Decoding the molecular crosstalk between grafted stem cells and the stroke-injured brain.

Stem cell therapy shows promise for multiple disorders; however, the molecular crosstalk between grafted cells and host tissue is largely unknown. Here, we take a step toward addressing this question. Using translating ribosome affinity purification (TRAP) with sequencing tools, we simultaneously decode the transcriptomes of graft and host for human neural stem cells (hNSCs) transplanted into the stroke-injured rat brain. Employing pathway analysis tools, we investigate the interactions between the two transcriptomes to predict molecular pathways linking host and graft genes; as proof of concept, we predict host-secreted factors that signal to the graft and the downstream molecular cascades they trigger in the graft. We identify a potential host-graft crosstalk pathway where BMP6 from the stroke-injured brain induces graft secretion of noggin, a known brain repair factor. Decoding the molecular interplay between graft and host is a critical step toward deciphering the molecular mechanisms of stem cell action.

The leadership and followership challenges of doctors in training during the COVID-19 pandemic.

Research carried out in 2016 by the authors investigated the challenges that doctors in training experience around leadership and followership in the NHS. The study explored contemporary healthcare leadership culture and the role of followership from the perspective of early career doctors. It found that the leadership and followership challenges for these doctors in training were associated with issues of social and professional identity, communication, the medical hierarchy, and relationships with senior colleagues (support and trust). These challenges were exacerbated by the busy and turbulent clinical environment in which they worked. To cope with various clinical situations and forms of leadership, doctors in training engage in a range of different followership behaviours and strategies. The study raised implications for medical education and training and suggested that followership should be included as part of formal training in communication and team working skills. The importance of both leadership and followership in the delivery of safe and effective patient care has been brought sharply into focus by the COVID-19 pandemic. This article revisits these challenges in light of the pandemic and its impact on the experiences of doctors in training.

The Experience of Being Jewish: Living with Antisemitism

Abstract In an anonymous online study of 242 Jewish-identified participants (71 men, 163 women, 8 other; mean age = 37.8 years) living in ethnically diverse communities we found levels of antisemitism significantly associated with depression, survivor guilt proneness, and self-hate. Involvement in the Jewish community was significantly associated with life satisfaction even when adjusting for the effects of discrimination. A subsample of 124 responded to open ended questions with narratives. Thirty percent indicated feeling unsafe when identifying as Jewish.

Resumen En un estudio online y anónimo de 242 participantes identificados como judíos (71 hombres, 163 mujeres, 8 otros; media de edad = 37,8 años) que viven en comunidades étnicamente diversas, encontramos niveles de antisemitismo significativamente asociados con la depresión, la propensión a la culpa del sobreviviente y el odio a sí mismo. La participación en la comunidad judía se asoció significativamente con la satisfacción con la vida, incluso cuando se ajusta a los efectos de la discriminación. Una sub muestra de 124 personas respondió a preguntas abiertas con narrativas. El treinta por ciento indicó sentirse inseguro al identificarse como judío.

Contextual fear memory retrieval by correlated ensembles of ventral CA1 neurons.

Ventral hippocampal CA1 (vCA1) projections to the amygdala are necessary for contextual fear memory. Here we used in vivo Ca2+ imaging in mice to assess the temporal dynamics by which ensembles of vCA1 neurons mediate encoding and retrieval of contextual fear memories. We found that a subset of vCA1 neurons were responsive to the aversive shock during context conditioning, their activity was necessary for memory encoding, and these shock-responsive neurons were enriched in the vCA1 projection to the amygdala. During memory retrieval, a population of vCA1 neurons became correlated with shock-encoding neurons, and the magnitude of synchronized activity within this population was proportional to memory strength. The emergence of these correlated networks was disrupted by inhibiting vCA1 shock responses during memory encoding. Thus, our findings suggest that networks of cells that become correlated with shock-responsive neurons in vCA1 are essential components of contextual fear memory ensembles.

Forgiveness Working: Forgiveness, Health, and Productivity in the Workplace.

PURPOSE: Associations between forgiveness and health promotion in the workplace were examined as mediating effects of workplace interpersonal stress. DESIGN: Cross-sectional. SETTING: Multiple Washington, DC, office-based and Midwestern manufacturing workplaces. PARTICIPANTS: Study 1: 108 employees (40 males and 68 females); mean age was 32.4 years. Study 2: 154 employees (14 males and 140 females); mean age was 43.9 years. MEASURES: Questionnaires measured forgiveness, unproductivity, absenteeism, stress, and health problems. ANALYSIS: Bivariate and multiple correlation/regression and structural equation models were used. Indirect effects were estimated with bootstrapping methods. RESULTS: In study 1, forgiveness of a specific workplace offense was inversely associated with unproductivity ( r = -.35, P < .001) and mental ( r = -.32, P = .001) and physical ( r = -.19, P = .044) health problems. In study 2, trait forgiveness was inversely associated with unproductivity (ß = -.20, P = .016) and mental (ß = -.31, P < .001) and physical health problems (ß = -.28, P = .001), and workplace interpersonal stress partially mediated these associations (indirect effects = -.03, -.04, -.05, respectively). CONCLUSION: The association of forgiveness and occupational outcomes is robust. Forgiveness may be associated with outcomes by (at least partially) reducing stress related to workplace offenses. Forgiveness may be an effective means of coping following being emotionally hurt on the job that may promote good health, well-being, and productivity.

A Genetic Screen To Assess Dopamine Receptor (DopR1) Dependent Sleep Regulation in Drosophila.

Sleep is an essential behavioral state of rest that is regulated by homeostatic drives to ensure a balance of sleep and activity, as well as independent arousal mechanisms in the central brain. Dopamine has been identified as a critical regulator of both sleep behavior and arousal. Here, we present results of a genetic screen that selectively restored the Dopamine Receptor (DopR/DopR1/dumb) to specific neuroanatomical regions of the adult Drosophila brain to assess requirements for DopR in sleep behavior. We have identified subsets of the mushroom body that utilizes DopR in daytime sleep regulation. These data are supported by multiple examples of spatially restricted genetic rescue data in discrete circuits of the mushroom body, as well as immunohistochemistry that corroborates the localization of DopR protein within mushroom body circuits. Independent loss of function data using an inducible RNAi construct in the same specific circuits also supports a requirement for DopR in daytime sleep. Additional circuit activation of discrete DopR+ mushroom body neurons also suggests roles for these subpopulations in sleep behavior. These conclusions support a new separable function for DopR in daytime sleep regulation within the mushroom body. This daytime regulation is independent of the known role of DopR in nighttime sleep, which is regulated within the Fan-Shaped Body (FSB). This study provides new neuroanatomical loci for exploration of dopaminergic sleep functions in Drosophila, and expands our understanding of sleep regulation during the day vs. night.

Does participation mediate the prospective relationships of impairment, injury severity, and pain to quality of life following burn injury?

We examined the prospective impact of injury severity, functional impairment, and pain on participation in the community and subsequently on life satisfaction and self-rated health of 260 burn survivors 5 years post-discharge. Predictor variables include injury severity and total body surface area burned (assessed during acute care), functional independence (assessed at 12 months post-discharge), pain (assessed at the 24th month), and participation (assessed at the 48th month). Participation predicted life satisfaction and self-rated health. Functional independence and injury severity had significant indirect influences on adjustment via their influence on participation. Pain predicted both outcome variables. Clinical and research implications are discussed.

Forgiveness-reconciliation and communication-conflict-resolution interventions versus retested controls in early married couples.

The first 6 months of marriage are optimal for marriage enrichment interventions. The Hope-Focused Approach to couple enrichment was presented as two 9-hr interventions--(a) Handling Our Problems Effectively (HOPE), which emphasized communication and conflict resolution, and (b) Forgiveness and Reconciliation through Experiencing Empathy (FREE). HOPE and FREE were compared with repeated assessment controls. Couples were randomly assigned and were assessed at pretreatment (t1); 1 month posttreatment (t2) and at 3- (t3), 6- (t4), and 12-month (t5) follow-ups using self-reports. In addition to self-report measures, couples were assessed at t1, t2, and t5 using salivary cortisol, and behavioral coding of decision making. Of 179 couples who began the study, 145 cases were analyzed. Both FREE and HOPE produced lasting positive changes on self-reports. For cortisol reactivity, HOPE and FREE reduced reactivity at t2, but only HOPE at t5. For coded behaviors, control couples deteriorated; FREE and HOPE did not change. Enrichment training was effective regardless of the focus of the training.

Resilience in the initial year of caregiving for a family member with a traumatic spinal cord injury.

OBJECTIVE: Individuals who assume caregiving duties for a family member disabled in a traumatic injury often exhibit considerable distress, yet few studies have examined characteristics of those who may be resilient in the initial year of caregiving. Reasoning from the influential Pearlin model of caregiving (Pearlin & Aneshensel, 1994) and the resilience process model (Bonanno, 2005), we expected a significant minority of caregivers would be chronically distressed and another group would be resilient throughout the inaugural year of caregiving for a person with a traumatic spinal cord injury (SCI), and these groups would differ significantly in primary and secondary stress and in personal resources and mediators. METHOD: Twenty men and 108 women who identified as caregivers for a family member who incurred a traumatic SCI consented to complete measures during the inpatient rehabilitation and at 1 month, 6 months, and 12 months postdischarge. RESULTS: Latent growth mixture modeling of depression symptoms over time revealed 3 groups of caregivers: chronic (24%), recovery (24%) and resilient (48%). The chronic group reported more anxiety, negative affect, and ill health than the other 2 groups throughout the year. The resilient group was best characterized by their enduring levels of positive affect and supportive social networks. CONCLUSIONS: A large percentage of individuals are resilient in the initial year of caregiving, and those who have problems adapting exhibit significant distress soon following the traumatic event. Early detection of and psychological interventions for individuals who have difficulty adjusting are indicated, as their distress is unlikely to abate untreated over the year.

Telephone-based problem-solving intervention for family caregivers of stroke survivors: a randomized controlled trial.

OBJECTIVE: Intervention trials for stroke caregivers after the early poststroke period are lacking. To address this gap, we examined the effectiveness of a problem-solving intervention (PSI) for stroke caregivers who provided care for at least 6 months and who experienced significant strain in their role. METHOD: One hundred twenty-two family caregivers (age = 66.2 years, 77.9% female) were randomly allocated to a PSI or control group. The PSI was composed of 2 home visits and 18 telephone calls delivered over a 3-month intensive intervention and a 9-month maintenance period. PSI and control groups received monthly information letters in addition to usual care. Primary caregiver outcomes were depressive symptoms (measure: Center for Epidemiologic Studies-Depression Scale) and sense of competence (measure: Sense of Competence Questionnaire). RESULTS: In covariance analyses, caregivers of the PSI group showed significantly lower levels of depressive symptoms after 3 months (p < .01, d = -.48) and after 12 months (p < .05, d = -.37), but no better sense of competence compared with the control group. Latent growth curve analyses revealed positive significant (p < .05) linear and quadratic effects of PSI on both primary outcomes. No effects, however, were found on caregiver social-problem-solving abilities. CONCLUSIONS: Although beneficial effects were observed among caregivers in the PSI group, the lack of effects on problem-solving abilities implies other characteristics of the intervention might account for these benefits. The relative intensity and therapeutic contact during the first 3 months of the intervention may be particularly helpful to caregivers of stroke survivors.

Trajectories of life satisfaction five years after medical discharge for traumatically acquired disability.

OBJECTIVES: We studied the predictive impact of family satisfaction, marital status, and functional impairment on the trajectories of life satisfaction over the first 5 years following medical treatment for traumatic spinal cord injury, burns, or interarticular fractures (total N = 662). It was anticipated that fewer functional impairments, being married, and greater family satisfaction would predict higher life satisfaction trajectories. METHOD: The Functional Independence Measure, the Family Satisfaction Scale, and the Life Satisfaction Index were administered 12, 24, 48, and 60 months postdischarge. RESULTS: Trajectory modeling revealed that greater functional impairment significantly predicted lower life satisfaction, regardless of injury type. However, this association diminished when marital status and family satisfaction were entered into the models. Greater family satisfaction and being married predicted greater life satisfaction across time. Moreover, there was no evidence for increases in life satisfaction trajectories over time: Trajectories were stable across time for all injury groups. CONCLUSIONS: Results suggest that being married and greater family satisfaction promote life satisfaction among those who traumatically acquire disability, and these beneficial effects may be more salient than the degree of functional impairment imposed by the condition.

Predicting quality of life 5 years after medical discharge for traumatic spinal cord injury.

OBJECTIVES: This study tested an a priori contextual model of the mediating effects of participation on the predictive relationships of functional impairment, family satisfaction, and pain to quality of life (QoL) following traumatic spinal cord injury (SCI). DESIGN: A longitudinal design was used to study 144 persons following discharge for traumatic SCI. Predictor variables included functional impairment and family satisfaction (at 12 months post-discharge) and the presence of pain (at 24 months), and mediating variables were two indicators of participation (assessed 48 months post-discharge). Life satisfaction and self-rated health status at 60 months post-discharge were the outcome variables. METHODS: A path model tested hypothesized prospective effects of functional impairment, family satisfaction and pain on participation and the subsequent effects of participation on the QoL variables. RESULTS: Greater functional impairment and pain were predictive of less participation, and participation significantly predicted both indicators of QoL. The two participation variables mediated the relationship of functional impairment and pain to life satisfaction over time. Family satisfaction had an indirect effect on QoL through its association with social integration. CONCLUSIONS: Participation appears to mediate the prospective influence of functional impairment, family satisfaction, and pain on QoL in the years following SCI. These findings provide insight into factors that can predict QoL post-SCI and support the use of contextual models to understand the temporal influence of disability and psychological variables on participation and subsequent QoL. STATEMENT OF CONTRIBUTION: What is already known on this subject? Life satisfaction and self-rated health status are important aspects of quality of life following traumatic spinal cord injury. Functional impairment has been inconsistently predictive of these variables over time. Prospective research to date has not examined the mediating effects of participation in predicting quality of life. What does this study add? The results indicate that greater functional impairment and pain are prospectively predictive of lower participation. Greater participation, in turn, is prospectively predictive of greater quality of life. Participation appears to mediate the prospective influence of functional impairment, family satisfaction, and pain to quality of life.

Modeling the prospective relationships of impairment, injury severity, and participation to quality of life following traumatic brain injury.

Identifying reliable predictors of positive adjustment following traumatic brain injury (TBI) remains an important area of inquiry. Unfortunately, much of available research examines direct relationships between predictor variables and outcomes without attending to the contextual relationships that can exist between predictor variables. Relying on theoretical models of well-being, we examined a theoretical model of adjustment in which the capacity to engage in intentional activities would be prospectively associated with greater participation, which in turn would predict subsequent life satisfaction and perceived health assessed at a later time. Structural equation modeling of data collected from 312 individuals (226 men, 86 women) with TBI revealed that two elements of participation--mobility and occupational activities--mediated the prospective influence of functional independence and injury severity to optimal adjustment 60 months following medical discharge for TBI. The model accounted for 21% of the variance in life satisfaction and 23% of the variance in self-rated health. Results indicate that the effects of functional independence and injury severity to optimal adjustment over time may be best understood in the context of participation in meaningful, productive activities. Implications for theoretical models of well-being and for clinical interventions that promote adjustment after TBI are discussed.

Predictors of health-related quality-of-life following traumatic brain injury.

PRIMARY OBJECTIVE: To examine the predictive associations of family satisfaction, functional impairment, pain, and depression on health-related quality-of-life (HRQoL) among persons with traumatic brain injury (TBI) through structural equation modelling (SEM). RESEARCH DESIGN: Participants were part of a larger longitudinal study of adjustment following TBI. Direct and indirect effects of predictor variables on HRQoL were analyzed through SEM. METHODS AND PROCEDURES: The sample included 131 participants with TBI (89 men, 42 women) who had been discharged from an acute care hospital. The Sickness Impact Profile was administered to measure HRQoL at or beyond 24 months post-discharge. Predictor variable measures included the Functional Independence Measure, Family Satisfaction Scale and single items assessing the presence of pain and depression. MAIN OUTCOMES AND RESULTS: SEM revealed direct effects of functional impairment (p < 0.001), family satisfaction (p < 0.01), depression (p < 0.05) and pain (p < 0.01) on HRQoL. Indirect effects from functional impairment (p < 0.05) and pain (p < 0.05) to HRQoL through depression were also present. CONCLUSIONS: The presence of pain and depression, greater functional impairment and lower family satisfaction were predictively associated with lower HRQoL. Depression further mediated the effects of pain and functional impairment on HRQoL. The present study advances understanding of the ways in which pain, depression and functional impairment predict HRQoL.

Six weeks of massage therapy produces changes in balance, neurological and cardiovascular measures in older persons.

OBJECTIVES: Falls in older adults represent a primary cause of decreased mobility and independence, increased morbidity, and accidental death. Research and clinical reports indicate that therapeutic massage (TM) may positively influence suggested causative factors. The second in a two-part study, this project assessed the effects of six weeks of TM treatment on balance, nervous system, and cardiovascular measures in older adults. DESIGN: A randomized controlled trial assessed the effects of six weekly 60-minute sessions of TM on balance, cardiovascular, and nervous system measures. Thirty-five volunteers (19 male and 16 female; ages 62.9 ± 4.6) were randomly assigned to relaxation control or TM groups. A 2 × 4 [treatment condition X time (week 1 and 6)] mixed factorial experimental design was utilized for cardiovascular/balance variables assessed at pretreatment baseline, immediate post-treatment, and 20- and 60-minutes post-treatment; nervous system measures were assessed only at pretreatment and at 60-minute follow-up (2 × 2 mixed design). Long-term benefits were assessed by comparing the TM and control groups on pretreatment baseline measures at week six and a follow-up assessment at week seven (2 × 3 mixed design). SETTING: Laboratory INTERVENTION: Six weekly 60-minute, full-body TM. OUTCOME MEASURES: Postural control/cardiovascular measures were assessed weeks one, six, and seven; pretreatment and immediate, 20- and 60-minutes post-treatment. Motoneuron pool excitability was assessed pretreatment and 60 minutes post-treatment. RESULTS: The TM group showed significant differences relative to controls in cardiovascular and displacement area/velocity after the week six session, with decreasing blood pressure and increasing stability over time from immediate post-TM to 60 minutes post-TM. The TM group revealed lower H-max/M-max ratios 60-minutes post-treatment. Long-term differences between the groups were detected at week seven in displacement area/velocity and systolic blood pressure. CONCLUSIONS: Results suggest six weeks of TM resulted in immediate and long-term improvements in postural stability and blood pressure, compared to a controlled condition.

Massage Therapy Produces Short-term Improvements in Balance, Neurological, and Cardiovascular Measures in Older Persons.

BACKGROUND: Falls are the primary cause of accidental death in older persons, producing increased morbidity, decreased independence, and billions in medical costs annually. Massage therapy (MT) may produce adaptations that decrease risk of falling. If MT can improve stability in older persons, it may provide a new intervention for this issue. PURPOSE: Determine the acute effects of a 60-minute MT treatment on static and functional balance, neurological measures, heart rate, and blood pressure in healthy, older individuals. SETTING: Laboratory RESEARCH DESIGN: A 2 by 4 (treatment by time) mixed factorial experimental design for the cardiovascular and postural control variables; independent variables were treatment with two levels (control, MT) and time with four levels (pretreatment baseline, immediate post-treatment, 20-minute post-treatment, 60-minute post-treatment). Neurological measures utilized a 2 by 2 mixed design, with testing conducted pre- and 60-minutes post-treatment. PARTICIPANTS: Thirty-five healthy, older volunteers (19 male and 16 female; ages 62.9 ± 4.6). INTERVENTION: A 60-minute full-body therapeutic massage. The control group rested quietly in the treatment room. MAIN OUTCOME MEASURES: Static (double-legged) and functional (single-legged) postural control with eyes-open and eyes-closed; Hoffmann-reflex measures; heart rate, and systolic and diastolic blood pressure. RESULTS: MT significantly decreased rectangular displacement area in both the eyes-open and eyes-closed, double-legged stance conditions (p < 0.05); displacement velocity in both eyes-open conditions (p < .05); and systolic and diastolic blood pressure (p < .05), while increasing heart rate (p < .05). MT also significantly lowered H(max)/M(max) ratios compared to controls (p = .002). Decreased H(max)/M(max) measures were correlated to improved stability. CONCLUSIONS: A single, 60-minute, full-body massage therapy treatment was shown to have a stabilizing effect on measures of static and dynamic balance and physiological factors related to stability in older adults. MT should be investigated as a potential intervention to decrease falls in older individuals.

Does problem-solving training for family caregivers benefit their care recipients with severe disabilities? A latent growth model of the Project CLUES randomized clinical trial.

OBJECTIVE: To examine whether an individualized problem-solving intervention provided to family caregivers of persons with severe disabilities provides benefits to both caregivers and their care recipients. DESIGN: Family caregivers were randomly assigned to an education-only control group or a problem-solving training (PST) intervention group. Participants received monthly contacts for 1 year. PARTICIPANTS: Family caregivers (129 women, 18 men) and their care recipients (81 women, 66 men) consented to participate. MAIN OUTCOME MEASURES: Caregivers completed the Social Problem-Solving Inventory-Revised, the Center for Epidemiological Studies-Depression scale, the Satisfaction with Life scale, and a measure of health complaints at baseline and in 3 additional assessments throughout the year. Care recipient depression was assessed with a short form of the Hamilton Depression Scale. RESULTS: Latent growth modeling was used to analyze data from the dyads. Caregivers who received PST reported a significant decrease in depression over time, and they also displayed gains in constructive problem-solving abilities and decreases in dysfunctional problem-solving abilities. Care recipients displayed significant decreases in depression over time, and these decreases were significantly associated with decreases in caregiver depression in response to training. CONCLUSIONS: PST significantly improved the problem-solving skills of community-residing caregivers and also lessened their depressive symptoms. Care recipients in the PST group also had reductions in depression over time, and it appears that decreases in caregiver depression may account for this effect.

Conciliatory gestures facilitate forgiveness and feelings of friendship by making transgressors appear more agreeable.

The authors examined how conciliatory gestures exhibited in response to interpersonal transgressions influence forgiveness and feelings of friendship with the transgressor. In Study 1, 163 undergraduates who had recently been harmed were examined longitudinally. Conciliatory gestures exhibited by transgressors predicted higher rates of forgiveness over 21 days, and this relationship was mediated by victims' perceptions of their transgressors' Agreeableness. Study 2 was an experiment including 145 undergraduates who experienced a breach in trust from an anonymous partner during an iterated prisoner's dilemma. When transgressors apologized and offered financial compensation, participants reported higher levels of forgiveness and feelings of friendship when compared to a control condition and an aggravating condition. The effects of apology/compensation on forgiveness and perceived friendship were mediated by victims' perceptions of their transgressors' Agreeableness. Results suggest that conciliatory gestures promote forgiveness in part by depicting transgressors as more sympathetic, considerate, fair, and just (i.e., agreeable).

Physiological and clinical changes after therapeutic massage of the neck and shoulders.

Little is known regarding the physiological and clinical effects of therapeutic massage (TM) even though it is often prescribed for musculoskeletal complaints such as chronic neck pain. This study investigated the influence of a standardized clinical neck/shoulder TM intervention on physiological measures assessing α-motoneurone pool excitability, muscle activity; and the clinical measure of range of motion (ROM) compared to a light touch and control intervention. Flexor carpi radialis (FCR) α-motoneurone pool excitability (Hoffmann reflex), electromyography (EMG) signal amplitude of the upper trapezius during maximal muscle activity, and cervical ROM were used to assess possible physiological changes and clinical effects of TM. Sixteen healthy adults participated in three, 20 min interventions: control (C), light touch (LT) and therapeutic massage (TM). Analysis of Covariance indicated a decrease in FCR α-motoneurone pool excitability after TM, compared to both the LT (p = 0.0003) or C (p = 0.0007) interventions. EMG signal amplitude decreased after TM by 13% (p < 0.0001), when compared to the control, and 12% (p < 0.0001) as compared to LT intervention. The TM intervention produced increases in cervical ROM in all directions assessed: flexion (p < 0.0001), lateral flexion (p < 0.0001), extension (p < 0.0001), and rotation (p < 0.0001). TM of the neck/shoulders reduced the α-motoneurone pool excitability of the flexor carpi radialis after TM, but not after the LT or C interventions. Moreover, decreases in the normalized EMG amplitude during MVIC of the upper trapezius muscle; and increases in cervical ROM in all directions assessed occurred after TM, but not after the LT or C interventions.