Objectives-The IκB kinase (IKK)-related kinase IKKε regulates type I interferon expression and responses as well as proinflammatory mediator production. We examined the role of IKKε in arthritis and its ability to enhance the therapeutic response to systemic interferon (IFN) β therapy in passive murine K/BxN arthritis.Methods-IKKε −/− , IFNα~βR −/− and wild type mice were given K/BxN serum and treated with polyinosinic polycytidylic acid (poly(I:C)), IFNβ, or normal saline. Clinical response and histological scores were assessed. Gene expression in the paws was measured by quantitative PCR. Serum interleukin 1a receptor agonist (IL1Ra) and IL10 were measured by ELISA and multiplex bead array.Results-Arthritis was almost completely blocked in wild type mice if arthritogenic K/BxN serum and the Toll-like receptor (TLR)3 ligand, poly(I:C), were coadministered at the onset of the model, but not in established disease. Mice deficient in IFNα~βR had an accelerated course of arthritis, and did not respond to poly(I:C). IKKε null mice had a modest decrease in clinical arthritis compared with heterozygous mice. Low doses of IFNβ that were ineffective in wild type mice significantly decreased clinical arthritis in IKKε null mice. Articular chemokine gene expression was reduced in the IKKε −/− mice with arthritis and secreted IL1Ra (sIL1Ra) mRNA was significantly increased. Serum levels of IL1Ra were increased in low dose IFNβ-treated IKKε −/− mice.Conclusions-Subtherapeutic doses of IFNβ enhance the anti-inflammatory effects of IKKε deficiency, possibly by increasing production of IL1Ra and unmasking the antichemokine effects. Combination therapy with low dose IFNβ and an IKKε inhibitor might improve efficacy of either agent alone and offers a novel approach to RA.Type I interferons (IFNs) stimulate antiviral responses, but they paradoxically exhibit antiinflammatory properties. For instance, IFNβ reduces tumour necrosis factor (TNF)α, interleukin (IL)1β and IL6 production and enhances the release of anti-inflammatory mediators such as IL1 receptor antagonist (IL1Ra) and IL10. 1-3 Preclinical studies emphasising the antiinflammatory functions of IFNβ strongly supported its therapeutic potential in rheumatoid arthritis (RA Serum transfer and arthritis scoringArthritic adult K/BxN mice were bled and the sera were pooled. Groups of three to eight recipient mice were injected with 150 µl intraperitoneally on day 0. Some groups of mice also received IFNβ (Chemicon (3.6 × 10 7 IU/mg; or 1000 IU=28 ng)), normal saline (NS) or polyinosinic polycytidylic acid (poly(I:C); Sigma, St Louis, Missouri, USA) at the indicated doses intraperitoneally. Clinical arthritis scores were evaluated using a scale of 0-4 for each paw for a total score of 16. Ankle thickness was measured with a calliper (Manostat, Herisau, Switzerland) in mm. 22 HistologyWhole knee joint sections were stained with haematoxylin and eosin and safranin O (HistoTox, Boulder, Colorado, USA). Histopathological scoring was performed as previously described on a ...

IntroductionEvidence-based interventions for training parents are proven to prevent onset and escalation of childhood mental health problems. However, participation in such programs is low, especially among hard-to-reach, underserved populations such as Filipino Americans. Filipinos, the largest Asian subgroup in California, have significant behavioral health disparities compared with non-Hispanic whites and other Asian subgroups. The purpose of this study was to learn about Filipinos’ barriers and facilitators to participating in “Incredible Years” (IY), a parenting program.MethodsWe conducted 4 focus groups in Los Angeles, California, in 2012; the groups consisted of 20 Filipino parents of children aged 6 to 12 years who recently completed the IY parenting program, which was offered as a prevention workshop. Three reviewers, including two co-authors (A.S., J.J.) and a research assistant used content analysis to independently code the interview transcripts and extract subthemes. Grounded theory analytic methods were used to analyze interview transcripts.ResultsParents’ perceived benefits of participation in IY were learning more effective parenting techniques, networking with other parents, improved spousal relationships, and improvements in their children's behavior. Parents’ most common motivating factor for enrollment in IY was to improve their parenting skills and their relationships with their children. The most common barriers to participation were being uncomfortable sharing problems with others and the fear of being stigmatized by others judging their parenting skills. Participants said that parent testimonials would be the most effective way to promote IY. Many recommended outreach at schools, pediatricians’ offices, and churches.ConclusionIncreasing Filipino American parent enrollment in IY in culturally relevant ways will reduce the incidence of mental health disorders among children in this growing population.

With increasing development of resistance to conventional synthetic acaricides in economically and medically important ixodid species, interest in finding alternative control tactics has intensified. Laboratory bioassays were conducted, using the lone star tick, Amblyomma americanum (L.), as a model species, to assess the efficacy of a diatomaceous earth-based product, Deadzone, in comparison with a silica gel-based product, CimeXa. CimeXa is already known to be highly lethal against A. americanum larvae and nymphs. The two dust treatments were 100% effective against larvae and nymphs within 24 h after contact occurred by immersion in dry dusts and after crawling across a surface treated with the dry dusts. Contact by crawling on a dried aqueous film of the dusts, even at a concentration of 10%, was not as effective as exposure to the dusts in dry powder form. As has been demonstrated with CimeXa, it is likely that Deadzone will be capable of providing prophylactic protection of cattle from economically important one-host ixodids, such as the southern cattle fever tick, Rhipicephalus microplus (Canestrini), which vectors the causal agents of babesiosis. Diatomaceous earth can be stored indefinitely, will remain efficacious for as long as sufficient quantities remain on the substrate, it is a natural (organic) substance, and it might be amenable for limited use in environmentally protected habitats.

Background and Purpose-Studies have demonstrated the importance of early stroke treatment. If a neuroprotective agent (NA) clinical trial is successful, the greatest benefit might be attained with early prehospital administration. This study determined the potential reduction in time to treatment of stroke patients when NAs were administered in the prehospital setting. Methods-Twenty-three urban emergency medical services (EMS) agencies participated in this study. Prehospital personnel completed a stroke assessment checklist on any potential stroke victim. The checklist collected clinical inclusion/exclusion criteria for NA administration and event/decision times. Patients meeting the hypothetical clinical inclusion criteria were enrolled into this study. Time data included scene arrival/departure, emergency department (ED) arrival, and estimated time of theoretical NA administration. The reduction in time to stroke treatment was calculated as the difference between the time of ED arrival and the reported time of NA administration. The t test and simple linear regression were used to probe for differences in treatment time reduction between selected subgroups. EMS personnel's ability to obtain informed consent for theoretical NA administration was calculated. Results-Two hundred twenty-two patients were enrolled in this study; of these, 75 were deemed eligible for hypothetical NA administration and had complete time data.

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