Obesity-induced adipose-tissue dysfunction is a critical contributor to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). B cell-activating factor (BAFF) is an adipokine related to impaired insulin sensitivity, and the serum BAFF concentration is associated with NAFLD severity. In this study, we aimed to determine the direct in vivo role of BAFF in the development of insulin resistance, adipocyte dysfunction, and hepatic steatosis using BAFF^−/− mice fed a high-fat diet (HFD). HFD-fed BAFF^−/− mice exhibited significantly improved insulin sensitivity despite their increased weight gain and adiposity relative to HFD-fed wild-type mice. Moreover, inflammation, especially the accumulation of CD11c⁺ adipose-tissue macrophages, and fibrosis of epididymal adipose tissue were reduced, contributing to healthy adipose-tissue expansion in obese BAFF^−/− mice. In line with metabolically healthy obesity, hepatic steatosis also decreased, and we observed attenuated de novo lipogenesis in both the livers and hepatocytes of BAFF^−/− mice. Our data revealed that BAFF serves as a potential stimulator of unhealthy adipose-tissue expansion by triggering inflammation and fibrosis and ultimately leading to enhanced insulin resistance and NAFLD. Therefore, these results suggest that BAFF is a promising target for diabetes and NAFLD treatment.

Although the outcomes of pancreatic cancer have been improved by gemcitabine, the changes in its characteristics and long-term outcomes within the gemcitabine era remain unclear. This study was conducted to identify clinical characteristics of pancreatic cancer patients within the gemcitabine era. A retrospective chart review was performed at 10 centers for 1,248 consecutive patients who were ever considered to have a diagnosis of pancreatic cancer between 2001 and 2010. Data collected included demographics, diagnosis date, clinical stage, treatment, and outcome; 1,082 patients met the inclusion criteria and were analyzed further. The chi-square test, Student’s t-test, and Mann–Whitney U-test were used for statistical analysis. Outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazards regression. Differences in survival analyses were determined using the log-rank test. The distribution of clinical stages was: I, 2.2%; II, 3.4%; III, 13%; IVa, 27%; and IVb, 55%. Chemotherapy alone was administered to 42% of patients and 17% underwent resection. The 1-, 3-, and 5-year survival rates were 39%, 13%, and 6.9%, respectively. The median survival time was 257 days, but differed considerably among treatments and clinical stages. Demographics, distribution of clinical stage, and cause of death did not differ between groups A (2001–2005, n = 406) and B (2006–2010, n = 676). However, group B included more patients who underwent chemotherapy (P < 0.0001) and fewer treated with best supportive care (P = 0.0004), mirroring improvements in this group’s long-term outcomes (P = 0.0063). Finally, factors associated with long-term outcomes derived from multivariate analysis were clinical stage (P < 0.0001), location of the tumor (P = 0.0294) and treatments (surgery, chemotherapy) (P < 0.0001). Long-term outcomes in pancreatic cancer has improved even within the gemcitabine era, suggesting the importance of offering chemotherapy to patients previously only considered for best supportive care. Most patients are still diagnosed at an advanced stage, making clinical strategy development for diagnosing pancreatic cancer at earlier stages essential.

We investigated serum total interleukin-12 (IL-12) levels in patients with Graves' disease and Hashimoto's thyroiditis. The serum IL-12 levels in Graves' disease were significantly increased in the hyperthyroid state, and were decreased during treatment with methimazole or propylthiouracil in accordance with the decline of free tri-iodothyronine (T(3)) levels, free thyroxine levels and thyroid-binding inhibiting immunoglobulin (TBII) levels. When T(3) was administered orally to normal subjects, serum IL-12 levels were slightly increased. These results suggest that IL-12 might be increased due to prolonged stimulation with thyroid hormone, and thyroid hormone by itself might be a self-perpetuating factor of Graves' disease via increased IL-12 production.

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Objectives: Hearing impairment (HI) in midlife may increase the risk of dementia. However, epidemiological research on the association between HI and mild cognitive impairment (MCI) is very limited. Design: The present cross-sectional study investigated the relationship between HI and MCI using baseline data from the Aidai Cohort Study. Study subjects were 995 Japanese adults aged 36 to 84 years. We used the audiometric definition of HI adopted by the World Health Organization, which identifies the speech-frequency pure-tone average hearing thresholds at 0.5, 1, 2, and 4 kHz tones. HI was defined as present when pure-tone average was >25 dB HL in the better hearing ear. MCI was defined as being present when a subject had a Japanese version of the Montreal Cognitive Assessment score of <26. Adjustment was made for age, sex, smoking status, alcohol consumption, leisure time physical activity, hypertension, dyslipidemia, diabetes mellitus, history of depression, body mass index, waist circumference, employment, education, and household income. Results: Among the 995 study subjects, the prevalence values of HI and MCI were 24.3% and 44.5%, respectively. HI was independently positively associated with MCI: the multivariate-adjusted odds ratio (95% confidence interval) was 1.86 (1.32 to 2.62). HI was independently related to a higher prevalence of MCI in those aged 60 to 69 years and those aged 70 years or older: the multivariate-adjusted odds ratios (95% confidence intervals) were 1.64 (1.03 to 2.62) and 2.30 (1.04 to 5.27), respectively. Conclusions: HI may be associated with a higher prevalence of MCI.