Acceptability and feasibility of CyberSenga: an Internet-based HIV-prevention program for adolescents in Mbarara,Uganda

Capitalizing on emerging data suggesting that HIV-preventive behaviors can be positively affected by Internet-based programs, we developed and tested CyberSenga, an Internet-based, comprehensive sexuality education program for adolescents in Mbarara, Uganda. Three hundred and sixty-six secondary school students were randomly assigned to either the five-lesson program (+ booster) or a treatment-as-usual control. At three-month follow-up, intervention participants provided feedback on the program acceptability. Six focus groups with intervention participants were additionally conducted after the final follow-up at 6 months. Data support a hypothesis of feasibility: despite schedule interruptions, 95% of intervention participants completed all the five modules; only 17% deviated from the once-a-week intended delivery schedule. Internet service was uninterrupted during the field period and, in general, the technology performed to specifications. The intervention also appears to be acceptable: 94% of intervention youth somewhat or strongly agreed that they learned a lot and 93% said they were somewhat or very likely to recommend the program. Although more than two in three youth somewhat or strongly agreed that the program talked too much about sex (70%) and condoms (75%), 89% somewhat or strongly disagreed that “I do not think kids like me should do the CyberSenga program.” Feedback from focus group participants further suggested that the content was generally acceptable and did not contradict local norms in most cases. In fact, despite concerns from some local stakeholders to the contrary, information about condoms did not appear to be confusing or contradictory for youth who were abstinent. Nonetheless, some of the sexual topics seemed to be unfamiliar or uncomfortable for some participants – particularly brief references to oral and anal sex. Together, both qualitative and quantitative data suggest that the program is a feasible and acceptable way of delivering HIV preventive information to both sexually experienced and inexperienced adolescents in Mbarara, Uganda.     

Initiation and Continuation of DNA Replication Are Not Associated with the Nuclear Envelope in Mammalian Cells

For determination of whether DNA replication is initiated at the nuclear envelope, synchronized Chinese hamster ovary cells labeled with [(3)H]thymidine were examined by electron microscope radioautography. The cells were synchronized initially by mitotic shake-off and held at the G(1)-S border by 5-fluorodeoxyuridine plus amethopterin. Cells were fixed at 1, 5, 10, and 30 min after the inhibitors were counteracted with [(3)H]thymidine. Radioautographic silver grains in each case were present over the more central parts of nuclei and were generally absent from the region of the nuclear envelope. We conclude that neither initiation nor continuation of DNA replication is associated with the nuclear envelope.     

The use of 7-amino actinomycin D in identifying apoptosis: simplicity of use and broad spectrum of application compared with other techniques

The detection and quantitation of apoptotic cells is becoming increasingly important in the investigation of the role of apoptosis in cellular proliferation and differentiation. The pathogenesis of hematologic disorders such as aplastic anemia and the development of neoplasia are believed to involve dysregulation of apoptosis. To quantitate accurately the proportion of apoptosis cells within different cell types of a heterogeneous cell population such as blood or bone marrow, a method is required that combines the analysis of large numbers of cells with concurrent immunophenotyping of cell surface antigens. In this study, we have evaluated such a method using the fluorescent DNA binding agent, 7-amino actinomycin D (7AAD), to stain three diverse human cell lines, induced to undergo apoptosis by three different stimuli. Flow cytometric analysis defines three populations on the basis of 7AAD fluorescence and forward light scatter. We have shown by cell sorting and subsequent morphological assessment and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling that the populations defined by 7AAD represent live, apoptotic, and late-apoptotic/dead cells. This method is quick, simple, reproducible, and cheap and will be a valuable tool in the investigation of the role of apoptosis in normal physiology and in disease states.     

Intracellular unesterified arachidonic acid signals apoptosis

Cyclooxygenase-2 (COX-2) is up-regulated in many cancers and is a rate-limiting step in colon carcinogenesis. Nonsteroidal antiinflammatory drugs, which inhibit COX-2, prevent colon cancer and cause apoptosis. The mechanism for this response is not clear, but it might result from an accumulation of the substrate, arachidonic acid, an absence of a prostaglandin product, or diversion of the substrate into another pathway. We found that colon adenocarcinomas overexpress another arachidonic acid-utilizing enzyme, fatty acid-CoA ligase (FACL) 4, in addition to COX-2. Exogenous arachidonic acid caused apoptosis in colon cancer and other cell lines, as did triacsin C, a FACL inhibitor. In addition, indomethacin and sulindac significantly enhanced the apoptosis-inducing effect of triacsin C. These findings suggested that unesterified arachidonic acid in cells is a signal for induction of apoptosis. To test this hypothesis, we engineered cells with inducible overexpression of COX-2 and FACL4 as "sinks" for unesterified arachidonic acid. Activation of the enzymatic sinks blocked apoptosis, and the reduction of cell death was inversely correlated with the cellular level of arachidonic acid. Inhibition of the COX-2 component by nonsteroidal antiinflammatory drugs restored the apoptotic response. Cell death caused by exposure to tumor necrosis factor alpha or to calcium ionophore also was prevented by removal of unesterified arachidonic acid. We conclude that the cellular level of unesterified arachidonic acid is a general mechanism by which apoptosis is regulated and that COX-2 and FACL4 promote carcinogenesis by lowering this level.     

Novel Mutations Including Deletions of the Entire OFD1 Gene in 30 Families with Type 1 Orofaciodigital Syndrome: A Study of the Extensive Clinical Variability

OFD1, now recognized as a ciliopathy, is characterized by malformations of the face, oral cavity and digits, and is transmitted as an X‐linked condition with lethality in males. Mutations in OFD1 also cause X‐linked Joubert syndrome (JBTS10) and Simpson–Golabi–Behmel syndrome type 2 (SGBS2). We have studied 55 sporadic and six familial cases of suspected OFD1. Comprehensive mutation analysis in OFD1 revealed mutations in 37 female patients from 30 families; 22 mutations have not been previously described including two heterozygous deletions spanning OFD1 and neighbouring genes. Analysis of clinical findings in patients with mutations revealed that oral features are the most reliable diagnostic criteria. A first, detailed evaluation of brain MRIs from seven patients with cognitive defects illustrated extensive variability with the complete brain phenotype consisting of complete agenesis of the corpus callosum, large single or multiple interhemispheric cysts, striking cortical infolding of gyri, ventriculomegaly, mild molar tooth malformation and moderate to severe cerebellar vermis hypoplasia. Although the OFD1 gene apparently escapes X‐inactivation, skewed inactivation was observed in seven of 14 patients. The direction of skewing did not correlate with disease severity, reinforcing the hypothesis that additional factors contribute to the extensive intrafamilial variability.     

Age-based construct validation using structural equation modeling

Abstract

In this paper we describe some mathematical and statistical models based on structural equation modeling (SEM) using computer programs like LISREL. We focus on SEM methodology for the simultaneous examination of the internal validity of psychological constructs and the external validity represented by age relations. To illustrate these ideas we use a latent variable path model to examine the organization of intellectual abilities measured by the WAIS-R in the standardization sample. We also examine different ways in which age can be used to structure this organization. This is primarily a methodological paper, but we try to integrate conceptual principles of modeling with some substantive issues of research on the psychology of aging.