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Objective To examine whether eating until full or eating quickly or combinations of these eating behaviours are associated with being overweight. Design and participants Cross sectional survey. Setting Two communities in Japan. Results 571 (50.9%) men and 1265 (58.4%) women self reported eating until full, and 523 (45.6%) men and 785 (36.3%) women self reported eating quickly. For both sexes the highest age adjusted mean values for height, weight, body mass index, and total energy intake were in the eating until full and eating quickly group compared with the not eating until full and not eating quickly group. The multivariable adjusted odds ratio of being overweight for eating until full was 2.00 (95% confidence interval 1.53 to 2.62) for men and 1.92 (1.53 to 2.40) for women and for eating quickly was 1.84 (1.42 to 2.38) for men and 2.09 (1.69 to 2.59) for women. The multivariable odds ratio of being overweight with both eating behaviours compared with neither was 3.13 (2.20 to 4.45) for men and 3.21 (2.41 to 4.29) for women. Conclusion Eating until full and eating quickly are associated with being overweight in Japanese men and women, and these eating behaviours combined may have a substantial impact on being overweight.

Clinical transplantation for the treatment of end-stage organ disease is limited by a shortage of donor organs. Successful xenotransplantation could immediately overcome this limitation. The development of homozygous a 1,3-galactosyltransferase knockout (GalT-KO) pigs removed hyperacute rejection as the major immunologic hurdle to xenotransplantation. Nevertheless, GalT-KO organs stimulate robust immunologic responses that are not prevented by immunosuppressive drugs. Murine studies show that recipient thymopoiesis in thymic xenografts induces xenotolerance. We transplanted life-supporting composite thymokidneys (composite thymus and kidneys) prepared in GalT-KO miniature swine to baboons in an attempt to induce tolerance in a preclinical xenotransplant model. Here, we report the results of seven xenogenic thymokidney transplants using a steroid-free immunosuppressive regimen that eliminated whole-body irradiation in all but one recipient. The regimen resulted in average recipient survival of over 50 days. This was associated with donor-specific unresponsiveness in vitro and early baboon thymopoiesis in the porcine thymus tissue of these grafts, suggesting the development of T-cell tolerance. The kidney grafts had no signs of cellular infiltration or deposition of IgG, and no grafts were lost due to rejection. These results show that xenogeneic thymus transplantation can support early primate thymopoiesis, which in turn may induce T-cell tolerance to solid organ xenografts.

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Spinal mobility and back extensor strength (BES) are important in determining quality of life (QOL) for elderly people. However, the impact of spinal factors on falls remains unclear. The purpose of this study was to clarify spinal factors related to falls in elderly people, including deformity of spinal curvature, spinal mobility and BES. Subjects comprised 92 elderly people divided into 3 groups: subjects without a history of falls or fear of falls (Non-falls group, n = 40); subjects with a history of fear of falls or requiring any support when walking (Fear of falls group, n = 36); and subjects with a history of falls (Falls group, n = 16). Kyphotic angles and mobility of the thoracic and/or lumbar spine, and spinal inclination were measured using a computer-assisted device. Postural imbalance was evaluated using a computerized stabilometer. Isometric BES was also measured. Angle of lumbar kyphosis, spinal inclination, and postural imbalance were significantly higher in the Falls group (p < 0.05) compared to those in the Non-falls group. Mobility of the lumbar spine and BES were significantly lower in the Falls group (p < 0.05) than in the Non-falls group. Multiple logistic regression analysis after adjusting for age, gender, height, and body weight showed grip strength (p = 0.0028), BES (p = 0.0052), lumbar kyphosis (p = 0.0057), spinal inclination (p = 0.0378), mobility of lumbar spine (0.027), and mobility of spinal inclination (p = 0.0282) were significantly associated with presence/absence of falls in elderly individuals.

Advances in the culture of mineralizing growth plate chondrocytes provided an opportunity to study endochondral calcification under controlled conditions. Here we report that these cultures synthesize large amounts of proteins characteristically associated with mineralization: type II and X collagens, sulfated proteoglycans, alkaline phosphatase, and the bone-related proteins, osteonectin and osteopontin. Certain chondrocytes appeared to accumulate large amounts of Ca2+ and Pi during the mineralization process: laser confocal imaging revealed high levels of intracellular Ca2+ in their periphery and X-ray microanalytical mapping revealed the presence of many Ca(2+)- and Pi-rich cell surface structures ranging from filamentous processes 0.14 +/- 0.02 microns by 0.5-2.0 microns, to spherical globules 0.70 +/- 0.27 microns in diameter. Removal of organic matter with alkaline sodium hypochlorite revealed numerous deposits of globular (0.77 +/- 0.19 micron) mineral (calcospherites) in the lacunae around these cells. The size and spatial distribution of these mineral deposits closely corresponded to the Ca(2+)-rich cell surface blebs. The globular mineral progressively transformed into clusters of crystallites. Taken with earlier studies, these findings indicate that cellular uptake of Ca2+ and Pi leads to formation of complexes of amorphous calcium phosphate, membrane lipids, and proteins that are released as cell surface blebs analogous to matrix vesicles. These structures initiate development of crystalline mineral. Thus, the current findings support the concept that the peripheral intracellular accumulation of Ca2+ and Pi is directly involved in endochondral calcification.

Dysregulation of lysine (K)-specific demethylase 1A (LSD1), also known as KDM1A, has been implicated in the development of various cancers, including leukemia. Here, we describe the antileukemic activity and mechanism of action of T-3775440, a novel irreversible LSD1 inhibitor. Cell growth analysis of leukemia cell lines revealed that acute erythroid leukemia (AEL) and acute megakaryoblastic leukemia cells (AMKL) were highly sensitive to this compound. T-3775440 treatment enforced transdifferentiation of erythroid/megakaryocytic lineages into granulomonocytic-like lineage cells. Mechanistically, T-3775440 disrupted the interaction between LSD1 and growth factor-independent 1B (GFI1B), a transcription factor critical for the differentiation processes of erythroid and megakaryocytic lineage cells. Knockdown of LSD1 and GFI1B recapitulated T-3775440-induced transdifferentiation and cell growth suppression, highlighting the significance of LSD1-GFI1B axis inhibition with regard to the anti-AML effects of T-3775440. Moreover, T-3775440 exhibited significant antitumor efficacy in AEL and AMKL xenograft models. Our findings provide a rationale for evaluating LSD1 inhibitors as potential treatments and indicate a novel mechanism of action against AML, particularly AEL and AMKL. Mol Cancer Ther; 16(2); 273-84. ©2016 AACR.

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