between CBTI and control, and assessed the relationship between DBAS change and the slope of change in outcomes from baseline to 6 months. RESULTS: Compared to controls, the CBTI group demonstrated stronger associations between improvement in DBAS-Consequences and subsequent improvement in PSQI, ISI, ESS, and FFS. The CBTI group also demonstrated stronger associations between improvement in DBAS-Worry/Helplessness and subsequent improvements in PSQI, ISI, and FFS; improvements in DBAS-Medication and PSQI; and improvements in DBAS-Sleep Expectations and wake after sleep onset (sleep diary) and FFS (all p < .05). CONCLUSIONS: Significant reduction in dysfunctional sleep-related beliefs following CBTI in older adults predicted improvement in several outcomes of sleep and daytime functioning. This suggests the importance of addressing sleep-related beliefs for sustained improvement with CBTI in older veterans. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00781963.

Considerations for integrated cognitive behavioural treatment for older adults with coexisting nocturia and insomnia.

Nocturia and chronic insomnia disorder are common conditions that frequently coexist in older adults. Existing medication treatments for each condition have risks, particularly in older adults. While treatment guidelines recommend starting with behavioural therapy for each condition, no existing program simultaneously addresses nocturia and insomnia. Existing behavioural interventions for nocturia or insomnia contain concordant and discordant components. An expert panel (including geriatricians with sleep or nocturia research expertise, sleep psychologists and a behavioural psychologist) was convened to combine and reconcile elements of behavioural treatment for each condition. Concordant treatment recommendations involve using situational self-management strategies such as urge suppression or techniques to influence homeostatic drive for sleep. Fluid modification such as avoiding alcohol and evening caffeine and regular self-monitoring through a daily diary is also appropriate for both conditions. The expert panel resolved discordant recommendations by eliminating overnight completion of voiding diaries (which can interfere with sleep) and discouraging routine overnight voiding (a stimulus control strategy). The final product is an integrated cognitive behavioural treatment that is delivered by advanced practice providers weekly over 5 weeks. This integrated program addresses the common scenario of coexisting nocturia and chronic insomnia disorder.

Research Priorities for Patients with Heart Failure and Central Sleep Apnea. An Official American Thoracic Society Research Statement.

Background: Central sleep apnea (CSA) is common among patients with heart failure and has been strongly linked to adverse outcomes. However, progress toward improving outcomes for such patients has been limited. The purpose of this official statement from the American Thoracic Society is to identify key areas to prioritize for future research regarding CSA in heart failure.Methods: An international multidisciplinary group with expertise in sleep medicine, pulmonary medicine, heart failure, clinical research, and health outcomes was convened. The group met at the American Thoracic Society 2019 International Conference to determine research priority areas. A statement summarizing the findings of the group was subsequently authored using input from all members.Results: The workgroup identified 11 specific research priorities in several key areas: 1) control of breathing and pathophysiology leading to CSA, 2) variability across individuals and over time, 3) techniques to examine CSA pathogenesis and outcomes, 4) impact of device and pharmacological treatment, and 5) implementing CSA treatment for all individualsConclusions: Advancing care for patients with CSA in the context of heart failure will require progress in the arenas of translational (basic through clinical), epidemiological, and patient-centered outcome research. Given the increasing prevalence of heart failure and its associated substantial burden to individuals, society, and the healthcare system, targeted research to improve knowledge of CSA pathogenesis and treatment is a priority.

Pilot RCT Testing A Mailing About Sleeping Pills and Cognitive Behavioral Therapy for Insomnia: Impact on Benzodiazepines and Z-Drugs.

OBJECTIVES: The aim is to pilot a low-touch program for reducing benzodiazepine receptor agonist (BZRA; benzodiazepines, z-drugs) prescriptions among older veterans. METHODS: Pilot randomized controlled trial consists of 2,009 veterans aged ≥ 65 years who received BZRA prescriptions from a Veterans Health Administration pharmacy (Colorado or Montana) during the prior 18 months. Active: Arm 1 was a mailed brochure about BZRA risks that also included information about a free, online cognitive behavioral therapy for the insomnia (CBTI) program. Arm 2 was a mailed brochure (same as arm 1) and telephone reinforcement call. Control: Arm 3 was a mailed brochure without insomnia treatment information. Active BZRA prescriptions at follow-up (6 and 12 months) were measured. RESULTS: In logistic regression analyses, the odds of BZRA prescription at 6- and 12-month follow-ups were not significantly different for arm 1 or 2 (active) versus arm 3 (control), including models adjusted for demographics and prescription characteristics (p-values >0.36). CONCLUSIONS: Although we observed no differences in active BZRA prescriptions, this pilot study provides guidance for conducting a future study, indicating a need for a more potent intervention. A full-scale trial testing an optimized program would provide conclusive results. CLINICAL IMPLICATIONS: Mailing information about BZRA risks and CBTI did not affect BZRA prescriptions.

Posttraumatic Stress Disorder Risk and Benzodiazepine Dependence in Older Veterans with Insomnia Symptoms.

OBJECTIVES: To measure the rate of benzodiazepine receptor agonist (BZA) dependence in older veterans with insomnia symptoms chronically using BZAs and to assess for associations between high posttraumatic stress disorder (PTSD) risk and BZA dependence. METHODS: A cross-sectional study was conducted among veterans aged 55 years and older with insomnia symptoms (current or historical) and chronic use of BZAs (≥3 months). Measurements included the Primary Care-PTSD screen (score >2 indicates high PTSD risk) and Benzodiazepine Dependence Questionnaire. Logistic regression was used to test for associations between PTSD risk and BZA dependence. RESULTS: A high PTSD risk was observed in 40% of the participants (N = 33). One-fifth (21.7%, N = 18) of participants met the criteria for benzodiazepine dependence (score ≥23 on Benzodiazepine Dependence Questionnaire). Veterans with high PTSD risk were significantly more likely to have BZA dependence (odds ratio 10.09, 95% CI [2.39, 42.54], p = .002). CONCLUSIONS: In older veterans with insomnia symptoms and chronic use of BZAs, high PTSD risk is associated with elevated risk for BZA dependence, which may make discontinuation of these medications difficult. CLINICAL IMPLICATIONS: Clinicians should consider the strong association between PTSD symptoms and benzodiazepine dependence when developing plans to taper a BZA in veterans with these symptoms.

Sleep Disruption Due to Stress in Women Veterans: A Comparison between Caregivers and Noncaregivers.

Objective/Background: Sleep problems are common in women and caregiving for an adult is a common role among women. However, the effects of caregiving on sleep and related daytime impairment are poorly understood among women veterans. This study compared stress-related sleep disturbances, insomnia symptoms, and sleep-related daytime impairment between women veterans who were caregivers and those who did not have a caregiving role. Participants: Of 12,225 women veterans who received care in one Veterans Administration Healthcare System, 1,457 completed data on a postal survey (mean age = 51.7 ± 15.9 years). Two hundred forty three (17%) respondents (mean age 53.8 ± 12.7 years) were caregivers for an adult, predominantly for a parent, providing transportation. Methods: The survey included items that addressed insomnia symptoms, total sleep time, sleep-related daytime impairments, caregiving characteristics, self-rated health, pain, stress, body mass index, and demographic information. Results: In adjusted analyses, caregiver status did not directly predict sleep complaints alone. However, in multiple regression analyses, being a caregiver (odds ratio 1.7, p = .001) significantly predicted stress-related sleep disturbance, even after adjusting for age, pain, self-rated health, and other characteristics. Furthermore, being a caregiver (ß = 3.9, p = .031) significantly predicted more symptoms of sleep-related daytime impairment after adjusting for age, pain, self-rated health, and other factors. Conclusions: Compared to noncaregivers, women veterans who were caregivers for an adult were more likely to report stress causing poor sleep, and more daytime impairment due to poor sleep. These findings suggest the need to target stress and other factors when addressing sleep disturbance among women veterans who are caregivers.

Insomnia Precipitating Events among Women Veterans: The Impact of Traumatic and Nontraumatic Events on Sleep and Mental Health Symptoms.

OBJECTIVE/BACKGROUND: The current study describes insomnia precipitating events reported by women Veterans and examines differences in sleep and psychological distress variables in those who endorsed traumatic, nontraumatic, or no insomnia precipitating events. PARTICIPANTS: Baseline data were collected from 347 women Veterans enrolled in a behavioral sleep intervention study (NCT02076165). METHODS: Participants completed self-report measures of insomnia symptoms, sleep quality, sleep efficiency (SE), nightmare frequency, and depression and posttraumatic stress disorder (PTSD) symptoms; SE was also assessed by wrist actigraphy. Participants responded to 2 open-ended questions assessing stressful life events and health changes that coincided with insomnia symptom onset. Responses were coded as traumatic, nontraumatic, and no events. Analyses of covariance examined the effect of insomnia precipitating event type on sleep and psychological symptom variables after controlling for sociodemographic factors. RESULTS: Overall, 25.80% of participants endorsed traumatic events, 65.80% endorsed only nontraumatic events, and 8.41% endorsed no events. Participants who endorsed traumatic events reported more severe insomnia (p = .003), PTSD (p = .001), and depression symptoms (p = .012), and poorer quality of sleep (p = .042) than participants who endorsed no events. Participants who endorsed traumatic events reported more severe PTSD symptoms (p = .004), a longer duration of sleep problems (p = .001), and poorer quality of sleep (p = .039) than participants who endorsed nontraumatic events. Participants who endorsed nontraumatic events reported more severe insomnia (p = .029) and PTSD (p = .049) symptoms than participants who endorsed no events. CONCLUSIONS: Trauma as a precipitant for insomnia may be related to higher symptom severity in women Veterans. Implications for treatment engagement and effectiveness remain unstudied.

The Management of Chronic Insomnia Disorder and Obstructive Sleep Apnea: Synopsis of the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guidelines.

Description: In September 2019, the U.S. Department of Veterans Affairs (VA) and the U.S. Department of Defense (DoD) approved a new joint clinical practice guideline for assessing and managing patients with chronic insomnia disorder and obstructive sleep apnea (OSA). This guideline is intended to give health care teams a framework by which to screen, evaluate, treat, and manage the individual needs and preferences of VA and DoD patients with either of these conditions. Methods: In October 2017, the VA/DoD Evidence-Based Practice Work Group initiated a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched and evaluated the literature, created three 1-page algorithms, and advanced 41 recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Recommendations: This synopsis summarizes the key recommendations of the guideline in 3 areas: diagnosis and assessment of OSA and chronic insomnia disorder, treatment and management of OSA, and treatment and management of chronic insomnia disorder. Three clinical practice algorithms are also included.

NMR fragment screening reveals a novel small molecule binding site near the catalytic surface of the disulfide-dithiol oxidoreductase enzyme DsbA from Burkholderia pseudomallei.

The presence of suitable cavities or pockets on protein structures is a general criterion for a therapeutic target protein to be classified as 'druggable'. Many disease-related proteins that function solely through protein-protein interactions lack such pockets, making development of inhibitors by traditional small-molecule structure-based design methods much more challenging. The 22 kDa bacterial thiol oxidoreductase enzyme, DsbA, from the gram-negative bacterium Burkholderia pseudomallei (BpsDsbA) is an example of one such target. The crystal structure of oxidized BpsDsbA lacks well-defined surface pockets. BpsDsbA is required for the correct folding of numerous virulence factors in B. pseudomallei, and genetic deletion of dsbA significantly attenuates B. pseudomallei virulence in murine infection models. Therefore, BpsDsbA is potentially an attractive drug target. Herein we report the identification of a small molecule binding site adjacent to the catalytic site of oxidized BpsDsbA. 1HN CPMG relaxation dispersion NMR measurements suggest that the binding site is formed transiently through protein dynamics. Using fragment-based screening, we identified a small molecule that binds at this site with an estimated affinity of KD ~ 500 µM. This fragment inhibits BpsDsbA enzymatic activity in vitro. The binding mode of this molecule has been characterized by NMR data-driven docking using HADDOCK. These data provide a starting point towards the design of more potent small molecule inhibitors of BpsDsbA.

Actigraphy to Measure Physical Activity in the Intensive Care Unit: A Systematic Review.

OBJECTIVE: In the intensive care unit (ICU), prolonged inactivity is common, increasing patients' risk for adverse outcomes, including ICU-acquired weakness. Hence, interventions to minimize inactivity are gaining popularity, highlighting actigraphy, a measure of activity involving a wristwatch-like accelerometer, as a method to inform these efforts. Therefore, we performed a systematic review of studies that used actigraphy to measure patient activity in the ICU setting. DATA SOURCES: We searched PubMed, EMBASE, CINAHL, Cochrane Library, and ProQuest from inception until December 2016. STUDY SELECTION: Two reviewers independently screened studies for inclusion. A study was eligible for inclusion if it was published in a peer-reviewed journal and used actigraphy to measure activity in ≥5 ICU patients. DATA EXTRACTION: Two reviewers independently performed data abstraction and risk of bias assessment. Abstracted actigraphy-based activity data included total activity time and activity counts. RESULTS: Of 16 studies (607 ICU patients) identified, 14 (88%) were observational, 2 (12%) were randomized control trials, and 5 (31%) were published after 2009. Mean patient activity levels per 15 to 60 second epoch ranged from 25 to 37 daytime and 2 to 19 nighttime movements. Actigraphy was evaluated in the context of ICU and post-ICU outcomes in 11 (69%) and 5 (31%) studies, respectively, and demonstrated potential associations between actigraphy-based activity levels and delirium, sedation, pain, anxiety, time to extubation, and length of stay. CONCLUSION: Actigraphy has demonstrated that patients are profoundly inactive in the ICU with actigraphy-based activity levels potentially associated with important measures, such as delirium, sedation, and length of stay. Larger and more rigorous studies are needed to further evaluate these associations and the overall utility of actigraphy in the ICU setting.

Exploration, Explanation, and Parent-Child Interaction in Museums.

Young children develop causal knowledge through everyday family conversations and activities. Children's museums are an informative setting for studying the social context of causal learning because family members engage together in everyday scientific thinking as they play in museums. In this multisite collaborative project, we investigate children's developing causal thinking in the context of family interaction at museum exhibits. We focus on explaining and exploring as two fundamental collaborative processes in parent-child interaction, investigating how families explain and explore in open-ended collaboration at gear exhibits in three children's museums in Providence, RI, San Jose, CA, and Austin, TX. Our main research questions examined (a) how open-ended family exploration and explanation relate to one another to form a dynamic for children's learning; (b) how that dynamic differs for families using different interaction styles, and relates to contextual factors such as families' science background, and (c) how that dynamic predicts children's independent causal thinking when given more structured tasks. We summarize findings on exploring, explaining, and parent-child interaction (PCI) styles. We then present findings on how these measures related to one another, and finally how that dynamic predicts children's causal thinking. In studying children's exploring we described two types of behaviors of importance for causal thinking: (a) Systematic Exploration: Connecting gears to form a gear machine followed by spinning the gear machine. (b) Resolute Behavior: Problem-solving behaviors, in which children attempted to connect or spin a particular set of gears, hit an obstacle, and then persisted to succeed (as opposed to moving on to another behavior). Older children engaged in both behaviors more than younger children, and the proportion of these behaviors were correlated with one another. Parents and children talked to each other while interacting with the exhibits. We coded causal language, as well as other types of utterances. Parents' causal language predicted children's causal language, independent of age. The proportion of parents' causal language also predicted the proportion of children's systematic exploration. Resolute behavior on the part of children did not correlate with parents' causal language, but did correlate with children's own talk about actions and the exhibit. We next considered who set goals for the play in a more holistic measure of parent-child interaction style, identifying dyads as parent-directed, child-directed, or jointly-directed in their interaction with one another. Children in different parent-child interaction styles engaged in different amounts of systematic exploration and had parents who engaged in different amounts of causal language. Resolute behavior and the language related to children engaging in such troubleshooting, seemed more consistent across the three parent-child interaction styles. Using general linear mixed modeling, we considered relations within sequences of action and talk. We found that the timing of parents' causal language was crucial to whether children engaged in systematic exploration. Parents' causal talk was a predictor of children's systematic exploration only if it occurred prior to the act of spinning the gears (while children were building gear machines). We did not observe an effect of causal language when it occurred concurrently with or after children's spinning. Similarly, children's talk about their actions and the exhibit predicted their resolute behavior, but only when the talk occurred while the child was encountering the problem. No effects were found for models where the talk happened concurrently or after resolving the problem. Finally, we considered how explaining and exploring related to children's causal thinking. We analyzed measures of children's causal thinking about gears and a free play measure with a novel set of gears. Principal component analysis revealed a latent factor of causal thinking in these measures. Structural equation modeling examined how parents' background in science related to children's systematic exploration, parents' causal language, and parent-child interaction style, and then how those factors predicted children's causal thinking. In a full model, with children's age and gender included, children's systematic exploration related to children's causal thinking. Overall, these data demonstrate that children's systematic exploration and parents' causal explanation are best studied in relation to one another, because both contributed to children's learning while playing at a museum exhibit. Children engaged in systematic exploration, which supported their causal thinking. Parents' causal talk supported children's exploration when it was presented at certain times during the interaction. In contrast, children's persistence in problem solving was less sensitive to parents' talk or interaction style, and more related to children's own language, which may act as a form of self-explanation. We discuss the findings in light of ongoing approaches to promote the benefit of parent-child interaction during play for children's learning and problem solving. We also examine the implications of these findings for formal and informal learning settings, and for theoretical integration of constructivist and sociocultural approaches in the study of children's causal thinking.

Why we march! Feminist activism in critical times: Lessons from the women's march on Washington.

As professors, we have witnessed, anecdotally, a shift in doing social justice advocacy teaching. We have witnessed within some of our classrooms a more empowered hostility and intolerance to conversations pertaining to social justice. We agree that this phenomenon is pedagogical because this language usage not only teaches, but also legitimizes hate speech. We have witnessed the illogical extension of this hate speech with an increase in hate crimes across the country since the 2016 election, Without peaceful protest and grassroots feminist activism, we fear that this speech, this pedagogy, will spread even more violent forms of hate. This research was conducted in and around the first Women's March of 2017. We wanted to know: What were marchers' prior histories of political activism prior to the election? If this was their first time participating in such a manner, how did the election and its early political fallout inspire marchers to attend? 2) What plans did marchers have for political activism after the march? 3) What can be learned from these participants about the current state of political activism in our current era? A total of 788 individuals had taken part in the online survey. Among the participants, 45% marched on Washington, and 55% participated in the march in their local cities. We found that issues of gender equality were of great concern to many of the marchers. In particular, issues related to economic and social equity, including salary. These findings are interesting as they speak to the broader implications of gender equality. And, as the past few years have demonstrated, these issues continue to be of concern.

Disulfide isomerase activity of the dynamic, trimeric Proteus mirabilis ScsC protein is primed by the tandem immunoglobulin-fold domain of ScsB.

Correct disulfide bond formation is essential for proper folding of many proteins, including bacterial virulence factors. The suppressor of copper sensitivity (Scs) proteins have roles in dithiol/disulfide interchange and the bacterial response to copper stress. Encoded in a four-gene cassette (ScsABCD) present in many Gram-negative bacteria, the Scs proteins are enigmatic and poorly characterized. Here, we show that the periplasmic α-domain of the membrane protein ScsB in the Gram-negative bacterium Proteus mirabilis forms a redox relay with the soluble periplasmic protein PmScsC. We also found that the periplasmic α-domain is sufficient to activate the disulfide isomerase activity of PmScsC. The crystal structure of PmScsBα at a resolution of 1.54 Å revealed that it comprises two structurally similar immunoglobulin-like folds, one of which includes a putative redox-active site with the sequence CXXXC. We confirmed the importance of these cysteine residues for PmScsBα function, and in addition, we engineered cysteine variants that produced a stable complex between PmScsC and PmScsBα. Using small-angle X-ray and neutron scattering analyses with contrast variation, we determined a low-resolution structure of the PmScsC-PmScsBα complex. The structural model of this complex suggested that PmScsBα uses both of its immunoglobulin-like folds to interact with PmScsC and revealed that the highly dynamic PmScsC becomes ordered upon PmScsBα binding. These findings add to our understanding of the poorly characterized Scs proteins.