中国における貿易自由化による地域経済効果の数量的分析

Tohoku University横川和男課

JAK3 as an emerging target for topical treatment of inflammatory skin diseases

The recent interest and elucidation of the JAK/STAT signaling pathway created new targets for the treatment of inflammatory skin diseases (ISDs). JAK inhibitors in oral and topical formulations have shown beneficial results in psoriasis and alopecia areata. Patients suffering from other ISDs might also benefit from JAK inhibition. Given the development of specific JAK inhibitors, the expression patterns of JAKs in different ISDs needs to be clarified. We aimed to analyze the expression of JAK/STAT family members in a set of prevalent ISDs: psoriasis, lichen planus (LP), cutaneous lupus erythematosus (CLE), atopic dermatitis (AD), pyoderma gangrenosum (PG) and alopecia areata (AA) versus healthy controls for (p) JAK1, (p) JAK2, (p) JAK3, (p) TYK2, pSTAT1, pSTAT2 and pSTAT3. The epidermis carried in all ISDs, except for CLE, a strong JAK3 signature. The dermal infiltrate showed a more diverse expression pattern. JAK1, JAK2 and JAK3 were significantly overexpressed in PG and AD suggesting the need for pan-JAK inhibitors. In contrast, psoriasis and LP showed only JAK1 and JAK3 upregulation, while AA and CLE were characterized by a single dermal JAK signal (pJAK3 and pJAK1, respectively). This indicates that the latter diseases may benefit from more targeted JAK inhibitors. Our in vitro keratinocyte psoriasis model displayed reversal of the psoriatic JAK profile following tofacitinib treatment. This direct interaction with keratinocytes may decrease the need for deep skin penetration of topical JAK inhibitors in order to exert its effects on dermal immune cells. In conclusion, these results point to the important contribution of the JAK/STAT pathway in several ISDs. Considering the epidermal JAK3 expression levels, great interest should go to the investigation of topical JAK3 inhibitors as therapeutic option of ISDs

Barriers and Facilitators to Civic Engagement Among Elderly African Immigrants in Oslo

The numbers of elderly immigrants are increasing in Norway and their participation in civic activities is recognized to be crucial to their health and wellbeing. A qualitative study of 24 African immigrants aged 50 years and over was carried out in Oslo. Semi-structured interviews were used to explore barriers and facilitators to civic engagement among elderly African immigrants. The study discovered a number of barriers to participation of elderly immigrants in civic organizations. These barriers include poor health conditions, lack of information about relevant organizations, language difficulties and mistrust towards organizations. The elderly immigrants also pointed to the effectiveness of organizations in addressing community issues as a factor motivating their civic engagement. We argue that the barriers identified by this study pose challenges to achieving Norwegian policy goals of integration and Norwegian policy for active ageing. Hence, there is a need for service providers and policy makers to ensure voluntary organizations address those barriers effectively

Types of social capital resources and self-rated health among the Norwegian adult population

<p>Abstract</p> <p>Background</p> <p>Social inequalities in health are large in Norway. In part, these inequalities may stem from differences in access to supportive social networks - since occupying disadvantaged positions in affluent societies has been associated with disposing poor network resources. Research has demonstrated that social networks are fundamental resources in the prevention of mental and physical illness. However, to determine potentials for public health action one needs to explore the health impact of <it>different types </it>of network resources and analyze if the association between socioeconomic position and self-rated health is partially explained by social network factors. That is the aim of this paper.</p> <p>Methods</p> <p>Cross-sectional data were collected in 2007, through a postal survey from a gross sample of 8000 Norwegian adults, of which 3,190 (about 40%) responded. The outcome variable was self-rated health. Our main explanatory variables were indicators of socioeconomic positions and social capital indicators that was measured by different indicators that were grouped under '<it>bonding'</it>, '<it>bridging' </it>and '<it>linking' </it>social capital. Demographic data were collected for statistical control. Generalized ordered logistic regression analysis was performed.</p> <p>Result</p> <p>Results indicated that those who had someone to talk to when distressed were more likely to rate their health as good compared to those deprived of such person(s) (OR: 2.17, 95% CI: 1.55, 3.02). Similarly, those who were active members in two or more social organisations (OR: 1.73, 95% CI: 1.34, 2.22) and those who count a medical doctor among their friends (OR: 1.51, 95% CI: 1.13, 2.00) report better health. The association between self-rated health and socio-economic background indicators were marginally attenuated when social network indicators were added into the model.</p> <p>Conclusion</p> <p>Among different types of network resources, close and strong friendship-based ties are of importance for people's health in Norway. Networks linking people to high-educated persons are also of importance. Measures aiming at strengthening these types of network resources for socially disadvantaged groups might reduce social inequalities in health.</p

Clinical significance of plasmacytoid dendritic cells and myeloid-derived suppressor cells in melanoma

Background: Immune markers in the peripheral blood of melanoma patients could provide prognostic information. However, there is currently no consensus on which circulating cell types have more clinical impact. We therefore evaluated myeloid-derived suppressor cells (MDSC), dendritic cells (DC), cytotoxic T-cells and regulatory T-cells (Treg) in a series of blood samples of melanoma patients in different stages of disease. Methods: Flow cytometry was performed on peripheral blood mononuclear cells of 69 stage I to IV melanoma patients with a median follow-up of 39 months after diagnosis to measure the percentage of monocytic MDSCs (mMDSCs), polymorphonuclear MDSCs (pmnMDSCs), myeloid DCs (mDCs), plasmacytoid DCs (pDCs), cytotoxic T-cells and Tregs. We also assessed the expression of PD-L1 and CTLA-4 in cytotoxic T-cells and Tregs respectively. The impact of cell frequencies on prognosis was tested with multivariate Cox regression modelling. Results: Circulating pDC levels were decreased in patients with advanced (P = 0.001) or active (P = 0.002) disease. Low pDC levels conferred an independent negative impact on overall (P = 0.025) and progression-free survival (P = 0.036). Even before relapse, a decrease in pDC levels was observed (P = 0.002, correlation coefficient 0.898). High levels of circulating MDSCs (>4.13%) have an independent negative prognostic impact on OS (P = 0.012). MDSC levels were associated with decreased CD3+ (P < 0.001) and CD3 + CD8+ (P = 0.017) T-cell levels. Conversely, patients with high MDSC levels had more PD-L1+ T-cells (P = 0.033) and more CTLA-4 expression by Tregs (P = 0.003). pDCs and MDSCs were inversely correlated (P = 0.004). The impact of pDC levels on prognosis and prediction of the presence of systemic disease was stronger than that of MDSC levels. Conclusion: We demonstrated that circulating pDC and MDSC levels are inversely correlated but have an independent prognostic value in melanoma patients. These cell types represent a single immunologic system and should be evaluated together. Both are key players in the immunological climate in melanoma patients, as they are correlated with circulating cytotoxic and regulatory T-cells. Circulating pDC and MDSC levels should be considered in future immunoprofiling efforts as they could impact disease management

Health disparities, and health behaviours of older immigrants & native population in Norway

publishedVersio

When female circumcision comes to the West: Attitudes toward the practice among Somali Immigrants in Oslo

Somalia is the country with the highest prevalence of female circumcision in the world, this affects Somali diaspora as well. The article investigates whether or not Somali immigrants’ attitudes in Oslo toward the practice has improved in favor of its abandonment.Soomaaliya waa dalka adduunka ugu badan gudniinka haweenka, arrintaanna waxay saamayn ku leedahay xitaa qurbajoogta soomaaliyeed. Maqaalku wuxuu baarayaa haddii qaxootiga soomaaliyeed ee Oslo uu wax iska beddelay kategidda adeegsiga gudniikaas.La Somalia è il paese con la più alta prevalenza di circoncisione femminile al mondo, e questo influisce anche sulla diaspora somala. L'articolo indaga se l'atteggiamento nei confronti di questa pratica degli immigrati somali a Oslo è migliorato a favore del suo abbandono

A phase I/II trial of fixed-dose stereotactic body radiotherapy with sequential or concurrent pembrolizumab in metastatic urothelial carcinoma : evaluation of safety and clinical and immunologic response

Background: Current first-line standard of therapy for metastatic urothelial carcinoma is platinum-based combination chemotherapy. Pembrolizumab in phase III has demonstrated a promising overall response rate of 21.1% in patients with progression or recurrence after platinum-based chemotherapy. Preclinical and clinical evidence suggests that radiotherapy has a systemic anti-cancer immune effect and can increase the level of PD-L1 and tumor infiltrating lymphocytes in the tumor microenvironment. These findings gave rise to the hypothesis that the combination of radiotherapy with anti-PD1 treatment could lead to a synergistic effect, hereby enhancing response rates. Methods: The phase I part will assess the dose limiting toxicity of the combination treatment of stereotactic body radiotherapy (SBRT) with four cycles of pembrolizumab (200 mg intravenously, every 3 weeks) in patients with metastatic urothelial carcinoma. The dose of both pembrolizumab and SBRT will be fixed, yet the patients will be randomized to receive SBRT either before the first cycle of pembrolizumab or before the third cycle of pembrolizumab. SBRT will be delivered (24 Gy in 3 fractions every other day) to the largest metastatic lesion. Secondary objectives include response rate according to RECIST v1.1 and immune related response criteria, progression-free survival and overall survival. The systemic immune effect triggered by the combination therapy will be monitored on various time points during the trial. The PD-L1/TIL status of the tumors will be analyzed via immunohistochemistry and response rates in the subgroups will be analyzed separately. A Simon's two-stage optimum design is used to select the treatment arm associated with the best response rate and with acceptable toxicity to proceed to the phase II trial. In this phase, 13 additional patients will be accrued to receive study treatment. Discussion: The progress made in the field of immunotherapy has lead to promising breakthroughs in various solid malignancies. Unfortunately, the majority of patients do not respond. The current trial will shed light on the toxicity and potential anti-tumor activity of the combination of radiotherapy with anti-PD1 treatment and may identify potential new markers for response and resistance to therapy