Ethics of asking trauma-related questions and exposing participants to arousal-inducing stimuli.

This study examined ethical concerns related to exposing participants with childhood victimization histories to both trauma-specific and non-trauma-specific stimuli. We asked participants questions about childhood victimization experiences and exposed participants to a negatively-arousing experimental condition. Following each of these procedures and at a one-week follow-up session, participants completed a measure designed to asses their reactions to participation. The measure included several questions to assess reactions including questions about distress, benefit, and willingness to participate in the study again. Overall, participants reported low levels of distress and described their participation experience as interesting, enjoyable, and somewhat beneficial. Participants also indicated that they would be willing to participate in the study again with the knowledge of what participation was actually like. Participants with childhood trauma histories and PTSD symptoms reported more distress during the childhood maltreatment screening compared to other participants. However, the level of distress they experienced was mild and transitory. Our findings add to the emerging data indicating that individuals find their participation in trauma-related research to be a positive experience overall, rather than a harmful one.     

Primary Health Care through a community based smoking-cessation program

The International Conference on Primary Health Care, meeting in Alma-Ata, in the Soviet Union, September 12, 1978, expressed the need for urgent action by all governments, all health and development workers and the world community, to protect and promote the health of all people of the world. The world was caught by the phrase which emerged from this conference, Health For All by the Year 2000 and many have examined the articles of the Alma-Ata declaration and tried to implement them in their corner of the world. This paper describes a community-based smoking-cessation program which was implemented in the province of Nova Scotia, Canada, during the years 1980–1984. Primary to this project was the belief that people have the right and the duty to participate individually and collectively in planning and implementing their health care. This paper describes one community's effort in putting this belief into practice.Carol Smillie, B.N. BE.d. M.S.c. is an Assistant Professor at the School of Nursing, Dalhousie University, Halifax, Nova Scotia, Canada B3H 3J5, Katherine Coffin, BA, MEd is the Program Officer, Nova Scotia Office, Health Promotion Directorate Health and Welfare Canada, 5251 Duke Street, Halifax, Nova Scotia. Canada B3J 1P3. Kathryn Porter, B.A. (Gen)., is the Information and Education Coordinator, Nova Scotia Division Canadian Cancer Society. Brenda Ryan, B.A., M.B.A. is Program Evaluation Analysist, Nova Scotia Department of Health, 6088 Hollis Street, Halifax. Nova Scotia, Canada. This Project was funded by Health and Welfare Canada, Nova Scotia Department of Health, Nova Scotia Division Canadian Cancer Society, Requests for reprints should be addressed to: Professor Carol Smillie.     

Costello syndrome: Clinical phenotype,genotype, and management guidelines

Costello syndrome (CS) is a RASopathy caused by activating germline mutations in HRAS. Due to ubiquitous HRAS gene expression, CS affects multiple organ systems and individuals are predisposed to cancer. Individuals with CS may have distinctive craniofacial features, cardiac anomalies, growth and developmental delays, as well as dermatological, orthopedic, ocular, and neurological issues; however, considerable overlap with other RASopathies exists. Medical evaluation requires an understanding of the multifaceted phenotype. Subspecialists may have limited experience in caring for these individuals because of the rarity of CS. Furthermore, the phenotypic presentation may vary with the underlying genotype. These guidelines were developed by an interdisciplinary team of experts in order to encourage timely health care practices and provide medical management guidelines for the primary and specialty care provider, as well as for the families and affected individuals across their lifespan. These guidelines are based on expert opinion and do not represent evidence‐based guidelines due to the lack of data for this rare condition.     

Increased circulating interleukin-7 levels in HIV-1-infected women

Sex-based differences in CD4 T-cell (CD4) counts are well recognized, but the basis for these differences has not been identified. Conceivably, homeostatic factors may play a role in this process by regulating T-cell maintenance and repletion. Interleukin (IL)-7 is essential for normal T-cell production and homeostasis. We hypothesized that differences in IL-7 might contribute to sex-based differences in CD4 counts. Circulating IL-7 levels were analyzed in 299 HIV-1-infected women and men. Regression analysis estimated that IL-7 levels were 40% higher in women than in men (P = 0.0032) after controlling for CD4 count, age, and race. Given the important role of IL-7 in T-cell development and homeostasis, these findings suggest that higher IL-7 levels may contribute to higher CD4 counts in women.     

Cytoskeletal changes during neurogenesis in cultures of avian neural crest cells

Summary Neural crest cells are motile and mitotic, whereas their neuronal derivatives are terminally post-mitotic and consist of stationary cell body from which processes grow. The present study documents changes in the cytoskeleton that occur during neurogenesis in cultures of avian neural crest cells. The undifferentiated neural crest cells contain dense bundles of actin filaments throughout their cytoplasm, and a splayed array of microtubules attached to the centrosome. In newly differentiating neurons, the actin bundles are disrupted and most of the remaining actin filaments are reorganized into a cortical layer underlying the plasma membrane of the cell body and processes. Microtubules are more abundant in newly-differentiating neurons than in the undifferentiated cells, and individual microtubules can be seen dissociated from the centrosome. Neuron-specific -III tubulin appears in some crest cells prior to cessation of motility and cell division, and expression increases with total microtubule levels during neurogenesis. To investigate how these early cytoskeletal changes might contribute to alterations in morphology during neurogenesis, we have disrupted the cytoskeleton with pharmacologic agents. Microfilament disruption by cytochalasin immediately arrests the movement of neural crest cells and causes them to round-up, but does not significantly change the morphology of the immature neurons. Microtubule depolymerization by nocodazole slows the movement of undifferentiated cells and causes retraction of processes extended by the immature neurons. These results suggest that changes in the actin and microtubule arrays within neural crest cells govern distinct aspects of their morphogenesis into neurons.     

Brief report: child-rearing practices of caregivers with and without a child with juvenile rheumatoid arthritis: perspectives of caregivers and professionals

OBJECTIVE: To evaluate predictions from professionals in pediatric rheumatology regarding the child-rearing practices of caregivers of children with juvenile rheumatoid arthritis (JRA) and healthy classmates. METHODS: Sixteen professionals identified items from the Child-Rearing Practices Report (CRPR) that were expected to differentiate between caregivers of children with JRA (64 mothers, 45 fathers) and caregivers of healthy classmates (64 mothers, 40 fathers). Families were interviewed, and physician ratings of disease severity were obtained. RESULTS: Experts predicted difficulties in protectiveness, discipline, and worry. Ratings from parents of children with JRA showed modest agreement with the professionals, surprising similarity to controls, and a limited association with disease factors. CONCLUSIONS: Contrary to expert opinion, JRA has only a modest influence on some child-rearing practices. Educating health care providers may minimize misperceptions about caring for children with JRA, and screening parents of children with more severe disease may assist in allocating education and services for families.     

A trade-off in replication in mosquito versus mammalian systems conferred by a point mutation in the NS4B protein of dengue virus type 4

An acceptable live-attenuated dengue virus vaccine candidate should have low potential for transmission by mosquitoes. We have identified and characterized a mutation in dengue virus type 4 (DEN4) that decreases the ability of the virus to infect mosquitoes. A panel of 1248 mutagenized virus clones generated previously by chemical mutagenesis was screened for decreased replication in mosquito C6/36 cells but efficient replication in simian Vero cells. One virus met these criteria and contained a single coding mutation: a C-to-U mutation at nucleotide 7129 resulting in a Pro-to-Leu change in amino acid 101 of the nonstructural 4B gene (NS4B P101L). This mutation results in decreased replication in C6/36 cells relative to wild-type DEN4, decreased infectivity for mosquitoes, enhanced replication in Vero and human HuH-7 cells, and enhanced replication in SCID mice implanted with HuH-7 cells (SCID-HuH-7 mice). A recombinant DEN4 virus (rDEN4) bearing this mutation exhibited the same set of phenotypes. Addition of the NS4B P101L mutation to rDEN4 bearing a 30 nucleotide deletion (Delta30) decreased the ability of the double-mutant virus to infect mosquitoes but increased its ability to replicate in SCID-HuH-7 mice. Although the NS4B P101L mutation decreases infectivity of DEN4 for mosquitoes, its ability to enhance replication in SCID-HuH-7 mice suggests that it might not be advantageous to include this specific mutation in an rDEN4 vaccine. The opposing effects of the NS4B P101L mutation in mosquito and vertebrate systems suggest that the NS4B protein is involved in maintaining the balance between efficient replication in the mosquito vector and the human host.     

Distinct expression and localization of serine protease HtrA1 in human endometrium and first-trimester placenta.

Mammalian embryos cannot survive without the placenta. Development of the human placenta requires trophoblast proliferation, differentiation, and invasion as well as highly coordinated modulation of the maternal uterus. HtrA1 is a member of the recently identified mammalian HtrA (high temperature requirement factor A) serine protease family with a high level of expression in the placenta. In this study, we examined whether HtrA1 expression (mRNA and protein) is associated with placental development in the human. HtrA1 is up-regulated in both endometrial glands and decidual cells during endometrial preparation for embryo implantation and during first-trimester pregnancy at placentation. HtrA1 expression was also detected in certain trophoblast subtypes during early pregnancy. The villous syncytiotrophoblast and cytotrophoblast showed the strongest expression while the interstitial extravillous trophoblast showed the lowest or no expression of HtrA1. The distinct distribution of HtrA1 at the maternal-trophoblast interface suggests that HtrA1 may play a role in placental development.