Screening of gap junction antagonists on dye coupling in the rabbit retina.

Many cell types in the retina are coupled via gap junctions and so there is a pressing need for a potent and reversible gap junction antagonist. We screened a series of potential gap junction antagonists by evaluating their effects on dye coupling in the network of A-type horizontal cells. We evaluated the following compounds: meclofenamic acid (MFA), mefloquine, 2-aminoethyldiphenyl borate (2-APB), 18-alpha-glycyrrhetinic acid, 18-beta-glycyrrhetinic acid (18-beta-GA), retinoic acid, flufenamic acid, niflumic acid, and carbenoxolone. The efficacy of each drug was determined by measuring the diffusion coefficient for Neurobiotin (Mills & Massey, 1998). MFA, 18-beta-GA, 2-APB and mefloquine were the most effective antagonists, completely eliminating A-type horizontal cell coupling at a concentration of 200 muM. Niflumic acid, flufenamic acid, and carbenoxolone were less potent. Additionally, carbenoxolone was difficult to wash out and also may be harmful, as the retina became opaque and swollen. MFA, 18-beta-GA, 2-APB and mefloquine also blocked coupling in B-type horizontal cells and AII amacrine cells. Because these cell types express different connexins, this suggests that the antagonists were relatively non-selective across several different types of gap junction. It should be emphasized that MFA was water-soluble and its effects on dye coupling were easily reversible. In contrast, the other gap junction antagonists, except carbenoxolone, required DMSO to make stock solutions and were difficult to wash out of the preparation at the doses required to block coupling in A-type HCs. The combination of potency, water solubility and reversibility suggest that MFA may be a useful compound to manipulate gap junction coupling.

Intervening to reach adolescents and affect health

Background. Assessing the health status of adolescents is challenging for health care providers. Personal disclosure has been associated with improved health outcomes. Story-centered care was examined as an intervention for promoting adolescent disclosure during an urgent care visit. ^ Objectives. This study explored: (1) the effectiveness of story-centered care for promoting adolescent disclosure; (2) health-associated words used by adolescents to describe pressing concerns after an urgent care visit when they had standard care (SC) or story-centered care (SCC) conducted by a Nurse Practitioner (NP). ^ Methods. Subjects were randomly assigned to SC or SCC. In SC, adolescent presenting concerns were identified and treated. In SCC, presenting concerns were treated and NP-adolescent dialogue, facilitated through a screening tool, queried matters of importance to adolescent life. After the visit, adolescents wrote about pressing concerns for 15 minutes. Written words were analyzed with Linguistic Inquiry and Word Count, a software program for analyzing narrative. Ratios were calculated for the number of words (adolescent: NP) used during the urgent care visit. Analysis of variance (ANOVA) was used to evaluate gender-intervention differences in health-associated words. ^ Results. One hundred and six adolescents [Hispanic (65%), White (35%)] completed the study. Fifty-five were female; the average age was 17 (sd = 2.1) years. ^ Adolescents in the story intervention used more words (adolescent: NP, 1:1.3) than those in standard intervention (adolescent: NP, 1:2.7) in proportion to the number of words used by the NP during the urgent care visit. There were gender-intervention differences (p < .01) in positive emotion words and past-tense words in writings about pressing concerns. Males who received the story intervention used more positive emotion and less past-tense words than adolescent males with standard care. Females used more social words (p < .01) in their writings regardless of intervention group. ^ Conclusion. SCC enhanced adolescent disclosure during an urgent care visit. Adolescents will talk to health care providers during episodic visits and males may benefit more than girls may from this approach. Evidence suggests there is value in attending to both presenting and pressing concerns of adolescents. ^

Characterization of Staphylococcus aureus adhesins important for respiratory tract infection

Staphylococcus aureus is a leading cause of lower respiratory tract infections in both adult and pediatric populations. In the past two decades, reports have described emergent incidence of severe necrotizing pneumonia in previously healthy individuals, frequently caused by antibiotic resistant strains. Additionally, S. aureus remains the most common cause of ventilator-associated pneumonia, contributing morbidity and mortality in intensive care units. As treatment of infection is made more difficult by the resistance to multiple antibiotics including vancomycin, there is a pressing need for novel strategies to prevent and treat S. aureus infections. Targeting essential mechanisms that promote infection such as adhesion, colonization, invasion, evasion of immune system and signaling may lead to inhibition of pathogenic surge. Staphylococcal adhesins of the MSCRAMM family (microbial surface components recognizing adherent matrix molecules) represent viable targets for such investigations. Understanding the molecular mechanism of binding is the first step toward the development of such therapies. Analysis of bacterial strains isolated from patients with staphylococcal pneumonia show increased expression of protein A, SdrD, SdrC and ClfB, cell surface proteins members of the MSCRAMM family. In this study the interaction of these MSCRAMMs with candidate ligands has been examined. We found that SdrD mediates S. aureus adherence to the lung epithelial cell line A549. Consistently, bacteria expressing SdrD have increased persistence in the lungs of infected mice after bronchoalveolar lavage in comparison with bacteria lacking this protein. Inhibition studies revealed that bacterial attachment can be abolished using neutralizing antibodies against SdrD. Using phage display, neurexin β isoforms were identified as SdrC binding partners. Previous reports postulated that MSCRAMMS bind their ligands by a 'dock, lock and latch' mechanism of interaction. Our data suggested that ClfB, an MSCRAMM responsible for nasal colonization, binds cytokeratin 10 by a 'dock and lock' variant of this model, in which the 'latching' event is not necessary. In summary, we have characterized aspects of molecular interaction between several MSCRAMMS and host components. We hope that continued delineation of these interactions will lead to identification of novel therapeutic targets or preventive strategies against S. aureus infections. ^

Evaluation of web-based resources for pregnant and parenting teens

Current teen pregnancy and repeat pregnancy rates reveal that there is a pressing need for comprehensive care for pregnant and parenting teens to address their unique needs. The Internet has become a source of various types of information and as a result, several efforts have begun to assess the quality of health information provided on websites. The objective of this study was to assess the functionality and quality of websites containing health information and resources for pregnant and parenting teens. The three most widely used search engines currently: Google, MSN, and Yahoo were searched using three general search terms “teen pregnancy”, “pregnant teen”, and “teen parent”. The first 5 pages of each search were reviewed and categorized to yield 12 websites which met inclusion criteria for content evaluation. The 12 websites were rated using a pre-existing instrument encompassing two domains: functionality and content analysis. Within the functionality domain, this sample highlighted the need to improve accessibility and credibility for the target population. The content analysis revealed that among the topics which are recommended for pregnant and parenting teens, the topics most commonly covered were mental health and primary and preventive health care. The majority of websites neglected sexual health topics including STI’s and family planning. This study provides the first glimpse into health information and resources for pregnant and parenting teens on the Internet. Researchers, health care providers, social workers, health educators, and website sponsors can use these results to maintain and recommend websites which offer easily accessible, accurate, and practical information for pregnant and parenting teens.^

Measuring Service Effectiveness for Families

While most professionals do not dispute the fact that evaluation is necessary to determine whether agencies and practitioners are truly providing services that meet clients’ needs, information regarding consistent measures on service effectiveness in human service organizations is sparse. A national survey of 250 not-for-profit family service organizations in the United States (52.8% return rate) yielded results relevant to client identified needs and agency effectiveness measures in serving today’s families. On an open-ended survey item, 52.3% agencies indicated that poverty represented the most pressing problem among today’s families because other psychological needs also take priority. Over two thirds of these agencies used multiple methods to evaluate their services. Clients’ feedback and outcome measures are the most popular methods. The findings reveal agencies' difficulties in determining what or who decides if the most appropriate services are being provided for the target population. Limited data collected on outcomes and impact may impose additional difficulties in program design and planning.