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Shih-Chi Wu,1,2,&ast; Te-An Chen,3,&ast; Han-Tsung Cheng,3 Yu-Jun Chang,4 Yu-Chun Wang,3 Chia-Wei Tzeng,3 Chia-Hao Hsu,3 Chih-Hsin Muo5 1School of Medicine, China Medical University, Taichung, Taiwan; 2Trauma and Emergency Center, China Medical University Hospital, Taichung, Taiwan; 3Department of Surgery, China Medical University Hospital, Taichung, Taiwan; 4Epidemiology and Biostatistics Center, Changhua Christian Hospital, Changhua, Taiwan; 5Management Office for Health Data, China Medical University and Hospital, Taichung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Shih-Chi WuTrauma and Emergency Center, China Medical University Hospital, No. 2 Yuh-Der Road, Taichung, 404, TaiwanTel +886-4-22052121 ext. 5043Fax +886-4-22334706Email rw114@mail.cmuh.org.twBackground: To evaluate the effect of different PN types on surgical critically ill trauma/acute care surgery patients with hepatic disorders at admission.Methods: This is a retrospective study. The PN types included lipid-free, soybean oil/medium-chain triglyceride, olive oil-based, and fish oil-containing PNs. Patients admitted with liver injury or liver surgery, elevated serum AST/ALT level, and elevated serum total bilirubin level were included. The exclusion criteria are as follows: 1) age < 18 years, 2) severe liver disease/cirrhosis, 3) received more than one type of PN and 4) serum total bilirubin > 4.9 mg/dl at admission. Demographics, severity, comorbidities, blood stream infection, hyperbilirubinemia (total bilirubin > 6.0 mg/dl), and mortality were collected for analysis. We also performed analysis stratified by separated lipid doses (g/kg/day).Results: A total of 156 patients were enrolled. There were no demographic differences among groups. The lipid-free group was associated with the highest mortality rate and incidence of hyperbilirubinemia. Compared to the lipid-free group, the olive oil-based group had the lowest risk of hyperbilirubinemia. After being stratified by separated lipid doses, the incidence of hyperbilirubinemia decreased when the lipid dosage increased. Regarding different types of lipids, patients who received more than the median dosage of lipids showed a significantly lower risk of hyperbilirubinemia, except in the fish oil-containing group.Conclusion: Our result suggested that lipid-free PN is associated with an increased risk of hyperbilirubinemia in surgical critically ill patients with admission hepatic disorder. Further studies are warranted.Keywords: hyperbilirubinemia, intravenous fat emulsion, parenteral nutrition, surgical critically ill

Background Synaptic damage and glutamate excitotoxicity have been implicated in the pathogenesis of vascular dementia (VD). Clathrin, RAB5B and N-methyl-d-aspartic acid receptor 1 (NMDAR1) proteins play a vital role in endocytosis of synaptic vesicles in neurons and glutamate over accumulation. Previous researches have been confirmed that Shenzhi Jiannao (SZJN) formula has an anti-apoptotic and neuroprotective effect in VD, but the underlying mechanisms are still unclear. In this study, we aimed to explore the effect of SZJN formula on cognitive impairment and glutamate excitotoxicity via clathrin-mediated endocytosis (CME) in vivo and in vitro. Methods SZJN formula consists of Panax ginseng C.A.Mey., Anemarrhena asphodeloides Bunge, and Paeonia anomala subsp. veitchii (Lynch) D.Y.Hong & K.Y.Pan. All herbs were prepared into granules. Both common carotid arteries were permanent occluded (2‐vessel occlusion, 2VO) in male Sprague Dawley (SD) rats to model VD. One day after operation, the rats began daily treatment with SZJN formula for 2 weeks. The neuroprotective effects of SZJN formula was subsequently assessed by the novel object recognition test, Morris water maze, hematoxylin–eosin (HE) staining and Nissl staining. Glutamate cytotoxicity was assessed by detecting cell viability and cell death of PC12 cells. Immunohistochemistry, immunofluorescence, Western blot, and quantitative real‐time PCR were used to detect the expression levels of clathrin, RAB5B, and NMDAR1. Results Administration of SZJN formula effectively improved short-term memory and spatial memory. SZJN formula treatment significantly reduced hippocampal neuronal loss, and recovered the arrangement and morphology of neurons and Nissl bodies. Moreover, SZJN formula promoted the proliferation of PC12 cells and inhibited glutamate-induced cell death. The down-regulation of clathrin and RAB5B, as well as the upregulation of NMDAR1 in the brain induced by 2VO or glutamate was also notably reversed by SZJN formula at both the protein and mRNA levels, which may contribute to SZJN formula induced improved neurological function. Conclusions Taken together, our findings provide evidence that the neuroprotective effects of SZJN formula in experimental VD maybe mediated through promoting the expression of clathrin-mediated endocytosis and reducing NMDARs‐associated glutamate excitotoxicity. SZJN formula serves as a promising alternative therapy and may be a useful herbal medicine for preventing progression of VD. Graphic abstract

This study evaluated the effect of extreme temperatures on events requiring emergency room visits (ERVs) for hypertensive disease, ischemic heart disease (IHD), cerebrovascular disease, and chronic kidney disease (CKD) for population stratified by sex and age living in Taiwan's metropolitan city from 2000 to 2014. The distributed lag non-linear model was adopted to examine the association between ambient temperature and area-age-sex-disease-specific ERVs for a population aged 40 years and above. The reference temperature was defined by a percentile value to describe the temperature in each city. Area-age-sex-disease-specific relative risk (RR) and 95% confidence intervals (CI) were estimated in association with extreme high (99th percentile) and low (5th percentile) temperatures. Temperature-related ERV risks varied by area, age, sex, and disease. Patients with CKD tend to have comorbidities with hypertensive disease. All study populations with hypertensive disease have significant risk associations with extreme low temperatures with the highest RR of 2.64 (95% CI: 2.08, 3.36) appearing in New Taipei City. The risk of IHD was significantly associated with extreme high temperature for male subpopulation aged 40-64 years. A less significant association was observed between the risks of cerebrovascular disease with extreme temperature. The risk of CKD was most significantly associated with extreme high temperature especially for a subpopulation aged 40-64 years. All study subpopulations with hypertensive disease have significant risk associations with extreme low temperature. Male subpopulations were more vulnerable to extreme temperatures, especially for those aged 40-64 years.

Background: To evaluate the role of red cell distribution width (RDW) fluctuations in the diagnosis of neonatal sepsis. Methods: In this retrospective cohort study of the Medical Information Mart for Intensive Care III database (version 1.4), newborns with sepsis were matched with patients without sepsis to analyze RDW as a diagnostic marker. Those newborns were analyzed based on gestational age, sex, and ethnicity. Receiver operating characteristic (ROC) analysis and multiple logistic regression were used to evaluate RDW fluctuation for sepsis diagnosis. Results: A total of 2456 neonates were included. RDW fluctuations showed better accuracy than the maximum RDW did (area under the curve (AUC): 0.88 vs. 0.81, sensitivity 92.10% vs. 78.70%; specificity 71.70% vs. 69.30%, respectively). Furthermore, logistic regression analysis showed a positive association between RDW fluctuation and the diagnosis of sepsis (odds ratio 1.13; 95% confidence interval, 1.08–1.18) after adjusting for gestational age, hemoglobin, and white blood cell count. Conclusion: RDW fluctuations might be a potential diagnostic marker for NICU patients with sepsis.

The vagal nervous system is central to the physiological responses and systemic diseases of the liver. We evaluated the subsequent risk of liver and intrahepatic cancer (HCC/ICC) in non-H. pylori (HP)-infected perforated peptic ulcer (PPU) patients with and without vagotomy. Hospitalized PPU patients who underwent simple closure or truncal vagotomy/pyloroplasty (TVP) in the National Health Insurance Research Database from 2000 to 2008 were enrolled. The exclusion criteria included: (1) Multiple surgeries for PPU were received at the same admission; (2) Any cancer history; (3) Previous peptic ulcer-associated surgery; (4) HP infection history; (5) Viral hepatitis infection history; (6) Follow-up duration

Background: This study evaluated the effect of extreme temperatures on events requiring emergency room visits (ERVs) for hypertensive disease, ischemic heart disease (IHD), cerebrovascular disease, and chronic kidney disease (CKD) for population stratified by sex and age living in Taiwan’s metropolitan city from 2000 to 2014. Methods: The distributed lag nonlinear model was adopted to examine the association between ambient temperature and area–age–sex–disease-specific ERVs for a population aged 40 years and above. The reference temperature was defined by a percentile value to describe the temperature in each city. Area–age–sex–disease-specific relative risk (RR) and 95% confidence intervals (CI) were estimated in association with extreme high (99th percentile) and low (5th percentile) temperatures. Results: Temperature-related ERV risks varied by area, age, sex, and disease. Patients with CKD tend to have comorbidities with hypertensive disease. All study populations with hypertensive disease have significant risk associations with extreme low temperatures with the highest RR of 2.64 (95% CI: 2.08, 3.36) appearing in New Taipei City. The risk of IHD was significantly associated with extreme high temperature for male subpopulation aged 40–64 years. A less significant association was observed between the risks of cerebrovascular disease with extreme temperature. The risk of CKD was most significantly associated with extreme high temperature especially for a subpopulation aged 40–64 years. Conclusions: All study subpopulations with hypertensive disease have significant risk associations with extreme low temperature. Male subpopulations were more vulnerable to extreme temperatures, especially for those aged 40–64 years. Funding Statement: This study was supported by grants from the Taiwan Ministry of Science and Technology (MOST 108-2625-M-033-002- and MOST 106-2221-E-033-006-MY2), National Health Research Institutes (NHRI-107A1-EMCO-3617191, NHRI-106A1-PDCO-3617191 and MOHW105-TDU-M-212-113003), and Taiwan CWB (MP10501-0125), the Ministry of Health and Welfare (MOHW109-TDU-B-212-114004). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: All methods were carried out in accordance with relevant guidelines and all protocols were approved by Taiwan Research Ethics Committee, National Health Research Institutes (code: EC1061209-F-E). All the health data were extracted from National Health Insurance database that provided to scientist in Taiwan for research purpose.

To develop a predictive model to identify hospitalized older patients at risk of functional decline. Older age, hearing impairment, history of falls within one year, risk of malnutrition, physical restraint, admission via emergency department and hospital stay ≥5 days were independent predictive factors for decline. A scoring system constructed from the above predictive factors ranged from 0-18 points and ≥6 points was chosen as the cut-off point. A scoring system, HAD-FREE Score developed from seven independent factors could predict functional decline with moderate discriminative ability and good validation. To develop a predictive model to identify hospitalized older patients at risk of functional decline. This retrospective cohort study recruited participants aged 65 years and over admitted to internal medicine wards of a tertiary medical center in Taiwan during May to October 2017 for developing predictive model (n = 1698) and those admitted during November to December 2017 for validation study (n = 530) of the model. Demographic data, geriatric assessments and hospital conditions (admission route and length of hospital stay) were collected for analysis. Overall, of the 1698 participants (mean age 75.8 ± 7.9 years, 60.9% male) enrolled in the development study, 20.1% had functional decline. Results of multivariate logistic regression showed that older age, hearing impairment, history of falls within one year, risk of malnutrition, physical restraint, admission via emergency department and hospital stay ≥ 5 days were independent predictive factors for decline. A scoring system, HAD-FREE Score, constructed from the above predictive factors ranged from 0 to 18 points and ≥ 6 points was chosen as the cut-off point. The area under the receiver operating characteristic analysis was 0.748 (95% confidence interval: 0.720–0.776), the sensitivity was 65.3% and the specificity was 71.3%. Validation of the HAD-FREE Score showed moderate discriminative ability in the validation study. A HAD-FREE Score developed from seven independent factors could predict functional decline with moderate discriminative ability and good validation. This scoring system can be the basis of an automatic dynamic tracking within the electronic medical record to identify those older patients at risk of functional decline during hospitalization.

Background Oral antiseizure medications (ASMs) are first-line treatments for patients with epilepsy. However, ASMs may alter sleep architecture, adversely affecting patient outcomes. The meta-analysis aimed to elucidate the effect of ASMs on sleep architecture. Methods PubMed, Embase, and Cochrane Central database (up to Febrary 2021) were searched for randomized control trials (RCT) with effects of ASMs on polysomnography parameters. A meta-analysis using a random-effects model was performed. We did not set limitation to the participants with underlying diagnosis of epilepsy. Results Eighteen randomized-controlled trials fulfilled the eligibility criteria. The effects of five main groups of ASMs (sodium channel blockers, calcium channel blockers, GABA enhancers, synaptic vesicle glycoprotein 2A [SV2A] ligand, and broad-spetrum ASMs) on slow-wave sleep (SWS), rapid eye movement (REM) sleep, and sleep efficiency (SE) were analyzed. Compared with placebo, calcium channel blockers and GABA enhancers significantly increased SWS. GABA enhancers also decreased REM sleep percentage, whereas calcium channel blockers significantly increased SE. Sodium channel blockers, SV2A ligand and broad-spectrum ASMs did not affect SWS, REM sleep, or SE. The subgroup analysis revealed that gabapentin, pregabalin, and tiagabine increased the percentage of SWS. Tiagabine also decreased REM sleep, whereas pregabalin increased SE. Finally, levetiracetam did not affect SWS, REM sleep, and SE. Conclusions This meta-analysis indicated that ASMs can have a statistically significant effect on sleep parameters; the effect differs between ASMs.

Introduction As populations age, sarcopenia becomes a major health problem among adults aged 65 years and older. However, little information is available about the relationship between sarcopenia and brain structure abnormalities. The objective of this study was to investigate associations between sarcopenia and brain atrophy in older adults and relationships with regional brain areas. Methods This prospective cohort study recruited 102 retirement community residents aged 65 years and older. All participants underwent gait speed measurement, handgrip strength measurement and muscle mass measurement by dual X-ray absorptiometry. Diagnosis of sarcopenia was made according to criteria of the Asian Working Group for Sarcopenia (AWGSOP). All patients underwent magnetic resonance imaging (MRI), and images were analysed for global cortical atrophy (GCA) (range 0–3), parietal atrophy (PA) (range 0–3) and medial temporal atrophy (MTA) (range 0–4). Results Among 102 older adult participants (81.4 ± 8.2 years), 47 (46.1%) were diagnosed with sarcopenia according to AWGSOP criteria. The sarcopenia group had more moderate to severe PA (Grade 2: 19.1% vs. 5.5%; grade 3:6.4% vs. 0%, P = 0.016) and GCA (Grade 2: 40.4% vs. 18.2%, P = 0.003) and a trend of more moderate to severe MTA (Grade 2: 46.8% vs. 30.9%; grade 3: 8.5% vs. 1.8%, P = 0.098) than the non-sarcopenia group. In univariate logistic regression, sarcopenia was significantly associated with PA (OR 5.94, 95% CI 1.56–22.60, P = 0.009), GCA (OR 3.05, 95% CI 1.24–7.51, P = 0.015), and MTA (OR 2.55, 95% CI 1.14–5.69, P = 0.023). In multivariable logistic regression analysis, sarcopenia was an independent risk factor for PA (adjusted OR 6.90, 95% CI 1.30–36.47, P = 0.023). After adjusting for all covariates, only age had a significant relationship with GCA (Adjusted OR 1.09, 95% CI 1.00–1.19, P = 0.044) and MTA (Adjusted OR 1.09, 95% CI 1.01–1.17, P = 0.022). Conclusions This is the first study to explore associations between sarcopenia and global as well as regional brain atrophy in older adults. The sarcopenia group had higher rates of moderate to severe PA, GCA and MTA than the non-sarcopenia group. PA was significantly associated with sarcopenia in older adults. Further longitudinal studies are needed to address the mechanism and pathogenesis of brain atrophy and sarcopenia.

Background Studies have demonstrated that exposure to extreme outdoor temperatures increases respiratory diseases related mortality and morbidity, especially in older adults. However, older adults spend over 80% of their time indoors, and the cumulative effects of exposure to indoor temperature on the risk of respiratory diseases have not been investigated. The objective of this study was to study the cumulative effect of indoor temperature exposure on emergency department visit due to respiratory diseases among older adults. Methods Participant data were collected from the Longitudinal Health Insurance Database from 2000 to 2014 in Taiwan. The cumulative degree hour was used to reflect the cumulative effect of indoor temperature exposure. A distributed lag nonlinear model was used to analyze the association between cumulative degree hour and emergency department visit due to respiratory diseases. Results Our findings revealed a significant risk of emergency department visits due to respiratory diseases at 27, 28, 29, 30, and 31 °C when cooling cumulative degree hours exceeded 60, 30, 19, 1, and 1, respectively, during the hot season (May to October) and at 19, 20, 21, 22, and 23 °C when heating cumulative degree hours exceeded 1, 1, 1, 39, and 49, respectively, during the cold season (November to April). Conclusions We conclude that the cumulative effects of indoor temperature exposure should be considered to reduce respiratory disease risk under climate change.

Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). The pre-S2 mutant large HBV surface antigen (LHBS) is highly associated with HCC. This study analyzed the expression of the large form of surface protein in tumors and evaluated the LHBS with mutations within the pre-S2 region as a high-risk recurrence marker in HCC patients after curative hepatic resection. By analyses using immunohistochemical staining (n = 12) and western blotting (n = 22), the HBV surface protein, which is mainly comprised of the major form of HBV surface antigen, was greatly diminished in the tumors. However, LHBS was not significantly decreased in tumorous regions, suggesting that LHBS maintains its expression in cancer development. A cohort of 175 patients with HBV-related HCC who underwent curative hepatic resection was analyzed for pre-S gene mutations using Pre-S Gene Chip. Results of the multivariate regression analysis showed that the serum pre-S2 mutant level and the American Joint Committee on Cancer stage were the two main independent high-risk factors for recurrence. A Cox proportional hazards analysis also revealed a prediction model, which indicated the recurrence-free survival rate along with the time after surgery; this was developed and further validated in an independent HCC cohort. Receiver operating characteristic curve analysis revealed that the model showed close sensitivities in the main and validation cohorts (area under the curve values, 0.741 and 0.704, respectively). Conclusion: Unlike the major HBV surface antigen, LHBS is mostly expressed in the tumorous regions of HBV-induced HCC, indicating that it plays a unique role in tumor progression; the relative level of pre-S2 mutant in serum is, independently of tumor stage, an important high-risk marker for HCC recurrence after primary hepatic resection. (Hepatology 2018).

BackgroundPelvic ring fracture is often combined with other injuries and such patients are considered at high risk of mortality and complications. There is controversy regarding the gold standard protocol for the initial treatment of pelvic fracture. The aim of this study was to assess which risk factors could affect the outcome and to analyze survival using our multidisciplinary institutional protocol for traumatic pelvic ring fracture.Material and methodsThis retrospective study reviewed patients who sustained an unstable pelvic ring fracture with Injury Severity Score (ISS) ≥ 5. All patients were admitted to the emergency department and registered in the Trauma Registry System of a level I trauma center from January 1, 2008, to December 31, 2017. The annular mortality rate after the application of our institutional protocol was analyzed. Patients with different systems of injury and treatments were compared, and regression analysis was performed to adjust for factors that could affect the rate of mortality and complications.ResultsDuring the 10-year study period, there were 825 unstable pelvic ring injuries, with a mean ISS higher than that of other non-pelvic trauma cases. The annual mortality rate declined from 7.8 to 2.4% and the mean length of stay was 18.1 days. A multivariable analysis showed that unstable initial vital signs, such as systolic blood pressure ISS > 15 (OR 4.84; CI 0.85–27.65), pulse rate ConclusionPoor initial vital signs and Glasgow Coma Scale score, higher ISS score, and comorbidity of diabetes mellitus affect the mortality rate of patients with unstable pelvic ring fractures. No single system of injury was found to increase mortality in these patients. The mortality rate was reduced through institutional efforts toward the application of guidelines for the initial management of pelvic fracture.

The study aimed to evaluate the impact of osteoporosis (OP) medication persistence on subsequent fractures and all-cause mortality in patients with hip fracture.In this retrospective cohort study, we included patients aged ≥ 40 years with fragility hip fracture from the Taiwan's National Health Insurance Research Database. OP medication persistence was categorized as yes (≥ 12 months) or no (12 months). A multivariate Cox proportional hazard model was used to evaluate the association between OP medication persistence and recurrent fractures (including hip, vertebral, and upper and lower limb fractures) and all-cause mortality.A total of 946 patients were included in the study (86.5 % of them aged ≥ 65 years) and 210 patients persistently received OP medications. Persistent OP medication use was associated with lower fracture risk (adjusted hazard ratio [aHR] = 0.64; 95 % CI = 0.41-0.99; P = .043) in the follow-up period. The strongest predictors for all-cause mortality were age ≥ 80 years (HR = 5.68, 95 % CI = 1.36-23.64, P = .017), male sex (HR = 1.55; 95 % CI = 1.18-2.03; P = .002), and Charlson Comorbidity Index ≥ 3 (aHR = 1.56; 95 % CI = 1.07-2.27; P = .022). Kaplan-Meier curves showed a lower cumulative incidence of recurrent fractures in the persistent group than that in the non-persistent group (P = .028).Persistent OP medication use was associated with a lower risk of recurrent fractures but not with mortality in patients with hip fracture.

We evaluated the trend of end-of-life healthcare utilization and life-sustaining interventions for older adults with dementia 3 to 4 years after the change in hospice policy.Population-based retrospective cohort study.We used the National Health Insurance Research database of enrolled patients ≥65 years of age diagnosed with dementia who died in 2010-2013 (n = 2062).Aggressive treatments, including healthcare utilization and life-sustaining interventions, were recorded within 6 months of death. Aggressive healthcare utilization included ≥1 emergency department visits, ≥1 hospitalizations,14 days of hospitalization, intensive care unit admission, and death in an acute care hospital. Life-sustaining interventions were enteral tube, artificial nutrition, blood transfusion, hemodialysis, invasive ventilation, and cardiopulmonary resuscitation.Compared with 2010‒2012, 2013 rates significantly decreased for all measures (P .001). Composite scores of healthcare utilization and life-sustaining treatments in 2013 were significantly lower than for 2010‒2012, after controlling for confounding variables (both P .001).Older patients with dementia had a trend of reduced healthcare utilization and fewer life-sustaining treatments near the end of life from 2010 to 2013 after a policy change.

No studies have yet examined the interrelationship of malnutrition and low handgrip strength in terms of mortality. The aim of the present study was to evaluate the potential synergistic effects of malnutrition and low handgrip strength on mortality among older adults living in a retirement community.This prospective longitudinal cohort study recruited subjects aged 65 years and over from a veterans care home in Taiwan in 2013. Nutritional status was assessed using the Mini-Nutritional Assessment-Short Form (MNA-SF, malnutrition was MNA-SF12); muscle strength was measured by handgrip strength (low handgrip strength was handgrip strength26 kg). The Kaplan-Meier method with the log-rank test was used to estimate survival differences between groups and Cox proportional regression model was used to estimate the adjusted difference in 4-year all-cause mortality between groups.Recruited for the present study were 333 male participants (mean age 85.4 ± 5.7 years). Of these, 50.2% had malnutrition and 54.7% had low handgrip strength. Compared with subjects with no malnutrition and low handgrip strength, those with malnutrition had significantly greater risk of 4-year all-cause mortality (adjusted hazards ratio: 2.05, 95% confident interval [CI]: 1.04-4.01); hazard ratio increased to 3.41 (95% CI 1.93-6.04) for those with both malnutrition and low handgrip strength.Malnutrition was an independent risk factor for 4-year all-cause mortality and low handgrip strength with malnutrition synergistically increased the mortality risk. Further study is needed to confirm the effectiveness of integrated programs to assist those at risk.

Changes in the carbohydrate structure on the surface of tumor cells is an important feature of cancer metastasis. The specific role of sialic acids in the glycoconjugate terminal has not yet been clearly elucidated in these processes. Previously, we reported that α2,3-sialic acid residues in breast cancer are associated with metastatic potential. The α2,3-sialyltransferase ST3Gal III, which adds α2,3-sialic acids to glycoproteins, is overexpressed in various tumors, and enzyme activity is correlated with tumor metastasis, yet its mechanistic role has not been fully evaluated. In the present study, we aimed to investigate the influence of ST3Gal III on key steps in the process of breast cancer metastasis. ST3Gal III-overexpressing and ST3Gal III-silenced breast cancer MDA-MB-231 cell lines were generated. They showed an increase or decrease in the tumor-associated antigen sialyl-Lewis X (SLeX). The E-selectin binding capacity of the transfectants was proportional to cell surface SLeX levels. Cell migration and invasion were positively correlated with ST3Gal III levels. Moreover, ST3Gal III expression modulated the protein expression of invasion-related molecules, including β1 integrin, matrix metalloproteinase (MMP)-2, MMP-9 and cyclooxygenase-2, which may account for the mechanism involved in the effects of ST3Gal III on breast cancer invasiveness. In conclusion, our findings in these novel models of ST3Gal III expression revealed a critical requirement for ST3Gal III in several steps of breast cancer metastasis. ST3Gal III modulates breast cancer cell adhesion and invasion by altering the expression of invasion-related molecules. This study provides novel insights into the mechanisms underlying metastasis and suggests a new target for the effective drug treatment of breast cancer metastasis.

Dengue fever is caused by four different serotypes of dengue virus (DENV) which is the leading cause of worldwide arboviral diseases in humans. Virus-like particles (VLPs) containing flavivirus prM/E proteins have been demonstrated to be a potential vaccine candidate; however, the structure of dengue VLP is poorly understood. Herein VLP derived from DENV serotype-2 were engineered becoming highly matured (mD2VLP) and showed variable size distribution with diameter of ~31 nm forming the major population under cryo-electron microscopy examination. Furthermore, mD2VLP particles of 31 nm diameter possess a T = 1 icosahedral symmetry with a groove located within the E-protein dimers near the 2-fold vertices that exposed highly overlapping, cryptic neutralizing epitopes. Mice vaccinated with mD2VLP generated higher cross-reactive (CR) neutralization antibodies (NtAbs) and were fully protected against all 4 serotypes of DENV. Our results highlight the potential of ‘epitope-resurfaced’ mature-form D2VLPs in inducing quaternary structure-recognizing broad CR NtAbs to guide future dengue vaccine design.

Dengue fever is caused by four different serotypes of dengue virus (DENV) which is the leading cause of worldwide arboviral diseases in humans. Virus-like particles (VLPs) containing flavivirus prM/E proteins have been demonstrated to be a potential vaccine candidate; however, the structure of dengue VLP is poorly understood. Herein we show for the first time that mD2VLP particles possess a T=1 icosahedral symmetry with a groove located within the E-protein dimers near the 2-fold vertices that exposed highly overlapping, cryptic neutralizing epitopes through cryo-electron microscopy reconstruction. Mice vaccinated with highly matured virus-like particles derived from DENV serotype 2 (mD2VLP) can generate higher cross reactive (CR) neutralization antibodies (NtAbs) and were protected against all 4 serotypes of DENV through clonal expansion supported by hybridoma and B-cell repertoire analysis. Our results revealed that a “epitope-resurfaced” mature-form dengue VLP has the potential to induce quaternary structure-recognizing broad CR NtAbs.

Objectives To evaluate the roles of preoperative anemia and intraoperative blood transfusion in the development of postoperative delirium among older patients undergoing elective orthopedic surgery. Methods This prospective cohort study recruited subjects aged 60 years old and above who were admitted for elective orthopedic surgery in a tertiary medical center during April 2011 to December 2013. Demographic data (age, gender, body mass index [BMI], and educational level), surgery-related factors (American Society of Anesthesiology [ASA] class, type of anesthesia and surgery, and intraoperative blood transfusion), results of geriatric assessment (hearing/visual impairment, cognition, depressive mood, comorbidity, malnutrition, polypharmacy, activities of daily living [ADL], and instrumental activities of daily living [IADL]), laboratory data, length of hospital stay, and the development of postoperative delirium were collected for analysis. Results Overall, 461 patients (mean age: 73.5 ± 7.5 years, 42.1% males) were enrolled for study, and 37 (8.0%) of them developed postoperative delirium. We categorized all subjects into four groups based on anemia on admission and blood transfusion during operation or not. Multivariate logistic regression showed that subjects with anemia on admission and received intraoperative blood transfusion were at higher risk of developing postoperative delirium (adjusted odds ratio 3.090; 95% confidence interval [CI], 1.070-8.926) and those without anemia on admission but received intraoperative blood transfusion were at marginal risk (adjusted odds ratio 2.906; 95% CI, 0.912-9.259) after adjustment for covariates. Conclusions Anemic older patients receiving intraoperative blood transfusion during operation were at the greatest risk for postoperative delirium when they underwent elective orthopedic surgery. Further intervention study is needed to reduce the risk of postoperative delirium for these patients.

Dengue fever is caused by four different serotypes of dengue virus (DENV) which is the leading cause of worldwide arboviral diseases in humans. The vaccine candidates under development require a tetravalent immunogen to induce a balanced immunity against all four serotypes of dengue virus. Herein we show that mice vaccinated with highly matured virus-like particles derived from DENV serotype 2 (mD2VLP) can generate higher and broader neutralization antibodies (NtAbs) against all 4 serotypes of DENV through clonal expansion supported by hybridoma and B-cell repertoire analysis. The cryo-electron microscopy reconstruction showed that mD2VLP particles possess a T=1 icosahedral symmetry with a groove located within the E-protein dimers near the 2-fold vertices that exposed highly overlapping, cryptic neutralizing epitopes. Most importantly, maternally transferred antibodies derived from mD2VLP-vaccinated female mice protected suckling mice from lethal challenge by all four serotypes of DENV. Our results support the fact that a universal dengue vaccine that protects against all four serotypes of dengue viruses can be achieved by using an immunogen such as mD2VLP.

Background This study evaluated risks of emergency room visit (ERV) for out-of-hospital cardiac arrest (OHCA) in 2005–2011, among patients with cardiologic and metabolic syndromes (CMS), in association with ambient environments. Methods Pooled and area-specific weather related cumulative six-day (lags 0 to 5) relative risks (RRs) and confidence intervals (CIs) of ERV for OHCA were evaluated for CMS cases, using distributed lag nonlinear models and multivariate meta-analytical second-stage model in association with the daily average temperatures and daily concentrations of air pollutants. Results ERV risk increased as average temperature dropped to

This study evaluated risks of emergency room visits (ERV) for all causes, circulatory diseases, and respiratory diseases associated with concentrations of particulate matter (PM10 and PM2.5) and Asian dust storms (ADS) from 2000 to 2008 in metropolitan Taipei. Cumulative 4-day (lag 0-3) relative risks (RR) and confidence intervals (CI) of cause-specific ERV associated with daily concentrations of PM10 or PM2.5 and ADS based on study period (ADS frequently inflicted period: 2000-2004 and less-inflicted period: 2005-2008) were estimated using a distributed lag non-linear model with Poisson distribution. Risks associated with ADS-inflicted season (winter and spring), strength (ratio of stations with Pollutant Standard Index above 100 is < 0.5 or ≥ 0.5), and duration (ADS lasting for 1-3 days or ≥ 4 days) were especially evaluated. In non-linear models, an increase in PM10 from 10 μg/m(3) to 50 μg/m(3) was associated with increased risk of ERV for all causes and respiratory disease with cumulative 4- day RR of 1.18 (95% CI: 1.13, 1.24) and 1.37 (95% CI: 1.23, 1.54), respectively. From 2005 to 2008, the cumulative 4-day RR for an ERV related to an increase in PM2.5 from 5 μg/m(3) to 30 μg/m(3) is 1.21 (95% CI: 1.03, 1.41) for respiratory diseases, and 1.15 (95% CI: 1.08, 1.22) for all causes. In comparison with normal days, elevated ERV of all causes and respiratory diseases was also associated with winter ADS (with corresponding RRs of 1.10 (95% CI: 1.07, 1.13) and 1.14 (95% CI: 1.08, 1.21)) and shorter and less area-affected ADS (with corresponding RRs of 1.07 (95% CI: 1.01, 1.10) and 1.09 (95% CI: 1.03, 1.14)) from 2000 to 2004. Results of this study demonstrate that population health risk varies not only with PM concentration, but also with the ADS characteristics.

Synaptic dysfunction is an early pathological feature of neurodegenerative diseases associated with Tau, including Alzheimer's disease. Interfering with early synaptic dysfunction may be therapeutically beneficial to prevent cognitive decline and disease progression, but the mechanisms underlying synaptic defects associated with Tau are unclear. In disease conditions, Tau mislocalizes into pre- and postsynaptic compartments; here we show that, under pathological conditions, Tau binds to presynaptic vesicles in Alzheimer's disease patient brain. We define that the binding of Tau to synaptic vesicles is mediated by the transmembrane vesicle protein Synaptogyrin-3. In fly and mouse models of Tauopathy, reduction of Synaptogyrin-3 prevents the association of presynaptic Tau with vesicles, alleviates Tau-induced defects in vesicle mobility, and restores neurotransmitter release. This work therefore identifies Synaptogyrin-3 as the binding partner of Tau on synaptic vesicles, revealing a new presynapse-specific Tau interactor, which may contribute to early synaptic dysfunction in neurodegenerative diseases associated with Tau.

Cholangiocarcinoma (CCA) is a cancer of the bile duct with high mortality rate and poor prognosis, owing to the difficulty in the early diagnosis and prognosis. The specific biomarkers or affinity reagents toward CCA cells could be great tools to assist in detection of CCA. However, screening of biomarkers/affinity reagents are generally labor-intensive, time-consuming and requiring large volume of samples and reagents. Therefore, we developed an integrated microfluidic system which could automatically perform selections of biomarkers and affinity reagents using phage display techniques. The experimental results showed that the selection of phage-displayed peptides bound to CCA cells was successfully demonstrated on the integrated microfluidic system using fewer reagents, samples and less time (5.25 h per biopanning round, and continuously performed for only 4 panning rounds). Three oligopeptides were screened, and their specificity and affinity toward CCA cells were characterized. Furthermore, comparing to conventional EpiEnrich beads for cancer cell capture, the screened CCA-specific peptides showed relatively low capture rate over control normal cells. It is envisioned that this microfluidic system may be a powerful tool for screening of biomarkers/affinity reagents in clinical diagnosis and target therapy for CCA.

Cholangiocarcinoma (CCA), a biliary tract malignancy, accounts for 20% of all liver cancers. There are several existing methods for diagnosis of CCA, though they are generally expensive, laborious, and suffer from low detection rates. Herein we first developed a means of partially purifying human bile for consequent injection into a microfluidic chip. Then, the novel microfluidic system, which featured 1) a cell capture module, 2) an immunofluorescence (IF) staining module featuring two CCA-specific biomarkers, and 3) an optical detection module for visualization of antibody probes bound to these CCA marker proteins, was used to detect bile duct cancer cells within partially purified bile samples. As a proof of concept, CCA cells were successfully captured and identified from CCA cell cultures, blood samples inoculated with CCA cells, and clinical bile specimens. In 7.5 ml of bile, this system could detect >2, 0, and 1 positive cells in advanced stage patients, healthy patients, and chemotherapy-treated patients, respectively. In conclusion, our microfluidic system could be a promising tool for detection of cancer cells in bile, even at the earliest stages of CCA when cancer cells are at low densities relative to the total population of epithelial cells.

Introduction Enteral nutrition (EN) is important in the management of critically illness. Yet, the best route (e.g. pre-pyloric or post-pyloric) for EN in critically ill patients remains to be investigated, especially in specific surgical patients group. In addition, EN could be associated with a higher risk of aspiration pneumonia. Therefore, we evaluate the effect of various EN routes in surgical critically ill perforated peptic ulcer (PPU) patients who underwent surgery and required mechanical ventilation. Method We collected data of surgical critically ill PPU patients admitted to intensive care unit. The patients were managed with appropriate care bundle and program. To reduce the impact of surgery types, we excluded those who had received other surgical procedures and included patients that only received simple closure. Patients were classified into nasogastric and jejunostomy feeding groups. The demographics, severity scores (e.g.: APACHE II, SOFA, and POSSUM), body mass index (BMI), comorbidities, ventilator days, use of proton pump inhibitors (PPIs), pneumonia occurrence, mortality and complications were collected for analysis. Results A total of 136 critically ill PPU patients that received surgery and mechanical ventilation were enrolled. There were 53 patients in NG group and 83 patients in FJ group. There were no differences in demographics, severity scores, BMI, comorbidities, ventilator days, use of PPIs, pneumonia occurrence, mortalities and complications between groups. Conclusion Our study indicates that there are no differences in mortalities and pneumonia occurrence using nasogastric or feeding jejunostomy in surgical critically ill PPU patients underwent surgery. However, further studies are required.

Alcohol-related motor vehicle collisions are a major cause of mortality in trauma patients. This prospective observational study investigated the influence of antecedent alcohol use on outcomes in trauma patients who survived to reach the hospital. From 2005 to 2011, all patients who were older than 18 years and were admitted as a result of motor vehicle crashes were included. Blood alcohol concentration (BAC) was routinely measured for each patient on admission. Patients were divided into four groups based on their BAC level, which included nondrinking, BAC less than 100, BAC 100 to 200, and BAC 200 mg/dL or greater. Patient demographics, physical status and injury severity on admission, length of hospital stay, and outcome were compared between the groups. Odds ratios of having a severe injury, prolonged hospital stay, and mortality were estimated. Patients with a positive BAC had an increased risk of sustaining craniofacial and thoracoabdominal injuries. Odds ratios of having severe injuries (Injury Severity Score [ISS] 16 or greater) and a prolonged hospital stay were also increased. However, for those patients whose ISS was 16 or greater and who also had a brain injury, risk of fatality was significantly reduced if they were intoxicated (BAC 200 mg/dL or greater) before injury. Alcohol consumption does not protect patients from sustaining severe injuries nor does it shorten the length of hospital stay. However, there were potential survival benefits related to alcohol consumption for patients with brain injuries but not for those without brain injuries. Additional research is required to investigate the mechanism of this association further.

This study aimed to identify optimal cold-temperature indices that are associated with the elevated risks of mortality from, and outpatient visits for all causes and cardiopulmonary diseases during the cold seasons (November to April) from 2000 to 2008 in Northern, Central and Southern Taiwan. Eight cold-temperature indices, average, maximum, and minimum temperatures, and the temperature humidity index, wind chill index, apparent temperature, effective temperature (ET), and net effective temperature and their standardized Z scores were applied to distributed lag non-linear models. Index-specific cumulative 26-day (lag 0–25) mortality risk, cumulative 8-day (lag 0–7) outpatient visit risk, and their 95% confidence intervals were estimated at 1 and 2 standardized deviations below the median temperature, comparing with the Z score of the lowest risks for mortality and outpatient visits. The average temperature was adequate to evaluate the mortality risk from all causes and circulatory diseases. Excess all-cause mortality increased for 17–24% when average temperature was at Z = − 1, and for 27–41% at Z = − 2 among study areas. The cold-temperature indices were inconsistent in estimating risk of outpatient visits. Average temperature and THI were appropriate indices for measuring risk for all-cause outpatient visits. Relative risk of all-cause outpatient visits increased slightly by 2–7% when average temperature was at Z = − 1, but no significant risk at Z = − 2. Minimum temperature estimated the strongest risk associated with outpatient visits of respiratory diseases. In conclusion, the relationships between cold temperatures and health varied among study areas, types of health event, and the cold-temperature indices applied. Mortality from all causes and circulatory diseases and outpatient visits of respiratory diseases has a strong association with cold temperatures in the subtropical island, Taiwan., Highlights • Cold temperature elevated mortality from all causes and circulatory diseases. • Cold temperatures caused greater impact on outpatient visits of respiratory diseases. • Average temperature was the optimal cold index in association with mortality. • Minimum temperature was most associated with outpatient visits of respiratory disease.

This study reported cumulative 6-day (lag 0–5 days) relative risks (RR) and confidence intervals (CI) of daily outpatient visits for total respiratory disease (RD), asthma, and chronic airway obstruction not otherwise classified (CAO) associated with three ozone metrics (daily 1-h maximum (O3, 1 h max), 8-h average maximum (O3, 8 h max), 24-h average (O3, 24 h avg)), and an alternative oxidant indicator (Ox) in Taipei Metropolitan, using distributed lag non-linear models after controlling for potential confounders. The Ox showed the strongest association with outpatient visits for total RD (RR = 1.10, 95% CI: 1.10, 1.11) and asthma (RR = 1.18, 95% CI: 1.00, 1.39) in the cold season. The O3, 24 h avg appeared to be the optimal ozone metric associating with total RD than O3, 1 h max and O3, 8 h max based on model selection. In conclusion, outpatient visits for total RD associated with ozone vary with ozone metrics, disease and season., Highlights ► The health risk of ozone varied by RD type and by the ozone metrics applied. ► O3, 24 h avg was a better metric to associate with outpatient visits of total RD. ► Ox most correlated with outpatient visits for total RD in the cold season., The O3, 24 h avg was a better metric than O3, 1 h max and O3, 8 h max to associate with outpatient visits of total respiratory diseases.

Proteome integrity is maintained by a coordinated network of molecular chaperones, by protein degradation machineries and by their regulators. Numerous human pathologies are considered as diseases of compromised protein homeostasis (proteostasis), including neurodegeneration. These are characterized by the accumulation of neuronal protein aggregates and by synaptic defects followed by loss of connectivity and cell death. While this suggests that synaptic terminals are particularly sensitive to proteostasis imbalance, our understanding of protein turnover mechanisms and regulation at the synapse remains limited. Recent reports show that different proteolytic pathways act at synapses, including several forms of autophagy. The role of chaperones in controlling the balance between synaptic protein refolding and degradation and how this complex network regulates neuronal function also begins to be unraveled.

Objective: To investigate lung function associated with asthma and body mass index (BMI) among adolescents at 96 northern Taiwan junior high schools participating in an asthma screening program. Methods: The questionnaires and lung function test results measured for 3669 boys and 3523 girls were included in this study for data analysis. Measures of forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and FEV1/FVC ratio were compared by sex, asthma status and BMI. Results: Overall mean FVC levels were similar between students with and without asthma, 3.71 L vs. 3.71 L for boys (p = 0.991) and 2.79 vs. 2.78 for girls (p = 0.517). The overall mean FEV1 levels were also similar between girls with and without asthma. Asthmatic boys had lower FEV1 than non-asthmatic boys. Mean FEV1/FVC was significantly lower in students with asthma than those without asthma. Mean FVC and FEV1 increased with BMI in both sexes. A lower mean FEV1/FVC was observed among students with asthma and high BMI, and was more pronounced in boys than in girls. Multivariable regression analysis also showed that FEV1/FVC ratios were negatively associated with asthma and high BMI, stronger in boys than in girls for asthma (β = −2.176 (standard errors (SE) = 0.268) vs. −1.085 (SE = 0.258) and for BMI (β = −0.309 (SE = 0.025) vs. −0.218 (SE = 0.029)). Conclusion: This northern Taiwan study suggests that FEV1/FVC is negatively associated with asthma and high BMI in adolescents, stronger for boys than for girls.

BACKGROUND Ablation of complex fractionated atrial electrograms (CFAE) is an important adjunctive therapy in atrial fibrillation (AF). The present study was to elucidate the substrate underlying CFAE. METHODS Nine adult mongrel dogs were involved in the present study. AF was induced through rapid atrial pacing with vagosympathetic nerve stimulation. CFAE was recorded during AF. Ablation was performed at CFAE sites. Based on the location of the ablation scar, the atrial specimens were divided into CFAE and non-CFAE sites. Serial sections of the atrium were stained respectively with hematoxylin-eosin (HE) and the general neural marker protein gene product 9.5 (PGP9.5). We compared the characteristics of the myocardium and the ganglionated plexus (GPs) distribution between the CFAE and non-CFAE sites. RESULTS The myocardium of non-CFAE sites was well-organized with little intercellular substance. However, the myocardium in the CFAE site was disorganized with more interstitial tissue ((61.7 ± 24.3)% vs. (34.1 ± 9.2)%, P < 0.01). GPs in the CFAE site were more abundant than in non-CFAE sites ((34.45 ± 37.46) bundles/cm(2) vs. (6.73 ± 8.22) bundles/cm(2), P < 0.01). CONCLUSION The heterogeneity of the myocardium and GPs distribution may account for the substrate of CFAE and serve as a potential target of ablation.

Laparoscopic surgery is frequently applied in the operative management of appendicitis and symptomatic cholelithiasis because it is a minimally invasive procedure. There are, however, some complications of laparoscopic cholecystectomy (LC) and laparoscopic appendectomy (LA) that result in the need for reoperation. In the current study, we examine the effects of repeat laparoscopic surgery on the treatment of complications arising from LC/LA. From April 2005 to March 2011, we examined a cohort of patients who had received LC or LA and experienced complications that required reoperations. We focused on patients with postoperative hemorrhages, postoperative peritonitis, early postoperative small bowel obstructions (EPSBO), and biliary complications (after LC) who were treated through a repeat laparoscopic approach. The general demographics of the patients, their postoperative complications, procedures for selecting the appropriate reoperation method, and repeat laparoscopic findings are described in detail. During the 6-year period examined, 1608 patients received LC and 1486 patients received LA at the hospitals participating in this study. In patients with complications requiring reoperation, the repeat laparoscopic approach was performed successfully (without the need for further laparotomy) in 50 per cent of the patients with postoperative hemorrhage (2 of 4), 50 per cent of the patients with postoperative peritonitis (2 of 4), 75 per cent of the EPSBO patients (3 of 5), and 50 per cent the of patients with biliary complications (1 of 2). The repeat laparoscopic approach is an appropriate method for the management of complications arising from laparoscopic surgery. In patients with postoperative hemorrhage, laparoscopic hemostasis and hematoma evacuations can be performed while maintaining stable hemodynamics. In addition, laparoscopic approaches are also feasible for selective post-LC ductal injuries, EPSBO, and unconfirmed diagnoses of peritonitis after laparoscopic surgery.

Gallbladder perforation is a rare but serious complication of cholecystitis. It was usually managed by percutaneous gallbladder drainage (PTGBD) followed by elective cholecystectomy. However, evidences are emerging that early laparoscopic cholecystectomy (LC) is still feasible under these conditions. We hypothesized that early LC may have comparable surgical results as to those of PTGBD + elective LC. From January 2005 to October 2011, patients admitted to China Medical University Hospital with a diagnosis of perforated cholecystitis were retrospectively reviewed. The diagnosis of gallbladder perforation was made by image and/or intraoperative findings. Those patients who had unstable hemodynamics that were not fitted for general anesthesia or those who had concomitant major operations were excluded. Patients were divided into three groups: early open cholecystectomy (group 1), early LC (group 2), and PTGBD followed by elective LC (group 3). The demographic features, surgical results, and patient outcome were analyzed and compared between groups. A total of 74 patients were included. All patients had similar demographic features except that patients in group 2 were younger (62 vs. 72 and 73.5 years) compared with group 1 and group 3 (p = 0.016). There were no differences in terms of operative time, blood loss, conversion, and complication rate between three groups. The length of hospital stay (LOS) was significant shorter in group 2 patients compared with that of groups 1 and 3. Although PTGBD followed by elective LC was still the mainstay for the treatment of gallbladder perforation, early LC had comparable surgical outcomes as that of PTGBD + LC but with a significantly shorter LOS. Early LC should be considered the optimal treatment for gallbladder perforation, and PTGBD + LC can be preserved for those who carried a high risk of operation.

Background With recent advances in radiologic diagnostic procedures, the use of diagnostic peritoneal lavage (DPL) has markedly declined. In this study, we reviewed data to reevaluate the role of DPL in the diagnosis of hollow organ perforation in patients with blunt abdominal trauma. Methods Adult patients who had sustained blunt abdominal trauma and who were hemodynamically stable after initial resuscitation underwent an abdominal computed tomographic (CT) scan. Diagnostic peritoneal lavage was performed for patients who were indicated to receive nonoperative management and where hollow organ perforation could not be ruled out. Results During a 60-month period, 64 patients who had received abdominal CT scanning underwent DPL. Nineteen patients were diagnosed as having a positive DPL based on cell count ratio of 1 or higher. There were 4 patients who sustained small bowel perforation. The sensitivity and specificity of the cell count ratio for a hollow organ perforation in this study were 100% and 75%, respectively. No missed hollow organ perforations were detected. Conclusion For patients with blunt abdominal trauma and hemoperitoneum who plan to receive nonoperative management, DPL is still a useful tool to exclude hollow organ perforation that is undetected by CT.

Traumatic brain injury (TBI) is a common diagnosis in the emergency department. Brain computed tomography (CT) has become a standard diagnostic tool with which to examine TBI patients. Conventional X-rays are ineffective for the evaluation of torso or extremity injuries. In the current study, we attempted to establish a diagnostic modality to evaluate systemically initially unconscious patients in the emergency department with a rapid screening technique characterized by sufficient information, low cost and low radiation exposure. From January 2008 to December 2009, patients with diminished level of consciousness received the Lodox/Statscan for evaluation of extracranial injuries were enrolled in this study. The accuracy of this diagnostic modality in detecting torso or extremity injuries in initially unconscious patients was analyzed by comparing the initial diagnosis (by the Lodox/Statscan) with the final diagnosis (confirmed by torso CT scan or after two weeks of follow-up). There were 1,210 patients with TBI whose extracranial injuries were evaluated by the Lodox/Statscan. After excluding intra-abdominal injuries, the overall sensitivity rates of the Lodox/Statscan in diagnosing torso injuries and extremity injuries were 89.7% and 90.2%, respectively. No long bone fracture was missed by the Lodox/Statscan. The sensitivity and specificity of the Lodox/Statscan in diagnosing long bone fractures were both 100%. Most patients with torso injuries that were missed by the Lodox/Statscan could be managed conservatively without further treatment or complications. All of the missed extremity injuries were distal bone fractures. The Lodox/Statscan can provide benefits for surveying extracranial injuries in patients with diminished level of consciousness. The Lodox/Statscan also emits a notably low dose of radiation and appears to be a relatively inexpensive adjunct to screen torso or extremity injuries in TBI patients.

There is controversy about the appropriate timing for renal replacement therapy in patients with acute kidney injury (AKI). We are interested in the appropriate timing for initiation of continuous renal replacement therapy in critically ill surgical patients with postoperative acute kidney injury. Seventy-three critically ill surgical patients with postoperative AKI who received continuous renal replacement therapy (CRRT) were enrolled. Indications for CRRT were: 1) AKI with hyperkalemia, 2) metabolic acidosis, 3) pulmonary edema refractory to diuretics, and 4) oliguria with progressive azotemia, especially in unstable hemodynamics. Using RIFLE (Risk, Injury, Failure, Loss, End stage) classification, patients who received CRRT in the “Risk” stage were defined as early group, whereas those in the “Injury/ Failure” stage were labeled as late group. We used continuous veno-venous hemofiltration as CRRT in this series. There were 20 patients in the early group and 53 patients in the late group. The mean ages were 61.5 ± 21.8 years versus 60.8 ± 17.5 years. The mortality rate was 50 per cent versus 84.9 per cent. There were no significant differences in demographic characteristics or type of surgery or physiological scores. Our data show that late initiation of CRRT is associated with a lower survival rate in critically ill surgical patients with postoperative AKI; however, further studies are required.

OBJECTIVE To investigate the association between rehabilitation timing and the occurrence of post-total knee arthroplasty complications and related medical service utilization. METHODS Data from Taiwan's National Health Insurance Research Database from 2003-2006 were used to perform a retrospective study on patients who received their initial total knee arthroplasty during 2004-2005 (a total of 21,143 subjects). All subjects were divided into 1 of 3 groups based on the timing of their rehabilitation after total knee arthroplasty, namely, the within 2 weeks group, the after 2 weeks group or the no-rehabilitation group. RESULTS We found that patients in the no-rehabilitation group and the after 2 weeks group had higher incidences of prosthetic infection (odds ratio (OR) =1.29, p=0.0409; OR=1.66, p=0.0012) and deep venous thrombosis (OR=1.51, p=0.0099; OR=2.07; p=0.0007) than in the within-2-weeks group. In addition, compared with the within-2-weeks group, the after 2 weeks group had higher total medical expenses (exponentiated regression coefficient: Exp. (β) =1.07, p=0.0211), and the no-rehabilitation group had lower total medical expenses (Exp. (β) =0.01, p

Previous studies have indicated that mode of delivery and/or season of delivery might be risk factors for postpartum depression (PD). However, only a few studies have provided support for this supposition. This study aim was to confirm the association between mode of delivery and/or season of delivery and PD.We analyzed 2003-2006 Taiwan National Health Insurance Research Database (NHIRD). A group of 2107 mothers who were diagnosed with PD within 6months of delivery in 2005 were selected as the case group and another 8428 mothers without PD during the same timeframe were selected as the control group. Logistic regression was performed after controlling for age, antepartum comorbidities and postpartum complications to confirm the degree of association with the risk of PD.The results of the logistic regression analysis showed that the risk of acquiring PD was lower in mothers with a normal vaginal delivery or an instrumental vaginal delivery compared to mothers with an emergency caesarean section (odds ratio [OR]=0.67, p0.0001; OR=0.56, p0.0001). But the women who elected to have a caesarean section was higher risk than an emergency caesarean section (OR=1.48, p=0.0168). In addition, the risk of PD for winter deliveries was higher compared to other seasons.This study provides a reference for gynecologists, obstetricians and health providers that should help with the prevention of PD among pregnant women and mothers.

Spinal cerebellar ataxia type 12 (SCA12) has been attributed to the elevated expression of ppp2r2b. To better elucidate the pathomechanism of the neuronal disorder and to search for a pharmacological treatment, Drosophila models of SCA12 were generated by overexpression of a human ppp2r2b and its Drosophila homolog tws. Ectopic expression of ppp2r2b or tws caused various pathological features, including neurodegeneration, apoptosis, and shortened life span. More detailed analysis revealed that elevated ppp2r2b and tws induced fission of mitochondria accompanied by increases in cytosolic reactive oxygen species (ROS), cytochrome c, and caspase 3 activity. Transmission electron microscopy revealed that fragmented mitochondria with disrupted cristae were engulfed by autophagosomes in photoreceptor neurons of flies overexpressing tws. Additionally, transgenic flies were more susceptible to oxidative injury induced by paraquat. By contrast, ectopic Drosophila Sod2 expression and antioxidant treatment reduced ROS and caspase 3 activity and extended the life span of the SCA12 fly model. In summary, our study demonstrates that oxidative stress induced by mitochondrial dysfunction plays a causal role in SCA12, and reduction of ROS is a potential therapeutic intervention for this neuropathy.

Background: Nonoperative management (NOM) of blunt splenic injuries has been widely accepted, and the application of splenic artery embolization (SAE) has become an effective adjunct to NOM. However, complications do occur after SAE. In this study, we assess the factors leading to the major complications associated with SAE. Materials and Methods: Focusing on the major complications after SAE, we retrospectively studied patients who received SAE and were admitted to 2 major referral trauma centers under the same established algorithm for management of blunt splenic injuries. The demographics, angiographic findings, and factors for major complications after SAE were examined. Major complications were considered to be direct adverse effects arising from SAE that were potentially fatal or were capable of causing disability. Results: There were a total of 261 patients with blunt splenic injuries in this study. Of the 261 patients, 53 underwent SAE, 11 (21%) of whom were noted to have 12 major complications: 8 cases of postprocedural bleeding, 2 cases of total infarction, 1 case of splenic abscess, and 1 case of splenic atrophy. Patients older than 65 years were more susceptible to major complications after SAE. Conclusion: Splenic artery embolization is considered an effective adjunct to NOM in patients with blunt splenic injuries. However, risks of major complications do exist, and being elderly is, in part, associated with a higher major complication incidence.

Diarrhea is an important public health problem in Taiwan. Climatic changes and an increase in extreme weather events (extreme heat, drought or rainfalls) have been strongly linked to the incidence of diarrhea-associated disease. This study investigated and quantified the relationship between climate variations and diarrhea-associated morbidity in subtropical Taiwan. Specifically, this study analyzed the local climatic variables and the number of diarrhea-associated infection cases from 1996 to 2007. This study applied a climate variation-guided Poisson regression model to predict the dynamics of diarrhea-associated morbidity. The proposed model allows for climate factors (relative humidity, maximum temperature and the numbers of extreme rainfall), autoregression, long-term trends and seasonality, and a lag-time effect. Results indicated that the maximum temperature and extreme rainfall days were strongly related to diarrhea-associated morbidity. The impact of maximum temperature on diarrhea-associated morbidity appeared primarily among children (0-14years) and older adults (40-64years), and had less of an effect on adults (15-39years). Otherwise, relative humidity and extreme rainfall days significantly contributed to the diarrhea-associated morbidity in adult. This suggested that children and older adults were the most susceptible to diarrhea-associated morbidity caused by climatic variation. Because climatic variation contributed to diarrhea morbidity in Taiwan, it is necessary to develop an early warning system based on the climatic variation information for disease control management.

Angioembolization is an effective adjunct to the management of blunt splenic injuries (BSI) that are not surgically treated. However, in some cases patients are unable to undergo angioembolization due to changes in their hemodynamic condition. In this study we attempt to define the characteristics of patients who need angioembolization in high-grade BSI. We retrospectively reviewed the charts of patients with BSI between January 2004 and June 2008. Patients with contrast extravasation (CE) on computed tomography (CT) scan were enrolled. The demographics, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS), the amount of blood transfused, and the type of CE were analyzed. A total of 69 patients were enrolled. Patients with intraperitoneal CE in BSI required a higher rate of immediate operation due to changed hemodynamics. Furthermore, these patients displayed higher ISS and higher blood transfusion amounts. In BSI patients, intraperitoneal CE is associated with a higher possibility of requiring surgical intervention. Early surgical intervention should be considered in BSI patients with intraperitoneal CE or with ISS ≥ 25.

It is futile to attempt resuscitation in a blunt injury patient with no vital signs upon arriving at the emergency department. Therefore, it is recommended that resuscitation be withheld in any blunt trauma patient without vital signs while emergency medical technicians arrive at the scene of the accident. This report presents a case of a blunt torso trauma patient who lost vital signs at the scene and still received cardiopulmonary resuscitation until recovery of spontaneous circulation at the emergency department. The patient was later diagnosed with commotio cordis, and survived to be discharged without any neurological sequelae. Therefore, aggressive resuscitation should be continued until a diagnosis and differential diagnosis of blunt trauma-related cardiac arrest are made by a thorough examination in the emergency department.

The significance of very early experience in the maturation of whisker-to-barrel system comes primarily from neonatal whisker or infraorbital nerve lesion studies conducted prior to the formation of cortical barrels. However, the surgical procedures damage the sensory pathway; it is difficult to examine the consequence after the recovery of sensory deprivation. To address this issue, we performed a neonatal whisker-cut (WC) paradigm and examined their behavioral performance during P30 to P35. With fully regrown whiskers, the rats that had whisker cut from the date of birth (P0) to postnatal day (P) 3 (WC 0–3) exhibited shorter crossable distance in the gap-crossing test. However, the rats had whisker cut at P3 only (WC 3) behaved normally in this test, suggesting the critical period for the development of whisker-specific tactile function is P0–P3, agreed with previous findings demonstrated by lesion methods. In the WC 0–3 rats, the cortical areas in the layer IV somatosensory region in relation to the trimmed whiskers were enlarged and the spiny stellate neurons within had larger dendritic span and greater spine density. Furthermore, more long and multiple-head spines were found in these rats. With abnormal structure and function in the somatosensory system, the WC 0–3 rats showed higher explorative activity and more frequent social interactions. Our results have demonstrated that the early tactile deprivation, similar to early visual deprivation, perturbed the developmental program of the brain and affected later behaviors in various aspects.

Helicobacter pylori is an important risk factor of duodenal ulcer (DU). Although many virulence factors of H. pylori have been identified, few have been reported to show an association with the pathogenesis of DU. The aims of this study were to identify H. pylori antigens showing a high seropositivity in DU and to develop a platform for rapid and easy diagnosis for DU. Because DU and gastric cancer (GC) are considered clinical divergent gastroduodenal diseases, we compared two-dimensional immunoblots of an acid-glycine extract of an H. pylori strain from a patient with DU probed with serum samples from 10 patients with DU and 10 with GC to identify DU-related antigens. Of the 11 proteins that were strongly recognized by serum IgG from DU patients, translation elongation factor EF-G (FusA), catalase (KatA), and urease alpha subunit (UreA) were identified as DU-related antigens, showing a higher seropositivity in DU samples (n = 124) than in GC samples (n = 95) (FusA, 70.2 versus 45.3%; KatA, 50.8 versus 41.1%; UreA, 44.4 versus 27.4%). In addition, we found that the use of multiple antigens improved the discrimination between patients with DU and those with GC as the odds ratios increased from 1.82 (95% confidence interval (CI), 0.79-4.21; p = 0.1607) for seropositivity for FusA, KatA, or UreA alone to 4.95 (95% CI, 2.05-12.0; p = 0.0004) for two of the three antigens and to 5.71 (95% CI, 1.86-17.6; p = 0.0024) for all three antigens. Moreover a protein array containing the three DU-related antigens was developed to test the idea of using multiple biomarkers in diagnosis. We conclude that FusA, KatA, and UreA are DU-related antigens of H. pylori, and the combination of these on a protein array provided a rapid and convenient method for detecting serum antibody patterns of DU patients.

Background:This study investigated the prevalence, incidence, and hospitalization for chronic airway obstruction (CAO) in a population cohort. Methods:Medical reimbursement claims from 1996 to 2002 based on a 1996 insured cohort of 167,372 persons from National Health Insurance, Taiwan, were used. We presented the chronological trends of CAO (International Classification of Diseases, Ninth Revision code 496) and the relationships between the CAO severity and age, sex, urbanization, and hospitalization and comorbidity for the population ≥ 40 years old. Results:The overall average annual prevalence and incidence rates were 2.48/100 and 0.66/100, respectively, for the population, among 4,568 patients with CAO cared during the study period. For the population aged ≥ 70 years, the prevalence rates had a peak of 8.83/100 in 1998 and afterward remained a plateau until 2002. The corresponding incidence decreased from 2.48/100 to 1.62/100, and the hospitalization rate for them had a peak of 2.22/100 in 1999. The multivariate logistic regression analysis showed that the risk of hospitalization for CAO was higher for patients with the comorbidity of renal failure, coronary artery disease, and pneumonia and influenza, but lower with skin and joint disorders. Conclusions:The national insurance program promotes patient care and provides a proper pathway for surveillance and identification of CAO.

Most of the published complete genome sequences of Helicobacter pylori strains are limited to clinical isolates associated with gastritis, peptic ulcers, or gastric cancer. The genome sequences of three H. pylori strains isolated from patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma are presented here to facilitate studies of H. pylori -associated MALT lymphomagenesis.