FOXP1 suppresses immune response signatures and MHC class II expression in activated B-cell-like diffuse large B-cell lymphomas.

The FOXP1 (forkhead box P1) transcription factor is a marker of poor prognosis in diffuse large B-cell lymphoma (DLBCL). Here microarray analysis of FOXP1-silenced DLBCL cell lines identified differential regulation of immune response signatures and major histocompatibility complex class II (MHC II) genes as some of the most significant differences between germinal center B-cell (GCB)-like DLBCL with full-length FOXP1 protein expression versus activated B-cell (ABC)-like DLBCL expressing predominantly short FOXP1 isoforms. In an independent primary DLBCL microarray data set, multiple MHC II genes, including human leukocyte antigen DR alpha chain (HLA-DRA), were inversely correlated with FOXP1 transcript expression (P<0.05). FOXP1 knockdown in ABC-DLBCL cells led to increased cell-surface expression of HLA-DRA and CD74. In R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)-treated DLBCL patients (n=150), reduced HLA-DRA (<90% frequency) expression correlated with inferior overall survival (P=0.0003) and progression-free survival (P=0.0012) and with non-GCB subtype stratified by the Hans, Choi or Visco-Young algorithms (all P<0.01). In non-GCB DLBCL cases with <90% HLA-DRA, there was an inverse correlation with the frequency (P=0.0456) and intensity (P=0.0349) of FOXP1 expression. We propose that FOXP1 represents a novel regulator of genes targeted by the class II MHC transactivator CIITA (MHC II and CD74) and therapeutically targeting the FOXP1 pathway may improve antigen presentation and immune surveillance in high-risk DLBCL patients

Signatures of malaria vaccine efficacy in ageing murine immune memory.

Malaria transmission occurs by mosquito bite. Thereafter, Plasmodium sporozoites specifically invade the liver, where they develop into thousands of merozoites that initiate blood-stage infection and clinical malaria. The pre-erythrocytic phase of a Plasmodium infection is the target of experimental whole-parasite vaccines against malaria. Repeated immunizations with high doses of live, metabolically active sporozoites can induce protracted protection against Plasmodium reinfection. Parasites lacking a Plasmodium-specific apicoplast protein, termed PALM, arrest very late during intrahepatic development just prior to liver merozoite release and can elicit sterile protection with two immunization doses only. In this report, we show in the robust Plasmodium berghei-C57BL/6 model that partial protection extends beyond 1 year after the last immunization. In ageing mice, intracellular cytokine staining of Plasmodium peptide-stimulated intrahepatic CD8+ T cells revealed elevated levels of interferon gamma in vaccinated mice. We conclude that antigen-specific T cells persist in the target organ and are critical signatures of lasting protection. Our data also support the notions that memory T-cell responses generated early in life remain largely intact well into old age and that murine Plasmodium vaccination and infection models are suitable to study the mechanisms of maintenance and efficiency of adaptive immunity during immunosenescence

Soil-transmitted helminthiasis in Uganda: epidemiology and cost of control.

A country-wide description of the distribution of soil-transmitted helminths in Uganda is reported, based on data for 20-185 school-children from 271 schools. The overall prevalence of Ascaris lumbricoides, Trichuris trichiura and hookworm was 6.3%, 5.0% and 43.5%, respectively. The prevalence of A. lumbricoides and T. trichiura was unevenly distributed in the country with prevalence greatest in south-western Uganda whereas hookworm was generally more homogeneously distributed. Based on preliminary cost analysis of an ongoing school-based control programme, the financial delivery cost per school-child treated with albendazole is estimated to be between US dollar 0.04 and 0.08 in different districts

Epidemiology and survival patterns of triple negative breast cancer patients with or without BRCA germline mutation in Chinese

Abstract & poster presentatio

Parental control and monitoring of young people's sexual behaviour in rural North-Western Tanzania: implications for sexual and reproductive health interventions

Background: parenting through control and monitoring has been found to have an effect on young people's sexual behaviour. There is a dearth of literature from sub-Saharan Africa on this subject. This paper examines parental control and monitoring and the implications of this on young people's sexual decision making in a rural setting in North-Western Tanzania.Methods: this study employed an ethnographic research design. Data collection involved 17 focus group discussions and 46 in-depth interviews conducted with young people aged 14-24 years and parents/carers of young people within this age-group. Thematic analysis was conducted with the aid of NVIVO 7 software.Results: parents were motivated to control and monitor their children's behaviour for reasons such as social respectability and protecting them from undesirable sexual and reproductive health (SRH) outcomes. Parental control and monitoring varied by family structure, gender, schooling status, a young person's contribution to the economic running of the family and previous experience of a SRH outcome such as unplanned pregnancy. Children from single parent families reported that they received less control compared to those from both parent families. While a father's presence in the family seemed important in controlling the activities of young people, a mother's did not have a similar effect. Girls especially those still schooling received more supervision compared to boys. Young women who had already had unplanned pregnancy were not supervised as closely as those who hadn't. Parents employed various techniques to control and monitor their children's sexual activities.Conclusions: despite parents making efforts to control and monitor their young people's sexual behaviour, they are faced with several challenges (e.g. little time spent with their children) which make it difficult for them to effectively monitor them. There is a need for interventions such as parenting skills building that might enable parents to improve their relationships with children. This would equip parents with the appropriate skills for positive guidance and monitoring of their children and avoid inappropriate parenting behaviour. As much as parents focus their attention on their school going daughters, there is a need to also remember the out-of-school young people as they are also vulnerable to adverse SRH outcome