STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing.

Signal transducer and activator of transcription (STAT) 3 is a pleiotropic transcription factor with important functions in cytokine signaling in a variety of tissues. However, the role of STAT3 in the intestinal epithelium is not well understood. We demonstrate that development of colonic inflammation is associated with the induction of STAT3 activity in intestinal epithelial cells (IECs). Studies in genetically engineered mice showed that epithelial STAT3 activation in dextran sodium sulfate colitis is dependent on interleukin (IL)-22 rather than IL-6. IL-22 was secreted by colonic CD11c(+) cells in response to Toll-like receptor stimulation. Conditional knockout mice with an IEC-specific deletion of STAT3 activity were highly susceptible to experimental colitis, indicating that epithelial STAT3 regulates gut homeostasis. STAT3(IEC-KO) mice, upon induction of colitis, showed a striking defect of epithelial restitution. Gene chip analysis indicated that STAT3 regulates the cellular stress response, apoptosis, and pathways associated with wound healing in IECs. Consistently, both IL-22 and epithelial STAT3 were found to be important in wound-healing experiments in vivo. In summary, our data suggest that intestinal epithelial STAT3 activation regulates immune homeostasis in the gut by promoting IL-22-dependent mucosal wound healing.

Rate and predictors of service disengagement in an epidemiological first-episode psychosis cohort.

OBJECTIVES: To assess the prevalence and predictors of service disengagement in a treated epidemiological cohort of first-episode psychosis (FEP) patients. METHODS: The Early Psychosis Prevention and Intervention Centre (EPPIC) in Australia admitted 786 FEP patients from January 1998 to December 2000. Treatment at EPPIC is scheduled for 18 months. Data were collected from patients' files using a standardized questionnaire. Seven hundred four files were available; 44 were excluded, because of a non-psychotic diagnosis at endpoint (n=43) or missing data on service disengagement (n=1). Rate of service disengagement was the outcome of interest, as well as pre-treatment, baseline, and treatment predictors of service disengagement, which were examined via Cox proportional hazards models. RESULTS: 154 patients (23.3%) disengaged from service. A past forensic history (Hazard ratio [HR]=1.69; 95%CI 1.17-2.45), lower severity of illness at baseline (HR=0.59; 95%CI 0.48-0.72), living without family at discharge (HR=1.75; 95%CI 1.22-2.50) and persistence of substance use disorder during treatment (HR=2.30; 95%CI 1.45-3.66) were significant predictors of disengagement from service. CONCLUSIONS: While engagement strategies are a core element in the treatment of first-episode psychosis, particular attention should be paid to these factors associated with disengagement. Involvement of the family in the treatment process, and focusing on reduction of substance use, need to be pursued in early intervention services.

Cité sous terre : des archéologues suisses explorent la cité grecque d'Erétrie. Catalogue de l'exposition à l'Antikenmuseum Basel und Sammlung Ludwig (22.09.2010-30.01.2011).

Erétrie est l'une de ces cités qui ont fait la grandeur de la Grèce antique. La ville a conservé d'importants vestiges, dont plusieurs chefs-d'oeuvre artistiques. Depuis 1964, des archéologues suisses en poursuivent l'exploration commencée il y a plus d'un siècle. De ces recherches, menées en étroite collaboration avec les autorités grecques, est né le projet d'offrir pour la première fois au public un aperçu de la vie d'une cité grecque à travers quelque 500 objets de prestige et de la vie courante. L'ouvrage accompagne une exposition, organisée par l'Ecole suisse d'archéologie en Grèce, en collaboration avec l'Antikenmuseum Basel und Sammlung Ludwig

Tau and neurofilaments in a family with frontotemporal dementia unlinked to chromosome 17q21-22.

A Swiss frontotemporal dementia (FTD) kindred with extrapyramidal-like features and without motor neuron disease shows a brain pathology with ubiquitin-positive but tau-negative inclusions. Tau and neurofilament modifications are now studied here in three recently deceased family members. No major and specific decrease of tau was observed as described by others in, e.g., sporadic cases of FTD with absence of tau-positive inclusions. However, a slight decrease of tau, neurofilament, and synaptic proteins, resulting from frontal atrophy was detected. In parallel, polymorphic markers on chromosome 17q21-22, the centromeric region of chromosome 3 and chromosome 9, were tested. Haplotype analysis showed several recombination events for chromosomes 3 and 17, but patients shared a haplotype on chromosome 9q21-22. However as one of the patients exhibited Alzheimer and vascular dementia pathology with uncertain concomitant FTD, this locus is questionable. Altogether, these data indicate principally that the Swiss kindred is unlinked to locus 17q21-22, and that tau is not at the origin of FTD in this family.

Influência dos parâmetros de reconstrução analíticos e iterativos na cintigrafia de perfusão do miocárdio

As guidelines de cardiologia nuclear europeia e americanas não são específicas na escolha dos melhores parâmetros de reconstrução de imagem a utilizar na Cintigrafia de Perfusão do Miocárdio (CPM). Assim, o presente estudo teve como objectivo estabelecer e comparar o efeito dos parâmetros quantitativos dos métodos de reconstrução: Retroprojecção Filtrada (FBP) e Ordered ‑Sub‑set Expectation Maximization (OSEM). Métodos: Foi utilizado um fantoma cardíaco, cujos valores do volume telediastólico (VTD), volume telesistólico (VTS) e fracção de ejecção ventricular esquerda (FEVE) eram conhecidos. O software Quantitative Gated SPECT/Quantitative Perfusion SPECT foi utilizado em modo semi‑automático, a fim de obter esses parâmetros quantitativos. O filtro Butterworth foi usado no FBP com as frequências de corte entre 0,2 e 0,8 ciclos/pixel combinadas com as ordens de 5, 10, 15 e 20. Na reconstrução OSEM, foram utilizados os subconjuntos 2, 4, 6, 8, 10, 12 e 16, combinados com os números de iterações de 2, 4, 6, 8, 10, 12, 16, 32 e 64. Durante a reconstrução OSEM efectuou‑se uma outra reconstrução baseada no número de iterações equivalentes - Expectation‑Maximization (EM) 12, 14, 16, 18, 20, 22, 26, 28, 30 e 32. Resultados: Após a reconstrução com FBP verificou‑se que os valores de VTD e VTS aumentavam com o aumento da frequência de corte, enquanto o valor da FEVE diminui. Esse mesmo padrão é verificado na reconstrução OSEM. No entanto, com OSEM há uma estimativa mais precisa dos parâmetros quantitativos, especialmente com as combinações 2I × 10S e 12S × 2I. Conclusão: A reconstrução OSEM apresenta uma melhor estimativa dos parâmetros quantitativos e uma melhor qualidade de imagem do que a reconstrução com FBP. Este estudo recomenda o uso de 2 iterações com 10 ou 12 subconjuntos para a reconstrução OSEM e uma frequência de corte de 0,5 ciclos/pixel com as ordens 5, 10 ou 15 para a reconstrução com FBP como a melhor estimativa para a quantificação da FEVE através da CPM.

18F-fluorodeoxyglucose positron emission tomography/computed tomography and magnetic resonance imaging in patients with liver metastases from uveal melanoma: results from a pilot study.

PURPOSE: F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and MRI are used for detecting liver metastases from uveal melanoma. The introduction of new treatment options in clinical trials might benefit from early response assessment. Here, we determine the value of FDG-PET/CT with respect to MRI at diagnosis and its potential for monitoring therapy. MATERIAL AND METHODS: Ten patients with biopsy-proven liver metastases of uveal melanoma enrolled in a randomized phase III trial (NCT00110123) underwent both FDG-PET coupled with unenhanced CT and gadolinium-diethylene triamine pentaacetic acid-enhanced liver MRI within 4 weeks. FDG-PET and MRI were evaluated blindly and then compared using the ratio of lesion to normal liver parenchyma PET-derived standardized uptake value (SUV). The influence of lesion size and response to chemotherapy were studied. RESULTS: Overall, 108 liver lesions were seen: 34 (31%) on both modalities (1-18 lesions/patient), four (4%) by PET/CT only, and 70 (65%) by MRI only. SUV correlated with MRI lesion size (r=0.81, P<0.0001). PET/CT detected 26 of 33 (79%) MRI lesions of more than or equal to 1.2 cm, whereas it detected only eight of 71 (11%) lesions of less than 1.2 cm (P<0.0001). MRI lesions without PET correspondence were small (0.6±0.2 vs. 2.1±1.1 cm, P<0.0001). During follow-up (six patients, 30 lesions), the ratio lesion-to-normal-liver SUV diminished in size-stable lesions (1.90±0.64-1.46±0.50, P<0.0001), whereas it increased in enlarging lesions (1.56±0.40-1.99±0.56, P=0.032). CONCLUSION: MRI outweighs PET/CT for detecting small liver metastases. However, PET/CT detected at least one liver metastasis per patient and changes in FDG uptake not related to size change, suggesting a role in assessing early therapy response.