CHARACTERIZATION OF HIGH MOBILITY GROUP AND HISTONE H1 PROTEIN LEVELS AND SYNTHESIS DURING SPERMATOGENESIS IN THE RAT

In order to propose a role for internucleosomal high mobility group proteins (HMGs), and HI histone variants study of their levels and synthesis in a system of development and differentiation--rat spermatogenesis--was undertaken. HMG1, 2, 14, and 17 were isolated from rat testes and found to be very similar to calf thymus HMGs. Testis levels of HMGs, relative to DNA, were equivalent to other rat tissues for HMG1 (13 ug/mg DNA), HMG14 (2 ug/mg DNA), and HMG17 (5 ug/mg DNA). HMG2 levels were different among rat tissues, with three groups observed: (1) nonproliferating tissues (1-5 ug/mg DNA); (2) proliferating tissues (8-13 ug/mg DNA); and (3) the testis (32 ug/mg DNA). Other species (toad, opposum, mouse, dog, and monkey) showed the same testis-specific increase of HMG2. Populations of purified testis cell types were separated by centrifugal elutriation and density gradient centrifugation from adult and immature rat testes. Pachytene spermatocytes and early spermatids (56 and 47 ug/mg DNA, respectively) caused the testis-specific increase of HMG2 levels. Cell types preceding pachytenes (types A and B spermatogonia, mixtures of spermatogonia and early primary spermatocytes, and early pachytenes contained HMG2 levels similar to proliferating tissues (12 ug/mg DNA). Late spermatids did not contain HMGs. Somatic Sertoli and Leydig cells (2 ug/mg DNA) exhibited HMG2 levels similar to nonproliferating tissues. HMGs synthesized in spermatogonia and spermatocytes had similar specific activities, but early spermatids did not synthesize HMGs. Germ cells also contained an HMG2 species (on acid-urea gels) not found in somatic tissues. Other investigators have shown that HMGs may be associated with transcriptional or replicative processes. Thus, it is proposed that HMG2 plays a role in modulatable gene expression, while HMG1 is associated with housekeeping functions.^ HI histone variants were also studied throughout spermatogenesis. The minor somatic variant, HIa, is the predominant variant in spermatogonia and early primary spermatocytes. In early pachytenes, the testis-specific variant, HIt, is first synthesized and appears, largely replacing somatic variants HIbcd and e by late pachytene stage. Early spermatids contain the same HI composition as pachytenes, but do not synthesize HI histones. HI('0) is present in low amounts in all germ cells. These results suggest that expression of HI variants is developmentally controlled.^

Development and validation of the Neuro Symptom Inventory in the primary brain tumor patient population

Symptoms has been shown to predict quality of life, treatment course and survival in solid tumor patients. Currently, no instrument exists that measures both cancer-related symptoms and the neurologic symptoms that are unique to persons with primary brain tumors (PBT). The aim of this study was to develop and validate an instrument to measure symptoms in patients who have PBT. A conceptual analysis of symptoms and symptom theories led to defining the symptoms experience as the perception of the frequency, intensity, distress, and meaning that occurs as symptoms are produced, perceived, and expressed. The M.D. Anderson Symptom Inventory (MDASI) measures both symptoms and how they interfere with daily functioning in patients with cancer, which is similar to the situational meaning defined in the analysis. A list of symptoms pertinent to the PBT population was added to the core MDASI and reviewed by a group of experts for validity. As a result, 18 items were added to the core MDASI (the MDASI-BT) for the next phase of instrument development, establishing validity and reliability through a descriptive, cross-sectional approach with PBT patients. Data were collected with a patient completed demographic data sheet, an investigator completed clinician checklist, and the MDASI-BT. Analysis evaluated the reliability and validity of the MDASI-BT in PBT patients. Data were obtained from 201 patients. The number of items was reduced to 22 by evaluation of symptom severity as well as cluster analysis. Regression analysis showed more than half (56%) of the variability in symptom severity was explained by the brain tumor module items. Factor analysis confirmed that the 22 item MDASI-BT measured six underlying constructs: (a) affective; (b) cognitive; (c) focal neurologic deficits; (d) constitutional symptoms; (e) treatment-related symptoms; and (f) gastrointestinal symptoms. The MDASI-BT was sensitive to disease severity and if the patient was hospitalized. The MDASI-BT is the first instrument to measure symptoms in PBT patients that has demonstrated reliability and validity. It is the first step in a program of research to evaluate the occurrence of symptoms and plan and evaluate interventions for PBT patients. ^

Determinants of patients' expectations about total knee arthroplasty outcomes

Knee osteoarthritis (OA) is the most prevalent form of arthritis in the US, affecting approximately 37% of adults. Approximately 300,000 total knee arthroplasty (TKA) procedures take place in the United States each year. Total knee arthroplasty is an elective procedure available to patients as an irreversible treatment after failure of previous medical treatments. Some patients sacrifice quality of life and endure many years of pain before making the decision to undergo total knee replacement. In making their decision, it is therefore imperative for patients to understand the procedure, risks and surgical outcomes to create realistic expectations and increase outcome satisfaction. ^ From 2004-2007, 236 OA patients who underwent TKA participated in the PEAKS (Patient Expectations About Knee Surgery) study, an observational longitudinal cohort study, completed baseline and 6 month follow-up questionnaires after the surgery. We performed a secondary data analysis of the PEAKS study to: (1) determine the specific presurgical patient characteristics associated with patients’ presurgical expectations of time to functional recovery; and (2) determine the association between presurgical expectations of time to functional recovery and postsurgical patient capabilities (6 months after TKA). We utilized the WOMAC to measure knee pain and function, the SF-36 to measure health-related quality of life, and the DASS and MOS-SSS to measure psychosocial quality of life variables. Expectation and capability measures were generated from panel of experts. A list of 10 activities was used for this analysis to measure functional expectations and postoperative functional capabilities. ^ The final cohort consisted of 236 individuals, was predominately White with 154 women and 82 men. The mean age was 65 years. Patients were optimistic about their time to functional recovery. Expectation time of being able to perform the list activities per patient had a median of less than 3 months. Patients who expected to be able to perform the functional activities by 3 months had better knee function, less pain and better overall health-related quality of life. Despite expectation differences, all patients showed significant improvement 6 months after surgery. Participant expectation of time to functional recovery was not an independent predictor of capability to perform functional activities at 6 months. Better presurgical patient characteristics were, however, associated with a higher likelihood of being able to perform all activities at 6 months. ^ This study gave us initial insight on the relationship between presurgical patient characteristics and their expectations of functional recovery after total knee replacement. Future studies clarifying the relationship between patient presurgical characteristics and postsurgical functional capabilities are needed.^

Use of a modified delphi process for establishing occupational exposure limits in support of health surveillance for space travelers

On-orbit exposures can come from numerous factors related to the space environment as evidenced by almost 50 years of environmental samples collected for water analysis, air analysis, radiation analysis, and physiologic parameters. For astronauts and spaceflight participants the occupational exposures can be very different from those experienced by workers performing similar tasks in workplaces on Earth, because the duration of the exposure could be continuous for very long orbital, and eventually interplanetary, missions. The establishment of long-term exposure standards is vital to controlling the quality of the spacecraft environment over long periods. NASA often needs to update and revise its prior exposure standards (Spacecrafts Maximum Allowable Concentrations (SMACs)). Traditional standards-setting processes are often lengthy, so a more rapid method to review and establish standards would be a substantial advancement in this area. This project investigates use of the Delphi method for this purpose. ^ In order to achieve the objectives of this study a modified Delphi methodology was tested in three trials executed by doctoral students and a panel of experts in disciplines related to occupational safety and health. During each test/trial modifications were made to the methodology. Prior to submission of the Delphi Questionnaire to the panel of experts a pilot study/trial was conducted using five doctoral students with the goals of testing and adjusting the Delphi questionnaire to improve comprehension, work out any procedural issues and evaluate the effectiveness of the questionnaire in drawing the desired responses. The remainder of the study consisted of two trials of the Modified Delphi process using 6 chemicals that currently have the potential of causing occupational exposures to NASA astronauts or spaceflight participants. To assist in setting Occupational Exposure Limits (OEL), the expert panel was established consisting of experts from academia, government and industry. Evidence was collected and used to create close-ended questionnaires which were submitted to the Delphi panel of experts for the establishment of OEL values for three chemicals from the list of six originally selected (trial 1). Once the first Delphi trial was completed, adjustments were made to the Delphi questionnaires and the process above was repeated with the remaining 3 chemicals (trial 2). ^ Results indicate that experience in occupational safety and health and with OEL methodologies can have a positive effect in minimizing the time experts take in completing this process. Based on the results of the questionnaires and comparison of the results with the SMAC already established by NASA, we conclude that use of the Delphi methodology is appropriate for use in the decision-making process for the selection of OELs.^