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1.  The Clinical and Occupational Correlates of Work Productivity Loss Among Employed Patients With Depression 
Employers who are developing strategies to reduce health-related productivity loss may benefit from aiming their interventions at the employees who need them most. We determined whether depression’s negative productivity impact varied with the type of work employees performed. Subjects (246 with depression and 143 controls) answered the Work Limitations Questionnaire and additional work questions. Occupational requirements were measured objectively. In multiple regression analyses, productivity was most influenced by depression severity (P < 0.01 in 5/5 models). However, certain occupations also significantly increased employee vulnerability to productivity loss. Losses increased when employees had occupations requiring proficiency in decision-making and communication and/or frequent customer contact (P < 0.05 in 3/5 models). The Work Limitations Questionnaire can help employers to reduce productivity loss by identifying health and productivity improvement priorities.
PMCID: PMC4283812  PMID: 15194895
2.  Unemployment, Job Retention, and Productivity Loss Among Employees With Depression 
Objective
This study comprehensively assessed the work outcomes of employees with depression.
Methods
We collected baseline and six-month follow-up survey data from 229 employees with depression and two employee comparison groups: a group of healthy patients for the control group (N=173) and a group with rheumatoid arthritis (N=87), a frequent source of work disability. Outcomes included new unemployment and, within the employed subgroup, job retention (versus job turnover), presenteeism (that is, diminished on-the-job performance and productivity), and absenteeism.
Results
At the six-month follow-up, persons with depression had more new unemployment—14 percent for persons in the dysthymia group, 12 percent for persons in the major depression group, and 15 percent for persons in the group with both dysthymia and major depression, compared with 2 percent for persons in the control group and 3 percent for persons in the rheumatoid arthritis group. Among participants who were still employed, those with depression had significantly more job turnover, presenteeism, and absenteeism.
Conclusions
In addition to helping employees with depression obtain high-quality depression treatment, new interventions may be needed to help them to overcome the substantial job upheaval that this population experiences.
doi:10.1176/appi.ps.55.12.1371
PMCID: PMC4283817  PMID: 15572564
3.  Decreased expression of microRNA-126 is associated with poor prognosis in patients with cervical cancer 
Diagnostic Pathology  2014;9(1):220.
Background
MicroRNA-126(miR-126) has been shown to be frequently down-regulated in a variety of malignancies and act as a potential tumor suppressor. However, its correlations with the clinicopathological characters of cervical cancer remain unclear.
Methods
TaqMan quantitative RT-PCR was used to determine the expression level of miR-126 in tissue samples. The associations of miR-126 expression with clinicopathologic variables were analyzed. Kaplan-Meier survival analysis was performed to analyze the association of miR-126 expression with overall survival (OS) of patients. Univariate and multivariate Cox regression analyses were performed.
Results
miR-126 expression level in human cervical cancer tissues was significantly lower than that in adjacent nontumorous tissues (mean ± SD: 0.59 ± 0.44 vs. 1.00 ± 0.51, P < 0.0001). Decreased miR-126 expression in cervical cancer was found to be significantly associated with lymphatic invasion (P = 0.002), distant metastasis (P < 0.001), FIGO stage (P = 0.009), and histological grade (P = 0.005). Kaplan-Meier analysis showed that patients with lower levels of miR-126 had significantly poorer survival than those with higher expression of this miRNA in patients, with a 5-year OS of 45.7% and 70.9%, respectively (P = 0.002). Multivariate analysis revealed that miR-126 expression (HR = 3.97, 95% CI: 2.01-20.22; P = 0.003) was independently associated with the OS.
Conclusion
Our data suggests the potential of miR-126 as a prognostic biomarker for cervical cancer.
Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_220
doi:10.1186/s13000-014-0220-x
PMCID: PMC4299682  PMID: 25551621
miRNA; miR-126; Cervical cancer; Quantitative RT-PCR; Prognosis
4.  Job Performance Deficits Due to Depression 
The American journal of psychiatry  2006;163(9):1569-1576.
Objective
This study assessed the relationship between depression severity and job performance among employed primary care patients.
Method
In a 2001–2004 longitudinal observational study of depression’s affect on work productivity, 286 patients with DSM-IV major depressive disorder and/or dysthymia were compared to 93 individuals with rheumatoid arthritis, a condition associated with work disability, and 193 depression-free healthy control subjects. Participants were employed at least 15 hours per week, did not plan to stop working, and had no major medical co-morbidities. Measures at baseline, six, 12, and 18 months included the Work Limitations Questionnaire for work outcomes, and the Patient Health Questionnaire-9 for depression.
Results
At baseline and each follow-up, the depression group had significantly greater deficits in managing mental-interpersonal, time, and output tasks, as measured by the Work Limitations Questionnaire: The rheumatoid arthritis group’s deficits in managing physical job demands surpassed those of either the depression or comparison groups. Improvements in job performance were predicted by symptom severity. However, the job performance of even the “clinically improved” subset of depressed patients remained consistently worse than the control groups.
Conclusions
Multiple dimensions of job performance are impaired by depression. This impact persisted after symptoms have improved. Efforts to reduce work-impairment secondary to depression are needed.
doi:10.1176/appi.ajp.163.9.1569
PMCID: PMC4269259  PMID: 16946182
5.  The work impact of dysthymia in a primary care population 
General hospital psychiatry  2004;26(4):269-276.
Physicians regard individuals with dysthymia as having relatively normal levels of functioning. This study examines in detail the work impact of dysthymia in a population of employed primary care patients. As part of an observational study conducted between 2001 and 2003 in clinics associated with three health plans in Massachusetts, we compared 69 patients diagnosed with DSM-IV dysthymia without concurrent major depressive disorder to 175 depression-free controls. Patients were employed at least 15 h per week, had no immediate plans to leave the labor market, and no major comorbid medical conditions. We assessed work absences and productivity loss due to on-the-job performance limitations (“presenteeism”). Patients with dysthymia, compared with controls, had less stable work histories and a greater frequency of significant problems at work. While absence rates were not significantly different (1.2 vs. 0.74 days, P < .09), individuals with dysthymia experienced significantly greater on-the-job productivity loss (6.3% vs. 2.8%, P < .0001). Dysthymia is an unrecognized cause of work impairment that has long-term negative consequences for individuals and their employers. The persistence of dysthymia with its serious impact on work functioning calls out for the development of new interventions.
doi:10.1016/j.genhosppsych.2004.04.004
PMCID: PMC4269288  PMID: 15234821
Dysthymia; Economic issues; Mood disorders; Outcome studies; Primary care; Work productivity
6.  Role of 2-[18F] Fluoro-2-Deoxy-D-Glucose-Positron Emission Tomography/Computed Tomography in the Post-Therapy Surveillance of Breast Cancer 
PLoS ONE  2014;9(12):e115127.
Purpose
To evaluate the usefulness of 2-[18F] fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in the early detection of breast cancer tumor recurrences and its role in post-therapy surveillance.
Methods
FDG-PET/CT was performed on patients with increased serum CA 15-3 levels and/or clinical/radiologic suspicion of recurrence. A group of asymptomatic patients who underwent FDG-PET/CT in the post-therapy surveillance of breast cancer served as the controls. The results were analyzed based on the patients' histological data, other imaging modalities and/or clinical follow-up. Recurrence was defined as evidence of recurrent lesions within 12 months of the FDG-PET/CT scan.
Results
Based on elevated serum CA15-3 levels (n = 31) and clinical/radiologic suspicion (n = 40), 71 scans were performed due to suspected recurrence, whereas 69 scans were performed for asymptomatic follow-up. The sensitivity and specificity of FDG-PET/CT were 87.5% and 87.1% in the patients with suspected recurrence and 77.8% and 91.7% in the asymptomatic patients. The positive predictive value in the patients with suspected recurrence (mainly due to elevated serum CA 15-3 levels) was higher than that in asymptomatic patients (P = 0.013). Recurrences were proven in 56.3% (40/71) of the patients with suspected recurrence and in 13% (9/69) of the asymptomatic patients (P<0.001). FDG-PET/CT resulted in changes in the planned management in 49.3% (35/71) of the patients with suspected recurrence and 10.1% (7/69) of the asymptomatic patients (P<0.001). After follow-up, 77.5% (55/71) of the patients with suspicious recurrences and 97.1% (67/69) of the asymptomatic patients were surviving at the end of the study (P<0.001).
Conclusions
FDG-PET/CT was able to detect recurrence, and the results altered the intended patient management in the post-therapy surveillance of breast cancer. FDG-PET/CT should be used as a priority in patients with increased serum CA 15-3 levels, or with clinical/radiologic suspicion of recurrence, and might be useful for asymptomatic patients.
doi:10.1371/journal.pone.0115127
PMCID: PMC4269411  PMID: 25517451
7.  Remembering faces with emotional expressions 
Frontiers in Psychology  2014;5:1439.
It is known that happy faces create more robust identity recognition memory than faces with some other expressions. However, this advantage was not verified against all basic expressions. Moreover, no research has assessed whether similar differences also exist among other expressions. To tackle these questions, we compared the effects of six basic emotional expressions on recognition memory using a standard old/new recognition task. The experiment also examined whether exposure to different emotional expressions at training creates variable effects on transfer of the trained faces to a new/neutral expression. Our results suggest that happy faces produced better identity recognition relative to disgusted faces, regardless of whether they were tested in the same image or a new image displaying a neutral expression. None of the other emotional expressions created measurable advantage for recognition memory. Overall, our data lend further support for the happy face advantage for long-term recognition memory. However, our detailed analyses also show that the advantage of happy expression on identity recognition may not be equally discernible from all other emotional expressions.
doi:10.3389/fpsyg.2014.01439
PMCID: PMC4261711  PMID: 25540634
facial expression; transfer of expression training; identity recognition; emotion; memory
8.  Human epidermal growth factor receptor 2 expression in breast cancer: correlation with clinical pathological features 
The overexpressed HER2 (human epidermal growth factor receptor 2) is a valuable therapeutic target. Precise assessment of HER2 status is thus crucial in the treatment of breast cancer. In this study, formalin-fixed, paraffin-embedded samples of tumors from 304 breast cancer patients who underwent curative surgery procedures between 2011 and 2014 were tested by immunohistochemistry (IHC) as a primary estimate of HER2 status, followed by fluorescence in situ hybridization (FISH). Concordance rate between IHC and FISH was evaluated. The Χ2 test was used to evaluate the correlation between HER2 gene amplification status and different clinical pathological features including: (estrogen receptor) ER and (progesterone receptor) PR expression, age, menopausal status and tumor size. The results show that 84.8% of IHC score 3+ cases and 6.2% of IHC score 0/1+ cases were amplified by FISH. After exclusion of group IHC 2+, the concordance rate between FISH and IHC was 87.4%. There was a significant inverse association between expression of hormone receptors (ER and PR) and HER2 amplification (P < 0.001) among the patients studied. However, no relationship was observed between HER2 amplification and age, menopausal status and tumor size (P > 0.05). The data demonstrate a relatively high level of concordance rate for HER2 testing between FISH and IHC, and HER2 overexpression was associated with the levels of ER and PR.
PMCID: PMC4314040
Breast cancer; HER2; clinical pathological features; immunohistochemistry (IHC); fluorescence in situ hybridization (FISH)
9.  Comparison between the cranial magnetic resonance imaging features of neuromyelitis optica spectrum disorder versus multiple sclerosis in Taiwanese patients 
BMC Neurology  2014;14(1):218.
Background
Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are inflammatory diseases of the central nervous system with different pathogenesis, brain lesion patterns, and treatment strategies. However, it is still difficult to distinguish these two disease entities by neuroimaging studies. Herein, we attempt to differentiate NMOSD from MS by comparing brain lesion patterns on magnetic resonance imaging (MRI).
Methods
The medical records and cranial MRI studies of patients with NMOSD diagnosed according to the 2006 Wingerchuk criteria and the presence of anti-aquaporin 4 (anti-AQP4) antibodies, and patients with MS diagnosed according to the Poser criteria, were retrospectively reviewed.
Results
Twenty-five NMOSD and 29 MS patients were recruited. The NMOSD patients became wheelchair dependent earlier than MS patients (log rank test; P = 0.036). Linear ependymal (28% vs. 0%, P = 0.003) and punctate lesions (64% vs. 28%, P = 0.013) were more frequently seen in NMOSD patients. Ten NMOSD patients (40%) had brain lesions that did not meet the Matthews criteria (MS were separated from NMOSD by the presence of at least 1 lesion adjacent to the body of the lateral ventricle and in the inferior temporal lobe; or the presence of a subcortical U-fiber lesion or a Dawson finger-type lesion). The different image patterns of NMOSD didn’t correlate with the clinical prognosis. However, NMOSD patients with more (≧10) brain lesions at onset became wheelchair dependence earlier than those with fewer (<10) brain lesions (log rank test; P < 0.001).
Conclusions
The diagnostic sensitivity of NMOSD criteria can be increased to 56% by combining the presence of linear ependymal lesions with unmet the Matthews criteria. The prognoses of NMOSD and MS are different. A specific imaging marker, the linear ependymal lesion, was present in some NMOSD patients. The diagnosis of NMOSD can be improved by following the evolution of this imaging feature when anti-AQP4 antibody test results are not available.
doi:10.1186/s12883-014-0218-8
PMCID: PMC4264553  PMID: 25433369
Neuromyelitis optica; Multiple sclerosis; Anti-aquaporin 4 antibody; Magnetic resonance imaging
10.  Clinical Correlations of Motor and Somatosensory Evoked Potentials in Neuromyelitis Optica 
PLoS ONE  2014;9(11):e113631.
Background
Motor and somatosensory evoked potentials (MEPs and SSEPs) are sensitive tools for detecting subclinical lesions, assessing disease severity, and determining the prognosis for outcomes of patients with inflammatory neurological diseases such as multiple sclerosis. However, their roles in neuromyelitis optica (NMO), a severe inflammatory neurological disease that predominantly involves optic nerves and spinal cord, have not yet been clarified.
Methods and Findings
Clinical symptoms and examination findings at relapses of 30 NMO patients were retrospectively reviewed. Abnormal MEPs were observed in 69.2% of patients. Patients with abnormal motor central conduction time (CCT) of the lower limbs had higher Kurtzke Expanded Disability Status Scale (EDSS) scores than those with normal responses (P = 0.027). Abnormal SSEPs were found in 69.0% of patients. Patients with abnormal lower limb sensory CCT had higher EDSS scores than those with normal responses (P = 0.019). In 28 patients followed up more than 6 months, only one of 11 patients (9.1%) with normal SSEPs of the lower limbs had new relapses within 6 months, whereas 8 of 17 patients (47.1%, P = 0.049) with abnormal SSEPs of the lower limbs had new relapses.
Conclusions
These results indicate MEPs and SSEPs of the lower limbs are good indicators for the disability status at relapses of NMO. Lower limb SSEPs may be a good tool for reflecting the frequency of relapses of NMO.
doi:10.1371/journal.pone.0113631
PMCID: PMC4244088  PMID: 25422930
11.  Statistical analysis of twenty years (1993 to 2012) of data from mainland China’s first intervention center for children with autism spectrum disorder 
Molecular Autism  2014;5:52.
Background
Autism spectrum disorder (ASD) is characterized by persistent deficits in social communication and interaction, and restrictive and repetitive patterns of behavior, interests or activities. This study aimed to analyze trends in ASD diagnosis and intervention in 20 years of data from the Beijing Stars and Rain Education Institute for Autism (SR), the first autism intervention center in mainland China, and from a recent survey of members of the Heart Alliance, an industry association of autism intervention centers in China.
Methods
We analyzed the registration data at the SR from 1993 to 2012 for a total of 2,222 children who had a parent-reported diagnosis of ASD and 612 of ‘autistic tendencies’. Most of the children who were the primary focus of our analyses were age six and under. We also analyzed results of a survey we conducted in 2013 of 100 member centers of the Heart Alliance. Generalized Estimating Equations, multiple linear regression and the Mann-Whitney test were used for data analysis. Statistically significant findings are reported here.
Results
The number of hospitals where SR children received their diagnosis increased from several in the early 1990s to 276 at present. The proportion of ‘autistic tendencies’ diagnosis increased 2.04-fold from 1998 to 2012 and was higher for children diagnosed at a younger age. The mean age at first diagnosis of ASD or ‘autistic tendencies’ decreased by 0.27 years every decade. A higher level of parental education was statistically significantly associated with an earlier diagnosis of the child. The mean parental age at childbirth increased by about 1.48 years per decade, and the mean maternal age was 1.40 and 2.10 years higher than that in the national population censuses of 2000 and 2010, respectively. At the time of the survey 3,957 children with ASD were being trained at the 100 autism intervention centers. Ninety-seven of these centers opened after the year 2000. Economically underdeveloped regions are still underserved.
Conclusions
This study revealed encouraging trends and remaining challenges in ASD diagnosis and intervention among children at the SR over the past 20 years and the 100 autism intervention centers in China at present.
Electronic supplementary material
The online version of this article (doi:10.1186/2040-2392-5-52) contains supplementary material, which is available to authorized users.
doi:10.1186/2040-2392-5-52
PMCID: PMC4332440
Autism spectrum disorder; Diagnosis; Intervention; Parental age; China
12.  Work Performance of Employees With Depression: The Impact of Work Stressors 
Purpose
Depressed employees are vulnerable to adverse work outcomes. We hypothesized that work performance is impaired by depression and is worsened by exposure to psychosocial work stressors.
Design
Longitudinal cohort study with surveys administered at baseline, 6, 12, and 18 months.
Setting
Recruitment in primary care offices.
Subjects
A total of 14,268 were screened; 286 depressed, employed adults (18–62 years) and 193 controls were enrolled.
Measures
At-work limitations (presenteeism) and absenteeism were measured with the Work Limitations Questionnaire (WLQ) and WLQ Work Absence Module, respectively. Work stressors were assessed using a modified version of the Job Content Questionnaire.
Analysis
Univariate and multivariate tests assessed the degree to which at-work limitations were related to depression and/or stressful work.
Results
Presenteeism and absenteeism were significantly worse for the depression group at each time point (p ≤ .001). In cross-sectional models, presenteeism was associated with more severe depression symptoms, poorer general physical health, psychologically demanding work, the interaction of psychologically demanding work with depression, and less job control (r2 range = .33–.54). Absences were explained by depression symptom severity and poorer general physical health but not work stressors (r2 = .19). Because of minimal change in the work stressors, their longitudinal effects on outcomes were mostly nonsignificant.
Conclusion
This study found that depression symptoms are related to work absences and impaired work performance, and results partly confirmed that work stressors add to this impact. Results suggest that workers with depression may benefit from care involving medical and vocational interventions.
doi:10.4278/ajhp.090313-QUAN-103
PMCID: PMC4174367  PMID: 20073388
Depression; Productivity; Work Stress; Job Performance; Prevention Research. Manuscript format: research; Research purpose: modeling/relationship testing; Study design: quasi-experimental; Outcome measure: productivity; absenteeism; Setting: clinical/health care; Health focus: presenteeism; absenteeism; Strategy: n/a; Target population: adults; Target population circumstances: employed
13.  Delta-like ligand 4: A predictor of poor prognosis in clear cell renal cell carcinoma 
Oncology Letters  2014;8(6):2627-2633.
Delta-like ligand 4 (Dll4)-Notch signaling is important in tumor angiogenesis; however, the prognostic value of D114 detection in patients with clear cell renal cell carcinoma (CCRCC) remains unclear. The present study aimed to determine whether the presence of high Dll4 expression levels was correlated with poor prognosis in CCRCC following curative resection. The D114 expression levels in four paired samples of CCRCC tissues and adjacent normal renal tissues were assayed by western blotting. Surgical specimens comprised 121 CCRCC tissue samples and 65 normal renal tissue samples, obtained from patients with CCRCC. The specimens were immunohistochemically assessed to determine Dll4 and vascular endothelial growth factor receptor 2 (VEGFR-2) expression levels. The prognostic significance of Dll4 expression levels was evaluated by the Kaplan-Meier method and Cox regression analysis. The correlation between Dll4 expression levels and VEGFR-2 expression levels, tumor stage, tumor grade and metastasis, was examined by χ2 test and multivariate logistic regression. As determined by the western blotting results, Dll4 protein expression levels were significantly increased in CCRCC tissues compared with those in adjacent non-cancerous tissues. From the analysis of the surgical specimens, 53 (43.8%) CCRCC patients exhibited immunohistochemically high Dll4 expression levels and 68 (56.2%) patients exhibited low Dll4 expression levels. The survival curves revealed that the patients with high Dll4 expression levels had significantly shorter survival times than the patients with low Dll4 expression levels (P<0.001). Multivariate survival analysis demonstrated that the presence of high Dll4 expression levels was independently associated with reduced overall survival and progression-free survival times (P=0.021 and 0.034, respectively). A positive correlation was also identified between Dll4 and VEGFR-2 expression levels (P=0.001). In conclusion, the results show that the presence of high Dll4 expression levels was clearly associated with high VEGFR-2 expression levels, tumor grade, tumor stage and poor prognosis in CCRCC patients. Therefore, inhibition of Dll4 may exert potent growth inhibitory effects on tumors resistant to anti-VEGF therapies for CCRCC.
doi:10.3892/ol.2014.2554
PMCID: PMC4214437  PMID: 25364440
delta-like ligand 4; clear cell renal cell carcinoma; survival; prognosis
14.  Effects of hook plate on shoulder function after treatment of acromioclavicular joint dislocation 
Introduction: Internal fixation with hook plate has been used to treat acromioclavicular joint dislocation. This study aims to evaluate the effect of its use on shoulder function, to further analyze the contributing factors, and provide a basis for selection and design of improved internal fixation treatment of the acromioclavicular joint dislocation in the future. Methods: A retrospective analysis was performed on patients treated with a hook plate for acromioclavicular joint dislocation in our hospital from January 2010 to February 2013. There were 33 cases in total, including 25 males and 8 females, with mean age of 48.27 ± 8.7 years. There were 29 cases of Rockwood type III acromioclavicular dislocation, 4 cases of type V. The Constant-Murley shoulder function scoring system was used to evaluate the shoulder function recovery status after surgery. Anteroposterior shoulder X-ray was used to assess the position of the hook plate, status of acromioclavicular joint reduction and the occurrence of postoperative complications. Results: According to the Constant-Murley shoulder function scoring system, the average scores were 78 ± 6 points 8 to 12 months after the surgery and before the removal of the hook plate, the average scores were 89 ± 5 minutes two months after the removal of hook plate. Postoperative X-ray imaging showed osteolysis in 10 cases (30.3%), osteoarthritis in six cases (18.1%), osteolysis associated with osteoarthritis in four cases(12.1%), and steel hook broken in one case (3%). Conclusion: The use of hook plate on open reduction and internal fixation of the acromioclavicular joint dislocation had little adverse effect on shoulder function and is an effective method for the treatment of acromioclavicular joint dislocation. Osteoarthritis and osteolysis are the two common complications after hook plate use, which are associated with the impairment of shoulder function. Shoulder function will be improved after removal of the hook plate.
PMCID: PMC4211760  PMID: 25356110
Acromioclavicular joint; dislocation; hook plate; function; osteolysis; osteoarthritis
15.  Enhancing mucosal immunity in mice by recombinant adenovirus expressing major epitopes of porcine circovirus-2 capsid protein delivered with cytosine-phosphate-guanosine oligodeoxynucleotides 
Journal of Veterinary Science  2014;15(3):399-407.
A recombinant replication-defective adenovirus expressing the major epitopes of porcine circovirus-2 (PCV-2) capsid protein (rAd/Cap/518) was previously constructed and shown to induce mucosal immunity in mice following intranasal delivery. In the present study, immune responses induced by intranasal immunization with a combination of rAd/Cap/518 and cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODN) were evaluated in mice. The levels of PCV-2-specific IgG in serum and IgA in saliva, lung, and intestinal fluids were significantly higher in the group immunized with rAd/Cap/518 and CpG ODN than animals immunized with rAd/Cap/518 alone. The frequencies of IL-2-secreting CD4+ T cells and IFN-γ-producing CD8+ T cells were significantly higher in the combined immunization group than mice immunized with rAd/Cap/518 alone. The frequencies of CD3+, CD3+CD4+CD8-, and CD3+CD4-CD8+ T cells in the combined immunization group were similar to that treated with CpG ODN alone, but significantly higher than mice that did not receive CpG ODN. PCV-2 load after challenge in the combined immunization group was significantly lower than that in the phosphate-buffered saline placebo group and approximately 7-fold lower in the group treated with CpG ODN alone. These results indicate that rAd/Cap/518 combined with CpG ODN can enhance systemic and local mucosal immunity in mice, and represent a promising synergetic mucosal vaccine against PCV-2.
doi:10.4142/jvs.2014.15.3.399
PMCID: PMC4178141  PMID: 24675838
cytosine-phosphate-guanosine oligodeoxynucleotides; mucosal immunity; porcine circovirus-2; rAd/Cap/518
16.  A synchronous hepatocellular carcinoma and renal cell carcinoma treated with radio-frequency ablation 
Clinical and Molecular Hepatology  2014;20(3):306-309.
Radio-frequency ablation (RFA) is a curative treatment for hepatocellular carcinoma (HCC). Percutaneous RFA has been shown to be beneficial for patients with small renal cell carcinoma (RCC) lacking indications for resection. We experienced the case of a 53-year-old male who had conditions that suggested HCC, RCC, and alcoholic liver cirrhosis. Abdominal contrast-enhanced computed tomography (CT) and magnetic resonance image showed liver cirrhosis with 2.8 cm ill-defined mass in segment 2 of the liver and 1.9 cm hypervascular mass in the left kidney. These findings were compatible with the double primary cancers of HCC and RCC. Transarterial chemoembolization (TACE) was performed to treat the HCC. After the TACE, a focal lipiodol uptake defect was noticed on a follow up CT images and loco-regional treatment was recommended. Therefore, we performed RFAs to treat HCC and RCC. There was no evidence of recurrence in the follow up image after 1 month.
doi:10.3350/cmh.2014.20.3.306
PMCID: PMC4197180  PMID: 25320735
Hepatocellular carcinoma; Renal cell carcinoma; Radiofrequency ablation
17.  Predictive Clinical Indicators of Biochemical Progression in Advanced Prostate Cancer Patients Receiving Leuplin Depot as Androgen Deprivation Therapy 
PLoS ONE  2014;9(8):e105091.
Therapeutic planning and counseling for advanced prostate cancer patients receiving androgen deprivation therapy (ADT) is complicated because the prognoses are highly variable. The purpose of this study is to identify predictive clinical indicators of biochemical progression (BCP). In this retrospective analysis, data from 107 newly diagnosed patients (from November 1995 to April 2008) with advanced prostate adenocarcinoma receiving Leuprorelin acetate depot were analyzed. Data was collected from the computerized registry of two collaborating medical centers in Taiwan. Cox regression and Kaplan-Meier analyses were used to evaluate the relationship between potential predictive parameters and BCP. Univariate analysis revealed that predictors of BCP included (1) initial serum prostate-specific antigen (PSA) (hazard ratio [HR], 1.00; 95% confidence interval [CI] 1.00–1.00); (2) log of initial PSA (HR, 1.35; 95% CI 1.17–1.56); (3) PSA density at diagnosis (HR, 1.00; 95% CI 1.00–1.01), and (4) pathological bone fracture (HR, 2.22; 95% CI 1.20–4.11). Age (HR, 0.94; 95% CI 0.91–0.98) and hemoglobin levels (HR, 0.86; 95% CI 0.76–0.97) were also associated with greater risk of BCP. After adjusting for age, pathologic fracture, and hemoglobin level, the initial PSA and PSA density were no longer significantly associated with BCP. However, age and hemoglobin levels continued to be associated with greater risk of BCP (P≤0.007). Using Kaplan-Meier analysis, patients with higher initial PSA concentration, pathological bone fracture, and low hemoglobin had a greater probability of BCP. Thus, low hemoglobin and age are predictive indicators of BCP and therefore early indicators of BCP despite ADT therapy.
doi:10.1371/journal.pone.0105091
PMCID: PMC4133301  PMID: 25121948
18.  TREM-1 as a potential therapeutic target in neonatal sepsis 
Objective: Bacterial sepsis in neonates is associated with elevated morbidity and mortality. A role for the pro-inflammatory Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) is suspected in the innate immune response to bacteria, but little is known about its activities in infants. To begin exploring the feasibility of treating neonatal sepsis by blocking leukocyte TREM-1, we compared TREM-1 membrane expression and mRNA in newborns without clinical or microbiological evidence of infection, to that of healthy adults. The functionality of pro-inflammatory reactions in leukocyte TREM-1 of newborns was also evaluated. Methods: Twenty term newborns were enrolled in this study and cord blood samples were collected at birth. For comparison, peripheral blood specimens were collected from 20 healthy adults (control adult, CA). The expression of TREM-1 protein and mRNA in leukocytes was detected with flow cytometry and real-time qPCR, respectively. Whole cord blood was also stimulated by Escherichia coli or blocked by the TREM-1-specific peptide LP17 to identify changes in the secretion of pro-inflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α, as well as soluble TREM-1 (sTREM-1) using enzyme linked immunosorbent assay (ELISA). Results: Mean fluorescence intensity (MFI) of TREM-1 on leukocytes of newborns appeared comparable to healthy adults [monocytes: 37.5 ± 6.7 vs. 37.6 ± 8.7; polymorphonuclear cells (PMNs): 32.9 ± 6.6 vs. 33.6 ± 5.8]. However, the percentage of PMNs positive for TREM-1 was lower in newborns than in healthy adults (82.3 ± 7.1 vs. 98.6 ± 4.8; P < 0.01); the percentage of TREM-1-positive CD14-positive monocytes was comparable to that of healthy adults (97.1 ± 8.3 vs. 97.5 ± 7.4). Exposure of cord blood to E. coli resulted in increased secretion of IL-6, IL-8, TNF-α, and sTREM-1. In contrast, the concentrations of IL-6, IL-8, and TNF-α decreased by a minimum of 15% when TREM-1 was blocked by LP17 then exposed to E. coli, versus E. coli alone. In addition, the concentration of sTREM-1 was positively correlated with the levels of TNF-α (r = 0.519, P < 0.05), IL-6 (r = 0.507, P < 0.05), and IL-8 (r = 0.538, P < 0.05). Conclusions: Healthy newborns exhibit expression of TREM-1 on monocytes similar to that in healthy adults, and most PMNs express TREM-1 at the newborn stage. Detection of sTREM-1 in neonatal peripheral blood should be further investigated as a potential method for the diagnosis of neonatal infection. Finally, blocking the TREM-1 signal transduction pathway may reduce inflammatory responses of neonate leukocytes and thereby provide a new strategy for treatment of neonatal infection.
PMCID: PMC4132125  PMID: 25126161
Triggering receptor expressed on myeloid cells-1; infant; leukocytes; sTREM-1
19.  Pathogenicity of Shigella in Chickens 
PLoS ONE  2014;9(6):e100264.
Shigellosis in chickens was first reported in 2004. This study aimed to determine the pathogenicity of Shigella in chickens and the possibility of cross-infection between humans and chickens. The pathogenicity of Shigella in chickens was examined via infection of three-day-old SPF chickens with Shigella strain ZD02 isolated from a human patient. The virulence and invasiveness were examined by infection of the chicken intestines and primary chicken intestinal epithelial cells. The results showed Shigella can cause death via intraperitoneal injection in SPF chickens, but only induce depression via crop injection. Immunohistochemistry and transmission electron microscopy revealed the Shigella can invade the intestinal epithelia. Immunohistochemistry of the primary chicken intestinal epithelial cells infected with Shigella showed the bacteria were internalized into the epithelial cells. Electron microscopy also confirmed that Shigella invaded primary chicken intestinal epithelia and was encapsulated by phagosome-like membranes. Our data demonstrate that Shigella can invade primary chicken intestinal epithelial cells in vitro and chicken intestinal mucosa in vivo, resulting in pathogenicity and even death. The findings suggest Shigella isolated from human or chicken share similar pathogenicity as well as the possibility of human-poultry cross-infection, which is of public health significance.
doi:10.1371/journal.pone.0100264
PMCID: PMC4064985  PMID: 24949637
20.  Polypoid colonic metastases from gastric stump carcinoma: A case report 
Oncology Letters  2014;8(3):1119-1122.
The present study aimed to investigate polypoid colonic metastases from gastric stump carcinoma by performing a retrospective analysis of the clinical data of a patient with such a diagnosis, and by discussing other previous case studies from the literature. The patient of the present study was an 80-year-old male who had undergone a gastrectomy 48 years previously for a benign perforated gastric ulcer. A colonoscopy revealed >10 multiple polypoid lesions of 6–10 mm in diameter distributed throughout the entire colon, except in the rectum. Each lesion had either erosion or a depression at the top and several were covered with a white fur-like substance. Biopsy specimens excised from the stomach showed a poorly-differentiated adenocarcinoma with diffuse signet ring cells, and a colonoscopy-guided biopsy revealed a signet ring cell adenocarcinoma. The patient was referred to the Oncology unit (Beijing Shijitan Hospital, Beijing, China) for assessment and chemotherapy treatment, which was initiated with 1,000 mg Xeloda orally administered twice a day for two-week courses every three weeks. The patient succumbed to upper gastrointestinal hemorrhage and pneumonia after three months. Gastric or gastric stump carcinoma may metastasize to the colon presenting as solitary or multiple colonic polyps. Thus, it is important to consider this diagnosis as such colon metastases may mimic solitary or multiple colonic polyps, which are commonly observed. A differential diagnosis is required in this complicated situation.
doi:10.3892/ol.2014.2254
PMCID: PMC4114702  PMID: 25120669
adenocarcinoma; signet ring cells; gastric stump cancer; metastasis; multiple colonic polyps
21.  Alcoholic fatty liver disease elevates estimated coronary heart disease risk to levels comparable with those of nonalcoholic fatty liver disease in the Korean population: a cross-sectional study 
Clinical and Molecular Hepatology  2014;20(2):154-161.
Background/Aims
A close relationship has been established between nonalcoholic fatty liver disease (NAFLD) and an elevated risk of coronary heart disease (CHD), but little is known about the association between alcoholic fatty liver disease (AFLD) and CHD risk. The aim of this study was to determine whether AFLD is associated with elevated CHD risk.
Methods
We retrospectively enrolled 10,710 subjects out of 11,469 individuals who visited the Konkuk University Health Care Center for a routine health checkup in 2010. AFLD was diagnosed made when the usual amount of alcohol consumption exceeded 210 g/week in males and 140 g/week in females for the previous 2 years and when hepatic steatosis was detected by liver ultrasonography. The 10-year risk for CHD was estimated using the Framingham Risk Score.
Results
Hepatic steatosis was diagnosed in 4,142 of the 10,710 individuals (38.7%); the remainder (i.e., n=6,568) became the control group. The 4,142 individuals with hepatic steatosis were divided into two groups: NAFLD (n=2,953) and AFLD (n=1,189). The risk of CHD was higher in AFLD (6.72±0.12) than in the control group (5.50±0.04, P<0.001), and comparable to that in NAFLD (7.32±0.07, P=0.02).
Conclusions
Individuals with AFLD have an elevated 10-year risk of CHD that is comparable to those with NAFLD. Therefore, AFLD should be considered a significant risk for future CHD, and preventive measures should be considered earlier.
doi:10.3350/cmh.2014.20.2.154
PMCID: PMC4099330  PMID: 25032181
Framingham risk score; Alcoholic fatty liver; Coronary heart disease risk
22.  Prevalence of renal dysfunction in patients with cirrhosis according to ADQI-IAC working party proposal 
Clinical and Molecular Hepatology  2014;20(2):185-191.
Background/Aims
A revised classification system for renal dysfunction in patients with cirrhosis was proposed by the Acute Dialysis Quality Initiative and the International Ascites Club Working Group in 2011. The aim of this study was to determine the prevalence of renal dysfunction according to the criteria in this proposal.
Methods
The medical records of cirrhotic patients who were admitted to Konkuk University Hospital between 2006 and 2010 were reviewed retrospectively. The data obtained at first admission were collected. Acute kidney injury (AKI) and chronic kidney disease (CKD) were defined using the proposed diagnostic criteria of kidney dysfunction in cirrhosis.
Results
Six hundred and forty-three patients were admitted, of whom 190 (29.5%), 273 (42.5%), and 180 (28.0%) were Child-Pugh class A, B, and C, respectively. Eighty-three patients (12.9%) were diagnosed with AKI, the most common cause for which was dehydration (30 patients). Three patients had hepatorenal syndrome type 1 and 26 patients had prerenal-type AKI caused by volume deficiency after variceal bleeding. In addition, 22 patients (3.4%) were diagnosed with CKD, 1 patient with hepatorenal syndrome type 2, and 3 patients (0.5%) with AKI on CKD.
Conclusions
Both AKI and CKD are common among hospitalized cirrhotic patients, and often occur simultaneously (16.8%). The most common type of renal dysfunction was AKI (12.9%). Diagnosis of type 2 hepatorenal syndrome remains difficult. A prospective cohort study is warranted to evaluate the clinical course in cirrhotic patients with renal dysfunction.
doi:10.3350/cmh.2014.20.2.185
PMCID: PMC4099334  PMID: 25032185
Hepatorenal syndrome; Cirrhosis; Acute kidney injury; Chronic kidney disease
23.  Micro-RNAs, New performers in multiple myeloma bone marrow microenvironment 
Biomarker Research  2014;2:10.
The established interaction between multiple myeloma cells and bone marrow microenvironment components provides malignant cells with various survival, growth and drug resistance signals. As a new concept, identification of miRNAs and their related gene/protein targets, signaling molecules and pathways in the context of bone marrow microenvironment will help understanding more deeply the pathogenesis of the disease and possible mechanisms underlying environment-induced drug resistance. Recent studies suggest that bone marrow stromal cells can modulate some miRNAs (miR-21, miR-15a/16) in multiple myeloma cells through direct adhesion, cytokine secretion or transfer of miRNA-containing exosomes, however; the specific miRNA targets are not clear. In spite of a remarkable progress in understanding myeloma biology and therapy, the disease persists to be hard to treat. This review will discuss the most recent findings on miRNAs expression and function in the context of bone marrow microenvironment highlighting the miRNAs as potential therapeutic targets in multiple myeloma.
doi:10.1186/2050-7771-2-10
PMCID: PMC4048053  PMID: 24910775
Multiple myeloma; miRNA; Bone marrow stroma; CAMDR
24.  Yiqihuoxuejiedu Formula Inhibits Vascular Remodeling by Reducing Proliferation and Secretion of Adventitial Fibroblast after Balloon Injury 
Vascular remodeling occurs in atherosclerosis, hypertension, and restenosis after percutaneous coronary intervention. Adventitial remodeling may be a potential therapeutic target. Yiqihuoxuejiedu formula uses therapeutic principles from Chinese medicine to supplement Qi, activate blood circulation, and resolve toxin and it has been shown to inhibit vascular stenosis. To investigate effects and mechanisms of the formula on inhibiting vascular remodeling, especially adventitial remodeling, rats with a balloon injury to their common carotid artery were used and were treated for 7 or 28 days after injury. The adventitial area and α-SMA expression increased at 7 days after injury, which indicated activation and proliferation of adventitial fibroblasts. Yiqihuoxuejiedu formula reduced the adventitial areas at 7 days, attenuated the neointima and vessel wall area, stenosis percent, and α-SMA expression in the neointima, and reduced collagen content and type I/III collagen ratio in the adventitia at 28 days. Yiqihuoxuejiedu formula had more positive effects than Captopril in reducing intimal proliferation and diminishing stenosis, although Captopril lowered neointimal α-SMA expression and reduced the collagen content at 28 days. Yiqihuoxuejiedu formula has inhibitory effects on positive and negative remodeling by reducing adventitial and neointimal proliferation, reducing content, and elevating adventitial compliance.
doi:10.1155/2014/849167
PMCID: PMC4058465  PMID: 24987435
25.  Emotion Identification Using Extremely Low Frequency Components of Speech Feature Contours 
The Scientific World Journal  2014;2014:757121.
The investigations of emotional speech identification can be divided into two main parts, features and classifiers. In this paper, how to extract an effective speech feature set for the emotional speech identification is addressed. In our speech feature set, we use not only statistical analysis of frame-based acoustical features, but also the approximated speech feature contours, which are obtained by extracting extremely low frequency components to speech feature contours. Furthermore, principal component analysis (PCA) is applied to the approximated speech feature contours so that an efficient representation of approximated contours can be derived. The proposed speech feature set is fed into support vector machines (SVMs) to perform multiclass emotion identification. The experimental results demonstrate the performance of the proposed system with 82.26% identification rate.
doi:10.1155/2014/757121
PMCID: PMC4055048  PMID: 24982991

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