OBJECTIVE -Older adults with type 2 diabetes are more likely to fall, but little is known about risk factors for falls in this population. We determined whether diabetes-related complications or treatments are associated with risk of falls in older diabetic adults.RESEARCH DESIGN AND METHODS -In the Health, Aging, and Body Composition cohort of well-functioning older adults, participants reported falls in the previous year at annual visits. Odds ratios (ORs) for more frequent falls among 446 diabetic participants whose mean age was 73.6 years, with an average follow-up of 4.9 years, were estimated with continuation ratio models.RESULTS -In the first year, 23% reported falling; 22, 26, 30, and 31% fell in subsequent years. In adjusted models, reduced peroneal nerve response amplitude (OR 1.50 Ϫ95% CI 1.07-2.12], worst quartile versus others); higher cystatin-C, a marker of reduced renal function (1.38 [1.11-1.71], for 1 SD increase); poorer contrast sensitivity (1.41 [0.97-2.04], worst quartile versus others); and low A1C in insulin users (4.36 [1.32-14.46], A1C Յ6 vs. Ͼ8%) were associated with risk of falls. In those using oral hypoglycemic medications but not insulin, low A1C was not associated with risk of falls (1.29 [0.65-2.54], A1C Յ6 vs. Ͼ8%). Adjustment for physical performance explained some, but not all, of these associations.CONCLUSIONS -In older diabetic adults, reducing diabetes-related complications may prevent falls. Achieving lower A1C levels with oral hypoglycemic medications was not associated with more frequent falls, but, among those using insulin, A1C Յ6% increased risk of falls. Diabetes Care 31:391-396, 2008O lder adults with type 2 diabetes have an increased risk of falls, but little is known about risk factors for falls in this population (1-4). Factors of particular concern include diabetesrelated complications of peripheral neuropathy, reduced vision, and renal function. Insulin therapy is associated with increased falls (3,5), possibly because of more severe disease and/or hypoglycemic episodes. Reduced balance, strength, and gait are likely intermediaries in any association between diabetesrelated complications and risk of falls. Previous studies of falls among older diabetic adults were cross-sectional or had limited data characterizing glycemic control and diabetes-related complications. We used longitudinal data for diabetic participants in the Health, Aging, and Body Composition (Health ABC) Study to determine whether factors associated with diabetes progression or treatment increase risk of falls and whether associations are mediated by poor performance on tests of balance, gait, and strength.RESEARCH DESIGN AND METHODS -Health ABC is a prospective study of 3,075 men and women aged 70 -79 years recruited at

The regional+alpha lymph node dissection enhanced the survival in the ICC patients with lymph node metastasis, and the exact nodal status could be confirmed by lymph node dissection in the pericholedochal lymph nodes.

In 2002, the Japan Pancreas Society (JPS) was the first in the world to propose diagnostic criteria for autoimmune pancreatitis (AIP). Since the concept of AIP has changed with the accumulation of AIP cases, the Research Committee of Intractable Pancreatic Diseases (RCIPD) provided by the Ministry of Health, Labour and Welfare of Japan and the JPS issued revised clinical diagnostic criteria of AIP in 2006. The Asan Medical Center of Korea also proposed diagnostic criteria for AIP in 2006. However, there are subtle but clinically challenging differences between the Japanese and Korean criteria. This inconsistency makes it difficult to compare data in studies from different centers and elucidate the characteristics of AIP. To reach a consensus on AIP, the RCIPD and the Korean Society of Pancreatobiliary Diseases established the following Asian criteria for the diagnosis of AIP: I-1. Imaging studies of pancreatic parenchyma show a diffuse/segmental/focally enlarged gland, occasionally with a mass and/or a hypoattenuation rim. I-2. Imaging studies of pancreaticobiliary ducts show diffuse/segmental/focal pancreatic ductal narrowing, often with stenosis of the bile duct. (Both I-1 and I-2 are required for diagnosis). II. Elevated level of serum IgG or IgG4, and detection of autoantibodies. III. Common lymphoplasmacytic infiltration and fibrosis, with abundant IgG4-positive cell infiltration. AIP should be diagnosed when criterion I and one of the other two criteria are satisfied, or when histology shows the presence of lymphoplasmacytic sclerosing pancreatitis in the resected pancreas. A diagnostic trial of steroid therapy can be applied carefully by expert pancreatologists only in patients fulfilling criterion I alone with negative diagnostic work-up results for pancreatobiliary cancer.

Accumulating evidence suggests that tumors are composed of a heterogeneous cell population with a small subset of cancer stem cells (CSCs) that sustain tumor formation and growth. Recently, there have been efforts to explain drug resistance of cancer cells based on the concept of CSCs having an intrinsic detoxifying mechanism. In the present study, to investigate the role of CSCs in acquiring chemoresistance in pancreatic cancer, gemcitabine‐resistant cells were established by exposure to serially escalated doses of gemcitabine in HPAC and CFPAC‐1 cells. Gemcitabine‐resistant cells were more tumorigenic in vitro and in vivo, and had greater sphere‐forming activity than parental cells. After high‐dose gemcitabine treatment to eliminate most of the cells, CD44+ cells proliferated and reconstituted the population of resistant cells. CD44+CD24+ESA+ cells remained as a small subset in the resistant cell population. Among ATP‐binding cassette (ABC) transporters, which are known as the mechanism of drug resistance in CSCs, ABCB1 (MDR1) was significantly augmented during the acquisition of drug resistance. ABC transporter inhibitor verapamil resensitized the resistant cells to gemcitabine in a dose‐dependent manner and RNA interference of CD44 inhibited the clonogenic activity of resistant cells. In human pancreatic cancer samples, CD44 expression was correlated with histologic grade and the patients with CD44‐positive tumors showed poor prognosis. These data indicate that cancer stem‐like cells were expanded during the acquisition of gemcitabine resistance and in therapeutic application, targeted therapy against the CD44 or ABC transporter inhibitors could be applied to overcome drug resistance in the treatment of pancreatic cancer. © 2009 UICC

The regulation of cellular activities in a controlled manner is one of the most challenging issues in fields ranging from cell biology to biomedicine. Nanoparticles have the potential of becoming useful tools for controlling cell signalling pathways in a space and time selective fashion. Here, we have developed magnetic nanoparticles that turn on apoptosis cell signalling by using a magnetic field in a remote and non-invasive manner. The magnetic switch consists of zinc-doped iron oxide magnetic nanoparticles (Zn(0.4)Fe(2.6)O(4)), conjugated with a targeting antibody for death receptor 4 (DR4) of DLD-1 colon cancer cells. The magnetic switch, in its On mode when a magnetic field is applied to aggregate magnetic nanoparticle-bound DR4s, promotes apoptosis signalling pathways. We have also demonstrated that the magnetic switch is operable at the micrometre scale and that it can be applied in an in vivo system where apoptotic morphological changes of zebrafish are successfully induced.