Search

Background Malignant obstruction and associated hydronephrosis is a common complication of advanced cervical cancer. Percutaneous nephrostomy (PCN) followed by antegrade stenting is often required to relieve obstruction as retrograde access fails in considerable proportion of such patients. Reno-pleural fistula is a rare complication of PCN which creates a patent connection between the renal collecting system and the thoracic cavity, and urine accumulation in the pleural space can cause pleural effusion (i.e., urinothorax). Upward or downward migration is a complication of indwelling ureteric stents. Further migration with extrusion outside of the urinary tract is uncommon. Herein we present an unprecedented case in adult of ureteric stent upward migration through a reno-pleural fistula into the thoracic cavity managed by thoracoscopy. Case presentation A 66-year-old female was diagnosed of advanced stage cervical cancer with suspicious bladder invasion. Given her bilateral hydronephrosis with impaired renal function, she underwent bilateral PCN and subsequent antegrade ureteric stenting. However, she presented with dyspnea, right back pain, and oliguria four days after bilateral PCN catheter removal. Computed tomography reported massive right pleural effusion and an intrathoracic ureteric stent within reno-pleural fistula. Thoracoscopy with thoracostomy was performed to remove the ureteric stent and urine in right pleural space. A week later, urinothorax had resolved and right PCN was performed again. She was discharged after regaining normal renal function with right PCN and a left ureteric stent in place. Conclusions A reno-pleural fistula can serve as a route for ureteric stent migration and that continuous drainage of urine can cause urinothorax once the stent reaches the thoracic cavity. Anytime a supracostal approach is used for PCN, even when using small caliber catheters, clinicians should pay special attention given the risk of pleural injury and subsequent complications.

BACKGROUND: Medical staff scheduling problems are complex and involve numerous constraints. OBJECTIVE: This research uses the task-technology fit (TTF) model to measure the technology characteristics of information technology (IT) systems as a reference for constructing a prototype for a medical staff scheduling system to identify function requirements and design human interfaces. METHOD: After the evaluation of the proposed scheduling system, this research excludes compatibility from the 13 technology characteristics and adds two technology characteristics for consideration: customization and scalability. RESULTS: Based on the revised technology characteristics of the TTF model, this research develops flexible scheduling functions to satisfy daily manpower requirements and allow predetermined schedules and day-off reservations for a hospital’s radiological technologists. Characterized by flexibility, customization, and scalability, the system can accommodate several algorithms to generate a better schedule that satisfies hard and soft constraints. Furthermore, the scheduler can choose the required hard and soft constraints from all constraints. The prototype of the scheduling system will be easily extended to add or modify constraints in the case of requirement or regulation changes. CONCLUSION: The results of this study provide a prototype for system developers to design a customized staff scheduling system for each medical unit.

Background The introduction of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) altered the practice of thyroid pathology and reduced the risk of malignancy (ROM) associated with the indeterminate categories in the Bethesda system for reporting thyroid cytopathology (TBSRTC). It has been proposed that the evaluation of the risk of neoplasm (RON) is important in cytologic-histologic correlation studies. Methods A total of 5224 thyroid aspirates were performed at our institution during an 8-year period. Of the 1475 cases (28%) with surgical follow-up, the histologic diagnoses comprised benign non-neoplastic (BNN, n = 669), follicular adenoma (FA, n = 188), NIFTP (n = 42), papillary microcarcinoma (PMC) (n = 223), and malignant neoplasm excluding PMC (n = 353). The RON was calculated to include neoplasia with low risk biologic behavior (FA, NIFTP, PMC) and malignant neoplasms. In contrast, the ROM was reserved for malignant neoplasms excluding PMC. Results The RON for each TBSRTC category was: nondiagnostic (ND) 38.3%, benign 20.9%, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) 63.2%, follicular neoplasm or suspicious for follicular neoplasm (FN/SFN) 83.9%, suspicious for malignancy (SFM) 94%, and malignant 100%. The ROM excluding PMC was: ND 14%, benign 1.6%, AUS/FLUS 17.8%, FN/SFN 28.4%, SFM 84.4%, and malignant 99.5%. Conclusions The RON and ROM support the recommended management guidelines from TBSRTC for all categories, except for FN/SFN. Histopathologic follow-up of FN/SFN aspirates in our study contain a very high rate of neoplasm (83.9%), which might support the management preference of conservative surgery.

Clinical empathy refers to the ability of healthcare providers (HP) to recognize and understand what patients feel. While neuroimaging investigations have identified a neural network of empathy, activation consistency of brain regions and their specific functions in clinical empathy remains unclear. Herein, we conducted meta-analyses of dispositional assessments using random-effects models and functional neuroimaging using Seed-based d Mapping with Permutation of Subject Images to ascertain the shared neural processes consistently identified as relevant to clinical empathy. The dispositional meta-analysis (n = 15) revealed that HP exhibited higher scores on empathic concern and perspective taking. The HP neuroimaging meta-analysis (n = 11) identified consistent activation of the anterior mid-cingulate cortex, anterior insula, and ventrolateral prefrontal cortex (vlPFC) while HP vs. controls comparison (n = 9) did not yield robust alterations. The vlPFC mediated positive and negative functional connectivity of the insula. We revisited the framework of emotion regulation in clinical empathy. The empathetic agent flexibly shifts between affective regulatory strategies to meet contextual demands, with vlPFC figuring as the key region where this neural mechanism takes place.

Squamous and anaplastic thyroid cancers are the most aggressive and life-threatening cancer types in humans, with the involvement of lymph nodes in 59% of cases and distant metastases in 26% of cases of all thyroid cancers. The median survival of squamous thyroid cancer patients is 8 months and therefore is of high clinical concern. Here, we show that both VEGFC and VEGFR2/KDR are overexpressed in thyroid cancers, indicating that VEGF/VEGFR signaling plays a carcinogenic role in thyroid cancer development. Using CRISPR/Cas9, we established a KDR knockout (KO) SW579 squamous thyroid cancer cell line that exhibited dramatically decreased colony formation and invasion abilities (30% and 60% reduction, respectively) when compared to scrambled control cells. To validate the potential of KDR as a therapeutic target for thyroid cancers, we used the KDR RTK inhibitor sunitinib. Protein analysis and live/dead assay were performed to demonstrate that sunitinib significantly inhibited cell growth signal transduction and induced cell apoptosis of SW579 cells. These results suggest that selective targeting of KDR may have potential for development into novel anti-cancer therapies to suppress VEGF/VEGFR-mediated cancer development in patients with clinical advanced thyroid cancer.

IntroductionThe aim of this study was to develop and validate a new diabetes distress scale suitable for Chinese and Taiwanese culture.MethodsThis study collected the current diabetes distress measurement tools, re-organized current definitions about the domains of diabetes distress, and then developed a new tool. Three hundred and ninety-five participants from four hospitals in northern Taiwan were recruited by cluster randomized sampling for validity test.ResultsWe found the new diabetes distress scale had appropriate reliability and validity, including an acceptable model fit for the 12-item scale.ConclusionsThis new diabetes distress scale might be more directly related to emotional distress issues blood glucose control, improve the clinical conspicuity of diabetes distress, and even benefit the overall care of diabetic patients in Taiwan. Further studies about the validity and reliability of this new tool in a nationwide setting are needed.

There is insufficient evidence to prove the effect of the Post-acute Care (PAC) program on post-stroke recovery. This study aimed to determine the effectiveness of the PAC versus traditional inpatient rehabilitation (non-PAC) for middle- and old-aged stroke survivors. This multicenter cohort study enrolled 334 stroke patients admitted for post-stroke rehabilitation. The outcome variables included the Barthel Index (BI), Functional Oral Intake Scale (FOIS), Mini Nutritional Assessment-Short Form (MNA-SF), EuroQoL-5D (EQ-5D), Lawton–Brody Instrumental Activities of Daily Living (ADL) Scale, and Mini-Mental State Examination (MMSE). The inverse-probability-of-treatment-weighting method was used to analyze the differences in outcomes between the PAC and non-PAC groups. The PAC group showed better improvements in BI, MNA-SF, EQ-5D, Instrumental ADL, and MMSE compared to the non-PAC group, with differences in effect sizes of 0.54 (95% confidence interval [CI] 0.38–0.71), 0.26 (95% CI 0.10–0.42), 0.50 (95% CI 0.33–0.66), 0.44 (95% CI 0.28–0.60) and 0.34 (95% CI 0.17–0.50), respectively. The PAC project showed more improvement in basic and instrumental ADL and status of swallowing, nutrition, and cognition than those of non-PAC, which had less length of stay restricted by the National Health Insurance. More studies are warranted to investigate the influence of hospital stay and duration from stroke onset on the PAC’s effectiveness.

Traumatic brain injury (TBI) is a global health issue that affects at least 10 million people per year. Neuronal cell death and brain injury after TBI, including apoptosis, inflammation, and excitotoxicity, have led to detrimental effects in TBI. 2, 3, 5, 4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG), a water-soluble compound extracted from the Chinese herb Polygonum multiflorum, has been shown to exert various biological functions. However, the effects of THSG on TBI is still poorly understood. THSG reduced L-glutamate-induced DNA fragmentation and protected glial and neuronal cell death after L-glutamate stimulation. Our results also showed that TBI caused significant behavioral deficits in the performance of beam walking, mNSS, and Morris water maze tasks in a mouse model. Importantly, daily administration of THSG (60 mg/kg/day) after TBI for 21 days attenuated the injury severity score, promoted motor coordination, and improved cognitive performance post-TBI. Moreover, administration of THSG also dramatically decreased the brain lesion volume. THSG reduced TBI-induced neuronal apoptosis in the brain cortex 24 h after TBI. Furthermore, THSG increased the number of immature neurons in the subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus. Our results demonstrate that THSG exerts neuroprotective effects on glutamate-induced excitotoxicity and glial and neuronal cell death. The present study also demonstrated that THSG effectively protects against TBI-associated motor and cognitive impairment, at least in part, by inhibiting TBI-induced apoptosis and promoting neurogenesis.

Background Virtual reality and arm cycling have been reported as effective treatments for improving upper limb motor recovery in patients with stroke. Intermittent theta burst stimulation (iTBS) can increase ipsilesional cortical excitability, and has been increasingly used in patients with stroke. However, few studies examined the augmented effect of iTBS on neurorehabilitation program. In this study, we investigated the augmented effect of iTBS on virtual reality-based cycling training (VCT) for upper limb function in patients with stroke. Methods In this randomized controlled trial, 23 patients with stroke were recruited. Each patient received either 15 sessions of iTBS or sham stimulation in addition to VCT on the same day. Outcome measures were assessed before and after the intervention. Primary outcome measures for the improvement of upper limb motor function and spasticity were Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and Modified Ashworth Scale Upper-Extremity (MAS-UE). Secondary outcome measures for activity and participation were Action Research Arm Test (ARAT), Nine Hole Peg Test (NHPT), Box and Block Test (BBT) and Motor Activity Log (MAL), and Stroke Impact Scale (SIS). Wilcoxon signed-rank tests were performed to evaluate the effectiveness after the intervention and Mann–Whitney U tests were conducted to compare the therapeutic effects between two groups. Results At post-treatment, both groups showed significant improvement in FMA-UE and ARAT, while only the iTBS + VCT group demonstrated significant improvement in MAS-UE, BBT, NHPT, MAL and SIS. The Mann–Whitney U tests revealed that the iTBS + VCT group has presented greater improvement than the sham group significantly in MAS-UE, MAL-AOU and SIS. However, there were no significant differences in the changes of the FMA-UE, ARAT, BBT, NHPT and MAL-QOM between groups. Conclusions Intermittent TBS showed augmented efficacy on VCT for reducing spasticity, increasing actual use of the affected upper limb, and improving participation in daily life in stroke patients. This study provided an integrated innovative intervention, which may be a promising therapy to improve upper limb function recovery in stroke rehabilitation. However, this study has a small sample size, and thus a further larger-scale study is warranted to confirm the treatment efficacy. Trial registration This trial was registered under ClinicalTrials.gov ID No. NCT03350087, retrospectively registered, on November 22, 2017

In this novel study, we isolated 28 compounds from the leaves of Aquilaria sinensis (Lour.) Gilg based on a bioassay-guided procedure and also discovered the possible matrix metalloprotease 2 (MMP-2) and 9 (MMP-9) modulatory effect of pheophorbide A (PA). To evaluate the regulatory activity on MMP-2 and MMP-9, the HT-1080 human fibrosarcoma cells were treated with various concentrations of extracted materials and isolated compounds. PA was extracted by methanol from the leaves of A. sinensis and separated from the fraction of the partitioned ethyl acetate layer. PA is believed to be an active component for MMP expression since it exhibited significant stimulation on MMP-2 and proMMP-9 activity. When treating with 50 μM of PA, the expression of MMP-2 and MMP-9 were increased 1.9-fold and 2.3-fold, respectively. PA also exhibited no cytotoxicity against HT-1080 cells when the cell viability was monitored. Furthermore, no significant MMP activity was observed when five PA analogues were evaluated. This study is the first to demonstrate that C-17 of PA is the deciding factor in determining the bioactivity of the compound. The MMP-2 and proMMP-9 modulatory activity of PA indicate its potential applications for reducing scar formation and comparative medical purposes.

Background The American College of Obstetricians and Gynecologists suggests the initiation of postpartum antihypertensive treatment for women with hypertension in the postpartum period, a systolic blood pressure of ≥150 mm Hg or diastolic blood pressure of ≥100 mm Hg on 2 occasions at least 4 to 6 hours apart; however, the utility and validity of this strategy for preventing postpartum hypertension-related readmission remain unknown. Objective The primary objective was to evaluate the accuracy of different blood pressure assessment strategies for predicting postpartum hypertension-related readmissions. The secondary objective was to consider the impact of using different blood pressure thresholds for initiating postpartum antihypertensive treatment vs the impact of using the current blood pressure threshold recommended by the American College of Obstetricians and Gynecologists. Study Design A retrospective cohort study of 24,917 women who delivered at a single midwestern academic hospital between January 1, 2009, and June 30, 2015. Of those women, 3830 were identified as hypertensive, and 112 of 3830 women (2.92%) were readmitted for hypertension management. Blood pressures measured between delivery and 72 hours after delivery were used to evaluate 3 different blood pressure assessment strategies: average systolic or diastolic blood pressure exceeding the predetermined threshold (strategy 1), maximum systolic or diastolic blood pressure exceeding the predetermined threshold on 1 occasion (strategy 2), and maximum systolic or diastolic blood pressure exceeding the predetermined threshold on 2 occasions at least 4 hours apart (strategy 3). Analyzed blood pressure thresholds included all the integer blood pressure values between 100/50 mm Hg to 160/110 mm Hg for strategy 1 and 120/70 mm Hg to 190/140 mm Hg for strategies 2 and 3. The primary outcome was hypertension-related postpartum readmission. Receiver operating characteristic curves and the area under the curve were used to measure the predictive value of these strategies. Results The American College of Obstetricians and Gynecologists’ recommendation of using blood pressure ≥150/100 mm Hg as a threshold had a sensitivity of 38% and specificity of 95%, whereas following strategy 3 and reducing the threshold to 140/90 mm Hg demonstrated a sensitivity of 71% and specificity of 84%. The area under the curve for the 3 strategies were as follows: strategy 1 (area under the curve, 0.81; 95% confidence interval, 76.95–85.08), strategy 2 (area under the curve, 0.79; 95% confidence interval, 74.70–82.81), and strategy 3 (area under the curve, 0.83; 95% confidence interval, 79.83–87.24). The difference between the areas under the curve of strategies 2 and 3 was statistically significant (P Conclusion The strategy of using the maximum systolic or diastolic blood pressure exceeding the blood pressure threshold on 2 occasions at least 4 hours apart at lower blood pressure thresholds can predict readmissions with higher sensitivity or specificity. Compared with the threshold of the American College of Obstetricians and Gynecologists’ recommended blood pressure of ≥150/100 mm Hg, if the threshold for the postpartum antihypertensive treatment initiation was lowered to a blood pressure of ≥140/90 mm Hg, it would significantly reduce postpartum readmissions.

Background Nasal colonization of Staphylococcus aureus is a risk factor for the pathogen transmission and the development of infections. Limited information is available on the prevalence and molecular characteristics of S. aureus colonization in pediatric intensive care unit (ICU) patients. Methods A cross-sectional, island-wide study was conducted in 2011. Nasal swabs were collected from pediatric ICU patients at six tertiary hospitals in Taiwan. Results Of 114 patients enrolled in total, nasal colonization of S. arueus was detected in 30 (26.3%) of them, among whom 20 (17.5%) with methicillin-resistant S. arueus (MRSA). The ST59/SCCmec IV and V clones were most common and accounted for 45% of MRSA isolates, followed by ST239/SCCmec III (25%) and ST45/SCCmec IV (20%) clones. Three ST59 MRSA isolates carried the Panton-Valentine Leukocidin genes. Conclusions The results indicated a high prevalence of S. arueus and MRSA nasal colonization among pediatric ICU patients in Taiwan. Identification of epidemic clones warrants the implement of infection control measures to reduce colonization and prevent the dissemination of MRSA in hospitals.

Summary Pathogen-derived lipopolysaccharide (LPS) and cytokine tumor necrosis factor (TNF) activate NFκB with distinct duration dynamics, but how immune response genes decode NFκB duration to produce stimulus-specific expression remains unclear. Here, detailed transcriptomic profiling of combinatorial and temporal control mutants identified 81 genes that depend on stimulus-specific NFκB duration for their stimulus-specificity. Combining quantitative experimentation with mathematical modeling, we found that for some genes a long mRNA half-life allowed effective decoding, but for many genes this was insufficient to account for the data; instead, we found that chromatin mechanisms, such as a slow transition rate between inactive and RelA-bound enhancer states, could also decode NFκB dynamics. Chromatin-mediated decoding is favored by genes acting as immune effectors (e.g., tissue remodelers and T cell recruiters) rather than immune regulators (e.g., signaling proteins and monocyte recruiters). Overall, our results delineate two gene regulatory strategies that decode stimulus-specific NFκB dynamics and determine distinct biological functions.

Background Obesity has been indicated to be a risk factor of diverticulosis. However, plausible relationship remained controversial. This cross-sectional study elucidated the association between percentage of body fat and the risk of diverticulosis. Methods The study was conducted at a single medical center in Taiwan from 2000–2016 which enrolled 5557 adults with age above 20 years old receiving a health examination including self-reported questionnaires, measurement of percentage of body fat (PBF), blood test and colonoscopy at the Tri-Service General Hospital (TSGH). Logistic regressions were used to analyze the association between PBF and diverticulosis. Further stratification of participants was based on age and gender and three extended models were established for multivariable adjustment. Results 243 of 3141 males and 103 of 2416 females were diagnosed with having diverticulosis. After covariates adjustment, only participants in the highest quartile of PBF (Q4 ≥33.8%) showed significantly positive association with the risk diverticulosis (OR 2.089, p Conclusions In conclusion, PBF was a potential risk factor of diverticulosis. Individuals with higher PBF exhibits increased risk of diverticulosis, especially in females. Furthermore, bioelectrical impedance analysis may create a simple, available and radiation-free way to assess the risk of diverticulosis.

Androgens have been shown to have a beneficial effect on brain injury and lower reactive astrocyte expression after TBI. Androgen receptors (ARs) are known to mediate the neuroprotective effects of androgens. However, whether ARs play a crucial role in TBI remains unknown. In this study, we investigated the role of ARs in TBI pathophysiology, using AR knockout (ARKO) mice. We used the controlled cortical impact model to produce primary and mechanical brain injuries and assessed motor function and brain-lesion volume. In addition, the AR knockout effects on necrosis and autophagy were evaluated after TBI. AR knockout significantly increased TBI-induced expression of the necrosis marker alpha-II-spectrin breakdown product 150 and astrogliosis marker glial fibrillary acidic protein. In addition, the TBI-induced astrogliosis increase in ARKO mice lasted for three weeks after a TBI. The autophagy marker Beclin-1 was also enhanced in ARKO mice compared with wild-type mice after TBI. Our results also indicated that ARKO mice showed a more unsatisfactory performance than wild-type mice in a motor function test following TBI. Further, they were observed to have more severe lesions than wild-type mice after injury. These findings strongly suggest that ARs play a role in TBI.

Deception has been reported to be influenced by task-relevant emotional information from an external stimulus. However, it remains unclear how task-irrelevant emotional information would influence deception. In the present study, facial expressions of different valence and emotion intensity were presented to participants, where they were asked to make either truthful or deceptive gender judgments according to the preceding cues. We observed the influence of facial expression intensity upon individuals' cognitive cost of deceiving (mean difference of individuals' truthful and deceptive response times). Larger cost was observed for high intensity faces compared to low intensity faces. These results provided insights on how automatic attraction of attention evoked by task-irrelevant emotional information in facial expressions influenced individuals' cognitive cost of deceiving.

Prodigiosin (PG), a red tripyrrole pigment, belongs to a member of the prodiginine family and is normally secreted by various sources including Serratia marcescens and other Gram-negative bacteria. The studies of PG have received innovative devotion as a result of reported antimicrobial, larvicidal and anti-nematoid immunomodulation and antitumor properties, owing to its antibiotic and cytotoxic activities. This review provides a comprehensive summary of research undertaken toward the isolation and structural elucidation of the prodiginine family of natural products. Additionally, the current evidence-based understanding of the biological activities and medicinal potential of PG is employed to determine the efficacy, with some reports of information related to pharmacokinetics, pharmacodynamics and toxicology.

In the current study, an NMR spectroscopic pattern-based procedure for probing scalarane derivatives was performed and four new 24-homoscalaranes, lendenfeldaranes A&ndash, D (1&ndash, 4), along with three known compounds, 12&alpha, acetoxy-22-hydroxy-24-methyl-24-oxoscalar-16-en- 25-al (5), felixin F (6), and 24-methyl-12,24,25-trioxoscalar-16-en-22-oic acid (7) were isolated from the sponge Lendenfeldia sp. The structures of scalaranes 1&ndash, 7 were elucidated on the basis of spectroscopic analysis. Scalaranes 1&ndash, 7 were further evaluated for their cytotoxicity toward a series of human cancer cell lines and the results suggested that 5 and 7 dominated in the anti- proliferative activity of the extract. The 18-aldehyde functionality was found to play a key role in their activity.

Hepatitis C virus (HCV) NS3 protein possesses protease and helicase activities and is considered an oncoprotein in virus-derived hepatocellular carcinoma. The NS3-associated oncogenesis has been studied but not fully understood. In this study, we have identified novel interactions of the NS3 protein with DNA repair factors, Werner syndrome protein (WRN) and Ku70, in both an HCV subgenomic replicon system and Huh7 cells expressing NS3. HCV NS3 protein inhibits WRN-mediated DNA repair and reduces the repair efficiency of nonhomologous end joining. It interferes with Ku70 recruitment to the double-strand break sites and alters the nuclear distribution of WRN-Ku repair complex. In addition, WRN is a substrate of the NS3/4A protease; the level of WRN protein is regulated by both the proteasome degradation pathway and HCV NS3/4A protease activity. The dual role of HCV NS3 and NS3/4A proteins in regulating the function and expression level of the WRN protein intensifies the effect of impairment on DNA repair. This may lead to an accumulation of DNA mutations and genome instability and, eventually, tumor development. IMPORTANCE HCV infection is a worldwide problem of public health and a major contributor to hepatocellular carcinoma. The single-stranded RNA virus with RNA-dependent RNA polymerase experiences a high error rate and develops strategies to escape the immune system and hepatocarcinogenesis. Studies have revealed the involvement of HCV proteins in the impairment of DNA repair. The present study aimed to further elucidate mechanisms by which the viral NS3 protein impairs the repair of DNA damage. Our results clearly indicate that HCV NS3/4A protease targets WRN for degradation, and, at the same time, diminishes the repair efficiency of nonhomologous end joining by interfering with the recruitment of Ku protein to the DNA double-strand break sites. The study describes a novel mechanism by which the NS3 protein influences DNA repair and provides new insight into the molecular mechanism of HCV pathogenesis.

Matriptase plays important roles in epithelial integrity and function, which depend on its sorting to the basolateral surface of cells, where matriptase zymogen is converted to an active enzyme in order to act on its substrates. After activation, matriptase undergoes HAI-1-mediated inhibition, internalization, transcytosis, and secretion from the apical surface into the lumen. Matriptase is a mosaic protein with several distinct protein domains and motifs, which are a reflection of matriptase's complex cellular itinerary, life cycle, and the tight control of its enzymatic activity. While the molecular determinants for various matriptase regulatory events have been identified, the motif(s) required for translocation of human matriptase to the basolateral plasma membrane is unknown. The motif previously identified in rat matriptase is not conserved between the rodent and the primate. We, here, revisit the question for human matriptase through the use of a fusion protein containing a green fluorescent protein linked to the matriptase N-terminal fragment ending at Gly-149. A conserved seven amino acid motif EEGEVFL, which is similar to the monoleucine C-terminal to an acidic cluster motif involved in the basolateral targeting for some growth factors, has been shown to be required for matriptase translocation to the basolateral plasma membrane of polarized MDCK cells. Furthermore, time-lapse video microscopy showed that the motif appears to be required for entry into the correct transport vesicles, by which matriptase can undergo rapid trafficking and translocate to the plasma membrane. Our study reveals that the EEGEVFL motif is necessary, but may not be sufficient, for matriptase basolateral membrane targeting and serves as the basis for further research on its pathophysiological roles.

Steroids are commonly used in patients with eosinophilic meningitis caused by A. cantonensis infections. The mechanism steroids act on eosinophilic meningitis remains unclear. In this mouse experiments, expressions of 14-3-3 isoform β and γ proteins significantly increased in the CSF 2-3 weeks after the infection, but not increasedin the dexamethasone-treated group. Expression of 14-3-3 β, γ, e, and θ isoforms increased in brain meninges over the 3-week period after infection and decreased due to dexamethasone treatment. In conclusion, administration of dexamethasone in mice with eosinophilic meningitis decreased expressions of 14-3-3 isoform proteins in the CSF and in brain meninges.

Mild traumatic brain injury (mTBI) is a major public health issue, representing 75–90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13–15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model. The mTBI rat model was generated by a mild controlled cortical impact (mCCI) and used to evaluate the therapeutic potential of GIP. We used the Morris water maze and novel object recognition tests, which are tasks for spatial and recognition memory, respectively, to identify the putative therapeutic effects of GIP on cognitive function. Further, beam walking and the adhesive removal tests were used to evaluate locomotor activity and somatosensory functions in rats with and without GIP administration after mCCI lesion. Lastly, we used immunohistochemical (IHC) staining and Western blot analyses to evaluate the inflammatory markers, glial fibrillary acidic protein (GFAP), amyloid-β precursor protein (APP), and bone marrow tyrosine kinase gene in chromosome X (BMX) in animals with mTBI. GIP was well tolerated and ameliorated mTBI-induced memory impairments, poor balance, and sensorimotor deficits after initiation in the post-injury period. In addition, GIP mitigated mTBI-induced neuroinflammatory changes on GFAP, APP, and BMX protein levels. These findings suggest GIP has significant benefits in managing mTBI-related symptoms and represents a novel strategy for mTBI treatment.

Columnaristerol A ( 1 ), a rare natural 19-norsterol possessing a 10β-hydroxy group was isolated from the Formosan octocoral Nephthea columnaris , and its structure was elucidated by spectroscopic methods. Sterol 1 was found to be a cytotoxic agent that exhibited in vitro moderate cytotoxic activity against MOLT-4 and SUP-T1 human leukemia–lymphoma cell lines.

A natural caulerpenyne-derived sesquiterpene, oxytoxin-2 (1), was isolated from a cultured mollusc Volvatella vigourouxi. The structure of 1 was elucidated on the basis of spectroscopic analysis and this compound was suggested to be a diet-derived metabolite from the green alga Caulerpa sertularioides.-This is the first study on the chemical constituents of V. vigourouxi. Oxytoxin-2 (1) was found to inhibit significantly the expression of the pro-inflammatory inducible nitric oxide synthase (iNOS) protein of lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells.

Background The link between elevated serum uric acid ( SUA ) levels and cardiovascular disease ( CVD )–related mortality in the elderly population remains inconclusive. Nutritional status influences both SUA and CVD outcomes. Therefore, we investigated whether SUA ‐predicted mortality and the effect‐modifying roles of malnourishment in older people. Methods and Results A longitudinal Taiwanese cohort including 127 771 adults 65 years and older participating in the Taipei City Elderly Health Examination Program from 2001 to 2010 were stratified by 1‐mg/dL increment of SUA . Low SUA (2 . Study outcomes were all‐cause and CVD ‐related mortality. Cox models were used to estimate hazard ratios ( HRs ) of mortality, after adjusting for 20 demographic and comorbid covariates. Over a median follow‐up of 5.8 years, there were 16 439 all‐cause and 3877 CVD ‐related deaths. Compared with the reference SUA strata of 4 to SUA HR , 1.16; 95% confidence interval, 1.07–1.25) and ≥8 mg/dL ( HR , 1.13; confidence interval, 1.06–1.21), with progressively elevated risks at both extremes. Similarly, increasingly higher CVD ‐related mortality was found at the SUA level HR , 1.19; confidence interval, 1.00–1.40) and ≥7 mg/dL ( HR , 1.17; confidence interval, 1.04–1.32). Remarkably, among the low SUA (CVD ‐related mortality. This modifying effect of malnourishment remained consistent across subgroups. Conclusions SUA ≥8 or CVD ‐related mortality in the elderly, particularly in those with malnourishment.

Summary Emerging azole resistance in Aspergillus fumigatus poses a serious threat to human health. This nationwide surveillance study investigated the prevalence and molecular characteristics of azole-resistant A. fumigatus environmental isolates in Taiwan, an island country with increasing use of azole fungicides. Of the 2,760 air and soil samples screened from 2014-2016, 451 A. fumigatus isolates were recovered from 266 samples, and 34 isolates from 29 samples displayed resistance to medical azoles (itraconazole, voriconazole, or posaconazole). The resistance prevalence was 10.9% and 7.5% in A. fumigatus-positive samples and isolates, respectively. Most (29, 85.3%) azole-resistant isolates harbored TR34/L98H mutations, which were widely distributed, clustered genetically with clinical isolates, and had growth rates that were similar to those of the wild-type isolates. Microsatellite genotyping revealed both the global spread of the TR34/L98H isolates and the occurrence of TR34/L98H/S297T/F495I isolates belonging to local microsatellite genotypes. AfuMDR3 and atrF, two efflux transporter genes, were constitutively upregulated in two individual resistant isolates without cyp51A mutations, highlighting their potential roles in azole resistance. These results emphasize the need for periodic environmental surveillance at the molecular level in regions in which azole fungicides are applied, and agricultural fungicide management strategies that generate less selective pressure should be investigated. This article is protected by copyright. All rights reserved.

This study explores the mediating effects of repetitive negative thinking in the relationship between perfectionism and adolescent sleep quality. A sample of 1664 Chinese adolescents with a mean age of 15.0 years was recruited, and they completed four measures relating to perfectionism, sleep quality, worry, and rumination. The results showed that maladaptive perfectionism was positively correlated with poor sleep quality in adolescents, which was mediated by both worry and rumination. However, adaptive perfectionism was not significantly associated with adolescent sleep quality, and this relationship was suppressed by rumination (but not worry). The implications of these results are also discussed.

Chemotherapy drugs for oral cancers always cause side effects and adverse effects. Currently natural sources and herbs are being searched for treated human oral squamous carcinoma cells (OSCC) in an effort to alleviate the causations of agents in oral cancers chemotherapy. This study investigates the effect of prodigiosin (PG), an alkaloid and natural red pigment as a secondary metabolite of Serratia marcescens, to inhibit human oral squamous carcinoma cell growth; thereby, developing a new drug for the treatment of oral cancer. In vitro cultured human OSCC models (OECM1 and SAS cell lines) were used to test the inhibitory growth of PG via cell cytotoxic effects (MTT assay), cell cycle analysis, and Western blotting. PG under various concentrations and time courses were shown to effectively cause cell death and cell-cycle arrest in OECM1 and SAS cells. Additionally, PG induced autophagic cell death in OECM1 and SAS cells by LC3-mediated P62/LC3-I/LC3-II pathway at the in vitro level. These findings elucidate the role of PG, which may target the autophagic cell death pathways as a potential agent in cancer therapeutics.

Micro-expression recognition is influenced by emotional contexts at the behavioral level. It is found that the recognition for micro-expressions is poorer following a negative context compared to the recognition following a neutral context. However, it remains unclear whether the modulation takes place in the early or later stage of the processing of micro-expressions as reflected in event-related potentials (ERPs). Using synthesized micro-expressions in this study, we investigated how emotional context modulates the ERP components that are elicited by micro-expressions. We observed that, compared to neutral contexts, negative and positive contexts elicited more positive amplitude trends for processing the subsequent target micro-expressions, and more positive P1 and N170 effects were elicited by target micro-expressions following negative and positive contexts compared to those following neutral contexts. Moreover, there were larger P1 effects elicited by the target micro-expressions when the context and target expressions were incongruent compared to when they were congruent. Our findings provide new ERP evidence to indicate that emotional contexts modulate micro-expression processing, and that the modulation of emotional contexts takes place at the early stage of facial-expression processing.

The length polymorphism of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter is associated with cardiovascular events and mortality in high-risk populations. Experimental data suggest that heme oxygenase-1 protects against kidney disease. However, the association between this polymorphism and long-term risk of CKD in high-risk patients is unknown. We analyzed the allelic frequencies of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter in 386 patients with coronary artery disease recruited from January 1999 to July 2001 and followed until August 31, 2012. The S allele represents short repeats (

The structures, names, bioactivities and references of 138 briarane-type diterpenoids, including 87 new compounds, are summarized in this review. All the briarane-type compounds mentioned in this review article were obtained from gorgonian corals including the genus Briareum, Dichotella, Junceella and Verrucella. Some of these compounds showed potential bioactivities.

A new eunicellin diterpenoid, cladieunicellin I (1), and a new natural eunicellin, litophynin I diacetate (2), were isolated from a Formosan soft coral identified as Cladiella sp. The structures of eunicellins 1 and 2 were elucidated by spectroscopic methods and by comparison of the spectral data with those of related analogues. Eunicellin 1 exhibited significant cytotoxicity toward the DLD-1 human colorectal adenocarcinoma cells.

Persistent inflammation and oxidative stress play a pathogenic role in the high cardiovascular morbidity and mortality of hemodialysis patients. Heme oxygenase-1 is considered to have anti-inflammatory and antioxidant properties. This study assessed the association between the length of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene microsatellite promoter and cardiovascular events and mortality among hemodialysis patients.Study participants were recruited from October 1, 2006 to December 31, 2006. The allelic frequencies of the length of guanosine thymidine dinucleotide repeats (the S allele represents shorter [27] repeats, and the L allele represents longer [≥ 27] repeats) in the heme oxygenase-1 gene promoter were analyzed in 1080 unrelated chronic hemodialysis patients and 365 healthy controls for distribution comparison. Cardiovascular events and mortality were the study outcomes, and the hemodialysis patients were followed until June 30, 2011.The genotype proportions were 20.6%, 48.8%, and 30.6% for S/S, S/L, and L/L, respectively, in the hemodialysis patients and comparable with those proportions in healthy controls. The patients with the L/L genotype had significantly higher baseline serum high-sensitivity C-reactive protein and malondialdehyde levels than the patients with the S/S or S/L genotypes. During a median follow-up of 50 months, 307 patients died. A Kaplan-Meier survival analysis showed the highest cardiovascular events and all-cause mortality in patients with the L/L genotype. The adjusted hazard ratios (95% confidence intervals) for each L allele in additive model were 1.42 (1.20 to 1.67 [P0.001]) for cardiovascular events and 1.19 (1.01 to 1.40 [P=0.03]) for all-cause mortality.Chronic hemodialysis patients with longer lengths of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter exhibit higher inflammation and oxidative stress. These patients have higher risk of long-term cardiovascular events and mortality.

A new sterol, (22R,23R,24R)-5α,8α-epidioxy-22,23-methylene-24-methyl-cholest-6,9(11)-dien-3β-ol (1), and two known sterols, (22R,23R,24R)-5α,8α-epidioxy-22,23-methylene-24-methylcholest-6-en-3β-ol (2) and 24-methylenecholestane-1α,3β,5α, 6β,11α-pentol (3), were isolated from the soft coral Sinularia gaweli. The structure of sterol 1 was established by spectroscopic methods and by comparison of the spectral data with those of known analogues. The cytotoxicity of sterols 1–3 towards various tumor cells is reported.

A total of 499 Salmonella isolates including 9 serovars from humans and various animal hosts were collected to compare prevalence of integron and antimicrobial resistance. The integron and gene cassette were detected by PCR, and then the gene cassette type was further determined by sequencing and restriction fragment length polymorphism (RFLP) analysis. The antimicrobial susceptibility test was conducted by disk diffusion method. The positivity percentage of class 1 integron and the diversity of gene cassettes carried by integron were quite different in various Salmonella serovars, especially comparing those from animals to humans. After sequencing and RFLP analysis, it was identified eight gene cassette types. The gene cassette type D carrying ampicillin/streptomycin resistance genes was the most common one (42.2%) in the integron-positive isolates. More diversity of gene cassette types was identified in humans comparing to that in animals. Several gene cassette types were identified for the first time in some Salmonella serovars. In this study, 31.5% (157/499) of the isolates were multi-resistant to ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, and tetracycline (ACSSuT). S. Choleraesuis isolates with the cassette type A1, but S. Typhimurium isolates with the cassette type E1, were frequently associated with ACSSuT-resistant (80.6% and 72.7%, respectively). There was a significant association between the presence of class 1 integron and quinolone resistance in S. Choleraesuis isolates, but not in S. Typhimurium. Our findings imply that transmission efficiency of various gene cassettes through the integron could be different in various Salmonella serovars.

The structures of pubinernoid A (1) and apo-9'-fucoxanthinone (2), isolated from a gorgonian coral Pinnigorgia sp., were elucidated on the basis of spectroscopic analysis and by comparison of their spectroscopic data with those of known compounds. This is the first report of 1 and 2 from an animal source. Apo-9'-fucoxanthinone (2) displayed a significant inhibitory effect on the release of elastase by human neutrophils, with an IC50 value of 5.75 μM.

Background Spironolactone has been shown to reduce cardiovascular death in patients with mild-to-moderate chronic kidney disease (CKD), but its risks and benefits in advanced CKD remain unsettled. We aimed to assess whether spironolactone reduces cardiovascular mortality and morbidity in pre-dialysis stage 5 CKD patients. Methods Using Taiwan's National Health Insurance Research Database from January 2000 to June 2009, we enrolled 27,213 pre-dialysis stage 5 CKD adult patients, in whom 1363 patients were treated with spironolactone (user) and 25,850 were not (nonuser). Outcomes were all-cause mortality, hospitalization for heart failure (HHF) and major adverse cardiac event (MACE, the composite of acute myocardial infarction and ischemic stroke). Patients were followed up till December 31, 2009. Results Over 85,758 person-years of follow-up, spironolactone users had higher incidence for all-cause mortality (24.7/100 person-years vs. 10.6/100 person-years), infection-related death (4.4/100 person-years vs. 1.7/100 person-years) and HHF (4.0/100 person-years vs. 1.4/100 person-years). Multivariable Cox hazards model showed that spironolactone users were associated with higher risks of all-cause mortality (adjusted hazard ratio [aHR] 1.35, 95% confidence interval [CI] 1.24–1.46), infection-related death (aHR 1.42, CI 1.16–1.73) and HHF (aHR 1.35, CI 1.08–1.67) as compared to nonusers. The risks for cardiovascular mortality, MACE and hyperkalemia-associated hospitalization were similar between two groups. After matching users and nonusers (1:3 ratio) by propensity scores, the results were consistent in matched cohort and across subgroups. Conclusions Spironolactone may be associated with higher risks for all-cause and infection-related mortality and HHF in pre-dialysis stage 5 CKD patients. Spironolactone should be used with caution in advanced CKD patients.

Bacteria associated with eight field-collected and five cultured soft corals of Briareum sp., Sinularia sp., Sarcophyton sp., Nephtheidae sp., and Lobophytum sp. were screened for their abilities in producing antimicrobial metabolites. Field-collected coral samples were collected from Nanwan Bay in southern Taiwan. Cultured corals were collected from the cultivating tank at National Museum of Marine Biology and Aquarium. A total of 1,526 and 1,138 culturable, heterotrophic bacteria were isolated from wild and cultured corals, respectively; seawater requirement and antimicrobial activity were then assessed. There is no significant difference between the ratio of seawater-requiring bacteria on the wild and cultured corals. The ratio of antibiotic-producing bacteria within the seawater-requiring bacteria did not differ between the corals. Nineteen bacterial strains that showed high antimicrobial activity were selected for 16S rDNA sequencing. Three strains could be assigned at the family level (Rhodobacteraceae). The remaining 16 strains belong to eight genera: Marinobacterium (2 strains), Pseudoalteromonas (1), Vibrio (5), Enterovibrio (1), Tateyamaria (1), Labrenzia (2), and Pseudovibrio (4). The crude extract from bacteria strains CGH2XX was found to have high cytotoxicity against the cancer cell line HL-60 (IC(50) = 0.94 μg/ml) and CCRF-CEM (IC(50) = 1.19 μg/ml). Our results demonstrate that the marine bacteria from corals have great potential in the discovery of useful medical molecules.

A novel 15C compound, pseudoalteromone B (1), possessing a novel carbon skeleton, was obtained from a marine bacterium Pseudoalteromonas sp. CGH2XX. This bacterium was originally isolated from a cultured-type octocoral Lobophytum crassum, that was growing in cultivating tanks equipped with a flow-through sea water system. The structure of 1 was established by spectroscopic methods. Pseudoalteromone B (1) displayed a modestly inhibitory effect on the release of elastase by human neutrophils.

OBJECTIVE The current study aimed to investigate whether microalbuminuria or moderately decreased glomerular filtration rate (GFR) is a better predictor for the development and progression of retinopathy in type 2 diabetic patients. RESEARCH DESIGN AND METHODS Type 2 diabetic patients without cardiovascular diseases, malignancy, pregnancy, and acute intercurrent illness were enrolled between 1 August 2001 and 31 December 2002. All participants provided their detailed medical history and underwent an eye fundus examination. They were followed up in outpatient clinics, and serum creatinine, urinary albumin-to-creatinine ratio (UACR), and retinal photographs were followed up annually until 31 December 2009. The primary outcomes were development and progression of diabetic retinopathy and nephropathy. The secondary outcomes were cardiovascular events and all-cause mortality. RESULTS Among 487 participants, 81 subjects had normoalbuminuria and moderate renal impairment (baseline eGFR 30–59.9 mL/min/1.73 m2), and 106 subjects had microalbuminuria and baseline eGFR ≥60 mL/min/1.73 m2. Patients with microalbuminuria and eGFR ≥60 mL/min/1.73 m2 had a significantly greater risk for development and progression of diabetic retinopathy (HR 3.34 [95% CI 1.04–10.70]) compared with those with moderate renal impairment and normoalbuminuria after multivariate adjustment. Risks for renal outcome, cardiovascular events, and all-cause mortality were not significantly different between the two groups. CONCLUSIONS Microalbuminuria has a greater impact on predicting the development and progression of diabetic retinopathy compared with moderate decline in GFR among type 2 diabetic patients.

Aberrant TGFβ signaling pathway may alter the expression of down-stream targets and promotes ovarian carcinogenesis. However, the mechanism of this impairment is not fully understood. Our previous study has identified RunX1T1 as a putative SMAD4 target in an immortalized ovarian surface epithelial cell line, IOSE. In this study, we report that transcription of RunX1T1 was confirmed to be positively regulated by SMAD4 in IOSE cells and epigenetically silenced in a panel of ovarian cancer cell lines by promoter hypermethylation and histone methylation at H3 lysine 9. SMAD4 depletion increased repressive histone modifications of RunX1T1 promoter without affecting promoter methylation in IOSE cells. Epigenetic treatment can restore RunX1T1 expression by reversing its epigenetic status in MCP3 ovarian cancer cells. When transiently treated with a demethylating agent, the expression of RunX1T1 was partially restored in MCP3 cells, but gradual re-silencing through promoter re-methylation was observed after the treatment. Interestingly, SMAD4 knockdown accelerated this re-silencing process, suggesting that normal TGF-beta signaling is essential for the maintenance of RunX1T1 expression. In vivo analysis confirmed that hypermethylation of RunX1T1 was detected in 35.7% (34/95) of ovarian tumors with high clinical stages (P=0.035) and in 83% (5/6) of primary ovarian cancer-initiating cells. Additionally, concurrent methylation of RunX1T1 and another SMAD4 target, FBXO32 which was previously found to be hypermethylated in ovarian cancer was observed in this same sample cohort (P< 0.05). Restoration of RunX1T1 inhibited cancer cell growth. Taken together, dysregulated TGFβ/SMAD4 signaling may lead to epigenetic silencing of a putative tumor suppressor, RunX1T1, during ovarian carcinogenesis.

The most common esophageal foreign body in adults is impacted food bolus. Polypectomy snares, Dormia baskets, retrieval nets, rat-tooth forceps, alligator forceps or polyp graspers are usually used to remove it. Here, we report the case of a 78-year-old woman whose esophagogastroduodenoscopy (EGD) showed a firm goose liver impacted tightly in the lower esophagus; all of the above-mentioned retrieval instruments could not remove it. We used a homemade device by attaching a modified nasogastric tube to an EGD and successfully removed the goose liver by suction under endoscopic visualization. The method is very effective to remove firm and tightly impacted materials in a narrow lumen. When the usual retrieval instruments fail, a homemade suction tube attached to an EGD is an alternative.

Objective To assess the effect of pioglitazone on renal outcome, including urinary albumin excretion and estimated glomerular filtration rate (eGFR), in diabetic patients. Design A prospective, randomized, open-labeled, controlled study. Setting Taipei Veterans General Hospital. Patients Sixty type 2 diabetic patients treated with sulfonylureas and metformin, whose glycated hemoglobin (HbA1c) levels were between 7% and 10% and eGFR was between 45 and 125 mL/min/1.73 m2. Intervention The patients were randomized to receive acarbose or pioglitazone and followed up for 6 months. Thirty patients were randomly assigned to receive acarbose, and 30 patients were assigned to receive pioglitazone. Measurements The primary study endpoint was the changes in the urinary albumin-to-creatinine ratio (UACR). The secondary endpoint was the changes in eGFR and other parameters. Results After 6 months of treatment, the mean changes in UACR were -18 ± 104 and 12 ± 85 (p = 0.25, between groups) for the acarbose and pioglitazone groups, respectively. The mean changes in eGFR were 0 ± 14 and -7 ± 16 mL/min/1.73 m2 (p = 0.09, between groups) for the acarbose and pioglitazone groups, respectively. The reductions in HbA1c were similar in both groups. Fasting blood glucose was lower in the pioglitazone group than in the acarbose group. Significant body weight gain was observed in the pioglitazone group as compared with the acarbose group (1.3 ± 2.8 vs. -0.6 ± 1.5 kg, p = 0.002). Conclusion In type 2 diabetic patients who were treated with sulfonylureas and metformin and possessed HbA1c levels between 7% and 10%, additional acarbose or pioglitazone for 6 months provided similar glycemic control and eGFR and UACR changes. In the pioglitazone group, the patients exhibited significant body weight gain. Trial registration ClinicalTrials.gov NCT01175486.

Background Complete or partial trisomy 10q involves a duplication of 10q, or the long arm of chromosome 10. Distal 10q trisomy is a well-recognized and defined but rare genetic syndrome in which duplication of distal segments of 10q results in a pattern of malformations. Although abnormal chromosome phenotypes are commonly detected by visualization of chromosomes by traditional cytogenetic techniques, this approach is marginal in both diagnostic sensitivity and potential for biological interpretation, thus making implementation of advanced techniques and analysis methods an important consideration in a health service. Case presentation The present study describes the case of a Taiwanese boy from healthy parents with mental, growth, and psychomotor retardations. Additional clinical features included facial dysmorphism, microcephaly, brain atrophy, camptodactyly, and—as the first reported case—bilateral renal atrophy with chronic kidney disease stage 2 and the presence of a renal cyst in one kidney. A novel 21.8 Mb copy number variation region in chromosome region 10q23.1–10q25.1 was verified by array-comparative genomic hybridization in combination with quantitative real-time polymerase chain reaction. Subsequently, 200 protein-coding genes were identified in this copy number variation region and analyzed for their biological meaning using the database for annotation, visualization and integrated discovery. Conclusion According to the result of gene functional enrichment analysis using database for annotation, visualization and integrated discovery, the Wnt signaling pathway is the most pertinent to the gene content in the copy number variation region. A change in the expression levels of some Wnt signaling pathway components and of NFKB2 and PTEN genes due to a gain in their gene copy number may be associated with the patient’s clinical outcomes including brain atrophy, bilateral renal atrophy with chronic kidney disease stage 2, a renal cyst in one kidney, and growth retardation. Electronic supplementary material The online version of this article (doi:10.1186/s13104-015-1213-x) contains supplementary material, which is available to authorized users.

Metformin is recommended as a first-line treatment for patients with type 2 diabetes. However, use of this drug has been contraindicated in individuals with impaired kidney function because of the perceived risk of lactic acidosis. Evidence now supports cautious use of metformin in people with mild-to-moderate chronic kidney disease. However, studies examining the use of metformin in patients with advanced chronic kidney disease are lacking. We aimed to assess the safety of metformin in patients with type 2 diabetes and advanced (approximately stage 5) chronic kidney disease.We did a retrospective, observational, cohort study of patients with type 2 diabetes who were enrolled prospectively in Taiwan's national health insurance research database between Jan 1, 2000, and June 30, 2009, and had follow-up data until Dec 31, 2009. We included individuals with a serum creatinine concentration greater than 530 μmol/L, which is approximately equivalent to stage 5 chronic kidney disease. From a consecutive sample of 12 350 patients with type 2 diabetes and chronic kidney disease, 1005 used metformin and 11 345 were non-users. We matched users and non-users of metformin by propensity score in a 1:3 ratio. Our primary outcome was all-cause mortality.813 metformin users were matched by propensity score to 2439 non-users. The two groups of patients did not differ significantly by 30 baseline clinical and socioeconomic variables. Median follow-up in the matched cohort was 2·1 years (range 0·3-9·8). All-cause mortality was reported in 434 (53%) of 813 metformin users and in 1012 (41%) of 2439 non-users. After multivariate adjustment, metformin use was an independent risk factor for mortality (adjusted hazard ratio 1·35, 95% CI 1·20-1·51; p0·0001). The increased mortality risk was dose-dependent and was consistent across all subgroup analyses. However, metformin use compared with no use was associated with a higher but non-significant risk of metabolic acidosis (1·6 vs 1·3 events per 100 patient-years; adjusted hazard ratio 1·30, 95% CI 0·88-1·93; p=0·19).Use of metformin in people with type 2 diabetes and a serum creatinine concentration greater than 530 μmol/L is associated with a significantly increased risk of all-cause mortality compared with non-users. Metformin use should not be encouraged in this patient group.Taipei Tzu Chi Hospital, Taipei Veterans General Hospital, Foundation for Poison Control, National Health Research Institutes, Ministry of Science and Technology of Taiwan.

With the growth in the number of elderly and people with chronic diseases, the number of hospital services will need to increase in the near future. With myriad of information technologies utilized daily and crucial information-sharing tasks performed at hospitals, understanding the relationship between task performance and information system has become a critical topic. This research explored the resource pooling of hospital management and considered a computed tomography (CT) patient-referral mechanism between two hospitals using the information system theory framework of Task-Technology Fit (TTF) model. The TTF model could be used to assess the `match' between the task and technology characteristics. The patient-referral process involved an integrated information framework consisting of a hospital information system (HIS), radiology information system (RIS), and picture archiving and communication system (PACS). A formal interview was conducted with the director of the case image center on the applicable characteristics of TTF model. Next, the Icam DEFinition (IDEF0) method was utilized to depict the As-Is and To-Be models for CT patient-referral medical operational processes. Further, the study used the `leagility' concept to remove non-value-added activities and increase the agility of hospitals. The results indicated that hospital information systems could support the CT patient-referral mechanism, increase hospital performance, reduce patient wait time, and enhance the quality of care for patients.

Thiazolidinediones (TZDs) reduce urinary albumin excretion and proteinuria in diabetic nephropathy. The effect of TZDs on hard renal outcome in diabetic patients with chronic kidney disease (CKD) is unknown. We investigate the association of TZDs and risk of long-term dialysis or death in diabetic patients with advanced CKD. The nationwide population-based cohort study was conducted using Taiwan’s National Health Insurance Research Database. From January 2000 to June 2009, 12350 diabetic patients with advanced CKD (serum creatinine levels greater than 6 mg/dL but not yet receiving renal replacement therapy) were selected for the study. We used multivariable Cox regression models and a propensity score-based matching technique to estimate hazard ratios (HRs) for development of long-term dialysis and the composite outcome of long-term dialysis or death for TZD users (n=1224) as compared to nonusers (n=11126). During a median follow-up of 6 months, 8270 (67.0%) patients required long-term dialysis and 2593 (21.0%) patients died before starting long-term dialysis. Using propensity score matched analysis, we found TZD users were associated with a lower risk for long-term dialysis (HR, 0.80; 95% confidence interval [CI], 0.74-0.86) and the composite outcome of long-term dialysis or death (HR, 0.85; 95% CI, 0.80-0.91). The results were consistent across most patient subgroups. Use of TZDs among diabetic patients with advanced CKD was associated with lower risk for progression to end-stage renal disease necessitating long-term dialysis or death. Further randomized controlled studies are required to validate this association.

The timing intervals initiated by voluntary pressing actions are subjectively compressed compared with those initiated by voluntary releasing actions. Event-related potentials (ERPs) were employed in the present study to uncover the temporal mechanisms underlying this temporal illusion. The results revealed that the mean amplitude of the P1 component over the frontal-central recording sites, but not the P2 component, was larger in the voluntary pressing condition than in the voluntary releasing condition at the time perception stage. In the fronto-central region, increases in oscillatory activities of delta-theta frequency range (1-7 Hz) were found in the voluntary pressing condition, which corresponded with the emergence of the P1 peak. In addition, the P1 amplitude was negatively related to the corresponding reported time length at the single-trial level. These results are discussed in terms of the functional role of the response-locked P1 in the time perception stage.

The present study used a single-task paradigm in which participants received guidance to focus more attention (waiting for someone) on the temporal intervals in the "waiting" condition and to stay relaxed in the control condition. The reported time was longer in the waiting condition than in the control condition. Functional near-infrared spectroscopy was used to measure simultaneously the activation levels of the dorsolateral prefrontal cortex (DLPFC) for each condition. Greater oxyhemoglobin (oxy-Hb) activation in the waiting condition was observed compared with the control condition, whilst deoxyhemoglobin data showed no difference between the two conditions. The gradual changes in oxy-Hb in the DLPFC in increments of 100 ms yielded further insights into the role of this region in the "watched pot never boils" phenomenon.

A robust automatic micro-expression recognition system would have broad applications in national safety, police interrogation, and clinical diagnosis. Developing such a system requires high quality databases with sufficient training samples which are currently not available. We reviewed the previously developed micro-expression databases and built an improved one (CASME II), with higher temporal resolution (200 fps) and spatial resolution (about 280×340 pixels on facial area). We elicited participants' facial expressions in a well-controlled laboratory environment and proper illumination (such as removing light flickering). Among nearly 3000 facial movements, 247 micro-expressions were selected for the database with action units (AUs) and emotions labeled. For baseline evaluation, LBP-TOP and SVM were employed respectively for feature extraction and classifier with the leave-one-subject-out cross-validation method. The best performance is 63.41% for 5-class classification.