The Impact of Family Functioning on Children's Adaptation During a Parent's Bone Marrow Transplantation

Indiana University-Purdue University Indianapolis (IUPUI)Bone marrow transplant (BMT) is being used ever more widely for advanced and refractory malignancies. The family unit and individual members are profoundly affected by this treatment process. Few studies have examined the effect of parental BMT on the family, and there are no known studies which have investigated the impact of parental BMT on children. A descriptive design with longitudinal data from 61 children, ages 10-18, examined children’s adaptation, characterized as emotional and behavioral response, during the acute phase of parental BMT. The study included 3 time points: pre-transplant, during parental hospitalization, and one month after transplantation. The Response to Stress Questionnaire, and subscales from the Child Health Questionnaire and Family Environment Scale were used to assess child, parent, and family variables associated with child adaptation. Child emotional and behavioral response significantly improved over the course of the parent’s transplant, and significant changes in children’s use of coping strategies at each time point were found. The model accounted for 27% to 46% of the explained variance in child behavioral response, and accounted for 41% of the explained variance in emotional response prior to the parent’s BMT and one month after BMT. The model did not explain the variance of child emotional response, however, during the parent’s hospitalization. Family structural change, family conflict, and disengagement coping were found to be the predominant variables significantly associated with more negative child behavioral response across the transplant trajectory. Female child gender and increased use of disengagement coping before the parent’s BMT, autologous BMT during the parent’s hospitalization, and increased family structural change when the parent returned home one month later were significantly associated with more negative emotional response in children. Additional cross-sectional and longitudinal studies, using mixed methods, and include both parent and child data, are needed to substantiate the validity of findings. The data also suggests that significant variables in this model could be further studied for their association with one another and for refining a more accurate and inclusive model that may better explain children’s adaptation

Preliminary efficacy of a brief family intervention to prevent declining quality of life secondary to parental bone marrow transplantation

The primary purpose of this research was to develop and evaluate the efficacy and feasibility of a brief, cost-effective family-focused intervention to promote adaptive coping and quality of life throughout a parent's bone marrow transplantation (BMT). Targeted outcomes were cohesion, decreased use of avoidance coping, open communication and effective management of emotional distress. Participants included an intervention group of 31 families and 29 families in a control group who received usual care. Each family included the BMT recipient, a partner/caregiver and children 10-18 years old. The intervention included two dyadic sessions for the BMT recipient and the partner/caregiver, one individual session for the caregiver and two digital video discs (DVDs) for children. Statistical analyses indicated that the intervention had a positive impact on at least one aspect of the adaptation of each family member. Caregivers reported the most distress but benefitted least from the intervention, whereas recipients and children reported improvement in distress. Ratings of satisfaction/acceptability were high, with 97% responding that they would recommend the intervention to others. Plans for future research include increased intervention intensity for the caregiver, a larger more diverse sample and implementation over an extended period post BMT

Differential impact of LPG-and PG-deficient Leishmania major mutants on the immune response of human dendritic cells

<div><p>Background</p><p><i>Leishmania major</i> infection induces robust interleukin-12 (IL12) production in human dendritic cells (hDC), ultimately resulting in Th1-mediated immunity and clinical resolution. The surface of <i>Leishmania</i> parasites is covered in a dense glycocalyx consisting of primarily lipophosphoglycan (LPG) and other phosphoglycan-containing molecules (PGs), making these glycoconjugates the likely pathogen-associated molecular patterns (PAMPS) responsible for IL12 induction.</p><p>Methodology/Principal Findings</p><p>Here we explored the role of parasite glycoconjugates on the hDC IL12 response by generating <i>L</i>. <i>major</i> Friedlin V1 mutants defective in LPG alone, (FV1 <i>lpg1-</i>), or generally deficient for all PGs, (FV1 <i>lpg2-</i>). Infection with metacyclic, infective stage, <i>L</i>. <i>major</i> or purified LPG induced high levels of <i>IL12B</i> subunit gene transcripts in hDCs, which was abrogated with FV1 <i>lpg1-</i> infections. In contrast, hDC infections with FV1 <i>lpg2-</i> displayed increased <i>IL12B</i> expression, suggesting other PG-related/<i>LPG2</i> dependent molecules may act to dampen the immune response. Global transcriptional profiling comparing WT, FV1 <i>lpg1-</i>, FV1 <i>lpg2-</i> infections revealed that FV1 <i>lpg1-</i> mutants entered hDCs in a silent fashion as indicated by repression of gene expression. Transcription factor binding site analysis suggests that LPG recognition by hDCs induces IL-12 in a signaling cascade resulting in Nuclear Factor κ B (NFκB) and Interferon Regulatory Factor (IRF) mediated transcription.</p><p>Conclusions/Significance</p><p>These data suggest that <i>L</i>. <i>major</i> LPG is a major PAMP recognized by hDC to induce IL12-mediated protective immunity and that there is a complex interplay between PG-baring <i>Leishmania</i> surface glycoconjugates that result in modulation of host cellular IL12.</p></div

Tumour suppressor p53 down-regulates the expression of the human hepatocyte nuclear factor 4α (HNF4α) gene

The liver is exposed to a wide variety of toxic agents, many of which damage DNA and result in increased levels of the tumour suppressor protein p53. We have previously shown that p53 inhibits the transactivation function of HNF (hepatocyte nuclear factor) 4α1, a nuclear receptor known to be critical for early development and liver differentiation. In the present study we demonstrate that p53 also down-regulates expression of the human HNF4α gene via the proximal P1 promoter. Overexpression of wild-type p53 down-regulated endogenous levels of both HNF4α protein and mRNA in Hep3B cells. This decrease was also observed when HepG2 cells were exposed to UV irradiation or doxorubicin, both of which increased endogenous p53 protein levels. Ectopically expressed p53, but not a mutant p53 defective in DNA binding (R249S), down-regulated HNF4α P1 promoter activity. Chromatin immunoprecipitation also showed that endogenous p53 bound the HNF4α P1 promoter in vivo after doxorubicin treatment. The mechanism by which p53 down-regulates the P1 promoter appears to be multifaceted. The down-regulation was partially recovered by inhibition of HDAC activity and appears to involve the positive regulator HNF6α. p53 bound HNF6α in vivo and in vitro and prevented HNF6α from binding DNA in vitro. p53 also repressed stimulation of the P1 promoter by HNF6α in vivo. However, since the R249S p53 mutant also bound HNF6α, binding HNF6α is apparently not sufficient for the repression. Implications of the p53-mediated repression of HNF4α expression in response to cellular stress are discussed

An alpha-Gal-containing neoglycoprotein-based vaccine partially protects against murine cutaneous leishmaniasis caused by Leishmania major

Submitted by Sandra Infurna ([email protected]) on 2018-02-08T14:28:28Z No. of bitstreams: 1 otacilio_moreira_etal_IOC_2017.pdf: 4048766 bytes, checksum: 739bd60ac93001eb3f167318d867f73c (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2018-02-08T14:43:56Z (GMT) No. of bitstreams: 1 otacilio_moreira_etal_IOC_2017.pdf: 4048766 bytes, checksum: 739bd60ac93001eb3f167318d867f73c (MD5)Made available in DSpace on 2018-02-08T14:43:57Z (GMT). No. of bitstreams: 1 otacilio_moreira_etal_IOC_2017.pdf: 4048766 bytes, checksum: 739bd60ac93001eb3f167318d867f73c (MD5) Previous issue date: 2017University of Texas at El Paso. Department of Biological Sciences. Border Biomedical Research Center. El Paso, Texas, USA.University of Texas at El Paso. Department of Chemistry. Border Biomedical Research Center. El Paso, Texas, USA.Liverpool School of Tropical Medicine. Department of Parasitology. Pembroke Place, Liverpool, United Kingdom.University of Texas at El Paso. Department of Biological Sciences. Border Biomedical Research Center. El Paso, Texas, USA.University of Texas at El Paso. Department of Chemistry. Border Biomedical Research Center. El Paso, Texas, USA.Liverpool School of Tropical Medicine. Department of Parasitology. Pembroke Place, Liverpool, United Kingdom.University of Texas at El Paso. Department of Biological Sciences. Border Biomedical Research Center. El Paso, Texas, USA.University of Texas at El Paso. Department of Biological Sciences. Border Biomedical Research Center. El Paso, Texas, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ. Brasil.Liverpool School of Tropical Medicine. Department of Parasitology. Pembroke Place, Liverpool, United Kingdom / Liverpool School of Tropical Medicine. Department of Vector Biology. Pembroke Place, Liverpool, United Kingdom.University of Texas at El Paso. Department of Chemistry. Border Biomedical Research Center. El Paso, Texas, USA.University of Texas at El Paso. Department of Biological Sciences. Border Biomedical Research Center. El Paso, Texas, USA.University of Texas at El Paso. Department of Biological Sciences. Border Biomedical Research Center. El Paso, Texas, USA.Protozoan parasites from the genus Leishmania cause broad clinical manifestations known as leishmaniases, which affect millions of people worldwide. Cutaneous leishmaniasis (CL), caused by L. major, is one the most common forms of the disease in the Old World. There is no preventive or therapeutic human vaccine available for L. major CL, and existing drug treatments are expensive, have toxic side effects, and resistant parasite strains have been reported. Hence, further therapeutic interventions against the disease are necessary. Terminal, non-reducing, and linear α-galactopyranosyl (α-Gal) epitopes are abundantly found on the plasma membrane glycolipids of L. major known as glycoinositolphospholipids. The absence of these α-Gal epitopes in human cells makes these glycans highly immunogenic and thus potential targets for vaccine development against CL