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Background: Caring for relatives with advanced cancer may cause psychological and physical ill health., Aims: To evaluate the effectiveness of increased support for distressed, informal carers of patients receiving palliative care., Method: The sample was composed of 271 informal carers who scored over 5 on the 28-item General Health Questionnaire (GHQ-28). The intervention comprised six weekly visits by a trained advisor. Primary outcome was carer distress (GHQ-28) at 4-week, 9-week and 12-week follow-up. Secondary outcomes were carer strain and quality of life, satisfaction with care, and bereavement outcome., Results: Scores on the GHQ-28 fell below the threshold of 5/6 in a third of participants in each trial arm at any follow-up point. Mean scores in the intervention group were lower at all time points but these differences were not significant. No difference was observed in secondary outcomes. Carers receiving the intervention reported qualitative benefit., Conclusions: The intervention might have been too brief, and ongoing help might have had accruing benefits. Alternatively, informal carers of patients with cancer may already receive considerable input and the advisor's help gave little additional advantage; or caring for a dying relative is extremely stressful and no amount of support is going to make it much better.

We measured six acidic analgesics or anti-inflammatories (aspirin, ibuprofen, naproxen, ketoprofen, fenoprofen, mefenamic acid), two phenolic antiseptics (thymol, triclosan), four amide pharmaceuticals (propyphenazone, crotamiton, carbamazepine, diethyltoluamide), three phenolic endocrine disrupting chemicals (nonylphenol, octylphenol, bisphenol A), and three natural estrogens (17beta-estradiol, estrone, estriol) in 24-h composite samples of influents and secondary effluents collected seasonally from five municipal sewage treatment plants in Tokyo. Aspirin was most abundant in the influent, with an average concentration of 7300 ng/L (n = 16), followed by crotamiton (921 ng/L), ibuprofen (669 ng/L), triclosan (511 ng/L), and diethyltoluamide (503 ng/L). These concentrations were 1 order of magnitude lower than those reported in the USA and Europe. This can be ascribed to lower consumption of the pharmaceuticals in Japan. Aspirin, ibuprofen, and thymol were removed efficiently during primary + secondary treatment (> 90% efficiency). On the other hand, amide-type pharmaceuticals, ketoprofen, and naproxen showed poor removal (< 50% efficiency), which is probably due to their lower hydrophobicity (logKow < 3). Because of the persistence of crotamiton during secondary treatment, crotamiton was most abundant among the target pharmaceuticals in the effluent. This is the first paper to report ubiquitous occurrence of crotamiton, a scabicide, in sewage. Because crotamiton is used worldwide and it is persistent during secondary treatment, it is a promising molecular marker of sewage and secondary effluent.

Accumulating research suggests that racism may be a major determinant of health. Here we report associations between self-reported experience of racial discrimination and health in New Zealand. Data from the 2002/2003 New Zealand Health Survey, a cross-sectional survey involving face-to-face interviews with 12,500 people, were analysed. Five items were included to capture racial discrimination in two dimensions: experience of ethnically motivated attack (physical or verbal), or unfair treatment because of ethnicity (by a health professional, in work or when gaining housing). Ethnicity was classified using self-identification to one of four ethnic groups: Māori, Pacific, Asian and European/Other peoples. Logistic regression, accounting for the survey design, age, sex, ethnicity and deprivation, was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Māori reported the highest prevalence of "ever" experiencing any of the forms of racial discrimination (34%), followed by similar levels among Asian (28%) and Pacific peoples (25%). Māori were almost 10 times more likely to experience multiple types of discrimination compared to European/Others (4.5% vs. 0.5%). Reported experience of racial discrimination was associated with each of the measures of health examined. Experience of any one of the five types of discrimination was significantly associated with poor or fair self-rated health; lower physical functioning; lower mental health; smoking; and cardiovascular disease. There was strong evidence of a dose-response relationship between the number of reported types of discrimination and each health measure. These results highlight the need for racism to be considered in efforts to eliminate ethnic inequalities in health.

Background: Inequalities in health between different ethnic groups in New Zealand are most pronounced between Māori and Europeans. Our aim was to assess the effect of self-reported racial discrimination and deprivation on health inequalities in these two ethnic groups., Methods: We used data from the 2002/03 New Zealand Health Survey to assess prevalence of experiences of self-reported racial discrimination in Māori (n=4108) and Europeans (n=6269) by analysing the responses to five questions about: verbal attacks, physical attacks, and unfair treatment by a health professional, at work, or when buying or renting housing. We did logistic regression analyses to assess the effect of adjustment for experience of racial discrimination and deprivation on ethnic inequalities for various health outcomes., Findings: Māori were more likely to report experiences of self-reported racial discrimination in all instances assessed, and were almost ten times more likely to experience discrimination in three or more settings than were Europeans (4.5% [95% CI 3.2-5.8] vs 0.5% [0.3-0.7]). After adjustment for discrimination and deprivation, odds ratios (95% CI) comparing Māori and European ethnic groups were reduced from 1.67 (1.35-2.08) to 1.18 (0.92-1.50) for poor or fair self-rated health, 1.70 (1.42-2.02) to 1.21 (1.00-1.47) for low physical functioning, 1.30 (1.11-1.54) to 1.02 (0.85-1.22) for low mental health, and 1.46 (1.12-1.91) to 1.11 (0.82-1.51) for cardiovascular disease., Interpretation: Racism, both interpersonal and institutional, contributes to Māori health losses and leads to inequalities in health between Māori and Europeans in New Zealand. Interventions and policies to improve Māori health and address these inequalities should take into account the health effects of racism.

Aims: To assess exposure to secondhand smoke (SHS) in New Zealand homes and cars and to describe attitudes and behaviours that relate to establishing smokefree settings., Methods: In 2004, a nationwide telephone survey randomly selected and interviewed 2731 respondents. This sample was weighted to represent the national population and was comprised of a general adult population sample (n=1507), a sample selected from the Maori electoral roll (n=924), and a sample of current smokers and people who had recently quit smoking (n=300)., Results: 19.6% of the general population and 42.7% of the Maori sample reported current smoking. Of all current smokers, 47.2% smoked indoors at home and 70.8% smoked in their cars. Maori participants were significantly more likely to be exposed to SHS in their homes than non-Maori participants. There was also some evidence for lower socioeconomic status being related to higher SHS exposure. Extrapolating from the adult exposure data in households with children, it was estimated that 18.9% of children were potentially exposed to SHS indoors at home. However, most respondents (73.6%) lived in homes with total smoking bans., Conclusions: SHS exposure remains a significant problem especially for Maori and low-income New Zealanders. There is a need for further public health campaigns to increase the prevalence of smokefree homes and cars.

The recognition of microbial components by Toll-like receptors (TLRs) is an event central to the activation of innate and adaptive immune systems. TLR activation triggers the induction of downstream target genes, wherein the TLR-interacting adaptor molecule MyD88 recruits various signaling molecules and transcription factors. Two members of the IFN regulatory factor (IRF) family of transcription factors, IRF-5 and IRF-7, interact with MyD88 and induce proinflammatory cytokines and type I IFNs, respectively. Here, we show that IRF-4 also interacts with MyD88 and acts as a negative regulator of TLR signaling. IRF-4 mRNA is induced by TLR activation, and IRF-4 competes with IRF-5, but not with IRF-7, for MyD88 interaction. The TLR-dependent induction of proinflammatory cytokines is markedly enhanced in peritoneal macrophages from mice deficient in the Irf4 gene, whereas the induction is inhibited by the ectopic expression of IRF-4 in a macrophage cell line. The critical function of IRF-4 in TLR signaling in vivo is underscored by the observation that Irf4-deficient mice show hypersensitivity to DNA-induced shock, with elevated serum proinflammatory cytokine levels. This study may provide an insight into the complex regulatory mechanisms of MyD88 signaling by IRFs.

IFN regulatory factor-4 (IRF-4) is a transcription factor that is involved in the development and the functions of lymphocytes, macrophages and dendritic cells. Despite their critical roles in immune system regulation, the target genes controlled by IRF-4 are poorly understood. In this study, we determined the consensus DNA-binding sequences preferred for IRF-4 by in vitro binding site selections. IRF-4 preferentially bound to the sequences containing tandem repeats of 5'-GAAA-3', flanked by CpC, in most cases. IRF-4 repressed the promoter bearing tandem copies of the selected binding sequence, while IRF-1 activated the same constructs. Interestingly, the IRF-1-dependent transactivation is inhibited in the presence of IRF-4, but not IRF-2. A series of deletion mutants of IRF-4 revealed that its DNA-binding domain was necessary and sufficient to antagonize the IRF-1-dependent transactivation. This dominant negative action of IRF-4 over IRF-1 was also observed in a natural promoter context, such as the TRAIL gene. These results indicate that IRF-4 acts as a natural antagonist against IRF-1 in immune cells.

A member of the IFN regulatory factor (IRF) family of transcription factors, IRF-4 is expressed in lymphocytes and macrophage/dendritic cells. Studies using IRF-4-deficient mice have revealed the critical roles of IRF-4 in lymphocyte responses. However, the role of IRF-4 in innate immune responses is not clearly understood. Here, we demonstrate that IRF-4 negatively regulates the production of proinflammatory cytokines by macrophages in response to Toll-like receptor (TLR) stimulation. Mice lacking IRF-4 are sensitive to LPS-induced shock, and their macrophages produce high levels of proinflammatory cytokines, including TNF-alpha and IL-6, in response to TLR ligands. The inhibitory role of IRF-4 in response to TLR stimulation was confirmed by the down-regulation of IRF-4 expression in normal macrophages by using the small interfering RNA technique and by the overexpression of IRF-4 in macrophage line RAW264.7. Activation of the important signaling pathways for cytokine production, NF-kappaB and JNK (c-Jun N-terminal kinase), was enhanced after LPS stimulation in IRF-4(-/-) macrophages. These results imply that IRF-4 negatively regulates TLR signaling and is inhibitory to the production of proinflammatory cytokines in response to TLR stimulation.

Leprosy is the most common cause of peripheral neuropathy in the developing world. It is not expected to be acquired by visitors traveling through these countries. We present a backpacker who contracted leprosy during brief stays in endemic countries.

Objectives: This paper presents preliminary evaluative findings from research on key areas of concern to Māori and forms part of a wider project on the 2001 health system reforms in New Zealand. The paper reports on the development and implementation of the Māori Health Strategy, representation in decision making at governance level in District Health Boards, the inclusion of the Treaty of Waitangi in legislation and workforce issues., Methods: Key informant interviews with 35 Māori and non-Māori respondents, in addition to data from five case study districts, were thematically analysed to gain an understanding of views on the health system reforms to date., Results: The development of a Māori Health Strategy and the mandatory inclusion of Māori in governance and consultation processes have had a positive effect on Māori participation in the public health sector. Whereas previously Māori participation was concentrated in health service provision, the inclusion of specific provisions in the New Zealand Public Health and Disability Act 2000 has resulted in greater Māori inclusion in governance, planning and decision-making roles. However, there are concerns over strategy implementation, sustainability and workforce development., Conclusions: Overall, the findings at this stage indicate that there is support for the post-2000 model. Māori and non-Māori alike have identified positive features of the model that could go some way towards contributing to improved Māori health. However challenges still remain.

IFN regulatory factors (IRFs) are a family of transcription factors that play an essential role in the homeostasis and function of immune systems. Recent studies indicated that IRF-8 is critical for the development of CD11b(low)CD8alpha(+) conventional dendritic cells (DCs) and plasmacytoid DCs. Here we show that IRF-4 is important for CD11b(high)CD8alpha(-) conventional DCs. The development of CD11b(high) DCs from bone marrow of IRF-4(-/-) mice was severely impaired in two culture systems supplemented with either GM-CSF or Flt3-ligand. In the IRF-4(-/-) spleen, the number of CD4(+)CD8alpha(-) DCs, a major subset of CD11b(high) DCs, was severely reduced. IRF-4 and IRF-8 were expressed in the majority of CD11b(high)CD4(+)CD8alpha(-) DCs and CD11b(low)CD8alpha(+) DCs, respectively, in a mutually exclusive manner. These results imply that IRF-4 and IRF-8 selectively play critical roles in the development of the DC subsets that express them.

One of the difficulties in developing an effective malaria vaccine is the antigenic change of the parasite during the life cycle. It is desirable that vaccine-induced protective immunity be effective at different stages of parasite development. Merozoite surface protein 1 (MSP1) is a candidate vaccine antigen against blood-stage malaria, but it is also expressed in the exoerythrocytic forms. It was not known, however, whether the anti-MSP1 immune response is effective against the liver-stage malaria parasite. We generated a recombinant protein of MSP1 fused to heat-shock cognate protein 70 (hsc70) and studied its vaccination effect. When C57BL/6 mice were immunized with the fusion protein prior to challenge infection with Plasmodium yoelii sporozoites, the onset of parasitemia was delayed or no parasitemia was observed. To determine whether this was due to the protective immunity against liver-stage parasites, P. yoelii-specific rRNA in the infected liver was quantitated by real-time reverse transcription-PCR analysis. The level of parasite-specific rRNA was reduced in mice immunized with the fusion protein of MSP1 and hsc70 but not with hsc70 alone, indicating that MSP1-specific immunity can be protective against the exoerythrocytic form of the parasite. Furthermore, the adoptive transfer experiments of immune lymphocytes and serum into naive mice suggested that the protective immunity was dependent on cellular and not humoral immunity. Finally, the vaccine-induced protection was also observed in A/J, C3H, and BALB/c mice, suggesting that MSP1-specific protective immunity at the exoerythrocytic stage can be induced in animals over a wide range of genetic backgrounds.

Objective: To explore the relation between spiritual beliefs and resolution of bereavement., Design: Prospective cohort study of people about to be bereaved with follow up continuing for 14 months after the death., Setting: A Marie Curie centre for specialist palliative care in London., Participants: 135 relatives and close friends of patients admitted to the centre with terminal illness., Main Outcome Measure: Core bereavement items, a standardised measure of grief, measured 1, 9, and 14 months after the patients' death., Results: People reporting no spiritual belief had not resolved their grief by 14 months after the death. Participants with strong spiritual beliefs resolved their grief progressively over the same period. People with low levels of belief showed little change in the first nine months but thereafter resolved their grief. These differences approached significance in a repeated measures analysis of variance (F=2.42, P=0.058). Strength of spiritual belief remained an important predictor after the explanatory power of relevant confounding variables was controlled for. At 14 months the difference between the group with no beliefs and the combined low and high belief groups was 7.30 (95% confidence interval 0.86 to 13.73) points on the core bereavement items scale. Adjusting for confounders in the final model reduced this difference to 4.64 (1.04 to 10.32) points., Conclusion: People who profess stronger spiritual beliefs seem to resolve their grief more rapidly and completely after the death of a close person than do people with no spiritual beliefs.