Brown Adipose Tissue PPARγ Is Required for the Insulin-Sensitizing Action of Thiazolidinediones

Brown adipose tissue (BAT) plays a critical role in metabolic homeostasis. BAT dysfunction is associated with the development of obesity through an imbalance between energy expenditure and energy intake. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is the master regulator of adipogenesis. However, the roles of PPARγ and thiazolidinediones (TZDs) in the regulation of BAT metabolism remain unclear. TZDs, which are selective PPARγ activators, improve systemic insulin resistance in animals and humans. In the present study, we generated brown adipocyte-specific PPARγ-deficient mice (BATγKO) to examine the in vivo roles of PPARγ and TZDs in BAT metabolism. In electron microscopic examinations, brown adipocyte-specific PPARγ deletion promoted severe whitening of brown fat and morphological alteration of mitochondria. Brown adipocyte-specific PPARγ deletion also reduced mRNA expression of BAT-selective genes. Although there was no difference in energy expenditure between control and BATγKO mice in calorimetry, norepinephrine-induced thermogenesis was impaired in BATγKO mice. Moreover, pioglitazone treatment improved diet-induced insulin resistance in the control mice but not in the BATγKO mice. These findings suggest that BAT PPARγ is necessary for the maintenance of brown adipocyte function and for the insulin-sensitizing action of TZDs

大腿四頭筋の等尺性収縮は、膝蓋上外側アプローチによる膝関節内注射の正確性を向上する

Background: Intra-articular injection is an important technique for treating rheumatoid arthritis and osteoarthritis of the knee. However, medication is often inaccurately injected outside of the joint. We devised an intra-articular injection method in which the needle is inserted into the suprapatellar bursa while the patient maintains isometric contraction of the quadriceps. This isometric contraction method is based on the concept that isometric contraction of the quadriceps induces contraction of the articularis genus muscle, thus expanding the lumen of the suprapatellar bursa. Methods: Intra-articular injections were performed on 150 osteoarthritic knees without effusion. The knees were alternately assigned to the isometric quadriceps method group (75 knees) and non-activated quadriceps method group (75 knees). Prior to joint injection, the anterior-posterior dimension of each suprapatellar bursa was measured to ascertain its expansion. The isometric quadriceps method was performed with the quadriceps and the articularis genus muscle maintained in a contracted state. The non-activated quadriceps method was performed in a relaxed state. Ultrasound guidance was not used for either method. Subsequently, an ultrasonic probe was used only to confirm whether the intra-articular injections were successful. We compared the accuracy of injections performed between the 2 groups. Results: Suprapatellar expansion was significantly larger (p < 0.001) using the isometric quadriceps method (2.1 ± 1.4 mm [range, 0 to 5 mm]) than using the non-activated quadriceps method (0.8 ± 0.7 mm [range, 0 to 2 mm]). The percentage of accurate intra-articular injections was significantly higher (p = 0.0287) using the isometric quadriceps method (93%) compared with the non-activated quadriceps method (80%). Conclusions: In comparison with the non-activated quadriceps method, the isometric quadriceps method led to a larger expansion of the suprapatellar bursa, which should lead to more accurate intra-articular injections. The isometric quadriceps method is effective in reducing inaccurate injections into the synovium or surrounding fatty tissues. Clinical relevance: Putting force on the quadriceps muscle increases the success rate of intra-articular injection of the knee. The results of this study could provide a clinically relevant injection technique for future treatment.博士（医学）・乙第1448号・令和元年12月5日Copyright © 2018 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal

Prevalence of Dementia and Mild Cognitive Impairment in the Rural Island Town of Ama-cho, Japan

Aims: In order to determine the prevalence of dementia and mild cognitive impairment (MCI), we conducted a population-based study in Japan. Methods: Participants included 924 subjects aged 65 years or older who resided in the town of Ama-cho. In phase 1 of the study, the Mini-Mental State Examination and Clinical Dementia Rating were administered for screening purposes. In phase 2 of the study, the subjects who screened positive were further examined by neurologists. Dementia and MCI were diagnosed by means of DSM-IV and International Working Group on MCI criteria, respectively. Results: By the prevalence date of June 1, 2010, 24 subjects had deceased or lived outside the town. In total, 723 of the remaining 900 subjects received a phase 1 test. In phase 2, 98 subjects were diagnosed with amnestic MCI, 113 subjects with non-amnestic MCI, and 82 subjects with dementia. Of the subjects who did not receive the phase 1 test, 66 subjects were diagnosed as having dementia according to data from their town medical card or the Long-term Care Insurance System. The crude prevalence of amnestic MCI, non-amnestic MCI, and dementia were 10.9, 12.6, and 16.4%, respectively. Conclusion: Consistent with the striking increase in the number of elderly individuals, we report higher prevalence of MCI and dementia in Japan than previously described

A Study on formation of the open space on the artificial ground and ownership / management from in Senri central district center

国内で都市形成に人工地盤が用いられた初期の事例として,開発から30年が経過し,街としての成熟が感じられる千里中央地区センターを取り上げ,人工地盤上における広場空間が都市活動の基盤として成立する要因を,広場空間の形成と所有･運営形態との関係を通じて明らかにした。事業主体や利用者による多くのアクティビティが当地区センターの人工地盤上の広場空間に活きた公共空間を形成しており,このような環境に成り得た要因として,鉄道の地下化,人工地盤が宅地上に構築されていること,広場が非常に開放的な空間であること等を述べた

Multimodel uncertainty changes in simulated river flows induced by human impact parameterizations

Human impacts increasingly affect the global hydrological cycle and indeed dominate hydrological changes in some regions. Hydrologists have sought to identify the human-impact-induced hydrological variations via parameterizing anthropogenic water uses in global hydrological models (GHMs). The consequently increased model complexity is likely to introduce additional uncertainty among GHMs. Here, using four GHMs, between-model uncertainties are quantified in terms of the ratio of signal to noise (SNR) for average river flow during 1971–2000 simulated in two experiments, with representation of human impacts (VARSOC) and without (NOSOC). It is the first quantitative investigation of between-model uncertainty resulted from the inclusion of human impact parameterizations. Results show that the between-model uncertainties in terms of SNRs in the VARSOC annual flow are larger (about 2% for global and varied magnitude for different basins) than those in the NOSOC, which are particularly significant in most areas of Asia and northern areas to the Mediterranean Sea. The SNR differences are mostly negative (-20% to 5%, indicating higher uncertainty) for basin-averaged annual flow. The VARSOC high flow shows slightly lower uncertainties than NOSOC simulations, with SNR differences mostly ranging from -20% to 20%. The uncertainty differences between the two experiments are significantly related to the fraction of irrigation areas of basins. The large additional uncertainties in VARSOC simulations introduced by the inclusion of parameterizations of human impacts raise the urgent need of GHMs development regarding a better understanding of human impacts. Differences in the parameterizations of irrigation, reservoir regulation and water withdrawals are discussed towards potential directions of improvements for future GHM development. We also discuss the advantages of statistical approaches to reduce the between-model uncertainties, and the importance of calibration of GHMs for not only better performances of historical simulations but also more robust and confidential future projections of hydrological changes under a changing environment

Development of the Community Water Model (CWatM v1.04) – a high-resolution hydrological model for global and regional assessment of integrated water resources management

We develop a new large-scale hydrological and water resources model, the Community Water Model (CWatM), which can simulate hydrology both globally and regionally at different resolutions from 30 arcmin to 30 arcsec at daily time steps. CWatM is open source in the Python programming environment and has a modular structure. It uses global, freely available data in the netCDF4 file format for reading, storage, and production of data in a compact way. CWatM includes general surface and groundwater hydrological processes but also takes into account human activities, such as water use and reservoir regulation, by calculating water demands, water use, and return flows. Reservoirs and lakes are included in the model scheme. CWatM is used in the framework of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP), which compares global model outputs. The flexible model structure allows for dynamic interaction with hydro-economic and water quality models for the assessment and evaluation of water management options. Furthermore, the novelty of CWatM is its combination of state-of-the-art hydrological modeling, modular programming, an online user manual and automatic source code documentation, global and regional assessments at different spatial resolutions, and a potential community to add to, change, and expand the open-source project. CWatM also strives to build a community learning environment which is able to freely use an open-source hydrological model and flexible coupling possibilities to other sectoral models, such as energy and agriculture