Gut commensal microbes shape the mucosal immune system by regulating the differentiation and expansion of several types of T cell. Clostridia, a dominant class of commensal microbe, can induce colonic regulatory T (Treg) cells, which have a central role in the suppression of inflammatory and allergic responses. However, the molecular mechanisms by which commensal microbes induce colonic Treg cells have been unclear. Here we show that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic Treg cells in mice. A comparative NMR-based metabolome analysis suggests that the luminal concentrations of short-chain fatty acids positively correlates with the number of Treg cells in the colon. Among short-chain fatty acids, butyrate induced the differentiation of Treg cells in vitro and in vivo, and ameliorated the development of colitis induced by adoptive transfer of CD4(+) CD45RB(hi) T cells in Rag1(-/-) mice. Treatment of naive T cells under the Treg-cell-polarizing conditions with butyrate enhanced histone H3 acetylation in the promoter and conserved non-coding sequence regions of the Foxp3 locus, suggesting a possible mechanism for how microbial-derived butyrate regulates the differentiation of Treg cells. Our findings provide new insight into the mechanisms by which host-microbe interactions establish immunological homeostasis in the gut.

Although accurate prediction of survival is essential for palliative care, few clinical methods of determining how long a patient is likely to live have been established. To develop a validated scoring system for survival prediction, a retrospective cohort study was performed with a training-testing procedure on two independent series of terminally ill cancer patients. Performance status (PS) and clinical symptoms were assessed prospectively. In the training set (355 assessments on 150 patients) the Palliative Prognostic Index (PPI) was defined by PS, oral intake, edema, dyspnea at rest, and delirium. In the testing sample (233 assessments on 95 patients) the predictive values of this scoring system were examined. In the testing set, patients were classified into three groups: group A (PPI< or =2.0), group B (2.04.0). Group B survived significantly longer than group C, and group A survived significantly longer than either of the others. Also, when a PPI of more than 6 was adopted as a cut-off point, 3 weeks' survival was predicted with a sensitivity of 80% and a specificity of 85%. When a PPI of more than 4 was used as a cutoff point, 6 weeks' survival was predicted with a sensitivity of 80% and a specificity of 77%. In conclusion, whether patients live longer than 3 or 6 weeks can be acceptably predicted by PPI.

The aim of this study was to develop a measure for evaluating good death from the bereaved family member's perspective, and to examine the validity and reliability of the assessment. A cross-sectional anonymous questionnaire was administered to bereaved family members of cancer patients who had died in a regional cancer center from September 2004 to February 2006. We measured the Good Death Inventory (GDI), Care Evaluation Scale, and an overall care satisfaction scale. A retest was conducted one month after sending the questionnaire. Of the 344 questionnaires sent to bereaved family members, 189 responses were analyzed (57%). A factor analysis of the responses to the GDI identified 10 core domains: ''environmental comfort,'' ''life completion,'' ''dying in a favorite place,'' ''maintaining hope and pleasure,'' ''independence,'' ''physical and psychological comfort,'' ''good relationship with medical staff,'' ''not being a burden to others,'' ''good relationship with family,'' and ''being respected as an individual.'' Eight optional domains also were identified: ''religious and spiritual comfort,'' ''receiving enough treatment,'' ''control over the future,'' ''feeling that one's life is worth living,'' ''unawareness of death,'' ''pride and beauty,'' ''natural death,'' and ''preparation for death.'' The GDI had sufficient concurrent validity with the Care Evaluation Scale and overall care satisfaction, sufficient internal consistency (alpha ¼ 0.74e0.95), and acceptable testeretest reliability (ICC ¼ 0.38e0.72). Finally, we developed a short version of the GDI. The GDI is a valid scale to measure end-of-life care comprehensive outcomes from the bereaved family member's perspective in Japan. J Pain Symptom Manage

We conclude that the Short-Term Life Review is effective in improving the spiritual well-being of terminally ill cancer patients, and alleviating psychosocial distress and promoting a good death.

Background: The aims of this study were to (i) conceptualize dimensions of a good death in Japanese cancer care,(ii) clarify the relative importance of each component of a good death and (iii) explore factors related to an individual's perception of the domains of a good death. Methods:The general population was sampled using a stratified random sampling method (n = 2548; response rate, 51%) and bereaved families from 12 certified palliative care units were surveyed as well (n = 513; 70%). We asked the subjects about the relative importance of 57 components of a good death.Results: Explanatory factor analysis demonstrated 18 domains contributing to a good death. Ten domains were classified as Ôconsistently important domainsÕ, including Ôphysical and psychological comfortÕ, Ôdying in a favorite placeÕ, Ôgood relationship with medical staffÕ, Ômaintaining hope and pleasureÕ, Ônot being a burden to othersÕ, Ôgood relationship with familyÕ, Ôphysical and cognitive controlÕ, Ôenvironmental comfortÕ, Ôbeing respected as an individualÕ and Ôlife completionÕ. Conclusions:We quantitatively identified 18 important domains that contribute to a good death in Japanese cancer care. The next step of our work should be to conduct a national survey to identify what is required to achieve a good death.