From the Woman's Viewpoint: Ethical Dilemmas Confronted by Women as Informal Caregivers of Frail Elders

Copyright 2004 Alliance for Children and FamiliesWomen as informal caregivers face complex ethical dilemmas in caring for a frail elder. Through indepth interviews with 13 ethnically diverse caregivers, this qualitative study explored women's ethical decision-making. Focus group interviews of home health staff, key informant caregivers, and interviewees provided guidance for research design, reflection on findings and development of implications. Findings are integrated into an ethical decision-making model that includes types of ethical dilemmas (e.g., protection of life vs. autonomy); feelings that permeate decision making (e.g., fear); processes for addressing ethical dilemmas (e.g., family collaboration); and supportive services. Implications include (a) expansion of services to meet caregivers' ongoing needs, (b) research that acknowledges multiple decision-making components, and (c) the use of caregiving vignettes in the classroom

Back to Addams and Richmond: Was Social Work Really A Divided House in the Beginning?

Social work has experienced unique tensions related to its professional identity and dual purpose of social reform and individualized treatment. Scholars have represented this dual purpose, epitomized by Jane Addams and Mary Richmond, as indicating irreconcilable differences. The purpose of this paper is to investigate the writings and speeches of Mary Richmond and Jane Addams, and, based on this inquiry, to assert that their respective approaches to social work are much more unified than often suggested. Specific themes examined include: acceptance and need for each other’s perspectives; compatibility and unity of perspectives; and their collaboration as critical for effecting social change. With this more complex understanding of Richmond and Addams, the authors speculate about how a more holistic approach to social work practice is needed in the 21st century

Back to Addams and Richmond: Was Social Work Really a Divided House in the Beginning?

Social work has experienced unique tensions related to its professional identity and dual purpose of social reform and individualized treatment. Scholars have represented this dual purpose, epitomized by Jane Addams and Mary Richmond, as indicating irreconcilable differences. The purpose of this paper is to investigate the writings and speeches of Mary Richmond and Jane Addams, and, based on this inquiry, to assert that their respective approaches to social work are much more unified than often suggested. Specific themes examined include: acceptance and need for each other’s perspectives; compatibility and unity of perspectives; and their collaboration as critical for effecting social change. With this more complex understanding of Richmond and Addams, the authors speculate about how a more holistic approach to social work practice is needed in the 21st century

Seychelles warblers: complexities of the helping paradox

IntroductionThe Seychelles warbler (Acrocephalus sechellensis), a passerine endemic to the Seychelles archipelago, is a facultatively cooperative breeder that lives either in pairs or small groups. Breeding groups normally consist of a dominant pair and one to three subordinates, although up to nine have been observed. Subordinates can be of either sex, and are often offspring that have delayed dispersal and remained in their natal territory (Komdeur 1992; Richardson et al. 2002; Eikenaar et al. 2008, 2010). By the 1960s the last remnant population of this then critically endangered species was confined to Cousin Island (Figure 12.1). Subsequent conservation actions, including the restoration of forest habitat and the establishment of new populations through translocations, have provided unique opportunities to study the evolutionary ecology of cooperative breeding in this species. We have followed the entire world population of the Seychelles warbler since our study started in 1981. In 1997, however, we increased the intensity of work on Cousin and since then nearly all individuals, including fledglings, have been captured, ringed, blood sampled, sexed, and monitored for breeding and status. Molecular tools have been used to assign the sex and genetic parentage of young birds and to determine levels of relatedness between individuals. In addition, a comprehensive set of behavioral, life history, and annual fitness parameters have been recorded for nearly all individuals, providing important opportunities for assessing changes in social behavior. The lack of interisland dispersal (Komdeur et al. 2004a), combined with sampling of the entire population, provides a rare opportunity to monitor the survival, reproduction, and lifetime fitness of all individuals within the population. Our long-term research program into cooperative breeding, hand-in-hand with conservation actions, has created an experimental system in which we can attempt to unravel the factors that alter the cost-benefit trade-offs of cooperative breeding. Over time, this system has become proof of the power of the experimental methods and of the corrective value of long-term studies, where iterative examination with longer-term data sheds new insights on short-term findings. Here we detail various findings that have allowed us to uncover how changing social and ecological factors influence the form and function of reproductive competition and cooperation in the Seychelles warbler. We also outline how molecular genetic tools have given us a better understanding of the species’ cooperative breeding system and the selective factors that favor switching between different forms of cooperative and independent breeding

Interferon-α Regulates Glutaminase 1 Promoter through STAT1 Phosphorylation: Relevance to HIV-1 Associated Neurocognitive Disorders

HIV-1 associated neurocognitive disorders (HAND) develop during progressive HIV-1 infection and affect up to 50% of infected individuals. Activated microglia and macrophages are critical cell populations that are involved in the pathogenesis of HAND, which is specifically related to the production and release of various soluble neurotoxic factors including glutamate. In the central nervous system (CNS), glutamate is typically derived from glutamine by mitochondrial enzyme glutaminase. Our previous study has shown that glutaminase is upregulated in HIV-1 infected monocyte-derived-macrophages (MDM) and microglia. However, how HIV-1 leads to glutaminase upregulation, or how glutaminase expression is regulated in general, remains unclear. In this study, using a dual-luciferase reporter assay system, we demonstrated that interferon (IFN) α specifically activated the glutaminase 1 (GLS1) promoter. Furthermore, IFN-α treatment increased signal transducer and activator of transcription 1 (STAT1) phosphorylation and glutaminase mRNA and protein levels. IFN-α stimulation of GLS1 promoter activity correlated to STAT1 phosphorylation and was reduced by fludarabine, a chemical that inhibits STAT1 phosphorylation. Interestingly, STAT1 was found to directly bind to the GLS1 promoter in MDM, an effect that was dependent on STAT1 phosphorylation and significantly enhanced by IFN-α treatment. More importantly, HIV-1 infection increased STAT1 phosphorylation and STAT1 binding to the GLS1 promoter, which was associated with increased glutamate levels. The clinical relevance of these findings was further corroborated with investigation of post-mortem brain tissues. The glutaminase C (GAC, one isoform of GLS1) mRNA levels in HIV associated-dementia (HAD) individuals correlate with STAT1 (p<0.01), IFN-α (p<0.05) and IFN-β (p<0.01). Together, these data indicate that both HIV-1 infection and IFN-α treatment increase glutaminase expression through STAT1 phosphorylation and by binding to the GLS1 promoter. Since glutaminase is a potential component of elevated glutamate production during the pathogenesis of HAND, our data will help to identify additional therapeutic targets for the treatment of HAND

Nuclear Pore Complex Protein Mediated Nuclear Localization of Dicer Protein in Human Cells

Human DICER1 protein cleaves double-stranded RNA into small sizes, a crucial step in production of single-stranded RNAs which are mediating factors of cytoplasmic RNA interference. Here, we clearly demonstrate that human DICER1 protein localizes not only to the cytoplasm but also to the nucleoplasm. We also find that human DICER1 protein associates with the NUP153 protein, one component of the nuclear pore complex. This association is detected predominantly in the cytoplasm but is also clearly distinguishable at the nuclear periphery. Additional characterization of the NUP153-DICER1 association suggests NUP153 plays a crucial role in the nuclear localization of the DICER1 protein

HIV-1 Replication in the Central Nervous System Occurs in Two Distinct Cell Types

Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) can lead to the development of HIV-1-associated dementia (HAD). We examined the virological characteristics of HIV-1 in the cerebrospinal fluid (CSF) of HAD subjects to explore the association between independent viral replication in the CNS and the development of overt dementia. We found that genetically compartmentalized CCR5-tropic (R5) T cell-tropic and macrophage-tropic HIV-1 populations were independently detected in the CSF of subjects diagnosed with HIV-1-associated dementia. Macrophage-tropic HIV-1 populations were genetically diverse, representing established CNS infections, while R5 T cell-tropic HIV-1 populations were clonally amplified and associated with pleocytosis. R5 T cell-tropic viruses required high levels of surface CD4 to enter cells, and their presence was correlated with rapid decay of virus in the CSF with therapy initiation (similar to virus in the blood that is replicating in activated T cells). Macrophage-tropic viruses could enter cells with low levels of CD4, and their presence was correlated with slow decay of virus in the CSF, demonstrating a separate long-lived cell as the source of the virus. These studies demonstrate two distinct virological states inferred from the CSF virus in subjects diagnosed with HAD. Finally, macrophage-tropic viruses were largely restricted to the CNS/CSF compartment and not the blood, and in one case we were able to identify the macrophage-tropic lineage as a minor variant nearly two years before its expansion in the CNS. These results suggest that HIV-1 variants in CSF can provide information about viral replication and evolution in the CNS, events that are likely to play an important role in HIV-associated neurocognitive disorders

Creating a data resource: what will it take to build a medical information commons?

National and international public–private partnerships, consortia, and government initiatives are underway to collect and share genomic, personal, and healthcare data on a massive scale. Ideally, these efforts will contribute to the creation of a medical information commons (MIC), a comprehensive data resource that is widely available for both research and clinical uses. Stakeholder participation is essential in clarifying goals, deepening understanding of areas of complexity, and addressing long-standing policy concerns such as privacy and security and data ownership. This article describes eight core principles proposed by a diverse group of expert stakeholders to guide the formation of a successful, sustainable MIC. These principles promote formation of an ethically sound, inclusive, participant-centric MIC and provide a framework for advancing the policy response to data-sharing opportunities and challenges

Proteomic Modeling for HIV-1 Infected Microglia-Astrocyte Crosstalk

Background: HIV-1-infected and immune competent brain mononuclear phagocytes (MP; macrophages and microglia) secrete cellular and viral toxins that affect neuronal damage during advanced disease. In contrast, astrocytes can affect disease by modulating the nervous system’s microenvironment. Interestingly, little is known how astrocytes communicate with MP to influence disease. Methods and Findings: MP-astrocyte crosstalk was investigated by a proteomic platform analysis using vesicular stomatitis virus pseudotyped HIV infected murine microglia. The microglial-astrocyte dialogue was significant and affected microglial cytoskeleton by modulation of cell death and migratory pathways. These were mediated, in part, through F-actin polymerization and filament formation. Astrocyte secretions attenuated HIV-1 infected microglia neurotoxicity and viral growth linked to the regulation of reactive oxygen species. Conclusions: These observations provide unique insights into glial crosstalk during disease by supporting astrocytemediated regulation of microglial function and its influence on the onset and progression of neuroAIDS. The results open new insights into previously undisclosed pathogenic mechanisms and open the potential for biomarker discovery an