Amino acid substitutions in the structural or nonstructural proteins of a vaccine strain of equine arteritis virus are associated with its attenuation

Comparative sequence analysis of a series of strains of equine arteritis virus (EAV) of defined virulence for horses, ranging from the horse-adapted virulent Bucyrus (VB) strain to a fully attenuated vaccine strain derived from it, identified 13 amino acid substitutions associated with attenuation. These include 4 substitutions in the replicase proteins and 9 in the structural proteins. Using reverse genetic techniques, these amino acid substitutions were introduced into a virulent infectious cDNA clone pEAVrVBS derived from the VB strain of EAV. Inoculation of horses with the recombinant viruses clearly demonstrated that changes in either the replicase (nsp1, nsp2 and nsp7) or structural proteins (GP2, GP4, GP5 and M) resulted in attenuation of the virulent VB strain. The recombinant virus with substitutions in the structural proteins was more attenuated than the recombinant virus with substitutions only in the replicase proteins.     

Leptin-induced decrease in food intake in chickens

The effect of intracerebroventricular (i.c.v.) injection of leptin was investigated using broiler and Single Comb White Leghorn (SCWL)-type chickens. These represent relatively fast- and slow-growing birds, respectively. The i.c.v. injection of leptin decreased food intake in both broilers and Leghorns in a dose-dependent manner. The most efficacious dose appeared to be 10 microg in both types of chickens. Water intake was generally not affected by leptin, indicating that this effect was not due to general malaise. It appears that leptin can act within the central nervous sytstem of birds to decrease food intake.     

Assessing the readiness of black churches to engage in health disparities research

We assessed church readiness to engage in health disparities research using a newly developed instrument, examined the correlates of readiness, and described strategies that churches used to promote health. We pilot tested the instrument with churches in a church-academic partnership (n = 12). We determined level of readiness to engage in research and assessed correlates of readiness. We also conducted interviews with participating pastors to explore strategies they had in place to support research engagement. Churches scored fairly high in readiness (average of 4.04 out of 5). Churches with a pastor who promoted the importance of good nutrition in a sermon or had a budget for health-related activities had significantly higher readiness scores than churches without such practices. Having a tool to evaluate church readiness to engage in research will inform targeted technical assistance and research projects that will strengthen church-academic partnerships and improve capacity to address health disparities.     

The diagnosis of dementia: demographic characteristics

The demographic characteristics of 242 clinic outpatients evaluated for dementia were examined. Each individual received a comprehensive assessment of medical status, psychological functioning, and social abilities. Diagnoses were arrived at by consensus, and appropriate treatment plans and follow-up recommendations were generated, with comprehensive feedback provided to family members and other caregivers. The results of this study help increase our knowledge of the characteristics of individuals with Alzheimer's disease, multi-infarct dementia, or other related disorders.     

Effect of compressive follower preload on the flexion-extension response of the human lumbar spine.

Traditional experimental methods are unable to study the kinematics of whole lumbar spine specimens under physiologic compressive preloads because the spine without active musculature buckles under just 120 N of vertical load. However, the lumbar spine can support a compressive load of physiologic magnitude (up to 1200 N) without collapsing if the load is applied along a follower load path. This study tested the hypothesis that the load-displacement response of the lumbar spine in flexion-extension is affected by the magnitude of the follower preload and the follower preload path. Twenty-one fresh human cadaveric lumbar spines were tested in flexion-extension under increasing compressive follower preload applied along two distinctly different optimized preload paths. The first (neutral) preload path was considered optimum if the specimen underwent the least angular change in its lordosis when the full range of preload (0-1200 N) was applied in its neutral posture. The second (flexed) preload path was optimized for an intermediate specimen posture between neutral and full flexion. A twofold increase in flexion stiffness occurred around the neutral posture as the preload was increased from 0 to 1200 N. The preload magnitude (400 N and larger) significantly affected the range of motion (ROM), with a 25% decrease at 1200 N preload applied along the neutral path. When the preload was applied along a path optimized for an intermediate forward-flexed posture, only a 15% decrease in ROM occurred at 1200 N. The results demonstrate that whole lumbar spine specimens can be subjected to compressive follower preloads of in vivo magnitudes while allowing physiologic mobility under flexion-extension moments. The optimized follower preload provides a method to simulate the resultant vector of the muscles that allow the spine to support physiologic compressive loads induced during flexion-extension activities.     

Incidence, etiology, and risk factors for fever following acute spinal cord injury

OBJECTIVE: To identify the incidence, etiology, and risk factors for fevers in individuals with traumatic spinal cord injury (SCI). DESIGN: A retrospective review of the medical records of consecutive adult traumatic SCI patients over a 2-year period was performed. SETTING: The study was performed at a tertiary care, Level I trauma center. PARTICIPANTS: Consecutive adult traumatic SCI admissions to acute care (n = 48) and rehabilitation (n = 40) were included in the study. MAIN OUTCOME MEASURES: Incidence, etiology, mean maximum temperature elevation, and duration of fevers (temperature >99.9 F) were measured. RESULTS: The incidence of fever was 60.4% and 50% (acute care and rehabilitation, respectively). Total number of fevers was 58 and 66, acute and rehabilitation, respectively. Respiratory and urinary tract were the most common identifiable fever etiologies. Unidentified fever etiologies were numerous in both the acute and rehabilitation groups, representing 66% and 56% of cases, respectively. Significant differences (P < 0.05) were found between identified vs unidentified fever etiology groups for mean maximal temperature (102.5 degrees F vs 101.1 degrees F on acute and 101.5 degrees F vs 100.7 degrees F on rehabilitation), duration of fever (10.3 days vs 2.2 on acute and 2.8 days vs 1.3 on rehabilitation), fevers above 101.4 degrees F (75% vs 29% on acute and 40% vs 8% on rehabilitation), cause of injury (gunshot wound on acute care) and completeness of injury (American Spinal Injury Association classification A on rehabilitation). CONCLUSIONS: This study suggests that fevers occur commonly in patients with SCI, with respiratory and genitourinary system etiologies most commonly identified. Unidentified etiologies were common and were associated with lower temperature elevation and shorter fever duration. Injury etiology and completeness of injury may comprise additional risk factors. These factors should be taken into account when initiating cost-efficient fever workup in individuals with SCI.     

Platelet-derived growth factor in vivo: levels, activity, and rate of clearance

Platelet-derived growth factor (PDGF) is a potent mitogen for many cultured connective tissue cells. It is present in concentrated form within the platelet alpha-granules and is believed to be released during platelet degranulation at sites of vascular injury. We have used a sensitive radioreceptor assay to measure PDGF levels in whole blood serum from normal humans [17.5 +/- 3.1 (SD) ng/mL] and baboons (2.7 +/- 1.2 ng/mL). PDGF was not detected in plasma from either species. In addition, plasma was found to substantially reduce the ability of added purified PDGF to bind to the cell surface PDGF receptor on cultured cells, suggesting that plasma may contain a PDGF-binding protein that would serve to inactivate PDGF released into plasma. Calculations of PDGF concentrations in serum have been corrected for the effects of the binding protein. 125I-PDGF injected intravenously into normal baboons was cleared rapidly from the plasma (t1/2 = two minutes). The rapid clearance of 125I-PDGF did not result from iodination damage, as purified unlabeled PDGF was cleared with comparable kinetics. The rapid clearance of purified and iodinated PDGF did not result from changes in PDGF structure during purification or from removal of PDGF-associated proteins during purification, as PDGF present in freeze-thaw lysates of fresh platelets was cleared equally rapidly. We conclude that release of PDGF at sites of vascular injury would greatly increase the local concentration of PDGF and that PDGF not localized to the site of injury would be rapidly cleared from the circulation.     

Male breast cancer: management and follow-up recommendations

National Comprehensive Cancer Network (NCCN) guidelines for female breast cancer treatment and surveillance are well established, but similar guidelines on male breast cancers are less recognized. As an NCCN institution, our objective was to examine practice patterns and follow-up for male breast cancer compared to established guidelines for female patients. After Institutional Review Board approval, a prospective breast database from 1990 to 2009 was queried for male patients. Medical records were examined for clinico-pathological factors and follow-up. The 5-year survival rates with 95% confidence intervals were estimated using Kaplan-Meier method and Greenwood formula. Of the 19,084 patients in the database, 73 (0.4%) were male patients; 62 had complete data. One patient had bilateral synchronous breast cancer. The median age was 68.8 years (range 29-85 years). The mean/median invasive tumor size was 2.2/1.6 cm (range 0.0-10.0 cm). All cases had mastectomy (29 with axillary node dissection, 23 with sentinel lymph node biopsy only, 11 with sentinel node biopsy followed by completion axillary dissection). Lymph node involvement occurred in 25/63 (39.7%). Based on NCCN guidelines, chemotherapy, hormonal therapy, and radiation are indicated in 34 cases, 62 cases, and 14 cases, respectively. Only 20/34 (59%) received chemotherapy, 51/62 (82%) received hormonal therapy, and 10/14 (71%) received post-mastectomy radiation. Median follow-up was 26.2 months (range: 1.6-230.9 months). The 5-year survival estimates for node positive and negative diseases were 68.5% and 87.5%, respectively (p = 0.3). Despite the rarity of male breast cancer, treatment options based on current female breast tumors produce comparable results to female breast cancer. Increased awareness and a national registry for patients could help improve outcomes and tailor treatment recommendations to the male variant.