Condom use among high-risk heterosexual women with concurrent sexual partnerships, Houston, Texas, USA

Concurrent sexual partnerships allow for enhanced transmission of sexually transmitted infections (STIs). Condom use dynamics in this context may be an important factor for transmission of HIV. We conducted a cross-sectional study to describe the frequency of concurrency among high-risk heterosexual women in Houston, Texas and determine the factors associated with condom use. A total of 553 participants were recruited using respondent-driven sampling and completed an anonymous questionnaire; 256 (49%) were identified as having a concurrent partnership. The prevalence of condom use at last sexual encounter was 26%. Women were significantly more likely to use condoms if their sexual encounter was with a casual partner and if alcohol and/or drugs were not used. The high prevalence of concurrent partnerships suggests the presence of a dense sexual network which may enable the rapid spread of STIs and HIV. The risk of transmission may be additionally increased due to the low prevalence of condom use.     

The use of a constrained acetabular component for recurrent dislocation

The poor results of surgical treatment of chronic instability after total hip arthroplasty (THA) led to the development of a constrained acetabular component. In this study, 87 constrained THAs implanted for recurrent instability were reviewed retrospectively. Eighty-five hips were available for follow-up evaluation, with an average follow-up period of 58 months. These 85 hips were evaluated at a minimum of 3 years. Two recurrent dislocations were seen, caused by dissociation of the liner from the shell. Four acetabular components and 1 femoral component were revised. Overall, a 2.4% dislocation rate and an 8.2% revision rate were seen. The recurrent dislocation rate of 2.4% represents a significant improvement over other methods reported. Repeat dislocation was only seen in dissociation of cemented liners into well-fixed shells. We do not recommend this mode of fixation.     

Wear Damage in Mobile-bearing TKA is as Severe as That in Fixed-bearing TKA

Background  

Mobile-bearing TKAs reportedly have no clinical superiority over fixed-bearing TKAs, but a potential benefit is improved polyethylene wear behavior.     

Superoxide production by macrophages and T cells is critical for the induction of autoreactivity and type 1 diabetes

OBJECTIVE

The role of reactive oxygen species (ROS) and their dissipation in type 1 diabetes pathogenesis have garnered considerable controversy. Our recent work has demonstrated the importance of NADPH oxidase (NOX) activity for type 1 diabetes development and modulating T-cell autoreactivity. We previously linked decreased monocyte ROS with diabetes resistance in the alloxan-resistant mouse, and NOD-Ncf1^m1J mice with a genetic ablation of NOX activity had reduced and delayed type 1 diabetes compared with NOD mice.

RESEARCH DESIGN AND METHODS

To determine the required cellular sources of ROS that are necessary for type 1 diabetes initiation, we used antibody depletion and adoptive transfer experiments into NOD and NOD-Scid females, respectively. After receiving treatment, female mice were monitored for hyperglycemia and overt diabetes.

RESULTS

Depletion of macrophages and neutrophils fully protected NOD mice from type 1 diabetes. However, elimination of neutrophils alone showed no significant reduction or delay. Type 1 diabetes induction in NOD-Scid mice by adoptive transfer with NOD-Ncf1^m1J splenocytes was significantly delayed compared with NOD splenocytes, suggesting macrophage ROS and modulation of effector responses are critical for diabetes. The adaptive immune response was also altered by the absence of NOX activity, as purified T cells from NOD-Ncf1^m1J mice exhibited delayed transfer kinetics. Cotransfer experiments demonstrated the defect was intrinsic to NOX-deficient CD8⁺ T cells. After stimulation, cytotoxic T cells exhibited decreased effector function in the absence of superoxide production.

CONCLUSIONS

These data demonstrate that the impaired autoreactive response of NOX-deficient NOD-Ncf1^m1J immune system results from an alteration in the antigen-presenting cell–T-cell axis rather than failure of neutrophils to act as effector cells and that ROS signaling is important for the initiation of β-cell–directed autoimmunity by T cells.Destruction of pancreatic β-cells is mediated by aberrant immune responses against islet antigens resulting in the development of type 1 diabetes. During the early stages of disease, an insulitic infiltrate consisting of macrophages, dendritic cells, T-cell subsets, and B cells accumulates in the pancreatic islets (1,2). Effector mechanisms, including direct T-cell cytotoxicity and indirect methods mediated by leukocytes, contribute to β-cell destruction and overt diabetes. Production of reactive oxygen species (ROS) has been proposed to be an important contributor to β-cell loss during type 1 diabetes pathogenesis. Endogenous free radicals produced by the β-cell in response to cytokines are one source of cytotoxic ROS: γ-interferon (IFN-γ) in combination with interleukin (IL)-1β and tumor necrosis factor-α (TNF-α) are cytotoxic to β-cells as a result of increased production of nitric oxide (NO) and superoxide. However, the roles of cellular sources of ROS during the development of spontaneous type 1 diabetes have not been fully defined (3,4).NADPH oxidase (NOX), a multicomponent enzymatic complex, is a major source of free radicals and important for the effector function of neutrophils and macrophages (5–7). Islet-infiltrating macrophages release high levels of ROS, including superoxide via NOX. Defects in NOX function have been associated with increased susceptibility to autoimmunity in experimental allergic encephalomyelitis and collagen-induced arthritis (8–12). In addition to contributing to toxicity, free radicals are also potent signaling molecules and are important in adaptive immune responses (13–16). Recent work has demonstrated that exogenous as well as endogenous sources of ROS are involved in initiating and dictating cytokine responses of CD4⁺ T cells (17). Likewise, antioxidant regulation significantly modifies proliferative (15,18) and effector responses of CD8⁺ cytotoxic T cells, reducing cytolytic function and cytokine production (15). To study the role of superoxide production via NOX in a type 1 diabetes–prone mouse model, a mutation in p47^phox subunit was congenically introduced into the NOD mouse (NOD-Ncf1^m1J) (19).Genetic ablation of NOX protects against type 1 diabetes development, as NOD-Ncf1^m1J mice have reduced incidence and delayed type 1 diabetes onset. To determine the innate immune cellular sources of ROS essential for type 1 diabetes pathogenesis, we depleted neutrophils and macrophages from NOD mice. Here we show that macrophages are essential for type 1 diabetes induction, whereas neutrophils are dispensable. In addition, NOD-Ncf1^m1J mice were protected from type 1 diabetes after adoptive transfer of BDC-2.5 T cells, demonstrating a requirement of NOX during CD4⁺ T-cell–mediated autoreactivity. NOX-deficient β-cells were not protected as NOD-Ncf1^m1J islets were susceptible to cytokine-mediated damage and mice developed diabetes induced by AI4 CD8⁺ T cells. We have previously shown that NOX function is important for T-helper cell lineage development and cytokine synthesis (15,16). NOX deficiency resulted in decreased production of Th₁-associated cytokines, including IFN-γ, TNF-α, IL-1β, and IL-12 p70. However, there was a marked increase in Th₁₇ cytokines, including IL-17 and IL-10 (19). Here we report the reduced diabetogenic capabilities of NOX-deficient leukocytes as purified splenocytes and T cells from NOD-Ncf1^m1J mice had delayed transfer kinetics of type 1 diabetes in contrast to NOD mice. It is noteworthy that this delay was associated with the source of CD8⁺ T cells, suggesting an important role for NOX in propagation of islet-directed cytotoxic T-cell activity. Examination of cytotoxic T-cell function associated decreased production of IFN-γ and granzyme B with NOX deficiency, demonstrating reduced effector responses when superoxide is lacking. Therefore, ROS production by macrophages and T cells is essential for the development and effector function of proinflammatory responses mediating β-cell destruction.     

EBV-encoded dUTPase induces immune dysregulation: Implications for the pathophysiology of EBV-associated disease

Epstein-Barr virus (EBV) encodes for several enzymes that are involved in viral DNA replication. There is evidence that some viral proteins, by themselves, can induce immune dysregulation that may contribute to the pathophysiology of the virus infection. In this study, we focused on the EBV-encoded deoxyuridine triphosphate nucleotidohydrolase (dUTPase) and present the first evidence that the dUTPase is able to induce immune dysregulation in vitro as demonstrated by the inhibition of the replication of stimulated peripheral blood mononuclear cells (PBMCs) and the upregulation of several proinflammatory cytokines including TNF-alpha, IL-1beta, IL-8, IL-6, and IL-10 produced by unstimulated PBMCs treated with purified EBV-encoded dUTPase. Depletion of CD14-positive cells (monocytes) eliminated the cytokine profile induced by EBV dUTPase treatment. The data support the hypothesis that at least one protein of the EBV early antigen complex can induce immune dysregulation and may be involved in the pathophysiology of EBV-associated disease.     

Repeated social defeat activates dendritic cells and enhances Toll-like receptor dependent cytokine secretion

Stress hormones significantly impact dendritic cell (DC) activation and function, typically in a suppressive fashion. However, a social stressor termed social disruption (SDR) has been shown to induce an increase in inflammatory responses and a state of glucocorticoid resistance in splenic CD11b+ monocytes. These experiments were designed to determine the effects of SDR on DC activation, Toll-like receptor-induced cytokine secretion, and glucocorticoid sensitivity. Compared to cells obtained from control animals, splenic DCs from SDR mice displayed increased levels of MHC I, CD80, and CD44, indicative of an activated phenotype. In addition, DCs from SDR mice produced comparatively higher TNF-alpha, IL-6, and IL-10 in response to in vitro stimulation with LPS and CpG DNA. Increased amounts of TNF-alpha and IL-6 were also evident in SDR DC cultures stimulated with poly(I:C). Furthermore, as shown previously in CD11b+ monocytes, the CD11c+ DCs obtained from SDR mice were glucocorticoid resistant. Taken together, the data suggest that social stress, in the absence of any immune challenge, activates DCs, increases DC cytokine secretion in response to Toll-specific stimuli and renders DCs glucocorticoid resistant.     

Engaging and Recruiting Counties in an Experiment on Implementing Evidence-based Practice in California

There is a growing consensus that implementation of evidence-based intervention and treatment models holds promise to improve the quality of services in child public service systems such as mental health, juvenile justice, and child welfare. Recent policy initiatives to integrate such research-based services into public service systems have created pressure to expand knowledge about implementation methods. Experimental strategies are needed to test multi-level models of implementation in real world contexts. In this article, the initial phase of a randomized trial that tests two methods of implementing Multidimensional Treatment Foster Care (an evidence-based intervention that crosses child public service systems) in 40 non-early adopting California counties is described. Results are presented that support the feasibility of using a randomized design to rigorously test contrasting implementation models and engaging system leaders to participate in the trial.     

Engagement and retention in services among formerly homeless adults with co-occurring mental illness and substance abuse: voices from the margins

This qualitative study analyzed 72 interviews with 39 formerly homeless psychiatric consumers to develop a grounded theory model of engagement and retention in mental health and substance abuse services. Person-centered themes included severity of mental illness and substance abuse (the latter also conflicting with programmatic abstinence requirements). System-related themes inhibiting service use included program rules and restrictions and a lack of one-on-one therapy. Those promoting service use were acts of kindness by staff, pleasant surroundings, and the promise (or attainment) of independent housing. Implications of these findings are discussed in terms of integrating consumers' opinions about services to enhance treatment engagement and retention.