Conformational Changes in an Epitope Localized to the NH2-terminal Region of Protein C

Murine monoclonal antibodies, developed following immunization with human protein C, were characterized for their ability tboin d antigen in thpe resence of either CaClz or excess EDTA. Three stablec lones were obtained which produced antiboditehsa t bound to protein C only itnh e presence of EDTA. Allt hree antibodies bound to the light choafi np rotein C on immunoblots and also bound to the homologous proteins factor X and prothrombin in solid-phase radioimmunoassays. One antibody, 7D7B10 was purified and studied further. The binding of 7D7B10 to human protein C was characterized bya KOo f 1.4 nM. In competition studies, it was found that the relative affinityo f the antibody for protein C was 20-40-fold higher than for prothrombin, fragment 1 of prothrombin, or factor X. In contrast, 7D7B10 was unable to bind to factor 1X or bovine protein C. The effect of varying Ca2+ concentration on the interaction of the antibody with protein C was complex. Low concentrations of Ca2+ enhanced the formation of the protein C-antibody complex with half-maximal effect occurring at approximately6 0 PM metal ion. However, higher concentrations of Ca2+ completely inhibited 7D7B10 binding to protein C with a K o .o~f 1.1 mM. Furthermore, millimolar concentrations of Mn2+, Ba2+, or Mg2+ also completely abolished antibody binding to protein C. The location of the epitope was delineatedby immunoblotting and peptide studies andf ound to be present in the NHz-termin1a5l residues of protein C. Although residues corresponding to positions 10-13 of human protein C wernee cessary for maximal binding of the antibody, they were not sufficient. No evidence could be found for involvement of the epitope in metal binding per se. Therefore, the effect of Ca2+ on antibody binding is thought to be due to metal-dependent conformational changes in protein C. It seems likelyth at Ca2+ occupatioonf a high affinity site, shown by others to be located in the epidermal growth factor-like domain, causes a conformational change in the NHz-terminarel gion of protein C which is favorable for antibody interaction, whereas Ca2+ binding to thleo w affinity site($, known to be present in the y-carboxyglutamic acid domain, causes an unfavorable conformational change

Symptom trajectories during chemotherapy in outpatients with lung cancer colorectal cancer, or lymphoma.

Purpose Pain, depression, distress, fatigue, and sleep disturbance are common symptoms in oncology patients, but little data are available that examine the trajectories of these symptoms during chemotherapy (CTX). The purposes of this study were to examine the trajectories of these symptoms during the first six cycles of CTX and to determine whether individual characteristics predicted the trajectories of these symptoms. Methods Oncology outpatients (n = 118) with newly diagnosed lung cancer, colorectal cancer, or lymphoma rated symptoms using an electronic patient care monitor system. Pain, fatigue, and sleep disturbance were rated on 0–10 numeric rating scales; depression and distress were evaluated using scales converted to normalized T scores. Latent growth curve analyses (LGCA) examined for intra- and inter-individual differences in the trajectories of these five symptoms during the six cycles of CTX. Results Symptoms were present at the initiation of CTX (p < 0.0001) for all symptoms (p < 0.05). Distress (p = 0.03) and pain (p = 0.02) intensity decreased significantly over the six cycles of CTX. Advanced disease and a higher number of comorbidities predicted higher fatigue at baseline (p = 0.02 and 0.01 respectively). A diagnosis of lung cancer predicted an increasing intensity of fatigue during CTX (p = 0.04). Concurrent radiation therapy predicted more intense pain over time (p = 0.03). Conclusions While symptom trajectories were highly variable in patients undergoing initial CTX, the majority of the symptom intensity scores decreased over time. However, patients with lung cancer, those with a higher number of comorbidities, and those with advanced disease experienced more intense fatigue and sleep disturbance over time

Genetic counseling communication with an African American BRCA1 kindred.

We studied communication in genetic counseling sessions conducted with an African American, Breast Cancer 1, Early Onset (BRCA1) kindred in the USA. The Roter Interaction Analysis System (RIAS) was used to code and compare two sessions of 46 participants (26 females and 20 males) before and after they underwent genetic testing. Three certified genetic counselors and one medical geneticist conducted the sessions. When compared to pre-test communication, most of the providers’ post-test communication was devoted to the provision of biomedical information (including screening recommendations) with fewer questions and psychosocial statements. Clients contributed a similar proportion to the total session dialogue in pre- and post-test sessions (40%). A larger proportion of their post-test session was devoted to indicating receptiveness to provider information than in the pre-test session. We found when providers were informing clients that they were BRCA1 mutation carriers, they provided more biomedical and psychosocial information and asked more psychosocial questions than when talking with non-carriers. This study provides the first description of genetic counseling communication for pre- and post-test BRCA1 sessions with African American individuals

Effectiveness of an intervention for colic.

Summary: An intervention for infant irritability or colic was evaluated in a randomized clinical trial. A total of 121 full-term irritable infants (2 to 6 weeks old) were randomized to routine care or the home-based intervention program. A third group (n=43) of irritable infants were entered into a post-test-only group. Following the 4-week intervention, the treatment group infants cried 1.7 hours less per day than the infants in the control group (p=0.02). The findings support the emerging view of infant colic as a behavioral pattern that is responsive to environmental modification and structured cue-based care

Test of a nursing intervention to promoting adjustment to fibromyalgia.

Purpose: This was a test to detect whether a 4-week cognitive behavioral nursing program was effective in increasing adjustment to fibromyalgia (FM) and if the treatment effect would last over time. Design: This was a control and treatment group experimental longitudinal study with outcome measures obtained at pretest and every 3 months for 1 year. Sample: A sample of 71 subjects continued their participation throughout the first year of the study. Findings: Treatment subjects had improved posttreatment adjustment and symptom severity compared to control subjects. When subjects with high pretest psychosocial distress (n = 5) were removed from the analysis, these findings were statistically significant. Implications for Nursing Practice: The article can provide direction for developing new comprehensive nursing intervention for patients seen with orthopaedic problems. The intervention schedule may help nurses expand their use of interventions for FM patients. Orthopaedic nurses are especially suited for this challenge

Pilot Testing a Web-Based System for the Assessment and Management of Chemotherapy-Induced Peripheral Neuropathy

Because numerous barriers hinder the assessment and management of chemotherapy-induced peripheral neuropathy in clinical practice, the Carevive Care Planning System, a novel Web-based platform, was developed to address these barriers. It provides patients an opportunity to report their symptoms before their clinic visit and generates customizable care plans composed of evidence-based management strategies. The purpose of this study was to evaluate patient and provider perspectives of feasibility, usability, acceptability, and satisfaction with the Carevive platform. We used a single-arm, pretest/posttest, prospective design and recruited 25 women with breast cancer who were receiving neurotoxic chemotherapy and six advanced practice providers from an academic hospital. At three consecutive clinical visits, patients reported their neuropathy symptoms on a tablet via the Carevive system. The Diffusion of Innovations Theory served as an overarching evaluation framework. The Carevive platform was feasible to use. However, patients had higher ratings of usability, acceptability, and satisfaction with the platform than did the providers, who disliked the amount of time required to use the platform and had difficulty logging into Carevive. If issues regarding provider dissatisfaction can be addressed, the Carevive platform may aid in the screening of neuropathy symptoms and facilitate the use of evidence-based management strategies

SAS macros for testing statistical mediation in data with binary mediators or outcomes.

Background: Statistical mediation is an important tool in behavioral health sciences, but it has been confined primarily to continuous variables. As prevention studies become increasingly common, more often the mediator or outcome is binary. Recent work by D. P. MacKinnon and J. H. Dwyer (1993) has explicated the steps necessary to estimate models for mediation when the mediator or the outcome is binary. Objective: To report the release of a set of SAS macros used to implement the statistical analyses required to analyze data with binary and continuous-level data. Approach: A brief introduction to the methodology of mediation analysis in the presence of a binary outcome, mediator, or both is provided. The macros are tested on a sample of 84 participants who were experiencing pain. It is hypothesized that the relationship between pain and fatigue is mediated by sleep disturbance. Results: The relationship between pain and fatigue was mediated by the presence of sleep disturbances, and the amount of mediation was 23.34%. Discussion: The SAS macros are available for download without charge from the second author's Web site. Instructions are provided in an included technical manual

Social cognitive factors associated with mother-adolescent communication about sex.

To better understand why some mothers talk to their children about sex and others do not, we examined the role of two social cognitive variables- self-efficacy and outcome expectancies- in explaining sex-based communication. The present study was part of a larger study to test the efficacy of two HIV prevention programs for mothers and their adolescents. Mothers and their adolescents were recruited from a large community organization that serves youth who live in disadvantaged circumstances. The sample for the present study included 486 mothers who averaged 38.4 years of age (SD = 6.73). The majority were African American (97.7%), not married (66.7%), and had a high school degree (89.5%). Their adolescents ranged in age from 11 through 14 years of age and most were male (61.3%). The results of the analysis revealed that mothers who expressed higher levels of self-efficacy and more favorable outcomes associated with talking to their children about sex were more likely to do so. In a regression analysis, we learned that the mother’s degree of efficacy beliefs, along with her expected outcomes associated with talking about sex, the importance of religious beliefs to her, and the age and sex of her adolescents were important factors associated with talking with them about sex

Patient-centered communication during oncology follow-up visits for breast cancer survivors: content and temporal structure

Purpose/Objectives: To understand the content and temporal structure of survivor-provider communication during breast cancer survivor follow-up visits. Design: Descriptive correlational. Setting: Private outpatient oncology practice. Sample: 55 breast cancer survivors; 6 oncology providers. Methods: A secondary analysis of audio recordings of survivor follow-up visits. Main Research Variables: Survivors: demographics, uncertainty, mood, length of survival, years receiving care from providers, survivor expectations. Providers: demographics, medical uncertainty, specialty (physician, nurse practitioner, or physician assistant). Outcomes: time spent in patient-centered communication, perception of patient-centeredness. Findings: Most visit time (55%) was spent waiting. Of the remaining 45%, silence represented the most time spent with providers, followed by symptom conversations. More specific survivor discussion plans predicted more time spent discussing symptoms and in reassurance interactions. More specificity of visit purpose predicted survivor perceptions of less patient-centeredness; however, more time in contextual conversations predicted a greater perception of patient-centeredness. Provider factors were not associated with time spent in patient-centered communication or survivor perceptions of patient-centeredness. All dimensions of patient-centered communication occurred during each visit section (before, during, and after the physical examination). Conclusions: Discussing symptoms and concerns with providers offers reassurance about cancer recurrence. When visit expectations are very high, achieving a survivor perception of patient-centered communication may be difficult. However, time spent understanding a survivor within the context of her life can enhance survivor perceptions of patient-centeredness. Implications for Nursing: Providers must be sensitive to concerns that are presented throughout a visit. When visit time is short, a second appointment may be necessary to address survivor concerns

Determinants of functional performance in long-term survivors of allogeneic hematopoietic stem cell transplantation with chronic graft-versus-host disease (cGVHD)

This study examined factors accounting for functional performance limitations in 100 long-term survivors of allogeneic hematopoietic stem cell transplantation with chronic graft-versus-host disease (cGVHD). Functional performance, measured by the SF-36 physical component summary score, was substantially lower (mean = 36.8 ± 10.7) than the US population norm of 50 (P<0.001). The most severe decrements were in physical function (mean = 38.8 ± 10.9) and physical role function (mean = 37.88 ± 11.88); 68% of respondents exceeded the five-point threshold of minimum clinically important difference below the norm on these subscales. Controlling for age and gender, six variables explained 56% of the variance in functional performance: time since cGVHD diagnosis, cGVHD severity, intensity of immunosuppression, comorbidity, functional capacity (distance walked in 2 min, grip strength, and range of motion), and cGVHD symptom bother (F=11.26; P<0.001).Significant independent predictors of impaired performance were intensive systemic immunosuppression, reduced capacity for ambulation, and greater cGVHD symptom bother (P<0.05). Symptom bother had a direct effect on functional performance, as well as an indirect effect partially mediated by functional capacity (Sobel test, P = 0.004). Results suggest two possible mechanisms underlying impaired functional performance in survivors with cGVHD and underscore the importance of testing interventions to enhance functional capacity and reduce symptom bother. Bone Marrow Transplantation (2010) 45, 762–769; doi:10.1038/bmt.2009.238; published online 28 September 200