It is not known whether non alcoholic fatty liver disease (NAFLD) is a risk factor for diabetes in non obese, non centrally-obese subjects. Our aim was to investigate relationships between fatty liver, insulin resistance and a biomarker score for liver fibrosis with incident diabetes at follow up, in subjects who were neither obese nor centrally-obese.
Methods and results
As many as 70,303 subjects with a body mass index (BMI) < 25 kg/m2 and without diabetes were followed up for a maximum of 7.9 years. At baseline, fatty liver was identified by liver ultrasound, insulin resistance (IR) by homeostatic model assessment of insulin resistance (HOMA-IR) ≥2.0, and central obesity by waist circumference (waist circumference ≥90 cm (men) and ≥85 cm (women). The Fibrosis-4 (FIB-4 score) was used to estimate extent of liver fibrosis. Cox proportional hazards models adjusted for confounders were used to estimate hazard ratios (aHRs) for incident diabetes. As many as 852 incident cases of diabetes occurred during follow up (median [IQR] 3.71 [2.03] years). Mean ± SD BMI was 22.8 ± 1.8 and 21.7 ± 2.0 kg/m2 in subjects with and without diabetes at follow up. In subjects without central obesity and with fatty liver, aHRs (95% CI) for incident diabetes at follow up were 2.17 (1.56, 3.03) for men, and 2.86 (1.50,5.46) for women. Similar aHRs for incident diabetes occurred with fatty liver, IR and the highest quartile of FIB-4 combined, in men; and there was a non significant trend toward increased risk in women.
Conclusions
In normal weight, non-centrally obese subjects NAFLD is an independent risk factor for incident diabetes. 相似文献
The ε4 allele of the APOE gene is thought to increase risk from amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease. Cognitive decline in the condition is increasingly considered to worsen functional disconnections in brain network composed of gray matter and white matter. Nevertheless, Whether APOEε4 targets specific white matter functional connectivity in patients with aMCI remains mostly unexplored, mainly due to the challenges of detecting BOLD signals in white matter. Here, we applied a novel approach to investigate APOEε4-related specific bundles and cortical area alterations in aMCI subjects, in order to characterize white matter-gray matter functional connectivity differences throughout the brain. We analyzed 75 patients with aMCI and 76 demographically matched normal controls. The aMCI APOEε4 carriers showed decreased functional connectivity located at left corticospinal tract, bilateral posterior limb of internal capsule, and right temporopolaris, which was different from the regions of aMCI-related changes. We further found that recognition scores were positively associated with the right temporopolaris in aMCI APOEε4 carriers. Collectively, the data provide new evidence that APOEε4 genotype exerts a negative impact on neural activity in both gray and white matter in aMCI, which potentially contributes to functional disconnection and memory decline. A novel method provides full-scale measuring effect of disease conditions on functional architecture throughout the brain. Trial registration: https://www.ClinicalTrials.gov (Identifier: NCT02225964). Registered January 2014.
An accurate dosage determination is required in neonates when antibiotics are used. The adult data cannot be simply extrapolated to the pediatric population due to significant individual differences. We aimed to identify factors impacting ceftazidime exposure in neonates and to provide drug dosing guidance to clinicians. Forty-three neonates aged less than 60 days with proven or suspected infections were enrolled in this study. After intravenous administration, blood samples were collected, and plasma ceftazidime concentration was determined using a HPLC method. Pharmacokinetic data were fitted using a nonlinear mixed-effects model approach. One-compartmental model could nicely characterize the ceftazidime in vivo behavior. The covariate test found that the postmenstrual age (day) was strongly associated with systemic drug clearance (L/h), and the effect of body weight (kg) was identified as the covariate on distribution volume (L). Compared with the base model, the addition of covariates improved the goodness-of-fit of the final model. Model validation (bootstrap, visual predictive check, and prediction-corrected visual predictive check) suggested a robust and reliable pharmacokinetic model was developed. Personalized dosage regimens were provided based on model simulations. The intravenous dose should be adjusted according to postmenstrual age, body weight, and minimum inhibitory concentration. 相似文献
PM10 exposure has been found to have significant effects on a variety of physical conditions. However, whether it acts on psychopathology remains unclear. This study used 8-year data to examine the relationship between PM10 concentration and daily clinic visits of anxiety disorders. All residents of Yunlin County, Taiwan, which is a high river-dust exposure area, were selected as subjects. Data from the Taiwan National Health Insurance Research Database (NHIRD), 2002–2009, were analyzed. Individuals with any ICD code of 300.0 and 300.2 were categorized as with anxiety disorders. PM10 data were based on the Lunbei station (located at Yunlin County) of EPA, Taiwan. Time-series analysis showed that, during the observed 8 years, the number of daily clinic visits for anxiety disorders increased with PM10 levels, and the relationship remained significant after unemployment rate, and the Weighted Price Index of Taiwan Stock Exchange in the same period were controlled for. In particular, we found that there is a linear dose-response effect between daily clinic visits and PM10 levels when PM10 <?300 μg/m3; whereas a dramatically elevated daily clinic visits of anxiety disorders was found when PM10 >?300 μg/m3. Findings from this study highlight that high level of PM10 exposure derived from severe weather or environment condition may affect the occurrence of anxiety disorders. In addition, there seems to have a threshold of PM10 in elevating the risk of anxiety disorders. 相似文献
A large number of studies have reported the high prevalence of problematic internet use (PIU) among adolescents and students (13-50%)1, and PIU has been associated with many psychiatric symptoms2. In contrast, only a few studies have investigated its prevalence among the adult population. To the best of our knowledge, there have been no studies investigating the prevalence and comorbidity of PIU in a psychiatric population although psychiatric symptoms might either induce PIU in patients with psychiatric illnesses, or PIU might induce or aggravate psychiatric symptoms. The aims of this study are to investigate the prevalence of PIU and psychiatric co-morbidity among adult psychiatric patients.
Methods
Three hundred thirty-three adult psychiatric patients with internet access were recruited at the outpatient clinic of psychiatry at the University Hospital, Kyoto Prefectural University of Medicine over a three-month period. Two hundred thirty-one of them completed the survey (response rate: 69.4%; Male/Female/Transgender: 90/139/2; mean age = 42.2). We divided participants into “normal internet users” and “problematic internet users” using a combination of Young’s Internet Addiction Test (IAT) and the Compulsive Internet Use Scale (CIUS), using established cut-off values. Demographic data and comorbid psychiatric symptoms were compared between the two groups, using self-rating scales measuring insomnia (Athens Insomnia Scale, AIS), depression (Beck Depression Inventory, BDI), anxiety (State-trait Anxiety Inventory, STAI), attention deficit hyperactivity disorder (ADHD) (Adult ADHD Self-report Scale, ASRS), autism (Autism Spectrum Quotient, AQ), obsessive-compulsive disorder (OCD) (Obsessive-Compulsive Inventory, OCI), social anxiety disorder (SAD) (Liebowitz Social Anxiety Scale, LSAS), alcohol abuse, and impulsivity (Barratt Impulsive Scale, BIS).
Results
Of our 231 respondents, 58 (25.1%) were defined as problematic internet users, as they scored high on either the IAT (40 or more) or CIUS (21 or more). The age of problematic internet users was significantly lower than that of normal internet users (35.9 vs 43.6, p<0.001, Mann-Whitney U test). The problematic internet users scored significantly higher on scales measuring sleep problems (AIS, 8.8 for problematic internet users vs 6.3 for normal internet users, p<0.001), depression (BDI, 27.4 vs 18.3, p<0.001), trait anxiety (STAI, 61.8 vs 53.9, p<0.001), ADHD (ASRS, part A 3.1 vs 1.8 and part B 3.5 vs 1.8, p<0.001), autism (AQ, 25.9 vs 21.6, p<0.001), OCD (OCI, 63.2 vs 36.3, p<0.001), SAD (LSAS, 71.4 vs 54.0, p<0.001), and impulsivity (BIS, 67.4 vs 63.5, p=0.004).
Conclusions
The prevalence of PIU among adult psychiatric patients is relatively high (25%). As previous studies reported in the general population, PIU among adult psychiatric patients was associated with lower age and higher psychiatric comorbidity. Longitudinal research is needed to determine any causal relations between problematic internet use and psychopathological illnesses. 相似文献
Pachymic acid (PA) is a lanostane type triterpenoid isolated from Poria cocos, which possesses an anti-tumor effect in breast cancer, prostate cancer, lung cancer, and bladder cancer cells. In this study, we investigated the effect of PA on the growth and apoptosis of human immortalized cell line (HOS) and primary osteosarcoma cells by a Cell Counting Kit-8 (CCK-8) and Annexin V and propidium iodide (PI) staining, respectively. Western blot was used to measure the expression of cleaved Caspase 3, PTEN, and AKT, as well as the AKT phosphorylation. The Caspase 3 activity was determined using the Caspase-3 Colorimetric Assay Kit. From the results, PA significantly reduced cell proliferation in a concentration- and time-dependent manner. PA also induced cell apoptosis in a dose-dependent fashion. PA treatment led to increased Caspase 3 activation and PTEN expression, as well as reduced AKT phosphorylation. Moreover, Ac-DEVD-CHO (a Caspase 3/7 inhibitor) pre-treatment or PTEN knockdown partially blocked the effects of PA on cell proliferation and apoptosis. Caspase 3/7 inhibitor had an additive effect with PTEN knockdown. Collectively, our results suggested that induction of apoptosis by PA was mediated in part by PTEN/AKT signaling and Caspase 3/7 activity. This study provides evidence that PA might be useful in the treatment of human osteosarcoma. 相似文献
Two new secoiridoid glucosides, ilexpublignoside (1), pubzenoside (2), and a new lignan, ilexlignan B (3), along with seven known compounds (4–10) were isolated from the roots of Ilex pubescens for the first time. Their chemical structures were elucidated on the basis of extensive spectroscopic methods, including IR, UV, HR-ESI–MS, CD, NMR experiments, as well as comparison with the reported data. 相似文献