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T cells, whereas KG-1 and THP-1 only induced a marginal response. Furthermore, MUTZ-3 displayed the phenotypic and transcriptional profiles of immature dendritic cells, after differentiation with granulocyte-macrophage colony-stimulating factor and interleukin-4. Upon activation with inflammatory cytokines, MUTZ-3 matured phenotypically and exhibited a gene induction similar to that of monocyte-derived dendritic cells. This delineation of the cellular and transcriptional activity of MUTZ-3, in response to maturational stimuli, demonstrates the significance of this cell line as a model for functional studies of inflammatory responses.

Blackfly larvae (Diptera: Simuliidae) are “allogenie ecosystem engineers” that capture fine particulate and dissolved matter from suspension and egest much larger fecal pellets. We investigated the effects of blackfly larvae on organic matter transport at 25 sites along a small stream that flowed 500 m from a lake to the sea. Blackfly density was high upstream (>6 × 105 ind. m−2) and the numbers of fecal pellets in suspension rose markedly downstream from the blackfly aggregation. A total of 1.6 × 109 fecal pellets (biomass 3.2 kg C d−1) were discharged to the sea each day and 8.0 × 108 pellets (biomass 1.6 kg C d−1) were lost from suspension. Sedimenting pellets were available to the benthic microbial and invertebrate communities.

The objectives were to identify factors that predict the use of home help services and transition into institutional care and to study to what extent care services were targeted according to the individuals' needs. A further objective was to study whether people who had moved into institutional care facilities had received home help prior to institutionalisation. A community-dwelling sample (=502) aged 81-100 was twice interviewed and assessed with medical examinations. Their use of public elderly care between 1994/1996 and 2000 was studied using survival analyses. , according to the Andersen Behavioural Model, were the most important predictors for the use of elderly care. Among people living alone, dementia, functional limitations, and depressive symptoms predicted the use of home help services and institutionalisation. Among non-demented cohabiting people, depressive symptoms and dependence in ADLs increased the likelihood of both home help and institutionalisation. Among cohabiting people with dementia, the effect of dementia was difficult to separate from the effects of ADL limitations and depression. were of importance among cohabiting people. A high level of education increased the likelihood of moving into institutional care, and informal extra-residential care increased the likelihood of both outcomes indicating that elderly care resources had not been targeted solely according to need. such as age and gender were of importance only among people living alone. Basically the same factors predicted both the receipt of home help and institutionalisation. Only 4% of people living alone and 5% of those cohabiting moved to institutions without previously receiving home help.

BackgroundOrphan drug development faces numerous challenges, including low disease prevalence, patient population heterogeneity, and strong presence of paediatric patient populations. Consequently, clinical trials for orphan drugs are often smaller than those of non-orphan drugs, and they require the development of efficient trial designs relevant to small populations to gain the most information from the available data. The International Rare Diseases Research Consortium (IRDiRC) is aimed at promoting international collaboration and advance rare diseases research worldwide, and has as one of its goals to contribute to 1000 new therapies for rare diseases. IRDiRC set up a Small Population Clinical Trials (SPCT) Task Force in order to address the shortcomings of our understanding in carrying out clinical trials in rare diseases.ResultsThe IRDiRC SPCT Task Force met in March 2016 to discuss challenges faced in the design of small studies for rare diseases and present their recommendations, structured around six topics: different study methods/designs and their relation to different characteristics of medical conditions, adequate safety data, multi-arm trial designs, decision analytic approaches and rational approaches to adjusting levels of evidence, extrapolation, and patients’ engagement in study design.ConclusionsRecommendations have been issued based on discussions of the Small Population Clinical Trials Task Force that aim to contribute towards successful therapy development and clinical use. While randomised clinical trials are still considered the gold standard, it is recommended to systematically take into consideration alternative trial design options when studying treatments for a rare disease. Combining different sources of safety data is important to give a fuller picture of a therapy’s safety profile. Multi-arm trials should be considered an opportunity for rare diseases therapy development, and funders are encouraged to support such trial design via international networks. Patient engagement is critical in trial design and therapy development, a process which sponsors are encouraged to incorporate when conducting trials and clinical studies. Input from multiple regulatory agencies is recommended early and throughout clinical development. Regulators are often supportive of new clinical trial designs, provided they are well thought through and justified, and they also welcome discussions and questions on this topic. Parallel advice for multiregional development programs should also be considered.

Recent meta-analyses of the methylenetetrahydrofolate reductase gene (MTHFR) have suggested association between two of its functional single gene polymorphisms (SNPs; C677T and A1298C) and schizophrenia. Studies have also suggested association between MTHFR C677T and A1298C variation and bipolar disorder. In a replication attempt the MTHFR C677T and A1298C SNPs were analyzed in three Scandinavian schizophrenia case-control samples. In addition, Norwegian patients with bipolar disorder were investigated. There were no statistically significant allele or genotype case-control differences. The present Scandinavian results do not verify previous associations between the putative functional MTHFR gene polymorphisms and schizophrenia or bipolar disorder. However, when combined with previous studies in meta-analyses there is still evidence for association between the MTHFR C677T polymorphism and schizophrenia. Additional studies are warranted to shed further light on these relationships.

The aim of this study was to map the psychological/psychiatric, odontological and medical aspects of patients with symptoms allegedly related to the side-effects of mercury in dental fillings. A total of 67 consecutive patients and 64 controls matched for age, sex and residential area were included in the study. The most striking result was the high prevalence of psychiatric disorders in the patients (89%) compared to the controls (6%), predominantly somatoform disorders. The personality traits differentiating the patients according to the Karolinska Scales of Personality (KSP) were somatic anxiety, muscular tension, psychasthenia and low socialization. More patients than controls showed alexithymic traits. The prevalence of diagnosed somatic diseases was higher, but not sufficiently so to explain the large difference in perceived health. The multiple symptoms and signs of distress displayed by the patients could not be explained either by the odontological data or by the medical examination. Our data indicate that the patients show sociodemographic and clinical patterns similar to those of somatizing patients. The medicalization of the suffering of these patients and the neglect of psychiatric problems prevent the use of appropriate psychotherapeutic approaches.