Taipei Veterans General Hospital

About: Taipei Veterans General Hospital is a healthcare organization based out in Taipei, Taiwan. It is known for research contribution in the topics: Population & Cancer. The organization has 11878 authors who have published 16478 publications receiving 363424 citations. The organization is also known as: Táiběi Róngmín Zǒngyī Yuàn.

Diabetes Remission and Insulin Secretion After Gastric Bypass in Patients with Body Mass Index <35 kg/m2

Abstract: Most morbidly obese patients who undergo gastric bypass experience rapid remission of type 2 diabetes mellitus (T2DM) but the response in non-morbidly obese patients is not clear. This trial prospectively assessed the effect of diabetes remission, glucose metabolism, and the serial changes of insulin secretion after gastric bypass in inadequately controlled T2DM patients with a BMI of 23–35 kg/m2. A total of 62 consecutive patients with T2DM and a BMI of 23–35 kg/m2 underwent gastric bypass. Data were prospectively collected before surgery and 1, 4, 12, 26, and 52 weeks and 2 years after surgery. Insulin secretion was measured by insulinogenic index and area under the curve (AUC) during a standard oral glucose tolerance test (OGTT). Remission of type 2 diabetes was defined as fasting glucose level <110 mg/dl and HbA1c <6.0% without any glycemic therapy. Of the 62 patients, 24 were men and 38 were women (age 43.1 ± 10.8 years). Their preoperative characteristics were as follows: BMI 30.1 ± 3.3 kg/m2, waist circumference 99.6 ± 9.6 cm, C-peptide 3.1 ± 1.4 ng/ml, and duration of T2DM 5.4 ± 5.1 years. The mean BMI decreased postoperatively to 22.6 ± 2.3 kg/m2 in 1 year and 23.0 ± 2.7 kg/m2 in 2 years. The mean HbA1c decreased from 9.7 ± 1.9% to 5.8 ± 0.5% in 1 year and 5.9 ± 0.5% in 2 years. Complete remission of T2DM was achieved in 57% in 1 year and 55% in 2 years after surgery. Before surgery, the OGTT test showed a blunted insulin secretion pattern with an insulinogenic index of 0.1 ± 0.2 and AUC of 2,324 ± 1,015 μIU min/ml. In 1 week after surgery, the insulinogenic index increased to 0.16 and AUC decreased to 1,366 μIU min/ml along with a rapid drop of insulin resistance. The insulinogenic index and AUC gradually increased to 0.27 and 3,220, respectively, 1 year after surgery and remained stable up to 2 years with a very low insulin resistance. Laparoscopic gastric bypass facilitates immediate improvement in the glucose metabolism of inadequately controlled non-severe obese T2DM patients, and the benefit is sustained up to 2 years after surgery. The benefit is regulated by the decrease in insulin resistance, increase in early insulin response, and total insulin secretion to glucose load.

Reduced cerebellar gray matter is a neural signature of physical frailty.

Abstract: Physical frailty has been recognized as a clinical syndrome resulting from declines in various physiological systems; however, the role of the central nervous system in the pathophysiology of frailty remains unclear. The I-Lan Longitudinal Aging Study randomly sampled community-dwelling people aged 50 or older for a brain magnetic resonance imaging study. All participants were assessed for frailty status (robust, prefrail, and frail) based on the presence of five frailty components: slow walking speed, muscle weakness, low physical activity, exhaustion and weight loss (Fried criteria). Gray matter volume (GMV) changes associated with frailty status and individual frailty components were examined. Overall, 456 participants (64.0 ± 8.5 years, 47.6% women) were included in this study. The prefrail (n = 178, 39.0%) and frail (n = 19, 4.2%) subjects were grouped for analysis. The prefrail–frail group showed reduced GMV, compared to the robust group (n = 259, 56.8%), in the cerebellum, hippocampi, middle frontal gyri, and several other cerebral regions (corrected P < 0.05). Each frailty component was associated with GMV changes in functionally related brain areas. Hierarchical cluster analysis categorized these components into three subsets. Motor-related components, including weakness, low activity, and slowness, comprised one subset with a common cerebellar involvement. Exhaustion and weight loss were the other two subsets without cerebellar changes. To conclude, physical frailty is associated with a decreased reserve in specific brain regions, especially cerebellum. Further longitudinal studies are needed to explore if the cerebellum- and noncerebellum-based frailty components reflect a distinctive future risk for developing frailty. Hum Brain Mapp 36:3666–3676, 2015. © 2015 Wiley Periodicals, Inc.

K63-polyubiquitinated HAUSP deubiquitinates HIF-1α and dictates H3K56 acetylation promoting hypoxia-induced tumour progression.

Abstract: Intratumoural hypoxia induces HIF-1α and promotes tumour progression, metastasis and treatment resistance. HIF-1α stability is regulated by VHL-E3 ligase-mediated ubiquitin-dependent degradation; however, the hypoxia-regulated deubiquitinase that stabilizes HIF-1α has not been identified. Here we report that HAUSP (USP7) deubiquitinase deubiquitinates HIF-1α to increase its stability, induce epithelial-mesenchymal transition and promote metastasis. Hypoxia induces K63-linked polyubiquitinated HAUSP at lysine 443 to enhance its functions. Knockdown of HAUSP decreases acetylation of histone 3 lysine 56 (H3K56Ac). K63-polyubiquitinated HAUSP interacts with a ubiquitin receptor CBP to specifically mediate H3K56 acetylation. ChIP-seq analysis of HAUSP and HIF-1α binding reveals two motifs responsive to hypoxia. HectH9 is the E3 ligase for HAUSP and a prognostic marker together with HIF-1α. This report demonstrates that hypoxia-induced K63-polyubiquitinated HAUSP deubiquitinates HIF-1α and causes CBP-mediated H3K56 acetylation on HIF-1α target gene promoters to promote EMT/metastasis, further defining HAUSP as a therapeutic target in hypoxia-induced tumour progression.

Enhanced affect/cognition-related brain responses during visceral placebo analgesia in irritable bowel syndrome patients.

Abstract: Placebo analgesia is a psychosocial context effect that is rarely studied in visceral pain. Patients with irritable bowel syndrome (IBS) exhibit visceral hyperalgesia and heightened affective/cognitive brain region activation during visceral stimuli. Psychological factors alter the pain and brain activation pattern, and these changes are more pronounced in IBS patients. Expectation constitutes the major neuropsychological mechanism in the placebo effect. This study confirmed the heightened affective/cognitive brain responses in IBS patients during visceral placebo analgesia using a placebo model with expectation, which was enhanced by suggestion and conditioning. Seventeen IBS patients and 17 age-/sex-matched controls were enrolled. Psychophysical inventories (Hospital Anxiety and Depression Scale [HADS], visual analogue scale, and short-form McGill questionnaire) were completed. Brain activity during placebo intervention and anticipation was assessed in response to rectal distension using 3T-functional magnetic resonance imaging. Suggestion-/conditioning-enhanced placebo was used to convince controls/patients of the efficacy of a newly developed intravenous drug (saline, in actuality) for the relief of rectal distension-induced visceral pain. A comparable visceral placebo analgesia was observed in IBS patients and control subjects. IBS patients demonstrated a higher HADS-anxiety score, which was predictive of a weak placebo effect. Suggestion-/conditioning-enhanced placebo evoked more activity in affective/cognitive brain regions (insula, midcingulate cortex, and ventrolateral prefrontal cortex [VLPFC]) in IBS patients than in healthy controls. VLPFC was also more active during anticipation in IBS patients. In conclusion, IBS patients and control subjects achieved comparable placebo analgesia during experimentally induced rectal pain. The visceral placebo analgesia produced heightened activity in affective/cognitive brain regions in IBS patients.