Evolution of the long terminal repeat and accessory genes of feline immunodeficiency virus genomes from naturally infected cougars

FIVpco is a member of the feline immunodeficiency virus family that is endemic in wild cougar populations. Virus replication is robust in FIVpco-infected cougars but there are no consequences of infection to cougar survival, fecundity or susceptibility to other infections. Unlike pathogenic lentiviruses, there is no evidence for positive selection on FIVpco gag or env. To better understand how lentivirus genomes evolve in natural infections, we evaluated the regulatory region and accessory genes from fourteen full-length FIVpco genomes, which represent the FIVpco diversity in the Northern Rockies Ecosystem. Our data demonstrate that the two sister groups of FIVpco have each acquired binding sites for different interferon response factors (IRF). The most variable gene in the FIVpco genome encodes OrfA, although there is no indication that it, or any other accessory gene, is under positive selection. There is a single-splice acceptor site for vif expression, which is conserved among all FIVpco genomes. However, there are several putative means to express rev and orfA, which differ between the phylogenetic groups of FIVpco. Our comparative study on divergent FIVpco genomes indicates that variation in potential gene regulation mechanisms, not changes in structural proteins, characterize the evolution of FIVpco in natural infections.     

Three-dimensional anatomy of the cancellous structures within the proximal femur from computed tomography data

Quantitative computed tomography was used to investigate the three-dimensional architecture and the density distribution of the cancellous structures of the proximal femur. We examined 10 femora from the cadavera of 10 individuals, 47-83 years old at the time of death. Three anatomic elements could be distinguished: the epiphysis, the epiphyseal scar, and the metaphysis. Although these elements constitute a functional unit, their individual cancellous patterns revealed significant structural differences. The epiphyseal segment had a more reticulate cancellous appearance, whereas the metaphysis demonstrated a more longitudinally oriented trabecular distribution. The three-dimensional reconstruction of the densest epiphyseal trabecular groups showed two different patterns: a dumbbell type (found in eight bones) and a hemispheric type (found in two bones). The epiphyseal scar was a clearly recognizable high-density structure found in all 10 bones. The epipyseal scar-diaphysis angle was 13–26° higher than the center column-diaphysis angle. The scar appeared as a tray supporting the epiphyseal cancellous structures, supported itself by the metaphyseal intersection of the main compressive and the arcuate trabecular systems. This intersection always occurred in a relatively small band-shaped zone under the central third of the epiphyseal scar. These three discrete anatomical segments within the proximal femur may reflect developmental and functional adaptations determined by joint incongruity or eccentric muscular activity. The present data will serve as a reference for future studies in which the cancellous patterns are used to help with the early diagnosis of states of disease.     

Screening clients for an augmentative and alternative communication clinic: a multitrait-multimethod approach

The aim of Augmentative and Alternative Communication (AAC) services is to support, enhance, or provide alternative methods of communication for individuals who are not independent verbal communicators. However, relatively little evaluative research has been conducted with adult AAC users. The establishment of Freeport Hospital's AAC Clinic for adults included the development of questionnaires to gather information for the selection and provision of services for its clients. The present study addresses the issue reliability and validity of three novel measures contained within the AAC Clinic's Background Information Questionnaire using a multitrait-multimethod (MTMM) design. Results from this evaluation are discussed in terms of clinical application and policy development.     

Radiographic comparison of cementing techniques in total hip arthroplasty

Using a single prosthetic design, the authors conducted a radiographic comparison of the results of changes in cementing techniques in 58 total hip arthroplasties with respect to the initial postoperative and equivalent follow-up radiographs. The study period, 1975-1982, spanned the advent of cement restrictors, canal preparation, and pressurization techniques. In matched patients, the use of modern cementing techniques and canal preparation led to a significant improvement in the initial postoperative radiographic appearance and subsequent loosening rate of the femoral component, suggesting that these techniques may change the expected rate of late femoral component loosening, based on previous studies done with prepressurization cementing techniques.     

Self-reported physical activity among South Carolina adults trying to maintain or lose weight

OBJECTIVES: The obesity epidemic is related to widespread physical inactivity in the United States. This study determined the proportion of South Carolinians trying to maintain or lose weight and within that subpopulation, the number who practiced a restricted diet and engaged in physical activity. METHODS: Data from the 2002 South Carolina Behavioral Risk Factor Surveillance System survey were used to classify adults who were trying to maintain weight or lose weight. Self-reported prevalence of restricted diet and participation in physical activity were investigated. Of those who reported weight control practices, levels of physical activity were analyzed to determine if those trying to maintain weight or lose weight were meeting the national guidelines for moderate or vigorous physical activity. RESULTS: More than 70% of South Carolina adults reported trying to control their weight and the majority reported using physical activity for weight control. Though the majority reported use of restricted diet and physical activity, more than one-half of those individuals did not meet the minimum standards for physical activity designed for heart health. CONCLUSIONS: Although most adults who are trying to maintain or lose weight are participating in physical activity, public health efforts need to focus on encouraging these adults to increase their levels of physical activity to meet the minimum standards for health benefits. Health care providers have an opportunity to educate and encourage patients about the recommended levels of physical activity to obtain maximum health benefits.     

Methyldopa inhibition of suppressor-lymphocyte function: a proposed cause of autoimmune hemolytic anemia

To test the hypothesis that methyldopa induces red-cell autoantibodies by inhibiting the activity of suppressor lymphocytes, we studied its effect on several immune functions. Methyldopa inhibited T-lymphocyte suppression of IgG production by peripheral-blood mononuclear cells stimulated by poke-weed mitogens. This effect occurred in isolated T cells incubated with methyldopa and in T cells obtained from patients taking methyldopa. In addition, the drug caused a 30 to 80 per cent reduction in the proliferative response of peripheral-blood mononuclear cells to mitogens in vitro, and this reduction primarily involved the activation of T lymphocytes. Methyldopa also caused a persistent elevation of intracellular lymphocyte cyclic AMP in vitro and in vivo. We postulate that methyldopa alters the immune system by causing a persistent increase in lymphocyte cyclic AMP, which inhibits suppressor T-cell function. These effects may lead to unregulated autoantibody production by B cells in some patients.     

Method for Assigning Priority Levels in Acute Care (MAPLe-AC) predicts outcomes of acute hospital care of older persons - a cross-national validation

Background

Although numerous risk factors for adverse outcomes for older persons after an acute hospital stay have been identified, a decision making tool combining all available information in a clinically meaningful way would be helpful for daily hospital practice. The purpose of this study was to evaluate the ability of the Method for Assigning Priority Levels for Acute Care (MAPLe-AC) to predict adverse outcomes in acute care for older people and to assess its usability as a decision making tool for discharge planning.

Methods

Data from a prospective multicenter study in five Nordic acute care hospitals with information from admission to a one year follow-up of older acute care patients were compared with a prospective study of acute care patients from admission to discharge in eight hospitals in Canada. The interRAI Acute Care assessment instrument (v1.1) was used for data collection. Data were collected during the first 24 hours in hospital, including pre-morbid and admission information, and at day 7 or at discharge, whichever came first. Based on this information a crosswalk was developed from the original MAPLe algorithm for home care settings to acute care (MAPLe-AC). The sample included persons 75 years or older who were admitted to acute internal medical services in one hospital in each of the five Nordic countries (n = 763) or to acute hospital care either internal medical or combined medical-surgical services in eight hospitals in Ontario, Canada (n = 393). The outcome measures considered were discharge to home, discharge to institution or death. Outcomes in a 1-year follow-up in the Nordic hospitals were: living at home, living in an institution or death, and survival. Logistic regression with ROC curves and Cox regression analyses were used in the analyses.

Results

Low and mild priority levels of MAPLe-AC predicted discharge home and high and very high priority levels predicted adverse outcome at discharge both in the Nordic and Canadian data sets, and one-year outcomes in the Nordic data set. The predictive accuracy (AUC's) of MAPLe-AC's was higher for discharge outcome than one year outcome, and for discharge home in Canadian hospitals but for adverse outcome in Nordic hospitals. High and very high priority levels in MAPLe-AC were also predictive of days to death adjusted for diagnoses in survival models.

Conclusion

MAPLe-AC is a valid algorithm based on risk factors that predict outcomes of acute hospital care. It could be a helpful tool for early discharge planning although further testing for active use in clinical practice is still needed.     

Diphenylpyridylethanamine (DPPE) derivatives as cholesteryl ester transfer protein (CETP) inhibitors

A series of diphenylpyridylethanamine (DPPE) derivatives was identified exhibiting potent CETP inhibition. Replacing the labile ester functionality in the initial lead 7 generated a series of amides and ureas. Further optimization of the DPPE series for potency resulted in the discovery of cyclopentylurea 15d, which demonstrated a reduction in cholesterol ester transfer activity (48% of predose level) in hCETP/apoB-100 dual transgenic mice. The PK profile of 15d was suboptimal, and further optimization of the N-terminus resulted in the discovery of amide 20 with an improved PK profile and robust efficacy in transgenic hCETP/apoB-100 mice and in hamsters. Compound 20 demonstrated no significant changes in either mean arterial blood pressure or heart rate in telemeterized rats despite sustained high exposures.