Social Networks among Elderly Women: Implications for Health Education Practice

The general aim of the present study was to examine and help clarify the properties of the distinctions between social networks and social support, their relationship to health status, and their impli cations for health education practice. More specifically, a secondary data analysis was conducted with 130 white women, community resi dents, between the ages of 60 and 68, which examined the relationship between psychological well-being and social network characteristics. These characteristics are categorized along three broad dimensions: structure—links in the overall network (size and density); interaction— nature of the linkages themselves (frequency, homogeneity, content, reciprocity, intensity, and dispersion); and functions which networks provide (affective support and instrumental support). A combination was made and relative strength investigated of several network char acteristics representative of the quality of interactions (i. e., reciprocal affective support, intensity, and affective support) and those repre senting the quantity of interactions (i.e., size, density, and frequency).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67277/2/10.1177_109019818301000304.pd

Analysis of the Initiating Events in HIV-1 Particle Assembly and Genome Packaging

HIV-1 Gag drives a number of events during the genesis of virions and is the only viral protein required for the assembly of virus-like particles in vitro and in cells. Although a reasonable understanding of the processes that accompany the later stages of HIV-1 assembly has accrued, events that occur at the initiation of assembly are less well defined. In this regard, important uncertainties include where in the cell Gag first multimerizes and interacts with the viral RNA, and whether Gag-RNA interaction requires or induces Gag multimerization in a living cell. To address these questions, we developed assays in which protein crosslinking and RNA/protein co-immunoprecipitation were coupled with membrane flotation analyses in transfected or infected cells. We found that interaction between Gag and viral RNA occurred in the cytoplasm and was independent of the ability of Gag to localize to the plasma membrane. However, Gag:RNA binding was stabilized by the C-terminal domain (CTD) of capsid (CA), which participates in Gag-Gag interactions. We also found that Gag was present as monomers and low-order multimers (e.g. dimers) but did not form higher-order multimers in the cytoplasm. Rather, high-order multimers formed only at the plasma membrane and required the presence of a membrane-binding signal, but not a Gag domain (the CA-CTD) that is essential for complete particle assembly. Finally, sequential RNA-immunoprecipitation assays indicated that at least a fraction of Gag molecules can form multimers on viral genomes in the cytoplasm. Taken together, our results suggest that HIV-1 particle assembly is initiated by the interaction between Gag and viral RNA in the cytoplasm and that this initial Gag-RNA encounter involves Gag monomers or low order multimers. These interactions per se do not induce or require high-order Gag multimerization in the cytoplasm. Instead, membrane interactions are necessary for higher order Gag multimerization and subsequent particle assembly in cells

Mindfulness-Based Childbirth and Parenting Education: Promoting Family Mindfulness During the Perinatal Period

We present the conceptual and empirical foundation and curriculum content of the Mindfulness-Based Childbirth and Parenting (MBCP) program and the results of a pilot study of n = 27 pregnant women participating in MBCP during their third trimester of pregnancy. MBCP is a formal adaptation of the Mindfulness-Based Stress Reduction program and was developed and refined over the course of 11 years of clinical practice with 59 groups of expectant couples. MBCP is designed to promote family health and well-being through the practice of mindfulness during pregnancy, childbirth, and early parenting. Quantitative results from the current study include statistically significant increases in mindfulness and positive affect, and decreases in pregnancy anxiety, depression, and negative affect from pre- to post-test (p < .05). Effect sizes for changes in key hypothesized intervention mediators were large (d > .70), suggesting that MBCP is achieving its intended effects on maternal well-being during pregnancy. Qualitative reports from participants expand upon the quantitative findings, with the majority of participants reporting perceived benefits of using mindfulness practices during the perinatal period and early parenting. Our future research will involve conducting a randomized controlled trial of MBCP to test effects on psychophysiological stress mechanisms and to examine effects on birth outcomes, family relationship quality, and child development outcomes

Pharmacologic Inhibition of the TGF-β Type I Receptor Kinase Has Anabolic and Anti-Catabolic Effects on Bone

During development, growth factors and hormones cooperate to establish the unique sizes, shapes and material properties of individual bones. Among these, TGF-β has been shown to developmentally regulate bone mass and bone matrix properties. However, the mechanisms that control postnatal skeletal integrity in a dynamic biological and mechanical environment are distinct from those that regulate bone development. In addition, despite advances in understanding the roles of TGF-β signaling in osteoblasts and osteoclasts, the net effects of altered postnatal TGF-β signaling on bone remain unclear. To examine the role of TGF-β in the maintenance of the postnatal skeleton, we evaluated the effects of pharmacological inhibition of the TGF-β type I receptor (TβRI) kinase on bone mass, architecture and material properties. Inhibition of TβRI function increased bone mass and multiple aspects of bone quality, including trabecular bone architecture and macro-mechanical behavior of vertebral bone. TβRI inhibitors achieved these effects by increasing osteoblast differentiation and bone formation, while reducing osteoclast differentiation and bone resorption. Furthermore, they induced the expression of Runx2 and EphB4, which promote osteoblast differentiation, and ephrinB2, which antagonizes osteoclast differentiation. Through these anabolic and anti-catabolic effects, TβRI inhibitors coordinate changes in multiple bone parameters, including bone mass, architecture, matrix mineral concentration and material properties, that collectively increase bone fracture resistance. Therefore, TβRI inhibitors may be effective in treating conditions of skeletal fragility

Complex systems and the technology of variability analysis

Characteristic patterns of variation over time, namely rhythms, represent a defining feature of complex systems, one that is synonymous with life. Despite the intrinsic dynamic, interdependent and nonlinear relationships of their parts, complex biological systems exhibit robust systemic stability. Applied to critical care, it is the systemic properties of the host response to a physiological insult that manifest as health or illness and determine outcome in our patients. Variability analysis provides a novel technology with which to evaluate the overall properties of a complex system. This review highlights the means by which we scientifically measure variation, including analyses of overall variation (time domain analysis, frequency distribution, spectral power), frequency contribution (spectral analysis), scale invariant (fractal) behaviour (detrended fluctuation and power law analysis) and regularity (approximate and multiscale entropy). Each technique is presented with a definition, interpretation, clinical application, advantages, limitations and summary of its calculation. The ubiquitous association between altered variability and illness is highlighted, followed by an analysis of how variability analysis may significantly improve prognostication of severity of illness and guide therapeutic intervention in critically ill patients

RNA interference approaches for treatment of HIV-1 infection

HIV/AIDS is a chronic and debilitating disease that cannot be cured with current antiretroviral drugs. While combinatorial antiretroviral therapy (cART) can potently suppress HIV-1 replication and delay the onset of AIDS, viral mutagenesis often leads to viral escape from multiple drugs. In addition to the pharmacological agents that comprise cART drug cocktails, new biological therapeutics are reaching the clinic. These include gene-based therapies that utilize RNA interference (RNAi) to silence the expression of viral or host mRNA targets that are required for HIV-1 infection and/or replication. RNAi allows sequence-specific design to compensate for viral mutants and natural variants, thereby drastically expanding the number of therapeutic targets beyond the capabilities of cART. Recent advances in clinical and preclinical studies have demonstrated the promise of RNAi therapeutics, reinforcing the concept that RNAi-based agents might offer a safe, effective, and more durable approach for the treatment of HIV/AIDS. Nevertheless, there are challenges that must be overcome in order for RNAi therapeutics to reach their clinical potential. These include the refinement of strategies for delivery and to reduce the risk of mutational escape. In this review, we provide an overview of RNAi-based therapies for HIV-1, examine a variety of combinatorial RNAi strategies, and discuss approaches for ex vivo delivery and in vivo delivery

Hardware-accelerated protein identification for mass spectrometry

An ongoing issue in mass spectrometry is the time it takes to search DNA sequences with MS/MS peptide fragments (see, e.g., Choudary et al., Proteomics 2001; 1: 651-667.) Search times are far longer than spectra acquisition time, and parallelization of search software on clusters requires doubling the size of a conventional computing cluster to cut the search time in half. Field programmable gate arrays (FPGAs) are used to create hardware-accelerated algorithms that reduce operating costs and improve search speed compared to large clusters. We present a novel hardware design that takes full spectra and computes 6-frame translation word searches on DNA databases at a rate of approximately 3 billion base pairs per second, with queries of up to 10 amino acids in length and arbitrary wildcard positions. Hardware post-processing identifies in silico tryptic peptides and scores them using a variety of techniques including mass frequency expected values. With faster FPGAs protein identifications from the human genome can be achieved in less than a second, and this makes it an ideal solution for a number of proteome-scale applications