Reliability and Validity of the State-Trait Hopelessness Scale in a Primarily Rural Population of Adults With Ischemic Heart Disease in the US Great Plains.

PURPOSE: Hopelessness and rurality are each independently associated with increased mortality in adults with ischemic heart disease (IHD), yet there is no known research examining hopelessness in rural patients with IHD. The authors of this study evaluated the reliability and validity of the State-Trait Hopelessness Scale (STHS) in a primarily rural population of adults with IHD living in West North Central United States (US Great Plains). METHODS: Reliability, concurrent validity, and convergent validity were evaluated for 115 adults hospitalized for IHD. Rural-Urban Commuting Area codes were used to stratify participants by rurality level, with 66% categorized as rural. Principal component analysis was used to examine potential factor structure of the STHS. FINDINGS: Cronbach α for the State and Trait Hopelessness subscales were 0.884 and 0.903, respectively. Concurrent validity was supported for the State and Trait subscales using the Patient Health Questionnaire-8 (State: r = 0.50, P < .001; Trait: r = 0.35, P < .001). Convergent validity was supported for the State subscale using the Duke Activity Status Index ( r = -0.23, P = .013). Principal component analysis showed 2 factors (hopelessness present and hopelessness absent) for the State and Trait subscales, accounting for 63% and 58% of variance, respectively. CONCLUSIONS: Findings support the reliability and validity of the STHS for evaluation of hopelessness in rural adults with IHD in clinical and research settings. Results replicated the same factor structure found in testing of the STHS in a primarily urban sample. Because of the prevalence of hopelessness in rural adults with IHD and association with increased mortality, hopelessness should be assessed during hospitalization and in the recovery period.

There is little association between prehospital delay, persistent symptoms, and post-discharge healthcare utilization in patients evaluated for acute coronary syndrome.

AIMS: Test for an association between prehospital delay for symptoms suggestive of acute coronary syndrome (ACS), persistent symptoms, and healthcare utilization (HCU) 30-days and 6-months post hospital discharge. BACKGROUND: Delayed treatment for ACS increases patient morbidity and mortality. Prehospital delay is the largest factor in delayed treatment for ACS. METHODS: Secondary analysis of data collected from a multi-center prospective study. Included were 722 patients presenting to the Emergency Department (ED) with symptoms that triggered a cardiac evaluation. Symptoms and HCU were measured using the 13-item ACS Symptom Checklist and the Froelicher's Health Services Utilization Questionnaire-Revised instrument. Logistic regression models were used to examine hypothesized associations. RESULTS: For patients with ACS (n = 325), longer prehospital delay was associated with fewer MD/NP visits (OR, 0.986) at 30 days. Longer prehospital delay was associated with higher odds of calling 911 for any reason (OR, 1.015), and calling 911 for chest related symptoms (OR, 1.016) 6 months following discharge. For non-ACS patients (n = 397), longer prehospital delay was associated with higher odds of experiencing chest pressure (OR, 1.009) and chest discomfort (OR, 1.008) at 30 days. At 6 months, longer prehospital delay was associated with higher odds of upper back pain (OR, 1.013), palpitations (OR 1.014), indigestion (OR, 1.010), and calls to the MD/NP for chest symptoms (OR, 1.014). CONCLUSIONS: There were few associations between prehospital delay and HCU for patients evaluated for ACS in the ED. Associations between prolonged delay and persistent symptoms may lead to increased HCU for those without ACS.

Negative Attitudes, Self-efficacy, and Relapse Management Mediate Long-Term Adherence to Exercise in Patients With Heart Failure.

BACKGROUND: Exercise is safe and provides considerable benefits for patients with heart failure (HF) including improved function, quality of life, and symptoms. However, patients with HF have difficulty initiating and adhering to an exercise regimen. To improve adherence, our team developed Heart Failure Exercise and Resistance Training (HEART) Camp, a multicomponent, theory-driven intervention that was efficacious in a randomized controlled trial of long-term adherence to exercise in patients with HF. Identifying active components of efficacious interventions is a priority. PURPOSE: The purpose of this study is to use mediation analysis to determine which interventional components accounted for long-term adherence to exercise in patients with HF. METHODS: This study included 204 patients with HF enrolled in a randomized controlled trial. Instruments measuring interventional components were completed at baseline, 6, 12, and 18 months. Hierarchical linear models generated slope estimates to be used as predictors in logistic regression models. Significant variables were tested for indirect effects using path analyses with 1,000 bootstrapped estimates. RESULTS: Significant mediation effects were observed for the interventional components of negative attitudes (ß NA = 0.368, s.e. = 0.062, p < .001), self-efficacy (ß SE = 0.190, s.e. = 0.047, p < .001), and relapse management (ß RM = 0.243, s.e. = 0.076, p = .001). CONCLUSIONS: These findings highlight improving attitudes, self-efficacy, and managing relapse as key interventional components to improve long-term adherence to exercise in patients with HF. Future interventions targeting adherence to exercise in patients with HF and other chronic illnesses should consider the incorporation of these active components.

Suicide Risk Management Protocol for a Randomized Controlled Trial of Cardiac Patients Reporting Hopelessness.

BACKGROUND: Investigators conducting studies that include potentially suicidal individuals are obligated to develop a suicide risk management (SRM) protocol. There is little available in the literature to guide researchers in SRM protocol development. OBJECTIVES: The aim of the study was to describe an SRM protocol developed for a randomized controlled trial (RCT) currently enrolling cardiac patients who report moderate to severe levels of hopelessness. METHODS: The SRM protocol identifies suicidal ideation and measures ideation severity through use of the Columbia-Suicide Severity Rating Scale risk factor questions. Based on responses, study participants are deemed safe or at low, moderate, or high risk for suicide. The SRM protocol guides research staff through a plan of action based on risk level. The protocol further guides staff through a plan over the course of this prospective study-from hospital enrollment to home-based visits. RESULTS: Research staff are well trained to identify suicidal ideation risk factors, initiate specific questioning about suicidal intent, determine level of risk, identify protective factors and a safe environment, and make referrals if needed. Of the 51 patients hospitalized with cardiac disease who reported moderate to severe hopelessness, 43 scored at a safe suicide risk level and 8 scored at low risk. Thirty-five of the 51 patients enrolled in the RCT. Of the 35 participants who received home visits to date, there have been three instances of low and one instance of moderate suicide risk. The SRM protocol has been consistently and accurately used by research personnel in both hospital and home settings. One modification has been made to the protocol since study activation, namely, the addition of an assessment of counseling history and encouragement of continued counseling. Booster training sessions of research staff will continue throughout the course of the RCT. DISCUSSION: Use of the SRM protocol identifies study participants who are safe or at risk for suicide in both hospital and home settings, and research staff can refer participants accordingly. CONCLUSION: The SRM protocol developed for this RCT can serve as a model in the development of SRM protocols for future research in acute care, community, or home-based settings.

Developing the first pan-Canadian survey on patient engagement in patient safety.

BACKGROUND: Patient safety is a worldwide problem, and the patient contribution to mitigate the risk of patient harm is now recognized as a cornerstone to its solution. In order to understand the nature of integrating patients into patient safety and healthcare organizations and to monitor their integration, a Canadian survey tool has been co-constructed by patients, researchers and the Canadian Patient Safety Institute (CPSI). This questionnaire has been adapted from the French version of the patient engagement (PE) in patient safety (PS) questionnaire created for the province of Quebec, Canada. METHODOLOGY: The pan-Canadian PE in PS survey tool was developed in a five-step process: (1) a literature review and revision of the initial tool developed in the province of Quebec; (2) translation of the French questionnaire into an English version tool; (3) creation of a Canadian expert advisory group; (4) adaptation of the English version tool based on feedback from the expert advisory group (assessment and development of the construct's dimensions, wording assessment and adaptation for pan-Canadian use, technical testing of the online platform for the survey); and (5) pilot testing and pre-validation of the tool before pan-Canadian use. RESULTS AND CONCLUSION: Eight pan-Canadian PE in PS surveys were completed from five Canadian provinces by the expert advisory group and six surveys were completed during the pilot project by participants from different provinces in Canada. This survey tool comprises 5 sections: (1) demographic identification of the participants (Q1 to Q5); (2) general questions (Q6 to Q17); (3) the patient engagement process (experience level of participants and organizational incentives for PE in general) (Q18 to Q33); (4) PE in PS processes, such as current activities, strategies, structures, resources and factors (Q34 to Q67); and (5) the context and impact of PE in PS initiatives in Canadian healthcare organizations (CHOs) (Q68 to Q75), including outcome identification, improvement mechanisms and strategies, evaluation mechanisms, and indicators.

ActiGraph and Short-term Heart Rate Variability Study Protocol: Amended for the COVID-19 Pandemic.

BACKGROUND: ActiGraph accelerometry is widely used in nursing research to estimate daily physical activity. Heart rate variability (HRV), a measure of autonomic modulation, can be assessed in conjunction with the ActiGraph using a Polar H7 Bluetooth heart rate monitor. There is a paucity of nursing literature to guide nurse researchers' protocol development when using the ActiGraph to assess both physical activity and short-term HRV via its Bluetooth capabilities. OBJECTIVES: The aim of this study was to describe a standardized research ActiGraph and HRV (ActiGraph HRV) protocol for an ongoing randomized controlled trial to measure physical activity and short-term HRV in patients with ischemic heart disease who report hopelessness. METHODS: We outline the study protocol for the standardization of reliable and rigorous physical activity and HRV data collection using the ActiGraph wGT3X-BT and Polar H7 Bluetooth heart rate monitor, and data analysis using ActiLife and Kubios software programs. RESULTS: Sixty-four participants enrolled in the randomized controlled trial to date, and 45 (70.3%) have completed or are actively participating in the study. Heart rate variability data have been collected on 43 of the 45 participants (96%) to date. During the first data collection time point, 42 of 44 participants (95.5%) wore the ActiGraph for a minimum of 5 valid days, followed by 28 of 31 participants (90.3%) and 25 of 26 participants (96.2%) at subsequent data collection time points. The intraclass correlation for physical activity in this study is 0.95 and 0.98 for HRV. DISCUSSION: Revisions to the protocol were successfully implemented at the onset of the COVID-19 pandemic for data collection using social distancing. The protocol was additionally amended in response to an unanticipated problem with ActiGraph battery life using Bluetooth technology. Use of the ActiGraph HRV protocol has led to a reliable and rigorous measurement of physical activity and HRV for patients with ischemic heart disease who report hopelessness in this randomized controlled trial. CONCLUSION: We provide an ActiGraph HRV protocol that can be adapted as a model in the development of ActiGraph HRV protocols for future nursing research in community and home-based settings while maximizing social distancing in the current and future pandemics.

Heart up! RCT protocol to increase physical activity in cardiac patients who report hopelessness: Amended for the COVID-19 pandemic.

Hopelessness is associated with decreased physical activity (PA) and increased adverse events and death in patients with ischemic heart disease (IHD). Rates of PA in patients with IHD continue to be low in both hospital-based cardiac rehabilitation and home settings. While researchers have investigated strategies to increase PA among patients with IHD, interventions to promote PA specifically in IHD patients who report hopelessness are lacking. We describe the protocol for a NIH-funded randomized controlled trial designed to establish the effectiveness of a 6-week intervention (Heart Up!) to promote increased PA in IHD patients who report hopelessness. Participants (n = 225) are randomized to one of three groups: (1) motivational social support (MSS) from a nurse, (2) MSS from a nurse plus significant other support (SOS), or (3) attention control. Aims are to: (1) test the effectiveness of 6 weeks of MSS and MSS with SOS on increasing mean minutes per day of moderate to vigorous PA; (2) determine the effects of change in moderate to vigorous PA on hopelessness; and (3) determine if perceived social support and motivation (exercise self-regulation) mediate the effects of the intervention on PA. A total of 69 participants have been enrolled to date. The protocol has been consistently and accurately used by research personnel. We address the protocol challenges presented by the COVID-19 pandemic and steps taken to maintain fidelity to the intervention. Findings from this study could transform care for IHD patients who report hopelessness by promoting self-management of important PA goals that can contribute to better health outcomes.

Reliability and Validity of the State-Trait Hopelessness Scale in Patients With Heart Disease and Moderate to Severe Hopelessness.

OBJECTIVE: The aim of this study was to evaluate the reliability and validity of the State-Trait Hopelessness Scale (STHS) in patients with heart disease who report moderate to severe state hopelessness. METHODS: Reliability, concurrent validity, and convergent validity were evaluated for 20 patients. RESULTS: Cronbach's α for the State and Trait subscales were .81 and .79, respectively. Strong correlations between the State Hopelessness Subscale and Patient Health Questionnaire-9 (r = 0.77, P < .001), State Hope Scale (r = -0.75, P < .001), EQ-5D-5L (r = 0.59, P < .005), and PROMIS-29 domains of depression (P = .72, P < .001), fatigue (P = .61, P < .001), and social roles (P = .45, P = .047) were found. There were strong correlations between the Trait Hopelessness Subscale and Trait Hope Scale (r = -0.58, P < .005), State Hope Scale (r = -0.49, P = .03), and PROMIS-29 fatigue domain (r = 0.54, P = .015). CONCLUSIONS: Findings support the reliability and validity of the STHS for evaluation of hopelessness in patients with heart disease.

Lack of perceived social support in patients with ischemic heart disease is associated with hopelessness.

OBJECTIVE: To evaluate perceived social support (PSS) in ischemic heart disease (IHD) patients who report hopelessness. METHODS: Using a cross-sectional design, 156 patients were screened during their hospitalization for moderate to severe state hopelessness. Twenty patients who reported hopelessness during hospitalization and maintained hopelessness one week after hospital discharge were included. RESULTS: A moderately strong negative correlation was identified between PSS and state hopelessness (r = -0.54, p = .014). PSS was significantly higher in married/partnered patients (26.7 ± 4.85) compared to unmarried/unpartnered patients (18 ± 9.18; t = 2.45, p = .035). CONCLUSIONS: Social support may help reduce hopelessness in vulnerable cardiac patients, especially those who are unpartnered.

Exploring variation in low-value care: a multilevel modelling study.

BACKGROUND: Whether patients receive low-value hospital care (care that is not expected to provide a net benefit) may be influenced by unmeasured factors at the hospital they attend or the hospital's Local Health District (LHD), or the patients' areas of residence. Multilevel modelling presents a method to examine the effects of these different levels simultaneously and assess their relative importance to the outcome. Knowing which of these levels has the greatest contextual effects can help target further investigation or initiatives to reduce low-value care. METHODS: We conducted multilevel logistic regression modelling for nine low-value hospital procedures. We fit a series of six models for each procedure. The baseline model included only episode-level variables with no multilevel structure. We then added each level (hospital, LHD, Statistical Local Area [SLA] of residence) separately and used the change in the c statistic from the baseline model as a measure of the contribution of the level to the outcome. We then examined the variance partition coefficients (VPCs) and median odds ratios for a model including all three levels. Finally, we added level-specific covariates to examine if they were associated with the outcome. RESULTS: Analysis of the c statistics showed that hospital was more important than LHD or SLA in explaining whether patients receive low-value care. The greatest increases were 0.16 for endoscopy for dyspepsia, 0.13 for colonoscopy for constipation, and 0.14 for sentinel lymph node biopsy for early melanoma. SLA gave a small increase in c compared with the baseline model, but no increase over the model with hospital. The VPCs indicated that hospital accounted for most of the variation not explained by the episode-level variables, reaching 36.8% (95% CI, 31.9-39.0) for knee arthroscopy. ERCP (8.5%; 95% CI, 3.9-14.7) and EVAR (7.8%; 95% CI, 2.9-15.8) had the lowest residual variation at the hospital level. The variables at the hospital, LHD and SLA levels that were available for this study generally showed no significant effect. CONCLUSIONS: Investigations into the causes of low-value care and initiatives to reduce low-value care might best be targeted at the hospital level, as the high variation at this level suggests the greatest potential to reduce low-value care.

Ethnic minority members may be at risk for state hopelessness following hospitalization for ischemic heart disease.

OBJECTIVE: To examine differences in state and trait hopelessness between ethnic minority and White patients hospitalized with ischemic heart disease (IHD). METHODS: A descriptive cross-sectional design was used to enroll 517 patients at one Midwestern U.S. hospital. The State-Trait Hopelessness Scale measured hopelessness. RESULTS: State hopelessness was higher in ethnic minority patients compared to Whites. Ethnic minority patients who had never been married had higher state hopelessness than those who were married or separated/divorced. There were no differences in trait hopelessness. CONCLUSIONS: Ethnic minority patients with IHD, who have never been married, may be at higher risk for state hopelessness.

Dog Ownership and Dog Walking: The Relationship With Exercise, Depression, and Hopelessness in Patients With Ischemic Heart Disease.

BACKGROUND: Dog ownership has been associated with increased physical activity in the general adult population. OBJECTIVE: The objective of this study was to examine dog ownership and dog walking and their relationship with home-based and phase II cardiac rehabilitation exercise, depression, and hopelessness in patients with ischemic heart disease. METHODS: A total of 122 patients with ischemic heart disease were included in this prospective observational study. Patients completed dog ownership/walking questions during their hospitalization. The Cardiac Rehabilitation Exercise Participation Tool, Patient Health Questionnaire-9, and State-Trait Hopelessness Scale were completed by mail at 3, 8, or 12 months later. Regression modeling was used to evaluate the significance of dog ownership/walking on exercise, depression and hopelessness. RESULTS: The sample was 34.4% female and had a mean age of 64.7 ± 9.1 years. Forty-two patients (34.4%) reported owning a dog. Patients who owned but did not walk their dog reported significantly lower levels of home exercise compared with patients who walked their dogs at least 1 day per week (36.8% for non-dog walkers vs 73.9% for dog walkers, P = .019). The odds of participating in home exercise were significantly higher for dog walkers compared with non-dog walkers (odds ratio, 8.1 [1.7, 38.5] vs 1.0). There were no differences in phase II cardiac rehabilitation exercise, depression, or hopelessness between dog owners and non-dog owners or between dog walkers and non-dog walkers. CONCLUSIONS: These findings show a beneficial effect on home-based exercise for those who dog-walk at least 1 day per week. Healthcare professionals should encourage dog walking to increase dog owners' physical activity levels.

Connexin-43 prevents hematopoietic stem cell senescence through transfer of reactive oxygen species to bone marrow stromal cells.

Hematopoietic stem cell (HSC) aging has become a concern in chemotherapy of older patients. Humoral and paracrine signals from the bone marrow (BM) hematopoietic microenvironment (HM) control HSC activity during regenerative hematopoiesis. Connexin-43 (Cx43), a connexin constituent of gap junctions (GJs) is expressed in HSCs, down-regulated during differentiation, and postulated to be a self-renewal gene. Our studies, however, reveal that hematopoietic-specific Cx43 deficiency does not result in significant long-term competitive repopulation deficiency. Instead, hematopoietic Cx43 (H-Cx43) deficiency delays hematopoietic recovery after myeloablation with 5-fluorouracil (5-FU). 5-FU-treated H-Cx43-deficient HSC and progenitors (HSC/P) cells display decreased survival and fail to enter the cell cycle to proliferate. Cell cycle quiescence is associated with down-regulation of cyclin D1, up-regulation of the cyclin-dependent kinase inhibitors, p21(cip1.) and p16(INK4a), and Forkhead transcriptional factor 1 (Foxo1), and activation of p38 mitogen-activated protein kinase (MAPK), indicating that H-Cx43-deficient HSCs are prone to senescence. The mechanism of increased senescence in H-Cx43-deficient HSC/P cells depends on their inability to transfer reactive oxygen species (ROS) to the HM, leading to accumulation of ROS within HSCs. In vivo antioxidant administration prevents the defective hematopoietic regeneration, as well as exogenous expression of Cx43 in HSC/P cells. Furthermore, ROS transfer from HSC/P cells to BM stromal cells is also rescued by reexpression of Cx43 in HSC/P. Finally, the deficiency of Cx43 in the HM phenocopies the hematopoietic defect in vivo. These results indicate that Cx43 exerts a protective role and regulates the HSC/P ROS content through ROS transfer to the HM, resulting in HSC protection during stress hematopoietic regeneration.

Carbon Monoxide Poisoning from Portable Electrical Generators.

BACKGROUND: Portable electrical generators have been responsible for over 800 accidental carbon monoxide (CO) poisoning deaths in the United States from 1999-2012. OBJECTIVES: Because mortality figures are typically the only data reported with regard to the adverse effects of generators, we describe a nonfatal segment of the poisoned population to further emphasize the significance of the problem. METHODS: Unidentifiable information about patients treated in the United States with hyperbaric oxygen for acute CO poisoning was prospectively reported by participating centers. Those patients poisoned by portable generators were selected for analysis. RESULTS: Of 1604 patients reported from August 1, 2008 to July 31, 2011, there were 264 accidentally poisoned by portable generators. Exposures occurred in 151 incidents in 33 states. In 99 incidents, poisoning occurred in a residence. Average patient age was 37 ± 20 years (range 1 to 90+ years). Of those poisoned, 146 (55%) were non-Hispanic white, 57 (22%) were black, 52 (20%) were Hispanic white, 4 (2%) were Asian, and 4 (2%) were Native American. English was spoken by 96%. The most common symptoms included headache (62%), dizziness (52%), and loss of consciousness (50%). Blood carboxyhemoglobin levels averaged 22.7 ± 9.0% (range 2.3-48.3%). Thirty-six patients demonstrated evidence of cardiac ischemia. CONCLUSIONS: Acute, severe CO poisoning from portable electric generators is common in the United States, likely affecting an estimated 4000 individuals annually, occurring predominantly in residential settings, and affecting English language-speaking individuals.

Bmi1 reprograms CML B-lymphoid progenitors to become B-ALL-initiating cells.

The characterization and targeting of Philadelphia chromosome positive (Ph(+)) acute lymphoblastic leukemia (ALL)-initiating cells remains unresolved. Expression of the polycomb protein Bmi1 is up-regulated in patients with advanced stages of chronic myelogenous leukemia (CML). We report that Bmi1 transforms and reprograms CML B-lymphoid progenitors into stem cell leukemia (Scl) promoter-driven, self-renewing, leukemia-initiating cells to result in B-lymphoid leukemia (B-ALL) in vivo. In vitro, highly proliferating and serially replatable myeloid and lymphoid colony-forming cultures could be established from BCR-ABL and Bmi1 coexpressing progenitors. However, unlike in vivo expanded CML B-lymphoid progenitors, hematopoietic stem cells, or multipotent progenitors, coexpressing BCR-ABL and Bmi1 did not initiate or propagate leukemia in a limiting dilution assay. Inducible genetic attenuation of BCR-ABL reversed Bmi1-driven B-ALL development, which was accompanied by induction of apoptosis of leukemic B-lymphoid progenitors and by long-term animal survival, suggesting that BCR-ABL is required to maintain B-ALL and that BCR-ABL and Bmi1 cooperate toward blast transformation in vivo. Our data indicate that BCR-ABL targeting itself is required to eradicate Ph(+)/Bmi1(+) B-ALL-initiating cells and confirm their addiction to BCR-ABL signaling.

Vav3 collaborates with p190-BCR-ABL in lymphoid progenitor leukemogenesis, proliferation, and survival.

Despite the introduction of tyrosine kinase inhibitor therapy, the prognosis for p190-BCR-ABL(+) acute lymphoblastic leukemia remains poor. In the present study, we present the cellular and molecular roles of the Rho GTPase guanine nucleotide exchange factor Vav in lymphoid leukemogenesis and explore the roles of Vav proteins in BCR-ABL-dependent signaling. We show that genetic deficiency of the guanine nucleotide exchange factor Vav3 delays leukemogenesis by p190-BCR-ABL and phenocopies the effect of Rac2 deficiency, a downstream effector of Vav3. Compensatory up-regulation of expression and activation of Vav3 in Vav1/Vav2-deficient B-cell progenitors increases the transformation ability of p190-BCR-ABL. Vav3 deficiency induces apoptosis of murine and human leukemic lymphoid progenitors, decreases the activation of Rho GTPase family members and p21-activated kinase, and is associated with increased Bad phosphorylation and up-regulation of Bax, Bak, and Bik. Finally, Vav3 activation only partly depends on ABL TK activity, and Vav3 deficiency collaborates with tyrosine kinase inhibitors to inhibit CrkL activation and impair leukemogenesis in vitro and in vivo. We conclude that Vav3 represents a novel specific molecular leukemic effector for multitarget therapy in p190-BCR-ABL-expressing acute lymphoblastic leukemia.

Connexin-43 in the osteogenic BM niche regulates its cellular composition and the bidirectional traffic of hematopoietic stem cells and progenitors.

Connexin-43 (Cx43), a gap junction protein involved in control of cell proliferation, differentiation and migration, has been suggested to have a role in hematopoiesis. Cx43 is highly expressed in osteoblasts and osteogenic progenitors (OB/P). To elucidate the biologic function of Cx43 in the hematopoietic microenvironment (HM) and its influence in hematopoietic stem cell (HSC) activity, we studied the hematopoietic function in an in vivo model of constitutive deficiency of Cx43 in OB/P. The deficiency of Cx43 in OB/P cells does not impair the steady state hematopoiesis, but disrupts the directional trafficking of HSC/progenitors (Ps) between the bone marrow (BM) and peripheral blood (PB). OB/P Cx43 is a crucial positive regulator of transstromal migration and homing of both HSCs and progenitors in an irradiated microenvironment. However, OB/P Cx43 deficiency in nonmyeloablated animals does not result in a homing defect but induces increased endosteal lodging and decreased mobilization of HSC/Ps associated with proliferation and expansion of Cxcl12-secreting mesenchymal/osteolineage cells in the BM HM in vivo. Cx43 controls the cellular content of the BM osteogenic microenvironment and is required for homing of HSC/Ps in myeloablated animals.

Demographic factors affect willingness to register as an organ donor more than a personal relationship with a transplant candidate.

BACKGROUND: Transplant candidate caregivers (TCCs) are an under-utilized but potentially devoted pool of advocates who themselves may be recruited to register for deceased organ donation. AIM: The purpose of this study was to assess and compare recruitment barriers to deceased donor registration efforts in TCCs and health fair attendees (HFAs). METHODS: A 42-item questionnaire assessing willingness to register as an organ donor and perceptions and knowledge about organ donation was administered to 452 participants (174 in Denver, 278 in San Francisco). Logistic regression, stratified by study site, was used to assess associations between explanatory variables and willingness to register as an organ donor. RESULTS: In Denver, 83 % of TCCs versus 68 % of HFAs indicated a willingness to register (p = 0.03). Controlling for study group (TCC vs HFA), predictors of willingness to register were female gender [odds ratio (OR) 2.4], Caucasian race (OR 2.3), college graduate (OR 11.1), married (OR 2.4) and higher positive perception of organ donation (OR 1.2), each p < 0.05. In San Francisco, 58 % of TCCs versus 70 % of HFAs indicated a willingness to register (p = 0.03). Controlling for study group (TCC vs HFA), predictors of willingness to register were Caucasian race (OR 3.5), college graduate (OR 2.2), married (OR 1.9), higher knowledge (OR 1.6) and higher positive perception of organ donation (OR 1.2), each p < 0.05. In both locales, Caucasians were more likely to have positive perceptions about organ donation and were more willing to register. CONCLUSIONS: Demographic characteristics, not personal connection to a transplant candidate, explain willingness to register as an organ donor.

Atypical protein kinase C (aPKCzeta and aPKClambda) is dispensable for mammalian hematopoietic stem cell activity and blood formation.

The stem-cell pool is considered to be maintained by a balance between symmetric and asymmetric division of stem cells. The cell polarity model proposes that the facultative use of symmetric and asymmetric cell division is orchestrated by a polarity complex consisting of partitioning-defective proteins Par3 and Par6, and atypical protein kinase C (aPKCζ and aPKCλ), which regulates planar symmetry of dividing stem cells with respect to the signaling microenvironment. However, the role of the polarity complex is unexplored in mammalian adult stem-cell functions. Here we report that, in contrast to accepted paradigms, polarization and activity of adult hematopoietic stem cell (HSC) do not depend on either aPKCζ or aPKCλ or both in vivo. Mice, having constitutive and hematopoietic-specific (Vav1-Cre) deletion of aPKCζ and aPKCλ, respectively, have normal hematopoiesis, including normal HSC self-renewal, engraftment, differentiation, and interaction with the bone marrow microenvironment. Furthermore, inducible complete deletion of aPKCλ (Mx1-Cre) in aPKCζ(-/-) HSC does not affect HSC polarization, self-renewal, engraftment, or lineage repopulation. In addition, aPKCζ- and aPKCλ-deficient HSCs elicited a normal pattern of hematopoietic recovery secondary to myeloablative stress. Taken together, the expression of aPKCζ, aPKCλ, or both are dispensable for primitive and adult HSC fate determination in steady-state and stress hematopoiesis, contrary to the hypothesis of a unique, evolutionary conserved aPKCζ/λ-directed cell polarity signaling mechanism in mammalian HSC fate determination.