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Sample records for early psa decrease

  1. Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer.

    PubMed

    Fujita, Kazutoshi; Hayashi, Takuji; Matsuzaki, Kyosuke; Nakata, Wataru; Masuda, Mika; Kawashima, Atsunari; Ujike, Takeshi; Nagahara, Akira; Tsuchiya, Mutsumi; Kobayashi, Yuka; Nojima, Satoshi; Uemura, Motohide; Morii, Eiichi; Miyoshi, Eiji; Nonomura, Norio

    2016-08-30

    Fucosylation is an important oligosaccharide modification associated with cancer and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA) levels could be used for the detection of high Gleason score prostate cancer. Urine samples were collected from men with abnormal digital rectal examination findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL) and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of urinary Fuc-PSA were significantly decreased in the men with prostate cancer compared with the men whose biopsies were negative for cancer (P = 0.026 and P < 0.001, respectively). Both were also significantly associated with the Gleason scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively). Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA-PhoSL were independent predictors of high Gleason score prostate cancer. The area under the receiver-operator characteristic curve (AUC) value for the prediction of cancers of Gleason score ≥ 7 was 0.69 for urinary PSA-AAL and 0.72 for urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA level is a potential marker for the detection of high Gleason score prostate cancer.

  2. Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer

    PubMed Central

    Fujita, Kazutoshi; Hayashi, Takuji; Matsuzaki, Kyosuke; Nakata, Wataru; Masuda, Mika; Kawashima, Atsunari; Ujike, Takeshi; Nagahara, Akira; Tsuchiya, Mutsumi; Kobayashi, Yuka; Nojima, Satoshi; Uemura, Motohide; Morii, Eiichi; Miyoshi, Eiji; Nonomura, Norio

    2016-01-01

    Fucosylation is an important oligosaccharide modification associated with cancer and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA) levels could be used for the detection of high Gleason score prostate cancer. Urine samples were collected from men with abnormal digital rectal examination findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL) and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of urinary Fuc-PSA were significantly decreased in the men with prostate cancer compared with the men whose biopsies were negative for cancer (P = 0.026 and P < 0.001, respectively). Both were also significantly associated with the Gleason scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively). Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA-PhoSL were independent predictors of high Gleason score prostate cancer. The area under the receiver-operator characteristic curve (AUC) value for the prediction of cancers of Gleason score ≥ 7 was 0.69 for urinary PSA-AAL and 0.72 for urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA level is a potential marker for the detection of high Gleason score prostate cancer. PMID:27494861

  3. Early diagnostic role of PSA combined miR-155 detection in prostate cancer.

    PubMed

    Guo, T; Wang, X-X; Fu, H; Tang, Y-C; Meng, B-Q; Chen, C-H

    2018-03-01

    As a kind of malignant tumor in the male genitourinary system, prostate cancer exhibits significantly increased occurrence. Prostate-specific antigen (PSA) expression can be seen in the prostate cancer, prostatitis, and other diseases, therefore, lack of diagnostic specificity. The miR-155 expression is abnormally increased in the tumors. Therefore, this study aims to explore the clinical significance of PSA combined miR-155 detection in the early diagnosis of prostate cancer. A total of 86 patients diagnosed with prostate cancer were enrolled in this study. PSA and miR-155 gene expression in tumor tissue were detected by using Real-time PCR. The serum levels of PSA were measured by using enzyme-linked immunosorbent assay (ELISA). The correlation of PSA and miR-155 expression with age, body mass index (BMI), tumor volume, tumor-node-metastasis (TNM) stage, lymph node metastasis (LNM), and other clinicopathological features were analyzed, respectively. Serum PSA expression and PSA gene in tumor tissue were significantly higher compared to that in adjacent tissues (p<0.05). PSA gene and protein increased significantly with the clinical stage of TNM and decreased following the increase of grade (p<0.05). The miR-155 level was significantly elevated in the tumor tissue compared with para-carcinoma tissue (p<0.05). PSA and miR-155 expressions were positively correlated with TNM stage, tumor volume, and LNM, and negatively correlated with grade (p<0.05). PSA and miR-155 were closely related to the clinicopathological features of prostate cancer. Combined detection is helpful for the early diagnosis of prostate cancer.

  4. Effectiveness of early adalimumab therapy in psoriatic arthritis patients from Reuma.pt - EARLY PsA.

    PubMed

    Santos, Helena; Eusébio, Mónica; Borges, Joana; Gonçalves, Diana; Ávila-Ribeiro, Pedro; Faria, Daniela Santos; Lopes, Carina; Rovisco, João; Águeda, Ana; Nero, Patrícia; Valente, Paula; Cravo, Ana Rita; Santos, Maria José

    2017-01-01

    Objective To compare outcomes in psoriatic arthritis (PsA) patients initiating adalimumab (ADA), with short- and long-term disease duration and to evaluate the potential effect of concomitant conventional synthetic disease-modifying antirheumatic drugs (csDMARD) or glucocorticoids. Methods Analyses included adult PsA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt) between June 2008-June 2016 who received ADA for ≥3 months. Psoriatic Arthritis Response Criteria (PsARC) response, tender and swollen joint count, inflammatory parameters, patient (PtGA) and physician global assessment (PhGA), Disease Activity Score-28 joints (DAS28), and Health Assessment Questionnaire Disability Index (HAQ-DI) were compared between patients with <5 years of disease (early PsA) and those with ≥5 years of disease duration (late PsA). Time to achieving PsARC response was estimated using the Kaplan-Meier method. Results Of 135 PsA patients treated with ADA, 126 had information on disease duration (earlyPsA, n=41). PsARC response was achieved by 72.9% of the patients (88.0% early PsA vs 62.2% late PsA; P=0.022) after 3 months and by 85.4% after 24 months (100% early PsA vs 75.9% late PsA; P=0.044). Early PsA patients achieved significantly less painful joints (2.7 vs 6.7, p=0.006), lower mean C-reactive protein (0.5 mg/dL vs 1.3 mg/dL; P=0.011), and PhGA (18.3 vs 28.1; P=0.020) at 3 months. In the long term, early PsA patients also had fewer swollen joints (0.3 vs 1.7; P=0.030) and lower PhGA (6.3 vs 21.9; P<0.001), C-reactive protein (0.4 mg/dL vs 1.0 mg/dL; P=0.026), and DAS28 (2.2 vs 3.2; P=0.030). HAQ-DI decreased in both groups reaching a mean value at 24 months of 0.4 and 0.8 (P=ns) in early and late PsA, respectively. Early PsA patients obtained PsARC response more rapidly than late PsA (3.8 and 7.4 months, respectively; P=0.008). Concomitant csDMARDs showed clinical benefit (2-year PsARC response, 88.3% vs 60.0%; P=0.044). Concomitant glucocorticoids

  5. Androgen deprivation decreases prostate specific antigen in the absence of tumor: implications for interpretation of PSA results.

    PubMed

    Wenisch, Judith M; Mayr, Florian B; Spiel, Alexander O; Radicioni, Milko; Jilma, Bernd; Jilma-Stohlawetz, Petra

    2014-03-01

    Prostate-specific antigen (PSA) is used as an outcome measure for relapsed disease in prostate cancer. Nonetheless, there are considerable concerns about its indiscriminate use as a surrogate endpoint for cell growth or survival. We hypothesized that treatment with a luteinizing hormone releasing hormone (LHRH) analog would decrease PSA levels even in the absence of malignant disease. We determined testosterone and PSA levels in 30 healthy volunteers after a single intramuscular injection of a LHRH depot formulation. Testosterone and PSA levels were quantified by radioimmunoassay and electrochemi-luminescence immunoassay, respectively. After an initial flare-up during the first 3 days testosterone decreased reaching castration levels in 18 of the 30 young men (60%). After the nadir on day 28, testosterone levels increased to normal again. Changes in PSA paralleled those of testosterone. Castration reduced PSA levels by 29% (95% CI 19%-39%) compared to baseline (p<0.0001). LHRH superagonists decrease PSA levels by testosterone deprivation. Conferring these findings to tumor patients, decreases in PSA after treatment with LHRH analogs might not only reflect disease regression but also a direct testosterone mediated effect on PSA. Thus, PSA levels should be cautiously interpreted when patients receive hormonal therapy.

  6. PSA Nadir of <0.5 ng/mL Following Brachytherapy for Early-Stage Prostate Adenocarcinoma is Associated With Freedom From Prostate-Specific Antigen Failure

    SciTech Connect

    Ko, Eric C.; Stone, Nelson N.; Department of Urology, Mount Sinai Medical Center, New York, NY

    2012-06-01

    Purpose: Because limited information exists regarding whether the rate or magnitude of PSA decline following brachytherapy predicts long-term clinical outcomes, we evaluated whether achieving a prostate-specific antigen (PSA) nadir (nPSA) <0.5 ng/mL following brachytherapy is associated with decreased PSA failure and/or distant metastasis. Methods and Materials: We retrospectively analyzed our database of early-stage prostate adenocarcinoma patients who underwent brachytherapy, excluding those receiving androgen-deprivation therapy and those with <2 years follow-up. Median and mean pretreatment PSA were 6 ng/mL and 7.16 ng/mL, respectively. By clinical stage, 775 were low risk ({<=}T2a), 126 were intermediate risk (T2b), and 20 were high riskmore » (>T2b). By Gleason score, 840 were low risk ({<=}6), 71 were intermediate risk (7), and 10 were high risk (>7). Patients were treated with brachytherapy only (I-125, n = 779, or Pd-103, n = 47), or brachytherapy + external-beam radiation therapy (n = 95). Median follow-up was 6.3 years. We noted whether nPSA <0.5 ng/mL was achieved and the time to achieve this nadir and tested for associations with pretreatment risk factors. We also determined whether this PSA endpoint was associated with decreased PSA failure or distant metastasis. Results: Absence of high-risk factors in clinical stage ({<=}T2b), Gleason score ({<=}7), and pretreatment PSA ({<=}20 ng/mL) was significantly associated with achieving nPSA <0.5 ng/mL. By Kaplan-Meier analysis, patients achieving nPSA <0.5 ng/mL had significantly higher long-term freedom from biochemical failure (FFBF) than nonresponders (5-year FFBF: 95.2 {+-} 0.8% vs. 71.5 {+-} 6.7%; p < 0.0005). Among responders, those who achieved nPSA <0.5 ng/mL in {<=}5 years had higher FFBF than those requiring >5 years (5-year FFBF: 96.7 {+-} 0.7% vs. 80.8 {+-} 4.6%; p < 0.0005). On multivariate analysis, patients who achieved nPSA <0.5 ng/mL in {<=}5 years had significantly higher FFBF than other

  7. PSA nadir of <0.5 ng/mL following brachytherapy for early-stage prostate adenocarcinoma is associated with freedom from prostate-specific antigen failure.

    PubMed

    Ko, Eric C; Stone, Nelson N; Stock, Richard G

    2012-06-01

    Because limited information exists regarding whether the rate or magnitude of PSA decline following brachytherapy predicts long-term clinical outcomes, we evaluated whether achieving a prostate-specific antigen (PSA) nadir (nPSA) <0.5 ng/mL following brachytherapy is associated with decreased PSA failure and/or distant metastasis. We retrospectively analyzed our database of early-stage prostate adenocarcinoma patients who underwent brachytherapy, excluding those receiving androgen-deprivation therapy and those with <2 years follow-up. Median and mean pretreatment PSA were 6 ng/mL and 7.16 ng/mL, respectively. By clinical stage, 775 were low risk (≤ T2a), 126 were intermediate risk (T2b), and 20 were high risk (>T2b). By Gleason score, 840 were low risk (≤ 6), 71 were intermediate risk (7), and 10 were high risk (>7). Patients were treated with brachytherapy only (I-125, n = 779, or Pd-103, n = 47), or brachytherapy + external-beam radiation therapy (n = 95). Median follow-up was 6.3 years. We noted whether nPSA <0.5 ng/mL was achieved and the time to achieve this nadir and tested for associations with pretreatment risk factors. We also determined whether this PSA endpoint was associated with decreased PSA failure or distant metastasis. Absence of high-risk factors in clinical stage (≤ T2b), Gleason score (≤ 7), and pretreatment PSA (≤ 20 ng/mL) was significantly associated with achieving nPSA <0.5 ng/mL. By Kaplan-Meier analysis, patients achieving nPSA <0.5 ng/mL had significantly higher long-term freedom from biochemical failure (FFBF) than nonresponders (5-year FFBF: 95.2 ± 0.8% vs. 71.5 ± 6.7%; p < 0.0005). Among responders, those who achieved nPSA <0.5 ng/mL in ≤ 5 years had higher FFBF than those requiring >5 years (5-year FFBF: 96.7 ± 0.7% vs. 80.8 ± 4.6%; p < 0.0005). On multivariate analysis, patients who achieved nPSA <0.5 ng/mL in ≤ 5 years had significantly higher FFBF than other patients. Pretreatment risk factors (clinical tumor

  8. Consequences of an Early PSA Response to Enzalutamide Treatment for Japanese Patients with Metastatic Castration-resistant Prostate Cancer.

    PubMed

    Kato, Haruo; Furuya, Yosuke; Miyazawa, Yoshiyuki; Miyao, Takeshi; Syuto, Takahiro; Nomura, Masashi; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Ito, Kazuto; Suzuki, Kazuhiro

    2016-11-01

    Recent studies have shown that an early prostate-specific antigen (PSA) response to androgen receptor (AR)-targeting agents in metastatic castration-resistant prostate cancer (mCRPC) is associated with a better prognosis. We analyzed early PSA response to enzalutamide and oncological outcomes to study their prognostic significance in the Japanese population. Fifty-one patients with mCRPC (26 of pre-docetaxel and 25 of post-docetaxel status) were treated with enzalutamide. The PSA progression-free survival (PFS), radiographic PFS (rPFS) and overall survival (OS) were assessed. The association of rPFS and OS in patients with an early PSA response at 4 weeks after commencement of enzalutamide was studied. Early PSA responses were significantly associated with a longer rPFS (median of 47.9 vs. 20.1 weeks, p<0.001, in patients exhibiting a 50% PSA response; median of 40.9 vs. 20.1 weeks, p=0.016, in patients exhibiting a 30% PSA response). OS was also significantly associated with an early PSA response (p=0.002 for patients exhibiting a 50% PSA response, p=0.003 for patients exhibiting a 30% PSA response). Multivariate analysis showed that the predictors of a 50% PSA response were an interval to mCRPC and a docetaxel treatment history, while the predictor of a 30% PSA response was a docetaxel treatment history. Furthermore, a 50% PSA response was independently prognostic of rPFS. An early PSA response to enzalutamide was significantly associated with a longer rPFS and OS. This information will aid in the management of patients treated with enzalutamide. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. GPs views and understanding of PSA testing, screening and early detection; survey.

    PubMed

    Sutton, J; Melia, J; Kirby, M; Graffy, J; Moss, S

    2016-05-01

    There is currently no national prostate cancer screening programme in the UK. However, patients 50 years and older are entitled to a prostate specific antigen (PSA) test, if informed on the advantages and disadvantages of testing and their risk of cancer. The Prostate Cancer Risk Management Programme (PCRMP) provides this guidance. The aim of this study was to access GPs' views and understanding of PSA testing, prostate cancer screening and early detection. A total of 708 questionnaires were returned by GPs across two English regions in 2013 and the GP questionnaire responses were quantitatively analysed. In the 699 completed questionnaires, the majority of GPs were well informed about PSA testing, screening and early detection. Only 32% used guidelines for referral, 14% knew all age-specific PSA referral levels, 71% that Black men have a higher prostate cancer risk than White men (22% correctly answered threefold increase) and 82% that family history is a risk factor. A further 78% thought electronic prompts during consultation would encourage PCRMP guideline usage and 75% had never been offered a PSA test and prostate cancer educational course, of which 73% would like to attend a course. Only 23% were aware of the latest PSA screening evidence and 94% would like an update. Participating GPs seem to be well informed but need more information and tools to help follow recommended guidance. In particular, increased awareness of PCRMP guidelines especially by automated methods, further educational courses and evidence updates would be beneficial. © 2016 John Wiley & Sons Ltd.

  10. Repeat prostate-specific antigen (PSA) test before prostate biopsy: a 20% decrease in PSA values is associated with a reduced risk of cancer and particularly of high-grade cancer.

    PubMed

    De Nunzio, Cosimo; Lombardo, Riccardo; Nacchia, Antonio; Tema, Giorgia; Tubaro, Andrea

    2018-07-01

    To analyse the impact of repeating a prostate-specific antigen (PSA) level assessment on prostate biopsy decision in a cohort of men undergoing prostate biopsy. From 2015 onwards, we consecutively enrolled, at a single institution in Italy, men undergoing 12-core transrectal ultrasonography-guided prostate needle biopsy. Indication for prostate biopsy was a PSA level of ≥4 ng/mL. Demographic, clinical, and histopathological data were collected. The PSA level was tested at enrolment (PSA 1 ) and 4 weeks later on the day before biopsy (PSA 2 ). Variations in PSA level were defined as: stable PSA 2 within a 10% variation, stable PSA 2 within a 20% variation, PSA 2 decreased by ≥10%, PSA 2 decreased by ≥20%, PSA 2 increased by ≥10%, PSA 2 increased by ≥20%, and PSA 2 <4 ng/mL. Percentages and multinomial logistic regression were used to analyse biopsy outcomes. High-grade cancer was defined as Grade group ≥3. Overall, 331 patients were enrolled. Prostate cancer was diagnosed in 153/331 (46%) patients and of them 80/153 (52%) had high-grade disease. When compared to the rest of the population, patients with a stable PSA within 20% variation had a higher risk of prostate cancer (odds ratio [OR] 1.80, P < 0.05) and high grade disease (OR 2.56, P < 0.05), patients with a PSA2 decreased by ≥20% had a lower risk of prostate cancer (OR 0.37, P < 0.05) and high grade disease (OR 0.13, P < 0.05), whilst patients with a PSA2 increased by ≥10% had an increased risk of high-grade prostate cancer (OR 1.93, P < 0.05). When PSA returned to normal values (<4 ng/mL) both risks of prostate cancer and high-grade disease were reduced (OR 0.33 and 0.01, respectively, P = 0.001). In a cohort of Italian men undergoing prostate biopsy, a reduction of ≥20% in PSA levels significantly reduced the risk of high-grade prostate cancer. Further multicentre studies should validate our present results. © 2018 The Authors BJU International © 2018 BJU International Published by John

  11. SERIAL PERCENT-FREE PSA IN COMBINATION WITH PSA FOR POPULATION-BASED EARLY DETECTION OF PROSTATE CANCER

    PubMed Central

    Ankerst, Donna Pauler; Gelfond, Jonathan; Goros, Martin; Herrera, Jesus; Strobl, Andreas; Thompson, Ian M.; Hernandez, Javier; Leach, Robin J.

    2016-01-01

    PURPOSE To characterize the diagnostic properties of serial percent-free prostate-specific antigen (PSA) in relation to PSA in a multi-ethnic, multi-racial cohort of healthy men. MATERIALS AND METHODS 6,982 percent-free PSA and PSA measures were obtained from participants in a 12 year+ Texas screening study comprising 1625 men who never underwent biopsy, 497 who underwent one or more biopsies negative for prostate cancer, and 61 diagnosed with prostate cancer. Area underneath the receiver-operating-characteristic-curve (AUC) for percent-free PSA, and the proportion of patients with fluctuating values across multiple visits were determined according to two thresholds (under 15% versus 25%) were evaluated. The proportion of cancer cases where percent-free PSA indicated a positive test before PSA > 4 ng/mL did and the number of negative biopsies that would have been spared by percent-free PSA testing negative were computed. RESULTS Percent-free PSA fluctuated around its threshold of < 25% (< 15%) in 38.3% (78.1%), 42.2% (20.9%), and 11.4% (25.7%) of patients never biopsied, with negative and positive biopsies, respectively. At the same thresholds, percent-free PSA tested positive earlier than PSA in 71.4% (34.2%) of cancer cases, and among men with multiple negative biopsies and a PSA > 4 ng/mL, percent-free PSA would have tested negative in 31.6% (65.8%) instances. CONCLUSIONS Percent-free PSA should accompany PSA testing in order to potentially spare unnecessary biopsies or detect cancer earlier. When near the threshold, both tests should be repeated due to commonly observed fluctuation. PMID:26979652

  12. The posterior semantic asymmetry (PSA): An early brain electrical signature of semantic activation from written words.

    PubMed

    Koppehele-Gossel, Judith; Schnuerch, Robert; Gibbons, Henning

    2018-06-06

    This study replicates and extends the findings of Koppehele-Gossel, Schnuerch, and Gibbons (2016) of a posterior semantic asymmetry (PSA) in event-related brain potentials (ERPs), which closely tracks the time course and degree of semantic activation from single visual words. This negativity peaked 300 ms after word onset, was derived by subtracting right- from left-side activity, and was larger in a semantic task compared to two non-semantic control tasks. The validity of the PSA in reflecting the effort to activate word meaning was again attested by a negative correlation between the meaning-specific PSA increase and verbal intelligence, even after controlling for nonverbal intelligence. Extending prior work, current source density (CSD) transformation was used. CSD results were consistent with a left temporo-parietal cortical origin of the PSA. Moreover, no PSA was found for pictorial material, suggesting that the component reflects early semantic processing specific to verbal stimuli. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Risk of Pathologic Upgrading or Locally Advanced Disease in Early Prostate Cancer Patients Based on Biopsy Gleason Score and PSA: A Population-Based Study of Modern Patients

    SciTech Connect

    Caster, Joseph M.; Falchook, Aaron D.; Hendrix, Laura H.

    Purpose: Radiation oncologists rely on available clinical information (biopsy Gleason score and prostate-specific antigen [PSA]) to determine the optimal treatment regimen for each prostate cancer patient. Existing published nomograms correlating clinical to pathologic extent of disease were based on patients treated in the 1980s and 1990s at select academic institutions. We used the Surveillance, Epidemiology, and End Results (SEER) database to examine pathologic outcomes (Gleason score and cancer stage) in early prostate cancer patients based on biopsy Gleason score and PSA concentration. Methods and Materials: This analysis included 25,858 patients whose cancer was diagnosed between 2010 and 2011, with biopsymore » Gleason scores of 6 to 7 and clinical stage T1 to T2 disease, who underwent radical prostatectomy. In subgroups based on biopsy Gleason score and PSA level, we report the proportion of patients with pathologically advanced disease (positive surgical margin or pT3-T4 disease) or whose Gleason score was upgraded. Logistic regression was used to examine factors associated with pathologic outcomes. Results: For patients with biopsy Gleason score 6 cancers, 84% of those with PSA <10 ng/mL had surgical T2 disease with negative margins; this decreased to 61% in patients with PSA of 20 to 29.9 ng/mL. Gleason score upgrading was seen in 43% (PSA: <10 ng/mL) to 61% (PSA: 20-29.9 ng/mL) of biopsy Gleason 6 patients. Patients with biopsy Gleason 7 cancers had a one-third (Gleason 3 + 4; PSA: <10 ng/mL) to two-thirds (Gleason 4 + 3; PSA: 20-29.9 ng/mL) probability of having pathologically advanced disease. Gleason score upgrading was seen in 11% to 19% of patients with biopsy Gleason 4 + 3 cancers. Multivariable analysis showed that higher PSA and older age were associated with Gleason score upgrading and pathologically advanced disease. Conclusions: This is the first population-based study to examine pathologic extent of disease and pathologic

  14. [Use of [-2] pro PSA and phi index for early detection of prostate cancer: a prospective of 452 patients].

    PubMed

    Houlgatte, A; Vincendeau, S; Desfemmes, F; Ramirez, J; Benoist, N; Bensalah, K; Durand, X

    2012-05-01

    Early detection of prostate cancer (Pca) is a real challenge to reduce morbidity and mortality while avoiding over-diagnosis and over-treatment. The prostate specific antigen (PSA) is characterized by its imperfections justifying the evaluation of new serum or urinary specific markers allowing a better selection of patients at risk of developing aggressive Pca. To compare the value of -2pro PSA and phi index to total and free PSA. Serum sampled from 452 patients from two university centers were used to determine levels of PSA before performing biopsies. The patients were included in this study based on the PSA serum concentration between 1.6 ng/mL and 8 ng/mL according to the WHO international standard. All biopsies were performed according to a standardized protocol consisting of 12 cores or more. Sera were analyzed centrally in one of the two institutions with on a single analyzer. Sera from 243 prostate cancer and 208 negative biopsies patients have been taken into account. Sera were analyzed blinded for total PSA, free PSA and [-2] proPSA using Access(®) immunoassay method from Beckman Coulter. The Prostate Health Index (phi) was calculated using the formula phi=([-2] proPSA/fPSA)×sqrt (PSA). The median value of the phi index is significantly (P>0.0001) higher for patients with cancer (phi=65.8) compared to patients with negative biopsies (phi=40.6). At a given sensitivity, the phi index significantly increases the specificity of detection of prostate cancer compared to other markers. The phi index currently appears as the best predictor of prostate cancer for patients with a total PSA between 1.6 and 8 ng/mL according to the WHO standard. The improvement in specificity of the phi index over tPSA could reduce significantly the numbers of unnecessary biopsies. Whether this new biomarker could be an indicator of aggressive prostate cancer remains to be confirmed. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  15. TARP vaccination is associated with slowing in PSA velocity and decreasing tumor growth rates in patients with Stage D0 prostate cancer.

    PubMed

    Wood, Lauren V; Fojo, Antonio; Roberson, Brenda D; Hughes, Meghan S B; Dahut, William; Gulley, James L; Madan, Ravi A; Arlen, Philip M; Sabatino, Marianna; Stroncek, David F; Castiello, Luciano; Trepel, Jane B; Lee, Min-Jung; Parnes, Howard L; Steinberg, Seth M; Terabe, Masaki; Wilkerson, Julia; Pastan, Ira; Berzofsky, Jay A

    2016-08-01

    T-cell receptor alternate reading frame protein (TARP) is a 58-residue protein over-expressed in prostate and breast cancer. We investigated TARP peptide vaccination's impact on the rise in PSA (expressed as Slope Log(PSA) or PSA Doubling Time (PSADT)), validated tumor growth measures, and tumor growth rate in men with Stage D0 prostate cancer. HLA-A*0201 positive men were randomized to receive epitope-enhanced (29-37-9V) and wild-type (27-35) TARP peptides administered as a Montanide/GM-CSF peptide emulsion or as an autologous peptide-pulsed dendritic cell vaccine every 3 weeks for a total of five vaccinations with an optional 6th dose of vaccine at 36 weeks based on immune response or PSADT criteria with a booster dose of vaccine for all patients at 48 and 96 weeks. 41 patients enrolled with median on-study duration of 75 weeks at the time of this analysis. Seventy-two percent of patients reaching 24 weeks and 74% reaching 48 weeks had a decreased Slope Log(PSA) compared to their pre-vaccination baseline (p = 0.0012 and p = 0.0004 for comparison of overall changes in Slope Log(PSA), respectively). TARP vaccination also resulted in a 50% decrease in median tumor growth rate (g): pre-vaccine g = 0.0042/day, post-vaccine g = 0.0021/day (p = 0.003). 80% of subjects exhibited new vaccine-induced TARP-specific IFNγ ELISPOT responses but they did not correlate with decreases in Slope Log(PSA). Thus, vaccination with TARP peptides resulted in significant slowing in PSA velocity and reduction in tumor growth rate in a majority of patients with PSA biochemical recurrence.

  16. Very Early PSA Response to Abiraterone in mCRPC Patients: A Novel Prognostic Factor Predicting Overall Survival.

    PubMed

    Facchini, Gaetano; Caffo, Orazio; Ortega, Cinzia; D'Aniello, Carmine; Di Napoli, Marilena; Cecere, Sabrina C; Della Pepa, Chiara; Crispo, Anna; Maines, Francesca; Ruatta, Fiorella; Iovane, Gelsomina; Pisconti, Salvatore; Montella, Maurizio; Berretta, Massimiliano; Pignata, Sandro; Cavaliere, Carla

    2016-01-01

    Abiraterone Acetate (AA) is approved for the treatment of mCRPC after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated and for treatment of mCRPC progressed during or after docetaxel-based chemotherapy regimen. The aim of this study is to evaluate the role of early PSA decline for detection of therapy success or failure in mCRPC patients treated with AA in post chemotherapy setting. We retrospectively evaluated 87 patients with mCRPC treated with AA. Serum PSA levels were evaluated after 15, 90 days and then monthly. The PSA flare phenomenon was evaluated, according to a confirmation value at least 1 week apart. The primary endpoint was to demonstrate that an early PSA decline correlates with a longer progression free survival (PFS) and overall survival (OS). The secondary endpoind was to demonstrate a correlation between better outcome and demographic and clinical patient characteristics. We have collected data of 87 patients between Sep 2011 and Sep 2014. Early PSA response (≥50% from baseline at 15 days) was found in 56% evaluated patients and confirmed in 29 patients after 90 days. The median PFS was 5.5 months (4.6-6.5) and the median OS was 17.1 months (8.8-25.2). In early responders patients (PSA RR ≥ 50% at 15 days), we found a significant statistical advantage in terms of PFS at 1 year, HR 0.28, 95%CI 0.12-0.65, p = 0.003, and OS, HR 0.21 95% CI 0.06-0.72, p = 0.01. The results in PFS at 1 years and OS reached statistical significance also in the evaluation at 90 days. A significant proportion (78.6%) of patients achieved a rapid response in terms of PSA decline. Early PSA RR (≥50% at 15 days after start of AA) can provide clinically meaningful information and can be considered a surrogate of longer PFS and OS.

  17. Long-term prediction of prostate cancer diagnosis and death using PSA and obesity related anthropometrics at early middle age: data from the malmö preventive project.

    PubMed

    Assel, Melissa J; Gerdtsson, Axel; Thorek, Daniel L J; Carlsson, Sigrid V; Malm, Johan; Scardino, Peter T; Vickers, Andrew; Lilja, Hans; Ulmert, David

    2018-01-19

    To evaluate whether anthropometric parameters add to PSA measurements in middle-aged men for risk assessment of prostate cancer (PCa) diagnosis and death. After adjusting for PSA, both BMI and weight were significantly associated with an increased risk of PCa death with the odds of a death corresponding to a 10 kg/m2 or 10 kg increase being 1.58 (95% CI 1.10, 2.28; p = 0.013) and 1.14 (95% CI 1.02, 1.26; p = 0.016) times greater, respectively. AUCs did not meaningfully increase with the addition of weight or BMI to prediction models including PSA. In 1974 to 1986, 22,444 Swedish men aged 44 to 50 enrolled in Malmö Preventive Project, Sweden, and provided blood samples and anthropometric data. Rates of PSA screening in the cohort were very low. Documentation of PCa diagnosis and disease-specific death up to 2014 was retrieved through national registries. Among men with anthropometric measurements available at baseline, a total of 1692 men diagnosed with PCa were matched to 4190 controls, and 464 men who died of disease were matched to 1390 controls. Multivariable conditional logistic regression was used to determine whether diagnosis or death from PCa were associated with weight and body mass index (BMI) at adulthood after adjusting for PSA. Men with higher BMI and weight at early middle age have an increased risk of PCa diagnosis and death after adjusting for PSA. However, in a multi-variable numerical statistical model, BMI and weight do not importantly improve the predictive accuracy of PSA. Risk-stratification of screening should be based on PSA without reference to anthropometrics.

  18. Long-term prediction of prostate cancer diagnosis and death using PSA and obesity related anthropometrics at early middle age: data from the malmö preventive project

    PubMed Central

    Assel, Melissa J.; Gerdtsson, Axel; Thorek, Daniel L.J.; Carlsson, Sigrid V.; Malm, Johan; Scardino, Peter T.; Vickers, Andrew; Lilja, Hans; Ulmert, David

    2018-01-01

    Objectives To evaluate whether anthropometric parameters add to PSA measurements in middle-aged men for risk assessment of prostate cancer (PCa) diagnosis and death. Results After adjusting for PSA, both BMI and weight were significantly associated with an increased risk of PCa death with the odds of a death corresponding to a 10 kg/m2 or 10 kg increase being 1.58 (95% CI 1.10, 2.28; p = 0.013) and 1.14 (95% CI 1.02, 1.26; p = 0.016) times greater, respectively. AUCs did not meaningfully increase with the addition of weight or BMI to prediction models including PSA. Materials and Methods In 1974 to 1986, 22,444 Swedish men aged 44 to 50 enrolled in Malmö Preventive Project, Sweden, and provided blood samples and anthropometric data. Rates of PSA screening in the cohort were very low. Documentation of PCa diagnosis and disease-specific death up to 2014 was retrieved through national registries. Among men with anthropometric measurements available at baseline, a total of 1692 men diagnosed with PCa were matched to 4190 controls, and 464 men who died of disease were matched to 1390 controls. Multivariable conditional logistic regression was used to determine whether diagnosis or death from PCa were associated with weight and body mass index (BMI) at adulthood after adjusting for PSA. Conclusions Men with higher BMI and weight at early middle age have an increased risk of PCa diagnosis and death after adjusting for PSA. However, in a multi-variable numerical statistical model, BMI and weight do not importantly improve the predictive accuracy of PSA. Risk-stratification of screening should be based on PSA without reference to anthropometrics. PMID:29464033

  19. Does Early Reading Failure Decrease Children's Reading Motivation?

    ERIC Educational Resources Information Center

    Morgan, Paul L.; Fuchs, Douglas; Compton, Donald L.; Cordray, David S.; Fuchs, Lynn S.

    2008-01-01

    The authors used a pretest-posttest control group design with random assignment to evaluate whether early reading failure decreases children's motivation to practice reading. First, they investigated whether 60 first-grade children would report substantially different levels of interest in reading as a function of their relative success or failure…

  20. Does early reading failure decrease children's reading motivation?

    PubMed

    Morgan, Paul L; Fuchs, Douglas; Compton, Donald L; Cordray, David S; Fuchs, Lynn S

    2008-01-01

    The authors used a pretest-posttest control group design with random assignment to evaluate whether early reading failure decreases children's motivation to practice reading. First, they investigated whether 60 first-grade children would report substantially different levels of interest in reading as a function of their relative success or failure in learning to read. Second, they evaluated whether increasing the word reading ability of 15 at-risk children would lead to gains in their motivation to read. Multivariate analyses of variance suggest marked differences in both motivation and reading practice between skilled and unskilled readers. However, bolstering at-risk children's word reading ability did not yield evidence of a causal relationship between early reading failure and decreased motivation to engage in reading activities. Instead, hierarchical regression analyses indicate a covarying relationship among early reading failure, poor motivation, and avoidance of reading.

  1. Endosperm turgor pressure decreases during early Arabidopsis seed development.

    PubMed

    Beauzamy, Léna; Fourquin, Chloé; Dubrulle, Nelly; Boursiac, Yann; Boudaoud, Arezki; Ingram, Gwyneth

    2016-09-15

    In Arabidopsis, rapid expansion of the coenocytic endosperm after fertilisation has been proposed to drive early seed growth, which is in turn constrained by the seed coat. This hypothesis implies physical heterogeneity between the endosperm and seed coat compartments during early seed development, which to date has not been demonstrated. Here, we combine tissue indentation with modelling to show that the physical properties of the developing seed are consistent with the hypothesis that elevated endosperm-derived turgor pressure drives early seed expansion. We provide evidence that whole-seed turgor is generated by the endosperm at early developmental stages. Furthermore, we show that endosperm cellularisation and seed growth arrest are associated with a drop in endosperm turgor pressure. Finally, we demonstrate that this decrease is perturbed when the function of POLYCOMB REPRESSIVE COMPLEX 2 is lost, suggesting that turgor pressure changes could be a target of genomic imprinting. Our results indicate a developmental role for changes in endosperm turgor pressure in the Arabidopsis seed. © 2016. Published by The Company of Biologists Ltd.

  2. Early Choline Levels From 3-Tesla MR Spectroscopy After Exclusive Radiation Therapy in Patients With Clinically Localized Prostate Cancer are Predictive of Plasmatic Levels of PSA at 1 Year

    SciTech Connect

    Crehange, Gilles, E-mail: gcrehange@cgfl.fr; Maingon, Philippe; Gauthier, Melanie

    2011-11-15

    Purpose: To investigate the time course response of prostate metabolism to irradiation using magnetic resonance spectroscopy (MRS) at 3-month intervals and its impact on biochemical control. Methods and Materials: Between January 2008 and April 2010, 24 patients with localized prostate cancer were prospectively enrolled in the Evaluation of the Response to Irradiation with MR Spectroscopy (ERIS) trial. All the patients had been treated with intensity-modulated radiation therapy with or without long-term adjuvant hormonal therapy (LTHT) and underwent 3-T MRS and prostate-specific antigen (PSA) assays at baseline and every 3 months thereafter up to 12 months. Results: After radiation, the meanmore » normalized citrate level (citrate/water) decreased significantly over time, both in the peripheral zone (PZ) (p = 0.0034) and in the entire prostate (p = 0.0008), whereas no significant change was observed in mean normalized choline levels (choline/water) in the PZ (p = 0.84) and in the entire prostate (p = 0.95). At 6 months after radiation, the mean choline level was significantly lower in the PZ for patients with a PSA value of {<=}0.5 ng/mL at 12 months (4.9 {+-} 1.7 vs. 7.1 {+-} 1.5, p = 0.0378). Similar results were observed at 12 months in the PZ (6.2 {+-} 2.3 vs. 11.4 {+-} 4.1, p = 0.0117 for choline level and 3.4 {+-} 0.7 vs. 16.1 {+-} 6.1, p = 0.0054 for citrate level) and also in the entire prostate (6.2 {+-} 1.9 vs. 10.4 {+-} 3.2, p = 0.014 for choline level and 3.0 {+-} 0.8 vs. 13.3 {+-} 4.7, p = 0.0054 for citrate level). For patients receiving LTHT, there was no correlation between choline or citrate levels and PSA value, either at baseline or at follow-up. Conclusions: Low normalized choline in the PZ, 6 months after radiation, predicts which patients attained a PSA {<=}0.5 ng/mL at 1 year. Further analyses with longer follow-up times are warranted to determine whether or not these new biomarkers can conclusively predict the early radiation response and

  3. Prostate-specific antigen (PSA) blood test

    MedlinePlus

    ... very early. But there is debate over the value of the PSA test for detecting prostate cancer. No single answer fits all men. Before having the test, talk to your provider about the pros and cons of having a PSA test. Ask ...

  4. Clinical performance of serum [-2]proPSA derivatives, %p2PSA and PHI, in the detection and management of prostate cancer.

    PubMed

    Huang, Ya-Qiang; Sun, Tong; Zhong, Wei-De; Wu, Chin-Lee

    2014-01-01

    Prostate-specific antigen (PSA) has been widely used as a serum marker for prostate cancer (PCa) screening or progression monitoring, which dramatically increased rate of early detection while significantly reduced PCa-specific mortality. However, a number of limitations of PSA have been noticed. Low specificity of PSA may lead to overtreatment in men who presenting with a total PSA (tPSA) level of < 10 ng/mL. As a type of free PSA (fPSA), [-2]proPSA is differentially expressed in peripheral zone of prostate gland and found to be elevated in serum of men with PCa. Two p2PSA-based derivatives, prostate health index (PHI) and %p2PSA, which were defined as [(p2PSA/fPSA) × √ tPSA] and [(p2PSA/fPSA) × 100] respectively, have been suggested to be increased in PCa and can better distinguish PCa from benign prostatic diseases than tPSA or fPSA. We performed a systematic review of the available scientific evidences to evaluate the potentials of %p2PSA and PHI in clinical application. Mounting evidences suggested that both %p2PSA and PHI possess higher area under the ROC curve (AUC) and better specificity at a high sensitivity for PCa detection when compare with tPSA and %fPSA. It indicated that measurements of %p2PSA and PHI significantly improved the accuracy of PCa detection and diminished unnecessary biopsies. Furthermore, elevations of %p2PSA and PHI are related to more aggressive diseases. %p2PSA and PHI might be helpful in reducing overtreatment on indolent cases or assessing the progression of PCa in men who undergo active surveillance. Further studies are needed before being applied in routine clinical practice.

  5. Can PSA Reflex Algorithm be a valid alternative to other PSA-based prostate cancer screening strategies?

    PubMed

    Caldarelli, G; Troiano, G; Rosadini, D; Nante, N

    2017-01-01

    The available laboratory tests for the differential diagnosis of prostate cancer, are represented by the total PSA, the free PSA, and the free/total PSA ratio. In Italy most of doctors tend to request both total and free PSA for their patients even in cases where the total PSA doesn't justify the further request of free PSA, with a consequent growth of the costs for the National Health System. The aim of our study was to predict the saving in Euro (due to reagents) and reduction in free PSA tests, applying the "PSA Reflex" algorithm. We calculated the number of total PSA and free PSA exams performed in 2014 in the Hospital of Grosseto and, simulating the application of the "PSA Reflex" algorithm in the same year, we calculated the decrease in the number of free PSA requests and we tried to predict the Euro savings in reagents, obtained from this reduction. In 2014 in the Hospital of Grosseto 25,955 total PSA tests have been performed: 3,631 (14%) resulted greater than 10 ng / ml; 7,686 (29.6%) between 2 and 10 ng / ml; 14,638 (56.4%) lower than 2 ng / ml. The performed free PSA tests were 16904. Simulating the use of "PSA Reflex" algorithm, the free PSA tests would be performed only in cases with total PSA values between 2 and 10 ng / mL with a saving of 54.5% of free PSA exams and of 8,971 euros, only for reagents. Our study showed that the "PSA Reflex" algorithm is a valid alternative leading to a reduction of the costs. The estimated intralaboratory savings, due to the reagents, seem to be modest, however, they are followed by the additional savings due to the other diagnostic processes for prostate cancers.

  6. Prostate Specific Antigen (PSA) as Predicting Marker for Clinical Outcome and Evaluation of Early Toxicity Rate after High-Dose Rate Brachytherapy (HDR-BT) in Combination with Additional External Beam Radiation Therapy (EBRT) for High Risk Prostate Cancer.

    PubMed

    Ecke, Thorsten H; Huang-Tiel, Hui-Juan; Golka, Klaus; Selinski, Silvia; Geis, Berit Christine; Koswig, Stephan; Bathe, Katrin; Hallmann, Steffen; Gerullis, Holger

    2016-11-10

    High-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT) is a common treatment option for locally advanced prostate cancer (PCa). Seventy-nine male patients (median age 71 years, range 50 to 79) with high-risk PCa underwent HDR-BT following EBRT between December 2009 and January 2016 with a median follow-up of 21 months. HDR-BT was administered in two treatment sessions (one week interval) with 9 Gy per fraction using a planning system and the Ir192 treatment unit GammaMed Plus iX. EBRT was performed with CT-based 3D-conformal treatment planning with a total dose administration of 50.4 Gy with 1.8 Gy per fraction and five fractions per week. Follow-up for all patients was organized one, three, and five years after radiation therapy to evaluate early and late toxicity side effects, metastases, local recurrence, and prostate-specific antigen (PSA) value measured in ng/mL. The evaluated data included age, PSA at time of diagnosis, PSA density, BMI (body mass index), Gleason score, D'Amico risk classification for PCa, digital rectal examination (DRE), PSA value after one/three/five year(s) follow-up (FU), time of follow-up, TNM classification, prostate volume, and early toxicity rates. Early toxicity rates were 8.86% for gastrointestinal, and 6.33% for genitourinary side effects. Of all treated patients, 84.81% had no side effects. All reported complications in early toxicity were grade 1. PSA density at time of diagnosis ( p = 0.009), PSA on date of first HDR-BT ( p = 0.033), and PSA on date of first follow-up after one year ( p = 0.025) have statistical significance on a higher risk to get a local recurrence during follow-up. HDR-BT in combination with additional EBRT in the presented design for high-risk PCa results in high biochemical control rates with minimal side-effects. PSA is a negative predictive biomarker for local recurrence during follow-up. A longer follow-up is needed to assess long-term outcome and toxicities.

  7. [PSA interest and prostatitis: literature review].

    PubMed

    Bruyère, F; Amine Lakmichi, M

    2013-12-01

    Prostatitis is easily diagnosed but sometimes associated with PSA measurement. An increased PSA in an asymptomatic patient may be associated with antibiotic use to eliminate the inflammatory part and to confirm prostate biopsy. It seems interesting to confirm or infirm these attitudes with a systematic review of the literature We performed a literature review using the words [prostatitis], [acute prostatitis], [prostate specific antigen], [PSA], in the MEDLINE, Pubmed and AMBASE database searching for articles in French or English published in the past 20 years. PSA is not always increased during an acute prostatitis episode. An increased PSA in an asymptomatic man does not seem to be systematically correlated to prostate inflammation. Analyzing the studies, it seems inaccurate to measure PSA value during a febrile urinary infection episode in men. Systematic use of antibiotic to decrease PSA and not performing prostate biopsy is not relevant and may induce resistance to antibiotic and doesn't induce a reduction risk of having prostate biopsy. PSA is unnecessary in case of febrile urinary tract infection in men. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  8. Decreased serum vitamin D levels in early spontaneous pregnancy loss.

    PubMed

    Hou, W; Yan, X-T; Bai, C-M; Zhang, X-W; Hui, L-Y; Yu, X-W

    2016-09-01

    Effects of vitamin D deficiency in pregnancy have been associated with some adverse pregnancy outcomes. The objective of this study was to analyze the relationship between vitamin D deficiency in childbearing aged women and pregnancy loss (PL) in the first trimester. This is a cross-sectional study. Plasma was collected from 60 nulliparous women with singleton at 7-9 weeks of gestation (30 with viable gestation and 30 with PL) and 60 non-gravid childbearing aged women (30 with a successful pregnancy history, and 30 with one or more spontaneous first-trimester PL history). Quantitation of serum 25-hydroxyvitamin D (25(OH)D) and 25-hydroxyvitamin D-1 alpha hydroxylase (CYP27B1) was assayed. By pregnancy/non-gravid, normal pregnant women had higher 25(OH)D (49.32 μg/l) and CYP27B1 (82.00 pg/ml) than PL women (34.49 μg/l and 37.87 pg/ml, both P<0.01); the non-gravid women with a successful pregnancy history also had higher 25(OH)D (39.56 μg/l) and CYP27B1 (39.04 pg/ml) than women with PL history (12.30 μg/l and 12.35 pg/ml, both P<0.01). The 96.7% of non-gravid women with PL history and 43.3% of PL women had serum 25(OH)D concentrations below 30 μg/l. There was a strong association between low vitamin D levels and PL (odds ratio 1.71; 95% confidence interval: 1.2-2.4, P<0.001). The regression analyses showed that PL was significantly inversely correlated with 25(OH)D (P<0.01) and CYP27B1 levels (P<0.01). Vitamin D deficiency associated with PL in the first trimester of pregnancy. Decreased serum vitamin D levels among childbearing aged women with the failed clinical pregnancies history may predispose to increased risk for PL.

  9. Up regulation of the steroid hormone synthesis regulator HSD3B2 is linked to early PSA recurrence in prostate cancer.

    PubMed

    Neubauer, Emily; Latif, Morwari; Krause, Jenny; Heumann, Asmus; Armbrust, Moritz; Luehr, Clara; Fraune, Christoph; Hube-Magg, Claudia; Kluth, Martina; Möller-Koop, Christina; Sauter, Guido; Simon, Ronald; Beyer, Burkhard; Pompe, Raisa S; Thederan, Imke; Schlomm, Thorsten; Büscheck, Franziska

    2018-05-24

    HSD3B2 plays a crucial role in steroid hormone biosynthesis and is thus of particular interest in hormone dependent tumors such as prostate cancer. To clarify the clinical relevance of HSD3B2 expression in prostate cancer, we analyzed HSD3B2 protein expression by immunohistochemistry on our preexisting tissue microarray with 12.247 annotated cancers. Compared with normal tissue cytoplasmic HSD3B2 staining was stronger in prostate cancers. In 9371 interpretable cancers, HSD3B2 expression was found in 95.5% of cancers and was considered weak in 29.9%, moderate in 40.7% and strong in 24.9%. HSD3B2 up regulation was linked to advanced pathological tumor stage (pT), high Gleason grade, elevated preoperative PSA levels (p < 0.0001 each), lymph node metastasis (p = 0.0019), accelerated cell proliferation (p < 0.0001), androgen receptor (AR) expression (p < 0.0001), and early biochemical recurrence (p < 0.0001). HSD3B2 up regulation was only marginally more frequent in ERG positive (98%) than in ERG negative cancers (94%; p < 0.0001) and was strongly linked to deletions of 5q and 6q (p < 0.0001 each). Multivariate analyses showed that the prognostic impact of HSD3B2 expression was independent of established preoperative, but not of postoperative prognostic parameters. In summary, the results of our study demonstrate that HSD3B2 is strongly up regulated in a fraction of prostate cancers that are characterized by increased AR signaling, adverse tumor phenotype and early biochemical recurrence. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. The effect of the USPSTF PSA screening recommendation on prostate cancer incidence patterns in the USA

    PubMed Central

    Fleshner, Katherine; Carlsson, Sigrid V.; Roobol, Monique J.

    2017-01-01

    Guidelines conflict regarding recommendations for prostate-specific antigen (PSA) screening for early detection of prostate cancer. The United States Preventive Services Task Force (USPSTF) assigned a grade of D (recommending against screening) for men 75 and older in 2008 and for men of all ages in 2012. We reviewed temporal trends in rates of screening before and after the 2012 recommendation based on a literature search for studies published between 2011/01/01–2016/10/03 on PSA utilization patterns, changes in prostate cancer incidence and biopsy patterns, and how the recommendation has shaped physician and patient attitudes about PSA screening and subsequent ordering of other screening tests. Rates of PSA screening decreased by 3–10 percentage points among all age groups and within most U.S. geographic regions. Rates of prostate biopsy and prostate cancer incidence have declined in unison, with a notable shift towards higher grade, stage and risk upon detection. Despite the recommendation, some physicians reported ongoing willingness to screen appropriately selected men, and men largely reported intending to continue to ask for the PSA test. In the coming years, we expect to have a better picture of whether these decreased rates of screening will impact prostate cancer metastasis and mortality. PMID:27995937

  11. Mutational analysis of photosystem I polypeptides in the cyanobacterium Synechocystis sp. PCC 6803. Targeted inactivation of psaI reveals the function of psaI in the structural organization of psaL

    NASA Technical Reports Server (NTRS)

    Xu, Q.; Hoppe, D.; Chitnis, V. P.; Odom, W. R.; Guikema, J. A.; Chitnis, P. R.; Spooner, B. S. (Principal Investigator)

    1995-01-01

    We cloned, characterized, and inactivated the psaI gene encoding a 4-kDa hydrophobic subunit of photosystem I from the cyanobacterium Synechocystis sp. PCC 6803. The psaI gene is located 90 base pairs downstream from psaL, and is transcribed on 0.94- and 0.32-kilobase transcripts. To identify the function of PsaI, we generated a cyanobacterial strain in which psaI has been interrupted by a gene for chloramphenicol resistance. The wild-type and the mutant cells showed comparable rates of photoautotrophic growth at 25 degrees C. However, the mutant cells grew slower and contained less chlorophyll than the wild-type cells, when grown at 40 degrees C. The PsaI-less membranes from cells grown at either temperature showed a small decrease in NADP+ photoreduction rate when compared to the wild-type membranes. Inactivation of psaI led to an 80% decrease in the PsaL level in the photosynthetic membranes and to a complete loss of PsaL in the purified photosystem I preparations, but had little effect on the accumulation of other photosystem I subunits. Upon solubilization with nonionic detergents, photosystem I trimers could be obtained from the wild-type, but not from the PsaI-less membranes. The PsaI-less photosystem I monomers did not contain detectable levels of PsaL. Therefore, a structural interaction between PsaL and PsaI may stabilize the association of PsaL with the photosystem I core. PsaL in the wild-type and PsaI-less membranes showed equal resistance to removal by chaotropic agents. However, PsaL in the PsaI-less strain exhibited an increased susceptibility to proteolysis. From these data, we conclude that PsaI has a crucial role in aiding normal structural organization of PsaL within the photosystem I complex and the absence of PsaI alters PsaL organization, leading to a small, but physiologically significant, defect in photosystem I function.

  12. Time to PSA rise differentiates the PSA bounce after HDR and LDR brachytherapy of prostate cancer.

    PubMed

    Burchardt, Wojciech; Skowronek, Janusz

    2018-02-01

    To investigate the differences in prostate-specific antigen (PSA) bounce (PB) after high-dose-rate (HDR-BT) or low-dose-rate (LDR-BT) brachytherapy alone in prostate cancer patients. Ninety-four patients with localized prostate cancer (T1-T2cN0), age ranged 50-81 years, were treated with brachytherapy alone between 2008 and 2010. Patients were diagnosed with adenocarcinoma, Gleason score ≤ 7. The LDR-BT total dose was 144-145 Gy, in HDR-BT - 3 fractions of 10.5 or 15 Gy. The initial PSA level (iPSA) was assessed before treatment, then PSA was rated every 3 months over the first 2 years, and every 6 months during the next 3 years. Median follow-up was 3.0 years. Mean iPSA was 7.8 ng/ml. In 58 cases, PSA decreased gradually without PB or biochemical failure (BF). In 24% of patients, PB was observed. In 23 cases (24%), PB was observed using 0.2 ng/ml definition; in 10 cases (11%), BF was diagnosed using nadir + 2 ng/ml definition. The HDR-BT and LDR-BT techniques were not associated with higher level of PB (26 vs. 22%, p = 0.497). Time to the first PSA rise finished with PB was significantly shorter after HDR-BT then after LDR-BT (median, 10.5 vs. 18.0 months) during follow-up. Predictors for PB were observed only after HDR-BT. Androgen deprivation therapy (ADT) and higher Gleason score decreased the risk of PB (HR = 0.11, p = 0.03; HR = 0.51, p = 0.01). The higher PSA nadir and longer time to PSA nadir increased the risk of PB (HR 3.46, p = 0.02; HR 1.04, p = 0.04). There was no predictors for PB after LDR-BT. HDR-BT and LDR-BT for low and intermediate risk prostate cancer had similar PB rate. The PB occurred earlier after HDR-BT than after LDR-BT. ADT and higher Gleason score decreased, and higher PSA nadir and longer time to PSA nadir increased the risk of PB after HDR-BT.

  13. Time to PSA rise differentiates the PSA bounce after HDR and LDR brachytherapy of prostate cancer

    PubMed Central

    Skowronek, Janusz

    2018-01-01

    Purpose To investigate the differences in prostate-specific antigen (PSA) bounce (PB) after high-dose-rate (HDR-BT) or low-dose-rate (LDR-BT) brachytherapy alone in prostate cancer patients. Materials and methods Ninety-four patients with localized prostate cancer (T1-T2cN0), age ranged 50-81 years, were treated with brachytherapy alone between 2008 and 2010. Patients were diagnosed with adenocarcinoma, Gleason score ≤ 7. The LDR-BT total dose was 144-145 Gy, in HDR-BT – 3 fractions of 10.5 or 15 Gy. The initial PSA level (iPSA) was assessed before treatment, then PSA was rated every 3 months over the first 2 years, and every 6 months during the next 3 years. Median follow-up was 3.0 years. Results Mean iPSA was 7.8 ng/ml. In 58 cases, PSA decreased gradually without PB or biochemical failure (BF). In 24% of patients, PB was observed. In 23 cases (24%), PB was observed using 0.2 ng/ml definition; in 10 cases (11%), BF was diagnosed using nadir + 2 ng/ml definition. The HDR-BT and LDR-BT techniques were not associated with higher level of PB (26 vs. 22%, p = 0.497). Time to the first PSA rise finished with PB was significantly shorter after HDR-BT then after LDR-BT (median, 10.5 vs. 18.0 months) during follow-up. Predictors for PB were observed only after HDR-BT. Androgen deprivation therapy (ADT) and higher Gleason score decreased the risk of PB (HR = 0.11, p = 0.03; HR = 0.51, p = 0.01). The higher PSA nadir and longer time to PSA nadir increased the risk of PB (HR 3.46, p = 0.02; HR 1.04, p = 0.04). There was no predictors for PB after LDR-BT. Conclusions HDR-BT and LDR-BT for low and intermediate risk prostate cancer had similar PB rate. The PB occurred earlier after HDR-BT than after LDR-BT. ADT and higher Gleason score decreased, and higher PSA nadir and longer time to PSA nadir increased the risk of PB after HDR-BT. PMID:29619050

  14. PHI in the Early Detection of Prostate Cancer.

    PubMed

    Fuchsova, Radka; Topolcan, Ondrej; Windrichova, Jindra; Hora, Milan; Dolejsova, Olga; Pecen, Ladislav; Kasik, Petr; Novak, Jaroslav; Casova, Miroslava; Smejkal, Jiri

    2015-09-01

    To evaluate changes in the serum levels of prostate specific antigen (PSA), %free PSA and -2proPSA biomarkers, and prostate health index (PHI) in the diagnostic algorithm of early prostate cancer. The Immunoanalytical Laboratory of the University Hospital in Pilsen examined sera from 263 patients being treated at the Hospital's Urology Department with suspected prostate cancer who had undergone biopsies and were divided into a benign and malignant group. The monitored biomarkers were measured using chemiluminescence. All statistical analyses were calculated using the SAS software. We found statistically significantly increased levels of -2proPSA, PHI and PSA and decreased levels of %freePSA in patients diagnosed with prostate cancer by prostate biopsy vs. patients with benign prostatic hypertrophy (median values: -2proPSA: 16 vs. 21 ng/l, PHI: 35 vs. 62, total PSA: 7.2 vs. 7.7 μg/l and %free PSA: 16.7 vs. 11.7%). Receiver operating characteristic curves showed the best performance for PHI compared to other markers. The assessment of -2proPSA and the calculation of PHI appear to be of great benefit for a more accurate differential diagnosis of benign hyperplasia and prostate cancer. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  15. Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects

    SciTech Connect

    Veen, Sonja J. van der; Faber, Hette; Ghobadi, Ghazaleh

    2016-01-01

    Purpose: Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the dose-limiting toxicity of a treatment. Recently, in our rat model, we found that early radiation-induced lung dysfunction (RILD) was closely related to irradiated volume dependent vascular remodeling besides inflammation. The exact relationship between early and late RILD is still unknown. Therefore, in this preclinical study we investigated the dose-volume relationship of late RILD, assessed its dependence on early and late pathologies and studied if decreasing irradiated volume changed themore » dose-limiting toxicity. Methods and Materials: A volume of 25%, 32%, 50%, 63%, 88%, or 100% of the rat lung was irradiated using protons. Until 26 weeks after irradiation, respiratory rates were measured. Macrovascular remodeling, pulmonary inflammation, and fibrosis were assessed at 26 weeks after irradiation. For all endpoints dose-volume response curves were made. These results were compared to our previously published early lung effects. Results: Early vascular remodeling and inflammation correlated significantly with early RILD. Late RILD correlated with inflammation and fibrosis, but not with vascular remodeling. In contrast to the early effects, late vascular remodeling, inflammation and fibrosis showed a primarily dose but not volume dependence. Comparison of respiratory rate increases early and late after irradiation for the different dose-distributions indicated that with decreasing irradiated volumes, the dose-limiting toxicity changed from early to late RILD. Conclusions: In our rat model, different pathologies underlie early and late RILD with different dose-volume dependencies. Consequently, the dose-limiting toxicity changed from early to late dysfunction when the irradiated volume was reduced. In patients, early and

  16. The role of dexamethasone in decreasing early recurrence of acute intussusception in children: A retrospective study.

    PubMed

    Efrati, Yigal; Klin, Baruch; Kozer, Eran; Abu-Kishk, Ibrahim

    2017-07-01

    Early recurrent intussusception (RI) is a concern after a successful pneumatic reduction. Steroids have been suggested as a treatment that decreases early RI. The purpose of this study was to examine the role of dexamethasone in decreasing early RI. A retrospective review of 174 pediatric patients that underwent successful pneumatic reduction was conducted. Two groups were identified: group 1 that received intravenous dexamethasone (0.5mg/kg/dose) on diagnosis or immediately after the reduction maneuver, and group 2 that were not given dexamethasone. There were 113 boys and 61 girls ranging in age from 2 to 36months. There were no statistical differences between the groups except for younger age in the dexamethasone group (P=0.03). There was no significant difference (p=0.08) in the rate of early RI between the non-steroid group (5.4%, 4/74) and the steroid group 14% (14/100). Mean admission length was 30h. The majority of RIs occurred in the first 8h of admission. We found that premedication of children with idiopathic intussusception with dexamethasone did not decrease early RI. Level III retrospective comparative study. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Time from first detectable PSA following radical prostatectomy to biochemical recurrence: A competing risk analysis

    PubMed Central

    de Boo, Leonora; Pintilie, Melania; Yip, Paul; Baniel, Jack; Fleshner, Neil; Margel, David

    2015-01-01

    Introduction: In this study, we estimated the time from first detectable prostate-specific antigen (PSA) following radical prostatectomy (RP) to commonly used definitions of biochemical recurrence (BCR). We also identified the predictors of time to BCR. Methods: We identified subjects who underwent a RP and had an undetectable PSA after surgery followed by at least 1 detectable PSA between 2000 and 2011. The primary outcome was time to BCR (PSA ≥0.2 and successive PSA ≥0.2) and prediction of the rate of PSA rise. Outcomes were calculated using a competing risk analysis, with univariable and multivariable Fine and Grey models. We employed a mixed effect model to test clinical predictors that are associated with the rate of PSA rise. Results: The cohort included 376 patients. The median follow-up from surgery was 60.5 months (interquartile range [IQR] 40.8–91.5) and from detectable PSA was 18 months (IQR 11–32). Only 45.74% (n = 172) had PSA values ≥0.2 ng/mL, while 15.16% (n = 57) reached the PSA level of ≥0.4 ng/mL and rising. On multivariable analysis, the values of the first detectable PSA and pathologic Gleason grade 8 or higher were consistently independent predictors of time to BCR. In the mixed effect model rate, the PSA rise was associated with time from surgery to first detectable PSA, Gleason score, and prostate volume. The main limitation of this study is the large proportion of patients that received treatment without reaching BCR. It is plausible that shorter estimated median times would occur at a centre that does not use salvage therapy at such an early state. Conclusion: The time from first detectable PSA to BCR may be lengthy. Our analyses of the predictors of the rate of PSA rise can help determine a personalized approach for patients with a detectable PSA after surgery. PMID:25624961

  18. Time from first detectable PSA following radical prostatectomy to biochemical recurrence: A competing risk analysis.

    PubMed

    de Boo, Leonora; Pintilie, Melania; Yip, Paul; Baniel, Jack; Fleshner, Neil; Margel, David

    2015-01-01

    In this study, we estimated the time from first detectable prostate-specific antigen (PSA) following radical prostatectomy (RP) to commonly used definitions of biochemical recurrence (BCR). We also identified the predictors of time to BCR. We identified subjects who underwent a RP and had an undetectable PSA after surgery followed by at least 1 detectable PSA between 2000 and 2011. The primary outcome was time to BCR (PSA ≥0.2 and successive PSA ≥0.2) and prediction of the rate of PSA rise. Outcomes were calculated using a competing risk analysis, with univariable and multivariable Fine and Grey models. We employed a mixed effect model to test clinical predictors that are associated with the rate of PSA rise. The cohort included 376 patients. The median follow-up from surgery was 60.5 months (interquartile range [IQR] 40.8-91.5) and from detectable PSA was 18 months (IQR 11-32). Only 45.74% (n = 172) had PSA values ≥0.2 ng/mL, while 15.16% (n = 57) reached the PSA level of ≥0.4 ng/mL and rising. On multivariable analysis, the values of the first detectable PSA and pathologic Gleason grade 8 or higher were consistently independent predictors of time to BCR. In the mixed effect model rate, the PSA rise was associated with time from surgery to first detectable PSA, Gleason score, and prostate volume. The main limitation of this study is the large proportion of patients that received treatment without reaching BCR. It is plausible that shorter estimated median times would occur at a centre that does not use salvage therapy at such an early state. The time from first detectable PSA to BCR may be lengthy. Our analyses of the predictors of the rate of PSA rise can help determine a personalized approach for patients with a detectable PSA after surgery.

  19. Elevated pretransplantation soluble CD30 is associated with decreased early allograft function after human lung transplantation.

    PubMed

    Shah, Ashish S; Leffell, M Sue; Lucas, Donna; Zachary, Andrea A

    2009-02-01

    Early allograft function after lung transplantation is variable. Clinical criteria have limited predictive value for early graft function. Recipient immunologic state before LTx may affect early lung function. We investigated the association between pretransplantation soluble CD30 (sCD30), a marker of Th2-type T-cell activation, and early clinical parameters of allograft function. Between September 2002 and January 2007, a total of 80 transplantations were performed at Johns Hopkins Hospital. Of the patients, 43 had a pretransplantation sCD30 level determined. Pre- and postoperative patient variables were collected, and patients were stratified into two groups: sCD30 <20 (low sCD30) and >20 (high sCD30). High sCD30 (n = 26) and low sCD30 (n = 17) groups were similar in age, gender, and ischemia time. In the high sCD30 group, a higher percentage of patients had pulmonary fibrosis and a lower percentage had emphysema. Oxygenation at 48 hours was significantly worse in the high sCD30 group as compared with the low sCD30 (p = 0.003). Moreover, prolonged intubation and 90-day mortality were greater in the high sCD30 group. This represents the first report of the use of sCD30 as a marker for early allograft function in human lung transplanation. Increased pretransplantation recipient sCD30 appears to be associated with decreased early post-transplantation gas exchange, prolonged intubation, and early mortality.

  20. Study of Serum Total PSA and Free PSA as an Oncological Marker in Breast Tumour.

    PubMed

    Jahir, Elteza Tahjiba; Devi, Runi; Borthakur, Bibhuti Bhushan

    2017-03-01

    Breast Cancer (BC) cases are rising alarmingly all over the world and India is not an exception. This rising trend is due to an increased age at first child birth, decreased breast feeding, and the changing lifestyle mostly in urban India. With the advent of more sensitive methodologies and research works in this field, it has been suggested that Prostate Specific Antigen (PSA) plays an important role in the pathogenesis of breast cancer besides other established tumour markers. To study the molecular forms of PSA-total and free PSA in benign and malignant tumours and to analyse their association with the tumour burden. The present study was conducted in collaboration with Gauhati Medical College and Hospital and Dr B Borooah Cancer Institute, Guwahati, Assam, India. Women in the age group of 18-65 years with recently diagnosed tumour (benign/malignant) in the breast were included in the study. Women taking Oral Contraceptive Pill (OCP), hormone replacement therapy, with past/present history of gynaecological/other malignancy and chronic endocrine disease like diabetes, thyroid disorders were excluded. The case group comprised of 50 female subjects with newly diagnosed Benign Breast Disease (BBD) and 50 subjects with BC, while 50 age matched healthy females without any signs and symptoms of breast discomfort were included in the control group. Laboratory tests done were Serum Total PSA (TPSA), Free PSA (FPSA), Fasting Blood Glucose (FBS), serum urea, serum creatinine and fasting lipid profile. TPSA and FPSA was measured again in both the test groups after 10-14 days of surgery/therapy. A fall in postoperative value of total and free PSA in BC case group was noticed. In Grade I tumours the mean value of total PSA (1.813 ng/ml) and free PSA (1.149 ng/ml) were higher than those with Grade III tumours (TPSA-1.07 ng/ml and FPSA-1.002 ng/ml). Mean value of Fasting Blood Sugar (FBG), total cholesterol and Low Density Lipoprotein (LDL) in BC case group was higher than the

  1. Decrease in Prostate Cancer Testing Following the US Preventive Services Task Force (USPSTF) Recommendations.

    PubMed

    Li, Jun; Berkowitz, Zahava; Hall, Ingrid J

    2015-01-01

    To assess changes of prostate-specific antigen (PSA) testing following recent US Preventive Services Task Force (USPSTF) prostate cancer screening recommendations using 2005 to 2013 National Health Interview Survey data. We calculated the percentage of PSA testing among men ≥40 years by age group and age-adjusted race for each survey year. Differences between years were assessed with linear contrasts after combining all years' data. The overall percentage of PSA testing was highest in 2008 and decreased significantly in 2013. Compared with 2008, each age group had significantly lower screening percentages in 2013, especially men ≥75 years old (-14.0% points; P < .001). Both men aged 50 to 74 and men aged ≥75 had significantly lower percentages in 2013 than in 2010. For white and black men, the PSA testing percentages were highest in 2008 and decreased significantly in 2013. Only white men had a significantly lower percentage in 2013 than in 2010. Significant declines in PSA testing from 2008 to 2013 in men ≥75 years old may reflect the impact of the 2008 USPSTF recommendations. While the cause of the decreases in PSA testing between 2010 and 2013 among men aged 50 to 74 years old and white men is unknown, the decreases may suggest the early effects of the 2012 recommendations. © Copyright 2015 by the American Board of Family Medicine.

  2. Ultra-sensitive PSA Following Prostatectomy Reliably Identifies Patients Requiring Post-Op Radiotherapy

    PubMed Central

    Kang, Jung Julie; Reiter, Robert; Steinberg, Michael; King, Christopher R.

    2015-01-01

    PURPOSE Integrating ultra-sensitive PSA (uPSA) into surveillance of high-risk patients following radical prostatectomy (RP) potentially optimizes management by correctly identifying actual recurrences, promoting an early salvage strategy and minimizing overtreatment. The power of uPSA following surgery to identify eventual biochemical failures is tested. PATIENTS AND METHODS From 1991–2013, 247 high-risk patients with a median follow-up was 44 months after RP were identified (extraprostatic extension and/or positive margin). Surgical technique, initial PSA (iPSA), pathology and post-op PSA were analyzed. The uPSA assay threshold was 0.01 ng/mL. Conventional biochemical relapse (cBCR) was defined as PSA ≥0.2 ng/mL. Kaplan Meier and Cox multivariate analyses (MVA) compared uPSA recurrence vs. cBCR rates. RESULTS Sensitivity analysis identified uPSA ≥0.03 as the optimal threshold identifying recurrence. First post-op uPSA ≥0.03, Gleason grade, T-stage, iPSA, and margin status predicted cBCR. On MVA, only first post-op uPSA ≥0.03, Gleason grade, and T-stage independently predicted cBCR. First post-op uPSA ≥0.03 conferred the highest risk (HR 8.5, p<0.0001) and discerned cBCR with greater sensitivity than undetectable first conventional PSA (70% vs. 46%). Any post-op PSA ≥0.03 captured all failures missed by first post-op value (100% sensitivity) with accuracy (96% specificity). Defining failure at uPSA ≥0.03 yielded a median lead-time advantage of 18 months (mean 24 months) over the conventional PSA ≥0.2 definition. CONCLUSION uPSA ≥0.03 is an independent factor, identifies BCR more accurately than any traditional risk factors, and confers a significant lead-time advantage. uPSA enables critical decisions regarding timing and indication for post-op RT among high-risk patients following RP. PMID:25463990

  3. In utero and early childhood exposure to arsenic decreases lung function in children

    PubMed Central

    Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R. Clark; Gandolfi, A. Jay; Gonzalez-De Alba, Cesar

    2016-01-01

    Background The lung is a target organ for adverse health outcomes following exposure to arsenic. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to arsenic through drinking water, however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of arsenic and its metabolites with lung function in children exposed in utero and in early childhood to high arsenic levels through drinking water. Methods A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic arsenic. Lung function was assessed by spirometry. Results Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 μg/L. The mean urinary arsenic level registered in the studied subjects was 141.2 μg/L and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percent of inorganic arsenic. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Conclusion Exposure to arsenic through drinking water during in utero and early life was associated with a decrease in FVC and with a restrictive spirometric pattern in the children evaluated. PMID:25131850

  4. In utero and early childhood exposure to arsenic decreases lung function in children.

    PubMed

    Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R Clark; Gandolfi, A Jay; Gonzalez-De Alba, Cesar

    2015-04-01

    The lung is a target organ for adverse health outcomes following exposure to As. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to As through drinking water; however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of As and its metabolites with lung function in children exposed in utero and in early childhood to high As levels through drinking water. A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic As. Lung function was assessed by spirometry. Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 µg l⁻¹. The mean urinary As level registered in the studied subjects was 141.2 µg l⁻¹ and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percentage of inorganic As. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Exposure to As through drinking water during in utero and early life was associated with a decrease in forced vital capacity and with a restrictive spirometric pattern in the children evaluated. Copyright © 2014 John Wiley & Sons, Ltd.

  5. Variability of assay methods for total and free PSA after WHO standardization.

    PubMed

    Foj, L; Filella, X; Alcover, J; Augé, J M; Escudero, J M; Molina, R

    2014-03-01

    The variability of total PSA (tPSA) and free PSA (fPSA) results among commercial assays has been suggested to be decreased by calibration to World Health Organization (WHO) reference materials. To characterize the current situation, it is necessary to know its impact in the critical cutoffs used in clinical practice. In the present study, we tested 167 samples with tPSA concentrations of 0 to 20 μg/L using seven PSA and six fPSA commercial assays, including Access, ARCHITECT i2000, ADVIA Centaur XP, IMMULITE 2000, Elecsys, and Lumipulse G1200, in which we only measured tPSA. tPSA and fPSA were measured in Access using the Hybritech and WHO calibrators. Passing-Bablok analysis was performed for PSA, and percentage of fPSA with the Hybritech-calibrated access comparison assay. For tPSA, relative differences were more than 10 % at 0.2 μg/L for ARCHITECT i2000, and at a critical concentration of 3, 4, and 10 μg/L, the relative difference was exceeded by ADVIA Centaur XP and WHO-calibrated Access. For percent fPSA, at a critical concentration of 10 %, the 10 % relative difference limit was exceeded by IMMULITE 2000 assay. At a critical concentration of 20 and 25 %, ADVIA Centaur XP, ARCHITECT i2000, and IMMULITE 2000 assays exceeded the 10 % relative difference limit. We have shown significant discordances between assays included in this study despite advances in standardization conducted in the last years. Further harmonization efforts are required in order to obtain a complete clinical concordance.

  6. Brain glutathione reductase induction increases early survival and decreases lipofuscin accumulation in aging frogs.

    PubMed

    López-Torres, M; Pérez-Campo, R; Fernandez, A; Barba, C; Barja de Quiroga, G

    1993-02-01

    Brain catalase was continuously depleted throughout the life span starting with a large population of initially young and old frogs. Free radical-related parameters were measured in the brain tissue once per year after 2.5, 14.5, and 26.5 months of experimentation. Brain lipofuscin accumulation was observed after 14.5 and 26.5 months, and survival was continuously followed during 33 months. The age of the animal did not decrease endogenous antioxidants nor increase tissue peroxidation either in cross-sectional or longitudinal comparisons. Continuous catalase depletion similarly affected young and old animals, inducing glutathione reductase, tending to decrease oxidized glutathione/reduced glutathione (GSSG/GSH) ratio, decreasing lipofuscin accumulation in the brain, and increasing survival from 46% to 91% after 14.5 months. At 26.5 months of experimentation the loss of the glutathione reductase induction in catalase-depleted animals was accompanied by the presence of higher lipofuscin deposits than in controls and was followed by a great increase in mortality rate. Even though the maximal life span (7 years) was the same in the control and treated animals which were already old (4.2 years) at the beginning of the experiment, the treated animals showed a strong reduction in the rates of early death. It is proposed that the maintenance of a high antioxidant/prooxidant balance in the vertebrate brain greatly increases the probability of the individual to reach the final segments of its species-specific life span.

  7. Early antiretroviral therapy and potent second-line drugs could decrease HIV incidence of drug resistance.

    PubMed

    Shen, Mingwang; Xiao, Yanni; Rong, Libin; Meyers, Lauren Ancel; Bellan, Steven E

    2017-06-28

    Early initiation of antiretroviral therapy (ART) reduces the risk of drug-sensitive HIV transmission but may increase the transmission of drug-resistant HIV. We used a mathematical model to estimate the long-term population-level benefits of ART and determine the scenarios under which earlier ART (treatment at 1 year post-infection, on average) could decrease simultaneously both total and drug-resistant HIV incidence (new infections). We constructed an infection-age-structured mathematical model that tracked the transmission rates over the course of infection and modelled the patients' life expectancy as a function of ART initiation timing. We fitted this model to the annual AIDS incidence and death data directly, and to resistance data and demographic data indirectly among men who have sex with men (MSM) in San Francisco. Using counterfactual scenarios, we assessed the impact on total and drug-resistant HIV incidence of ART initiation timing, frequency of acquired drug resistance, and second-line drug effectiveness (defined as the combination of resistance monitoring, biomedical drug efficacy and adherence). Earlier ART initiation could decrease the number of both total and drug-resistant HIV incidence when second-line drug effectiveness is sufficiently high (greater than 80%), but increase the proportion of new infections that are drug resistant. Thus, resistance may paradoxically appear to be increasing while actually decreasing. © 2017 The Author(s).

  8. Early intravenous ibuprofen decreases narcotic requirement and length of stay after traumatic rib fracture.

    PubMed

    Bayouth, Lilly; Safcsak, Karen; Cheatham, Michael L; Smith, Chadwick P; Birrer, Kara L; Promes, John T

    2013-11-01

    Pain control after traumatic rib fracture is essential to avoid respiratory complications and prolonged hospitalization. Narcotics are commonly used, but adjunctive medications such as nonsteroidal anti-inflammatory drugs may be beneficial. Twenty-one patients with traumatic rib fractures treated with both narcotics and intravenous ibuprofen (IVIb) (Treatment) were retrospectively compared with 21 age- and rib fracture-matched patients who received narcotics alone (Control). Pain medication requirements over the first 7 hospital days were evaluated. Mean daily IVIb dose was 2070 ± 880 mg. Daily intravenous morphine-equivalent requirement was 19 ± 16 vs 32 ± 24 mg (P < 0.0001). Daily narcotic requirement was significantly decreased in the Treatment group on Days 3 through 7 (P < 0.05). Total weekly narcotic requirement was significantly less among Treatment patients (P = 0.004). Highest and lowest daily pain scores were lower in the Treatment group (P < 0.05). Hospital length of stay was 4.4 ± 3.4 versus 5.4 ± 2.9 days (P = 0.32). There were no significant complications associated with IVIb therapy. Early IVIb therapy in patients with traumatic rib fractures significantly decreases narcotic requirement and results in clinically significant decreases in hospital length of stay. IVIb therapy should be initiated in patients with traumatic rib fractures to improve patient comfort and reduce narcotic requirement.

  9. Does contact by a family nurse practitioner decrease early school absence?

    PubMed

    Kerr, Jill; Price, Marva; Kotch, Jonathan; Willis, Stephanie; Fisher, Michael; Silva, Susan

    2012-02-01

    Chronic early school absence (preschool through third grade) is associated with school failure. The presence of school nurses may lead to fewer absences, and nurse practitioners in school-based health centers (SBHCs) can facilitate a healthier population resulting in improved attendance. Efforts to get students back to school are unexplored in nursing literature. This article describes a nursing intervention to decrease early school absence in two elementary schools K-3 (N = 449) and a Head Start program (N = 130). The Head Start Family Nurse Practitioner (FNP) contacted families of chronically and excessively absent students by telephone, clinic visit at school, or home visit. The aggregate percentage attendance was evaluated by grades (preschool to third grade), schools (Head Start, Elementary Schools 1 and 2), and grades and schools and compared with publicly available school district aggregate data. There were statistically significant increases in attendance from Year 1 to Year 2 at p < .05 at the elementary level but not at the Head Start level. Student demographics, types of contacts, absence reasons (including sick child), and medical diagnoses are described.

  10. Preoperative Gabapentin Decreases Anxiety and Improves Early Functional Recovery From Knee Surgery

    PubMed Central

    Ménigaux, Christophe; Adam, Frédéric; Guignard, Bruno; Sessler, Daniel I.; Chauvin, Marcel

    2005-01-01

    Gabapentin has antihyperalgesic and anxiolytic properties. We thus tested the hypothesis that premedication with gabapentin would decrease preoperative anxiety and improve postoperative analgesia and early postoperative knee mobilization in patients undergoing arthroscopic anterior cruciate ligament repair under general anesthesia. Forty patients were randomly assigned to receive 1200 mg oral gabapentin or placebo 1-2 h before surgery; anesthesia was standardized. Patients received morphine, 0.1 mg/kg, 30 min before the end of surgery and postoperatively via a patient-controlled pump. Pain scores and morphine consumption were recorded over 48 hours. Degrees of active and passive knee flexion and extension were recorded during physiotherapy on days 1 and 2. Preoperative anxiety scores were less in the Gabapentin than Control group (visual analog [VAS] score of 28 ± 16 mm versus 66 ± 15 mm; P < 0.001). The Gabapentin group required less morphine than the Control group (29 ± 22 mg versus 69 ± 40 mg; P < 0.001). VAS pain scores at rest and after mobilization were significantly reduced in the Gabapentin group. First and maximal passive and active knee flexions at 24 and 48 hours were significantly more extensive in the Gabapentin than in the Control group. In conclusion, premedication with 1200 mg gabapentin improved preoperative anxiolysis, postoperative analgesia, and early knee mobilization after arthroscopic anterior cruciate ligament repair. PMID:15845693

  11. Decrease in Urinary Creatinine Excretion in Early Stage Chronic Kidney Disease

    PubMed Central

    Tynkevich, Elena; Flamant, Martin; Haymann, Jean-Philippe; Metzger, Marie; Thervet, Eric; Boffa, Jean-Jacques; Vrtovsnik, François; Houillier, Pascal; Froissart, Marc; Stengel, Bénédicte

    2014-01-01

    Background Little is known about muscle mass loss in early stage chronic kidney disease (CKD). We used 24-hour urinary creatinine excretion rate to assess determinants of muscle mass and its evolution with kidney function decline. We also described the range of urinary creatinine concentration in this population. Methods We included 1072 men and 537 women with non-dialysis CKD stages 1 to 5, all of them with repeated measurements of glomerular filtration rate (mGFR) by 51Cr-EDTA renal clearance and several nutritional markers. In those with stage 1 to 4 at baseline, we used a mixed model to study factors associated with urinary creatinine excretion rate and its change over time. Results Baseline mean urinary creatinine excretion decreased from 15.3±3.1 to 12.1±3.3 mmol/24 h (0.20±0.03 to 0.15±0.04 mmol/kg/24 h) in men, with mGFR falling from ≥60 to <15 mL/min/1.73 m2, and from 9.6±1.9 to 7.6±2.5 (0.16±0.03 to 0.12±0.03) in women. In addition to mGFR, an older age, diabetes, and lower levels of body mass index, proteinuria, and protein intake assessed by urinary urea were associated with lower mean urinary creatinine excretion at baseline. Mean annual decline in mGFR was 1.53±0.12 mL/min/1.73 m2 per year and that of urinary creatinine excretion rate, 0.28±0.02 mmol/24 h per year. Patients with fast annual decline in mGFR of 5 mL/min/1.73 m2 had a decrease in urinary creatinine excretion more than twice as big as in those with stable mGFR, independent of changes in urinary urea as well as of other determinants of low muscle mass. Conclusions Decrease in 24-hour urinary creatinine excretion rate may appear early in CKD patients, and is greater the more mGFR declines independent of lowering protein intake assessed by 24-hour urinary urea. Normalizing urine analytes for creatininuria may overestimate their concentration in patients with reduced kidney function and low muscle mass. PMID:25401694

  12. Loss of Bmal1 decreases oocyte fertilization, early embryo development and implantation potential in female mice.

    PubMed

    Xu, Jian; Li, Yan; Wang, Yizi; Xu, Yanwen; Zhou, Canquan

    2016-10-01

    Biological clock genes expressed in reproductive tissues play important roles in maintaining the normal functions of reproductive system. However, disruption of female circadian rhythm on oocyte fertilization, preimplantation embryo development and blastocyst implantation potential is still unclear. In this study, ovulation, in vivo and in vitro oocyte fertilization, embryo development, implantation and intracellular reactive oxygen species (ROS) levels in ovary and oviduct were studied in female Bmal1+/+ and Bmal1-/- mice. The number of naturally ovulated oocyte in Bmal1-/- mice decreased (5.2 ± 0.8 vs 7.8 ± 0.8, P < 0.001), with an increasing abnormal oocyte ratio (20.4 ± 3.5 vs 11.7 ± 2.0%, P = 0.001) after superovulation. Significantly lower fertilization rate and obtained blastocyst number were observed in Bmal1-/- female mice either mated with wild-type in vivo or fertilized by sperm from wild-type male mice in vitro (all P < 0.05). Interestingly, in vitro fertilization rate of oocytes derived from Bmal1-/- increased significantly compared with in vivo study (P < 0.01). After transferring blastocysts derived from Bmal1+/+ and Bmal1-/- female mice to pseudopregnant mice, the implantation sites of the latter decreased 5 days later (8.0 ± 0.8 vs 5.3 ± 1.0, P = 0.005). The intracellular ROS levels in the ovary on proestrus day and in the oviduct on metestrus day increased significantly in Bmal1-/- mice compared with that of Bmal1+/+ mice. Deletion of the core biological clock gene Bmal1 significantly decreases oocyte fertilization rate, early embryo development and implantation potential in female mice, and these may be possibly caused by excess ROS levels generated in ovary and oviduct.

  13. Decreased serum estrogen improves fat graft retention by enhancing early macrophage infiltration and inducing adipocyte hypertrophy.

    PubMed

    Mok, Hsiaopei; Feng, Jingwei; Hu, Wansheng; Wang, Jing; Cai, Junrong; Lu, Feng

    2018-06-18

    Fat grafting is a commonly used procedure; however, the mechanisms that regulate graft outcomes are not clear. Estrogen has been associated with vascularization, inflammation and fat metabolism, yet its role in fat grafting is unclear. Mice were implanted with 17β-estradiol pellets (high estrogen, HE), underwent ovariectomy (low estrogen level, OVX) or sham surgery (normal estrogen level, CON). 45 days later, inguinal fat of mice was autografted subcutaneously. At 1, 2, 4, and 12 weeks post-transplantation, grafts were dissected, weighed, and assessed for histology, angiogenesis and inflammation level. Serum estrogen level correlated to estrogen manipulation. 12 weeks after autografting, the retention rate was significantly higher in the OVX (79% ± 30%) than in the HE (16% ± 8%) and CON (35% ± 13%) groups. OVX-grafts had the least necrosis and most hypertrophic fat. OVX recruited the most pro-inflammatory macrophages and demonstrated a faster dead tissue removal process, however a higher fibrogenic tendency was found in this group. HE grafts had the most Sca1+ local stem cells and CD31  +  capillary content; however, with a low level of acute inflammation and insufficient adipokine PPAR-γ expression, their retention rate was impaired. Elevated serum estrogen increased stem cell density and early vascularization; however, by inhibiting the early inflammation, it resulted in delayed necrotic tissue removal and finally led to impaired adipose restoration. A low estrogen level induced favorable inflammation status and adipocyte hypertrophy to improve fat graft retention, but a continuing decreased estrogen level led to fat graft fibrosis. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. How Safe Is Ginger Rhizome for Decreasing Nausea and Vomiting in Women during Early Pregnancy?

    PubMed Central

    Stanisiere, Julien; Mousset, Pierre-Yves; Lafay, Sophie

    2018-01-01

    Ginger, Zingiber officinale Roscoe, is increasingly consumed as a food or in food supplements. It is also recognized as a popular nonpharmacological treatment for nausea and vomiting of pregnancy (NVP). However, its consumption is not recommended by all countries for pregnant women. Study results are heterogeneous and conclusions are not persuasive enough to permit heath care professionals to recommend ginger safely. Some drugs are also contraindicated, leaving pregnant women with NVP with few solutions. We conducted a review to assess effectiveness and safety of ginger consumption during early pregnancy. Systematic literature searches were conducted on Medline (via Pubmed) until the end of December 2017. For the evaluation of efficacy, only double-blind, randomized, controlled trials were included. For the evaluation of the safety, controlled, uncontrolled, and pre-clinical studies were included in the review. Concerning toxicity, none can be extrapolated to humans from in vitro results. In vivo studies do not identify any major toxicities. Concerning efficacy and safety, a total of 15 studies and 3 prospective clinical studies have been studied. For 1 g of fresh ginger root per day for four days, results show a significant decrease in nausea and vomiting and no risk for the mother or her future baby. The available evidence suggests that ginger is a safe and effective treatment for NVP. However, beyond the ginger quantity needed to be effective, ginger quality is important from the perspective of safety. PMID:29614764

  15. Unexpected Decrease in Milk Production after Fenbendazole Treatment of Dairy Cows during Early Grazing Season

    PubMed Central

    Ravinet, Nadine; Chartier, Christophe; Bareille, Nathalie; Lehebel, Anne; Ponnau, Adeline; Brisseau, Nadine; Chauvin, Alain

    2016-01-01

    Gastrointestinal nematodes (GIN) infection can impair milk production (MP) in dairy cows. To investigate whether MP would be optimized by spring targeted-selective anthelmintic treatment in grazing cows, we assessed (1) the effect on MP of an anthelmintic treatment applied 1.5 to 2 months after turn-out, and (2) herd and individual indicators associated with the post-treatment MP response. A randomized controlled clinical trial was conducted in 13 dairy farms (578 cows) in western France in spring 2012. In each herd, lactating cows of the treatment group received fenbendazole orally, control cows remained untreated. Daily cow MP was recorded from 2 weeks before until 15 weeks after treatment. Individual serum pepsinogen and anti-Ostertagia antibody levels (expressed as ODR), faecal egg count and bulk tank milk (BTM) Ostertagia ODR were measured at treatment time. Anthelmintic treatment applied during the previous housing period was recorded for each cow. In each herd, information regarding heifers’ grazing and anthelmintic treatment history was collected to assess the Time of Effective Contact (TEC, in months) with GIN infective larvae before the first calving. The effect of treatment on weekly MP averages and its relationships with herd and individual indicators were studied using linear mixed models with two nested random effects (cow within herd). Unexpectedly, spring treatment had a significant detrimental effect on MP (-0.92 kg/cow/day on average). This negative MP response was particularly marked in high producing cows, in cows not treated during the previous housing period or with high pepsinogen levels, and in cows from herds with a high TEC or a high BTM ODR. This post-treatment decrease in MP may be associated with immuno-inflammatory mechanisms. Until further studies can assess whether this unexpected result can be generalized, non-persistent treatment of immunized adult dairy cows against GIN should not be recommended in early grazing season. PMID

  16. Unexpected Decrease in Milk Production after Fenbendazole Treatment of Dairy Cows during Early Grazing Season.

    PubMed

    Ravinet, Nadine; Chartier, Christophe; Bareille, Nathalie; Lehebel, Anne; Ponnau, Adeline; Brisseau, Nadine; Chauvin, Alain

    2016-01-01

    Gastrointestinal nematodes (GIN) infection can impair milk production (MP) in dairy cows. To investigate whether MP would be optimized by spring targeted-selective anthelmintic treatment in grazing cows, we assessed (1) the effect on MP of an anthelmintic treatment applied 1.5 to 2 months after turn-out, and (2) herd and individual indicators associated with the post-treatment MP response. A randomized controlled clinical trial was conducted in 13 dairy farms (578 cows) in western France in spring 2012. In each herd, lactating cows of the treatment group received fenbendazole orally, control cows remained untreated. Daily cow MP was recorded from 2 weeks before until 15 weeks after treatment. Individual serum pepsinogen and anti-Ostertagia antibody levels (expressed as ODR), faecal egg count and bulk tank milk (BTM) Ostertagia ODR were measured at treatment time. Anthelmintic treatment applied during the previous housing period was recorded for each cow. In each herd, information regarding heifers' grazing and anthelmintic treatment history was collected to assess the Time of Effective Contact (TEC, in months) with GIN infective larvae before the first calving. The effect of treatment on weekly MP averages and its relationships with herd and individual indicators were studied using linear mixed models with two nested random effects (cow within herd). Unexpectedly, spring treatment had a significant detrimental effect on MP (-0.92 kg/cow/day on average). This negative MP response was particularly marked in high producing cows, in cows not treated during the previous housing period or with high pepsinogen levels, and in cows from herds with a high TEC or a high BTM ODR. This post-treatment decrease in MP may be associated with immuno-inflammatory mechanisms. Until further studies can assess whether this unexpected result can be generalized, non-persistent treatment of immunized adult dairy cows against GIN should not be recommended in early grazing season.

  17. RP105 deficiency attenuates early atherosclerosis via decreased monocyte influx in a CCR2 dependent manner.

    PubMed

    Wezel, Anouk; van der Velden, Daniël; Maassen, Johanna M; Lagraauw, H Maxime; de Vries, Margreet R; Karper, Jacco C; Kuiper, Johan; Bot, Ilze; Quax, Paul H A

    2015-01-01

    Toll like receptor 4 (TLR4) plays a key role in inflammation and previously it was established that TLR4 deficiency attenuates atherosclerosis. RadioProtective 105 (RP105) is a structural homolog of TLR4 and an important regulator of TLR4 signaling, suggesting that RP105 may also be an important effector in atherosclerosis. We thus aimed to determine the role of RP105 in atherosclerotic lesion development using RP105 deficient mice on an atherosclerotic background. Atherosclerosis was induced in Western-type diet fed low density lipoprotein receptor deficient (LDLr(-/-)) and LDLr/RP105 double knockout (LDLr(-/-)/RP105(-/-)) mice by means of perivascular carotid artery collar placement. Lesion size was significantly reduced by 58% in LDLr(-/-)/RP105(-/-) mice, and moreover, plaque macrophage content was markedly reduced by 40%. In a model of acute peritonitis, monocyte influx was almost 3-fold reduced in LDLr(-/-)/RP105(-/-) mice (P = 0.001), while neutrophil influx remained unaltered, suggestive of an altered migratory capacity of monocytes upon deletion of RP105. Interestingly, in vitro stimulation of monocytes with LPS induced a downregulation of CCR2, a chemokine receptor crucially involved in monocyte influx to atherosclerotic lesions, which was more pronounced in LDLr(-/-)/RP105(-/-) monocytes as compared to LDLr(-/-) monocytes. We here show that RP105 deficiency results in reduced early atherosclerotic plaque development with a marked decrease in lesional macrophage content, which may be due to disturbed migration of RP105 deficient monocytes resulting from CCR2 downregulation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Complement inhibition decreases early fibrogenic events in the lung of septic baboons.

    PubMed

    Silasi-Mansat, Robert; Zhu, Hua; Georgescu, Constantin; Popescu, Narcis; Keshari, Ravi S; Peer, Glenn; Lupu, Cristina; Taylor, Fletcher B; Pereira, Heloise Anne; Kinasewitz, Gary; Lambris, John D; Lupu, Florea

    2015-11-01

    Acute respiratory distress syndrome (ARDS) induced by severe sepsis can trigger persistent inflammation and fibrosis. We have shown that experimental sepsis in baboons recapitulates ARDS progression in humans, including chronic inflammation and long-lasting fibrosis in the lung. Complement activation products may contribute to the fibroproliferative response, suggesting that complement inhibitors are potential therapeutic agents. We have been suggested that treatment of septic baboons with compstatin, a C3 convertase inhibitor protects against ARDS-induced fibroproliferation. Baboons challenged with 10(9) cfu/kg (LD50) live E. coli by intravenous infusion were treated or not with compstatin at the time of challenge or 5 hrs thereafter. Changes in the fibroproliferative response at 24 hrs post-challenge were analysed at both transcript and protein levels. Gene expression analysis showed that sepsis induced fibrotic responses in the lung as early as 24 hrs post-bacterial challenge. Immunochemical and biochemical analysis revealed enhanced collagen synthesis, induction of profibrotic factors and increased cell recruitment and proliferation. Specific inhibition of complement with compstatin down-regulated sepsis-induced fibrosis genes, including transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), tissue inhibitor of metalloproteinase 1 (TIMP1), various collagens and chemokines responsible for fibrocyte recruitment (e.g. chemokine (C-C motif) ligand 2 (CCL2) and 12 (CCL12)). Compstatin decreased the accumulation of myofibroblasts and proliferating cells, reduced the production of fibrosis mediators (TGF-β, phospho-Smad-2 and CTGF) and inhibited collagen deposition. Our data demonstrate that complement inhibition effectively attenuates collagen deposition and fibrotic responses in the lung after severe sepsis. Inhibiting complement could prove an attractive strategy for preventing sepsis-induced fibrosis of the lung. © 2015 The Authors

  19. Strong expression of the neuronal transcription factor FOXP2 is linked to an increased risk of early PSA recurrence in ERG fusion-negative cancers.

    PubMed

    Stumm, Laura; Burkhardt, Lia; Steurer, Stefan; Simon, Ronald; Adam, Meike; Becker, Andreas; Sauter, Guido; Minner, Sarah; Schlomm, Thorsten; Sirma, Hüseyin; Michl, Uwe

    2013-07-01

    Transcription factors of the forkhead box P (FOXP1-4) family have been implicated in various human cancer types before. The relevance and role of neuronal transcription factor FOXP2 in prostate cancer is unknown. A tissue microarray containing samples from more than 11 000 prostate cancers from radical prostatectomy specimens with clinical follow-up data was analysed for FOXP2 expression by immunohistochemistry. FOXP2 data were also compared with pre-existing ERG fusion (by fluorescence in situ hybridisation and immunohistochemistry) and cell proliferation (Ki67 labelling index) data. There was a moderate to strong FOXP2 protein expression in basal and secretory cells of normal prostatic glands. As compared with normal cells, FOXP2 expression was lost or reduced in 25% of cancers. Strong FOXP2 expression was linked to advanced tumour stage, high Gleason score, presence of lymph node metastases and early tumour recurrence (p<0.0001; each) in ERG fusion-negative, but not in ERG fusion-positive cancers. High FOXP2 expression was linked to high Ki67 labelling index (p<0.0001) in all cancers irrespective of ERG fusion status. These data demonstrate that similar high FOXP2 protein levels as in normal prostate epithelium exert a 'paradoxical' oncogenic role in 'non fusion-type' prostate cancer. It may be speculated that interaction of FOXP2 with members of pathways that are specifically activated in 'non fusion-type' cancers may be responsible for this phenomenon.

  20. Prostate-Specific Antigen (PSA) Bounce After Dose-Escalated External Beam Radiation Therapy Is an Independent Predictor of PSA Recurrence, Metastasis, and Survival in Prostate Adenocarcinoma Patients.

    PubMed

    Romesser, Paul B; Pei, Xin; Shi, Weiji; Zhang, Zhigang; Kollmeier, Marisa; McBride, Sean M; Zelefsky, Michael J

    2018-01-01

    To evaluate the difference in prostate-specific antigen (PSA) recurrence-free, distant metastasis-free, overall, and cancer-specific survival between PSA bounce (PSA-B) and non-bounce patients treated with dose-escalated external beam radiation therapy (DE-EBRT). During 1990-2010, 1898 prostate adenocarcinoma patients were treated with DE-EBRT to ≥75 Gy with ≥5 years follow-up. Patients receiving neoadjuvant/concurrent androgen-deprivation therapy (n=1035) or with fewer than 4 PSA values obtained 6 months or more after post-EBRT completion (n=87) were excluded. The evaluable 776 patients were treated (median, 81.0 Gy). Prostate-specific antigen bounce was defined as a ≥0.2-ng/mL increase above the interval PSA nadir, followed by a decrease to nadir or below. Prostate-specific antigen relapse was defined as post-radiation therapy PSA nadir + 2 ng/mL. Median follow-up was 9.2 years (interquartile range, 6.9-11.3 years). One hundred twenty-three patients (15.9%) experienced PSA-B after DE-EBRT at a median of 24.6 months (interquartile range, 16.1-38.5 months). On multivariate analysis, younger age (P=.001), lower Gleason score (P=.0003), and higher radiation therapy dose (P=.0002) independently predicted PSA-B. Prostate-specific antigen bounce was independently associated with decreased risk for PSA relapse (hazard ratio [HR] 0.53; 95% confidence interval [CI] 0.33-0.85; P=.008), distant metastatic disease (HR 0.34; 95% CI 0.12-0.94; P=.04), and all-cause mortality (HR 0.53; 95% CI 0.29-0.96; P=.04) on multivariate Cox analysis. Because all 50 prostate cancer-specific deaths in patients without PSA-B were in the non-bounce cohort, competing-risks analysis was not applicable. A nonparametric competing-risks test demonstrated that patients with PSA-B had superior cancer-specific survival compared with patients without PSA-B (P=.004). Patients treated with dose-escalated radiation therapy for prostate adenocarcinoma who experience posttreatment PSA-B have

  1. Interpreting the gamma statistic in phylogenetic diversification rate studies: a rate decrease does not necessarily indicate an early burst.

    PubMed

    Fordyce, James A

    2010-07-23

    Phylogenetic hypotheses are increasingly being used to elucidate historical patterns of diversification rate-variation. Hypothesis testing is often conducted by comparing the observed vector of branching times to a null, pure-birth expectation. A popular method for inferring a decrease in speciation rate, which might suggest an early burst of diversification followed by a decrease in diversification rate is the gamma statistic. Using simulations under varying conditions, I examine the sensitivity of gamma to the distribution of the most recent branching times. Using an exploratory data analysis tool for lineages through time plots, tree deviation, I identified trees with a significant gamma statistic that do not appear to have the characteristic early accumulation of lineages consistent with an early, rapid rate of cladogenesis. I further investigated the sensitivity of the gamma statistic to recent diversification by examining the consequences of failing to simulate the full time interval following the most recent cladogenic event. The power of gamma to detect rate decrease at varying times was assessed for simulated trees with an initial high rate of diversification followed by a relatively low rate. The gamma statistic is extraordinarily sensitive to recent diversification rates, and does not necessarily detect early bursts of diversification. This was true for trees of various sizes and completeness of taxon sampling. The gamma statistic had greater power to detect recent diversification rate decreases compared to early bursts of diversification. Caution should be exercised when interpreting the gamma statistic as an indication of early, rapid diversification.

  2. Cost implications of PSA screening differ by age.

    PubMed

    Rao, Karthik; Liang, Stella; Cardamone, Michael; Joshu, Corinne E; Marmen, Kyle; Bhavsar, Nrupen; Nelson, William G; Ballentine Carter, H; Albert, Michael C; Platz, Elizabeth A; Pollack, Craig E

    2018-05-09

    Multiple guidelines seek to alter rates of prostate-specific antigen (PSA)-based prostate cancer screening. The costs borne by payers associated with PSA-based screening for men of different age groups-including the costs of screening and subsequent diagnosis, treatment, and adverse events-remain uncertain. We sought to develop a model of PSA costs that could be used by payers and health care systems to inform cost considerations under a range of different scenarios. We determined the prevalence of PSA screening among men aged 50 and higher using 2013-2014 data from a large, multispecialty group, obtained reimbursed costs associated with screening, diagnosis, and treatment from a commercial health plan, and identified transition probabilities for biopsy, diagnosis, treatment, and complications from the literature to generate a cost model. We estimated annual total costs for groups of men ages 50-54, 55-69, and 70+ years, and varied annual prostate cancer screening prevalence in each group from 5 to 50% and tested hypothetical examples of different test characteristics (e.g., true/false positive rate). Under the baseline screening patterns, costs of the PSA screening represented 10.1% of the total costs; costs of biopsies and associated complications were 23.3% of total costs; and, although only 0.3% of all screen eligible patients were treated, they accounted for 66.7% of total costs. For each 5-percentage point decrease in PSA screening among men aged 70 and older for a single calendar year, total costs associated with prostate cancer screening decreased by 13.8%. For each 5-percentage point decrease in PSA screening among men 50-54 and 55-69 years old, costs were 2.3% and 7.3% lower respectively. With constrained financial resources and with national pressure to decrease use of clinically unnecessary PSA-based prostate cancer screening, there is an opportunity for cost savings, especially by focusing on the downstream costs disproportionately associated with

  3. Optimization of PSA screening policies: a comparison of the patient and societal perspectives.

    PubMed

    Zhang, Jingyu; Denton, Brian T; Balasubramanian, Hari; Shah, Nilay D; Inman, Brant A

    2012-01-01

    To estimate the benefit of PSA-based screening for prostate cancer from the patient and societal perspectives. A partially observable Markov decision process model was used to optimize PSA screening decisions. Age-specific prostate cancer incidence rates and the mortality rates from prostate cancer and competing causes were considered. The model trades off the potential benefit of early detection with the cost of screening and loss of patient quality of life due to screening and treatment. PSA testing and biopsy decisions are made based on the patient's probability of having prostate cancer. Probabilities are inferred based on the patient's complete PSA history using Bayesian updating. The results of all PSA tests and biopsies done in Olmsted County, Minnesota, from 1993 to 2005 (11,872 men and 50,589 PSA test results). Patients' perspective: to maximize expected quality-adjusted life years (QALYs); societal perspective: to maximize the expected monetary value based on societal willingness to pay for QALYs and the cost of PSA testing, prostate biopsies, and treatment. From the patient perspective, the optimal policy recommends stopping PSA testing and biopsy at age 76. From the societal perspective, the stopping age is 71. The expected incremental benefit of optimal screening over the traditional guideline of annual PSA screening with threshold 4.0 ng/mL for biopsy is estimated to be 0.165 QALYs per person from the patient perspective and 0.161 QALYs per person from the societal perspective. PSA screening based on traditional guidelines is found to be worse than no screening at all. PSA testing done with traditional guidelines underperforms and therefore underestimates the potential benefit of screening. Optimal screening guidelines differ significantly depending on the perspective of the decision maker.

  4. Prostate-specific antigen (PSA) density in the diagnostic algorithm of prostate cancer.

    PubMed

    Nordström, Tobias; Akre, Olof; Aly, Markus; Grönberg, Henrik; Eklund, Martin

    2018-04-01

    Screening for prostate cancer using prostate-specific antigen (PSA) alone leads to un-necessary biopsying and overdiagnosis. PSA density is easily accessible, but early evidence on its use for biopsy decisions was conflicting and use of PSA density is not commonly recommended in guidelines. We analyzed biopsy outcomes in 5291 men in the population-based STHLM3 study with PSA ≥ 3 ng/ml and ultrasound-guided prostate volume measurements by using percentages and regression models. PSA density was calculated as total PSA (ng/ml) divided by prostate volume (ml). Main endpoint was clinically significant cancer (csPCa) defined as Gleason Score ≥ 7. The median PSA-density was 0.10 ng/ml 2 (IQR 0.075-0.14). PSA-density was associated with the risk of finding csPCa both with and without adjusting for the additional clinical information age, family history, previous biopsies, total PSA and free/total PSA (OR 1.06; 95% CI:1.05-1.07 and OR 1.07, 95% CI 1.06-1.08). Discrimination for csPCa was better when PSA density was added to a model with additional clinical information (AUC 0.75 vs. 0.73, P < 0.05). The proportion of men with Gleason Score 6 (ISUP 1) was similar across stratas of PSA-density. Omitting prostate biopsy for men with PSA-density ≤0.07 ng/ml 2 would save 19.7% of biopsy procedures, while missing 6.9% of csPCa. PSA-density cutoffs of 0.10 ng/ml 2 and 0.15 ng/ml 2 resulted in detection of 77% (729/947) and 49% (461/947) of Gleason Score ≥7 tumors. PSA-density might inform biopsy decisions, and spare some men from the morbidity associated with a prostate biopsy and diagnosis of low-grade prostate cancer.

  5. Early Exercise in the Burn Intensive Care Unit Decreases Hospital Stay, Improves Mental Health, and Physical Performance

    DTIC Science & Technology

    2016-10-01

    AD______________ AWARD NUMBER: W81XWH-14-2-0160 TITLE: Early Exercise in the Burn Intensive Care Unit Decreases Hospital Stay, Improves... designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public reporting burden for this collection of... Care Unit Decreases Hospital Stay, Improves Mental Health, and Physical Performance 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Oscar E

  6. Early-life disruption of amphibian microbiota decreases later-life resistance to parasites.

    PubMed

    Knutie, Sarah A; Wilkinson, Christina L; Kohl, Kevin D; Rohr, Jason R

    2017-07-20

    Changes in the early-life microbiota of hosts might affect infectious disease risk throughout life, if such disruptions during formative times alter immune system development. Here, we test whether an early-life disruption of host-associated microbiota affects later-life resistance to infections by manipulating the microbiota of tadpoles and challenging them with parasitic gut worms as adults. We find that tadpole bacterial diversity is negatively correlated with parasite establishment in adult frogs: adult frogs that had reduced bacterial diversity as tadpoles have three times more worms than adults without their microbiota manipulated as tadpoles. In contrast, adult bacterial diversity during parasite exposure is not correlated with parasite establishment in adult frogs. Thus, in this experimental setup, an early-life disruption of the microbiota has lasting reductions on host resistance to infections, which is possibly mediated by its effects on immune system development. Our results support the idea that preventing early-life disruption of host-associated microbiota might confer protection against diseases later in life.Early-life microbiota alterations can affect infection susceptibility later in life, in animal models. Here, Knutie et al. show that manipulating the microbiota of tadpoles leads to increased susceptibility to parasitic infection in adult frogs, in the absence of substantial changes in the adults' microbiota.

  7. Early Palliative Care for Patients With Brain Metastases Decreases Inpatient Admissions and Need for Imaging Studies.

    PubMed

    Habibi, Akram; Wu, S Peter; Gorovets, Daniel; Sansosti, Alexandra; Kryger, Marc; Beaudreault, Cameron; Chung, Wei-Yi; Shelton, Gary; Silverman, Joshua; Lowy, Joseph; Kondziolka, Douglas

    2018-01-01

    Early encounters with palliative care (PC) can influence health-care utilization, clinical outcome, and cost. To study the effect of timing of PC encounters on brain metastasis patients at an academic medical center. All patients diagnosed with brain metastases from January 2013 to August 2015 at a single institution with inpatient and/or outpatient PC records available for review (N = 145). Early PC was defined as having a PC encounter within 8 weeks of diagnosis with brain metastases; late PC was defined as having PC after 8 weeks of diagnosis. Propensity score matched cohorts of early (n = 46) and late (n = 46) PC patients were compared to control for differences in age, gender, and Karnofsky Performance Status (KPS) at diagnosis. Details of the palliative encounter, patient outcomes, and health-care utilization were collected. Early PC versus late PC patients had no differences in baseline KPS, age, or gender. Early PC patients had significantly fewer number of inpatient visits per patient (1.5 vs 2.9; P = .004), emergency department visits (1.2 vs 2.1; P = .006), positron emission tomography/computed tomography studies (1.2 vs 2.7, P = .005), magnetic resonance imaging scans (5.8 vs 8.1; P = .03), and radiosurgery procedures (0.6 vs 1.3; P < .001). There were no differences in overall survival (median 8.2 vs 11.2 months; P = .2). Following inpatient admissions, early PC patients were more likely to be discharged home (59% vs 35%; P = .04). Timely PC consultations are advisable in this patient population and can reduce health-care utilization.

  8. Does Contact by a Family Nurse Practitioner Decrease Early School Absence?

    ERIC Educational Resources Information Center

    Kerr, Jill; Price, Marva; Kotch, Jonathan; Willis, Stephanie; Fisher, Michael; Silva, Susan

    2012-01-01

    Chronic early school absence (preschool through third grade) is associated with school failure. The presence of school nurses may lead to fewer absences, and nurse practitioners in school-based health centers (SBHCs) can facilitate a healthier population resulting in improved attendance. Efforts to get students back to school are unexplored in…

  9. Qualities for Early Childhood Care and Education in an Age of Increasing Superdiversity and Decreasing Biodiversity

    ERIC Educational Resources Information Center

    Ritchie, Jenny

    2016-01-01

    In this article it is argued that notions of "quality" in early childhood education have been captured by neo-liberal discourses. These discourses perpetuate the western, individualistic, normativising and exploitative attitudes and practices that are contributing to the climate crisis currently imperilling our planet. Educators may…

  10. Decreased endometrial vascularity and receptivity in unexplained recurrent miscarriage patients during midluteal and early pregnancy phases.

    PubMed

    Tan, Shu-Yin; Hang, Fu; Purvarshi, Gowreesunkur; Li, Min-Qing; Meng, Da-Hua; Huang, Ling-Ling

    2015-10-01

    To evaluate the predictive value of three-dimensional (3D)-power Doppler sonography on recurrent miscarriage. The study patients were divided into a recurrent miscarriage group (30 cases) and a normal pregnancy group (21 cases). Measurement of endometrial thickness was performed using two-dimensional transvaginal ultrasound in the midluteal phase. The endometrial volume, vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) in midluteal and placenta volume, as well as the VI, FI, and VFI of early pregnancy were measured using Virtual Organ Computer-aided Analysis of 3D-power Doppler ultrasound. Endometrial thickness, endometrial volume, endometrial vascular data, VI, FI, and VFI of the midluteal phase were lower in the recurrent miscarriage group compared with the normal pregnancy group (p < 0.05). Placental volume, VI, and VFI during early pregnancy were lower in the miscarriage group compared with the normal pregnancy group (p < 0.05). There was no significant change in FI between the recurrent miscarriage and control groups during early pregnancy (p > 0.05). The predictive accuracy of endometrial thickness, endometrial volume, VI, FI, and VFI in the midluteal phase, and placenta volume, VI, FI, and VFI in early pregnancy as measured by the receiver operating characteristic curve to predict miscarriage before 12 gestational weeks in participants was 0.681, 0.876, 0.770, 0.720, 0.879, 0.771, 0.907, 0.592, respectively. The 3D-power Doppler ultrasound is a more comprehensive and sensitive method for evaluating endometrial receptivity. Endometrial volume, VI, FI, and VFI in the midluteal phase, as well as VI in early pregnancy, can be considered as predictive factors for recurrent miscarriage. Copyright © 2015. Published by Elsevier B.V.

  11. Awareness that early cancer lump is painless could decrease breast cancer mortality in developing countries.

    PubMed

    Garg, Pankaj

    2016-06-10

    There are several factors which contribute to patients' reporting late to healthcare facility even after detecting the breast lump (patient delay). Amongst these, one of the important factors in low- and middle-income countries is lack of awareness that early cancer lump is painless (ECLIPs). Pain is often taken as a danger sign and absence of pain is often not taken seriously. The studies have shown that up to 98% of women in low-income countries are unaware that a painless lump could be a warning sign of early breast cancer. This fact is significant because this could be one of the prime reasons for the women having discovered a painless lump in the breast, accidentally or by breast self-examination, presume it to be harmless and don't report early to health care facility. Therefore, creating awareness about ECLIPs could be an effective strategy to reduce mortality due to breast cancer in low- and middle-income countries. Moreover, unlike modifying risk factors which requires long term behavior modification, creating awareness about ECLIPs is easy and cost effective.

  12. Decreasing Excessive Bids for Attention in a Simulated Early Education Classroom

    ERIC Educational Resources Information Center

    Becraft, Jessica L.; Borrero, John C.; Mendres-Smith, Amber E.; Castillo, Mariana I.

    2017-01-01

    Differential-reinforcement-of-low-rate (DRL) schedules can be used to decrease, but not eliminate, excessive bids for teacher attention in a classroom. There are two primary methods of implementing a DRL: full session and spaced responding. Some research suggests that the full-session DRL may eliminate target responding. The purpose of the current…

  13. Early exposure to ultraviolet-B radiation decreases immune function later in life

    PubMed Central

    Ceccato, Emma; Cramp, Rebecca L.; Seebacher, Frank; Franklin, Craig E.

    2016-01-01

    Amphibians have declined dramatically worldwide. Many of these declines are occurring in areas where no obvious anthropogenic stressors are present. It is proposed that in these areas, environmental factors such as elevated solar ultraviolet-B (UV-B) radiation could be responsible. Ultraviolet-B levels have increased in many parts of the world as a consequence of the anthropogenic destruction of the ozone layer. Amphibian tadpoles are particularly sensitive to the damaging effects of UV-B radiation, with exposure disrupting growth and fitness in many species. Given that UV-B can disrupt immune function in other animals, we tested the hypothesis that early UV-B exposure suppresses the immune responses of amphibian tadpoles and subsequent juvenile frogs. We exposed Limnodynastes peronii tadpoles to sublethal levels of UV-B radiation for 6 weeks after hatching, then examined indices of immune function in both the tadpoles and the subsequent metamorphs. There was no significant effect of UV-B on tadpole leucocyte counts or on their response to an acute antigen (phytohaemagglutinin) challenge. However, early UV-B exposure resulted in a significant reduction in both metamorph leucocyte abundance and their response to an acute phytohaemagglutinin challenge. These data demonstrate that early UV-B exposure can have carry-over effects on later life-history traits even if the applied stressor has no immediately discernible effect. These findings have important implications for our understanding of the effects of UV-B exposure on amphibian health and susceptibility to diseases such as chytridiomycosis. PMID:27668081

  14. Cone photopigment in older subjects: decreased optical density in early age-related macular degeneration

    NASA Astrophysics Data System (ADS)

    Elsner, Ann E.; Burns, Stephen A.; Weiter, John J.

    2002-01-01

    We measured changes to cone photoreceptors in patients with early age-related macular degeneration. The data of 53 patients were compared with normative data for color matching measurements of long- and middle-wavelength-sensitive cones in the central macula. A four-parameter model quantified cone photopigment optical density and kinetics. Cone photopigment optical density was on average less for the patients than for normal subjects and was uncorrelated with visual acuity. More light was needed to reduce the photopigment density by 50% in the steady state for patients. These results imply that cone photopigment optical density is reduced by factors other than slowed kinetics.

  15. Neurochemical Characterization of PSA-NCAM+ Cells in the Human Brain and Phenotypic Quantification in Alzheimer's Disease Entorhinal Cortex.

    PubMed

    Murray, Helen C; Swanson, Molly E V; Dieriks, B Victor; Turner, Clinton; Faull, Richard L M; Curtis, Maurice A

    2018-02-21

    Polysialylated neural cell adhesion molecule (PSA-NCAM) is widely expressed in the adult human brain and facilitates structural remodeling of cells through steric inhibition of intercellular NCAM adhesion. We previously showed that PSA-NCAM immunoreactivity is decreased in the entorhinal cortex in Alzheimer's disease (AD). Based on available evidence, we hypothesized that a loss of PSA-NCAM + interneurons may underlie this reduction. PSA-NCAM expression by interneurons has previously been described in the human medial prefrontal cortex. Here we used postmortem human brain tissue to provide further evidence of PSA-NCAM + interneurons throughout the human hippocampal formation and additional cortical regions. Furthermore, PSA-NCAM + cell populations were assessed in the entorhinal cortex of normal and AD cases using fluorescent double labeling and manual cell counting. We found a significant decrease in the number of PSA-NCAM + cells per mm 2 in layer II and V of the entorhinal cortex, supporting our previous description of reduced PSA-NCAM immunoreactivity. Additionally, we found a significant decrease in the proportion of PSA-NCAM + cells that co-labeled with NeuN and parvalbumin, but no change in the proportion that co-labeled with calbindin or calretinin. These results demonstrate that PSA-NCAM is expressed by a variety of interneuron populations throughout the brain. Furthermore, that loss of PSA-NCAM expression by NeuN + cells predominantly contributes to the reduced PSA-NCAM immunoreactivity in the AD entorhinal cortex. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Decreased Expression of the Early Mitotic Gene, CHFR, Contributes to the Acquisition of Breast Cancer Phenotypes

    DTIC Science & Technology

    2008-03-01

    immortalization with the human papilloma virus (HPV) E6 and E7 proteins, which had decreased CHFR expression by RNAi did not have an altered apoptotic response...septation initiation network (SIN). Dev Cell 2002; 3:779–90. 40. Band V, Zajchowski D, Kulesa V, Sager R. Human papilloma virus DNAs immortalize normal... papilloma virus (HPV)–immortalized series of nontumorigenic mammary cell lines were developed and provided by S.P. Ethier, Karmanos Cancer Institute

  17. Transplantation of Ex Vivo Expanded Umbilical Cord Blood (NiCord) Decreases Early Infection and Hospitalization.

    PubMed

    Anand, Sarah; Thomas, Samantha; Hyslop, Terry; Adcock, Janet; Corbet, Kelly; Gasparetto, Cristina; Lopez, Richard; Long, Gwynn D; Morris, Ashley K; Rizzieri, David A; Sullivan, Keith M; Sung, Anthony D; Sarantopoulos, Stefanie; Chao, Nelson J; Horwitz, Mitchell E

    2017-07-01

    Delayed hematopoietic recovery contributes to increased infection risk following umbilical cord blood (UCB) transplantation. In a Phase 1 study, adult recipients of UCB stem cells cultured ex vivo for 3 weeks with nicotinamide (NiCord) had earlier median neutrophil recovery compared with historical controls. To evaluate the impact of faster neutrophil recovery on clinically relevant early outcomes, we reviewed infection episodes and hospitalization during the first 100 days in an enlarged cohort of 18 NiCord recipients compared with 86 standard UCB recipients at our institution. The median time to neutrophil engraftment was shorter in NiCord recipients compared with standard UCB recipients (12.5 days versus 26 days; P < .001). Compared with standard UCB recipients, NiCord recipients had a significantly reduced risk for total infection (RR, 0.69; P = .01), grade 2-3 (moderate to severe) infection (RR, 0.36; P < .001), bacterial infection (RR, 0.39; P = .003), and grade 2-3 bacterial infection (RR, 0.21; P = .003) by Poisson regression analysis; this effect persisted after adjustment for age, disease stage, and grade II-IV acute GVHD. NiCord recipients also had significantly more time out of the hospital in the first 100 days post-transplantation after adjustment for age and Karnofsky Performance Status (69.9 days versus 49.7 days; P = .005). Overall, transplantation of NiCord was associated with faster neutrophil engraftment, fewer total and bacterial infections, and shorter hospitalization in the first 100 days compared with standard UCB transplantation. In conclusion, rapid hematopoietic recovery from an ex vivo expanded UCB transplantation approach is associated with early clinical benefit. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  18. Predictive factors of 18F-choline PET/CT positivity in patients with prostate cancer recurrence after radiation therapy: is the impact of PSA nadir underestimated?

    PubMed

    Johnson, Alison C; Dugué, Audrey Emmanuelle; Silva, Marlon; Moise, Laura; Tillou, Xavier; Joly, Florence; Aide, Nicolas

    2016-12-01

    The objective of this study is to explore the impact of PSA nadirs on detection rates of prostate cancer (PCa) recurrence with 18 F-choline (CH) PET/CT after external beam radiation therapy (EBRT). In this retrospective study, data were collected from 54 patients with suspicion of PCa biochemical recurrence after EBRT (28 patients treated initially with EBRT and 26 as salvage therapy in the absence of PSA decrease after initial treatment), who underwent 18 F-CH PET/CT between 2010 and 2015. PSA nadir and trigger PSA were collected from patient files. Relative PSA was calculated by subtracting the nadir from the trigger PSA. Median PSA nadir was 0.31 (0.01-13.31) ng/mL, trigger PSA was 7.85 (0.47-111.60) ng/mL, and relative PSA was 6.05 (0.24-104.59) ng/mL. Overall, 40 (74%) PET/CT scans were positive: recurrence was local and/or regional in 29 patients, distant in 15 and combined both in four, with no association between PSA values and sites of recurrence. In univariate analysis, trigger (p = 0.015) and relative (p = 0.0005) PSA values and PSA velocity (p = 0.01) were significantly linked to positive PET/CT, but PSA nadir was not. In subgroup analysis, these significant differences were only found in the salvage EBRT group. Akaike Information Criterion multivariate model comparison found that relative PSA was a better predictor of positive PET/CT than trigger PSA (PSAt). 18 F-CH PET/CT detection rates increased with trigger and relative PSA: 0% (0/4 patients), 71% (5/7 patients), and 81% (35/43 patients) for PSAt <2 ng/mL, 2≤ PSAt ≤4 ng/mL, and PSAt >4 ng/mL, respectively, and 14% (1/7 patients), 50% (5/10 patients), and 92% (34/37 patients) when relative PSA was taken into account instead of trigger PSA, with seven (13%) patients changing subgroups. We found a high overall detection rate and an increase in detection rates proportional to trigger and relative PSAs. Although relative PSA, taking into account PSA nadir, was a better predictive

  19. Decreased Knee Joint Loading Associated With Early Knee Osteoarthritis After Anterior Cruciate Ligament Injury.

    PubMed

    Wellsandt, Elizabeth; Gardinier, Emily S; Manal, Kurt; Axe, Michael J; Buchanan, Thomas S; Snyder-Mackler, Lynn

    2016-01-01

    Anterior cruciate ligament (ACL) injury predisposes individuals to early-onset knee joint osteoarthritis (OA). Abnormal joint loading is apparent after ACL injury and reconstruction. The relationship between altered joint biomechanics and the development of knee OA is unknown. Altered knee joint kinetics and medial compartment contact forces initially after injury and reconstruction are associated with radiographic knee OA 5 years after reconstruction. Case-control study; Level of evidence, 3. Individuals with acute, unilateral ACL injury completed gait analysis before (baseline) and after (posttraining) preoperative rehabilitation and at 6 months, 1 year, and 2 years after reconstruction. Surface electromyographic and knee biomechanical data served as inputs to an electromyographically driven musculoskeletal model to estimate knee joint contact forces. Patients completed radiographic testing 5 years after reconstruction. Differences in knee joint kinetics and contact forces were compared between patients with and those without radiographic knee OA. Patients with OA walked with greater frontal plane interlimb differences than those without OA (nonOA) at baseline (peak knee adduction moment difference: 0.00 ± 0.08 N·m/kg·m [nonOA] vs -0.15 ± 0.09 N·m/kg·m [OA], P = .014; peak knee adduction moment impulse difference: -0.001 ± 0.032 N·m·s/kg·m [nonOA] vs -0.048 ± 0.031 N·m·s/kg·m [OA], P = .042). The involved limb knee adduction moment impulse of the group with osteoarthritis was also lower than that of the group without osteoarthritis at baseline (0.087 ± 0.023 N·m·s/kg·m [nonOA] vs 0.049 ± 0.018 N·m·s/kg·m [OA], P = .023). Significant group differences were absent at posttraining but reemerged 6 months after reconstruction (peak knee adduction moment difference: 0.02 ± 0.04 N·m/kg·m [nonOA] vs -0.06 ± 0.11 N·m/kg·m [OA], P = .043). In addition, the OA group walked with lower peak medial compartment contact forces of the involved limb

  20. Decrease in early right alpha band phase synchronization and late gamma band oscillations in processing syntax in music.

    PubMed

    Ruiz, María Herrojo; Koelsch, Stefan; Bhattacharya, Joydeep

    2009-04-01

    The present study investigated the neural correlates associated with the processing of music-syntactical irregularities as compared with regular syntactic structures in music. Previous studies reported an early ( approximately 200 ms) right anterior negative component (ERAN) by traditional event-related-potential analysis during music-syntactical irregularities, yet little is known about the underlying oscillatory and synchronization properties of brain responses which are supposed to play a crucial role in general cognition including music perception. First we showed that the ERAN was primarily represented by low frequency (<8 Hz) brain oscillations. Further, we found that music-syntactical irregularities as compared with music-syntactical regularities, were associated with (i) an early decrease in the alpha band (9-10 Hz) phase synchronization between right fronto-central and left temporal brain regions, and (ii) a late ( approximately 500 ms) decrease in gamma band (38-50 Hz) oscillations over fronto-central brain regions. These results indicate a weaker degree of long-range integration when the musical expectancy is violated. In summary, our results reveal neural mechanisms of music-syntactic processing that operate at different levels of cortical integration, ranging from early decrease in long-range alpha phase synchronization to late local gamma oscillations. 2008 Wiley-Liss, Inc.

  1. Adiponectin may be a biomarker of early atherosclerosis of smokers and decreased by nicotine through KATP channel in adipocytes.

    PubMed

    Fan, Li Hong; He, Ying; Xu, Wei; Tian, Hong Yan; Zhou, Yan; Liang, Qi; Huang, Xin; Huo, Jian Hua; Li, Hong Bin; Bai, Ling; Ma, Ai Qun

    2015-01-01

    Plasm adiponectin is decreased in smokers. Adiponectin is emerging as a potential key molecular marker in atherosclerosis and other cardiovascular diseases. The aim of this study was to investigate the association between serum adiponectin levels and early atherosclerosis in smokers. Furthermore, the role of the KATP channel in the down-regulation of adiponectin by smoking was preliminarily explored. We consecutively enrolled 96 men, including 50 smokers with atherosclerosis and 46 nonsmokers. Serum adiponectin was detected with enzyme-linked immunosorbent assay - in all participants. Large (C1) and small (C2) artery elasticity indices and carotid intima-media thickness (IMT) were measured as evaluation indexes of early atherosclerosis in smokers. Finally, the effect of nicotine via ATP-dependent potassium (KATP) channels on adiponectin secretion by 3T3-L1 preadipocytes was examined in vitro. Adiponectin levels of smokers were statistically negatively correlated to IMT (r = -.440; P < 0.001) and positively correlated to C1 (r = 0.448; P < 0.001) as well as C2 (r = 0.426; P = 0.002). In 3-T3-L1 preadipocytes, nicotine treatment significantly decreased adiponectin levels (P = 0.003), whereas the adiponectin level was rescued by the inhibition of KATP channel (P < 0.001). Serum adiponectin level was an independent predictor of early atherosclerosis in smokers. Nicotine might decrease adiponectin in part through altering KATP channels in adipocytes. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Matrix metalloproteinase (MMP)-2 decreases calponin-1 levels and contributes to arterial remodeling in early hypertension.

    PubMed

    Belo, Vanessa de Almeida; Parente, Juliana Montenegro; Tanus-Santos, José Eduardo; Castro, Michele M

    2016-10-15

    Increased matrix metalloproteinase (MMP)-2 is implicated in the vascular remodeling of hypertension. Calponin-1 is a contractile protein, and its absence is associated with vascular smooth muscle cell (VSMC) phenotype switch, which leads to migration and remodeling. We evaluated whether increased MMP-2 activity precedes chronic vascular remodeling by decreasing calponin-1 and inducing VSMC proliferation. Sham or two kidney-one clip (2K1C) rats were treated with doxycycline at 30mg/kg/day. Systolic blood pressure was increased in the 2K1C rats after 1 and 2weeks post-surgery, and doxycycline was effective to reduce it only at 2weeks of hypertension (p<0.05). Increased activity of MMP-2 was observed in aortas from 2K1C at 1 and 2weeks of hypertension, followed by increased VSMC proliferation, and those effects were abolished by treating 2K1C rats with doxycycline (p<0.05). Increased aortic media to lumen ratio started to emerge in 2K1C rats at 1week of hypertension, and it was established by 2weeks. MMP-2 and calponin-1 co-localized in the cytosol of VSMC. Aortas from 2K1C rats showed a significant reduction in calponin-1 levels at 1week of hypertension, and doxycycline prevented its loss (p<0.05). However, at 2weeks of hypertension, calponin-1 was upregulated in 2K1C (p<0.05 vs. Sham groups). The mRNA levels of calponin-1 were not altered in the aortas of 2K1C at 1week of hypertension. MMP-2 may contribute to the post-translational decrease in calponin-1, thus culminating in hypertension-induced maladaptive arterial remodeling. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Decreased Knee Joint Loading Associated With Early Knee Osteoarthritis After Anterior Cruciate Ligament Injury

    PubMed Central

    Wellsandt, Elizabeth; Gardinier, Emily S.; Manal, Kurt; Axe, Michael J.; Buchanan, Thomas S.; Snyder-Mackler, Lynn

    2015-01-01

    Background Anterior cruciate ligament (ACL) injury predisposes individuals to early-onset knee joint osteoarthritis (OA). Abnormal joint loading is apparent after ACL injury and reconstruction. The relationship between altered joint biomechanics and the development of knee OA is unknown. Hypothesis Altered knee joint kinetics and medial compartment contact forces initially after injury and reconstruction are associated with radiographic knee OA 5 years after reconstruction. Study Design Case-control study; Level of evidence, 3. Methods Individuals with acute, unilateral ACL injury completed gait analysis before (baseline) and after (posttraining) preoperative rehabilitation and at 6 months, 1 year, and 2 years after reconstruction. Surface electromyographic and knee biomechanical data served as inputs to an electromyographically driven musculoskeletal model to estimate knee joint contact forces. Patients completed radiographic testing 5 years after reconstruction. Differences in knee joint kinetics and contact forces were compared between patients with and those without radiographic knee OA. Results Patients with OA walked with greater frontal plane interlimb differences than those without OA (nonOA) at baseline (peak knee adduction moment difference: 0.00 ± 0.08 N·m/kg·m [nonOA] vs −0.15 ± 0.09 N·m/kg·m [OA], P = .014; peak knee adduction moment impulse difference: −0.001 ± 0.032 N·m·s/kg·m [nonOA] vs −0.048 ± 0.031 N·m·s/kg·m [OA], P = .042). The involved limb knee adduction moment impulse of the group with osteoarthritis was also lower than that of the group without osteoarthritis at baseline (0.087 ± 0.023 N·m·s/kg·m [nonOA] vs 0.049 ± 0.018 N·m·s/kg·m [OA], P = .023). Significant group differences were absent at posttraining but reemerged 6 months after reconstruction (peak knee adduction moment difference: 0.02 ± 0.04 N·m/kg·m [nonOA] vs −0.06 ± 0.11 N·m/kg·m [OA], P = .043). In addition, the OA group walked with lower peak

  4. A novel classification of prostate specific antigen (PSA) biosensors based on transducing elements.

    PubMed

    Najeeb, Mansoor Ani; Ahmad, Zubair; Shakoor, R A; Mohamed, A M A; Kahraman, Ramazan

    2017-06-01

    During the last few decades, there has been a tremendous rise in the number of research studies dedicated towards the development of diagnostic tools based on bio-sensing technology for the early detection of various diseases like cardiovascular diseases (CVD), many types of cancer, diabetes mellitus (DM) and many infectious diseases. Many breakthroughs have been developed in the areas of improving specificity, selectivity and repeatability of the biosensor devices. Innovations in the interdisciplinary areas like biotechnology, genetics, organic electronics and nanotechnology also had a great positive impact on the growth of bio-sensing technology. As a product of these improvements, fast and consistent sensing policies have been productively created for precise and ultrasensitive biomarker-based disease diagnostics. Prostate-specific antigen (PSA) is widely considered as an important biomarker used for diagnosing prostate cancer. There have been many publications based on various biosensors used for PSA detection, but a limited review was available for the classification of these biosensors used for the detection of PSA. This review highlights the various biosensors used for PSA detection and proposes a novel classification for PSA biosensors based on the transducer type used. We also highlight the advantages, disadvantages and limitations of each technique used for PSA biosensing which will make this article a complete reference tool for the future researches in PSA biosensing. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Crude glycerin decreases nonesterified fatty acid concentration in ewes during late gestation and early lactation.

    PubMed

    Polizel, D M; Susin, I; Gentil, R S; Ferreira, E M; de Souza, R A; Freire, A P A; Pires, A V; Ferraz, M V C; Rodrigues, P H M; Eastridge, M L

    2017-02-01

    Crude glycerin is a gluconeogenic substrate in ruminants and may help to decrease the occurrence of pregnancy toxemia. The objective in this trial was to determine the effects of feeding a diet containing crude glycerin on DMI, milk yield, milk composition, and blood metabolites in periparturient ewes and lamb performance. One hundred eighteen 90 (±1.1)-d pregnant Santa Inês ewes were used. After lambing, 32 ewes (62.8 ± 1.3 kg BW) were allotted in a randomized complete block design defined by prelambing diet, BW, BCS, lambing date, type of birth (single or twin), and sex of offspring. Diets were isonitrogenous (13.0 ± 0.3% CP, DM basis), composed of concentrate and raw sugarcane bagasse (70:30 ratio, DM basis), and fed ad libitum daily. Crude glycerin (83.6% glycerol) levels were 0 or 10% (DM basis), corresponding to the experimental diets G0 and G10, respectively. From 8 until 56 d of lactation, DMI was determined. In the same period, once a week at 1000 h, the ewes were separated from the lambs and mechanically milked after intravenous administration of 10 IU of synthetic oxytocin. Three hours after the first milking, ewes were milked again and milk yield and composition were determined. Glucose, NEFA, and β-hydroxybutyrate (BHBA) were determined at -14, -7, 0, 7, 14, 28, and 56 d relative to lambing and insulin was determined at -14, -7, 0, and 7 d. Crude glycerin did not affect DMI (2.2 kg/d for G0 vs. 2.2 kg/d for G10; = 0.93) or milk production (171 g/3 h for G0 vs. 164 g/3 h for G10; = 0.66). However, there was a decrease ( = 0.01) in milk fat percentage (8.1% for G0 vs. 7.0% for G10) for ewes fed glycerin. Ewes fed the G10 diet had decreased ( < 0.01) NEFA concentration (0.27 mmol/L for G0 vs. 0.18 mmol/L for G10). There was an interaction between diet × time for glucose ( = 0.04), insulin ( = 0.05), and BHBA ( = 0.01); feeding glycerin increased glucose (5.61 mmol/L for G0 vs. 7.42 mmol/L for G10; < 0.01) and insulin concentrations (10.5 μIU for G0

  6. Early Life Adversity Is Associated With Elevated Levels of Circulating Leptin, Irisin, and Decreased Levels of Adiponectin in Midlife Adults

    PubMed Central

    Joung, Kyoung Eun; Park, Kyung-Hee; Zaichenko, Lesya; Sahin-Efe, Ayse; Thakkar, Bindiya; Brinkoetter, Mary; Usher, Nicole; Warner, Dorothy; Davis, Cynthia R.; Crowell, Judith A.

    2014-01-01

    Context: Early-life adversity, defined as physical, emotional, or sexual abuse and neglect before 18 years of age, is associated with metabolic syndrome, obesity, and type 2 diabetes mellitus in adult life. However, the underlying mechanism is not fully understood, and whether adipomyokines are associated with early-life adversity independent of other factors such as body mass index, psychosocial risks, and health behaviors is not known. Objectives: The objective of the study was to evaluate the association between early-life adversity and circulating the levels of the adipomyokines such as leptin, adiponectin, and irisin and the inflammatory marker, C-reactive protein (CRP). Design/Subjects/Setting: This study was a cross-sectional study of 95 adults at a university-based research center. We collected venous blood from participants and analyzed serum for leptin, adiponectin, irisin, and CRP. Results: Circulating leptin, irisin, and CRP levels were significantly higher in the highest adversity tertile group compared with low and middle tertile groups (P < .001 for leptin, P = .01 for irisin, and P = .02 for CRP). Adiponectin levels were lower in the highest tertile group compared with the low and middle tertile groups (P = .03). After adjusting for demographic variables, physical activity, diet, current mental health, and body mass index, the associations between early-life adversity leptin, irisin, and did not change. However, adiponectin and CRP levels were no longer significantly related to early life adversity. Conclusion: Early-life adversity is directly associated with elevated circulating leptin and irisin, and indirectly associated with elevated CRP and decreased adiponectin. These findings suggest that these adipomyokines may play a role in the pathogenesis of metabolic abnormality in a population with significant early life adversity. PMID:24650014

  7. Early Results of a Helmetless-Tackling Intervention to Decrease Head Impacts in Football Players

    PubMed Central

    Swartz, Erik E.; Broglio, Steven P.; Cook, Summer B.; Cantu, Robert C.; Ferrara, Michael S.; Guskiewicz, Kevin M.; Myers, Jay L.

    2015-01-01

    Objective To test a helmetless-tackling behavioral intervention for reducing head impacts in National Collegiate Athletic Association Division I football players. Design Randomized controlled clinical trial. Setting Football field. Patients or Other Participants Fifty collegiate football players (intervention = 25, control = 25). Intervention(s) The intervention group participated in a 5-minute tackling drill without their helmets and shoulder pads twice per week in the preseason and once per week through the season. During this time, the control group performed noncontact football skills. Main Outcome Measure(s) Frequency of head impacts was recorded by an impact sensor for each athlete-exposure (AE). Data were tested with a 2 × 3 (group and time) repeated-measures analysis of variance. Significant interactions and main effects (P < .05) were followed with t tests. Results Head impacts/AE decreased for the intervention group compared with the control group by the end of the season (9.99 ± 6.10 versus 13.84 ± 7.27, respectively). The intervention group had 30% fewer impacts/AE than the control group by season's end (9.99 ± 6.10 versus 14.32 ± 8.45, respectively). Conclusion A helmetless-tackling training intervention reduced head impacts in collegiate football players within 1 season. PMID:26651278

  8. Prevalence and causes of abnormal PSA recovery.

    PubMed

    Lautenbach, Noémie; Müntener, Michael; Zanoni, Paolo; Saleh, Lanja; Saba, Karim; Umbehr, Martin; Velagapudi, Srividya; Hof, Danielle; Sulser, Tullio; Wild, Peter J; von Eckardstein, Arnold; Poyet, Cédric

    2018-01-26

    Prostate-specific antigen (PSA) test is of paramount importance as a diagnostic tool for the detection and monitoring of patients with prostate cancer. In the presence of interfering factors such as heterophilic antibodies or anti-PSA antibodies the PSA test can yield significantly falsified results. The prevalence of these factors is unknown. We determined the recovery of PSA concentrations diluting patient samples with a standard serum of known PSA concentration. Based on the frequency distribution of recoveries in a pre-study on 268 samples, samples with recoveries <80% or >120% were defined as suspect, re-tested and further characterized to identify the cause of interference. A total of 1158 consecutive serum samples were analyzed. Four samples (0.3%) showed reproducibly disturbed recoveries of 10%, 68%, 166% and 4441%. In three samples heterophilic antibodies were identified as the probable cause, in the fourth anti-PSA-autoantibodies. The very low recovery caused by the latter interference was confirmed in serum, as well as heparin- and EDTA plasma of blood samples obtained 6 months later. Analysis by eight different immunoassays showed recoveries ranging between <10% and 80%. In a follow-up study of 212 random plasma samples we found seven samples with autoantibodies against PSA which however did not show any disturbed PSA recovery. About 0.3% of PSA determinations by the electrochemiluminescence assay (ECLIA) of Roche diagnostics are disturbed by heterophilic or anti-PSA autoantibodies. Although they are rare, these interferences can cause relevant misinterpretations of a PSA test result.

  9. Massage therapy decreases cancer-related fatigue: Results from a randomized early phase trial.

    PubMed

    Kinkead, Becky; Schettler, Pamela J; Larson, Erika R; Carroll, Dedric; Sharenko, Margaret; Nettles, James; Edwards, Sherry A; Miller, Andrew H; Torres, Mylin A; Dunlop, Boadie W; Rakofsky, Jeffrey J; Rapaport, Mark Hyman

    2018-02-01

    Cancer-related fatigue (CRF) is a prevalent and debilitating symptom experienced by cancer survivors, yet treatment options for CRF are limited. In this study, we evaluated the efficacy of weekly Swedish massage therapy (SMT) versus an active control condition (light touch [LT]) and waitlist control (WLC) on persistent CRF in breast cancer survivors. This early phase, randomized, single-masked, 6-week investigation of SMT, LT, and WLC enrolled 66 female stage 0-III breast cancer survivors (age range, 32-72 years) who had received surgery plus radiation and/or chemotherapy/chemoprevention with CRF (Brief Fatigue Inventory > 25). The primary outcome was the Multidimensional Fatigue Inventory (MFI), with the National Institutes of Health PROMIS Fatigue scale secondary. Mean baseline MFI scores for 57 evaluable subjects were 62.95 for SMT, 55.00 for LT, and 60.41 for WLC. SMT resulted in a mean (standard deviation) 6-week reduction in MFI total scores of -16.50 (6.37) (n = 20) versus -8.06 (6.50) for LT (n = 20) and an increase of 5.88 (6.48) points for WLC (n = 17) (treatment-by-time P < .0001). The mean baseline PROMIS Fatigue scores were SMT, 22.25; LT, 22.05; and WLC, 23.24. The mean (standard deviation) reduction in PROMIS Fatigue scores was -5.49 (2.53) points for SMT versus -3.24 (2.57) points for LT and -0.06 (1.88) points for WLC (treatment-by-time P = .0008). Higher credibility, expectancy, and preference for SMT than for LT did not account for these results. SMT produced clinically significant relief of CRF. This finding suggests that 6 weeks of a safe, widely accepted manual intervention causes a significant reduction in fatigue, a debilitating sequela for cancer survivors. Cancer 2018;124:546-54. © 2017 American Cancer Society. © 2017 American Cancer Society.

  10. Early transcutaneous electrical nerve stimulation reduces hyperalgesia and decreases activation of spinal glial cells in mice with neuropathic pain.

    PubMed

    Matsuo, Hideaki; Uchida, Kenzo; Nakajima, Hideaki; Guerrero, Alexander Rodriguez; Watanabe, Shuji; Takeura, Naoto; Sugita, Daisuke; Shimada, Seiichiro; Nakatsuka, Terumasa; Baba, Hisatoshi

    2014-09-01

    Although transcutaneous electrical nerve stimulation (TENS) is widely used for the treatment of neuropathic pain, its effectiveness and mechanism of action in reducing neuropathic pain remain uncertain. We investigated the effects of early TENS (starting from the day after surgery) in mice with neuropathic pain, on hyperalgesia, glial cell activation, pain transmission neuron sensitization, expression of proinflammatory cytokines, and opioid receptors in the spinal dorsal horn. Following nerve injury, TENS and behavioral tests were performed every day. Immunohistochemical, immunoblot, and flow cytometric analysis of the lumbar spinal cord were performed after 8 days. Early TENS reduced mechanical and thermal hyperalgesia and decreased the activation of microglia and astrocytes (P<0.05). In contrast, the application of TENS at 1 week (TENS-1w) or 2 weeks (TENS-2w) after injury was ineffective in reducing hyperalgesia (mechanical and thermal) or activation of microglia and astrocytes. Early TENS decreased p-p38 within microglia (P<0.05), the expression levels of protein kinase C (PKC-γ), and phosphorylated anti-phospho-cyclic AMP response element-binding protein (p-CREB) in the superficial spinal dorsal horn neurons (P<0.05), mitogen-activated protein (MAP) kinases, and proinflammatory cytokines, and increased the expression levels of opioid receptors (P<0.05). The results suggested that the application of early TENS relieved hyperalgesia in our mouse model of neuropathic pain by inhibiting glial activation, MAP kinase activation, PKC-γ, and p-CREB expression, and proinflammatory cytokines expression, as well as maintenance of spinal opioid receptors. The findings indicate that TENS treatment is more effective when applied as early after nerve injury as possible. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  11. Early deep sedation is associated with decreased in-hospital and two-year follow-up survival.

    PubMed

    Balzer, Felix; Weiß, Björn; Kumpf, Oliver; Treskatsch, Sascha; Spies, Claudia; Wernecke, Klaus-Dieter; Krannich, Alexander; Kastrup, Marc

    2015-04-28

    There is increasing evidence that deep sedation is detrimental to critically ill patients. The aim of this study was to examine effects of deep sedation during the early period after ICU admission on short- and long-term survival. In this observational, matched-pair analysis, patients receiving mechanical ventilation that were admitted to ICUs of a tertiary university hospital in six consecutive years were grouped as either lightly or deeply sedated within the first 48 hours after ICU admission. The Richmond Agitation-Sedation Score (RASS) was used to assess sedation depth (light sedation: -2 to 0; deep: -3 or below). Multivariate Cox regression was conducted to investigate the impact of early deep sedation within the first 48 hours of admission on in-hospital and two-year follow-up survival. In total, 1,884 patients met inclusion criteria out of which 27.2% (n = 513) were deeply sedated. Deeply sedated patients had longer ventilation times, increased length of stay and higher rates of mortality. Early deep sedation was associated with a hazard ratio of 1.661 (95% CI: 1.074 to 2.567; P = 0.022) for in-hospital survival and 1.866 (95% CI: 1.351 to 2.576; P < 0.001) for two-year follow-up survival. Early deep sedation during the first 48 hours of intensive care treatment was associated with decreased in-hospital and two-year follow-up survival. Since early deep sedation is a modifiable risk factor, this data shows an urgent need for prospective clinical trials focusing on light sedation in the early phase of ICU treatment.

  12. The impact of socioeconomic status on stage specific prostate cancer survival and mortality before and after introduction of PSA test in Finland.

    PubMed

    Seikkula, Heikki A; Kaipia, Antti J; Ryynänen, Heidi; Seppä, Karri; Pitkäniemi, Janne M; Malila, Nea K; Boström, Peter J

    2018-03-01

    Socioeconomic status (SES) has an impact on prostate cancer (PCa) outcomes. Men with high SES have higher incidence and lower mortality of PCa versus lower SES males. PCa cases diagnosed in Finland in 1985-2014 (N = 95,076) were identified from the Finnish Cancer Registry. Information on education level (EL) was obtained from Statistics Finland. EL was assessed with three-tiered scale: basic, upper secondary and higher education. PCa stage at diagnosis was defined as localized, metastatic or unknown. Years of diagnosis 1985-1994 were defined as pre-PSA period and thereafter as post-PSA period. We report PCa-specific survival (PCSS) and relative risks (RR) for PCa specific mortality (PCSM) among cancer cases in Finland, where healthcare is 100% publicly reimbursed and inequality in healthcare services low. Men with higher EL had markedly better 10-year PCSS: 68 versus 63% in 1985-1994 and 90 versus 85% in 1995-2004 compared to basic EL in localized PCa. The RR for PCSM among men with localized PCa and higher EL compared to basic EL was 0.76(95%confidence interval (CI) 0.66-0.88) in 1985-1994 and 0.61(95%CI 0.53-0.70) in 1995-2004. Variation in PCSS and PCSM between EL categories was evident in metastatic PCa, too. The difference in PCSM between EL categories was larger in the first 10-year post-PSA period than before that but decreased thereafter in localized PCa, suggesting PSA testing became earlier popular among men with high EL. In summary, higher SES/EL benefit PCa survival both in local and disseminated disease and the effect of EL was more pronounced in early post-PSA period. © 2017 UICC.

  13. Decreased Glucose Metabolism in Medial Prefrontal Areas is Associated with Nutritional Status in Patients with Prodromal and Early Alzheimer's Disease.

    PubMed

    Sugimoto, Taiki; Nakamura, Akinori; Kato, Takashi; Iwata, Kaori; Saji, Naoki; Arahata, Yutaka; Hattori, Hideyuki; Bundo, Masahiko; Ito, Kengo; Niida, Shumpei; Sakurai, Takashi

    2017-01-01

    Weight loss is frequently observed in patients with Alzheimer's disease (AD); however, the underlying mechanisms are not well understood. To clarify the associations between nutritional status and AD-related brain changes using Pittsburgh Compound-B (PiB)-PET, fluorodeoxyglucose (FDG)-PET, and structural MRI. The subjects were 34 amyloid-β (Aβ)-positive individuals with mild cognitive impairment or early AD (prodromal/early AD), and 55 Aβ-negative cognitively normal (CN) subjects who attended the Multimodal Neuroimaging for AD Diagnosis (MULNIAD) study. Nutritional status of the subjects was assessed by body mass index and waist to height ratio (waist circumference/height). The associations between nutritional status and brain changes were examined by multiple regression analysis using statistical parametric mapping. In the prodromal/early AD group, nutritional status was significantly positively correlated with regional cerebral glucose metabolism (rCGM) in the medial prefrontal cortices, while different topographical associations were seen in the CN group, suggesting these changes were AD-specific. Aβ deposition and gray matter volume were not significantly associated with nutritional status. Sub-analysis in the prodromal/early AD group demonstrated that fat mass index, but not fat-free mass index, was positively correlated with rCGM in the medial prefrontal areas. This present study provides preliminary results suggesting that hypometabolism in the medial prefrontal areas is specifically associated with AD-related weight loss, and decrease in fat mass may have a key role.

  14. Early arthritis induces disturbances at bone nanostructural level reflected in decreased tissue hardness in an animal model of arthritis

    PubMed Central

    Cascão, Rita; Finnilä, Mikko A. J.; Lopes, Inês P.; Saarakkala, Simo; Zioupos, Peter; Canhão, Helena; Fonseca, João E.

    2018-01-01

    Introduction Arthritis induces joint erosions and skeletal bone fragility. Objectives The main goal of this work was to analyze the early arthritis induced events at bone architecture and mechanical properties at tissue level. Methods Eighty-eight Wistar rats were randomly housed in experimental groups, as follows: adjuvant induced arthritis (AIA) (N = 47) and a control healthy group (N = 41). Rats were monitored during 22 days for the inflammatory score, ankle perimeter and body weight and sacrificed at different time points (11 and 22 days post disease induction). Bone samples were collected for histology, micro computed tomography (micro-CT), 3-point bending and nanoindentation. Blood samples were also collected for bone turnover markers and systemic cytokine quantification. Results At bone tissue level, measured by nanoindentation, there was a reduction of hardness in the arthritic group, associated with an increase of the ratio of bone concentric to parallel lamellae and of the area of the osteocyte lacuna. In addition, increased bone turnover and changes in the microstructure and mechanical properties were observed in arthritic animals, since the early phase of arthritis, when compared with healthy controls. Conclusion We have shown in an AIA rat model that arthritis induces very early changes at bone turnover, structural degradation and mechanical weakness. Bone tissue level is also affected since the early phase of arthritis, characterized by decreased tissue hardness associated with changes in bone lamella organization and osteocyte lacuna surface. These observations highlight the pertinence of immediate control of inflammation in the initial stages of arthritis. PMID:29315314

  15. Probability of an Abnormal Screening PSA Result Based on Age, Race, and PSA Threshold

    PubMed Central

    Espaldon, Roxanne; Kirby, Katharine A.; Fung, Kathy Z.; Hoffman, Richard M.; Powell, Adam A.; Freedland, Stephen J.; Walter, Louise C.

    2014-01-01

    Objective To determine the distribution of screening PSA values in older men and how different PSA thresholds affect the proportion of white, black, and Latino men who would have an abnormal screening result across advancing age groups. Methods We used linked national VA and Medicare data to determine the value of the first screening PSA test (ng/mL) of 327,284 men age 65+ who underwent PSA screening in the VA healthcare system in 2003. We calculated the proportion of men with an abnormal PSA result based on age, race, and common PSA thresholds. Results Among men age 65+, 8.4% had a PSA >4.0ng/mL. The percentage of men with a PSA >4.0ng/mL increased with age and was highest in black men (13.8%) versus white (8.0%) or Latino men (10.0%) (P<0.001). Combining age and race, the probability of having a PSA >4.0ng/mL ranged from 5.1% of Latino men age 65–69 to 27.4% of black men age 85+. Raising the PSA threshold from >4.0ng/mL to >10.0ng/mL, reclassified the greatest percentage of black men age 85+ (18.3% absolute change) and the lowest percentage of Latino men age 65–69 (4.8% absolute change) as being under the biopsy threshold (P<0.001). Conclusions Age, race, and PSA threshold together affect the pre-test probability of an abnormal screening PSA result. Based on screening PSA distributions, stopping screening among men whose PSA < 3ng/ml means over 80% of white and Latino men age 70+ would stop further screening, and increasing the biopsy threshold to >10ng/ml has the greatest effect on reducing the number of older black men who will face biopsy decisions after screening. PMID:24439009

  16. Long-term clinical impact of PSA surge in castration-resistant prostate cancer patients treated with abiraterone.

    PubMed

    Conteduca, Vincenza; Caffo, Orazio; Lolli, Cristian; Aieta, Michele; Scarpi, Emanuela; Bianchi, Emanuela; Maines, Francesca; Schepisi, Giuseppe; Salvi, Samanta; Massari, Francesco; Carrozza, Francesco; Veccia, Antonello; Chiuri, Vincenzo E; Campadelli, Enrico; Facchini, Gaetano; De Giorgi, Ugo

    2017-06-01

    Early changes in PSA have been evaluated in association to treatment outcome. The aim of this study was to assess PSA surge phenomenon in castration-resistant prostate cancer (CRPC) patients treated with abiraterone and to correlate those variations with long-term treatment outcome. We retrospectively evaluated 330 CRPC patients in 11 Italian hospitals, monitoring PSA levels at baseline and every 4 weeks. Other clinical, biochemical and molecular parameters were determined at baseline. We considered PSA surge as PSA increase within the first 8 weeks from starting abiraterone more than 1% from baseline followed by a PSA decline. The log-rank test was applied to compare survival between groups of patients according to PSA surge. The impact of PSA surge on survival was evaluated by Cox regression analyses. A total of 330 patients with CRPC, median age 74 years (range, 45-90), received abiraterone (281 chemotherapy-treated and 49 chemotherapy-naïve). PSA surge was observed in 20 (7%) post-chemotherapy and 2 (4%) chemotherapy-naïve patients. For overall patients presenting PSA surge, timing of PSA peak from baseline was 5 ± 1.8 weeks and PSA rise from baseline was 21 ± 18.4%. The overall median follow-up was 23 months (range 1-62). No significant differences in progression-free survival and overall survival were observed between patients with and without PSA surge (P = 0.16 and =0.86, respectively). In addition, uni- and multivariate analyses showed no baseline factors related to PSA surge. PSA surge occurs in both chemotherapy-treated and chemotherapy-naïve patients treated with abiraterone resulting, however, in no long-term impact on outcome. Physicians and patients should be aware of PSA surge challenge to prevent a premature discontinuation of potentially effective therapy with abiraterone. Further larger and prospective studies are warranted to investigate this not infrequent phenomenon. © 2017 Wiley Periodicals, Inc.

  17. Re-examining Prostate-specific Antigen (PSA) Density: Defining the Optimal PSA Range and Patients for Using PSA Density to Predict Prostate Cancer Using Extended Template Biopsy.

    PubMed

    Jue, Joshua S; Barboza, Marcelo Panizzutti; Prakash, Nachiketh S; Venkatramani, Vivek; Sinha, Varsha R; Pavan, Nicola; Nahar, Bruno; Kanabur, Pratik; Ahdoot, Michael; Dong, Yan; Satyanarayana, Ramgopal; Parekh, Dipen J; Punnen, Sanoj

    2017-07-01

    To compare the predictive accuracy of prostate-specific antigen (PSA) density vs PSA across different PSA ranges and by prior biopsy status in a prospective cohort undergoing prostate biopsy. Men from a prospective trial underwent an extended template biopsy to evaluate for prostate cancer at 26 sites throughout the United States. The area under the receiver operating curve assessed the predictive accuracy of PSA density vs PSA across 3 PSA ranges (<4 ng/mL, 4-10 ng/mL, >10 ng/mL). We also investigated the effect of varying the PSA density cutoffs on the detection of cancer and assessed the performance of PSA density vs PSA in men with or without a prior negative biopsy. Among 1290 patients, 585 (45%) and 284 (22%) men had prostate cancer and significant prostate cancer, respectively. PSA density performed better than PSA in detecting any prostate cancer within a PSA of 4-10 ng/mL (area under the receiver operating characteristic curve [AUC]: 0.70 vs 0.53, P < .0001) and within a PSA >10 mg/mL (AUC: 0.84 vs 0.65, P < .0001). PSA density was significantly more predictive than PSA in detecting any prostate cancer in men without (AUC: 0.73 vs 0.67, P < .0001) and with (AUC: 0.69 vs 0.55, P < .0001) a previous biopsy; however, the incremental difference in AUC was higher among men with a previous negative biopsy. Similar inferences were seen for significant cancer across all analyses. As PSA increases, PSA density becomes a better marker for predicting prostate cancer compared with PSA alone. Additionally, PSA density performed better than PSA in men with a prior negative biopsy. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Early cognitive impairment along with decreased stress-induced BDNF in male and female patients with newly diagnosed multiple sclerosis.

    PubMed

    Prokopova, Barbora; Hlavacova, Natasa; Vlcek, Miroslav; Penesova, Adela; Grunnerova, Lucia; Garafova, Alexandra; Turcani, Peter; Kollar, Branislav; Jezova, Daniela

    2017-01-15

    The aim of this study was to evaluate neuroendocrine activation during stress in patients with recently diagnosed multiple sclerosis before starting the immunomodulatory therapy (EDSS score≤2.0). We verified the hypothesis that certain cognitive and affective dysfunction is present already at this early stage of the disease. The sample consisted of 38 subjects, which involved patients who were recently diagnosed multiple sclerosis and age- and sex-matched healthy volunteers. Stroop test served as mental stress model enabling measurement of cognitive performance. Present results showed increased state anxiety, depression scores and poorer performance in the Stroop test in the group of patients compared to healthy subjects. The cognitive dysfunction was particularly evident in male patients with simultaneously decreased concentrations of the brain-derived neurotrophic factor (BDNF) in plasma. The patients at this stage of the disease have not yet developed the hyperactivity of the hypothalamic-pituitary-adrenocortical axis. They showed normal levels of plasma copeptin and reduced aldosterone response to mental stress test in women only. Concentrations of plasma copeptin were higher in men compared to women. Very early stages of multiple sclerosis are accompanied by disturbances in psychological well-being, mild cognitive dysfunction and decreased plasma concentrations of BDNF, particularly in male patients. Copyright © 2016. Published by Elsevier B.V.

  19. Progressive Decrease of Peripapillary Angioflow Vessel Density During Structural and Visual Field Progression in Early Primary Open-angle Glaucoma.

    PubMed

    Holló, Gábor

    2017-07-01

    To present a case of early primary open-angle glaucoma in which retinal nerve fiber layer thickness (RNFLT), ganglion cell complex (GCC), and visual field progression were accompanied with significant progression of peripapillary angioflow vessel density (PAFD) measured with optical coherence tomographic angiography. A 68-year-old female patient who was under topical intraocular pressure (IOP) lowering medication for 20 years for ocular hypertension of the right and preperimetric primary open-angle glaucoma of the left eye (with reproducible inferotemporal and superotemporal neuroretinal rim and RNFL loss) was prospectively imaged with the AngioVue OCT for RNFLT, GCC thickness, and PAFD, and investigated with the Octopus Normal G2 visual field test on the same days at 6-month intervals for 18 months, while the IOP of the left eye escaped from control. IOP of the left eye fluctuated between 14 and 30 mm Hg in the study period. RNFLT, GCC thickness, and peripapillary PAFD all decreased significantly (linear regression analysis, P=0.030, 0.040, and 0.020, respectively), and a significant 2.1 dB/y progression was seen for a superior visual field cluster. The RNFLT, peripapillary PAFD, and visual field of the right eye remained normal and unchanged. In our case IOP elevation, glaucomatous visual field conversion, and structural progression were accompanied with significant progressive decrease of peripapillary PAFD. The simultaneous thinning of RNFLT and GCC and decrease of peripapillary PAFD suggest that PAFD may potentially be an additional indicator of early progression in primary open-angle glaucoma.

  20. LOW PRETERM BIRTH RATE WITH DECREASING EARLY NEONATAL MORTALITY IN BOSNIA AND HERZEGOVINA DURING 2007-2014

    PubMed Central

    Hudic, Igor; Stray-Pedersen, Babill; Skokic, Fahrija; Fatusic, Zlatan; Zildzic-Moralic, Aida; Skokic, Maida; Fatusic, Jasenko

    2016-01-01

    The aim: of the study was to determine the situation of preterm births and early neonatal mortality during 2007-2014 in Tuzla Canton, Bosnia and Herzegovina. Methods: The study covers a 8-year period and is based on the protocols at the Tuzla Clinic for Gynecology and Obstetrics that covers all birth in Tuzla Canton area. We analyzed the gestational age of all newborns and recorded the number of neonatal deaths in the first week after birth. Demographics, pregnancy and birth characteristics were collected from the maternal records. Results: The total number of births in the period was 32738. Preterm birth was identified in 2401 (7.3%) cases with 12,5% occurring before 32 gestational weeks and 64% in 35-36 gestational weeks. The mothers of the 24-31 gws preterm group were significantly younger that those in the 32-36 group. In the 32-36 group there were significantly greater proportions of mothers with assisted reproductive technology and pre-eclampsia and 16.7% was medical induced preterm births versus 11.4 % in the 24-31 PTB group, p<0.05. The incidence of PTB did no vary significantly during the period, the lowest rate was found in 2010 (6.4%). A total of 221 children died giving a early mortality rate of 6.8 per 1000 live born over the 8 years. The majority 156 dying infants (70.6%) were preterm, only 5.7% died being born in the 35-36 gestational week (5.9 per 1000). Overall the preterm early mortality (7.3 per 1000) has shown a decreasing tendency during the latter years. Conclusion: During the last 8 years there have been no significant decline in preterm birth in the Tuzla region while a decline in early neonatal death has been registered. PMID:27047264

  1. Enzymatic Activity of Free-Prostate-Specific Antigen (f-PSA) Is Not Required for Some of its Physiological Activities

    PubMed Central

    Chadha, Kailash C.; Nair, Bindukumar B.; Chakravarthi, Srikant; Zhou, Rita; Godoy, Alejandro; Mohler, James L.; Aalinkeel, Ravikumar; Schwartz, Stanley A.; Smith, Gary J.

    2015-01-01

    BACKGROUND Prostate specific antigen (PSA) is a well known biomarker for early diagnosis and management of prostate cancer. Furthermore, PSA has been documented to have anti-angiogenic and anti-tumorigenic activities in both in vitro and in vivo studies. However, little is known about the molecular mechanism(s) involved in regulation of these processes, in particular the role of the serine-protease enzymatic activity of PSA. METHODS Enzymatic activity of PSA isolated directly from seminal plasma was inhibited specifically (>95%) by incubation with zinc2+. Human umbilical vein endothelial cells (HUVEC) were utilized to compare/contrast the physiological effects of enzymatically active versus inactive PSA. RESULTS Equimolar concentrations of enzymatically active PSA and PSA enzymatically inactivated by incubation with Zn2+ had similar physiological effects on HUVEC, including inhibiting the gene expression of pro-angiogenic growth factors, like VEGF and bFGF, and up-regulation of expression of the anti-angiogenic growth factor IFN-γ; suppression of mRNA expression for markers of blood vessel development, like FAK, FLT, KDR, TWIST-1; P-38; inhibition of endothelial tube formation in the in vitro Matrigel Tube Formation Assay; and inhibition of endothelial cell invasion and migration properties. DISCUSSION Our data provides compelling evidence that the transcriptional regulatory and the anti-angiogenic activities of human PSA are independent of the innate enzymatic activity PMID:21446007

  2. The ESA Planetary Science Archive User Group (PSA-UG)

    NASA Astrophysics Data System (ADS)

    Pio Rossi, Angelo; Cecconi, Baptiste; Fraenz, Markus; Hagermann, Axel; Heather, David; Rosenblatt, Pascal; Svedhem, Hakan; Widemann, Thomas

    2014-05-01

    ESA has established a Planetary Science Archive User Group (PSA-UG), with the task of offering independent advice to ESA's Planetary Science Archive (e.g. Heather et al., 2013). The PSA-UG is an official and independent body that continuously evaluates services and tools provided by the PSA to the community of planetary data scientific users. The group has been tasked with the following top level objectives: a) Advise ESA on future development of the PSA. b) Act as a focus for the interests of the scientific community. c) Act as an advocate for the PSA. d) Monitor the PSA activities. Based on this, the PSA-UG will report through the official ESA channels. Disciplines and subjects represented by PSA-UG members include: Remote Sensing of both Atmosphere and Solid Surfaces, Magnetospheres, Plasmas, Radio Science and Auxilliary data. The composition of the group covers ESA missions populating the PSA both now and in the near future. The first members of the PSA-UG were selected in 2013 and will serve for 3 years, until 2016. The PSA-UG will address the community through workshops, conferences and the internet. Written recommendations will be made to the PSA coordinator, and an annual report on PSA and the PSA-UG activities will be sent to the Solar System Exploration Working Group (SSEWG). Any member of the community and planetary data user can get in touch with individual members of the PSA-UG or with the group as a whole via the contacts provided on the official PSA-UG web-page: http://archives.esac.esa.int/psa/psa-ug. The PSA is accessible via: http://archives.esac.esa.int/psa References: Heather, D., Barthelemy, M., Manaud, N., Martinez, S., Szumlas, M., Vazquez, J. L., Osuna, P. and the PSA Development Team (2013) ESA's Planetary Science Archive: Status, Activities and Plans. EuroPlanet Sci. Congr. #EPSC2013-626

  3. Prostate-specific antigen (PSA) as a possible biomarker in non-prostatic cancer: A review.

    PubMed

    Pérez-Ibave, Diana Cristina; Burciaga-Flores, Carlos Horacio; Elizondo-Riojas, Miguel-Ángel

    2018-06-01

    Prostate-specific antigen (PSA) is a serine protease produced by epithelial prostatic cells and its main function is to liquefy seminal coagulum. Currently, PSA is a biomarker for the diagnosis and screening of prostate cancer and it was the first cancer biomarker approved by the FDA. The quantity and serum isoforms of male PSA, allows distinguishing between carcinoma and benign inflammatory disease of the prostate. Initially, it was thought that PSA was produced only by the prostate, and thus, a protein that was expressed exclusively in men. However, several authors report that PSA is a protein that is expressed by multiple non-prostatic tissues not only in men but also in women. Some authors also report that in women, the expression of this protein is highly related to breast and colon cancer and therefore can act as a possible biomarker for early detection, diagnosis and prognosis of these cancers in women. In this review, we will focus on the characteristics of the PSA at a molecular level, its current clinical implications, the expression of this protein in non-prostatic tissues, and its relationship with cancer, especially in women. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. PDS4 Challenges in the PSA

    NASA Astrophysics Data System (ADS)

    Saiz, J.; Barbarisi, I.; Docasal, R.; Rios, C.; Montero, A.; Macfarlane, A.; Laantee, C.; Besse, S.; Vallat, C.; Marcos, J.; Arenas, J.; Osinde, J.; Arviset, C.

    2018-04-01

    The Planetary Science Archive (PSA) stores products from all planetary ESA missions. Adopting PDS4 as the standard for new missions, while being compatible with existing PDS3 products, has driven a design with several difficulties to overcome.

  5. Prostate-Specific Antigen (PSA) Test

    MedlinePlus

    ... incidence of prostate cancer than men in the control group but the same rate of deaths from the ... the PLCO trial who were assigned to the control group had nevertheless undergone PSA screening. This analysis suggested ...

  6. [Prostate cancer screening at Tatebayashi City in Gunma prefecture--results of screening with PSA alone between 2003 and 2005].

    PubMed

    Nakamura, Toshiyuki; Etsunaga, Toru; Sasaki, Yasushi; Nitta, Takashi; Okugi, Yasunobu; Okazaki, Hiroshi; Katou, Nobuo; Yamamoto, Takumi; Suzuki, Kazuhiro

    2007-05-01

    Since 2003, a basic health checkup has involved prostate cancer screening with prostate specific antigen (PSA) alone. We investigated the results between 2003 and 2005. Among males aged over 50 years who underwent a basic health checkup, the subjects were those who desired prostate cancer screening. Cancer screening with PSA alone was performed; mass screening or individual screening in hospitals in the city. We employed PSA with respect to age stratification. On the primary screening, written informed consent regarding the analysis of the screening results was obtained. In 2003, there were 15,303 males aged over 50 years in Tatebayashi City. In 2003, 2004, and 2005, 11.8%, 12.2%, and 12.7% of the males underwent PSA screening, respectively. The rate of elevated PSA levels between 2003 and 2005 was 20.6%. Furthermore, 208, 165, and 179 males required secondary screening, and 80.3%, 61.2%, and 55.3% of the males underwent secondary screening, respectively. Of the males who underwent secondary screening, prostate biopsy was performed in 123 (73.2%), 54 (53.5%), and 38 (38.4%). Prostate cancer was detected in 60, 28, and 16 males, respectively. These values corresponded to 3.4%, 1.5%, and 0.8% of the males who underwent primary screening. The incidence of prostate cancer was 1.85% during the 3 years, and 3.2% in males who underwent the initial health checkup. Of 101 males in whom the stage was evaluated, the clinical stage was evaluated as B in 86 (85.1%), C in 9 (8.9%), and D in 6 (5.9%). Of the 101 males, endocrine therapy was performed in 46 (45.5%), surgery in 31 (30.7%), external irradiation in 5 (5.0%), and followup without treatment in 6 (5.9%). In addition, 7 (6.3%) desired treatment in another hospital, and 6 (5.9%) refused treatment. Prostate cancer was detected in 1.85% of males who underwent primary screening between 2003 and 2005. Of 101 males in whom the stage was evaluated, the clinical stage was evaluated as B in 86 (85.1%), and the early treatment of

  7. The impact of comorbidity and PSA doubling time on the risk of death in men experiencing PSA failure following radiation therapy with or with androgen deprivation therapy for unfavorable-risk prostate cancer.

    PubMed

    Patel, S A; Chen, M-H; Loffredo, M; Renshaw, A; Kantoff, P W; D'Amico, A V

    2017-06-01

    The optimal management of men with PSA failure following initial prostate cancer (PC) therapy stratified by comorbidity is unknown. We investigated the impact that PSA doubling time (DT) and comorbidity had on the risk of all-cause mortality (ACM), prostate cancer-specific mortality (PCSM) and other-cause mortality (OCM) following PSA failure. Between 1995 and 2001, 206 men with unfavorable-risk PC were randomized to receive radiation therapy alone or in combination with 6 months of androgen deprivation therapy (ADT); 108 men experienced PSA failure and formed the study cohort. Cox and Fine-Gray regression analysis was used to determine whether PSA DT was associated with the risk of ACM and PCSM/OCM, respectively, stratified by comorbidity status using a validated metric. After a median follow-up of 13.71 years following PSA failure, 81 of the 108 men (75%) died. Longer PSA DT was associated with a decreased risk of PCSM in men with no/minimal (adjusted hazard ratio (AHR) 0.33, 95% confidence interval (CI) 0.17-0.65, P=0.001) and moderate/severe comorbidity (AHR 0.014, 95% CI 0.002-0.129, P=0.0002). However, because of the different contributions of the risk of OCM to risk of ACM within comorbidity subgroups, increasing PSA DT was only associated with a decreased risk of ACM in men with no/minimal (AHR 0.69, 95% CI 0.50-0.96, P=0.03) but not moderate/severe comorbidity (AHR 0.95, 95% CI 0.51-1.78, P=0.87). Both the extent of comorbidity and the PSA DT should be taken into consideration when deciding on appropriate management and/or clinical trial eligibility at the time of PSA failure.

  8. [Survival is associated with time to reach PSA nadir (DAN) and the ratio DAN/nadir value after androgen deprivation for prostate cancer].

    PubMed

    Gagnat, A; Larré, S; Fromont, G; Pirès, C; Doré, B; Irani, J

    2011-05-01

    The objective of this study was to assess the prognostic decrease rate of PSA in patients treated with androgen suppression (AS) for prostate cancer (PCa). We identified in our database CaP patients with histologically documented, treated with SA alone and for whom vital status with a minimum follow-up of 6 months (except death beforehand) was established. Patient characteristics and CaP and PSA at baseline, PSA nadir, time of reaching the nadir PSA (DAN) and the ratio of the DAN/nadir value (ratio DAN/Nadir) were analyzed in relation to progression-free survival, specific and overall survival. One hundred ninety eight patients met the inclusion criteria and the median was 61.5 months (range 4.8 to 233). The median PSA at the start of the SA were 37.1 ng/mL and the median nadir PSA was 0.48 ng/mL. The median time to progression was 23.6 months. The median specific and overall survivals were 94 and 78 months, respectively. In univariate analysis, predictors of progression-free survival were PSA before SA, PSA nadir, DAN, DAN ratio/nadir, Gleason score, the percentage of core positive prostate biopsy and the status of bone scintigraphy. Except for PSA before SA which was no longer significant, predictors of specific and overall survival were similar and added the biochemical response (decrease of more than 50% of PSA) to a second hormonal manipulation during the biological progression. In multivariate analysis, the nadir PSA and the ratio DAN/Nadir remained significant predictors. These results have confirmed in one hand the predictive value of survival in patients DAN SA for CaP: achieving faster nadir PSA was associated with shorter survival. They have introduced in the other hand the new concept of DAN/Nadir PSA which provides independent prognostic information. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  9. Rapamycin decreased blood-brain barrier permeability in control but not in diabetic rats in early cerebral ischemia.

    PubMed

    Chi, Oak Z; Kiss, Geza K; Mellender, Scott J; Liu, Xia; Weiss, Harvey R

    2017-07-27

    Diabetes causes functional and structural changes in blood-brain barrier (BBB). The mammalian target of rapamycin (mTOR) has been associated with glucose metabolism, diabetes, and altering BBB permeability. Since there is only a narrow therapeutic window (3h) for stroke victims, it is important to investigate BBB disruption in the early stage of cerebral ischemia. We compared the degree of BBB disruption in diabetic and in control rats at two hours of reperfusion after one hour of middle cerebral artery (MCA) occlusion with or without inhibition of mTOR. Two weeks after streptozotocin ip to induce diabetes, MCA occlusion was performed. In half of the rats, an mTOR inhibitor, rapamycin was given for 2days before MCA occlusion. After one hour of MCA occlusion and two hours of the reperfusion, the transfer coefficient (K i ) of 14 C-α-aminoisobutyric acid was determined to quantify degree of BBB disruption. Ischemia-reperfusion increased the K i in the control animals. Streptozotocin increased the K i in the ischemic-reperfused (IR-C, +22%) as well as in the contralateral cortex (CC, +40%). Rapamycin decreased the K i in the IR-C (-32%) as well as in the CC (-26%) in the control rats. However, rapamycin did not affect K i in the IR-C or in the CC in the diabetic rats. Our data demonstrated a greater BBB disruption in diabetes in the ischemic as well as non-ischemic cortex even in the early stage of cerebral ischemia-reperfusion and that acute administration of rapamycin did not significantly affect BBB permeability in diabetes. From our quantitative analysis of BBB disruption, the vulnerability of BBB in diabetes has been emphasized in the early stage of cerebral ischemia-reperfusion and a less important role of the mTOR pathway is suggested in altering BBB permeability in diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Early handling, but not maternal separation, decreases emotional responses in two paradigms of fear without changes in mesolimbic dopamine.

    PubMed

    Madruga, Clarice; Xavier, Léder L; Achaval, Matilde; Sanvitto, Gilberto L; Lucion, Aldo B

    2006-01-30

    This study aimed at identifying the effects of neonatal handling (H) and maternal separation (MS) on two paradigms of fear, learned and innate, and on the tyrosine hydroxylase (TH) immunoreactive cells in adult life. Wistar rats were daily handled with a brief maternal separation, maternal separated for 3 h or left undisturbed during the first 10 days of life. Behavioural responses in the open-field (innate fear) and conditioned fear (learned fear) were evaluated. Moreover, a semi-quantitative analysis of TH immunoreactivity in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNpc) was performed using optical densitometry and confirmed by planar measurements of neuronal density. Early handling decreased behaviour responses of innate and learned fear in adult life, while maternal separation had no significant long-lasting effect on these responses compared to the non-handled group. The behavioural effects of early handling could not be explained by changes in the density of midbrain dopaminergic cells, which were not affected by handling or maternal separation.

  11. Early Decrease in Respiration and Uncoupling Event Independent of Cytochrome c Release in PC12 Cells Undergoing Apoptosis

    PubMed Central

    Berghella, Libera; Ferraro, Elisabetta

    2012-01-01

    Cytochrome c is a key molecule in mitochondria-mediated apoptosis. It also plays a pivotal role in cell respiration. The switch between these two functions occurs at the moment of its release from mitochondria. This process is therefore extremely relevant for the fate of the cell. Since cytochrome c mediates respiration, we studied the changes in respiratory chain activity during the early stages of apoptosis in order to contribute to unravel the mechanisms of cytochrome c release. We found that, during staurosporine (STS)- induced apoptosis in PC12 cells, respiration is affected before the release of cytochrome c, as shown by a decrease in the endogenous uncoupled respiration and an uncoupling event, both occurring independently of cytochrome c release. The decline in the uncoupled respiration occurs also upon Bcl-2 overexpression (which inhibits cytochrome c release), while the uncoupling event is inhibited by Bcl-2. We also observed that the first stage of nuclear condensation during STS-induced apoptosis does not depend on the release of cytochrome c into the cytosol and is a reversibile event. These findings may contribute to understand the mechanisms affecting mitochondria during the early stages of apoptosis and priming them for the release of apoptogenic factors. PMID:22666257

  12. Disease activity decrease is associated with improvement in work productivity over 1 year in early axial spondyloarthritis (SPondyloArthritis Caught Early cohort).

    PubMed

    van Lunteren, Miranda; Ez-Zaitouni, Zineb; Fongen, Camilla; Landewé, Robert; Ramonda, Roberta; van der Heijde, Désirée; van Gaalen, Floris A

    2017-12-01

    To assess if a change in disease activity is associated with a change in work productivity loss (WPL) over 1 year in early axial SpA (axSpA) patients. Baseline and 1 year data of axSpA patients in the SPondyloArthritis Caught Early cohort were analysed. Linear regression models were built explaining the change in the Ankylosing Spondylitis Disease Activity Score (ASDAS) over time by the change in absenteeism, presenteeism, WPL and activity impairment over time. Effect modification and confounding were tested for age, gender, arm of Assessment of SpondyloArthritis international Society classification criteria, HLA-B27, duration of chronic back pain, profession and medication. At baseline, in 105 axSpA patients (48% female, mean age 30.8 years, mean symptom duration 13.6 months, 92% HLA-B27 positive, 24% radiographic sacroiliitis), the mean ASDAS was 2.4 (s.d. 1.0), absenteeism 9% (s.d. 23), presenteeism 33% (s.d. 28), WPL 36% (s.d. 30) and activity impairment 37% (s.d. 25). After 1 year, the mean ASDAS decreased to 2.0 (s.d. 0.8) and absenteeism, presenteeism, WPL and activity impairment improved to 6% (s.d. 22), 26% (s.d. 26), 27% (s.d. 29) and 27% (s.d. 26), respectively. Models showed that if ASDAS decreased 1 unit, absenteeism, presenteeism, WPL and activity impairment improved by 5, 17, 16 and 18%, respectively. The impact of disease activity on work productivity was higher in patients with shorter symptom duration and the impact on absenteeism was higher in patients starting pharmacological treatment. In early axSpA patients, work productivity and daily activities are seriously impacted at baseline and 1 year. However, decreasing disease activity is associated with marked improvements in work productivity and daily activities. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  13. The ESA Planetary Science Archive User Group (PSA-UG)

    NASA Astrophysics Data System (ADS)

    Rossi, A. P.; Cecconi, B.; Fraenz, M.; Hagermann, A.; Heather, D.; Rosenblatt, P.; Svedhem, H.; Widemann, T.

    2014-04-01

    ESA has established a Planetary Science Archive User Group (PSA-UG), with the task of offering independent advice to ESA's Planetary Science Archive (e.g. Heather et al., 2013). The PSA-UG is an official and independent body that continuously evaluates services and tools provided by the PSA to the community of planetary data scientific users. The group has been tasked with the following top level objectives: a) Advise ESA on future development of the PSA. b) Act as a focus for the interests of the scientific community. c) Act as an advocate for the PSA. d) Monitor the PSA activities. Based on this, the PSA-UG will report through the official ESA channels. Disciplines and subjects represented by PSA-UG members include: Remote Sensing of both Atmosphere and Solid Surfaces, Magnetospheres, Plasmas, Radio Science and Auxilliary data. The composition of the group covers ESA missions populating the PSA both now and in the near future. The first members of the PSA-UG were selected in 2013 and will serve for 3 years, until 2016. The PSA-UG will address the community through workshops, conferences and the internet. Written recommendations will be made to the PSA coordinator, and an annual report on PSA and the PSA-UG activities will be sent to the Solar System Exploration Working Group (SSEWG). Any member of the community and planetary data user can get in touch with individual members of the PSA-UG or with the group as a whole via the contacts provided on the official PSA-UG web-page: http://archives.esac.esa.int/psa/psa-ug The PSA is accessible via: http://archives.esac.esa.int/psa

  14. Overweight and obesity decreased in Greek schoolchildren from 2009 to 2012 during the early phase of the economic crisis.

    PubMed

    Kleanthous, Kleanthis; Dermitzaki, Eleni; Papadimitriou, Dimitrios T; Papaevangelou, Vassiliki; Papadimitriou, Anastasios

    2016-02-01

    We examined the weight status of Greek schoolchildren from November 2009 to May 2012, shortly before, and during the early years, of the Greek economic crisis. This was a mixed longitudinal study that formed part of the West Attica Growth Study and followed children at the ages of 6-7, 9-10, 12-13 and 15-16 years every six months for 2.5 years. Each child's height and weight were measured and their body mass index calculated. We were able to determine the weight status of 1327 children (53% boys) based on their first and last measurements. Overweight, obesity and underweight were defined using the International Obesity Task Force criteria. During the 2.5-year study period, there was a decrease in the total prevalence of overweight and obesity, which reached a statistical significance for both sexes. It decreased from 43% to 37.3% (p = 0.02) in boys and from 33.4% to 26.9% (p = 0.0056) in girls. There was also a statistically significant increase in normal weight children and a slight but insignificant increase in underweight children of both sexes. During the initial years of the Greek economic crisis, there was a statistically significant reduction in overweight and obesity in children from six to 16 years of age. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  15. Adverse early life environment increases hippocampal microglia abundance in conjunction with decreased neural stem cells in juvenile mice.

    PubMed

    Cohen, Susan; Ke, Xingrao; Liu, Qiuli; Fu, Qi; Majnik, Amber; Lane, Robert

    2016-12-01

    Adverse maternal lifestyle resulting in adverse early life environment (AELE) increases risks for neuropsychiatric disorders in offspring. Neuropsychiatric disorders are associated with impaired neurogenesis and neuro-inflammation in the hippocampus (HP). Microglia are neuro-inflammatory cells in the brain that regulate neurogenesis via toll-like receptors (TLR). TLR-9 is implicated in neurogenesis inhibition and is responsible for stress-related inflammatory responses. We hypothesized that AELE would increase microglia cell count and increase TLR-9 expression in juvenile mouse HP. These increases in microglia cell count and TLR-9 expression would be associated with decrease neural stem cell count and neuronal cell count. We developed a mouse model of AELE combining Western diet and a stress environment. Stress environment consisted of random change from embryonic day 13 (E13) to E17 as well as static change in maternal environment from E13 to postnatal day 21(P21). At P21, we measured hippocampal cell numbers of microglia, neural stem cell and neuron, as well as hippocampal TLR-9 expression. AELE significantly increased total microglia number and TLR-9 expression in the hippocampus. Concurrently, AELE significantly decreased neural stem cell and neuronal numbers. AELE increased the neuro-inflammatory cellular response in the juvenile HP. We speculate that increased neuro-inflammatory responses may contribute to impaired neurogenesis seen in this model. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

  16. PSA levels as a predictor of 68Ga PSMA PET/CT positivity in patients with prostate cancer?

    PubMed

    Soydal, Cigdem; Urun, Yuksel; Suer, Evren; Nak, Demet; Ozkan, Elgin; Kucuk, Ozlem N

    2018-05-10

    The aim of this study is to evaluate predictive factors of 68Gallium (68Ga) Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET)/Computed Tomography (CT) positivity. Relationships between serum Prostate Specific Antigen (PSA), Lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) levels, Gleason Score (GS) and positivity of 68Ga PSMA PET in patients who underwent 68Ga PSMA PET/CT for restaging for PCa were evaluated retrospectively. One hundred and four (median age: 67; range: 51-88) patients were included in this study. Of these patients, PSMA PET was positive in 75 (72%) patients. Mean serum PSA levels for PET negative and positive groups were 0.76±1.00 and 180.85±324.93 ng/ml (p<0.001). The sensitivity and specificity of 68Ga PSMA PET/CT for detection of disease recurrence were calculated as 92% and 80%, respectively, for the 1.4 ng/ml PSA cut-off and 92% and 90%, respectively, for the 2 ng/ml PSA cut-off values. The positivity rates for patients with PSA levels <1.4 ng/ml and ≥1.4 ng/ml were 21% and 90%, respectively (p<0.001). 68Ga PSMA PET/CT seems to be a highly sensitive in patients with early PSA recurrence. Patients with higher GS and early PSA recurrence could benefit from 68Ga PSMA PET/CT.

  17. Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes.

    PubMed

    Llop, Esther; Ferrer-Batallé, Montserrat; Barrabés, Sílvia; Guerrero, Pedro Enrique; Ramírez, Manel; Saldova, Radka; Rudd, Pauline M; Aleixandre, Rosa N; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

    2016-01-01

    New markers based on PSA isoforms have recently been developed to improve prostate cancer (PCa) diagnosis. However, novel approaches are still required to differentiate aggressive from non-aggressive PCa to improve decision making for patients. PSA glycoforms have been shown to be differentially expressed in PCa. In particular, changes in the extent of core fucosylation and sialylation of PSA N-glycans in PCa patients compared to healthy controls or BPH patients have been reported. The objective of this study was to determine these specific glycan structures in serum PSA to analyze their potential value as markers for discriminating between BPH and PCa of different aggressiveness. In the present work, we have established two methodologies to analyze the core fucosylation and the sialic acid linkage of PSA N-glycans in serum samples from BPH (29) and PCa (44) patients with different degrees of aggressiveness. We detected a significant decrease in the core fucose and an increase in the α2,3-sialic acid percentage of PSA in high-risk PCa that differentiated BPH and low-risk PCa from high-risk PCa patients. In particular, a cut-off value of 0.86 of the PSA core fucose ratio, could distinguish high-risk PCa patients from BPH with 90% sensitivity and 95% specificity, with an AUC of 0.94. In the case of the α2,3-sialic acid percentage of PSA, the cut-off value of 30% discriminated between high-risk PCa and the group of BPH, low-, and intermediate-risk PCa with a sensitivity and specificity of 85.7% and 95.5%, respectively, with an AUC of 0.97. The latter marker exhibited high performance in differentiating between aggressive and non-aggressive PCa and has the potential for translational application in the clinic.

  18. Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes

    PubMed Central

    Llop, Esther; Ferrer-Batallé, Montserrat; Barrabés, Sílvia; Guerrero, Pedro Enrique; Ramírez, Manel; Saldova, Radka; Rudd, Pauline M.; Aleixandre, Rosa N.; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

    2016-01-01

    New markers based on PSA isoforms have recently been developed to improve prostate cancer (PCa) diagnosis. However, novel approaches are still required to differentiate aggressive from non-aggressive PCa to improve decision making for patients. PSA glycoforms have been shown to be differentially expressed in PCa. In particular, changes in the extent of core fucosylation and sialylation of PSA N-glycans in PCa patients compared to healthy controls or BPH patients have been reported. The objective of this study was to determine these specific glycan structures in serum PSA to analyze their potential value as markers for discriminating between BPH and PCa of different aggressiveness. In the present work, we have established two methodologies to analyze the core fucosylation and the sialic acid linkage of PSA N-glycans in serum samples from BPH (29) and PCa (44) patients with different degrees of aggressiveness. We detected a significant decrease in the core fucose and an increase in the α2,3-sialic acid percentage of PSA in high-risk PCa that differentiated BPH and low-risk PCa from high-risk PCa patients. In particular, a cut-off value of 0.86 of the PSA core fucose ratio, could distinguish high-risk PCa patients from BPH with 90% sensitivity and 95% specificity, with an AUC of 0.94. In the case of the α2,3-sialic acid percentage of PSA, the cut-off value of 30% discriminated between high-risk PCa and the group of BPH, low-, and intermediate-risk PCa with a sensitivity and specificity of 85.7% and 95.5%, respectively, with an AUC of 0.97. The latter marker exhibited high performance in differentiating between aggressive and non-aggressive PCa and has the potential for translational application in the clinic. PMID:27279911

  19. Prevention and Early Detection of Prostate Cancer

    PubMed Central

    Cuzick, Jack; Thorat, Mangesh A.; Andriole, Gerald; Brawley, Otis W.; Brown, Powel H.; Culig, Zoran; Eeles, Rosalind A.; Ford, Leslie G.; Hamdy, Freddie C.; Holmberg, Lars; Ilic, Dragan; Key, Timothy J.; La Vecchia, Carlo; Lilja, Hans; Marberger, Michael; Meyskens, Frank L.; Minasian, Lori M.; Parker, Chris; Parnes, Howard L.; Perner, Sven; Rittenhouse, Harry; Schalken, Jack; Schmid, Hans-Peter; Schmitz-Dräger, Bernd J.; Schröder, Fritz H.; Stenzl, Arnulf; Tombal, Bertrand; Wilt, Timothy J.; Wolk, Alicja

    2014-01-01

    Prostate cancer is one of the most common cancers in men and the global burden of this disease is rising. Lifestyle modifications like smoking cessation, exercise and weight control offer opportunities to decrease the risk of developing prostate cancer. Early detection of prostate cancer by PSA screening remains controversial; yet, changes in PSA threshold, frequency of screening, and addition of other biomarkers have potential to minimise overdiagnosis associated with PSA screening. Several new biomarkers appear promising in individuals with elevated PSA levels or those diagnosed with prostate cancer, these are likely to guide in separating individuals who can be spared of aggressive treatment from those who need it. Several pharmacological agents like 5α-reductase inhibitors, aspirin etc. have a potential to prevent development of prostate cancer. In this review, we discuss the current evidence and research questions regarding prevention, early detection of prostate cancer and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer. PMID:25281467

  20. Transarterial chemoembolization for early stage hepatocellular carcinoma decrease local tumor control and overall survival compared to radiofrequency ablation

    PubMed Central

    Hocquelet, Arnaud; Seror, Olivier; Blanc, Jean-Frédéric; Frulio, Nora; Salut, Cécile; Nault, Jean-Charles; Hervé Trillaud

    2017-01-01

    Background & Aims To compare treatment failure and survival associated with ultrasound-guided radiofrequency ablation (RFA) and trans-arterial chemoembolization (TACE) for early-stage HCC in Child-Pugh A cirrhosis patients. Methods 122 cirrhotic patients (RFA: 61; TACE: 61) were well matched according to cirrhosis severity; tumor size and serum alpha-fetoprotein. TACE was performed in case of inconspicuous nodule on US or nodule with “at risk location”. Treatment failure was defined as local tumor progression (LTP) and primary treatment failure (failing to obtain complete response after two treatment session). Treatment failure and overall survival (OS) were compared after coarsened exact matching. Cox proportional model to assess independent predictive factors was performed. Results No significant difference was seen for baseline characteristics between the two groups. Mean tumor size was 3cm in both group with 41% HCC>3cm. Treatment failure rates after TACE was 42.6% (14 primary treatment failures and 12 LTP) and 9.8% after RFA (no primary treatment failure and 6 LTP) P < 0.001. TACE was the only predictive factor of treatment failure (Hazard ratio: 5.573). The 4-years OS after RFA and TACE were 54.1% and 31.5% (P = 0.042), respectively. Conclusion For Child-Pugh A patients with early-stage HCC, alternative treatment as supra-selective TACE to RFA regarded as too challenging using common US guidance decrease significantly the local tumor control and overall survival. Efforts to improve feasibility of RFA especially for inconspicuous target have to be made. PMID:27793027

  1. Race, Genetic West African Ancestry, and Prostate Cancer Prediction by PSA in Prospectively Screened High-Risk Men

    PubMed Central

    Giri, Veda N.; Egleston, Brian; Ruth, Karen; Uzzo, Robert G.; Chen, David Y.T.; Buyyounouski, Mark; Raysor, Susan; Hooker, Stanley; Torres, Jada Benn; Ramike, Teniel; Mastalski, Kathleen; Kim, Taylor Y.; Kittles, Rick

    2008-01-01

    Introduction “Race-specific” PSA needs evaluation in men at high-risk for prostate cancer (PCA) for optimizing early detection. Baseline PSA and longitudinal prediction for PCA was examined by self-reported race and genetic West African (WA) ancestry in the Prostate Cancer Risk Assessment Program, a prospective high-risk cohort. Materials and Methods Eligibility criteria are age 35–69 years, FH of PCA, African American (AA) race, or BRCA1/2 mutations. Biopsies have been performed at low PSA values (<4.0 ng/mL). WA ancestry was discerned by genotyping 100 ancestry informative markers. Cox proportional hazards models evaluated baseline PSA, self-reported race, and genetic WA ancestry. Cox models were used for 3-year predictions for PCA. Results 646 men (63% AA) were analyzed. Individual WA ancestry estimates varied widely among self-reported AA men. “Race-specific” differences in baseline PSA were not found by self-reported race or genetic WA ancestry. Among men with ≥ 1 follow-up visit (405 total, 54% AA), three-year prediction for PCA with a PSA of 1.5–4.0 ng/mL was higher in AA men with age in the model (p=0.025) compared to EA men. Hazard ratios of PSA for PCA were also higher by self-reported race (1.59 for AA vs. 1.32 for EA, p=0.04). There was a trend for increasing prediction for PCA with increasing genetic WA ancestry. Conclusions “Race-specific” PSA may need to be redefined as higher prediction for PCA at any given PSA in AA men. Large-scale studies are needed to confirm if genetic WA ancestry explains these findings to make progress in personalizing PCA early detection. PMID:19240249

  2. Early decreased neutrophil responsiveness is related to late onset sepsis in multitrauma patients: An international cohort study.

    PubMed

    Groeneveld, Kathelijne M; Koenderman, Leo; Warren, Brian L; Jol, Saskia; Leenen, Luke P H; Hietbrink, Falco

    2017-01-01

    Severe trauma can lead to the development of infectious complications after several days, such as sepsis. Early identification of patients at risk will aid anticipating these complications. The aim of this study was to test the relation between the acute (<24 hours) inflammatory response after injury measured by neutrophil responsiveness and the late (>5 days) development of septic complications and validate this in different trauma populations. Two prospective, observational, cohort series in the Netherlands and South Africa, consisting of severely injured trauma patients. Neutrophil responsiveness by fMLF-induced active FcγRII was measured in whole blood flowcytometry, as read out for the systemic immune response within hours after trauma. Sepsis was scored daily. Ten of the 36 included Dutch patients developed septic shock. In patients with septic shock, neutrophils showed a lower expression of fMLF-induced active FcγRII immediately after trauma when compared to patients without septic shock (P = 0.001). In South Africa 11 of 73 included patients developed septic shock. Again neutrophils showed lower expression of fMLF induced active FcγRII (P = 0.001). In the combined cohort, all patients who developed septic shock demonstrated a decreased neutrophil responsiveness. Low responsiveness of neutrophils for the innate stimulus fMLF immediately after trauma preceded the development of septic shock during admission by almost a week and did not depend on a geographical/racial background, hospital protocols and health care facilities. Decreased neutrophil responsiveness appears to be a prerequisite for septic shock after trauma. This might enable anticipation of this severe complication in trauma patients.

  3. Insulin promotes cell migration by regulating PSA-NCAM

    SciTech Connect

    Monzo, Hector J.; Coppieters, Natacha; Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland

    Cellular interactions with the extracellular environment are modulated by cell surface polysialic acid (PSA) carried by the neural cell adhesion molecule (NCAM). PSA-NCAM is involved in cellular processes such as differentiation, plasticity, and migration, and is elevated in Alzheimer's disease as well as in metastatic tumour cells. Our previous work demonstrated that insulin enhances the abundance of cell surface PSA by inhibiting PSA-NCAM endocytosis. In the present study we have identified a mechanism for insulin-dependent inhibition of PSA-NCAM turnover affecting cell migration. Insulin enhanced the phosphorylation of the focal adhesion kinase leading to dissociation of αv-integrin/PSA-NCAM clusters, and promoted cellmore » migration. Our results show that αv-integrin plays a key role in the PSA-NCAM turnover process. αv-integrin knockdown stopped PSA-NCAM from being endocytosed, and αv-integrin/PSA-NCAM clusters co-labelled intracellularly with Rab5, altogether indicating a role for αv-integrin as a carrier for PSA-NCAM during internalisation. Furthermore, inhibition of p-FAK caused dissociation of αv-integrin/PSA-NCAM clusters and counteracted the insulin-induced accumulation of PSA at the cell surface and cell migration was impaired. Our data reveal a functional association between the insulin/p-FAK-dependent regulation of PSA-NCAM turnover and cell migration through the extracellular matrix. Most importantly, they identify a novel mechanism for insulin-stimulated cell migration. - Highlights: • Insulin modulates PSA-NCAM turnover through upregulation of p-FAK. • P-FAK modulates αv-integrin/PSA-NCAM clustering. • αv-integrin acts as a carrier for PSA-NCAM endocytosis. • Cell migration is promoted by cell surface PSA. • Insulin promotes PSA-dependent migration in vitro.« less

  4. Decreased SAP expression in T cells from patients with SLE contributes to early signaling abnormalities and reduced IL-2 production

    PubMed Central

    Karampetsou, Maria P.; Comte, Denis; Kis-Toth, Katalin; Terhorst, Cox; Kyttaris, Vasileios C.; Tsokos, George C.

    2016-01-01

    T cells from patients with systemic lupus erythematosus (SLE) display a number of functions including increased early signaling events following engagement of the T cell receptor (TCR). Signaling lymphocytic activation molecule family (SLAMF) cell surface receptors and the X-chromosome-defined signaling lymphocytic activation molecule-associated protein (SAP) adaptor are important in the development of several immunocyte lineages and modulating immune response. Here we present evidence that SAP protein levels are decreased in T cells and in their main subsets isolated from 32 women and 3 men with SLE independently of disease activity. In SLE T cells the SAP protein is also subject to increased degradation by a caspase-3. Forced expression of SAP in SLE T cells simultaneously heightened IL-2 production, calcium (Ca2+) responses and tyrosine phosphorylation of a number of proteins. Exposure of normal T cells to SLE serum IgG, known to contain anti-CD3/TCR antibodies, resulted in SAP downregulation. We conclude that SLE T cells display reduced levels of the adaptor protein SAP probably as a result of continuous T cell activation and degradation by caspase-3. Restoration of SAP levels in SLE T cells corrects the overexcitable lupus T cell phenotype. PMID:27183584

  5. Developmentally dynamic genome: Evidence of genetic influences on increases and decreases in conduct problems from early childhood to adolescence

    PubMed Central

    Pingault, Jean-Baptiste; Rijsdijk, Frühling; Zheng, Yao; Plomin, Robert; Viding, Essi

    2015-01-01

    The development of conduct problems in childhood and adolescence is associated with adverse long-term outcomes, including psychiatric morbidity. Although genes constitute a proven factor of stability in conduct problems, less is known regarding their role in conduct problems’ developmental course (i.e. systematic age changes, for instance linear increases or decreases).Mothers rated conduct problems from age 4 to 16 years in 10,038 twin pairs from the Twins Early Development Study. Individual differences in the baseline level (.78; 95% CI: .68-.88) and the developmental course of conduct problems (.73; 95% CI: .60-.86) were under high and largely independent additive genetic influences. Shared environment made a small contribution to the baseline level but not to the developmental course of conduct problems. These results show that genetic influences not only contribute to behavioural stability but also explain systematic change in conduct problems. Different sets of genes may be associated with the developmental course versus the baseline level of conduct problems. The structure of genetic and environmental influences on the development of conduct problems suggests that repeated preventive interventions at different developmental stages might be necessary to achieve a long-term impact. PMID:25944445

  6. Developmentally dynamic genome: Evidence of genetic influences on increases and decreases in conduct problems from early childhood to adolescence.

    PubMed

    Pingault, Jean-Baptiste; Rijsdijk, Frühling; Zheng, Yao; Plomin, Robert; Viding, Essi

    2015-05-06

    The development of conduct problems in childhood and adolescence is associated with adverse long-term outcomes, including psychiatric morbidity. Although genes constitute a proven factor of stability in conduct problems, less is known regarding their role in conduct problems' developmental course (i.e. systematic age changes, for instance linear increases or decreases).Mothers rated conduct problems from age 4 to 16 years in 10,038 twin pairs from the Twins Early Development Study. Individual differences in the baseline level (.78; 95% CI: .68-.88) and the developmental course of conduct problems (.73; 95% CI: .60-.86) were under high and largely independent additive genetic influences. Shared environment made a small contribution to the baseline level but not to the developmental course of conduct problems. These results show that genetic influences not only contribute to behavioural stability but also explain systematic change in conduct problems. Different sets of genes may be associated with the developmental course versus the baseline level of conduct problems. The structure of genetic and environmental influences on the development of conduct problems suggests that repeated preventive interventions at different developmental stages might be necessary to achieve a long-term impact.

  7. Childhood fractures are associated with decreased bone mass gain during puberty: an early marker of persistent bone fragility?

    PubMed

    Ferrari, Serge L; Chevalley, Thierry; Bonjour, Jean-Philippe; Rizzoli, René

    2006-04-01

    Whether peak bone mass is low among children with fractures remains uncertain. In a cohort of 125 girls followed over 8.5 years, 42 subjects reported 58 fractures. Among those, BMC gain at multiple sites and vertebral bone size at pubertal maturity were significantly decreased. Hence, childhood fractures may be markers of low peak bone mass acquisition and persistent skeletal fragility. Fractures in childhood may result from a deficit in bone mass accrual during rapid longitudinal growth. Whether low bone mass persists beyond this period however remains unknown. BMC at the spine, radius, hip, and femur diaphysis was prospectively measured over 8.5 years in 125 girls using DXA. Differences in bone mass and size between girls with and without fractures were analyzed using nonparametric tests. The contribution of genetic factors was evaluated by mother-daughter correlations and that of calcium intake by Cox proportional hazard models. Fifty-eight fractures occurred in 42 among 125 girls (cumulative incidence, 46.4%), one-half of all fractures affecting the forearm and wrist. Girls with and without fractures had similar age, height, weight. and calcium intake at all time-points. Before and during early puberty, BMC and width of the radius diaphysis was lower in the fracture compared with no-fracture group (p < 0.05), whereas aBMD and BMAD were similar in the two groups. At pubertal maturity (Tanner's stage 5, mean age +/- SD, 16.4 +/- 0.5 years), BMC at the ultradistal radius (UD Rad.), femur trochanter, and lumbar spine (LS), and LS projected bone area were all significantly lower in girls with fractures. Throughout puberty, BMC gain at these sites was also decreased in the fracture group (LS, -8.0%, p = 0.015; UD Rad., -12.0%, p = 0.004; trochanter, -8.4%, p = 0.05 versus no fractures). BMC was highly correlated between prepuberty and pubertal maturity (R = 0.54-0.81) and between mature daughters and their mothers (R = 0.32-0.46). Calcium intake was not related to

  8. Proteolytic Activity of Prostate-Specific Antigen (PSA) towards Protein Substrates and Effect of Peptides Stimulating PSA Activity

    PubMed Central

    Mattsson, Johanna M.; Ravela, Suvi; Hekim, Can; Jonsson, Magnus; Malm, Johan; Närvänen, Ale; Stenman, Ulf-Håkan; Koistinen, Hannu

    2014-01-01

    Prostate-specific antigen (PSA or kallikrein-related peptidase-3, KLK3) exerts chymotrypsin-like proteolytic activity. The main biological function of PSA is the liquefaction of the clot formed after ejaculation by cleavage of semenogelins I and II in seminal fluid. PSA also cleaves several other substrates, which may explain its putative functions in prostate cancer and its antiangiogenic activity. We compared the proteolytic efficiency of PSA towards several protein and peptide substrates and studied the effect of peptides stimulating the activity of PSA with these substrates. An endothelial cell tube formation model was used to analyze the effect of PSA-degraded protein fragments on angiogenesis. We showed that PSA degrades semenogelins I and II much more efficiently than other previously identified protein substrates, e.g., fibronectin, galectin-3 and IGFBP-3. We identified nidogen-1 as a new substrate for PSA. Peptides B2 and C4 that stimulate the activity of PSA towards small peptide substrates also enhanced the proteolytic activity of PSA towards protein substrates. Nidogen-1, galectin-3 or their fragments produced by PSA did not have any effect on endothelial cell tube formation. Although PSA cleaves several other protein substrates, in addition to semenogelins, the physiological importance of this activity remains speculative. The PSA levels in prostate are very high, but several other highly active proteases, such as hK2 and trypsin, are also expressed in the prostate and may cleave protein substrates that are weakly cleaved by PSA. PMID:25237904

  9. Alterations in expressed prostate secretion-urine PSA N-glycosylation discriminate prostate cancer from benign prostate hyperplasia

    PubMed Central

    Sun, Chenxia; Wen, Fuping; Wang, Haifeng; Guo, Huaizu; Gao, Xu; Xu, Chuanliang; Xu, Chuanliang; Yang, Chenghua; Sun, Yinghao

    2017-01-01

    The prostate specific antigen (PSA) test is widely used for early diagnosis of prostate cancer (PCa). However, its limited sensitivity has led to over-diagnosis and over-treatment of PCa. Glycosylation alteration is a common phenomenon in cancer development. Different PSA glycan subforms have been proposed as diagnostic markers to better differentiate PCa from benign prostate hyperplasia (BPH). In this study, we purified PSA from expressed prostate secretions (EPS)-urine samples from 32 BPH and 30 PCa patients and provided detailed PSA glycan profiles in Chinese population. We found that most of the PSA glycans from EPS-urine were complex type biantennary glycans. We observed two major patterns in PSA glycan profiles. Overall there was no distinct separation of PSA glycan profiles between BPH and PCa patients. However, we detected a significant increase of glycan FA2 and FM5A2G2S1 in PCa when compared with BPH patients. Furthermore, we observed that the composition of FA2 glycan increased significantly in advanced PCa with Gleason score ≥8, which potentially could be translated to clinic as a marker for aggressive PCa. PMID:29100363

  10. Alterations in expressed prostate secretion-urine PSA N-glycosylation discriminate prostate cancer from benign prostate hyperplasia.

    PubMed

    Jia, Gaozhen; Dong, Zhenyang; Sun, Chenxia; Wen, Fuping; Wang, Haifeng; Guo, Huaizu; Gao, Xu; Xu, Chuanliang; Xu, Chuanliang; Yang, Chenghua; Sun, Yinghao

    2017-09-29

    The prostate specific antigen (PSA) test is widely used for early diagnosis of prostate cancer (PCa). However, its limited sensitivity has led to over-diagnosis and over-treatment of PCa. Glycosylation alteration is a common phenomenon in cancer development. Different PSA glycan subforms have been proposed as diagnostic markers to better differentiate PCa from benign prostate hyperplasia (BPH). In this study, we purified PSA from expressed prostate secretions (EPS)-urine samples from 32 BPH and 30 PCa patients and provided detailed PSA glycan profiles in Chinese population. We found that most of the PSA glycans from EPS-urine were complex type biantennary glycans. We observed two major patterns in PSA glycan profiles. Overall there was no distinct separation of PSA glycan profiles between BPH and PCa patients. However, we detected a significant increase of glycan FA2 and FM5A2G2S1 in PCa when compared with BPH patients. Furthermore, we observed that the composition of FA2 glycan increased significantly in advanced PCa with Gleason score ≥8, which potentially could be translated to clinic as a marker for aggressive PCa.

  11. Cat exposure in early life decreases asthma risk from the 17q21 high-risk variant.

    PubMed

    Stokholm, Jakob; Chawes, Bo L; Vissing, Nadja; Bønnelykke, Klaus; Bisgaard, Hans

    2018-05-01

    Early-life exposure to cats and dogs has shown diverging associations with childhood asthma risk, and gene-environment interaction is one possible explanation. We investigated interactions between cat and dog exposure and single nucleotide polymorphism rs7216389 variants in the chromosome 17q21 locus, the strongest known genetic risk factor for childhood asthma. Genotyping was performed in 377 children from the at-risk Copenhagen Prospective Studies on Asthma in Childhood 2000 . The primary end point was the development of asthma until age 12 years. The secondary end point was the number of episodes with pneumonia and bronchiolitis from 0 to 3 years of age. Exposures included cat and dog ownership from birth and cat and dog allergen levels in bedding at age 1 year. Replication was performed in the unselected COPSAC 2010 cohort with follow-up until 5 years of age. Cat and/or dog exposure from birth was associated with a lower prevalence of asthma among children with the rs7216389 high-risk TT genotype (adjusted hazard ratio, 0.16; 95% CI, 0.04-0.71; P = .015), with no effect in those with the CC/CT genotype (adjusted P = .283), demonstrating interaction between cat and dog exposure and the rs7216389 genotype (adjusted P = .044). Cat allergen levels were inversely associated with asthma development in children with the TT genotype (adjusted hazard ratio, 0.83; 95% CI, 0.71-0.97; P = .022), supporting the cat-rs7216389 genotype interaction (adjusted P = .008). Dog allergen exposure did not show such interaction. Furthermore, the TT genotype was associated with higher risk of pneumonia and bronchiolitis, and this increased risk was likewise decreased in children exposed to cat. Replication showed similar effects on asthma risk. The observed gene-environment interaction suggests a role of early-life exposure, especially to cat, for attenuating the risk of childhood asthma, pneumonia, and bronchiolitis in genetically susceptible subjects. Copyright © 2017

  12. Gains in income during early childhood are associated with decreases in BMI z scores among children in the United States.

    PubMed

    Oddo, Vanessa M; Jones-Smith, Jessica C

    2015-06-01

    Evidence suggests that changes in family income are an important determinant of children's body mass index (BMI). However, few studies have leveraged longitudinal data to investigate the association of changes in family income on changes in BMI z score. This study aimed to assess whether gains in family income are associated with changes in BMI z score among children in the United States by using the nationally representative Early Childhood Longitudinal Survey Birth Cohort (ECLS-B). We used longitudinal data from the ECLS-B to assess whether gains in family income, assessed by using the poverty to income ratio (PIR), were associated with changes in BMI z score among children aged 2-6 y. Child anthropometric characteristics and family income were assessed at 2-y, 4-y, 5-y, and 6-y visits. Sex-stratified, individual fixed-effects linear regression models compared children with themselves over time to control for time-invariant measured and unmeasured confounding factors. Models also controlled for time-varying confounders, including number of siblings, household structure (2 parents, one parent, or unrelated guardian), age, and age squared. Children (n = ~9200) had a mean ± SE change in BMI z score of 0.12 ± 0.022, and family income increased by ~$3361 ± $536 during the 4-y period of observation (2003-2007). The association between increased PIR and change in BMI z score varied by sex but not by race-ethnicity. Among girls, an increase in PIR was associated with a statistically significant decrease in BMI z score (βPIR = -0.022; 95% CI: -0.042, -0.0016). There was a statistically significant association between PIR and BMI z score among preterm boys (βPIR + β PIRXpreterm = -0.067; 95% CI: -0.12, -0.018), but the relation was not statistically significant among boys born at term (βPIR = -0.0049; 95% CI: -0.024, 0.014). By comparing children with themselves over time, we overcome many barriers that typically impede causal inference in observational studies. In

  13. Rosetta Planetary Science Archive (PSA) Status

    NASA Astrophysics Data System (ADS)

    Wirth, Kristin R.; Cardesin, A.; Barthelemy, M.; Diaz del Rio, J.; Zender, J.; Arviset, C.

    2006-09-01

    The Planetary Science Archive (PSA) is an online database (accessible via http://www.rssd.esa.int/PSA) implemented by ESA/RSSD. Currently the PSA contains the science data from the Giotto (Halley), Mars Express and SMART-1 (Moon) missions, and the Rosetta Supplementary Archive (Wirtanen). The PSA user is offered a broad range of search possibilities. Search queries can be combined without restrictions and are executed across the whole database. The PSA utilizes the Planetary Data System (PDS) standard. In spring 2007 the PSA will provide the first science and engineering data collected by Rosetta. In preparation for the initial Peer Review to be performed before publication of these data, an Internal Review was held in March 2006, executed by staff internal to the organizations responsible for the Rosetta archiving (ESA, PDS, CNES). The Internal Reviewers identified shortcomings in documentation, data structures, and completeness of the data delivery. They recommended the usage of unified conventions and formats across different instruments. Work is ongoing to include standardized geometry information in the datasets. Rosetta was launched in March 2004 to rendezvous with comet 67P/Churyumov-Gerasimenko (C-G) in May 2014. After having placed a lander on the comet's surface, the Rosetta orbiter will continue to orbit C-G and accompany the comet through perihelion. Rosetta makes use of three Earth swingbys and one Mars swingby in order to reach C-G. Rosetta will also perform close flybys at two asteroids, namely 2867 Steins in September 2008 and 21 Lutetia in July 2010. In addition, Rosetta makes scientific observations of targets of opportunity, e.g. lightcurves of the flyby asteroids to study the rotation, and plasma measurements when passing through cometary ion tails or meteoroid streams. Rosetta continuously monitored the encounter of the Deep Impact probe with comet 9P/Tempel 1 over an extended period of 16 days around the impact on 4 July 2005.

  14. Decrease of murine cytomegalovirus-induced retinitis by intravenous delivery of immediate early protein-3-specific siRNA.

    PubMed

    Marshall, Brendan; Mo, Juan; Covar, Jason; Atherton, Sally S; Zhang, Ming

    2014-06-06

    Retinitis induced by both human and murine cytomegaloviruses following immunosuppression is characterized by progressive loss of retinal architecture, due to necrosis of virus-infected cells as well as widespread apoptosis of uninfected bystander cells. Because small inhibitory RNA molecules (siRNA) can reduce murine cytomegalovirus (MCMV) gene expression and thereby inhibit virus replication in vitro, we tested siRNAs directed against MCMV immediate early protein-3 (IE-3) to determine if MCMV-induced retinitis could be alleviated in vivo. Immunosuppressed Balb/c mice (2.0 mg methylprednisolone acetate every 3 days beginning on day -2) were infected with 5 × 10(3) pfu of the K181 strain of MCMV via the supraciliary route. At day 2 post infection, mice were treated with various doses of IE-3-specific siRNA ranging from 0.1 nmol to 10 nmol, in a volume of 20 μL PBS via tail vein injection. Injected eyes were collected at various times post inoculation and subjected to plaque assay for virus titer, MCMV antigen staining, H&E staining, TUNEL assay, and Western blot for MCMV IE-3 protein. Small but significant amounts of fluorescently labeled IE-3-specific siRNA localized to the RPE layer 48 hours after intravenous injection. IE-3-specific siRNA significantly reduced virus titers at all concentrations tested (ranging from 0.1 nmol to 10 nmol), but the most potent effect of siRNA was observed at a dose of 1 nmol. We also observed that IE-3-specific siRNA produced a substantial decrease in MCMV titers and a substantial reduction in bystander cell apoptosis over the time course of virus infection. Systemic administration of IE-3-specific siRNA could alleviate MCMV retinitis by inhibiting virus replication and subsequent death of uninfected retinal cells. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  15. Early exposure of bay scallops (Argopecten irradians) to high CO₂ causes a decrease in larval shell growth.

    PubMed

    White, Meredith M; McCorkle, Daniel C; Mullineaux, Lauren S; Cohen, Anne L

    2013-01-01

    Ocean acidification, characterized by elevated pCO₂ and the associated decreases in seawater pH and calcium carbonate saturation state (Ω), has a variable impact on the growth and survival of marine invertebrates. Larval stages are thought to be particularly vulnerable to environmental stressors, and negative impacts of ocean acidification have been seen on fertilization as well as on embryonic, larval, and juvenile development and growth of bivalve molluscs. We investigated the effects of high CO₂ exposure (resulting in pH = 7.39, Ω(ar) = 0.74) on the larvae of the bay scallop Argopecten irradians from 12 h to 7 d old, including a switch from high CO₂ to ambient CO₂ conditions (pH = 7.93, Ω(ar) = 2.26) after 3 d, to assess the possibility of persistent effects of early exposure. The survival of larvae in the high CO₂ treatment was consistently lower than the survival of larvae in ambient conditions, and was already significantly lower at 1 d. Likewise, the shell length of larvae in the high CO₂ treatment was significantly smaller than larvae in the ambient conditions throughout the experiment and by 7 d, was reduced by 11.5%. This study also demonstrates that the size effects of short-term exposure to high CO₂ are still detectable after 7 d of larval development; the shells of larvae exposed to high CO₂ for the first 3 d of development and subsequently exposed to ambientCO₂ were not significantly different in size at 3 and 7 d than the shells of larvae exposed to high CO₂ throughout the experiment.

  16. Increased PSA expression on prostate cancer exosomes in in vitro condition and in cancer patients.

    PubMed

    Logozzi, Mariantonia; Angelini, Daniela F; Iessi, Elisabetta; Mizzoni, Davide; Di Raimo, Rossella; Federici, Cristina; Lugini, Luana; Borsellino, Giovanna; Gentilucci, Alessandro; Pierella, Federico; Marzio, Vittorio; Sciarra, Alessandro; Battistini, Luca; Fais, Stefano

    2017-09-10

    exosomes, such as PSA-exosomes, may represent a novel, non-invasive clinical tool for the screening and early diagnosis of prostate cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Activation of innate immunity by prostate specific antigen (PSA).

    PubMed

    Kodak, James A; Mann, Dean L; Klyushnenkova, Elena N; Alexander, Richard B

    2006-11-01

    Prostate specific antigen (PSA) is a serine protease secreted by the prostatic epithelium. The only known function of the protein is to cleave seminogelin. We wished to determine if PSA activated peripheral blood mononuclear cells (PBMC). PBMC and selected sub-populations were cultured with purified PSA. Secretion of IFNgamma was measured by cytokine capture flow cytometry and enzyme-linked immunosorbent assay. We observed secretion of IFNgamma and a proliferative response in PBMC cultured with PSA. We found that NK cells were the source of the IFNgamma but NK cells were not directly stimulated by PSA. Rather, a soluble factor secreted primarily by CD14 monocytes in response to PSA stimulated NK cells to secrete IFNgamma. PSA induces a pro-inflammatory response that results in the secretion of INFgamma by NK cells. The presence of large amounts of PSA could contribute to the common finding of inflammatory infiltrates in the prostate.

  18. Molecular Form Differences Between Prostate-Specific Antigen (PSA) Standards Create Quantitative Discordances in PSA ELISA Measurements

    PubMed Central

    McJimpsey, Erica L.

    2016-01-01

    The prostate-specific antigen (PSA) assays currently employed for the detection of prostate cancer (PCa) lack the specificity needed to differentiate PCa from benign prostatic hyperplasia and have high false positive rates. The PSA calibrants used to create calibration curves in these assays are typically purified from seminal plasma and contain many molecular forms (intact PSA and cleaved subforms). The purpose of this study was to determine if the composition of the PSA molecular forms found in these PSA standards contribute to the lack of PSA test reliability. To this end, seminal plasma purified PSA standards from different commercial sources were investigated by western blot (WB) and in multiple research grade PSA ELISAs. The WB results revealed that all of the PSA standards contained different mass concentrations of intact and cleaved molecular forms. Increased mass concentrations of intact PSA yielded higher immunoassay absorbance values, even between lots from the same manufacturer. Standardization of seminal plasma derived PSA calibrant molecular form mass concentrations and purification methods will assist in closing the gaps in PCa testing measurements that require the use of PSA values, such as the % free PSA and Prostate Health Index by increasing the accuracy of the calibration curves. PMID:26911983

  19. Molecular Form Differences Between Prostate-Specific Antigen (PSA) Standards Create Quantitative Discordances in PSA ELISA Measurements

    NASA Astrophysics Data System (ADS)

    McJimpsey, Erica L.

    2016-02-01

    The prostate-specific antigen (PSA) assays currently employed for the detection of prostate cancer (PCa) lack the specificity needed to differentiate PCa from benign prostatic hyperplasia and have high false positive rates. The PSA calibrants used to create calibration curves in these assays are typically purified from seminal plasma and contain many molecular forms (intact PSA and cleaved subforms). The purpose of this study was to determine if the composition of the PSA molecular forms found in these PSA standards contribute to the lack of PSA test reliability. To this end, seminal plasma purified PSA standards from different commercial sources were investigated by western blot (WB) and in multiple research grade PSA ELISAs. The WB results revealed that all of the PSA standards contained different mass concentrations of intact and cleaved molecular forms. Increased mass concentrations of intact PSA yielded higher immunoassay absorbance values, even between lots from the same manufacturer. Standardization of seminal plasma derived PSA calibrant molecular form mass concentrations and purification methods will assist in closing the gaps in PCa testing measurements that require the use of PSA values, such as the % free PSA and Prostate Health Index by increasing the accuracy of the calibration curves.

  20. Molecular Form Differences Between Prostate-Specific Antigen (PSA) Standards Create Quantitative Discordances in PSA ELISA Measurements.

    PubMed

    McJimpsey, Erica L

    2016-02-25

    The prostate-specific antigen (PSA) assays currently employed for the detection of prostate cancer (PCa) lack the specificity needed to differentiate PCa from benign prostatic hyperplasia and have high false positive rates. The PSA calibrants used to create calibration curves in these assays are typically purified from seminal plasma and contain many molecular forms (intact PSA and cleaved subforms). The purpose of this study was to determine if the composition of the PSA molecular forms found in these PSA standards contribute to the lack of PSA test reliability. To this end, seminal plasma purified PSA standards from different commercial sources were investigated by western blot (WB) and in multiple research grade PSA ELISAs. The WB results revealed that all of the PSA standards contained different mass concentrations of intact and cleaved molecular forms. Increased mass concentrations of intact PSA yielded higher immunoassay absorbance values, even between lots from the same manufacturer. Standardization of seminal plasma derived PSA calibrant molecular form mass concentrations and purification methods will assist in closing the gaps in PCa testing measurements that require the use of PSA values, such as the % free PSA and Prostate Health Index by increasing the accuracy of the calibration curves.

  1. Interoperability in the Planetary Science Archive (PSA)

    NASA Astrophysics Data System (ADS)

    Rios Diaz, C.

    2017-09-01

    The protocols and standards currently being supported by the recently released new version of the Planetary Science Archive at this time are the Planetary Data Access Protocol (PDAP), the EuroPlanet- Table Access Protocol (EPN-TAP) and Open Geospatial Consortium (OGC) standards. We explore these protocols in more detail providing scientifically useful examples of their usage within the PSA.

  2. Decreased choline and creatine concentrations in centrum semiovale in patients with generalized anxiety disorder: relationship to IQ and early trauma.

    PubMed

    Coplan, Jeremy D; Mathew, Sanjay J; Mao, Xiangling; Smith, Eric L P; Hof, Patrick R; Coplan, Paul M; Rosenblum, Leonard A; Gorman, Jack M; Shungu, Dikoma C

    2006-06-30

    We have demonstrated, using proton magnetic resonance spectroscopy imaging ((1)H-MRSI), elevations of N-acetyl-aspartate/creatine (NAA/CR) in right dorsolateral prefrontal cortex (DLPFC) in patients with generalized anxiety disorder (GAD) in comparison to healthy volunteers. A recent study indicates that the volume of prefrontal cortical white matter may be disproportionately increased in man in comparison to other primate species, with evolutionary implications. We therefore re-analyzed the identical scans with a specific focus on the centrum semiovale (CSO) as a representative region of interest of cerebral white matter. The central hypothesis was, in accordance with our gray matter findings, that patients with GAD, in comparison to healthy controls, would exhibit either an increase in NAA in CSO, or alternatively demonstrate reductions in concentrations of choline (CHO)-containing compounds and/or creatine+phosphocreatine (CR). MRSI scans that were obtained from an earlier [Mathew, S.J., Mao, X., Coplan, J.D., Smith, E.L., Sackeim, H.A., Gorman, J.M., Shungu, D.C., 2004. Dorsolateral prefrontal cortical pathology in generalized anxiety disorder: a proton magnetic resonance spectroscopic imaging study. American Journal of Psychiatry 161, 1119-1121] sample of 15 patients with GAD [6 with early trauma (ET)] and 15 healthy age- and sex-matched volunteers were analyzed further for CSO metabolite alterations. Self-reported worry was scored using the Penn State Worry Questionnaire (PSWQ) and intelligence was assessed using the Wechsler Abbreviated Scale of Intelligence (WASI). Serial multislice/multivoxel MRSI scans had been performed on a 1.5-T MRI. Using absolute quantification methods for metabolite concentrations, we examined NAA, CHO and CR. GAD patients without ET exhibited bilaterally decreased concentrations of CHO and CR in CSO in comparison to healthy volunteers, whereas GAD patients with ET were indistinguishable from controls. In patients with GAD, high IQ

  3. Comparison of clinical and survival characteristics between prostate cancer patients of PSA-based screening and clinical diagnosis in China.

    PubMed

    Xu, Libo; Wang, Jinguo; Guo, Baofeng; Zhang, Haixia; Wang, Kaichen; Wang, Ding; Dai, Chang; Zhang, Ling; Zhao, Xuejian

    2018-01-02

    Prostate-specific antigen (PSA)-based mass screening remains the most controversial topic in prostate cancer. PSA-based mass screening has not been widely used in China yet. The aim of our study was to evaluate the effect of the PSA-based screening in China. The cohort consisted of 1,012 prostate cancer patients. Data were retrospectively collected and clinical characteristics of the cohorts were investigated. Survival was analyzed for prostatic carcinoma of both PSA screened and clinically diagnosed patients according to clinical characteristics and the National Comprehensive Cancer Network (NCCN) risk classification. Cox Proportional Hazards Model analysis was done for risk predictor identification. The median age was 71 years old. Five-year overall and prostate-cancer-specific survival in prostatic adenocarcinoma patients were 77.52% and 79.65%; 10-year survivals were 62.57% and 68.60%, respectively. Survival was significantly poorer in patients with metastases and non-curative management. T staging and Gleason score by NCCN classification effectively stratified prostatic adenocarcinoma patients into different risk groups. T staging was a significant predictor of survival by COX Proportional Hazard Model. PSA screened patients had a significantly higher percentage diagnosed in early stage. PSA screened prostatic adenocarcinoma patients had a better prognosis in both overall and prostate cancer-specific survivals. This Chinese cohort had a lower overall and prostate cancer survival rate than it is reported in western countries. The incidence of early-stage prostate cancer found in PSA-based mass screening was high and there were significant differences in both overall and prostate cancer-specific survival between the PSA-screened and clinically diagnosed patients.

  4. Comparison of clinical and survival characteristics between prostate cancer patients of PSA-based screening and clinical diagnosis in China

    PubMed Central

    Xu, Libo; Wang, Jinguo; Guo, Baofeng; Zhang, Haixia; Wang, Kaichen; Wang, Ding; Dai, Chang; Zhang, Ling; Zhao, Xuejian

    2018-01-01

    Prostate-specific antigen (PSA)-based mass screening remains the most controversial topic in prostate cancer. PSA-based mass screening has not been widely used in China yet. The aim of our study was to evaluate the effect of the PSA-based screening in China. The cohort consisted of 1,012 prostate cancer patients. Data were retrospectively collected and clinical characteristics of the cohorts were investigated. Survival was analyzed for prostatic carcinoma of both PSA screened and clinically diagnosed patients according to clinical characteristics and the National Comprehensive Cancer Network (NCCN) risk classification. Cox Proportional Hazards Model analysis was done for risk predictor identification. The median age was 71 years old. Five-year overall and prostate-cancer-specific survival in prostatic adenocarcinoma patients were 77.52% and 79.65%; 10-year survivals were 62.57% and 68.60%, respectively. Survival was significantly poorer in patients with metastases and non-curative management. T staging and Gleason score by NCCN classification effectively stratified prostatic adenocarcinoma patients into different risk groups. T staging was a significant predictor of survival by COX Proportional Hazard Model. PSA screened patients had a significantly higher percentage diagnosed in early stage. PSA screened prostatic adenocarcinoma patients had a better prognosis in both overall and prostate cancer-specific survivals. This Chinese cohort had a lower overall and prostate cancer survival rate than it is reported in western countries. The incidence of early-stage prostate cancer found in PSA-based mass screening was high and there were significant differences in both overall and prostate cancer-specific survival between the PSA-screened and clinically diagnosed patients. PMID:29416625

  5. Decreased sensitivity of early imaging with In-111 oxine-labeled leukocytes in detection of occult infection: concise communication

    SciTech Connect

    Datz, F.L.; Jacobs, J.; Baker, W.

    1984-03-01

    Imaging with leukocytes labeled with indium-111 oxine is a sensitive technique for detecting sites of occult infection. Traditionally, imaging is performed 24 hr after injection. The authors undertook a prospective study of 35 patients (40 studies) with possible occult infection to see whether a 24-hr delay in imaging is really necessary. Patients were imaged at 1-4 hr and again at 24 hr after injection. The early images had a sensitivity of only 33%, compared with 95% for the 24-hr images. Of the seven studies that were positive on both early and delayed images, 71% had more intense uptake at 24more » hr. There were no false-positive early images. It was concluded that imaging 1-4 hr after injection with In-111 oxine-labeled leukocytes has a low sensitivity for detecting occult infection. However, a positive early image is specific for a site of infection.« less

  6. Impact of an Early Decrease in Systolic Blood Pressure on The Risk of Contrast-Induced Nephropathy after Percutaneous Coronary Intervention.

    PubMed

    Li, Hualong; Huang, Shuijin; He, Yiting; Liu, Yong; Liu, Yuanhui; Chen, Jiyan; Zhou, Yingling; Tan, Ning; Duan, Chongyang; Chen, Pingyan

    2016-02-01

    The early postprocedural period was thought to be the rush hour of contrast media excretion, causing rapid and prolonged renal hypoperfusion, which was the critical time window for contrast-induced nephropathy (CIN). 349 consecutive patients were enrolled into the study. The relation between an early postprocedural decrease in systolic blood pressure (SBP) and the risk of CIN was assessed using multivariate logistic regression. A postprocedural decrease in SBP was observed in 63% of patients and CIN developed in 28 (8.0%) patients. The CIN group had a lower postprocedural SBP (114.5±13.5 vs. 123.7±15.6mmHg, P=0.003) and a greater postprocedural decrease in SBP (16.2±19.1 vs. 5.9±18.7mmHg, P=0.005) than the no-CIN group. ROC analysis revealed that the optimum cutoff value for the SBP decrease in detecting CIN was >10mmHg (sensitivity 60.7%, specificity 59.5%, AUC=0.66). Multivariate logistic regression analysis found that a postprocedural decrease in SBP >10mmHg was a significant independent predictor of CIN (OR 2.368, 95%CI: 1.043-5.379, P=0.039), after adjustment for other risk factors. An early moderate postprocedural decrease in SBP may increase the risk of CIN in patients undergoing PCI. Copyright © 2015. Published by Elsevier B.V.

  7. On-treatment decrease of NKG2D correlates to early emergence of clinically evident hepatocellular carcinoma after interferon-free therapy for chronic hepatitis C.

    PubMed

    Chu, Po-Sung; Nakamoto, Nobuhiro; Taniki, Nobuhito; Ojiro, Keisuke; Amiya, Takeru; Makita, Yuko; Murata, Hiroko; Yamaguchi, Akihiro; Shiba, Shunsuke; Miyake, Rei; Katayama, Tadashi; Ugamura, Aya; Ikura, Akihiko; Takeda, Karin; Ebinuma, Hirotoshi; Saito, Hidetsugu; Kanai, Takanori

    2017-01-01

    Interferon (IFN)- free direct antiviral agents (DAAs) with rapid HCV eradication might evoke immunological reconstitutions, and some early recurrences of HCC after IFN-free DAAs have been reported. This study aimed to investigate whether natural killer group 2, member D (NKG2D) predicts early emergence of HCC after IFN-free DAAs. We conducted a clinical practice-based observational study of 101 patients infected with genotype 1 HCV who received IFN-free (DAAs), and stratified them into those who did or did not develop early (i.e., during the 6-month surveillance period following treatment.) recurrence or occurrence of clinically evident HCC. We also analyzed the peripheral blood mononuclear cells, both before treatment and at end of treatment (EOT), of 24 of the patients who received IFN-free DAAs, and 16 who received IFN-combined protease inhibitor. We found early emergence of clinically evident HCC after IFN-free DAAs in 12 (12%) patients. Higher pre-treatment NKG2D expression, higher FIB-4 score, previous HCC history and failure to achieve sustained viral response were significant factors correlating to early HCC emergence. After IFN-free DAAs, a rapid decrease of NKG2D at EOT correlated with early HCC emergence in the IFN-free DAA-treated patients, but not in patients treated with the IFN-combined regimen. The decrease of NKG2D until EOT was predictive of early HCC emergence at a cut-off of -52% (AUC = 0.92). On-treatment decrease of NKG2D may be a useful predictor of early emerging HCC in patients treated with IFN-free DAAs.

  8. The impact of the United States Preventive Services Task Force (USPTSTF) recommendations against prostate-specific antigen (PSA) testing on PSA testing in Australia.

    PubMed

    Zargar, Homayoun; van den Bergh, Roderick; Moon, Daniel; Lawrentschuk, Nathan; Costello, Anthony; Murphy, Declan

    2017-01-01

    To assess the impact of the United States Preventive Services Task Force (USPTSTF) recommendations on prostate-specific antigen (PSA) testing, prostate biopsy, and prostatectomy in Australian men based on the available Medicare data. Events were identified using Medicare item numbers for PSA testing (66655, 66659), prostate biopsy (37219), prostatectomy (37210), and prostatectomy with lymph node dissection (37211). The occurrences of each procedure was queried per 100 000 capita for consecutive financial years over the period 2000-2015. For each item number, reports were also generated for all Australian States. For PSA testing the data was stratified into three age groups of 45-54, 55-64, and 65-74 years. For assessing the rate of prostatectomy the capita rate values for two item numbers of prostatectomy (37210) and prostatectomy with lymph node dissection (37211) were combined. Steady declines in per capita incidences of all five item numbers assessed were seen for the three consecutive financial years (2013-2015) since the publication of the USPTSTF recommendation statement. These declines were seen across all Australian States. When examining the rate of PSA testing for the three age brackets 45-54, 55-64, and 65-74 years, similar trends were identified. Since the introduction of the USPTSTF recommendation statement there has been a steady nationwide decline in per capita incidences of PSA testing, prostate biopsy, and prostatectomy based on the Australian Medicare data. Whether these declines are in the right direction toward reduction in over-diagnosis and overtreatment of clinically insignificant prostate cancer or stage migration toward more locally advanced disease due to lost opportunity in diagnosing and treating early clinically significant prostate cancer will remain to be seen. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

  9. An AKT activity threshold regulates androgen-dependent and androgen-independent PSA expression in prostate cancer cell lines.

    PubMed

    Paliouras, Miltiadis; Diamandis, Eleftherios P

    2008-06-01

    The androgen receptor (AR) plays an important role in early prostate cancer by activating transcription of a number of genes participating in cell proliferation and growth and cancer progression. However, as the cancer progresses, prostate cancer cells transform from an androgen-dependent to an androgen-independent state. Androgen-independent prostate cancer can manifest itself in several forms, including a percentage of cancers that show reduced levels of prostate-specific antigen (PSA) and can progress without the need for the ligand or active receptor. Therefore, our goal was to examine the role of intracellular signaling pathways in an androgen-independent prostate cancer in vitro model. Using the cell line PC3(AR)(2), we stimulated cells with 5-alpha-dihydrotestosterone (DHT) and epidermal growth factor (EGF) and then analyzed PSA expression. We observed lower PSA expression when cells were jointly stimulated with DHT and EGF, and this was associated with an increase in AKT activity. We examined the role of AKT in AR activity and PSA expression by creating stable PC3(AR)(2) cell lines transfected with a PI3K-Ras-effector loop mutant. These cell lines showed lower DHT-stimulated PSA expression that correlated to changes in the phosphorylated state of AR. Therefore, we propose an in vitro androgen-independent model in which a PI3K/AKT activity threshold and subsequent AR transactivation regulate PSA expression.

  10. Early Exercise in the Burn Intensive Care Unit Decreases Hospital Stay, Improves Mental Health, and Physical Performance

    DTIC Science & Technology

    2017-10-01

    Decreases Hospital Stay, Improves Mental Health , and Physical Performance 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Oscar E. Suman, PhD...Multicenter Study of the Effect of In-Patient Exercise Training on Length of Hospitalization, Mental Health , and Physical Performance in Burned...Intensive Care Unit Decreases Hospital Stay, Improves Mental Health , and Physical Performance,” Proposal Log Number 13214039, Award Number W81XWH-14

  11. Early Childhood Risk Factors for Decreased FEV1 at Age Six to Seven Years in Young Children with Cystic Fibrosis.

    PubMed

    Sanders, Don B; Emerson, Julia; Ren, Clement L; Schechter, Michael S; Gibson, Ronald L; Morgan, Wayne; Rosenfeld, Margaret

    2015-08-01

    There are limited objective measures of the severity of lung disease before children are able to routinely perform spirometry, generally at age 6 years. Identifying risk factors for reduced lung function at age 6 provides opportunities to intervene and slow the progression of cystic fibrosis (CF) lung disease. To evaluate early childhood predictors of lung function at age 6-7 in a large U.S. CF cohort in the current era of widespread early eradication therapy for Pseudomonas aeruginosa (P. aeruginosa). Participants were children with CF enrolled before age 4 in the Early Pseudomonas Infection Control (EPIC) Observational Study, a multicenter, longitudinal study that enrolled P. aeruginosa-negative children not exceeding 12 years of age. Linear regression was used to estimate the association between potential early childhood risk factors and the best FEV1% predicted at age 6-7 years. Four hundred and eighty-four children (of 1,797 enrolled in the EPIC Observational Study) met the eligibility criteria for this analysis. Mean (SD) age at enrollment was 2.0 (1.3) years. In a multivariable model adjusted for age at enrollment, the following risk factors were significantly associated with lower mean (95% confidence interval) FEV1% predicted at age 6-7: weight percentile less than 10% during the year of enrollment (-5.3 [-9.1, -1.5]), P. aeruginosa positive during the year of enrollment (-2.8 [-5.7, 0.0]), crackles or wheeze during the year of enrollment (-5.7 [-9.4, -1.9]), mother's education of high school or less (-4.2 [-7.3, -1.2]), and mother smoked during pregnancy (-4.4 [-8.8, 0.1]). In this large U.S. cohort, we identified several early childhood risk factors for lower FEV1 at age 6-7 years, most of which are modifiable. Clinical trial registered with www.clinicaltrials.gov (NCT00097773).

  12. Recombinant Forms of Leishmania amazonensis Excreted/Secreted Promastigote Surface Antigen (PSA) Induce Protective Immune Responses in Dogs.

    PubMed

    Petitdidier, Elodie; Pagniez, Julie; Papierok, Gérard; Vincendeau, Philippe; Lemesre, Jean-Loup; Bras-Gonçalves, Rachel

    2016-05-01

    Preventive vaccination is a highly promising strategy for interrupting leishmaniasis transmission that can, additionally, contribute to elimination. A vaccine formulation based on naturally excreted secreted (ES) antigens was prepared from L. infantum promastigote culture supernatant. This vaccine achieved successful results in Phase III trials and was licensed and marketed as CaniLeish. We recently showed that newly identified ES promastigote surface antigen (PSA), from both viable promastigotes and axenically-grown amastigotes, represented the major constituent and the highly immunogenic antigen of L. infantum and L. amazonensis ES products. We report here that three immunizations with either the recombinant ES LaPSA-38S (rPSA) or its carboxy terminal part LaPSA-12S (Cter-rPSA), combined with QA-21 as adjuvant, confer high levels of protection in naive L. infantum-infected Beagle dogs, as checked by bone marrow parasite absence in respectively 78.8% and 80% of vaccinated dogs at 6 months post-challenge. The parasite burden in infected vaccinated dogs was significantly reduced compared to placebo group, as measured by q-PCR. Moreover, our results reveal humoral and cellular immune response clear-cut differences between vaccinated and control dogs. An early increase in specific IgG2 antibodies was observed in rPSA/QA-21- and Cter-rPSA/QA-21-immunized dogs only. They were found functionally active in vitro and were highly correlated with vaccine protection. In vaccinated protected dogs, IFN-γ and NO productions, as well as anti-leishmanial macrophage activity, were increased. These data strongly suggest that ES PSA or its carboxy-terminal part, in recombinant forms, induce protection in a canine model of zoonotic visceral leishmaniasis by inducing a Th1-dominant immune response and an appropriate specific antibody response. These data suggest that they could be considered as important active components in vaccine candidates.

  13. Positive associations between galectin-3 and PSA levels in prostate cancer patients: a prospective clinical study-I.

    PubMed

    Nakajima, Kosei; Heilbrun, Lance K; Hogan, Victor; Smith, Daryn; Heath, Elisabeth; Raz, Avraham

    2016-12-13

    Galectin-3 (Gal-3), an oncogenic pro-inflammatory protein, has been suggested as a possible complementary diagnostic candidate to prostate specific antigen (PSA) blood test for prostate cancer patients. The presence of the proteins in the circulation (biomarkers) may elicit an intrinsic humoral immune reaction by generating autoantibodies, which consequently could alter the detection levels. Here, we report the associations of the two prostate cancer biomarkers, Gal-3 and PSA in patients at different clinical states of prostate cancer while taking into account the autoantibody levels. A blind, prospective, single institution, pilot study was conducted. A total of 95 men were classified into 5 groups: healthy controls (Group1), newly diagnosed patients (Group2), no recurrence after local therapy (Group3), rising PSA after local therapy (Group4), and metastatic patients (Group5). Gal-3 and PSA level were divided by their respective autoantibodies, which yielded relative PSA and relative Gal-3 levels. After the adjustments, Spearman's rank correlations and linear regression modeling revealed the positive associations between relative Gal-3 and relative PSA levels among all 95 men combined (rho = 0.446, P < 0.0001; fitted slope 0.448, P < 0.0001), in Group2 (rho = 0.616, P = 0.0050; fitted slope 0.438, P =0.0011), and Group3 (rho = 0.484, P = 0.0360; fitted slope 0.470, P = 0.0187). The data show positive associations of relative Gal-3 and relative PSA levels in prostate cancer patients, notably at early clinical time course. Allowing for the influence of autoantibodies, Gal-3 level might be considered as a potential biomarker since it is positively associated with PSA level.

  14. Recombinant Forms of Leishmania amazonensis Excreted/Secreted Promastigote Surface Antigen (PSA) Induce Protective Immune Responses in Dogs

    PubMed Central

    Petitdidier, Elodie; Pagniez, Julie; Papierok, Gérard; Vincendeau, Philippe; Lemesre, Jean-Loup; Bras-Gonçalves, Rachel

    2016-01-01

    Preventive vaccination is a highly promising strategy for interrupting leishmaniasis transmission that can, additionally, contribute to elimination. A vaccine formulation based on naturally excreted secreted (ES) antigens was prepared from L. infantum promastigote culture supernatant. This vaccine achieved successful results in Phase III trials and was licensed and marketed as CaniLeish. We recently showed that newly identified ES promastigote surface antigen (PSA), from both viable promastigotes and axenically-grown amastigotes, represented the major constituent and the highly immunogenic antigen of L. infantum and L. amazonensis ES products. We report here that three immunizations with either the recombinant ES LaPSA-38S (rPSA) or its carboxy terminal part LaPSA-12S (Cter-rPSA), combined with QA-21 as adjuvant, confer high levels of protection in naive L. infantum-infected Beagle dogs, as checked by bone marrow parasite absence in respectively 78.8% and 80% of vaccinated dogs at 6 months post-challenge. The parasite burden in infected vaccinated dogs was significantly reduced compared to placebo group, as measured by q-PCR. Moreover, our results reveal humoral and cellular immune response clear-cut differences between vaccinated and control dogs. An early increase in specific IgG2 antibodies was observed in rPSA/QA-21- and Cter-rPSA/QA-21-immunized dogs only. They were found functionally active in vitro and were highly correlated with vaccine protection. In vaccinated protected dogs, IFN-γ and NO productions, as well as anti-leishmanial macrophage activity, were increased. These data strongly suggest that ES PSA or its carboxy-terminal part, in recombinant forms, induce protection in a canine model of zoonotic visceral leishmaniasis by inducing a Th1-dominant immune response and an appropriate specific antibody response. These data suggest that they could be considered as important active components in vaccine candidates. PMID:27223609

  15. Insulin promotes cell migration by regulating PSA-NCAM.

    PubMed

    Monzo, Hector J; Coppieters, Natacha; Park, Thomas I H; Dieriks, Birger V; Faull, Richard L M; Dragunow, Mike; Curtis, Maurice A

    2017-06-01

    Cellular interactions with the extracellular environment are modulated by cell surface polysialic acid (PSA) carried by the neural cell adhesion molecule (NCAM). PSA-NCAM is involved in cellular processes such as differentiation, plasticity, and migration, and is elevated in Alzheimer's disease as well as in metastatic tumour cells. Our previous work demonstrated that insulin enhances the abundance of cell surface PSA by inhibiting PSA-NCAM endocytosis. In the present study we have identified a mechanism for insulin-dependent inhibition of PSA-NCAM turnover affecting cell migration. Insulin enhanced the phosphorylation of the focal adhesion kinase leading to dissociation of αv-integrin/PSA-NCAM clusters, and promoted cell migration. Our results show that αv-integrin plays a key role in the PSA-NCAM turnover process. αv-integrin knockdown stopped PSA-NCAM from being endocytosed, and αv-integrin/PSA-NCAM clusters co-labelled intracellularly with Rab5, altogether indicating a role for αv-integrin as a carrier for PSA-NCAM during internalisation. Furthermore, inhibition of p-FAK caused dissociation of αv-integrin/PSA-NCAM clusters and counteracted the insulin-induced accumulation of PSA at the cell surface and cell migration was impaired. Our data reveal a functional association between the insulin/p-FAK-dependent regulation of PSA-NCAM turnover and cell migration through the extracellular matrix. Most importantly, they identify a novel mechanism for insulin-stimulated cell migration. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Decreased expression of the stress protein HSP70 is an early event in murine erythroleukemic cell differentiation.

    PubMed Central

    Hensold, J O; Housman, D E

    1988-01-01

    Two-dimensional protein gels were used to systematically assess changes in gene expression in Friend erythroleukemia cells after exposure to inducers of differentiation. A rapid decrease in expression of the stress protein HSP70 was observed after exposure to inducers. The kinetics of this change suggest that it may be related to the cellular events that regulate the onset of differentiation. Images PMID:3164440

  17. Four-dimensional geometric assessment of tricuspid annulus movement in early functional tricuspid regurgitation patients indicates decreased longitudinal flexibility

    PubMed Central

    Maeba, Satoru; Taguchi, Takahiro; Midorikawa, Hirofumi; Kanno, Megumu; Sueda, Taijiro

    2013-01-01

    OBJECTIVES Functional tricuspid regurgitation (FTR) is generally caused by the dilation of the tricuspid annulus (TA) and the tethering of tricuspid leaflets; however, it also occurs in patients without dilatation of the TA. The aim of this study was to develop and to use a four-dimensional tracking system, utilizing cardiac magnetic resonance imaging (MRI), and to assess TA flexibility in patients with early FTR without right ventricle dilation as a preliminary investigation for the mechanism of early FTR. METHODS The structure and movement of the TA were examined in 20 healthy subjects and 19 FTR patients whose right ventricle was not dilated. We analysed the short axis and longitudinal movement of a mid-septal point (S), a mid-lateral point (L), a mid-anterior point (A) and a mid-posterior point (P) on the TA throughout the cardiac cycle. The tethering distance of the tricuspid leaflets and the integrated orbiting volume of the TA were also measured. RESULTS The TA area (mm2) and AP and LS distances (mm) did not differ significantly between the two groups, but the longitudinally moving distances (mm) of the four points were significantly shorter in patients with FTR than in healthy subjects. Also, the mean tethering distance (mm) was significantly longer in patients with FTR than in healthy subjects (9.0 ± 1.5 vs 4.0 ± 1.3, respectively; P < 0.001), and the integrated volume (mm3) of the annular moving track, throughout the cardiac cycle, was significantly larger in healthy subjects than in patients with FTR (40 428 ± 10 951 vs 22 967 ± 6079, P < 0.001). CONCLUSIONS The longitudinal flexibility of the TA in FTR patients was significantly less than that in the healthy subjects, and the tethering of the tricuspid leaflets occurred in FTR patients despite the absence of TA and RV dilation, which can be one triggering factor of early FTR. Four-dimensional geometric assessment, using cardiac MRI and the tracking program that we have developed, is capable of

  18. Four-dimensional geometric assessment of tricuspid annulus movement in early functional tricuspid regurgitation patients indicates decreased longitudinal flexibility.

    PubMed

    Maeba, Satoru; Taguchi, Takahiro; Midorikawa, Hirofumi; Kanno, Megumu; Sueda, Taijiro

    2013-06-01

    Functional tricuspid regurgitation (FTR) is generally caused by the dilation of the tricuspid annulus (TA) and the tethering of tricuspid leaflets; however, it also occurs in patients without dilatation of the TA. The aim of this study was to develop and to use a four-dimensional tracking system, utilizing cardiac magnetic resonance imaging (MRI), and to assess TA flexibility in patients with early FTR without right ventricle dilation as a preliminary investigation for the mechanism of early FTR. The structure and movement of the TA were examined in 20 healthy subjects and 19 FTR patients whose right ventricle was not dilated. We analysed the short axis and longitudinal movement of a mid-septal point (S), a mid-lateral point (L), a mid-anterior point (A) and a mid-posterior point (P) on the TA throughout the cardiac cycle. The tethering distance of the tricuspid leaflets and the integrated orbiting volume of the TA were also measured. The TA area (mm(2)) and AP and LS distances (mm) did not differ significantly between the two groups, but the longitudinally moving distances (mm) of the four points were significantly shorter in patients with FTR than in healthy subjects. Also, the mean tethering distance (mm) was significantly longer in patients with FTR than in healthy subjects (9.0 ± 1.5 vs 4.0 ± 1.3, respectively; P < 0.001), and the integrated volume (mm(3)) of the annular moving track, throughout the cardiac cycle, was significantly larger in healthy subjects than in patients with FTR (40 428 ± 10 951 vs 22 967 ± 6079, P < 0.001). The longitudinal flexibility of the TA in FTR patients was significantly less than that in the healthy subjects, and the tethering of the tricuspid leaflets occurred in FTR patients despite the absence of TA and RV dilation, which can be one triggering factor of early FTR. Four-dimensional geometric assessment, using cardiac MRI and the tracking program that we have developed, is capable of determining TA structure and flexibility.

  19. Experiences of Uncertainty in Men With an Elevated PSA.

    PubMed

    Biddle, Caitlin; Brasel, Alicia; Underwood, Willie; Orom, Heather

    2015-05-15

    A significant proportion of men, ages 50 to 70 years, have, and continue to receive prostate specific antigen (PSA) tests to screen for prostate cancer (PCa). Approximately 70% of men with an elevated PSA level will not subsequently be diagnosed with PCa. Semistructured interviews were conducted with 13 men with an elevated PSA level who had not been diagnosed with PCa. Uncertainty was prominent in men's reactions to the PSA results, stemming from unanswered questions about the PSA test, PCa risk, and confusion about their management plan. Uncertainty was exacerbated or reduced depending on whether health care providers communicated in lay and empathetic ways, and provided opportunities for question asking. To manage uncertainty, men engaged in information and health care seeking, self-monitoring, and defensive cognition. Results inform strategies for meeting informational needs of men with an elevated PSA and confirm the primary importance of physician communication behavior for open information exchange and uncertainty reduction. © The Author(s) 2015.

  20. Experiences of Uncertainty in Men With an Elevated PSA

    PubMed Central

    Biddle, Caitlin; Brasel, Alicia; Underwood, Willie; Orom, Heather

    2016-01-01

    A significant proportion of men, ages 50 to 70 years, have, and continue to receive prostate specific antigen (PSA) tests to screen for prostate cancer (PCa). Approximately 70% of men with an elevated PSA level will not subsequently be diagnosed with PCa. Semistructured interviews were conducted with 13 men with an elevated PSA level who had not been diagnosed with PCa. Uncertainty was prominent in men’s reactions to the PSA results, stemming from unanswered questions about the PSA test, PCa risk, and confusion about their management plan. Uncertainty was exacerbated or reduced depending on whether health care providers communicated in lay and empathetic ways, and provided opportunities for question asking. To manage uncertainty, men engaged in information and health care seeking, self-monitoring, and defensive cognition. Results inform strategies for meeting informational needs of men with an elevated PSA and confirm the primary importance of physician communication behavior for open information exchange and uncertainty reduction. PMID:25979635

  1. Evaluating the Phoenix definition of biochemical failure after (125)I prostate brachytherapy: Can PSA kinetics distinguish PSA failures from PSA bounces?

    PubMed

    Thompson, Anna; Keyes, Mira; Pickles, Tom; Palma, David; Moravan, Veronika; Spadinger, Ingrid; Lapointe, Vincent; Morris, W James

    2010-10-01

    To evaluate the prostate-specific antigen (PSA) kinetics of PSA failure (PSAf) and PSA bounce (PSAb) after permanent (125)I prostate brachytherapy (PB). The study included 1,006 consecutive low and "low tier" intermediate-risk patients treated with (125)I PB, with a potential minimum follow-up of 4 years. Patients who met the Phoenix definition of biochemical failure (nadir + 2 ng/mL(-1)) were identified. If the PSA subsequently fell to ≤0.5 ng/mL(-1)without intervention, this was considered a PSAb. All others were scored as true PSAf. Patient, tumor and dosimetric characteristics were compared between groups using the chi-square test and analysis of variance to evaluate factors associated with PSAf or PSAb. Median follow-up was 54 months. Of the 1,006 men, 57 patients triggered the Phoenix definition of PSA failure, 32 (56%) were true PSAf, and 25 PSAb (44%). The median time to trigger nadir + 2 was 20.6 months (range, 6-36) vs. 49 mo (range, 12-83) for PSAb vs. PSAf groups (p < 0.001). The PSAb patients were significantly younger (p < 0.0001), had shorter time to reach the nadir (median 6 vs. 11.5 months, p = 0.001) and had a shorter PSA doubling time (p = 0.05). Men younger than age 70 who trigger nadir +2 PSA failure within 38 months of implant have an 80% likelihood of having PSAb and 20% chance of PSAf. With adequate follow-up, 44% of PSA failures by the Phoenix definition in our cohort were found to be benign PSA bounces. Our study reinforces the need for adequate follow-up when reporting PB PSA outcomes, to ensure accurate estimates of treatment efficacy and to avoid unnecessary secondary interventions. 2010. Published by Elsevier Inc. All rights reserved.

  2. Early decrease of insulin sensitivity in offspring of individuals with type 2 diabetes. The Mexican Diabetes Prevention Study.

    PubMed

    Pérez-Fuentes, Ricardo; Baez-Duarte, Blanca G; Zamora-Ginez, Irma; Ruiz-Vivanco, Guadalupe; Pulido-Pérez, Patricia; Nieva-Vázquez, Adriana; Gonzalez-Mejia, M Elba; Torres-Rasgado, Enrique

    2014-04-01

    Defects in insulin sensitivity (IS) and insulin secretion have been recognized as risk factors for type 2 diabetes (T2D) and its complications. We undertook this study to establish the relationship between healthy type 2 diabetic offspring (OFD) from a Mexican population with IS. A total of 602 Mexican subjects, 359 first-degree offspring of T2D (OFD+) and 243 first-degree non-offspring of T2D (OFD-) were classified as young adults (age range, 18-44 years) and middle-aged adults (age range, 45-65 years). Groups were clinically and biochemically characterized. Quantitative insulin sensitivity check index (QUICKI) was used to estimate IS and the homeostasis model assessment B (HOMA-B) was used to estimate B cell function. IS decreased significantly (p <0.05) in OFD+ middle-aged (QUICKI 0.330 ± 0.03) compared with OFD- (0. 370 ± 0.03). Middle-aged adults (OFD+) had the highest prevalence of increased fasting insulin levels (FIL) (13.6%) and decreased IS (22.9%) compared with OFD- groups (3.2%). A binary regression analysis showed the association of OFD+ with increased FIL (odds ratio [OR], 3.71; 95% confidence interval [95% CI], 1.68-8.2; p = 0.001), and QUICKI (OR, 10.87; 95% CI, 2.36-44.69; p <0.01) adjusted by gender, age, and obesity. Our results suggest that decreased IS itself could be recognized as one of the earliest detectable abnormalities in middle-aged adults. Moreover, prevalence increases with age and is associated with type 2 diabetic offspring, regardless of obesity. Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.

  3. Investigating the prostate specific antigen, body mass index and age relationship: is an age-BMI-adjusted PSA model clinically useful?

    PubMed

    Harrison, Sean; Tilling, Kate; Turner, Emma L; Lane, J Athene; Simpkin, Andrew; Davis, Michael; Donovan, Jenny; Hamdy, Freddie C; Neal, David E; Martin, Richard M

    2016-12-01

    Previous studies indicate a possible inverse relationship between prostate-specific antigen (PSA) and body mass index (BMI), and a positive relationship between PSA and age. We investigated the associations between age, BMI, PSA, and screen-detected prostate cancer to determine whether an age-BMI-adjusted PSA model would be clinically useful for detecting prostate cancer. Cross-sectional analysis nested within the UK ProtecT trial of treatments for localized cancer. Of 18,238 men aged 50-69 years, 9,457 men without screen-detected prostate cancer (controls) and 1,836 men with prostate cancer (cases) met inclusion criteria: no history of prostate cancer or diabetes; PSA < 10 ng/ml; BMI between 15 and 50 kg/m 2 . Multivariable linear regression models were used to investigate the relationship between log-PSA, age, and BMI in all men, controlling for prostate cancer status. In the 11,293 included men, the median PSA was 1.2 ng/ml (IQR: 0.7-2.6); mean age 61.7 years (SD 4.9); and mean BMI 26.8 kg/m 2 (SD 3.7). There were a 5.1% decrease in PSA per 5 kg/m 2 increase in BMI (95% CI 3.4-6.8) and a 13.6% increase in PSA per 5-year increase in age (95% CI 12.0-15.1). Interaction tests showed no evidence for different associations between age, BMI, and PSA in men above and below 3.0 ng/ml (all p for interaction >0.2). The age-BMI-adjusted PSA model performed as well as an age-adjusted model based on National Institute for Health and Care Excellence (NICE) guidelines at detecting prostate cancer. Age and BMI were associated with small changes in PSA. An age-BMI-adjusted PSA model is no more clinically useful for detecting prostate cancer than current NICE guidelines. Future studies looking at the effect of different variables on PSA, independent of their effect on prostate cancer, may improve the discrimination of PSA for prostate cancer.

  4. Widespread Albedo Decreasing and Induced Melting of Himalayan Snow and Ice in the Early 21st Century

    PubMed Central

    Ming, Jing; Wang, Yaqiang; Du, Zhencai; Zhang, Tong; Guo, Wanqin; Xiao, Cunde; Xu, Xiaobin; Ding, Minghu; Zhang, Dongqi; Yang, Wen

    2015-01-01

    Background The widely distributed glaciers in the greater Himalayan region have generally experienced rapid shrinkage since the 1850s. As invaluable sources of water and because of their scarcity, these glaciers are extremely important. Beginning in the twenty-first century, new methods have been applied to measure the mass budget of these glaciers. Investigations have shown that the albedo is an important parameter that affects the melting of Himalayan glaciers. Methodology/Principal Findings The surface albedo based on the Moderate Resolution Imaging Spectroradiometer (MODIS) data over the Hindu Kush, Karakoram and Himalaya (HKH) glaciers is surveyed in this study for the period 2000–2011. The general albedo trend shows that the glaciers have been darkening since 2000. The most rapid decrease in the surface albedo has occurred in the glacial area above 6000 m, which implies that melting will likely extend to snow accumulation areas. The mass-loss equivalent (MLE) of the HKH glacial area caused by surface shortwave radiation absorption is estimated to be 10.4 Gt yr-1, which may contribute to 1.2% of the global sea level rise on annual average (2003–2009). Conclusions/Significance This work probably presents a first scene depicting the albedo variations over the whole HKH glacial area during the period 2000–2011. Most rapidly decreasing in albedo has been detected in the highest area, which deserves to be especially concerned. PMID:26039088

  5. Widespread albedo decreasing and induced melting of Himalayan snow and ice in the early 21st century.

    PubMed

    Ming, Jing; Wang, Yaqiang; Du, Zhencai; Zhang, Tong; Guo, Wanqin; Xiao, Cunde; Xu, Xiaobin; Ding, Minghu; Zhang, Dongqi; Yang, Wen

    2015-01-01

    The widely distributed glaciers in the greater Himalayan region have generally experienced rapid shrinkage since the 1850s. As invaluable sources of water and because of their scarcity, these glaciers are extremely important. Beginning in the twenty-first century, new methods have been applied to measure the mass budget of these glaciers. Investigations have shown that the albedo is an important parameter that affects the melting of Himalayan glaciers. The surface albedo based on the Moderate Resolution Imaging Spectroradiometer (MODIS) data over the Hindu Kush, Karakoram and Himalaya (HKH) glaciers is surveyed in this study for the period 2000-2011. The general albedo trend shows that the glaciers have been darkening since 2000. The most rapid decrease in the surface albedo has occurred in the glacial area above 6000 m, which implies that melting will likely extend to snow accumulation areas. The mass-loss equivalent (MLE) of the HKH glacial area caused by surface shortwave radiation absorption is estimated to be 10.4 Gt yr-1, which may contribute to 1.2% of the global sea level rise on annual average (2003-2009). This work probably presents a first scene depicting the albedo variations over the whole HKH glacial area during the period 2000-2011. Most rapidly decreasing in albedo has been detected in the highest area, which deserves to be especially concerned.

  6. Serum PSA levels in the Indian population: Is it different?

    PubMed

    Agrawal, Amit; Karan, Shailesh Chandra

    2017-04-01

    Serum prostate-specific antigen (PSA) is an important tumour, marker which is widely used to trigger trans-rectal ultrasound (TRUS)-guided prostate biopsy. However, the PSA levels vary with race and ethnicity. Therefore, there is a need to have an Indian reference range. All adult male patients meeting the inclusion and exclusion criteria were enrolled in this study. They were subjected to assessment of serum total PSA, digital rectal examination and trans-abdominal ultrasound. If any one or more of these were found abnormal, then a TRUS-guided 12-core prostate biopsy was done. Patients who were detected to have prostatic cancer were excluded from the final analysis. The data so obtained was grouped among the following three age groups: 40-49, 50-59 and 60-70 years, and the age-specific PSA values, prostatic volume and PSA density were found. A total of 1772 patients were analysed. The mean serum total PSA was 1.76 ng/ml with a standard deviation of 2.566 ng/ml. Group-wise age distribution of the mean serum total PSA was 1.22, 1.97 and 2.08 ng/ml in 40-49, 50-59 and 60-70 years age groups. The mean total PSA and the age-specific PSA range tend to be lower in the Indians than the Western population.

  7. 5-Episinuleptolide Decreases the Expression of the Extracellular Matrix in Early Biofilm Formation of Multi-Drug Resistant Acinetobacter baumannii.

    PubMed

    Tseng, Sung-Pin; Hung, Wei-Chun; Huang, Chiung-Yao; Lin, Yin-Shiou; Chan, Min-Yu; Lu, Po-Liang; Lin, Lin; Sheu, Jyh-Horng

    2016-07-29

    Nosocomial infections and increasing multi-drug resistance caused by Acinetobacter baumannii have been recognized as emerging problems worldwide. Moreover, A. baumannii is able to colonize various abiotic materials and medical devices, making it difficult to eradicate and leading to ventilator-associated pneumonia, and bacteremia. Development of novel molecules that inhibit bacterial biofilm formation may be an alternative prophylactic option for the treatment of biofilm-associated A. baumannii infections. Marine environments, which are unlike their terrestrial counterparts, harbor an abundant biodiversity of marine organisms that produce novel bioactive natural products with pharmaceutical potential. In this study, we identified 5-episinuleptolide, which was isolated from Sinularia leptoclados, as an inhibitor of biofilm formation in ATCC 19606 and three multi-drug resistant A. baumannii strains. In addition, the anti-biofilm activities of 5-episinuleptolide were observed for Gram-negative bacteria but not for Gram-positive bacteria, indicating that the inhibition mechanism of 5-episinuleptolide is effective against only Gram-negative bacteria. The mechanism of biofilm inhibition was demonstrated to correlate to decreased gene expression from the pgaABCD locus, which encodes the extracellular polysaccharide poly-β-(1,6)-N-acetylglucosamine (PNAG). Scanning electron microscopy (SEM) indicated that extracellular matrix of the biofilm was dramatically decreased by treatment with 5-episinuleptolide. Our study showed potentially synergistic activity of combination therapy with 5-episinuleptolide and levofloxacin against biofilm formation and biofilm cells. These data indicate that inhibition of biofilm formation via 5-episinuleptolide may represent another prophylactic option for solving the persistent problem of biofilm-associated A. baumannii infections.

  8. 5-Year Downstream Outcomes Following Prostate-Specific Antigen (PSA) Screening in Older Men

    PubMed Central

    Walter, Louise C.; Fung, Kathy Z.; Kirby, Katharine A.; Shi, Ying; Espaldon, Roxanne; O'Brien, Sarah; Freedland, Stephen J.; Powell, Adam A.; Hoffman, Richard M.

    2013-01-01

    Background Despite ongoing controversies surrounding PSA screening, large numbers of men age 65+ undergo screening. However, there are few data quantifying the chain of events following screening in clinical practice to better inform decisions. The objective of this study is to quantify 5-year downstream outcomes following a PSA screening result > 4 ng/ml in older men. Methods Longitudinal cohort study of 295,645 men age 65+ who underwent PSA screening in the VA healthcare system in 2003 and were followed for 5 years using national VA and Medicare data. Among men whose index screening PSA was > 4 ng/ml we determined the number who underwent biopsy, were diagnosed with prostate cancer, were treated and survived 5-years, according to baseline characteristics. Biopsy and treatment complications were also assessed. Results 25,208 (8.5%) men had an index PSA > 4 ng/ml. During 5-year follow-up, 8,313 (33%) men underwent at least one biopsy, 5,220 (63%) of men biopsied were diagnosed with prostate cancer of whom 4,284 (82%) were treated. Receipt of biopsy decreased with advancing age and worsening comorbidity (P<0.001), whereas the percentage treated for biopsy-detected cancer exceeded 75% even among men age 85+, those with Charlson score 3+, and those with low-risk cancer. Among men with biopsy-detected cancer, the risk of dying of non-prostate cancer causes increased with advancing age and comorbidity (P<0.001). 468 (6%) of men had 7-day biopsy complications. Treatment complications included 584 (14%) men with new incontinence and 588 (14%) men with new erectile dysfunction. Conclusions Receipt of biopsy is low in older men with abnormal screening PSA and decreases with advancing age and comorbidity. However, once biopsy detects cancer most men undergo immediate treatment regardless of advancing age, comorbidity, or low-risk cancer. Understanding downstream outcomes in clinical practice should better inform individualized decisions among older men considering PSA

  9. Up-regulation of mismatch repair genes MSH6, PMS2 and MLH1 parallels development of genetic instability and is linked to tumor aggressiveness and early PSA recurrence in prostate cancer.

    PubMed

    Wilczak, Waldemar; Rashed, Semin; Hube-Magg, Claudia; Kluth, Martina; Simon, Ronald; Büscheck, Franziska; Clauditz, Till Sebastian; Grupp, Katharina; Minner, Sarah; Tsourlakis, Maria Christina; Möller-Koop, Christina; Graefen, Markus; Adam, Meike; Haese, Alexander; Wittmer, Corinna; Sauter, Guido; Izbicki, Jakob Robert; Huland, Hartwig; Schlomm, Thorsten; Steurer, Stefan; Krech, Till; Lebok, Patrick

    2017-01-01

    DNA mismatch repair (MMR) is integral to the maintenance of genetic stability. We aimed to evaluate the clinical impact of MMR gene expression in prostate cancer. The MMR genes MSH6, MLH1 and PMS2 were analyzed by immunohistochemistry on a tissue microarray containing 11152 prostate cancer specimens. Results were compared with ETS-related gene status and deletions of PTEN, 3p13, 5q21 and 6q15. MSH6, MLH1 and PMS2 expression was detectable in 89.5%, 85.4% and 85.0% of cancers and was particularly strong in cancers with advanced pathological tumor stage (P < 0.0001 each), high Gleason grade (P < 0.0001 each), nodal metastasis (P ≤ 0.0083) and early biochemical recurrence (P < 0.0001). High levels of MMR gene expression paralleled features of genetic instability, such as the number of genomic deletions per cancer; strong expression of all three MMR genes was found in 24%, 29%, 30%, 33% and 42% of cancers with no, one, two, three or four to five deletions (P < 0.0001). The prognostic value of the analyzed MMR genes was largely driven by the subset of cancers lacking ERG fusion (P < 0.0001), while the prognostic impact of MMR gene overexpression was only marginal in ERG-positive cancers. Multivariate analyses suggested an independent prognostic relevance of MMR genes in ERG-negative prostate cancers when compared with prognostic parameters available at the time of initial biopsy. In conclusion, MMR overexpression is common in prostate cancer and is linked to poor outcome as well as features indicating genetic instability. ERG fusion should be analyzed along with MMR gene expression in potential clinical tests. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Loss of CD28 on Peripheral T Cells Decreases the Risk for Early Acute Rejection after Kidney Transplantation

    PubMed Central

    Dedeoglu, Burç; Meijers, Ruud W. J.; Klepper, Mariska; Hesselink, Dennis A.; Baan, Carla C.; Litjens, Nicolle H. R.; Betjes, Michiel G. H.

    2016-01-01

    Background End-stage renal disease patients have a dysfunctional, prematurely aged peripheral T-cell system. Here we hypothesized that the degree of premature T-cell ageing before kidney transplantation predicts the risk for early acute allograft rejection (EAR). Methods 222 living donor kidney transplant recipients were prospectively analyzed. EAR was defined as biopsy proven acute allograft rejection within 3 months after kidney transplantation. The differentiation status of circulating T cells, the relative telomere length and the number of CD31+ naive T cells were determined as T-cell ageing parameters. Results Of the 222 patients analyzed, 30 (14%) developed an EAR. The donor age and the historical panel reactive antibody score were significantly higher (p = 0.024 and p = 0.039 respectively) and the number of related donor kidney transplantation was significantly lower (p = 0.018) in the EAR group. EAR-patients showed lower CD4+CD28null T-cell numbers (p<0.01) and the same trend was observed for CD8+CD28null T-cell numbers (p = 0.08). No differences regarding the other ageing parameters were found. A multivariate Cox regression analysis showed that higher CD4+CD28null T-cell numbers was associated with a lower risk for EAR (HR: 0.65, p = 0.028). In vitro, a significant lower percentage of alloreactive T cells was observed within CD28null T cells (p<0.001). Conclusion Immunological ageing-related expansion of highly differentiated CD28null T cells is associated with a lower risk for EAR. PMID:26950734

  11. Baseline PSA in a Spanish male population aged 40-49 years anticipates detection of prostate cancer.

    PubMed

    Angulo, J C; Viñas, M A; Gimbernat, H; Fata, F Ramón de; Granados, R; Luján, M

    2015-12-01

    We researched the usefulness of optimizing prostate cancer (PC) screening in our community using baseline PSA readings in men between 40-49 years of age. A retrospective study was performed that analyzed baseline PSA in the fifth decade of life and its ability to predict the development of PC in a population of Madrid (Spain). An ROC curve was created and a cutoff was proposed. We compared the evolution of PSA from baseline in patients with consecutive readings using the Friedman test. We established baseline PSA ranges with different risks of developing cancer and assessed the diagnostic utility of the annual PSA velocity (PSAV) in this population. Some 4,304 men aged 40-49 years underwent opportunistic screening over the course of 17 years, with at least one serum PSA reading (6,001 readings) and a mean follow-up of 57.1±36.8 months. Of these, 768 underwent biopsy of some organ, and 104 underwent prostate biopsy. Fourteen patients (.33%) were diagnosed with prostate cancer. The median baseline PSA was .74 (.01-58.5) ng/mL for patients without PC and 4.21 (.76-47.4) ng/mL for those with PC. The median time from the reading to diagnosis was 26.8 (1.5-143.8) months. The optimal cutoff for detecting PC was 1.9ng/mL (sensitivity, 92.86%; specificity, 92.54%; PPV, 3.9%; NPV, 99.97%), and the area under the curve was 92.8%. In terms of the repeated reading, the evolution of the PSA showed no statistically significant differences between the patients without cancer (p=.56) and those with cancer (P=.64). However, a PSAV value >.3ng/mL/year revealed high specificity for detecting cancer in this population. A baseline PSA level ≥1.9ng/mL in Spanish men aged 40-49 years predicted the development of PC. This value could therefore be of use for opportunistic screening at an early age. An appropriate follow-up adapted to the risk of this population needs to be defined, but an annual PSAV ≥.3ng/mL/year appears of use for reaching an early diagnosis. Copyright © 2015 AEU

  12. PSA and beyond: alternative prostate cancer biomarkers

    PubMed Central

    2016-01-01

    Background The use of biomarkers for prostate cancer screening, diagnosis and prognosis has the potential to improve the clinical management of the patients. Owing to inherent limitations of the biomarker prostate-specific antigen (PSA), intensive efforts are currently directed towards a search for alternative prostate cancer biomarkers, particularly those that can predict disease aggressiveness and drive better treatment decisions. Methods A literature search of Medline articles focused on recent and emerging advances in prostate cancer biomarkers was performed. The most promising biomarkers that have the potential to meet the unmet clinical needs in prostate cancer patient management and/or that are clinically implemented were selected. Conclusions With the advent of advanced genomic and proteomic technologies, we have in recent years seen an enormous spurt in prostate cancer biomarker research with several promising alternative biomarkers being discovered that show an improved sensitivity and specificity over PSA. The new generation of biomarkers can be tested via serum, urine, or tissue-based assays that have either received regulatory approval by the US Food and Drug Administration or are available as Clinical Laboratory Improvement Amendments-based laboratory developed tests. Additional emerging novel biomarkers for prostate cancer, including circulating tumor cells, microRNAs and exosomes, are still in their infancy. Together, these biomarkers provide actionable guidance for prostate cancer risk assessment, and are expected to lead to an era of personalized medicine. PMID:26790878

  13. Prostate-Specific Antigen (PSA) Test: MedlinePlus Lab Test Information

    MedlinePlus

    ... gov/labtests/prostatespecificantigenpsatest.html Prostate-Specific Antigen (PSA) Test To use the sharing features on this page, ... JavaScript. What is a prostate-specific antigen (PSA) test? A prostate-specific antigen (PSA) test measures the ...

  14. Some Issues of Electrical Systems Modeling in Course of PSA

    SciTech Connect

    Lankin, Michael

    2002-07-01

    Electrical power supply systems are one of the essential parts of nuclear power plants. The distinctive feature of these systems from the PSA analyst's point of view is significant amount of bi-directional dependencies present within electrical systems. This paper describes an approach that has been used for electrical systems modeling in course of Kola 4 NPP Level 1 PSA. (authors)

  15. Prostate Cancer Screening: Should You Get a PSA Test?

    MedlinePlus

    ... Mayo Clinic Staff Cancer screening tests — including the prostate-specific antigen (PSA) test to look for signs of prostate ... of harm to the person undergoing the testing. Prostate-specific antigen (PSA) is a protein produced by both cancerous ( ...

  16. PSA-NCAM expression in the teleost optic tectum is related to ecological niche and use of vision in finding food.

    PubMed

    Labak, I; Pavić, V; Zjalić, M; Blažetić, S; Viljetić, B; Merdić, E; Heffer, M

    2017-08-01

    In this study, tangential migration and neuronal connectivity organization were analysed in the optic tectum of seven different teleosts through the expression of polysialylated neural cell adhesion molecule (PSA-NCAM) in response to ecological niche and use of vision. Reduced PSA-NCAM expression in rainbow trout Oncorhynchus mykiss optic tectum occurred in efferent layers, while in pike Esox lucius and zebrafish Danio rerio it occurred in afferent and efferent layers. Zander Sander lucioperca and European eel Anguilla anguilla had very low PSA-NCAM expression in all tectal layers except in the stratum marginale. Common carp Cyprinus carpio and wels catfish Silurus glanis had the same intensity of PSA-NCAM expression in all tectal layers. The optic tectum of all studied fishes was also a site of tangential migration with sustained PSA-NCAM and c-series ganglioside expression. Anti-c-series ganglioside immunoreactivity was observed in all tectal layers of all analysed fishes, even in layers where PSA-NCAM expression was reduced. Since the optic tectum is indispensable for visually guided prey capture, stabilization of synaptic contact and decrease of neurogenesis and tangential migration in the visual map are an expected adjustment to ecological niche. The authors hypothesize that this stabilization would probably be achieved by down-regulation of PSA-NCAM rather than c-series of ganglioside. © 2017 The Fisheries Society of the British Isles.

  17. Beyond PSA: are new prostate cancer biomarkers of potential value to New Zealand doctors?

    PubMed

    Ng, Lance; Karunasinghe, Nishi; Benjamin, Challaraj S; Ferguson, Lynnette R

    2012-04-20

    The widespread introduction of prostate-specific antigen (PSA) screening has enhanced the early detection of prostate cancer within New Zealand. However, uncertainties associated with the test make it difficult to confidently differentiate low-risk patients from those that require a definitive diagnostic biopsy. In consequence, the decisions surrounding prostate cancer treatment become extremely difficult. A number of new tests have become available which might have the potential to complement the current PSA screens. We review a number of the best validated of these which provide data that, although currently not available in clinical practice, some of these might have considerable potential to aid diagnosis, prognosis and therapeutic decisions for men with prostate cancer in New Zealand.

  18. Improvements in diagnostic tools for early detection of psoriatic arthritis.

    PubMed

    D'Angelo, Salvatore; Palazzi, Carlo; Gilio, Michele; Leccese, Pietro; Padula, Angela; Olivieri, Ignazio

    2016-11-01

    Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease characterized by a wide clinical spectrum. The early diagnosis of PsA is currently a challenging topic. Areas covered: The literature was extensively reviewed for studies addressing the topic area "diagnosis of psoriatic arthritis". This review will summarize improvements in diagnostic tools, especially referral to the rheumatologist, the role of patient history and clinical examination, laboratory tests, and imaging techniques in getting an early and correct diagnosis of PsA. Expert commentary: Due to the heterogeneity of its expression, PsA may be easily either overdiagnosed or underdiagnosed. A diagnosis of PsA should be taken into account every time a patient with psoriasis or a family history of psoriasis shows peripheral arthritis, especially if oligoarticular or involving the distal interphalangeal joints, enthesitis or dactylitis. Magnetic resonance imaging and ultrasonography are useful for diagnosing PsA early, particularly when isolated enthesitis or inflammatory spinal pain occur.

  19. The influence of PSA-RNA yield on the analysis of expressed prostatic secretions (EPS) for prostate cancer diagnosis.

    PubMed

    Whelan, Christopher; Crocitto, Laura; Kawachi, Mark; Chan, Kevin; Smith, David; Wilson, Timothy; Smith, Steven

    2013-02-01

    In patients with prostate cancer, luminal prostate-specific antigen (PSA) enters the circulation because the basement membrane and glandular epithelium are damaged. Given that excess mobilization of prostate cells during prostatic massage can influence normalization in diagnostic testing, we studied PSA mRNA levels in expressed prostatic secretions (EPS) from patients undergoing biopsy for prostate cancer to determine if prostate cells are preferentially mobilized from patients with prostate cancer during prostatic massage. Quantitative Reverse-Transcription PCR (qRT-PCR) was used to measure the RNA levels of GAPDH, PSA, TMPRSS2:ERG and PCA3 in EPS specimens obtained from patients undergoing biopsy for prostate cancer. The level of PSA mRNA is significantly elevated in EPS specimens obtained from patients with a subsequent diagnosis of prostate cancer. This correlation influenced diagnostic testing results from EPS in two ways. First, when used as an exclusion parameter it appears to improve the diagnostic performance of TMPRSS2:ERG in EPS. Second, when used as a normalization parameter it appears to decrease the performance of these same tests. When comparing the results of mRNA based prostate cancer diagnostics in EPS it will be essential to consider PSA mRNA as a prostate specific gene and not a housekeeping gene.

  20. Age of the magnetically active WW Psa and TX Psa members of the β Pictoris association

    NASA Astrophysics Data System (ADS)

    Messina, S.; Santallo, R.; Tan, T. G.; Elliott, P.; Feiden, G. A.; Buccino, A.; Mauas, P.; Petrucci, R.; Jofré, E.

    2017-05-01

    Context. There are a variety of different techniques available to estimate the ages of pre-main-sequence stars. Components of physical pairs, thanks to their strict coevality and the mass difference, such as the binary system analyzed in this paper, are best suited to test the effectiveness of these different techniques. Aims: We consider the system WW Psa + TX Psa whose membership of the 25-Myr β Pictoris association has been well established by earlier works. We aim to investigate which age-dating technique provides the best agreement between the age of the system and that of the association. Methods: We have photometrically monitored WW Psa and TX Psa and measured their rotation periods as P = 2.37 d and P = 1.086 d, respectively. We have retrieved their Li equivalent widths from the literature and measured their effective temperatures and luminosities. We investigated whether the ages of these stars derived using three independent techniques, that is based on rotation, Li equivalent widths, and the position in the HR diagram are consistent with the age of the β Pictoris association. Results: We find that the rotation periods and the Li contents of both stars are consistent with the distribution of other bona fide members of the cluster. On the contrary, the isochronal fitting provides similar ages for both stars, but a factor of about four younger than the quoted age of the association, or about 30% younger when the effects of magnetic fields are included. Conclusions: We explore the origin of the discrepant age inferred from isochronal fitting, including the possibilities that either the two components may be unresolved binaries or that the basic stellar parameters of both components are altered by enhanced magnetic activity. The latter is found to be the more reasonable cause, suggesting that age estimates based on Li content are more reliable than isochronal fitting for pre-main-sequence stars with pronounced magnetic activity.

  1. Bubble nasal CPAP, early surfactant treatment, and rapid extubation are associated with decreased incidence of bronchopulmonary dysplasia in very-low-birth-weight newborns: efficacy and safety considerations.

    PubMed

    Friedman, Charles A; Menchaca, Robert C; Baker, Mary C; Rivas, Clarissa K; Laberge, Raymond N; Rios, Enrique H; Haider, Syed H; Romero, Edgar J; Eason, Elizabeth B; Fraley, J Kennard; Woldesenbet, Mesfin

    2013-07-01

    Current literature has been inconsistent in demonstrating that minimizing the duration of mechanical ventilation in very-low-birth-weight (VLBW) newborns reduces lung damage. To determine if introduction of bubble nasal CPAP (bnCPAP), early surfactant treatment, and rapid extubation (combined bnCPAP strategy) in our community-based neonatal ICU reduced bronchopulmonary dysplasia (BPD). This was a 7-year retrospective,single-institution review of respiratory outcomes in 633 VLBW babies before and after introduction of the combined bnCPAP strategy. Coincident changes in newborn care were taken into account with a logistic regression model. The average percentage of VLBW newborns with BPD decreased to 25.8% from 35.4% (P = .02), reaching a minimum in the last post-bnCPAP year of22.1% (P = .02). When other coincident changes in newborn care during the study years were taken into account, VLBW babies in the post-bnCPAP years had a 43% lower chance of developing BPD(P = .003, odds ratio 0.43, 95% CI 0.25– 0.75). Decreases occurred in mechanical ventilation and the percentage of infants discharged on diuretics and on supplemental oxygen. Among the subset of extremely-low-birth-weight newborns, improved respiratory outcomes in the post-bnCPAP years,as compared to outcomes in the pre-bnCPAP years, included an increase in the percentage alive and off mechanical ventilation at 1 week postnatal age (P < .001), a more rapid extubation rate(P < .03), a decrease in the median days on mechanical ventilation (P = .002), and a decrease in the percentage with BPD plus died (P = .01). Post-bnCPAP extremely-low-birth-weight babies had a statistically significant decrease in retinopathy of prematurity, an increase in low-grade intraventricular hemorrhage, and a decrease in ductal ligations. A combined BnCPAP strategy may contribute to a reduction of BPD, after adjusting for concurrent treatments.

  2. Decrease in tick bite consultations and stabilization of early Lyme borreliosis in the Netherlands in 2014 after 15 years of continuous increase.

    PubMed

    Hofhuis, Agnetha; Bennema, Sita; Harms, Margriet; van Vliet, Arnold J H; Takken, Willem; van den Wijngaard, Cees C; van Pelt, Wilfrid

    2016-05-23

    Nationwide surveys have shown a threefold increase in general practitioner (GP) consultations for tick bites and early Lyme borreliosis from 1994 to 2009 in the Netherlands. We now report an update on 2014, with identical methods as for the preceding GP surveys. To all GPs in the Netherlands, a postal questionnaire was sent inquiring about the number of consultations for tick bites and erythema migrans diagnoses (most common manifestation of early Lyme borreliosis) in 2014, and the size of their practice populations. Contrasting to the previously rising incidence of consultations for tick bites between 1994 and 2009, the incidence decreased in 2014 to 488 consultations for tick bites per 100,000 inhabitants, i.e., 82,000 patients nationwide. This survey revealed a first sign of stabilization of the previously rising trend in GP diagnosed erythema migrans, with 140 diagnoses per 100,000 inhabitants of the Netherlands. This equals about 23,500 annual diagnoses of erythema migrans nationwide in 2014. In contrast to the constantly rising incidence of GP consultations for tick bites and erythema migrans diagnoses in the Netherlands between 1994 and 2009, the current survey of 2014 showed a first sign of stabilization of erythema migrans diagnoses and a decreased incidence for tick bite consultations.

  3. Heparan sulfates and the decrease of N-glycans promote early adipogenic differentiation rather than myogenesis of murine myogenic progenitor cells.

    PubMed

    Grassot, Vincent; Bouchatal, Amel; Da Silva, Anne; Chantepie, Sandrine; Papy-Garcia, Dulce; Maftah, Abderrahman; Gallet, Paul-François; Petit, Jean-Michel

    In vitro, extracted muscle satellite cells, called myogenic progenitor cells, can differentiate either in myotubes or preadipocytes, depending on environmental factors and the medium. Transcriptomic analyses on glycosylation genes during satellite cells differentiation into myotubes showed that 31 genes present a significant variation of expression at the early stages of murine myogenic progenitor cells (MPC) differentiation. In the present study, we analyzed the expression of 383 glycosylation related genes during murine MPC differentiation into preadipocytes and compared the data to those previously obtained during their differentiation into myotubes. Fifty-six glycosylation related genes are specifically modified in their expression during early adipogenesis. The variations correspond mainly to: a decrease of N-glycans, and of alpha (2,3) and (2,6) linked sialic acids, and to a high level of heparan sulfates. A high amount of TGF-β1 in extracellular media during early adipogenesis was also observed. It seems that the increases of heparan sulfates and TGF-β1 favor pre-adipogenic differentition of MPC and possibly prevent their myogenic differentiation. Copyright © 2016 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  4. PSA-NCAM-Negative Neural Crest Cells Emerging during Neural Induction of Pluripotent Stem Cells Cause Mesodermal Tumors and Unwanted Grafts

    PubMed Central

    Lee, Dongjin R.; Yoo, Jeong-Eun; Lee, Jae Souk; Park, Sanghyun; Lee, Junwon; Park, Chul-Yong; Ji, Eunhyun; Kim, Han-Soo; Hwang, Dong-Youn; Kim, Dae-Sung; Kim, Dong-Wook

    2015-01-01

    Summary Tumorigenic potential of human pluripotent stem cells (hPSCs) is an important issue in clinical applications. Despite many efforts, PSC-derived neural precursor cells (NPCs) have repeatedly induced tumors in animal models even though pluripotent cells were not detected. We found that polysialic acid-neural cell adhesion molecule (PSA-NCAM)− cells among the early NPCs caused tumors, whereas PSA-NCAM+ cells were nontumorigenic. Molecular profiling, global gene analysis, and multilineage differentiation of PSA-NCAM− cells confirm that they are multipotent neural crest stem cells (NCSCs) that could differentiate into both ectodermal and mesodermal lineages. Transplantation of PSA-NCAM− cells in a gradient manner mixed with PSA-NCAM+ cells proportionally increased mesodermal tumor formation and unwanted grafts such as PERIPHERIN+ cells or pigmented cells in the rat brain. Therefore, we suggest that NCSCs are a critical target for tumor prevention in hPSC-derived NPCs, and removal of PSA-NCAM− cells eliminates the tumorigenic potential originating from NCSCs after transplantation. PMID:25937368

  5. Minimally Informative Prior Distributions for PSA

    SciTech Connect

    Dana L. Kelly; Robert W. Youngblood; Kurt G. Vedros

    2010-06-01

    A salient feature of Bayesian inference is its ability to incorporate information from a variety of sources into the inference model, via the prior distribution (hereafter simply “the prior”). However, over-reliance on old information can lead to priors that dominate new data. Some analysts seek to avoid this by trying to work with a minimally informative prior distribution. Another reason for choosing a minimally informative prior is to avoid the often-voiced criticism of subjectivity in the choice of prior. Minimally informative priors fall into two broad classes: 1) so-called noninformative priors, which attempt to be completely objective, in that themore » posterior distribution is determined as completely as possible by the observed data, the most well known example in this class being the Jeffreys prior, and 2) priors that are diffuse over the region where the likelihood function is nonnegligible, but that incorporate some information about the parameters being estimated, such as a mean value. In this paper, we compare four approaches in the second class, with respect to their practical implications for Bayesian inference in Probabilistic Safety Assessment (PSA). The most commonly used such prior, the so-called constrained noninformative prior, is a special case of the maximum entropy prior. This is formulated as a conjugate distribution for the most commonly encountered aleatory models in PSA, and is correspondingly mathematically convenient; however, it has a relatively light tail and this can cause the posterior mean to be overly influenced by the prior in updates with sparse data. A more informative prior that is capable, in principle, of dealing more effectively with sparse data is a mixture of conjugate priors. A particular diffuse nonconjugate prior, the logistic-normal, is shown to behave similarly for some purposes. Finally, we review the so-called robust prior. Rather than relying on the mathematical abstraction of entropy, as does the

  6. Early decreased TLR2 expression on monocytes is associated with their reduced phagocytic activity and impaired maturation in a porcine polytrauma model

    PubMed Central

    Schimunek, Lukas; Serve, Rafael; Teuben, Michel P. J.; Störmann, Philipp; Auner, Birgit; Woschek, Mathias; Pfeifer, Roman; Horst, Klemens; Simon, Tim-P.; Kalbitz, Miriam; Sturm, Ramona; Pape, Hans-C.; Hildebrand, Frank; Marzi, Ingo

    2017-01-01

    immediately and remained lower during the first 3.5 h after trauma, but increased after 24 h. Antagonizing TLR2 significantly decreased the phagocytizing activity of monocytes. Both, decreased percentage of activated as well as TLR2 expressing monocytes persisted as long as the reduced phagocytosis was observed. Moreover, neutralizing TLR2 led to a reduced capability of phagocytosis as well. Therefore, we assume that reduced TLR2 expression may be responsible for the decreased phagocytizing capacity of circulating monocytes in the early post-traumatic phase. PMID:29125848

  7. PSA Velocity Does Not Improve Prostate Cancer Detection

    Cancer.gov

    A rapid increase in prostate-specific antigen (PSA) levels is not grounds for automatically recommending a prostate biopsy, according to a study published online February 24, 2011, in the Journal of the National Cancer Institute.

  8. Early-life experience decreases drug-induced reinstatement of morphine CPP in adulthood via microglial-specific epigenetic programming of anti-inflammatory IL-10 expression.

    PubMed

    Schwarz, Jaclyn M; Hutchinson, Mark R; Bilbo, Staci D

    2011-12-07

    A critical component of drug addiction research involves identifying novel biological mechanisms and environmental predictors of risk or resilience to drug addiction and associated relapse. Increasing evidence suggests microglia and astrocytes can profoundly affect the physiological and addictive properties of drugs of abuse, including morphine. We report that glia within the rat nucleus accumbens (NAcc) respond to morphine with an increase in cytokine/chemokine expression, which predicts future reinstatement of morphine conditioned place preference (CPP) following a priming dose of morphine. This glial response to morphine is influenced by early-life experience. A neonatal handling paradigm that increases the quantity and quality of maternal care significantly increases baseline expression of the anti-inflammatory cytokine IL-10 within the NAcc, attenuates morphine-induced glial activation, and prevents the subsequent reinstatement of morphine CPP in adulthood. IL-10 expression within the NAcc and reinstatement of CPP are negatively correlated, suggesting a protective role for this specific cytokine against morphine-induced glial reactivity and drug-induced reinstatement of morphine CPP. Neonatal handling programs the expression of IL-10 within the NAcc early in development, and this is maintained into adulthood via decreased methylation of the IL-10 gene specifically within microglia. The effect of neonatal handling is mimicked by pharmacological modulation of glia in adulthood with ibudilast, which increases IL-10 expression, inhibits morphine-induced glial activation within the NAcc, and prevents reinstatement of morphine CPP. Taken together, we have identified a novel gene × early-life environment interaction on morphine-induced glial activation and a specific role for glial activation in drug-induced reinstatement of drug-seeking behavior.

  9. Early-Life Experience Decreases Drug-Induced Reinstatement of Morphine CPP in Adulthood via Microglial-Specific Epigenetic Programming of Anti-Inflammatory IL-10 Expression

    PubMed Central

    Schwarz, Jaclyn M.; Hutchinson, Mark R.; Bilbo, Staci D.

    2012-01-01

    A critical component of drug addiction research involves identifying novel biological mechanisms and environmental predictors of risk or resilience to drug addiction and associated relapse. Increasing evidence suggests microglia and astrocytes can profoundly affect the physiological and addictive properties of drugs of abuse, including morphine. We report that glia within the rat Nucleus Accumbens (NAcc) respond to morphine with an increase in cytokine/chemokine expression, which predicts future reinstatement of morphine conditioned place preference (CPP) following a priming dose of morphine. This glial response to morphine is influenced by early-life experience. A neonatal handling paradigm that increases the quantity and quality of maternal care significantly increases baseline expression of the anti-inflammatory cytokine IL-10 within the NAcc, attenuates morphine-induced glial activation, and prevents the subsequent reinstatement of morphine CPP in adulthood. IL-10 expression within the NAcc and reinstatement of CPP are negatively correlated, suggesting a protective role for this specific cytokine against morphine-induced glial reactivity and drug-induced reinstatement of morphine CPP. Neonatal handling programs the expression of IL-10 within the NAcc early in development, and this is maintained into adulthood via decreased methylation of the IL-10 gene specifically within microglia. The effect of neonatal handling is mimicked by pharmacological modulation of glia in adulthood with Ibudilast, which increases IL-10 expression, inhibits morphine-induced glial activation within the NAcc, and prevents reinstatement of morphine CPP. Taken together, we have identified a novel gene X early-life environment interaction on morphine-induced glial activation, and a specific role for glial activation in drug-induced reinstatement of drug-seeking behavior. PMID:22159099

  10. [Use of prostatic specific antigen in primary care (PSA)].

    PubMed

    Panach-Navarrete, J; Gironés-Montagud, A; Sánchez-Cano, E; Doménech-Pérez, C; Martínez-Jabaloyas, J M

    2017-04-01

    In the literature it is shown that the use of PSA is occasionally wrong, by requesting this marker in very young or very old men, and repeated measurements in short periods of time. The main objective of this study was to describe the use of PSA in daily practice by primary care physicians in our area, dealing with aspects such as the importance of patient age, the value in the screening for prostate cancer, or the subjective beliefs about its usefulness. A secondary objective was the comparison of use, and beliefs among doctors who claim to know PSA well, and those who do not. A descriptive and comparative study was conducted using questionnaires that were handed to primary care doctors in all health centres in our area. A descriptive analysis was performed and response rates among doctors who thought they had enough information about PSA, and those who did not, were compared using the Chi-squared test. A total of 103 questionnaires were received from the physicians, with 83.5% claiming to have sufficient knowledge about the PSA. The professionals in this latter group request PSA at an earlier age (P=.029), with a higher frequency (P=.011) and have more doubts about its usefulness (P=.009) than those with less knowledge. Almost half (49.5%) said they request less than 50 determinations per year, and 33% between 50 and 100. More than half (53.4%) of doctors would not request the first PSA on a patient until their 50s, and up to 49% request it up to 80 years. The true value of PSA has been established many times by 64.1% of requesters, and 29.1% believe it is unhelpful in the diagnosis of cancer. In our study, 64% of primary care physicians have considered the true value of the PSA several times, and 29% believe it to be of little use in the diagnosis of prostate cancer. In addition, some data suggest it has limited use due to the fact that 50% made less than 50 PSA requests per years, and 28% of the professionals would never request it on a male without urinary

  11. Randomized, Noncomparative, Phase II Trial of Early Switch From Docetaxel to Cabazitaxel or Vice Versa, With Integrated Biomarker Analysis, in Men With Chemotherapy-Naïve, Metastatic, Castration-Resistant Prostate Cancer

    PubMed Central

    Tagawa, Scott T.; Galletti, Giuseppe; Worroll, Daniel; Ballman, Karla; Vanhuyse, Marie; Sonpavde, Guru; North, Scott; Albany, Costantine; Tsao, Che-Kai; Stewart, John; Zaher, Atef; Szatrowski, Ted; Zhou, Wei; Gjyrezi, Ada; Tasaki, Shinsuke; Portella, Luigi; Bai, Yang; Lannin, Timothy B.; Suri, Shalu; Gruber, Conor N.; Pratt, Erica D.; Kirby, Brian J.; Eisenberger, Mario A.; Nanus, David M.; Saad, Fred; Giannakakou, Paraskevi

    2017-01-01

    Purpose The TAXYNERGY trial (ClinicalTrials.gov identifier: NCT01718353) evaluated clinical benefit from early taxane switch and circulating tumor cell (CTC) biomarkers to interrogate mechanisms of sensitivity or resistance to taxanes in men with chemotherapy-naïve, metastatic, castration-resistant prostate cancer. Patients and Methods Patients were randomly assigned 2:1 to docetaxel or cabazitaxel. Men who did not achieve ≥ 30% prostate-specific antigen (PSA) decline by cycle 4 (C4) switched taxane. The primary clinical endpoint was confirmed ≥ 50% PSA decline versus historical control (TAX327). The primary biomarker endpoint was analysis of post-treatment CTCs to confirm the hypothesis that clinical response was associated with taxane drug-target engagement, evidenced by decreased percent androgen receptor nuclear localization (%ARNL) and increased microtubule bundling. Results Sixty-three patients were randomly assigned to docetaxel (n = 41) or cabazitaxel (n = 22); 44.4% received prior potent androgen receptor–targeted therapy. Overall, 35 patients (55.6%) had confirmed ≥ 50% PSA responses, exceeding the historical control rate of 45.4% (TAX327). Of 61 treated patients, 33 (54.1%) had ≥ 30% PSA declines by C4 and did not switch taxane, 15 patients (24.6%) who did not achieve ≥ 30% PSA declines by C4 switched taxane, and 13 patients (21.3%) discontinued therapy before or at C4. Of patients switching taxane, 46.7% subsequently achieved ≥ 50% PSA decrease. In 26 CTC-evaluable patients, taxane-induced decrease in %ARNL (cycle 1 day 1 v cycle 1 day 8) was associated with a higher rate of ≥ 50% PSA decrease at C4 (P = .009). Median composite progression-free survival was 9.1 months (95% CI, 4.9 to 11.7 months); median overall survival was not reached at 14 months. Common grade 3 or 4 adverse events included fatigue (13.1%) and febrile neutropenia (11.5%). Conclusion The early taxane switch strategy was associated with improved PSA response rates

  12. End-of-radiation PSA as a novel prognostic factor in patients undergoing definitive radiation and androgen deprivation therapy for prostate cancer.

    PubMed

    Narang, A K; Trieu, J; Radwan, N; Ram, A; Robertson, S P; He, P; Gergis, C; Griffith, E; Singh, H; DeWeese, T A; Honig, S; Annadanam, A; Greco, S; DeVille, C; McNutt, T; DeWeese, T L; Song, D Y; Tran, P T

    2017-06-01

    In men undergoing definitive radiation for prostate cancer, it is unclear whether early biochemical response can provide additional prognostic value beyond pre-treatment risk stratification. Prostate cancer patients consecutively treated with definitive radiation at our institution by a single provider from 1993 to 2006 and who had an end-of-radiation (EOR) PSA (n=688, median follow-up 11.2 years). We analyzed the association of an EOR PSA level, obtained during the last week of radiation, with survival outcomes. Multivariable-adjusted cox proportional hazards models were constructed to assess associations between a detectable EOR PSA (defined as ⩾0.1 ng ml -1 ) and biochemical failure-free survival (BFFS), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS) and overall survival (OS). Kaplan-Meier survival curves were constructed, with stratification by EOR PSA. At the end of radiation, the PSA level was undetectable in 30% of patients. Men with a detectable EOR PSA experienced inferior 10-year BFFS (49.7% versus 64.4%, P<0.001), 10-year MFS (84.8% versus 92.0%, P=0.003), 10-year PCSS (94.3% versus 98.2%, P=0.007) and 10-year OS (75.8% versus 82.5%, P=0.01), as compared to men with an undetectable EOR PSA. Among National Comprehensive Care Network (NCCN) intermediate- and high-risk men who were treated with definitive radiation and androgen deprivation therapy (ADT), a detectable EOR PSA was more strongly associated with PCSS than initial NCCN risk level (EOR PSA: HR 5.89, 95% CI 2.37-14.65, P<0.001; NCCN risk level: HR 2.01, 95% CI 0.74-5.42, P=0.168). Main study limitations are retrospective study design and associated biases. EOR PSA was significantly associated with survival endpoints in men who received treatment with definitive radiation and ADT. Whether the EOR PSA can be used to modulate treatment intensity merits further investigation.

  13. End-of-radiation PSA as a novel prognostic factor in patients undergoing definitive radiation and androgen deprivation therapy for prostate cancer

    PubMed Central

    Narang, Amol K.; Trieu, Janson; Radwan, Noura; Ram, Ashwin; Robertson, Scott P.; He, Pei; Gergis, Carol; Griffith, Emily; Singh, Harleen; DeWeese, Tate A.; Honig, Stephanie; Annadanam, Anvesh; Greco, Stephen; DeVille, Curtiland; McNutt, Todd; DeWeese, Theodore L.; Song, Daniel Y.; Tran, Phuoc T.

    2016-01-01

    Background In men undergoing definitive radiation for prostate cancer, it is unclear whether early biochemical response can provide additional prognostic value beyond pre-treatment risk stratification. Methods Prostate cancer patients consecutively treated with definitive radiation at our institution by a single provider from 1993–2006 and who had an EOR PSA (n=688, median follow-up 11.2 years). We analyzed the association of an end-of-radiation (EOR) prostate-specific antigen (PSA) level, obtained during the last week of radiation, with survival outcomes. Multivariable-adjusted cox proportional hazards models were constructed to assess associations between a detectable EOR PSA (defined as ≥0.1 ng ml−1) and biochemical failure-free survival (BFFS), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS). Kaplan-Meier survival curves were constructed, with stratification by EOR PSA. Results At the end of radiation, the PSA level was undetectable in 30% of patients. Men with a detectable EOR PSA experienced inferior 10-year BFFS (49.7% vs. 64.4%, p<0.001), 10-year MFS (84.8% vs. 92.0%, p=0.003), 10-year PCSS (94.3% vs. 98.2%, p=0.007), and 10-year OS (75.8% vs. 82.5%, p=0.01), as compared to men with an undetectable EOR PSA. Among NCCN intermediate- and high-risk men who were treated with definitive radiation and androgen deprivation therapy (ADT), a detectable EOR PSA was more strongly associated with PCSS than initial NCCN risk level (EOR PSA: HR 5.89, 95% CI 2.37–14.65, p<0.001; NCCN risk level: HR 2.01, 95% CI 0.74–5.42, p=0.168). Main study limitations are retrospective study design and associated biases. Conclusions EOR PSA was significantly associated with survival endpoints in men who received treated with definitive radiation and ADT. Whether the EOR PSA can be used to modulate treatment intensity merits further investigation. PMID:28094250

  14. Murine Polyomavirus Virus-Like Particles Carrying Full-Length Human PSA Protect BALB/c Mice from Outgrowth of a PSA Expressing Tumor

    PubMed Central

    Eriksson, Mathilda; Andreasson, Kalle; Weidmann, Joachim; Lundberg, Kajsa; Tegerstedt, Karin

    2011-01-01

    Virus-like particles (VLPs) consist of capsid proteins from viruses and have been shown to be usable as carriers of protein and peptide antigens for immune therapy. In this study, we have produced and assayed murine polyomavirus (MPyV) VLPs carrying the entire human Prostate Specific Antigen (PSA) (PSA-MPyVLPs) for their potential use for immune therapy in a mouse model system. BALB/c mice immunized with PSA-MPyVLPs were only marginally protected against outgrowth of a PSA-expressing tumor. To improve protection, PSA-MPyVLPs were co-injected with adjuvant CpG, either alone or loaded onto murine dendritic cells (DCs). Immunization with PSA-MPyVLPs loaded onto DCs in the presence of CpG was shown to efficiently protect mice from tumor outgrowth. In addition, cellular and humoral immune responses after immunization were examined. PSA-specific CD4+ and CD8+ cells were demonstrated, but no PSA-specific IgG antibodies. Vaccination with DCs loaded with PSA-MPyVLPs induced an eight-fold lower titre of anti-VLP antibodies than vaccination with PSA-MPyVLPs alone. In conclusion, immunization of BALB/c mice with PSA-MPyVLPs, loaded onto DCs and co-injected with CpG, induces an efficient PSA-specific tumor protective immune response, including both CD4+ and CD8+ cells with a low induction of anti-VLP antibodies. PMID:21858228

  15. Effects of decreasing metabolizable protein and rumen-undegradable protein on milk production and composition and blood metabolites of Holstein dairy cows in early lactation.

    PubMed

    Bahrami-Yekdangi, H; Khorvash, M; Ghorbani, G R; Alikhani, M; Jahanian, R; Kamalian, E

    2014-01-01

    This study was conducted to evaluate the effects of decreasing dietary protein and rumen-undegradable protein (RUP) on production performance, nitrogen retention, and nutrient digestibility in high-producing Holstein cows in early lactation. Twelve multiparous Holstein lactating cows (2 lactations; 50 ± 7 d in milk; 47 kg/d of milk production) were used in a Latin square design with 4 treatments and 3 replicates (cows). Treatments 1 to 4 consisted of diets containing 18, 17.2, 16.4, and 15.6% crude protein (CP), respectively, with the 18% CP diet considered the control group. Rumen-degradable protein levels were constant across the treatments (approximately 10.9% on a dry matter basis), whereas RUP was gradually decreased. All diets were calculated to supply a postruminal Lys:Met ratio of about 3:1. Dietary CP had no significant effects on milk production or milk composition. In fact, 16.4% dietary CP compared with 18% dietary CP led to higher milk production; however, this effect was not significant. Feed intake was higher for 16.4% CP than for 18% CP (25.7 vs. 24.3 kg/d). Control cows had greater CP and RUP intakes, which resulted in higher concentrations of plasma urea nitrogen and milk urea nitrogen; cows receiving 16.4 and 15.6% CP, respectively, exhibited lower concentrations of milk urea nitrogen (15.2 and 15.1 vs. 17.3 mg/dL). The control diet had a significant effect on predicted urinary N. Higher CP digestibility was recorded for 18% CP compared with the other diets. Decreasing CP and RUP to 15.6 and 4.6% of dietary dry matter, respectively, had no negative effects on milk production or composition when the amounts of Lys and Met and the Lys:Met ratio were balanced. Furthermore, decreasing CP and RUP to 16.4 and 5.4%, respectively, increased dry matter intake. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  16. Metastatic prostate cancer in the modern era of PSA screening

    PubMed Central

    Fontenot, Philip A.; Nehra, Avinash; Parker, William; Wyre, Hadley; Mirza, Moben; Duchene, David A.; Holzbeierlein, Jeffrey; Thrasher, James Brantley; Veldhuizen, Peter Van; Lee, Eugene K.

    2017-01-01

    ABSTRACT Introduction To characterize initial presentation and PSA screening status in a contemporary cohort of men treated for metastatic prostate cancer at our institution. Materials and methods We reviewed records of 160 men treated for metastatic prostate cancer between 2008-2014 and assessed initial presentation, categorizing patients into four groups. Groups 1 and 2 presented with localized disease and received treatment. These men suffered biochemical recurrence late (>1 year) or earlier (<1 year), respectively, and developed metastases. Groups 3 and 4 had asymptomatic and symptomatic metastases at the outset of their diagnosis. Patients with a first PSA at age 55 or younger were considered to have guideline-directed screening. Results Complete records were available on 157 men for initial presentation and 155 men for PSA screening. Groups 1, 2, 3 and 4 included 27 (17%), 7 (5%), 69 (44%) and 54 (34%) patients, respectively. Twenty (13%) patients received guideline-directed PSA screening, 5/155 (3%) patients presented with metastases prior to age 55 with their first PSA, and 130/155 (84%) had their first PSA after age 55, of which 122/130 (94%) had metastasis at the time of diagnosis. Conclusion Despite widespread screening, most men treated for metastatic prostate cancer at our institution presented with metastases rather than progressed after definitive treatment. Furthermore, 25 (16%) patients received guideline-directed PSA screening at or before age 55. These data highlight that, despite mass screening efforts, patients treated for incurable disease at our institution may not have been a result of a failed screening test, but a failure to be screened. PMID:28338310

  17. Cyber-Physical Security Assessment (CyPSA) Toolset

    SciTech Connect

    Garcia, Luis; Patapanchala, Panini; Zonouz, Saman

    CyPSA seeks to organize and gain insight into the diverse sets of data that a critical infrastructure provider must manage. Specifically CyPSA inventories, manages, and analyzes assets and relations among those assets. A variety of interfaces are provided. CyPSA inventories assets (both cyber and physical). This may include the cataloging of assets through a common interface. Data sources used to generate a catalogue of assets include PowerWorld, NPView, NMap Scans, and device configurations. Depending upon the role of the person using the tool the types of assets accessed as well as the data sources through which asset information is accessedmore » may vary. CyPSA allows practitioners to catalogue relations among assets and these may either be manually or programmatically generated. For example, some common relations among assets include the following: Topological Network Data: Which devices and assets are connected and how? Data sources for this kind of information include NMap scans, NPView topologies (via Firewall rule analysis). Security Metrics Outputs: The output of various security metrics such as overall exposure. Configure Assets:CyPSA may eventually include the ability to configure assets including relays and switches. For example, a system administrator would be able to configure and alter the state of a relay via the CyPSA interface. Annotate Assets: CyPSA also allows practitioners to manually and programmatically annotate assets. Sources of information with which to annotate assets include provenance metadata regarding the data source from which the asset was loaded, vulnerability information from vulnerability databases, configuration information, and the output of an analysis in general.« less

  18. Early HIV Diagnosis Leads to Significantly Decreased Costs in the First 2 Years of HIV Care in an Urban Charity Hospital in New Orleans.

    PubMed

    Halperin, Jason; Katz, Morgan; Pathmanathan, Ishani; Myers, Leann; Van Sickels, Nicholas; Seal, Paula Sereebutra; Richey, Lauren E

    We undertook a retrospective cohort study of patients with a positive HIV test in the emergency department who were then linked to care. Inpatient, outpatient, and emergency costs were collected for the first 2 years after HIV diagnosis. Fifty-six patients met the inclusion criteria; they were predominantly uninsured (73%) and African American (89%). The median total cost for a newly diagnosed patient over the first 2 years was US$36 808, driven predominantly by outpatient costs of US$17 512. Median inpatient and total costs were significantly different between the lowest (<200 cells/mm 3 ) and highest (>499 cells/mm 3 ) CD4 count categories (US$21 878 vs US$6607, P <.05; US$61 378 vs US$18 837, P <.05, respectively). Total costs were significantly different between viral load categories <100 000 HIV-RNA copies/mL and ≥100 000 HIV-RNA copies/mL (US$28 219 vs US$49 482, P <.05). Costs were significantly lower among patients diagnosed earlier in their disease. Decreased cost is another factor supporting early diagnosis and linkage to care for patients with HIV.

  19. Decreased SAP Expression in T Cells from Patients with Systemic Lupus Erythematosus Contributes to Early Signaling Abnormalities and Reduced IL-2 Production.

    PubMed

    Karampetsou, Maria P; Comte, Denis; Kis-Toth, Katalin; Terhorst, Cox; Kyttaris, Vasileios C; Tsokos, George C

    2016-06-15

    T cells from patients with systemic lupus erythematosus (SLE) display a number of abnormalities, including increased early signaling events following engagement of the TCR. Signaling lymphocytic activation molecule family cell surface receptors and the X-chromosome-defined signaling lymphocytic activation molecule-associated protein (SAP) adaptor are important in the development of several immunocyte lineages and modulating the immune response. We present evidence that SAP protein levels are decreased in T cells and in their main subsets isolated from 32 women and three men with SLE, independent of disease activity. In SLE T cells, SAP protein is also subject to increased degradation by caspase-3. Forced expression of SAP in SLE T cells normalized IL-2 production, calcium (Ca(2+)) responses, and tyrosine phosphorylation of a number of proteins. Exposure of normal T cells to SLE serum IgG, known to contain anti-CD3/TCR Abs, resulted in SAP downregulation. We conclude that SLE T cells display reduced levels of the adaptor protein SAP, probably as a result of continuous T cell activation and degradation by caspase-3. Restoration of SAP levels in SLE T cells corrects the overexcitable lupus T cell phenotype. Copyright © 2016 by The American Association of Immunologists, Inc.

  20. A Diet, Physical Activity, and Stress Reduction Intervention in Men with Rising Prostate-Specific Antigen (PSA) after Treatment for Prostate Cancer

    PubMed Central

    Hébert, James R.; Hurley, Thomas G.; Harmon, Brook E.; Heiney, Sue; Hebert, Christine J.; Steck, Susan E.

    2011-01-01

    Background Nearly 35% of men treated for prostate cancer (PrCA) will experience biochemically defined recurrence, noted by a rise in PSA, within ten years of definitive therapy. Diet, physical activity, and stress reduction may affect tumor promotion and disease progression. Methods A randomized trial of an intensive diet, physical activity, and meditation intervention was conducted in men with rising post-treatment PSA after definitive treatment for PrCA. Intention-to-treat methods were used to compare usual care to the intervention in 47 men with complete data. Signal detection methods were used to identify dietary factors associated with PSA change. Results The intervention and control groups did not differ statistically on any demographic or disease-related factor. Although the intervention group experienced decreases of 39% in intakes of saturated fatty acid (SFA as percent of total calories) (p<0.0001) and 12% in total energy intake (218 kcal/day p<0.05)], no difference in PSA change was observed by intervention status. Signal detection methods indicated that in men increasing their consumption of fruit, 56% experienced no rise in PSA (vs. 29% in men who did not increase their fruit intake). Among men who increased fruit and fiber intakes, PSA increased in 83% of participants who also increased saturated fatty acid intake (vs. 44% in participants who decreased or maintained saturated fatty acid intake). Conclusion Results are discussed in the context of conventional treatment strategies that were more aggressive when this study was being conducted in the mid-2000s. Positive health changes in a number of lifestyle parameters were observed with the intervention, and both increased fruit and reduced saturated fat intakes were associated with maintaining PSA levels in men with biochemically recurrent disease. PMID:22018935

  1. Obesity Increases the Risk of Primary Nonfunction and Early Access Loss, and Decreases Overall Patency in Patients Who Underwent Hemodialysis Reliable Outflow Device Placement.

    PubMed

    Naffouje, Samer A; Tzvetanov, Ivo; Bui, James T; Gaba, Ron; Bernardo, Karrel; Jeon, Hoonbae

    2016-10-01

    Hemodialysis reliable outflow (HeRO) catheters were introduced in 2008, and have been since providing a reliable alternative for hemodialysis patients who are deemed "access challenged." However, its outcomes have not been extensively investigated due to its relatively young age. Here, we report our 6-year single institution experience, and demonstrate the significant impact of obesity on HeRO graft outcomes, an aspect not previously studied in the literature. Patients who underwent HeRO graft placement at the University of Illinois Hospital between April 2009 and August 2015 were included retrospectively. Data were collected from patients' electronic medical records and analyzed using SPSS software. Thirty-three patients who underwent 34 HeRO catheter placements were included. Mean age was 47 ± 12 years, and mean body mass index (BMI) was 30.75 ± 10.22. Median follow-up was 635 days. Overall catheter-related complications were thrombosis (70.59%), infection (20.59%), arterial steal (8.82%), and pseudoaneurysms requiring intervention (8.82%). Overall primary and secondary patency rates after 6 and 12 months were 31.25%, 25%, 78.13%, and 71.86%, respectively. Primary nonfunction rate was 14.7%. Obese patients had significantly higher rate of primary nonfunction (38.46% vs. 0%, P = 0.0046), and relative risk 3.62 (95% confidence interval [CI] 2.01-6.52). They also had a significantly decreased rate of graft patency after 12 months (10.53% vs. 53.85%, P = 0.0227), leading to a relative risk of "early" graft loss within 1 year of 5.12 (95% CI 1.26-20.83). Overall median graft patency in obese patients was significantly shorter than that of nonobese patients (311 vs. 1295 days, P = 0.014). BMI, as a continuous variable, was a significant predictor of primary nonfunction (P = 0.046) and early graft loss (0.020) when tested against age, sex, race, and diabetes in a multivariate logistic regression analysis. HeRO catheters offer a reliable, and possibly

  2. Diversity of viral photosystem-I psaA genes

    PubMed Central

    Hevroni, Gur; Enav, Hagay; Rohwer, Forest; Béjà, Oded

    2015-01-01

    Marine photosynthesis is one of the major contributors to the global carbon cycle and the world's oxygen supply. This process is largely driven by cyanobacteria, namely Synechococcus and Prochlorococcus. Genes encoding photosystem-II (PSII) reaction center proteins are found in many cyanophage genomes, and are expressed during the infection of their hosts. On the basis of metagenomics, cyanophage photosystem-I (PSI) gene cassettes were recently discovered with two gene arrangements psaJF→C→A→B→K→E→D and psaD→C→A→B. It was suggested that the horizontal transfer of PSII and PSI genes is increasing phage fitness. To better understand their diversity, we designed degenerate primers to cover a wide diversity of organisms, and using PCR we targeted the psaC→A arrangement, which is unique to cyanophages cassettes. We examined viral concentrates from four islands in the Pacific Ocean and found samples containing the psaC→A arrangement. Analyses of the amplified viral psaA gene revealed six subgroups varying in their level of similarity and %G+C content, suggesting that the diversity of cyanophage PSI genes is greater than originally thought. PMID:25535938

  3. The Efficacy of Buccal Infiltration of 4% Articaine and PSA Injection of 2% Lidocaine on Anesthesia of Maxillary Second Molars.

    PubMed

    Maljaei, Ensiyeh; Pourkazemi, Maryam; Ghanizadeh, Milad; Ranjbar, Rana

    2017-01-01

    During the early mixed dentition period, the location of the deciduous maxillary second molar results in ineffectiveness of the infiltration technique in this area. In such cases, administration of posterior superior alveolar (PSA) nerve block is recommended; however, such a technique has some complications. The present study was undertaken to compare the effects of buccal infiltration of 4% Articaine and PSA technique with 2% Lidocaine on the success of anesthesia of maxillary deciduous second molars in 6 to 9-year old children. In the present double-blind randomized clinical trial, 56 children aged 6-9 years requiring vital pulp therapy of deciduous maxillary second molar were included. In group 1, 4% Articaine was injected using a buccal infiltration technique. In group 2, 2% Lidocaine was injected using the PSA nerve block technique. After 10 min, the caries was removed and access cavity preparation was instituted. The patients were asked to report the presence or absence of pain during the procedure. Therefore, the existence of pain was measured by the patient's self-report. Data were analyzed with descriptive statistical methods and the chi -squared test. Pain was reported by 6 (21.4%) and 9 (32.1%) subjects in the Articaine and Lidocaine groups, respectively. Chi -squared test did not reveal any significant differences between the two groups ( P =0.54). Under the limitations of the present study, there was no significant differences between the results of Articaine buccal infiltration and Lidocaine PSA technique, so Articaine buccal infiltration can be used as a substitute for the PSA technique.

  4. The Efficacy of Buccal Infiltration of 4% Articaine and PSA Injection of 2% Lidocaine on Anesthesia of Maxillary Second Molars

    PubMed Central

    Maljaei, Ensiyeh; Pourkazemi, Maryam; Ghanizadeh, Milad; Ranjbar, Rana

    2017-01-01

    Introduction: During the early mixed dentition period, the location of the deciduous maxillary second molar results in ineffectiveness of the infiltration technique in this area. In such cases, administration of posterior superior alveolar (PSA) nerve block is recommended; however, such a technique has some complications. The present study was undertaken to compare the effects of buccal infiltration of 4% Articaine and PSA technique with 2% Lidocaine on the success of anesthesia of maxillary deciduous second molars in 6 to 9-year old children. Methods and Materials: In the present double-blind randomized clinical trial, 56 children aged 6-9 years requiring vital pulp therapy of deciduous maxillary second molar were included. In group 1, 4% Articaine was injected using a buccal infiltration technique. In group 2, 2% Lidocaine was injected using the PSA nerve block technique. After 10 min, the caries was removed and access cavity preparation was instituted. The patients were asked to report the presence or absence of pain during the procedure. Therefore, the existence of pain was measured by the patient's self-report. Data were analyzed with descriptive statistical methods and the chi-squared test. Results: Pain was reported by 6 (21.4%) and 9 (32.1%) subjects in the Articaine and Lidocaine groups, respectively. Chi-squared test did not reveal any significant differences between the two groups (P=0.54). Conclusion: Under the limitations of the present study, there was no significant differences between the results of Articaine buccal infiltration and Lidocaine PSA technique, so Articaine buccal infiltration can be used as a substitute for the PSA technique. PMID:28808450

  5. Use of mobile phones and text messaging to decrease the turnaround time for early infant HIV diagnosis and notification in rural Zambia: an observational study.

    PubMed

    Sutcliffe, Catherine G; Thuma, Philip E; van Dijk, Janneke H; Sinywimaanzi, Kathy; Mweetwa, Sydney; Hamahuwa, Mutinta; Moss, William J

    2017-03-08

    Early infant diagnosis of HIV infection is challenging in rural sub-Saharan Africa as blood samples are sent to central laboratories for HIV DNA testing, leading to delays in diagnosis and treatment initiation. Simple technologies to rapidly deliver results to clinics and notify mothers of test results would decrease many of these delays. The feasibility of using mobile phones to contact mothers was evaluated. In addition, the first two years of implementation of a national short message service (SMS) reporting system to deliver test results from the laboratory to the clinic were evaluated. The study was conducted in Macha, Zambia from 2013 to 2015 among mothers of HIV-exposed infants. Mothers were interviewed about mobile phone use and willingness to be contacted directly or through their rural health center. Mothers were contacted according to their preferred method of communication when test results were available. Mothers of positive infants were asked to return to the clinic as soon as possible. Dates of sample collection, delivery of test results to the clinic and notification of mothers were documented in addition to test results. Four hundred nineteen mothers and infants were enrolled. Only 30% of mothers had ever used a mobile phone. 96% of mobile phone owners were reached by study staff and 98% of mothers without mobile phones were contacted through their rural health center. Turnaround times for mothers of positive infants were approximately 2 weeks shorter than for mothers of negative infants. Delivery of test results by the national SMS system improved from 2013 to 2014, with increases in the availability of texted results (38 vs. 91%) and arrival of the texted result prior to the hardcopy report (27 vs. 83%). Texted results arriving at the clinic before the hardcopy were received a median of 19 days earlier. Four discrepancies between texted and hardcopy results were identified out of 340 tests. Mobile phone and text messaging technology has the

  6. Developmental triclosan exposure decreases maternal, fetal, and early neonatal thyroxine: a dynamic and kinetic evaluation of a putative mode-of-action.

    PubMed

    Paul, Katie B; Hedge, Joan M; Bansal, Ruby; Zoeller, R Thomas; Peter, Robert; DeVito, Michael J; Crofton, Kevin M

    2012-10-09

    This work tests the mode-of-action (MOA) hypothesis that maternal and developmental triclosan (TCS) exposure decreases circulating thyroxine (T4) concentrations via up-regulation of hepatic catabolism and elimination of T4. Time-pregnant Long-Evans rats received TCS po (0-300mg/kg/day) from gestational day (GD) 6 through postnatal day (PND) 21. Serum and liver were collected from dams (GD20, PND22) and offspring (GD20, PND4, PND14, PND21). Serum T4, triiodothyronine (T3), and thyroid-stimulating hormone (TSH) concentrations were measured by radioimmunoassay. Ethoxy-O-deethylase (EROD), pentoxyresorufin-O-depentylase (PROD) and uridine diphosphate glucuronyltransferase (UGT) enzyme activities were measured in liver microsomes. Custom Taqman(®) qPCR arrays were employed to measure hepatic mRNA expression of select cytochrome P450s, UGTs, sulfotransferases, transporters, and thyroid hormone-responsive genes. TCS was quantified by LC/MS/MS in serum and liver. Serum T4 decreased approximately 30% in GD20 dams and fetuses, PND4 pups and PND22 dams (300mg/kg/day). Hepatic PROD activity increased 2-3 fold in PND4 pups and PND22 dams, and UGT activity was 1.5 fold higher in PND22 dams only (300mg/kg/day). Minor up-regulation of Cyp2b and Cyp3a expression in dams was consistent with hypothesized activation of the constitutive androstane and/or pregnane X receptor. T4 reductions of 30% for dams and GD20 and PND4 offspring with concomitant increases in PROD (PND4 neonates and PND22 dams) and UGT activity (PND22 dams) suggest that up-regulated hepatic catabolism may contribute to TCS-induced hypothyroxinemia during development. Serum and liver TCS concentrations demonstrated greater fetal than postnatal internal exposure, consistent with the lack of T4 changes in PND14 and PND21 offspring. These data support the MOA hypothesis that TCS exposure leads to hypothyroxinemia via increased hepatic catabolism; however, the minor effects on thyroid hormone metabolism may reflect the

  7. Once-daily milking during a feed deficit decreases milk production but improves energy status in early lactating grazing dairy cows.

    PubMed

    Kay, J K; Phyn, C V C; Rius, A G; Morgan, S R; Grala, T M; Roche, J R

    2013-10-01

    The objective of this study was to investigate the effect of milking frequency (MF) at 2 feeding levels (FL) on milk production, body condition score, and metabolic indicators of energy status in grazing dairy cows during early lactation. Multiparous Holstein-Friesian and Holstein-Friesian × Jersey cows (n=120) grazed pasture and were milked twice daily (2×) from calving until 34 ± 6 d in milk (mean ± standard deviation). Cows were then allocated to 1 of 4 treatments in a 2 × 2 factorial arrangement. Treatments consisted of 2 FL: adequately fed [AF; 14.3 kg dry matter intake (DMI)/cow per d] or underfed (UF; 8.3 kg of DMI/cow per d) and 2 MF: 2× or once daily (1×). Treatments were imposed for 3 wk. After the treatment period, all cows were offered a generous pasture allowance (grazing residuals >1,600 kg of dry matter/ha) and milked 2×. During the 3-wk treatment period, we observed an interaction between FL and MF for energy-corrected milk (ECM), such that the decrease due to 1× milking was greater in AF than in UF cows (20 and 14% decrease, respectively). No interactions were found posttreatment. Cows previously UF produced 7% less ECM than AF cows during wk 4 to 12; however, no subsequent effect was observed of the previous underfeeding. Cows previously milked 1× produced 5% less ECM during wk 4 to 12, and differences remained during wk 13 to 23. During the 3-wk treatment period, UF cows lost 0.2 body condition score units (1-10 scale) and this was not affected by 1× milking. During the treatment period, UF cows had lower plasma glucose, insulin, and insulin-like growth factor I, and greater nonesterified fatty acids and β-hydroxybutyrate concentrations than AF cows. Cows milked 1× had greater plasma glucose, insulin, and insulin-like growth factor I, and lower nonesterified fatty acids and β-hydroxybutyrate concentrations compared with cows milked 2×. In conclusion, energy status was improved by 1× milking; however, when UF cows were milked 1

  8. Decrease of Murine Cytomegalovirus–Induced Retinitis by Intravenous Delivery of Immediate Early Protein-3–Specific siRNA

    PubMed Central

    Marshall, Brendan; Mo, Juan; Covar, Jason; Atherton, Sally S.; Zhang, Ming

    2014-01-01

    Purpose. Retinitis induced by both human and murine cytomegaloviruses following immunosuppression is characterized by progressive loss of retinal architecture, due to necrosis of virus-infected cells as well as widespread apoptosis of uninfected bystander cells. Because small inhibitory RNA molecules (siRNA) can reduce murine cytomegalovirus (MCMV) gene expression and thereby inhibit virus replication in vitro, we tested siRNAs directed against MCMV immediate early protein-3 (IE-3) to determine if MCMV-induced retinitis could be alleviated in vivo. Methods. Immunosuppressed Balb/c mice (2.0 mg methylprednisolone acetate every 3 days beginning on day −2) were infected with 5 × 103 pfu of the K181 strain of MCMV via the supraciliary route. At day 2 post infection, mice were treated with various doses of IE-3–specific siRNA ranging from 0.1 nmol to 10 nmol, in a volume of 20 μL PBS via tail vein injection. Injected eyes were collected at various times post inoculation and subjected to plaque assay for virus titer, MCMV antigen staining, H&E staining, TUNEL assay, and Western blot for MCMV IE-3 protein. Results. Small but significant amounts of fluorescently labeled IE-3–specific siRNA localized to the RPE layer 48 hours after intravenous injection. IE-3–specific siRNA significantly reduced virus titers at all concentrations tested (ranging from 0.1 nmol to 10 nmol), but the most potent effect of siRNA was observed at a dose of 1 nmol. We also observed that IE-3–specific siRNA produced a substantial decrease in MCMV titers and a substantial reduction in bystander cell apoptosis over the time course of virus infection. Conclusions. Systemic administration of IE-3–specific siRNA could alleviate MCMV retinitis by inhibiting virus replication and subsequent death of uninfected retinal cells. PMID:24906861

  9. Prepartum supplementation of conjugated linoleic acids (CLA) increased milk energy output and decreased serum fatty acids and β-hydroxybutyrate in early lactation dairy cows

    PubMed Central

    Oliveira, Rafael Caputo; Pralle, Ryan S.; de Resende, Lucas C.; Nova, Carlos Henrique P. C.; Caprarulo, Valentina; Jendza, Joshua A.; Troescher, Arnulf

    2018-01-01

    Prepartum supplementation with conjugated linoleic acid (CLA) may influence lipolysis and hyperketonemia in dairy cows. The objective of this study was to examine the effect of prepartum CLA supplementation on lactation performance and serum fatty acids (FA) and β-hydroxybutyrate (BHB) in early lactation dairy cows, and secondarily on reproductive performance. Multiparous cows were enrolled in the study at 18 days prior to expected calving date, and randomly assigned 100 g/day of Lutrell Pure (BASF, Ludwigshafen, Germany; 75% FA), providing 10 g/day of each CLA isomer (trans-10 cis-12 and cis-9 trans-11 CLA) or equivalent amount of rumen inert fatty acids as control (78 g/day of Energy Booster 100; Milk Specialties Global, Eden Prairie, MN). Treatments were top dressed daily to individual cows from enrollment to calving and all cows were offered the same ration. Blood samples were collected on the first day of supplementation, 10 days prepartum, and 1, 7, 14, and 30 days postpartum. Hyperketonemia was defined as serum BHB ≥ 1.2 mM. Milk yield was recorded daily until 60 days postpartum and averaged weekly. Milk samples were obtained weekly for component analysis. Prepartum CLA supplementation tended to increase serum concentration of cis-9, trans-11 CLA and increased trans-10, cis-12 CLA prepartum. Cows supplemented with CLA had increased milk protein yield and tended to have increased milk fat yield and milk yield, which together resulted in greater energy content of milk. Cows supplemented with CLA had lower serum FA on day 1 and 7 postpartum and overall lower serum BHB postpartum, which resulted in decreased prevalence of hyperketonemia on day 14 postpartum. There were no differences in body condition score change, other health disorders, or reproductive outcomes by treatment. Together, these findings indicate that prepartum CLA supplementation may be a plausible strategy to positively influence postpartum performance. PMID:29772023

  10. Decreased expression of 14-3-3 σ, an early event of malignant transformation of respiratory epithelium, also facilitates progression of squamous cell lung cancer

    PubMed Central

    Sun, Nan; Wu, Yongkai; Huang, Bo; Liu, Qian; Dong, Yinan; Ding, Jianqiao; Liu, Yongyu

    2015-01-01

    Background It has been shown that 14-3-3 σ serves as a tumor suppressor gene, and is downregulated in various tumor tissues. However, the role of 14-3-3 σ during the initiation and progression of lung squamous cell carcinoma (SqCC) is not well understood. Methods The expression status of 14-3-3 σ in archival tissue samples from 40 lung SqCC patients (36 with normal bronchia, 19 squamous metaplasia, and 17 dysplasia/carcinoma in situ, in their tissue samples) was examined by immunohistochemical analysis. The proliferation rate and tumor formation ability of the H520 cell transfected with 14-3-3 σ was tested with methyl thiazolyl tetrazolium assay and nude mice subcutaneous injection, respectively. Results In the normal bronchial epithelia, 14-3-3 σ was highly expressed, whereas it was significantly decreased in precancerous and cancerous tissues. Compared with matched invasive cancer tissues, the expression level of 14-3-3 σ in squamous metaplasia was significantly higher (P = 0.049), while that in dysplasia/carcinoma in situ showed no significant changes (P = 0.135). Statistical analysis showed that the expression level of 14-3-3 σ in tumor tissue was associated with the differentiation grade of the tumor (P = 0.001) and the prognosis of the patient (P = 0.003). The overexpression of 14-3-3 σ significantly suppressed the proliferation of H520 cells in vitro and in vivo. Conclusion The inactivation of 14-3-3 σ may be a very early event in tumorigenesis and could facilitate the initiation and progression of lung SqCC in a sustainable way. PMID:26557909

  11. Decreased Libido

    MedlinePlus

    ... Cancer Featured Resource Find an Endocrinologist Search Decreased Libido Editors Bradley Anawalt, MD Maria Yialamas, MD Additional Resources: Mayo Clinic NIDDK MedlinePlus What is libido? Libido is the desire to engage in sexual ...

  12. Appetite - decreased

    MedlinePlus

    Loss of appetite; Decreased appetite; Anorexia ... Any illness can reduce appetite. If the illness is treatable, the appetite should return when the condition is cured. Loss of appetite can cause weight ...

  13. Review of APR+ Level 2 PSA. Revision 2

    SciTech Connect

    Lehner, John R.; Mubayi, Vinod; Pratt, W. Trevor

    2012-02-17

    Brookhaven National Laboratory (BNL) assisted the Korea Institute of Nuclear Safety (KINS) in reviewing the Level 2 Probabilistic Safety Assessment (PSA) of the APR+ Advanced Pressurized Water Reactor (PWR) prepared by the Korea Hydro & Nuclear Power Co., Ltd (KHNP) and KEPCO Engineering & Construction Co., Inc. (KEPCO-E&C). The work described in this report involves a review of the APR+ Level 2 PSA submittal [Ref. 1]. The PSA and, therefore, the review is limited to consideration of accidents initiated by internal events. As part of the review process, the review team also developed three sets of Requests for Additional Informationmore » (RAIs). These RAIs were provided to KHNP and KEPCO-E&C for their evaluation and response. This final detailed report documents the review findings for each technical element of the PSA and includes consideration of all of the RAIs made by the reviewers as well as the associated responses. This final report was preceded by an interim report [Ref. 2] that focused on identifying important issues regarding the PSA. In addition, a final meeting on the project was held at BNL on November 21-22, 2011, where BNL and KINS reviewers discussed their preliminary review findings with KHNP and KEPCO-E&C staffs. Additional information obtained during this final meeting was also used to inform the review findings of this final report. The review focused not only on the robustness of the APR+ design to withstand severe accidents, but also on the capability and acceptability of the Level 2 PSA in terms of level of detail and completeness. The Korean nuclear regulatory authorities will decide whether the PSA is acceptable and the BNL review team is providing its comments for KINS consideration. Section 2.0 provides the basis for the BNL review. Section 3.0 presents the review of each technical element of the PSA. Conclusions and a summary are presented in Section 4.0. Section 5.0 contains the references.« less

  14. Novel rolling circle amplification and DNA origami-based DNA belt-involved signal amplification assay for highly sensitive detection of prostate-specific antigen (PSA).

    PubMed

    Yan, Juan; Hu, Chongya; Wang, Ping; Liu, Rui; Zuo, Xiaolei; Liu, Xunwei; Song, Shiping; Fan, Chunhai; He, Dannong; Sun, Gang

    2014-11-26

    Prostate-specific antigen (PSA) is one of the most important biomarkers for the early diagnosis and prognosis of prostate cancer. Although many efforts have been made to achieve significant progress for the detection of PSA, challenges including relative low sensitivity, complicated operation, sophisticated instruments, and high cost remain unsolved. Here, we have developed a strategy combining rolling circle amplification (RCA)-based DNA belts and magnetic bead-based enzyme-linked immunosorbent assay (ELISA) for the highly sensitive and specific detection of PSA. At first, a 96-base circular DNA template was designed and prepared for the following RCA. Single stranded DNA (ssDNA) products from RCA were used as scaffold strand for DNA origami, which was hybridized with three staple strands of DNA. The resulting DNA belts were conjugated with multiple enzymes for signal amplification and then employed to magnetic bead based ELISA for PSA detection. Through our strategy, as low as 50 aM of PSA can be detected with excellent specificity.

  15. Measurements of free and total PSA, tissue polypeptide-specific antigen (TPS), and CYFRA 21-1 in prostate cancer patients under intermittent androgen suppression therapy.

    PubMed

    Theyer, G; Dürer, A; Theyer, U; Haberl, I; Ulsperger, E; Baumgartner, G; Hamilton, G

    1999-10-01

    The present study evaluated monthly measurements of free and total prostate-specific antigen (PSA), and the tumor proliferation markers tissue polypeptide-specific antigen (TPS) and cytokeratin fragment 21-1 (CYFRA 21-1) in patients with advanced prostate cancer receiving intermittent androgen suppression therapy (IAS). Thirty-four men received alternating cycles of 8 month androgen suppression and treatment cessation (mean duration, 10.3 months) until PSA increased to >20 microg/l. Measurements of testosterone, percentage of free PSA, TPS, and CYFRA 21-1 were performed using ELISA and RIA assays. Periods of androgen suppression resulted in reversible reductions of testosterone (from 6 +/- 0.8 to <0.58 ng/ml), PSA (from 31.2 +/- 4.5 to <1.7 microg/l), and prostatic volume (mean reduction, 22.2 +/- 4.6%), indicating apoptotic regression of the tumors. Upon treatment cessation, testosterone increased to 6.1 +/- 0.56 ng/ml within 2 months, followed by an increase of PSA to 5.8 +/- 0.8 microg/l. The mean percentage of free PSA (15.1 +/- 2.6%) exhibited no significant change during the whole IAS cycle. TPS showed a decrease of 50% after 3 months, and CYFRA 21-1 a 25% decrease after 7 months of androgen suppression treatment. During treatment cessation, TPS exceeded the normal cutoff value of 90 U/l late in tumor regrowth (9-11 months), whereas CYFRA 21-1 remained below the normal cutoff value of 3.3 ng/ml. PSA is the best and most sensitive marker of prostate cancer regression and regrowth during IAS cycles of the markers tested in this study. Free PSA constitutes approximately 15% of total PSA (range, 5-32%), and its percentage showed no significant change during IAS cycles. The TPS and CYFRA 21-1 proliferation marker changes in IAS seem to be related mainly to effects on normal androgen-dependent tissues. Copyright 1999 Wiley-Liss, Inc.

  16. Relationship of chronic histologic prostatic inflammation in biopsy specimens with serum isoform [-2]proPSA (p2PSA), %p2PSA, and prostate health index in men with a total prostate-specific antigen of 4-10 ng/ml and normal digital rectal examination.

    PubMed

    Lazzeri, Massimo; Abrate, Alberto; Lughezzani, Giovanni; Gadda, Giulio Maria; Freschi, Massimo; Mistretta, Francesco; Lista, Giuliana; Fossati, Nicola; Larcher, Alessandro; Kinzikeeva, Ella; Buffi, Nicolòmaria; Dell'Acqua, Vincenzo; Bini, Vittorio; Montorsi, Francesco; Guazzoni, Giorgio

    2014-03-01

    To investigate the relationship between serum [-2]proPSA (p2PSA) and derivatives with chronic histologic prostatic inflammation (CHPI) in men undergoing prostate biopsy for suspected prostate cancer (PCa). This nested case-control study resulted from an observational prospective trial for the definition of sensibility, specificity, and accuracy of p2PSA, %p2PSA, and Beckman Coulter Prostate Health Index (PHI), in men undergoing prostate biopsy, with a total prostate-specific antigen (PSA) of 4-10 ng/mL and normal digital rectal examination. CHPI was the outcome of interest and defined as the presence of moderate to large infiltration of lymphomononuclear cells with interstitial and/or glandular disruption in absence of PCa. p2PSA, %p2PSA, and PHI were considered the index tests and compared with the established biomarker reference standard tests: tPSA, fPSA, %fPSA. Of 267 patients subjected to prostate biopsy, 73 (27.3%) patients were diagnosed with CHPI. Comparing CHPI with PCa patients, %p2PSA and PHI were found to be significantly lower, whereas fPSA and %fPSA were significantly higher. %p2PSA and PHI were the most accurate predictors of CHPI at biopsy, significantly outperforming tPSA, fPSA, and %fPSA. On the contrary, no significant differences were found in PSA, p2PSA, and derivatives between CHPI and benign prostatic hyperplasia (BPH) patients. Our findings showed that p2PSA, %p2PSA, and PHI values might discriminate PCa from CHPI or BPH, but not CHPI from BPH, in men with a total PSA 4-10 ng/mL and normal digital rectal examination. p2PSA isoform and its derivatives could be useful in clinical decision making to avoid unnecessary biopsies in patients with CHPI and elevated tPSA value. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Understanding PSA and its derivatives in prediction of tumor volume: addressing health disparities in prostate cancer risk stratification

    PubMed Central

    Chinea, Felix M; Lyapichev, Kirill; Epstein, Jonathan I; Kwon, Deukwoo; Smith, Paul Taylor; Pollack, Alan; Cote, Richard J; Kryvenko, Oleksandr N

    2017-01-01

    Objectives To address health disparities in risk stratification of U.S. Hispanic/Latino men by characterizing influences of prostate weight, body mass index, and race/ethnicity on the correlation of PSA derivatives with Gleason score 6 (Grade Group 1) tumor volume in a diverse cohort. Results Using published PSA density and PSA mass density cutoff values, men with higher body mass indices and prostate weights were less likely to have a tumor volume <0.5 cm3. Variability across race/ethnicity was found in the univariable analysis for all PSA derivatives when predicting for tumor volume. In receiver operator characteristic analysis, area under the curve values for all PSA derivatives varied across race/ethnicity with lower optimal cutoff values for Hispanic/Latino (PSA=2.79, PSA density=0.06, PSA mass=0.37, PSA mass density=0.011) and Non-Hispanic Black (PSA=3.75, PSA density=0.07, PSA mass=0.46, PSA mass density=0.008) compared to Non-Hispanic White men (PSA=4.20, PSA density=0.11 PSA mass=0.53, PSA mass density=0.014). Materials and Methods We retrospectively analyzed 589 patients with low-risk prostate cancer at radical prostatectomy. Pre-operative PSA, patient height, body weight, and prostate weight were used to calculate all PSA derivatives. Receiver operating characteristic curves were constructed for each PSA derivative per racial/ethnic group to establish optimal cutoff values predicting for tumor volume ≥0.5 cm3. Conclusions Increasing prostate weight and body mass index negatively influence PSA derivatives for predicting tumor volume. PSA derivatives’ ability to predict tumor volume varies significantly across race/ethnicity. Hispanic/Latino and Non-Hispanic Black men have lower optimal cutoff values for all PSA derivatives, which may impact risk assessment for prostate cancer. PMID:28160549

  18. Understanding PSA and its derivatives in prediction of tumor volume: Addressing health disparities in prostate cancer risk stratification.

    PubMed

    Chinea, Felix M; Lyapichev, Kirill; Epstein, Jonathan I; Kwon, Deukwoo; Smith, Paul Taylor; Pollack, Alan; Cote, Richard J; Kryvenko, Oleksandr N

    2017-03-28

    To address health disparities in risk stratification of U.S. Hispanic/Latino men by characterizing influences of prostate weight, body mass index, and race/ethnicity on the correlation of PSA derivatives with Gleason score 6 (Grade Group 1) tumor volume in a diverse cohort. Using published PSA density and PSA mass density cutoff values, men with higher body mass indices and prostate weights were less likely to have a tumor volume <0.5 cm3. Variability across race/ethnicity was found in the univariable analysis for all PSA derivatives when predicting for tumor volume. In receiver operator characteristic analysis, area under the curve values for all PSA derivatives varied across race/ethnicity with lower optimal cutoff values for Hispanic/Latino (PSA=2.79, PSA density=0.06, PSA mass=0.37, PSA mass density=0.011) and Non-Hispanic Black (PSA=3.75, PSA density=0.07, PSA mass=0.46, PSA mass density=0.008) compared to Non-Hispanic White men (PSA=4.20, PSA density=0.11 PSA mass=0.53, PSA mass density=0.014). We retrospectively analyzed 589 patients with low-risk prostate cancer at radical prostatectomy. Pre-operative PSA, patient height, body weight, and prostate weight were used to calculate all PSA derivatives. Receiver operating characteristic curves were constructed for each PSA derivative per racial/ethnic group to establish optimal cutoff values predicting for tumor volume ≥0.5 cm3. Increasing prostate weight and body mass index negatively influence PSA derivatives for predicting tumor volume. PSA derivatives' ability to predict tumor volume varies significantly across race/ethnicity. Hispanic/Latino and Non-Hispanic Black men have lower optimal cutoff values for all PSA derivatives, which may impact risk assessment for prostate cancer.

  19. GIS Technologies for the Planetary Science Archive (PSA)

    NASA Astrophysics Data System (ADS)

    Docasal, R.

    2017-09-01

    In my abstract I try to show how a GIS and 3D visual tools architecture could handle the different approaches for visualizing the spatial info, depending on the nature and shape of the object (planet, satellite, comet...etc) to be mapped in a multi-mission website such as the new PSA.

  20. Lifestyle and Clinical Health Behaviors and PSA Tests

    ERIC Educational Resources Information Center

    Norris, Cynthia; McFall, Stephanie

    2006-01-01

    This study assessed the association of lifestyle and clinical health behaviors with prostate specific antigen (PSA) tests. The study used cross-sectional data from the 2002 Behavioral Risk Factor Surveillance System (BRFSS). We used Stata 8.0 to take into account the complex sample design in analyses. Both lifestyle and clinical health behaviors…

  1. Early Ambulation Decreases Length of Hospital Stay, Perioperative Complications and Improves Functional Outcomes in Elderly Patients Undergoing Surgery for Correction of Adult Degenerative Scoliosis.

    PubMed

    Adogwa, Owoicho; Elsamadicy, Aladine A; Fialkoff, Jared; Cheng, Joseph; Karikari, Isaac O; Bagley, Carlos

    2017-09-15

    Ambispective cohort review. To examine the effects of early mobilization on patient outcomes, complications profile, and 30-day readmission rates. Prolonged immobilization after surgery can result in functional decline and an increased risk of hospital-associated complications. We conducted an ambispective study of 125 elderly patients (>65 years) undergoing elective spinal surgery for correction of adult degenerative scoliosis. We identified all unplanned readmissions within 30 days of discharge. Unplanned readmissions were defined to have occurred as a result of either a surgical or a nonsurgical complication. "Days of immobility" was defined as the number of days until a patient moved out of bed beyond a chair. Patients in the top and bottom quartiles were dichotomized into "early ambulators" and "late ambulators", respectively. Early ambulators were ambulatory within 24 hours of surgery, whereas late ambulators were ambulatory at a minimum of 48 hours after surgery. Complication rates, duration of hospital stay, and 30-day readmission rates were compared between early ambulators and late ambulators. Baseline characteristics were similar between both cohorts. Compared with patients with a longer duration of immobility (i.e., late ambulators), the prevalence of at least one perioperative complication was significantly lower in the early ambulators cohort (30% vs. 54%, P = 0.06). The length of inhospital stay was 34% shorter in the early ambulators cohort (5.33 days vs. 8.11 days, P = 0.01). Functional independence was superior in the early ambulators cohort, with the majority of patients discharged directly home after surgery compared with late ambulators (71.2% vs. 22.0%, P = 0.01). Early ambulation after surgery significantly reduces the incidence of perioperative complications, shortens duration of inhospital stay, and contributes to improved perioperative functional status in elderly patients. Even a delay of 24 hours to ambulation is

  2. GIS Technologies For The New Planetary Science Archive (PSA)

    NASA Astrophysics Data System (ADS)

    Docasal, R.; Barbarisi, I.; Rios, C.; Macfarlane, A. J.; Gonzalez, J.; Arviset, C.; De Marchi, G.; Martinez, S.; Grotheer, E.; Lim, T.; Besse, S.; Heather, D.; Fraga, D.; Barthelemy, M.

    2015-12-01

    Geographical information system (GIS) is becoming increasingly used for planetary science. GIS are computerised systems for the storage, retrieval, manipulation, analysis, and display of geographically referenced data. Some data stored in the Planetary Science Archive (PSA), for instance, a set of Mars Express/Venus Express data, have spatial metadata associated to them. To facilitate users in handling and visualising spatial data in GIS applications, the new PSA should support interoperability with interfaces implementing the standards approved by the Open Geospatial Consortium (OGC). These standards are followed in order to develop open interfaces and encodings that allow data to be exchanged with GIS Client Applications, well-known examples of which are Google Earth and NASA World Wind as well as open source tools such as Openlayers. The technology already exists within PostgreSQL databases to store searchable geometrical data in the form of the PostGIS extension. An existing open source maps server is GeoServer, an instance of which has been deployed for the new PSA, uses the OGC standards to allow, among others, the sharing, processing and editing of data and spatial data through the Web Feature Service (WFS) standard as well as serving georeferenced map images through the Web Map Service (WMS). The final goal of the new PSA, being developed by the European Space Astronomy Centre (ESAC) Science Data Centre (ESDC), is to create an archive which enables science exploitation of ESA's planetary missions datasets. This can be facilitated through the GIS framework, offering interfaces (both web GUI and scriptable APIs) that can be used more easily and scientifically by the community, and that will also enable the community to build added value services on top of the PSA.

  3. Correlation between the complex PSA/total PSA ratio and the free PSA/total PSA ratio, sensitivity and specificity of both markers for the diagnosis of prostate cancer.

    PubMed

    Pérez-Lanzac-Lorca, A; Barco-Sánchez, A; Romero, E; Martinez-Peinado, A; López-Elorza, F; Sanchez-Sanchez, E; Alvarez-Ossorio-Fernandez, J L; Castiñeiras-Fernández, J

    2013-09-01

    To compare the behaviour of the PSAcomplex/PSAtotal percentage (PSAc%) against the PSA free/PSA total (PSAl%) and analyse both markers for their usefulness in diagnosing prostate cancer. We measured total PSA (PSAt), free PSA (PSAl), complex PSA (PSAc), PSAl% and PSAc% levels in 158 patients. Of these, 98 (62%) were biopsied for presenting PSAt≥3 ng/dl and PSAl%<20, PSAt>10, suspicious rectal examination or suspicious ultrasound node. We performed linear regression and Passing-Bablok regression analyses. The ROC curves were calculated to study the sensitivity and specificity of PSAl% and PSAc% and were compared to each other. The prostate cancer diagnoses were analysed by PSAl% and PSAc% by applying the χ(2) test. The correlation coefficient (r) was good (0.7447, P<.0001), and the index of determination (r(2)) was 0,5. The result of the Passing-Bablok analysis was a slope of 1.658 (1.452 to 1.897) and an intersection of 2.044 (-0,936 to 5.393). The optimal cutoff for PSAl% (≤14.7854) showed a sensitivity of 89.29% [95% CI, 0,642-0,823] and a specificity of 54.29% (95% CI, 0,642-0,823). The optimal cutoff for PSAc% (>89.7796) had a sensitivity of 71.43% (95% CI, 0,616-0,802) and a specificity of 71.43% (95% CI, 0,616-0,802). There were no significant differences when comparing the areas under the curve of both markers (P=.59). The PPV of PSAl% was less than that of PSAc% (45.7% vs. 71%). There was a good correlation between PSAl% and PSAc%. PSAc% has demonstrated greater specificity and efficacy than PSAl% in the diagnosis of prostate cancer. Copyright © 2012 AEU. Published by Elsevier Espana. All rights reserved.

  4. PSCA expression is associated with favorable tumor features and reduced PSA recurrence in operated prostate cancer.

    PubMed

    Heinrich, Marie-Christine; Göbel, Cosima; Kluth, Martina; Bernreuther, Christian; Sauer, Charlotte; Schroeder, Cornelia; Möller-Koop, Christina; Hube-Magg, Claudia; Lebok, Patrick; Burandt, Eike; Sauter, Guido; Simon, Ronald; Huland, Hartwig; Graefen, Markus; Heinzer, Hans; Schlomm, Thorsten; Heumann, Asmus

    2018-05-31

    Prostate Stem Cell Antigen (PSCA) is frequently expressed in prostate cancer but its exact function is unclear. To clarify contradictory findings on the prognostic role of PSCA expression, a tissue microarray containing 13,665 prostate cancers was analyzed by immunohistochemistry. PSCA staining was absent in normal epithelial and stromal cells of the prostate. Membranous and cytoplasmic PSCA staining was seen in 53.7% of 9642 interpretable tumors. Staining was weak in 22.4%, moderate in 24.5% and strong in 6.8% of tumors. PSCA expression was associated with favorable pathological and clinical tumor features: Early pathological tumor stage (p < 0.0001), low Gleason grade (p < 0.0001), absence of lymph node metastasis (p < 0.0001), low pre-operative PSA level (p = 0.0118), negative surgical margin (p < 0.0001) and reduced PSA recurrence (p < 0.0001). PSCA expression was an independent predictor of prognosis in multivariate analysis (hazard ratio 0.84, p < 0.0001). The absence of statistical relationship to TMPRSS2:ERG fusion status, chromosomal deletion or high tumor cell proliferation argues against a major role of PSCA for regulation of cell cycle or genomic integrity. PSCA expression is linked to favorable prognosis. PSCA measurement is a candidate for inclusion in multi-parametric prognostic prostate cancer tests.

  5. Decreased early mortality associated with the treatment of acute myeloid leukemia at National Cancer Institute-designated cancer centers in California.

    PubMed

    Ho, Gwendolyn; Wun, Ted; Muffly, Lori; Li, Qian; Brunson, Ann; Rosenberg, Aaron S; Jonas, Brian A; Keegan, Theresa H M

    2018-05-01

    To the authors' knowledge, few population-based studies to date have evaluated the association between location of care, complications with induction therapy, and early mortality in patients with acute myeloid leukemia (AML). Using linked data from the California Cancer Registry and Patient Discharge Dataset (1999-2014), the authors identified adult (aged ≥18 years) patients with AML who received inpatient treatment within 30 days of diagnosis. A propensity score was created for treatment at a National Cancer Institute-designated cancer center (NCI-CC). Inverse probability-weighted, multivariable logistic regression models were used to determine associations between location of care, complications, and early mortality (death ≤60 days from diagnosis). Of the 7007 patients with AML, 1762 (25%) were treated at an NCI-CC. Patients with AML who were treated at NCI-CCs were more likely to be aged ≤65 years, live in higher socioeconomic status neighborhoods, have fewer comorbidities, and have public health insurance. Patients treated at NCI-CCs had higher rates of renal failure (23% vs 20%; P = .010) and lower rates of respiratory failure (11% vs 14%; P = .003) and cardiac arrest (1% vs 2%; P = .014). After adjustment for baseline characteristics, treatment at an NCI-CC was associated with lower early mortality (odds ratio, 0.46; 95% confidence interval, 0.38-0.57). The impact of complications on early mortality did not differ by location of care except for higher early mortality noted among patients with respiratory failure treated at non-NCI-CCs. The initial treatment of adult patients with AML at NCI-CCs is associated with a 53% reduction in the odds of early mortality compared with treatment at non-NCI-CCs. Lower early mortality may result from differences in hospital or provider experience and supportive care. Cancer 2018;124:1938-45. © 2018 American Cancer Society. © 2018 American Cancer Society.

  6. Fire decreases arthropod abundance but increases diversity: Early and late season prescribed fire effects in a Sierra Nevada mixed-conifer forest

    USGS Publications Warehouse

    Ferrenberg, Scott; Schwilk, Dylan W.; Knapp, Eric E.; Groth, Eric; Keeley, Jon E.

    2006-01-01

    Prior to fire suppression in the 20th century, the mixed-conifer forests of the Sierra Nevada, California, U.S.A., historically burned in frequent fires that typically occurred during the late summer and early fall. Fire managers have been attempting to restore natural ecosystem processes through prescription burning, and have often favored burning during the fall in order to mimic historical fire regimes. Increasingly, however, prescription burning is also being done during the late spring and early summer in order to expand the window of opportunity for needed fuel reduction burning. The effect of prescribed fires outside of the historical fire season on forest arthropods is not known. The objective of this study was to compare the short-term effects of prescribed fires ignited in the early and late fire season on forest floor arthropods. Arthropod abundance and diversity were assessed using pitfall trapping in replicated burn units in Sequoia National Park, California. Overall, abundance of arthropods was lower in the burn treatments than in the unburned control. However, diversity tended to be greater in the burn treatments. Fire also altered the relative abundances of arthropod feeding guilds. No significant differences in arthropod community structure were found between early and late season burn treatments. Instead, changes in the arthropod community appeared to be driven largely by changes in fuel loading, vegetation, and habitat heterogeneity, all of which differed more between the burned and unburned treatments than between early and late season burn treatments.

  7. Planarian homolog of puromycin-sensitive aminopeptidase DjPsa is required for brain regeneration.

    PubMed

    Wu, Suge; Liu, Bin; Yuan, Zuoqing; Zhang, Xiufang; Liu, Hong; Pang, Qiuxiang; Zhao, Bosheng

    2017-06-01

    Puromycin-sensitive aminopeptidase (PSA) belongs to the M1 zinc metallopeptidase family. PSA is the most abundant aminopeptidase in the brain and plays a role in the metabolism of neuropeptides including those involved in neurodegeneration. A cDNA DjPsa was identified from the planarian Dugesia japonica cDNA library. It contains a 639-bp open reading frame corresponding to a deduced protein of 212 amino acids. Whole mount in situ hybridization revealed that DjPsa is expressed in the brain and ventral nerve cords of intact and regenerating animals and demonstrates a tissue and stage-specific expression pattern of DjPsa in developing embryos and larvae. Knocking down DjPsa gene expression with RNA interference during planarian regeneration inhibits the brain reformation completely. The results suggest that DjPsa is required for planarian brain regeneration.

  8. Fire decreases arthropod abundance but increases diversity: early and late season prescribed fire effects in a Sierra Nevada mixed-conifer forest

    Treesearch

    Scott M. Ferrenberg; Dylan W. Schwilk; Eric E. Knapp; Eric Groth; Jon E. Keeley

    2006-01-01

    Prior to fire suppression in the 20th century, the mixed-conifer forests of the Sierra Nevada, California, U.S.A., historically burned in frequent fires that typically occurred during the late summer and early fall. Fire managers have been attempting to restore natural ecosystem processes through prescription burning, and have often favored burning during the fall in...

  9. What does postradiotherapy PSA nadir tell us about freedom from PSA failure and progression-free survival in patients with low and intermediate-risk localized prostate cancer?

    PubMed

    DeWitt, K D; Sandler, H M; Weinberg, V; McLaughlin, P W; Roach, M

    2003-09-01

    To determine whether the post-external beam radiotherapy (RT) prostate-specific antigen nadir (nPSA) improves our ability to predict freedom from PSA failure, progression-free survival (PFS), and overall survival. Controversy regarding the importance of nPSA after external beam RT as a prognostic indicator for patients with localized prostate cancer has continued. This analysis was based on the data from 748 patients with low and intermediate-risk localized prostate cancer treated with external beam RT alone. Patients were categorized by nPSA quartile groups with cutpoints of less than 0.3, 0.3 to less than 0.6, 0.6 to less than 1.2, and 1.2 ng/mL or greater. Both univariate and multivariate analyses were used to determine the significance of nPSA on PSA failure (American Society for Therapeutic Radiology Oncology consensus definition), PFS (death after PSA failure), and overall survival (death from any cause). Freedom from PSA failure was strongly associated with nadir quartile groups (P <0.0001). PFS was also significantly different statistically among nadir quartile groups (P = 0.02). No statistically significant difference was found in overall survival associated with nPSA at this point. nPSA is a strong independent predictor of freedom from PSA failure and PFS in patients with low and intermediate-risk localized prostate cancer treated with RT alone. Longer follow-up and larger patient numbers are required to confirm these observations.

  10. A single administration of methamphetamine to mice early in the light period decreases running wheel activity observed during the dark period

    PubMed Central

    Kitanaka, Nobue; Kitanaka, Junichi; Hall, F. Scott; Uhl, George R.; Watabe, Kaname; Kubo, Hitoshi; Takahashi, Hitoshi; Tatsuta, Tomohiro; Morita, Yoshio; Takemura, Motohiko

    2014-01-01

    Repeated intermittent administration of amphetamines acutely increases appetitive and consummatory aspects of motivated behaviors as well as general activity and exploratory behavior, including voluntary running wheel activity. Subsequently, if the drug is withdrawn, the frequency of these behaviors decrease, which is thought to be indicative of dysphoric symptoms associated with amphetamine withdrawal. Such decreases may be observed after chronic treatment or even after single drug administrations. In the present study, the effect of acute methamphetamine (METH) on running wheel activity, horizontal locomotion, appetitive behavior (food access), and consummatory behavior (food and water intake) was investigated in mice. A multi-configuration behavior apparatus designed to monitor the five behaviors was developed, where combined measures were recorded simultaneously. In the first experiment, naïve male ICR mice showed gradually increasing running wheel activity over three consecutive days after exposure to a running wheel, while mice without a running wheel showed gradually decreasing horizontal locomotion, consistent with running wheel activity being a positively motivated form of natural motor activity. In experiment 2, increased horizontal locomotion and food access, and decreased food intake, were observed for the initial 3 h after acute METH challenge. Subsequently, during the dark phase period decreased running wheel activity and horizontal locomotion were observed. The reductions in running wheel activity and horizontal locomotion may be indicative of reduced dopaminergic function, although it remains to be seen if these changes may be more pronounced after more prolonged METH treatments. PMID:22079320

  11. Decreased numbers of chemotactic factor receptors in chronic neutropenia with defective chemotaxis: spontaneous recovery from the neutrophil abnormalities during early childhood

    SciTech Connect

    Yasui, K.; Yamazaki, M.; Miyagawa, Y.

    Childhood chronic neutropenia with decreased numbers of chemotactic factor receptors as well as defective chemotaxis was first demonstrated in an 8-month-old girl. Chemotactic factor receptors on neutrophils were assayed using tritiated N-formyl-methionyl-leucyl-phenylalanine (/sup 3/H-FMLP). The patient's neutrophils had decreased numbers of the receptors: numbers of the receptors were 20,000 (less than 3 SD) as compared with those of control cells of 52,000 +/- 6000 (mean +/- SD) (n = 10). The neutropenia disappeared spontaneously by 28 months of age parallel with the improvement of chemotaxis and increase in numbers of chemotactic factor receptors. These results demonstrate a transient decrease ofmore » neutrophil chemotactic factor receptors as one of the pathophysiological bases of a transient defect of neutrophil chemotaxis in this disorder.« less

  12. PSA nadir as a predictive factor for biochemical disease-free survival and overall survival following whole-gland salvage HIFU following radiotherapy failure.

    PubMed

    Shah, T T; Peters, M; Kanthabalan, A; McCartan, N; Fatola, Y; van der Voort van Zyp, J; van Vulpen, M; Freeman, A; Moore, C M; Arya, M; Emberton, M; Ahmed, H U

    2016-09-01

    Treatment options for radio-recurrent prostate cancer are either androgen-deprivation therapy or salvage prostatectomy. Whole-gland high-intensity focussed ultrasound (HIFU) might have a role in this setting. An independent HIFU registry collated consecutive cases of HIFU. Between 2005 and 2012, we identified 50 men who underwent whole-gland HIFU following histological confirmation of localised disease following prior external beam radiotherapy (2005-2012). No upper threshold was applied for risk category, PSA or Gleason grade either at presentation or at the time of failure. Progression was defined as a composite with biochemical failure (Phoenix criteria (PSA>nadir+2 ng ml(-1))), start of systemic therapies or metastases. Median age (interquartile range (IQR)), pretreatment PSA (IQR) and Gleason score (range) were 68 years (64-72), 5.9 ng ml(-1) (2.2-11.3) and 7 (6-9), respectively. Median follow-up was 64 months (49-84). In all, 24/50 (48%) avoided androgen-deprivation therapies. Also, a total of 28/50 (56%) achieved a PSA nadir <0.5 ng ml(-1), 15/50 (30%) had a nadir ⩾0.5 ng ml(-1) and 7/50 (14%) did not nadir (PSA non-responders). Actuarial 1, 3 and 5-year progression-free survival (PFS) was 72, 40 and 31%, respectively. Actuarial 1, 3 and 5-year overall survival (OS) was 100, 94 and 87%, respectively. When comparing patients with PSA nadir <0.5 ng ml(-1), nadir ⩾0.5 and non-responders, a statistically significant difference in PFS was seen (P<0.0001). Three-year PFS in each group was 57, 20 and 0%, respectively. Five-year OS was 96, 100 and 38%, respectively. Early in the learning curve, between 2005 and 2007, 3/50 (6%) developed a fistula. Intervention for bladder outlet obstruction was needed in 27/50 (54%). Patient-reported outcome measure questionnaires showed incontinence (any pad-use) as 8/26 (31%). In our series of high-risk patients, in whom 30-50% may have micro-metastases, disease control rates were promising in PSA

  13. Decreased Bacterial Diversity Characterizes an Altered Gut Microbiota in Psoriatic Arthritis and Resembles Dysbiosis of Inflammatory Bowel Disease

    PubMed Central

    Scher, Jose U.; Ubeda, Carles; Artacho, Alejandro; Attur, Mukundan; Isaac, Sandrine; Reddy, Soumya M.; Marmon, Shoshana; Neimann, Andrea; Brusca, Samuel; Patel, Tejas; Manasson, Julia; Pamer, Eric G.; Littman, Dan R.; Abramson, Steven B.

    2014-01-01

    Objective To characterize the diversity and taxonomic relative abundance of the gut microbiota in patients with never-treated, recent-onset psoriatic arthritis (PsA). Methods High-throughput 16S rRNA pyrosequencing was utilized to compare community composition of gut microbiota in PsA patients (n=16), subjects with psoriasis of the skin (Ps) (n=15) and healthy, matched-controls (n=17). Samples were further assessed for the presence and levels of fecal and serum secretory immunoglobulin A (sIgA), pro-inflammatory proteins and fatty-acids. Results The gut microbiota observed in PsA and Ps patients was less diverse when compared to healthy controls. These could be attributed to the reduced presence of several taxa. While both groups showed a relative decrease in Coprococcus spp., PsA samples were characterized by a significant reduction in Akkermansia, Ruminococcus, and Pseudobutyrivibrio. Supernatants of fecal samples from PsA patients revealed an increase in sIgA and a decrease in receptor activator of nuclear factor kappa-B ligand (RANKL) levels. Fatty acid analysis revealed low levels of hexanoate and heptanoate in PsA and Ps patients. Conclusion PsA and Ps patients had a lower relative abundance of multiple intestinal bacteria. Although some genera were concomitantly decreased in both conditions, PsA samples had lower abundance of reportedly beneficial taxa. This gut microbiota profile in PsA was similar to that published for patients with IBD and was associated with changes in specific inflammatory proteins unique to this group, and distinct from Ps and controls. Thus, the role of gut microbiota in the continuum of Ps-PsA pathogenesis and the associated immune response merits further study. PMID:25319745

  14. A trust-region algorithm for the optimization of PSA processes using reduced-order modeling

    SciTech Connect

    Agarwal, A.; Biegler, L.; Zitney, S.

    2009-01-01

    -step PSA process used for separating a hydrogen-methane mixture in [3]. The reduced order model developed was successfully used to optimize this process to maximize hydrogen recovery within a trust-region. We extend this approach in this work to develop a rigorous trust-region algorithm for ROM-based optimization of PSA processes. The trust-region update rules and sufficient decrease condition for the objective is used to determine the size of the trust-region. Based on the decrease in the objective function and error in the ROM, a ROM updation strategy is designed [4, 5]. The inequalities and bounds are handled in the algorithm using exact penalty formulation, and a non-smooth trust-region algorithm by Conn et al. [6] is used to handle non-differentiability. To ensure that the first order consistency condition is met and the optimum obtained from ROM-based optimization corresponds to the optimum of the original problem, a scaling function, such as one proposed by Alexandrov et al. [7], is incorporated in the objective function. Such error control mechanism is also capable of handling numerical inconsistencies such as unphysical oscillations in the state variable profiles. The proposed methodology is applied to optimize a PSA process to concentrate CO{sub 2} from a nitrogen-carbon dioxide mixture. As in [3], separate ROMs are developed for each operating step with different POD modes for each state variable. Numerical results will be presented for optimization case studies which involve maximizing CO{sub 2} recovery, feed throughput or minimizing overall power consumption.« less

  15. Long-term longitudinal changes in baseline PSA distribution and estimated prevalence of prostate cancer in male Japanese participants of population-based PSA screening.

    PubMed

    Oki, Ryo; Ito, Kazuto; Suzuki, Rie; Fujizuka, Yuji; Arai, Seiji; Miyazawa, Yoshiyuki; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Suzuki, Kazuhiro

    2018-04-26

    Japan has experienced a drastic increase in the incidence of prostate cancer (PC). To assess changes in the risk for PC, we investigated baseline prostate specific antigen (PSA) levels in first-time screened men, across a 25-year period. In total, 72,654 men, aged 50-79, underwent first-time PSA screening in Gunma prefecture between 1992 and 2016. Changes in the distribution of PSA levels were investigated, including the percentage of men with a PSA above cut-off values and linear regression analyses comparing log 10 PSA with age. The 'ultimate incidence' of PC and clinically significant PC (CSPC) were estimated using the PC risk calculator. Changes in the age-standardized incidence rate (AIR) during this period were analyzed. The calculated coefficients of linear regression for age versus log 10 PSA fluctuated during the 25-year period, but no trend was observed. In addition, the percentage of men with a PSA above cut-off values varied in each 5-year period, with no specific trend. The 'risk calculator (RC)-based AIR' of PC and CSPC were stable between 1992 and 2016. Therefore, the baseline risk for developing PC has remained unchanged in the past 25 years, in Japan. The drastic increase in the incidence of PC, beginning around 2000, may be primarily due to increased PSA screening in the country. © 2018 UICC.

  16. Clinical outcomes and nadir prostate-specific antigen (PSA) according to initial PSA levels in primary androgen deprivation therapy for metastatic prostate cancer.

    PubMed

    Kitagawa, Yasuhide; Ueno, Satoru; Izumi, Kouji; Kadono, Yoshifumi; Mizokami, Atsushi; Hinotsu, Shiro; Akaza, Hideyuki; Namiki, Mikio

    2016-03-01

    To investigate the clinical outcomes of metastatic prostate cancer patients and the relationship between nadir prostate-specific antigen (PSA) levels and different types of primary androgen deprivation therapy (PADT). This study utilized data from the Japan Study Group of Prostate Cancer registry, which is a large, multicenter, population-based database. A total of 2982 patients treated with PADT were enrolled. Kaplan-Meier analysis was used to compare progression-free survival (PFS) and overall survival (OS) in patients treated using combined androgen blockade (CAB) and non-CAB therapies. The relationships between nadir PSA levels and PADT type according to initial serum PSA levels were also investigated. Among the 2982 enrolled patients, 2101 (70.5 %) were treated with CAB. Although CAB-treated patients had worse clinical characteristics, their probability of PFS and OS was higher compared with those treated with a non-CAB therapy. These results were due to a survival benefit with CAB in patients with an initial PSA level of 500-1000 ng/mL. Nadir PSA levels were significantly lower in CAB patients than in non-CAB patients with comparable initial serum PSA levels. A small survival benefit for CAB in metastatic prostate cancer was demonstrated in a Japanese large-scale prospective cohort study. The clinical significance of nadir PSA levels following PADT was evident, but the predictive impact of PSA nadir on OS was different between CAB and non-CAB therapy.

  17. Developmental Triclosan Exposure Decreases Maternal,Fetal, and Early Neonatal Thyroxine: Dynamic and Kinetic Data Support for a Mode-of-Action

    EPA Science Inventory

    This work tests the mode-of-action (MOA) hypothesis that perinatal triclosan (TCS) exposure decreases circulating thyroxine (T4) concentrations via activation of pregnane X and/or constitutive androstane receptors (PXR, CAR), resulting in up-regulation of hepatic catabolism and e...

  18. Analysis of urinary PSA glycosylation is not indicative of high-risk prostate cancer.

    PubMed

    Barrabés, Sílvia; Llop, Esther; Ferrer-Batallé, Montserrat; Ramírez, Manel; Aleixandre, Rosa N; Perry, Antoinette S; de Llorens, Rafael; Peracaula, Rosa

    2017-07-01

    The levels of core fucosylation and α2,3-linked sialic acid in serum Prostate Specific Antigen (PSA), using the lectins Pholiota squarrosa lectin (PhoSL) and Sambucus nigra agglutinin (SNA), can discriminate between Benign Prostatic Hyperplasia (BPH) and indolent prostate cancer (PCa) from aggressive PCa. In the present work we evaluated whether these glycosylation determinants could also be altered in urinary PSA obtained after digital rectal examination (DRE) and could also be useful for diagnosis determinations. For this purpose, α2,6-sialic acid and α1,6-fucose levels of urinary PSA from 53 patients, 18 biopsy-negative and 35 PCa patients of different aggressiveness degree, were analyzed by sandwich ELLA (Enzyme Linked Lectin Assay) using PhoSL and SNA. Changes in the levels of specific glycosylation determinants, that in serum PSA samples were indicative of PCa aggressiveness, were not found in PSA from DRE urine samples. Although urine is a simpler matrix for analyzing PSA glycosylation compared to serum, an immunopurification step was necessary to specifically detect the glycans on the PSA molecule. Those specific glycosylation determinants on urinary PSA were however not useful to improve PCa diagnosis. This could be probably due to the low proportion of PSA from the tumor in urine samples, which precludes the identification of aberrantly glycosylated PSA. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Prenatal and Early Postnatal Exposure to Cigarette Smoke Decreases BDNF/TrkB Signaling and Increases Abnormal Behaviors Later in Life

    PubMed Central

    Xiao, Lan; Kish, Vincent L.; Benders, Katherine M.

    2016-01-01

    Background: Cigarette smoke exposure during prenatal and early postnatal periods increases the incidence of a variety of abnormal behaviors later in life. The purpose of this study was to identify the possible critical period of susceptibility to cigarette smoke exposure and evaluate the possibe effects of cigarette smoke during early life on brain-derived neurotrophic factor/neurotrophic tyrosine kinase receptor B signaling in the brain. Methods: Three different age of imprinting control region mice were exposed to cigarette smoke or filtered air for 10 consecutive days beginning on either gestational day 7 by maternal exposure, or postnatal days 2 or 21 by direct inhalation. A series of behavioral profiles and neurotrophins in brain were measured 24 hours after mice received acute restraint stress for 1 hour on postnatal day 59. Results: Cigarette smoke exposure in gestational day 7 and postnatal day 2 produced depression-like behaviors as evidenced by significantly increased immobility in both tail suspension and forced-swim test. Increased entry latencies, but not ambulation in the open field test, were also observed in the gestational day 7 and postnatal day 2 cigarette smoke exposure groups. Genetic analysis showed that gestational day 7 cigarette smoke exposure significantly altered mRNA level of brain-derived neurotrophic factor/tyrosine kinase receptor B in the hippocampus. However, behavioral profiles and brain-derived neurotrophic factor/tyrosine kinase receptor B signaling were not significantly changed in PND21 cigarette smoke exposure group compared with FA group. Conclusions: These results suggest that a critical period of susceptibility to cigarette smoke exposure exists in the prenatal and early postnatal period, which results a downregulation in brain-derived neurotrophic factor/tyrosine kinase receptor B signaling in the hippocampus and enhances depression-like behaviors later in life. PMID:26503133

  20. Early nutritional support is associated with decreased length of hospitalization in dogs with septic peritonitis: A retrospective study of 45 cases (2000-2009).

    PubMed

    Liu, Debra T; Brown, Dorothy C; Silverstein, Deborah C

    2012-08-01

    To determine whether the timing and route of nutritional support strategy affect length of hospitalization in dogs with naturally occurring septic peritonitis. Retrospective study encompassing cases from 2000 to 2009. University teaching hospital. Forty-five dogs that survived septic peritonitis. None. Nutritional strategy for each dog was categorized as either enteral nutrition (EN: free choice voluntary eating or assisted tube feeding) or central parenteral nutrition (CPN). Early nutritional support was defined as consistent caloric intake initiated within 24 hours postoperatively. Consistent caloric intake occurring after 24 hours was defined as delayed nutritional support. Data reflective of nutritional status included body condition score, serum albumin concentration, and duration of inappetence before and during hospitalization. Body weight change from the beginning to the end of hospitalization was calculated. A modified Survival Prediction Index 2 score was calculated for each dog at admission. Additional clinical data recorded for comparison of illness severity included indicators of severe inflammation (eg, presence of toxic changes in neutrophils and immature neutrophils), coagulopathy (eg, prolonged prothrombin time and activated partial thromboplastin time), the use of vasopressors and blood transfusions, and presence of concurrent illnesses. Nutrition-related complications were classified as mechanical, metabolic, or septic complications. Multivariate linear regression analyses were used to determine the relationship of nutritional strategy with hospitalization length, while considering the presence of nutrition-related complications, the nutritional status- and illness severity-related variables. While controlling for other variables, dogs that received early nutrition had significantly shorter hospitalization length (by 1.6 days). No statistically significant association was found between route of nutrition and hospitalization length. The presence

  1. PSA kinetics following primary focal cryotherapy (hemiablation) in organ-confined prostate cancer patients.

    PubMed

    Kongnyuy, Michael; Islam, Shahidul; Mbah, Alfred K; Halpern, Daniel M; Werneburg, Glenn T; Kosinski, Kaitlin E; Chen, Connie; Habibian, David J; Schiff, Jeffrey T; Corcoran, Anthony T; Katz, Aaron E

    2018-02-01

    We aim to evaluate prostate-specific antigen (PSA) trends in post-primary focal cryotherapy (PFC) patients. This was an institutional review board-approved retrospective study of PFC patients from 2010 to 2015. Patients with at least one post-PFC PSA were included in the study. Biochemical recurrence (BCR) was determined using the Phoenix criteria. PSA bounce was also assessed. We analyzed rates of change of PSA over time of post-PFC between BCR and no BCR groups. PSA-derived variables were analyzed as potential predictors of BCR. A total of 104 PFC patients were included in our analysis. Median (range) age and follow-up time were 66 (48-82) years and 19 (6.3-38.6) months, respectively. Four (3.8%) patients experienced PSA bounce. The median percent drop in first post-PFC PSA of 80.0% was not associated with BCR (p = 0.256) and may indicate elimination of the index lesion. The rate of increase of PSA in BCR patients was significantly higher compared to patients who did not recur (median PSA velocity (PSAV): 0.15 vs 0.04 ng/ml/month, p = 0.001). Similar to PSAV (HR 9.570, 95% CI 3.725-24.592, p < 0.0001), PSA nadir ≥ 2 ng/ml [HR (hazard ratio) 1.251, 95% CI 1.100-1.422, p = 0.001] was independently associated with BCR. A significant drop in post-PFC PSA may indicate elimination of the index lesion. Patients who are likely to recur biochemically have a significantly higher PSAV compared to those who do not recur. Nadir PSA of less than 2 ng/ml may be considered the new normal PSA in focal cryotherapy (hemiablation) follow-up.

  2. Early onset of action and sleep-improving effect are crucial in decreasing suicide risk: the role of quetiapine XR in the treatment of unipolar and bipolar depression.

    PubMed

    Pompili, Maurizio; Rihmer, Zoltan; Gonda, Xenia; Serafini, Gianluca; Sher, Leo; Girardi, Paolo

    2012-01-01

    Although the possibilities of antidepressive pharmacotherapy are continuously improving, the rate of nonresponders or partial responders is still relatively high. Suicidal behavior, the most tragic consequence of untreated or unsuccessfully treated depression, commonly observed in the first few weeks of antidepressive treatment before the onset of therapeutic action, is strongly related to certain symptoms of depression like insomnia. The present paper reviews the newly discovered and well-documented antidepressive effect of quetiapine in bipolar and unipolar depression with special focus on its early onset of action and its sleep-improving effects. Both beneficial effects play an important role in the reduction of suicidal risk frequently observed in depressed patients.

  3. [Early drop-outs and retentions in substance abuse outpatient clinics: a cross-sectional comparative study of factors that increase or decrease adherence].

    PubMed

    Calvo, Fran; Carbonell, Xavier; Valero, Ramón; Costa, Jordi; Turró, Oriol; Giralt, Cristina; Ramírez, Marissa

    2017-08-23

    The aim of this study is to define the risk factors associated with early discharge in out-patients clinics. Cross-sectional and observational study. Substance abuse clinics in Girona (Catalonia, Spain). A total of 264 individuals were included in the sample, and 34.8% of them abandoned the process within two months of starting the therapy (n=92). Clinical and socio-demographic variables of the clinical history were compared between participants with/without adherence. The Student t test was used to measure the comparison, and the chi-squared test was used for the analysis of qualitative variables. A binary logistic regression model was adjusted, with adherence as the dependent variable. The results indicated that attending the appointments unaccompanied (OR=3.13), being female (OR=2.44), having cocaine related issues (OR=1.14), and being younger (OR=0.89) are the factors which increase the risk early abandonment. Contrarily, being referred to specialists from a Primary Health Centre reduces the risk (OR=0.28). It is concluded that special attention must be devoted to the patients' families, women, and young patients. Moreover, the appropriate coordination between specialist services and basic services increases adherence to treatment among drug users. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  4. Loss of body fat and associated decrease in leptin in early lactation are related to shorter duration of postpartum anovulation in healthy US women.

    PubMed

    Domer, Mary Colleen; Beerman, Kathy A; Ahmadzadeh, Amin; Dasgupta, Nairanjana; Williams, Janet E; McGuire, Mark A; McGuire, Michelle K

    2015-05-01

    The mechanisms regulating postpartum anovulation (PPA) are not well understood, although poor nutritional status and "intense" breastfeeding behaviors are associated with longer durations. This study was designed primarily to investigate the hypothesis that higher body fat and leptin concentrations are related to shorter PPA in healthy, lactating US women. Nutrient intake, breastfeeding behaviors, prolactin, and insulin levels were also evaluated. Fasting serum was collected during the third trimester of pregnancy, at 2 and 4 weeks postpartum, and every 4 weeks until the occurrence of the first postpartum menses. Body composition and breastfeeding behaviors were assessed at the same times postpartum. Women (n = 13) were categorized based on initial percentage body fat and timing of first postpartum menses. There were no consistent relationships between body composition, leptin, or breastfeeding behaviors and duration of PPA. However, there was an interaction (P = .005) between ovulation group and time on adiposity; earlier ovulating women had less percentage body fat in early lactation than did later ovulating women. There was also an interaction (P = .1) between ovulation group and time postpartum on leptin, such that leptin concentrations tended to be greater in later than earlier ovulating groups beginning at 12 weeks postpartum. In summary, although baseline percentage body fat and leptin were not related to duration of PPA, fertility returned earlier in women who lost greater percentage body fat during the early postpartum period. © The Author(s) 2015.

  5. The percentage of prostate-specific antigen (PSA) isoform [-2]proPSA and the Prostate Health Index improve the diagnostic accuracy for clinically relevant prostate cancer at initial and repeat biopsy compared with total PSA and percentage free PSA in men aged ≤65 years.

    PubMed

    Boegemann, Martin; Stephan, Carsten; Cammann, Henning; Vincendeau, Sébastien; Houlgatte, Alain; Jung, Klaus; Blanchet, Jean-Sebastien; Semjonow, Axel

    2016-01-01

    To prospectively test the diagnostic accuracy of the percentage of prostate specific antigen (PSA) isoform [-2]proPSA (%p2PSA) and the Prostate Health Index (PHI), and to determine their role for discrimination between significant and insignificant prostate cancer at initial and repeat prostate biopsy in men aged ≤65 years. The diagnostic performance of %p2PSA and PHI were evaluated in a multicentre study. In all, 769 men aged ≤65 years scheduled for initial or repeat prostate biopsy were recruited in four sites based on a total PSA (t-PSA) level of 1.6-8.0 ng/mL World Health Organization (WHO) calibrated (2-10 ng/mL Hybritech-calibrated). Serum samples were measured for the concentration of t-PSA, free PSA (f-PSA) and p2PSA with Beckman Coulter immunoassays on Access-2 or DxI800 instruments. PHI was calculated as (p2PSA/f-PSA × √t-PSA). Uni- and multivariable logistic regression models and an artificial neural network (ANN) were complemented by decision curve analysis (DCA). In univariate analysis %p2PSA and PHI were the best predictors of prostate cancer detection in all patients (area under the curve [AUC] 0.72 and 0.73, respectively), at initial (AUC 0.67 and 0.69) and repeat biopsy (AUC 0.74 and 0.74). t-PSA and %f-PSA performed less accurately for all patients (AUC 0.54 and 0.62). For detection of significant prostate cancer (based on Prostate Cancer Research International Active Surveillance [PRIAS] criteria) the %p2PSA and PHI equally demonstrated best performance (AUC 0.70 and 0.73) compared with t-PSA and %f-PSA (AUC 0.54 and 0.59). In multivariate analysis PHI we added to a base model of age, prostate volume, digital rectal examination, t-PSA and %f-PSA. PHI was strongest in predicting prostate cancer in all patients, at initial and repeat biopsy and for significant prostate cancer (AUC 0.73, 0.68, 0.78 and 0.72, respectively). In DCA for all patients the ANN showed the broadest threshold probability and best net benefit. PHI as single parameter

  6. [Rates of total and free PSA prescriptions in France (2012-2014)].

    PubMed

    Tuppin, Philippe; Leboucher, Claire; Peyre-Lanquar, Gabrielle; Lamy, Pierre-Jean; Gabach, Pierre; Rébillard, Xavier

    2017-10-01

    In 2010, the French Haute Autorité de santé (National Health Authority) confirmed the limited value of prostate cancer (PCa) screening by total prostate-specific antigen (PSA) assay. This study was designed to determine the modalities of ordering total PSA or free PSA assays (in the absence of PCa) according to various parameters and the corresponding sums reimbursed. Men aged 40 years and older covered by the national health insurance general scheme (73% of the French population) between 2012 and 2014 were selected. Data were derived from the Système national d'information inter-régimes de l'assurance maladie (Sniiram) (National health insurance information system) database. In 2014, 27% of the 11.6 million men 40 years and older underwent at least one total PSA assay and 5.6% underwent at least one free PSA assay, with marked variations according to the presence or absence of treated lower urinary tract symptoms (LUTS) (53% and 15% vs 24% and 5%) and from one administrative department to another. The peak total PSA assay rate was observed between the ages of 65 and 74 years: 64% of men with LUTS, 46% without LUTS. Between 2012 and 2014, men in whom at least one PSA assay had been performed underwent a mean of 1.8 total PSA assays and 1.7 free PSA assays, with means of 2.3 and 2, respectively, in the presence of LUTS. General practice specialists ordered 91% of the PSA tests reimbursed in 2014 (92% for total PSA and 87% for free PSA) and urologists ordered 4% of reimbursed tests. The total sum reimbursed was €28.5 million, comprising €8.7 million for free PSA. An average of 10 laboratory tests was performed at the same time as the PSA assay in the absence of treated LUTS. Total PSA and free PSA assays are performed in a large number of men, although the value of these tests as first-line test before biopsy remains controversial. These PSA assays are associated with many other laboratory tests looking for possible abnormalities, especially in younger

  7. Early Removal of Double-J Stents Decreases Urinary Tract Infections in Living Donor Renal Transplantation: A Prospective, Randomized Clinical Trial.

    PubMed

    Liu, S; Luo, G; Sun, B; Lu, J; Zu, Q; Yang, S; Zhang, X; Dong, J

    2017-03-01

    The optimal timing for stent removal after renal transplantation remains controversial. This article describes an interim analysis of a randomized, prospective, double-blind trial aimed at detecting differences in urological complications between early ureteral stent removal at 1 week and routine ureteral stent removal at 4 weeks. Between October 2010 and March 2015, 103 patients who underwent living donor renal transplantation at a single center were pre-operatively randomly assigned to the early ureteral stent removal (at 1 week) group or the routine ureteral stent removal (at 4 weeks) group. Urinary symptoms, auxiliary examination results, and obstruction events were recorded during 3 months of follow-up. A cost analysis of both the hospitalization and postoperative periods was discussed. In total, 52 patients in the 1-week stent group and 51 patients in the 4-week stent group were analyzed. No serious adverse events were reported. Three episodes of urinary tract infections (UTIs) occurred in the 1-week stent group, and 18 such episodes were recorded in the 4-week stent group (5.8% vs 29.4%; P = .002). After adjusting for age, sex, ischemia time, renal artery number, body mass index, multiple arteries, and associated medical illness, regression analysis indicated that only stent duration was associated with UTI (OR, 8.791; 95% CI, 1.984-38.943; P = .004). The results of our study demonstrate that ureteral stent removal at 1 week reduces the risk of UTIs compared with routine removal at 4 weeks. Similar effects of ureteral stent removal on complication rates are observed for these two removal times. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Cevimeline-induced monophasic salivation from the mouse submandibular gland: decreased Na+ content in saliva results from specific and early activation of Na+/H+ exchange.

    PubMed

    Kondo, Yusuke; Nakamoto, Tetsuji; Mukaibo, Taro; Kidokoro, Manami; Masaki, Chihiro; Hosokawa, Ryuji

    2011-04-01

    Cevimeline and pilocarpine are muscarinic agonists used clinically to treat dry mouth. In this study, we explored fluid secretion from mouse submandibular glands to determine the mechanism of cevimeline, pilocarpine, and an experimentally used agent carbachol. Cevimeline evoked almost the same amount of secretion at concentrations from 30 μM to 1 mM. Pilocarpine also induced secretion at a concentration as low as 1 μM and was the most powerful secretagogue at 10 μM. Secretion was induced by carbachol at 0.1 μM, with maximum secretion at 1.0 μM. Cevimeline induced monophasic secretion at all concentrations tested, whereas higher concentrations of pilocarpine and carbachol induced secretion with variable kinetics, i.e., an initial transient high flow rate, followed by decreased secretion after 2 to 3 min. In the presence of an epithelial Na(+) channel blocker, amiloride, neither carbachol nor pilocarpine affected the Na(+) level of secreted saliva; however, it significantly increased the Na(+) content of cevimeline-induced saliva. The intracellular Ca(2+) response of acinar cells was almost identical among all three agents, although recovery after drug removal was slower for cevimeline and pilocarpine. A profound decrease in intracellular pH was observed during pilocarpine and carbachol treatment, whereas intracellular acidification induced by cevimeline was only seen in the presence of a Na(+)/H(+) exchange inhibitor. When external HCO(3)(-) was removed, cevimeline-induced saliva significantly decreased. These findings suggest that cevimeline specifically activates Na(+)/H(+) exchange and may promote Na(+) reabsorption by stabilizing epithelial sodium channel activity.

  9. Prebiopsy biparametric MRI: differences of PI-RADS version 2 in patients with different PSA levels.

    PubMed

    Choi, M H; Lee, Y J; Jung, S E; Rha, S E; Byun, J Y

    2018-06-09

    To validate the diagnostic accuracy of Prostate Imaging-Reporting and Data System (PI-RADS) version 2 in detecting clinically significant prostate cancer (csPCa, Gleason score ≥7) on prebiopsy biparametric MRI (bpMRI) in patients with different prostate-specific antigen (PSA) levels. This retrospective study included 184 patients who underwent prebiopsy bpMRI followed by transrectal ultrasonography-guided biopsy between June 2015 and February 2017. Reader 1 performed a combination of systematic and targeted biopsy with cognitive fusion after reviewing bpMRI and reader 2 reviewed the bpMRIs retrospectively. PI-RADS categories 4 and 5 were considered positive, and the results of the biopsy were considered the reference standard. Diagnostic performance of PI-RADS of bpMRI was evaluated in two PSA groups with a PSA cut-off level of 10 ng/ml and compared to PSA and the PSA density using receiver operating characteristics (ROC) curve analysis. csPCa was diagnosed in 24 of 123 patients (19.5%) and 26 of 61 patients (42.6%) in the low and high PSA groups, respectively. A PI-RADS v2 category by either readers 1 or 2 had a significantly better performance to detect csPCa than PSA in both PSA groups. In the high PSA group, only one csPCa was missed by reader 2, but none by reader 1. In the low PSA group, readers 1 and 2 were unable to detect seven and five of the 24 csPCas, respectively. Prebiopsy bpMRI has good performance for detecting csPCa in the high PSA group but may miss small-volume csPCa in the low PSA group. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  10. Genetically-Adjusted PSA Values May Prevent Delayed Biopsies in African-American Men

    PubMed Central

    Donin, Nicholas; Loeb, Stacy; Cooper, Phillip R.; Roehl, Kimberly A.; Baumann, Nikola A.; J.Catalona, William; Helfand, Brian T.

    2014-01-01

    Purpose Genetic variants called PSA-single nucleotide polymorphisms (PSA-SNPs) have been associated with serum PSA levels. We previously demonstrated that genetic correction of serum PSA in Caucasian men could reduce both potentially unnecessary biopsies by 15% to 20% and potentially delayed biopsies by 3%. Our objective was to evaluate whether genetic correction with the PSA-SNPs could reduce potentially unnecessary and/or delayed biopsies in African-American (AA) men. Materials and Methods We compared the genotypes of 4 PSA-SNPs between 964 Caucasian and 363 AA men without known PC. We adjusted PSA values based upon an individual's PSA-SNP carrier status, and calculated the percentage of men that would meet commonly used PSA thresholds for biopsy (≥2.5 or ≥4.0ng/mL) before and after genetic correction. Potentially unnecessary and delayed biopsies were defined as those men who went below and above the biopsy threshold after genetic correction, respectively. Results Overall, 349 (96.1%) and 354 (97.5%) AA men had measured PSA levels <2.5 and <4.0 ng/mL. Genetic correction in AA men did not avoid any potentially unnecessary biopsies, but resulted in a significant (p<0.001) reduction in potentially delayed biopsies by 2.5% and 3.9% based upon the biopsy threshold cutoff. Conclusions There are significant differences in the influence of the PSA-SNPs between AA and Caucasian men without known PC, as genetic correction resulted in an increased proportion of AA men crossing the threshold for biopsy. These results raise the question whether genetic differences in PSA might contribute to delayed PC diagnosis in AA patients. PMID:24712975

  11. Zoledronic acid induces a significant decrease of circulating endothelial cells and circulating endothelial precursor cells in the early prostate cancer neoadjuvant setting.

    PubMed

    Santini, Daniele; Zoccoli, Alice; Gregorj, Chiara; Di Cerbo, Melania; Iuliani, Michele; Pantano, Francesco; Zamarchi, Rita; Sergi, Federico; Flammia, Gerardo; Buscarini, Maurizio; Rizzo, Sergio; Cicero, Giuseppe; Russo, Antonio; Vincenzi, Bruno; Avvisati, Giuseppe; Tonini, Giuseppe

    2013-01-01

    Published data demonstrated that zoledronic acid (ZOL) exhibits antiangiogenetic effects. A promising tool for monitoring antiangiogenic therapies is the measurement of circulating endothelial cells (CECs) and circulating endothelial precursor cells (CEPs) in the peripheral blood of patients. Our aim was to investigate the effects of ZOL on levels of CECs and CEPs in localized prostate cancer. Ten consecutive patients with a histologic diagnosis of low-risk prostate adenocarcinoma were enrolled and received an intravenous infusion of ZOL at baseline (T0), 28 days (T28) and 56 days (T56). Blood samples were collected at the following times: T0 (before the first infusion of ZOL), T3 (72 h after the first dose), T28, T56 (both just before the ZOL infusion) and T84 (28 days after the last infusion of ZOL) and CEC/CEP levels were directly quantified by flow cytometry at all these time points. Our analyses highlighted a significant reduction of mean percentage of CECs and CEPs after initiation of ZOL treatment [p = 0.014 (at day 3) and p = 0.012 (at day 84), respectively]. These preliminary results demonstrate that ZOL could exert an antiangiogenic effect in early prostate cancer through CEP and CEC modulation.

  12. Early Stages of Sea-Level Rise Lead To Decreased Salt Marsh Plant Diversity through Stronger Competition in Mediterranean-Climate Marshes.

    PubMed

    Noto, Akana E; Shurin, Jonathan B

    2017-01-01

    Climate change shuffles species ranges and creates novel interactions that may either buffer communities against climate change or exacerbate its effect. For instance, facilitation can become more prevalent in salt marshes under stressful conditions while competition is stronger in benign environments. Sea-level rise (SLR) is a consequence of climate change that affects the distribution of stress from inundation and salinity. To determine how interactions early in SLR are affected by changes in these two stressors in Mediterranean-climate marshes, we transplanted marsh turfs to lower elevations to simulate SLR and manipulated cover of the dominant plant species, Salicornia pacifica (formerly Salicornia virginica). We found that both S. pacifica and the subordinate species were affected by inundation treatments, and that subordinate species cover and diversity were lower at low elevations in the presence of S. pacifica than when it was removed. These results suggest that the competitive effect of S. pacifica on other plants is stronger at lower tidal elevations where we also found that salinity is reduced. As sea levels rise, stronger competition by the dominant plant will likely reduce diversity and cover of subordinate species, suggesting that stronger species interactions will exacerbate the effects of climate change on the plant community.

  13. The Planetary Science Archive (PSA): Exploration and discovery of scientific datasets from ESA's planetary missions

    NASA Astrophysics Data System (ADS)

    Vallat, C.; Besse, S.; Barbarisi, I.; Arviset, C.; De Marchi, G.; Barthelemy, M.; Coia, D.; Costa, M.; Docasal, R.; Fraga, D.; Heather, D. J.; Lim, T.; Macfarlane, A.; Martinez, S.; Rios, C.; Vallejo, F.; Said, J.

    2017-09-01

    The Planetary Science Archive (PSA) is the European Space Agency's (ESA) repository of science data from all planetary science and exploration missions. The PSA provides access to scientific datasets through various interfaces at http://psa.esa.int. All datasets are scientifically peer-reviewed by independent scientists, and are compliant with the Planetary Data System (PDS) standards. The PSA has started to implement a number of significant improvements, mostly driven by the evolution of the PDS standards, and the growing need for better interfaces and advanced applications to support science exploitation.

  14. Immunohistochemical staining of precursor forms of prostate-specific antigen (proPSA) in metastatic prostate cancer.

    PubMed

    Parwani, Anil V; Marlow, Cameron; Demarzo, Angelo M; Mikolajczyk, Stephen D; Rittenhouse, Harry G; Veltri, Robert W; Chan, Theresa Y

    2006-10-01

    Precursors of prostate-specific antigen (proPSA) have been previously shown to be more concentrated in prostate cancer tissue. This study characterizes the immunohistochemical staining (IHS) of proPSA forms in metastatic prostate cancer compared with prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). A tissue microarray, consisting of 74 cases of metastatic prostate carcinoma and control tissues, was used. IHS, using monoclonal antibodies against proPSA with a truncated proleader peptide containing 2 amino acids ([-2]pPSA), native ([-5/-7]pPSA), PSA, and PAP, was analyzed. The monoclonal antibodies were specific for both benign and malignant prostatic glandular tissue. IHS with [-5/-7]pPSA showed the least number of cases with negative staining (3%), and the most number of cases with moderate or strong staining (76%). In the 60 cases where all 4 stains could be evaluated, none of them were negative for proPSA and positive for PSA or PAP, and all 7 cases that were negative for both PSA and PAP showed IHS to proPSA. [-5/-7]pPSA (native proPSA) may be a better marker than PSA and PAP in characterizing metastatic prostate adenocarcinoma, with most of the cases showing positivity for the marker. Even cases that were negative for PSA and PAP, were reactive for proPSA. Such enhanced detection is particularly important in poorly differentiated carcinomas involving metastatic sites where prostate carcinoma is a consideration. A panel of markers, including proPSA, should be performed when metastatic prostate carcinoma is in the differential diagnosis.

  15. Serum complexed and free prostate-specific antigen (PSA) for the diagnosis of the polycystic ovarian syndrome (PCOS).

    PubMed

    Diamandis, Eleftherios P; Stanczyk, Frank Z; Wheeler, Sarah; Mathew, Anu; Stengelin, Martin; Nikolenko, Galina; Glezer, Eli N; Brown, Marshall D; Zheng, Yingye; Chen, Yen-Hao; Wu, Hsiao-Li; Azziz, Ricardo

    2017-10-26

    Polycystic ovarian syndrome (PCOS) is a common cause of reproductive and metabolic dysfunction. We hypothesized that serum prostate-specific antigen (PSA) may constitute a new biomarker for hyperandrogenism in PCOS. We conducted a cross-sectional study of 45 women with PCOS and 40 controls. Serum from these women was analyzed for androgenic steroids and for complexed PSA (cPSA) and free PSA (fPSA) with a novel fifth- generation assay with a sensitivity of ~10 fg/mL for cPSA and 140 fg/mL for fPSA. cPSA and fPSA levels were about three times higher in PCOS compared to controls. However, in PCOS, cPSA and fPSA did not differ according to waist-to-hip ratio, Ferriman-Gallwey score, or degree of hyperandrogenemia or oligo-ovulation. In PCOS and control women, serum cPSA and fPSA levels were highly correlated with each other, and with free and total testosterone levels, but not with other hormones. Adjusting for age, body mass index (BMI) and race, cPSA was significantly associated with PCOS, with an odds ratio (OR) of 5.67 (95% confidence interval [CI]: 1.86, 22.0). The OR of PCOS for fPSA was 7.04 (95% CI: 1.65, 40.4). A multivariate model that included age, BMI, race and cPSA yielded an area-under-the-receiver-operating-characteristic curve of 0.89. Serum cPSA and fPSA are novel biomarkers for hyperandrogenism in PCOS and may have value for disease diagnosis.

  16. Can early extubation and intensive physiotherapy decrease length of stay of acute quadriplegic patients in intensive care? A retrospective case control study.

    PubMed

    Berney, Sue; Stockton, Kellie; Berlowitz, David; Denehy, Linda

    2002-01-01

    Respiratory complications remain a major cause of morbidity and mortality in the acute quadriplegic patient population. The literature has suggested that early insertion of a tracheostomy facilitated pulmonary management and an earlier discharge from the intensive care unit (ICU). Recently, a change in practice has meant that these patients are considered for extubation and intensive physiotherapy treatment, including an overnight on-call service, rather than tracheostomy. The aim of the present retrospective, case-controlled study was to determine if either practice resulted in a difference in length of stay in intensive care and if an on-call physiotherapy service for these patients was cost effective. A case control design was used. Between April 1997 and November 1999, seven patients who did not require a tracheostomy were identified; case control subjects were matched for severity with seven patients who did receive a tracheostomy. Length of stay in intensive care and on the acute ward, days from injury to fixation and the overall number of respiratory physiotherapy and night physiotherapy treatments were recorded. Five of the seven patients in the non-tracheostomy group received on-call overnight physiotherapy treatment, with an average of five sessions over a total of three nights. This group's length of stay in an ICU was significantly less than patients who were tracheostomized (p = 0.02). The overall number of physiotherapy treatments between the two groups was not significantly different. The results of this study suggest that if extubation and intensive physiotherapy is undertaken for suitable patients, the length of stay in intensive care can be significantly reduced. This represents a considerable cost saving for ICUs and more than covers the added cost of providing an after hours on-call physiotherapy treatment service. A prospective evaluation is required to confirm these findings.

  17. Phosphorylcholine decreases early inflammation and promotes the establishment of stable biofilm communities of nontypeable Haemophilus influenzae strain 86-028NP in a chinchilla model of otitis media.

    PubMed

    Hong, Wenzhou; Mason, Kevin; Jurcisek, Joseph; Novotny, Laura; Bakaletz, Lauren O; Swords, W Edward

    2007-02-01

    Nontypeable Haemophilus influenzae (NTHi) is a leading causative agent of otitis media. Much of the inflammation occurring during NTHi disease is initiated by lipooligosaccharides (LOS) on the bacterial surface. Phosphorylcholine (PCho) is added to some LOS forms in a phase-variable manner, and these PCho(+) variants predominate in vivo. Thus, we asked whether this modification confers some advantage during infection. Virulence of an otitis media isolate (NTHi strain 86-028NP) was compared with that of an isogenic PCho transferase (licD) mutant using a chinchilla (Chinchilla lanigera) model of otitis media. Animals infected with NTHi 86-028NP licD demonstrated increased early inflammation and a delayed increase in bacterial counts compared to animals infected with NTHi 86-028NP. LOS purified from chinchilla-passed NTHi 86-028NP had increased PCho content compared to LOS purified from the inoculum. Both strains were recovered from middle ear fluids as long as 14 days postinfection. Biofilms were macroscopically visible in the middle ears of euthanized animals infected with NTHi 86-028NP 7 days and 14 days postchallenge. Conversely, less dense biofilms were observed in animals infected with NTHi 86-028NP licD 7 days postinfection, and none of the animals infected with NTHi 86-028NP licD had a visible biofilm by 14 days. Fluorescent antibody staining revealed PCho(+) variants within biofilms, similar to our prior results with tissue culture cells in vitro (S. L. West-Barnette, A. Rockel, and W. E. Swords, Infect. Immun. 74:1828-1836, 2006). Animals coinfected with equal proportions of both strains had equal persistence of each strain and somewhat greater severity of disease. We thus conclude that PCho promotes NTHi infection and persistence by reducing the host inflammatory response and by promoting formation of stable biofilm communities.

  18. Updating the Psoriatic Arthritis (PsA) Core Domain Set: A Report from the PsA Workshop at OMERACT 2016.

    PubMed

    Orbai, Ana-Maria; de Wit, Maarten; Mease, Philip J; Callis Duffin, Kristina; Elmamoun, Musaab; Tillett, William; Campbell, Willemina; FitzGerald, Oliver; Gladman, Dafna D; Goel, Niti; Gossec, Laure; Hoejgaard, Pil; Leung, Ying Ying; Lindsay, Chris; Strand, Vibeke; van der Heijde, Désirée M; Shea, Bev; Christensen, Robin; Coates, Laura; Eder, Lihi; McHugh, Neil; Kalyoncu, Umut; Steinkoenig, Ingrid; Ogdie, Alexis

    2017-10-01

    To include the patient perspective in accordance with the Outcome Measures in Rheumatology (OMERACT) Filter 2.0 in the updated Psoriatic Arthritis (PsA) Core Domain Set for randomized controlled trials (RCT) and longitudinal observational studies (LOS). At OMERACT 2016, research conducted to update the PsA Core Domain Set was presented and discussed in breakout groups. The updated PsA Core Domain Set was voted on and endorsed by OMERACT participants. We conducted a systematic literature review of domains measured in PsA RCT and LOS, and identified 24 domains. We conducted 24 focus groups with 130 patients from 7 countries representing 5 continents to identify patient domains. We achieved consensus through 2 rounds of separate surveys with 50 patients and 75 physicians, and a nominal group technique meeting with 12 patients and 12 physicians. We conducted a workshop and breakout groups at OMERACT 2016 in which findings were presented and discussed. The updated PsA Core Domain Set endorsed with 90% agreement by OMERACT 2016 participants included musculoskeletal disease activity, skin disease activity, fatigue, pain, patient's global assessment, physical function, health-related quality of life, and systemic inflammation, which were recommended for all RCT and LOS. These were important, but not required in all RCT and LOS: economic cost, emotional well-being, participation, and structural damage. Independence, sleep, stiffness, and treatment burden were on the research agenda. The updated PsA Core Domain Set was endorsed at OMERACT 2016. Next steps for the PsA working group include evaluation of PsA outcome measures and development of a PsA Core Outcome Measurement Set.

  19. Losing the Dark: A Planetarium PSA about Light Pollution

    NASA Astrophysics Data System (ADS)

    Petersen, Carolyn Collins; Walker, Constance

    2015-03-01

    Losing the Dark is a six-minute PSA video created for fulldome theaters by Loch Ness Productions, the International Dark Sky Association Education Committee headed by Dr. Constance Walker of the National Optical Astronomy Observatories, Dome3, Adler Planetarium, and Babak Tafreshi (The World at Night). It explains light pollution, its effects, and ways to implement ``wise lighting`` practices to mitigate light pollution. The show is also made in flat-screen HD format for classical planetariums, non-dome theaters, and for presentatons by IDA speakers.

  20. An association between preoperative anemia and decreased survival in early-stage non-small-cell lung cancer patients treated with surgery alone

    SciTech Connect

    Yovino, Susannah; Kwok, Young; Krasna, Mark

    2005-08-01

    decreased overall survival in the anemic patients (2-year OS of 65.6% vs. 90.9%, p = 0.07). For Stage II patients (n = 10), the 2-year RFS and OS were 60.0% and 66.7%. In the Cox multivariate regression analysis, the only factor that achieved statistical significance was preoperative Hgb, with patients with Hgb <12 mg/dL having decreased RFS (RR 4.1, p = 0.020) and OS (RR 2.9, p = 0.026). There was a trend toward worse RFS (p = 0.056) and OS (p = 0.068) in p53-negative patients (n = 39). Stage, histologic type, type of surgery performed, age, and sex did not affect outcome. Conclusions: In our cohort of mostly Stage I NSCLC patients treated with surgery only, preoperative Hgb <12 mg/dL predicted for worse outcome. This effect was observed even in the traditionally low-risk subgroup of completely resected stage IA patients. Much has been written in the literature about anemia causing possible worsening of tumor hypoxia within solid tumors, thereby increasing radio-resistance. This has been a popular argument to explain poorer outcomes of anemic patients with solid tumors who undergo radiotherapy. However, our data suggest that anemia may be a sign of a more aggressive tumor that is at an increased risk of failure independent of the treatment modality.« less

  1. Diet supplementation during early lactation with non-alcoholic beer increases the antioxidant properties of breastmilk and decreases the oxidative damage in breastfeeding mothers.

    PubMed

    Codoñer-Franch, Pilar; Hernández-Aguilar, María T; Navarro-Ruiz, Almudena; López-Jaén, Ana B; Borja-Herrero, Cintia; Valls-Bellés, Victoria

    2013-04-01

    After delivery and birth, mothers and neonates are exposed to oxidative stress. We tested whether supplementing the diet of breastfeeding mothers with non-alcoholic beer, a product rich in antioxidants, could improve their oxidative status and the antioxidant content of their milk. A prospective trial begun on Day 2 postpartum was conducted in mother-infant dyads. Sixty breastfeeding mothers and their infants were allocated to either a control group (n=30) on a free diet or a study group (n=30) on a free diet supplemented with 660 mL of non-alcoholic beer/day. The oxidative status of the mothers' breastmilk, plasma, and urine and the infant's urine was analyzed on Days 2 and 30 postpartum. The before-after difference was compared within and between the groups. The increase in antioxidant capacity and coenzyme Q10 content in the breastmilk of the study group at Day 30 was higher than in that of the control group (p<0.001). There was also a change in the oxidative status of the mothers' plasma in the supplemented group regarding the control group; higher values of total antioxidant capacity (p<0.05) and lower levels of 8-hydroxydeoxyguanosine (p<0.05), indicative of DNA oxidative damage, were found. These results indicate a positive effect of non-alcoholic beer supplementation on oxidative stress in mothers. However, no difference in oxidant markers was found in the infant's urine. The consumption of non-alcoholic beer appears to enhance the antioxidant capacity of breastmilk and decrease oxidative damage in breastfeeding mothers.

  2. Impact of Prostate-specific Antigen (PSA) Screening Trials and Revised PSA Screening Guidelines on Rates of Prostate Biopsy and Postbiopsy Complications.

    PubMed

    Gershman, Boris; Van Houten, Holly K; Herrin, Jeph; Moreira, Daniel M; Kim, Simon P; Shah, Nilay D; Karnes, R Jeffrey

    2017-01-01

    Prostate biopsy and postbiopsy complications represent important risks of prostate-specific antigen (PSA) screening. Although landmark randomized trials and updated guidelines have challenged routine PSA screening, it is unclear whether these publications have affected rates of biopsy or postbiopsy complications. To evaluate whether publication of the 2008 and 2012 US Preventive Services Task Force (USPSTF) recommendations, the 2009 European Randomized Study of Screening for Prostate Cancer and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, or the 2013 American Urological Association (AUA) guidelines was associated with changes in rates of biopsy or postbiopsy complications, and to identify predictors of postbiopsy complications. This quasiexperimental study used administrative claims of 5279315 commercially insured US men aged ≥40 yr from 2005 to 2014, of whom 104584 underwent biopsy. Publications on PSA screening. Interrupted time-series analysis was used to evaluate the association of publications with rates of biopsy and 30-d complications. Logistic regression was performed to identify predictors of complications. From 2005 to 2014, biopsy rates fell 33% from 64.1 to 42.8 per 100000 person-months, with immediate reductions following the 2008 USPSTF recommendations (-10.1; 95% confidence interval [CI], -17.1 to -3.0; p<0.001), 2012 USPSTF recommendations (-13.8; 95% CI, -21.0 to -6.7; p<0 .001), and 2013 AUA guidelines (-8.8; 95% CI, -16.7 to -0.92; p=0.03). Concurrently, complication rates decreased 10% from 8.7 to 7.8 per 100000 person-months, with a reduction following the 2012 USPSTF recommendations (-2.5; 95% CI, -4.5 to -0.45; p=0.02). However, the proportion of men undergoing biopsy who experienced complications increased from 14% to 18%, driven by nonsepsis infectious complications (p<0.001). Predictors of complications included prior fluoroquinolone use (odds ratio [OR]: 1.27; 95% CI, 1.22-1.32; p<0.001), anticoagulant use (OR: 1

  3. Stability and accuracy of total and free PSA values in samples stored at room temperature.

    PubMed

    Forde, J C; Blake, O; Crowley, V E; Lynch, T H

    2016-11-01

    In 2010, an estimated 476,076 total PSA tests were performed in Ireland, at a cost of €3.6 million with the majority ordered by general practitioners. We aimed to replicate storage conditions at room temperature and see if prolonged storage affected total and free PSA values. Blood samples were taken from 20 male patients in four VACUETTE ® Serum Separator tubes (Greiner-Bio-One, Austria) and stored at room temperature (22 °C) for different time intervals (4, 8, 24, 48 h) before being centrifuged and analyzed. Total PSA (tPSA) and free PSA (fPSA) values were determined using the Tosoh AIA 1800 assay (Tokyo, Japan). Mean tPSA values were measured at 4, 8, 24 and 48 h with values of 7.9, 8.1, 7.8 and 8.0 μg/L, respectively. Values ranged from -1.26 to +2.53 % compared to the initial 4 h interval reading, indicating tPSA remained consistent at room temperature. The tPSA showed no significance between groups (ANOVA, p = 0.283). Mean fPSA values at 4, 8, 24 and 48 h were 2.05, 2.04, 1.83, 1.82 μg/L, respectively. At 24 and 48 h there was 10.73 and 11.22 % reduction, respectively, in fPSA compared to the 4-h time interval, indicating prolonged storage resulted in reduced fPSA values. After 24 h, there was an 8.8 % reduction in the free/total PSA %. The fPSA showed significant differences between groups (ANOVA, p = 0.024). Our recommendation is that samples that have been stored for prolonged amounts of time (greater than 24 h) should not be used for free PSA testing.

  4. Immune Impact Induced by PROSTVAC (PSA-TRICOM), a Therapeutic Vaccine for Prostate Cancer

    PubMed Central

    Gulley, James L.; Madan, Ravi A.; Tsang, Kwong Y.; Jochems, Caroline; Marté, Jennifer L.; Farsaci, Benedetto; Tucker, Jo A.; Hodge, James W.; Liewehr, David J.; Steinberg, Seth M.; Heery, Christopher R.; Schlom, Jeffrey

    2013-01-01

    PSA-TRICOM (PROSTVAC) is a novel vector-based vaccine designed to generate a robust immune response against prostate-specific antigen (PSA)–expressing tumor cells. The purpose of this report is to present an overview of both published studies and new data in the evaluation of immune responses to the PSA-TRICOM vaccine platform, currently in phase III testing. Of 104 patients tested for T-cell responses, 57% (59/104) demonstrated a ≥ 2-fold increase in PSA-specific T cells 4 weeks after vaccine (median 5-fold increase) compared with pre-vaccine, and 68% (19/28) of patients tested mounted post-vaccine immune responses to tumor-associated antigens not present in the vaccine (antigen-spreading). The PSA-specific immune responses observed 28 days after vaccine (i.e., likely memory cells) are quantitatively similar to the levels of circulating T cells specific for influenza seen in the same patients. Measurements of systemic immune response to PSA may underestimate the true therapeutic immune response (as this does not account for cells that have trafficked to the tumor) and does not include antigen-spreading. Furthermore, while the entire PSA gene is the vaccine, only one epitope of PSA is evaluated in the T-cell responses. Since this therapeutic vaccine is directed at generating a cellular/Th1 immune response (T-cell costimulatory molecules and use of a viral vector), it is not surprising that < 0.6% of patients (2/349) tested have evidence of PSA antibody-induction following vaccine. This suggests that post-vaccine PSA kinetics were not affected by PSA antibodies. An ongoing phase III study will evaluate the systemic immune responses and correlation with clinical outcomes. PMID:24778277

  5. PSA-stratified detection rates for [68Ga]THP-PSMA, a novel probe for rapid kit-based 68Ga-labeling and PET imaging, in patients with biochemical recurrence after primary therapy for prostate cancer.

    PubMed

    Derlin, Thorsten; Schmuck, Sebastian; Juhl, Cathleen; Zörgiebel, Johanna; Schneefeld, Sophie M; Walte, Almut C A; Hueper, Katja; von Klot, Christoph A; Henkenberens, Christoph; Christiansen, Hans; Thackeray, James T; Ross, Tobias L; Bengel, Frank M

    2018-06-01

    [ 68 Ga]Tris(hydroxypyridinone)(THP)-PSMA is a novel radiopharmaceutical for one-step kit-based radiolabelling, based on direct chelation of 68 Ga 3+ at low concentration, room temperature and over a wide pH range, using direct elution from a 68 Ge/ 68 Ga-generator. We evaluated the clinical detection rates of [ 68 Ga]THP-PSMA PET/CT in patients with biochemically recurrent prostate cancer after prostatectomy. Consecutive patients (n=99) referred for evaluation of biochemical relapse of prostate cancer by [ 68 Ga]THP-PSMA PET/CT were analyzed retrospectively. Patients underwent a standard whole-body PET/CT (1 h p.i.), followed by delayed (3 h p.i.) imaging of the abdomen. PSA-stratified cohorts of positive PET/CT results, standardized uptake values (SUVs) and target-to-background ratios (TBRs) were analyzed, and compared between standard and delayed imaging. At least one lesion suggestive of recurrent or metastatic prostate cancer was identified on PET images in 52 patients (52.5%). Detection rates of [ 68 Ga]THP-PSMA PET/CT increased with increasing PSA level: 94.1% for a PSA value of ≥10 ng/mL, 77.3% for a PSA value of 2 to <10 ng/mL, 54.5% for a PSA value of 1 to <2 ng/mL, 14.3% for a PSA value of 0.5 to <1 ng/mL, 20.0% for a PSA value of >0.2 to <0.5, and 22.2% for a PSA value of 0.01 to 0.2 ng/mL. [ 68 Ga]THP-PSMA uptake (SUVs) in metastases decreased over time, whereas TBRs improved. Delayed imaging at 3 h p.i. exclusively identified pathologic findings in 2% of [ 68 Ga]THP-PSMA PET/CT scans. Detection rate was higher in patients with a Gleason score ≥8 (P=0.02) and in patients receiving androgen deprivation therapy (P=0.003). In this study, [ 68 Ga]THP-PSMA PET/CT showed suitable detection rates in patients with biochemical recurrence of prostate cancer and PSA levels ≥ 2 ng /mL. Detections rates were lower than in previous studies evaluating other PSMA ligands, though prospective direct radiotracer comparison studies are mandatory particularly in

  6. Evaluation of PSA-age volume score in predicting prostate cancer in Chinese populationArticle Subject.

    PubMed

    Wu, Yi-Shuo; Wu, Xiao-Bo; Zhang, Ning; Jiang, Guang-Liang; Yu, Yang; Tong, Shi-Jun; Jiang, Hao-Wen; Mao, Shan-Hua; Na, Rong; Ding, Qiang

    2018-02-06

    This study was performed to evaluate prostate-specific antigen-age volume (PSA-AV) scores in predicting prostate cancer (PCa) in a Chinese biopsy population. A total of 2355 men who underwent initial prostate biopsy from January 2006 to November 2015 in Huashan Hospital were recruited in the current study. The PSA-AV scores were calculated and assessed together with PSA and PSA density (PSAD) retrospectively. Among 2133 patients included in the analysis, 947 (44.4%) were diagnosed with PCa. The mean age, PSA, and positive rates of digital rectal examination result and transrectal ultrasound result were statistically higher in men diagnosed with PCa (all P < 0.05). The values of area under the receiver operating characteristic curves (AUCs) of PSAD and PSA-AV were 0.864 and 0.851, respectively, in predicting PCa in the entire population, both performed better than PSA (AUC = 0.805; P < 0.05). The superiority of PSAD and PSA-AV was more obvious in subgroup with PSA ranging from 2.0 ng ml-1 to 20.0 ng ml-1. A PSA-AV score of 400 had a sensitivity and specificity of 93.7% and 40.0%, respectively. In conclusion, the PSA-AV score performed equally with PSAD and was better than PSA in predicting PCa. This indicated that PSA-AV score could be a useful tool for predicting PCa in Chinese population.

  7. Interoperability In The New Planetary Science Archive (PSA)

    NASA Astrophysics Data System (ADS)

    Rios, C.; Barbarisi, I.; Docasal, R.; Macfarlane, A. J.; Gonzalez, J.; Arviset, C.; Grotheer, E.; Besse, S.; Martinez, S.; Heather, D.; De Marchi, G.; Lim, T.; Fraga, D.; Barthelemy, M.

    2015-12-01

    As the world becomes increasingly interconnected, there is a greater need to provide interoperability with software and applications that are commonly being used globally. For this purpose, the development of the new Planetary Science Archive (PSA), by the European Space Astronomy Centre (ESAC) Science Data Centre (ESDC), is focused on building a modern science archive that takes into account internationally recognised standards in order to provide access to the archive through tools from third parties, for example by the NASA Planetary Data System (PDS), the VESPA project from the Virtual Observatory of Paris as well as other international institutions. The protocols and standards currently being supported by the new Planetary Science Archive at this time are the Planetary Data Access Protocol (PDAP), the EuroPlanet-Table Access Protocol (EPN-TAP) and Open Geospatial Consortium (OGC) standards. The architecture of the PSA consists of a Geoserver (an open-source map server), the goal of which is to support use cases such as the distribution of search results, sharing and processing data through a OGC Web Feature Service (WFS) and a Web Map Service (WMS). This server also allows the retrieval of requested information in several standard output formats like Keyhole Markup Language (KML), Geography Markup Language (GML), shapefile, JavaScript Object Notation (JSON) and Comma Separated Values (CSV), among others. The provision of these various output formats enables end-users to be able to transfer retrieved data into popular applications such as Google Mars and NASA World Wind.

  8. PET/CT with (18)F-choline after radical prostatectomy in patients with PSA ≤2 ng/ml. Can PSA velocity and PSA doubling time help in patient selection?

    PubMed

    Chiaravalloti, Agostino; Di Biagio, Daniele; Tavolozza, Mario; Calabria, Ferdinando; Schillaci, Orazio

    2016-07-01

    To investigate the performance of (18)F-fluorocholine ((18)F-FCH) PET/CT in relation to the prostate-specific antigen (PSA) kinetic indexes, PSA doubling time (PSAdt) and PSA velocity (PSAve), in detecting recurrent prostate cancer (PC) in a selected population of patients treated with radical prostatectomy and with PSA ≤2 ng/ml. The study group comprised 79 patients (mean age 70 ± 7 years, range 58 - 77 years) who had been treated with radical surgery 30 to 90 months previously and with biochemical failure (defined as a measurable serum PSA level) who were evaluated with (18)F-FCH PET/CT. In order to establish the optimal threshold for PSAdt and PSAve, the diagnostic performance of PSA, PSAdt and PSAve were compared by receiver operating characteristic analysis. In the population examined, PSA (mean ± SD) was 1.37 ± 0.44 ng/ml (range 0.21 - 2 ng/ml) before PET/CT examination, PSAdt was 10.04 ± 16.67 months and PSAve was 2.75 ± 3.11 ng/ml per year. (18)F-FCH PET/CT was positive in 44 patients (55 %). PSAve and PSAdt were significantly different between patients with a positive and a negative (18)F-FCH PET/CT scan. Thresholds of 6 months for PSAdt and 1 ng/ml per year for PSAve were selected. For PSAdt ≤6 months the detection rate (DR) was 65 %, and for PSAve >1 ng/ml per year the DR was 67 %. PSA values were not significantly different between patients with a positive and a negative PET/CT scan. The results of our study suggest that (18)F-FCH PET/CT could be considered for the evaluation of patients with biochemical recurrence of PC and with low PSA levels. Fast PSA kinetics could be useful in the selection of these patients.

  9. Alcohol consumption and PSA-detected prostate cancer risk—A case-control nested in the ProtecT study

    PubMed Central

    Zuccolo, Luisa; Lewis, Sarah J; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E; Smith, George Davey

    2013-01-01

    Alcohol is an established carcinogen but not an established risk factor for prostate cancer, despite some recent prospective studies suggesting increased risk among heavy drinkers. The aim of this study was to investigate the role of alcohol on prostate-specific antigen (PSA) levels and prostate cancer risk. Two thousand four hundred PSA detected prostate cancer cases and 12,700 controls matched on age and general practice were identified through a case-control study nested in the PSA-testing phase of a large UK-based randomized controlled trial for prostate cancer treatment (ProtecT). Linear and multinomial logistic regression models were used to estimate ratios of geometric means (RGMs) of PSA and relative risk ratios (RRRs) of prostate cancer by stage and grade, with 95% confidence intervals (CIs), associated with weekly alcohol intake and drinking patterns. We found evidence of lower PSA (RGM 0.98, 95% CI: 0.98–0.99) and decreased risk of low Gleason-grade (RRR 0.96; 95%CI 0.93–0.99) but increased risk of high-grade prostate cancer (RRR 1.04; 95%CI 0.99–1.08; pdifference=0.004) per 10 units/week increase in alcohol consumption, not explained by current BMI, blood pressure, comorbidities, or reverse causation. This is the first large population-based study to find evidence of lower PSA levels for increasing alcohol consumption, with potential public health implications for the detection of prostate cancer. Our results also support a modestly higher risk of high-grade disease for heavy drinkers, but require independent replication to establish the nature of the association of alcohol with low-grade disease, preferably in cohorts with a heterogeneous case-mix. What's new? Alcohol is not an established risk factor for prostate cancer; however, the current work suggests that heavy drinking could cause a small increase in risk of the more aggressive forms. If the results are confirmed to be causal, prostate cancer risk will be added to the many long-term health

  10. Extreme-Risk Prostate Adenocarcinoma Presenting With Prostate-Specific Antigen (PSA) >40 ng/ml: Prognostic Significance of the Preradiation PSA Nadir

    SciTech Connect

    Alexander, Abraham S.; University of British Columbia, Vancouver, British Columbia; Mydin, Aminudin

    2011-12-01

    Purpose: To examine the impact of patient, disease, and treatment characteristics on survival outcomes in patients treated with neoadjuvant androgen deprivation therapy (ADT) and radical external-beam radiotherapy (RT) for clinically localized, extreme-risk prostate adenocarcinoma with a presenting prostate-specific antigen (PSA) concentration of >40 ng/ml. Methods and Materials: A retrospective chart review was conducted of 64 patients treated at a single institution between 1991 and 2000 with ADT and RT for prostate cancer with a presenting PSA level of >40 ng/ml. The effects of patient age, tumor (presenting PSA level, Gleason score, and T stage), and treatment (total ADT duration andmore » pre-RT PSA level) characteristics on rates of biochemical disease-free survival (bDFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were examined. Results: Median follow-up time was 6.45 years (range, 0.09-15.19 years). Actuarial bDFS, PCSS, and OS rates at 5 years were 39%, 87%, and 78%, respectively, and 17%, 64%, and 45%, respectively, at 10 years. On multivariate analysis, the pre-RT PSA level ({<=}0.1 versus >0.1 ng/ml) was the single most significant prognostic factor for bDFS (p = 0.033) and OS (p = 0.018) rates, whereas age, T stage, Gleason score, and ADT duration ({<=}6 versus >6 months) were not predictive of outcomes. Conclusion: In prostate cancer patients with high presenting PSA levels, >40 ng/ml, treated with combined modality, neoadjuvant ADT, and RT, the pre-RT PSA nadir, rather than ADT duration, was significantly associated with improved survival. This observation supports the use of neoadjuvant ADT to drive PSA levels to below 0.1 ng/ml before initiation of RT, to optimize outcomes for patients with extreme-risk disease.« less

  11. Excess cases of prostate cancer and estimated overdiagnosis associated with PSA testing in East Anglia

    PubMed Central

    Pashayan, N; Powles, J; Brown, C; Duffy, S W

    2006-01-01

    This study aimed to estimate the extent of ‘overdiagnosis' of prostate cancer attributable to prostate-specific antigen (PSA) testing in the Cambridge area between 1996 and 2002. Overdiagnosis was defined conceptually as detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient's lifetime. Records of PSA tests in Addenbrookes Hospital were linked to prostate cancer registrations by NHS number. Differences in prostate cancer registration rates between those receiving and not receiving prediagnosis PSA tests were calculated. The proportion of men aged 40 years or over with a prediagnosis PSA test increased from 1.4 to 5.2% from 1996 to 2002. The rate of diagnosis of prostate cancer was 45% higher (rate ratios (RR)=1.45, 95% confidence intervals (CI) 1.02–2.07) in men with a history of prediagnosis PSA testing. Assuming average lead times of 5 to 10 years, 40–64% of the PSA-detected cases were estimated to be overdiagnosed. In East Anglia, from 1996 to 2000, a 1.6% excess of cases was associated with PSA testing (around a quarter of the 5.3% excess incidence cases observed in East Anglia from 1996 to 2000). Further quantification of the overdiagnosis will result from continued surveillance and from linkage of incidence to testing in other hospitals. PMID:16832417

  12. PSA response to cabazitaxel is associated with improved progression-free survival in metastatic castration-resistant prostate cancer: the non-interventional QoLiTime study.

    PubMed

    Hammerer, Peter; Al-Batran, Salah-Eddin; Windemuth-Kieselbach, Christine; Keller, Martin; Hofheinz, Ralf-Dieter

    2018-03-01

    To evaluate the association between prostate-specific antigen (PSA) response and progression-free and overall survival in men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel. Men with mCRPC receiving cabazitaxel (25 mg/m 2 , every 3 weeks) plus oral prednis(ol)one (10 mg/day) were enrolled in the non-interventional, prospective QoLiTime study. Main outcome measures were progression-free survival and overall survival, in all patients and in those who showed a ≥ 50 or a ≥ 30% decrease in PSA relative to baseline after four cycles of cabazitaxel, as well as quality-of-life parameters. Of the 527 men (median age 72 years), 266 received ≥ 4 cycles of cabazitaxel and had PSA response data. After four cycles, 34.6% of men achieved a PSA decrease ≥ 50% and 49.6% a decrease ≥ 30%. Median progression-free survival was 7.7 (95% CI 6.2, 9.5) months, and overall survival was 19.5 (95% CI 16.0, 30.9) months, corresponding to 1-year event rates of 39.4 and 78.8%, respectively. Median progression-free survival was longer in PSA responders versus non-responders (15.7 vs 5.5 months at 50% cut-off; 15.7 vs 5.3 months for 30% cut-off; both P < 0.0001). Overall survival (50% cut-off) was 23.3 months in responders and 16.0 months in non-responders (P = 0.068); corresponding data at the 30% cut-off are 21.7 and 16.0 months (P = 0.057). Overall, 55.4% of men experienced ≥ 1 adverse event, 59.6% of whom had a serious adverse event. PSA response after four cycles of cabazitaxel is associated with improved progression-free survival in men with mCRPC treated with cabazitaxel plus prednis(ol)one.

  13. The influence of PSA autoantibodies in prostate cancer patients: a prospective clinical study-II.

    PubMed

    Nakajima, Kosei; Heilbrun, Lance K; Smith, Daryn; Hogan, Victor; Raz, Avraham; Heath, Elisabeth

    2017-03-14

    The U.S. Preventive Services Task Force (USPSTF) has recommended against PSA-based screening for prostate cancer due to potential possibilities of false-results. Since no alternative test is available to replace it, we have initiated a trial with the purpose of establishing whether Galectin-3 (Gal-3) serum level and/or the patients' immune response to PSA and Gal-3 antigens could complement the PSA test as diagnostic tools for prostate cancer patients. A blind, prospective, single institution, pilot study was conducted. A total of 95 men were recruited and classified into 5 different groups: healthy controls (Group1), newly diagnosed patients (Group2), no recurrence after local therapy (Group3), rising PSA after local therapy (Group4), and metastatic patients (Group5). The primary endpoints were the levels of serum PSA, PSA autoantibodies (AAPSA), Gal-3, and Gal-3 autoantibodies (AAGal-3). Data were analyzed by Spearman's rank correlation (rho) and least squares linear regression modeling. The expression levels of PSA, AAPSA, Gal-3, and AAGal-3 were determined in both healthy controls and prostate cancer patients. Negative correlations were observed between PSA and AAPSA levels among all 95 men combined (rho = -0.321, P = 0.0021; fitted slope -0.288, P = 0.0048), and in metastatic patients (rho = -0.472, P = 0.0413; fitted slope -1.145, P = 0.0061). We suggest an association between PSA and AAPSA, whereby the AAPSA may alter PSA levels. It provides a novel outlook for prostate cancer diagnosis, and should serve as a basis for an all-inclusive diagnostic trial centering on patients with metastasis.

  14. ``Losing the Dark:'' A Planetarium PSA about Light Pollution

    NASA Astrophysics Data System (ADS)

    Productions, L. N.; Walker, D. C.

    2013-04-01

    Losing the Dark is a PSA video being created for fulldome theaters by Loch Ness Productions under the direction of the International Dark Sky Association Education Committee headed by Dr. Constance Walker of the National Optical Astronomy Observatories. It explains the problems with light pollution, its effects on life, and three ways in which people can implement “wise lighting” practices to mitigate light pollution. The show is also being produced in a flat-screen HD format for use in classical planetarium and non-dome theaters, for presentations by IDA speakers when addressing planning boards, etc. and will be posted on the IDA and other web sites. The final length is six minutes for both versions. Funding has been provided by The International Planetarium Society and the International Dark-Sky Association.

  15. Hybrid membrane--PSA system for separating oxygen from air

    DOEpatents

    Staiger, Chad L [Albuquerque, NM; Vaughn, Mark R [Albuquerque, NM; Miller, A Keith [Albuquerque, NM; Cornelius, Christopher J [Blackburg, VA

    2011-01-25

    A portable, non-cryogenic, oxygen generation system capable of delivering oxygen gas at purities greater than 98% and flow rates of 15 L/min or more is described. The system consists of two major components. The first component is a high efficiency membrane capable of separating argon and a portion of the nitrogen content from air, yielding an oxygen-enriched permeate flow. This is then fed to the second component, a pressure swing adsorption (PSA) unit utilizing a commercially available, but specifically formulated zeolite compound to remove the remainder of the nitrogen from the flow. The system is a unique gas separation system that can operate at ambient temperatures, for producing high purity oxygen for various applications (medical, refining, chemical production, enhanced combustion, fuel cells, etc . . . ) and represents a significant advance compared to current technologies.

  16. FOXM1 promotes the progression of prostate cancer by regulating PSA gene transcription.

    PubMed

    Liu, Youhong; Liu, Yijun; Yuan, Bowen; Yin, Linglong; Peng, Yuchong; Yu, Xiaohui; Zhou, Weibing; Gong, Zhicheng; Liu, Jianye; He, Leye; Li, Xiong

    2017-03-07

    Androgen/AR is the primary contributor to prostate cancer (PCa) progression by regulating Prostate Specific Antigen (PSA) gene transcription. The disease inevitably evolves to androgen-independent (AI) status. Other mechanisms by which PSA is regulated and develops to AI have not yet been fully determined. FOXM1 is a cell proliferation-specific transcription factor highly expressed in PCa cells compared to non-malignant prostate epithelial cells, suggesting that the aberrant overexpression of FOXM1 contributes to PCa development. In addition to regulating AR gene transcription and cell cycle-regulatory genes, FOXM1 selectively regulates the gene transcription of KLK2 and PSA, typical androgen responsive genes. Screening the potential FOXM1-binding sites by ChIP-PCR, we found that FOXM1 directly binds to the FHK binding motifs in the PSA promoter/enhancer regions. AI C4-2 cells have more FOXM1 binding sites than androgen dependent LNCaP cells. The depletion of FOXM1 by small molecular inhibitors significantly improves the suppression of PSA gene transcription by the anti-AR agent Cadosax. This is the first report showing that FOXM1 promotes PCa progression by regulating PSA gene transcription, particularly in AI PCa cells. The combination of anti-AR agents and FOXM1 inhibitors has the potential to greatly improve therapy for late-stage PCa patients by suppressing PSA levels.

  17. Clinical performance of serum prostate-specific antigen isoform [-2]proPSA (p2PSA) and its derivatives, %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer: results from a multicentre European study, the PROMEtheuS project.

    PubMed

    Lazzeri, Massimo; Haese, Alexander; Abrate, Alberto; de la Taille, Alexandre; Redorta, Joan Palou; McNicholas, Thomas; Lughezzani, Giovanni; Lista, Giuliana; Larcher, Alessandro; Bini, Vittorio; Cestari, Andrea; Buffi, Nicolòmaria; Graefen, Markus; Bosset, Olivier; Le Corvoisier, Philippe; Breda, Alberto; de la Torre, Pablo; Fowler, Linda; Roux, Jacques; Guazzoni, Giorgio

    2013-08-01

    To test the sensitivity, specificity and accuracy of serum prostate-specific antigen isoform [-2]proPSA (p2PSA), %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer (PCa) undergoing prostate biopsy for suspected PCa. To evaluate the potential reduction in unnecessary biopsies and the characteristics of potentially missed cases of PCa that would result from using serum p2PSA, %p2PSA and PHI. The analysis consisted of a nested case-control study from the PRO-PSA Multicentric European Study, the PROMEtheuS project. All patients had a first-degree relative (father, brother, son) with PCa. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis. Of the 1026 patients included in the PROMEtheuS cohort, 158 (15.4%) had a first-degree relative with PCa. p2PSA, %p2PSA and PHI values were significantly higher (P < 0.001), and free/total PSA (%fPSA) values significantly lower (P < 0.001) in the 71 patients with PCa (44.9%) than in patients without PCa. Univariable accuracy analysis showed %p2PSA (area under the receiver-operating characteristic curve [AUC]: 0.733) and PHI (AUC: 0.733) to be the most accurate predictors of PCa at biopsy, significantly outperforming total PSA ([tPSA] AUC: 0.549), free PSA ([fPSA] AUC: 0.489) and %fPSA (AUC: 0.600) (P ≤ 0.001). For %p2PSA a threshold of 1.66 was found to have the best balance between sensitivity and specificity (70.4 and 70.1%; 95% confidence interval [CI]: 58.4-80.7 and 59.4-79.5 respectively). A PHI threshold of 40 was found to have the best balance between sensitivity and specificity (64.8 and 71.3%, respectively; 95% CI 52.5-75.8 and 60.6-80.5). At 90% sensitivity, the thresholds for %p2PSA and PHI were 1.20 and 25.5, with a specificity of 37.9 and 25.5%, respectively. At a %p2PSA threshold of 1.20, a total of 39 (24.8%) biopsies could have been avoided, but two cancers with a Gleason score (GS) of 7 would have been missed

  18. The inverse relationship between prostate-specific antigen (PSA) and obesity.

    PubMed

    Aref, Adel; Vincent, Andrew D; O'Callaghan, Michael; Martin, Sean; Sutherland, Peter; Hoy, Andrew; Butler, Lisa M; Wittert, Gary

    2018-06-25

    Obese men have lower serum prostate-specific antigen (PSA) than comparably aged lean men, but the underlying mechanism remains unclear. The aim of this study was to determine the effect of obesity on PSA and the potential contributing mechanisms. A cohort of 1195 men aged 35 years and over at recruitment, with demographic, anthropometric (body mass index (BMI), waist circumference (WC)) and serum hormone (serum testosterone (T), estradiol (E2)), PSA and hematology assessments obtained over two waves was assessed. Men with a history of prostate cancer or missing PSA were excluded, leaving 970 men for the final analysis. Mixed-effects regressions and mediation analyses adjusting for hormonal and volumetric factors explore the potential mechanisms relating obesity to PSA. After adjusting for age, PSA levels were lower in men with greater WC (p=0.001). In a multivariable model including WC, age, E2/T and PlasV as predictors, no statistically significant associations were observed between with PSA and either WC (p=0.36) or PlasV (p=0.49), while strong associations were observed with both E2/T (p<0.001) and age (p<0.001). In the mediation analyses with PlasV as the mediator, the average causal mediation effect (ACME) explained roughly 0.2 of the total effect of WC on PSA (p=0.31), while when E2/T is a mediator; the ACME explained roughly 0.5 of the effect (p<0.001). Our findings indicate that lower PSA levels in obese men, as compared to normal weight men, can be explained both by hormonal changes (elevated E2/T ratio) and haemodilution. Hormonal factors therefore represent a substantial but underappreciated mediating pathway.

  19. Real-life experience of using conventional disease-modifying anti-rheumatic drugs (DMARDs) in psoriatic arthritis (PsA). Retrospective analysis of the efficacy of methotrexate, sulfasalazine, and leflunomide in PsA in comparison to spondyloarthritides other than PsA and literature review of the use of conventional DMARDs in PsA

    PubMed Central

    Roussou, Euthalia; Bouraoui, Aicha

    2017-01-01

    Objective With the aim of assessing the response to treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs) used in patients with psoriatic arthritis (PsA), data on methotrexate, sulfasalazine (SSZ), and leflunomide were analyzed from baseline and subsequent follow-up (FU) questionnaires completed by patients with either PsA or other spondyloarthritides (SpAs). Material and Methods A single-center real-life retrospective analysis was performed by obtaining clinical data via questionnaires administered before and after treatment. The indices used were erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Function Index (BASFI), wellbeing (WB), and treatment effect (TxE). The indices measured at baseline were compared with those measured on one occasion in a FU visit at least 1 year later. Results A total of 73 patients, 51 with PsA (mean age 49.8±12.8 years; male-to-female ratio [M:F]=18:33) and 22 with other SpAs (mean age 50.6±16 years; M:F=2:20), were studied. BASDAI, BASFI, and WB displayed consistent improvements during FU assessments in both PsA patients and controls in comparison to baseline values. SSZ exhibited better efficacy as confirmed by TxE in both PsA patients and controls. ESR and CRP displayed no differences in either the PsA or the SpA group between the cases before and after treatment. Conclusion Real-life retrospective analysis of three DMARDs used in PsA (and SpAs other than PsA) demonstrated that all three DMARDs that were used brought about improvements in BASDAI, BASFI, TxE, and WB. However, the greatest improvements at FU were seen with SSZ use in both PsA and control cohorts. PMID:28293446

  20. PSA doubling time of prostate carcinoma managed with watchful observation alone.

    PubMed

    Choo, R; DeBoer, G; Klotz, L; Danjoux, C; Morton, G C; Rakovitch, E; Fleshner, N; Bunting, P; Kapusta, L; Hruby, G

    2001-07-01

    To study prostate-specific antigen (PSA) doubling time of untreated, favorable grade, prostate carcinoma. A prospective single-arm cohort study has been in progress to assess the feasibility of a watchful observation protocol with selective delayed intervention using clinical, histologic, or PSA progression as treatment indication in untreated, localized, favorable grade prostate adenocarcinoma (T1b-T2bN0 M0, Gleason Score < or = 7, and PSA < or = 15 ng/mL). Patients are conservatively managed with watchful observation alone, as long as they do not meet the arbitrarily defined disease progression criteria. Patients are followed regularly and undergo blood tests including PSA at each visit. PSA doubling time (Td) is estimated from a linear regression of ln(PSA) on time, assuming a simple exponential growth model. As of March 2000, 134 patients have been on the study for a minimum of 12 months (median, 24; range, 12-52) and have a median frequency of PSA measurement of 7 times (range, 3-15). Median age is 70 years. Median PSA at enrollment is 6.3 (range, 0.5-14.6). The distribution of Td is as follows: <2 years, 19 patients; 2-5 years, 46; 5-10 years, 25; 10-20 years, 11; 20-50 years, 6; > 50 years, 27. The median Td is 5.1 years. In 44 patients (33%), Td is greater than 10 years. There was no correlation between Td and patient age, clinical T stage, Gleason score, or initial PSA level. Td of untreated prostate cancer varies widely. In our cohort, 33% have Td > 10 years. Td may be a useful tool to guide treatment intervention for patients managed conservatively with watchful observation alone.

  1. Incorporating Known Genetic Variants Does Not Improve the Accuracy of PSA Testing to Identify High Risk Prostate Cancer on Biopsy

    PubMed Central

    Gilbert, Rebecca; Martin, Richard M.; Evans, David M.; Tilling, Kate; Davey Smith, George; Kemp, John P.; Lane, J. Athene; Hamdy, Freddie C.; Neal, David E.; Donovan, Jenny L.; Metcalfe, Chris

    2015-01-01

    Introduction Prostate-specific antigen (PSA) testing is a widely accepted screening method for prostate cancer, but with low specificity at thresholds giving good sensitivity. Previous research identified four single nucleotide polymorphisms (SNPs) principally associated with circulating PSA levels rather than with prostate cancer risk (TERT rs2736098, FGFR2 rs10788160, TBX3 rs11067228, KLK3 rs17632542). Removing the genetic contribution to PSA levels may improve the ability of the remaining biologically-determined variation in PSA to discriminate between high and low risk of progression within men with identified prostate cancer. We investigate whether incorporating information on the PSA-SNPs improves the discrimination achieved by a single PSA threshold in men with raised PSA levels. Materials and Methods Men with PSA between 3-10ng/mL and histologically-confirmed prostate cancer were categorised as high or low risk of progression (Low risk: Gleason score≤6 and stage T1-T2a; High risk: Gleason score 7–10 or stage T2C). We used the combined genetic effect of the four PSA-SNPs to calculate a genetically corrected PSA risk score. We calculated the Area under the Curve (AUC) to determine how well genetically corrected PSA risk scores distinguished men at high risk of progression from low risk men. Results The analysis includes 868 men with prostate cancer (Low risk: 684 (78.8%); High risk: 184 (21.2%)). Receiver operating characteristic (ROC) curves indicate that including the 4 PSA-SNPs does not improve the performance of measured PSA as a screening tool for high/low risk prostate cancer (measured PSA level AU C = 59.5% (95% CI: 54.7,64.2) vs additionally including information from the 4 PSA-SNPs AUC = 59.8% (95% CI: 55.2,64.5) (p-value = 0.40)). Conclusion We demonstrate that genetically correcting PSA for the combined genetic effect of four PSA-SNPs, did not improve discrimination between high and low risk prostate cancer in men with raised PSA levels (3-10ng

  2. The role of IGF-1 and the distribution of body fat in decreasing the number of prostate rebiopsies.

    PubMed

    Morán, E; Martínez, M; Budía, A; Broseta, E; Cámara, R; Boronat, F

    2017-03-01

    To assess the usefulness of IGF-1 and internal organ fat measured by bioelectrical impedance audiometry to avoid rebiopsies in patients with persistently high prostate-specific antigen (PSA) levels. A prospective study was conducted with 92 patients who underwent prostate rebiopsy due to high PSA levels with negative results in the rectal examination and a lack of preneoplastic lesions. The patients previously had their IGF-1 levels measured and had undergone an impedance audiometry test using the abdominal Fat Analyser AB-140 TANITA system. We calculated the receiver operating characteristic (ROC) curves for the PSA levels, %PSA, internal organ fat and IGF-1 and PSA density. Twenty-five patients were diagnosed with prostate cancer. These patients had significantly higher PSA, PSAd and IGF-1 values and a tendency towards higher internal organ fat levels and lower %PSA readings (p=.001, p=.003, p=.001, p=.24 and P=0.28, respectively). The ROC curve showed an area under the curve for IGF-1 and PSA of .82 and .81, respectively. Using the cutoff points for 95% sensitivity and using the 3 criteria as an indication of rebiopsy, 74% of the biopsies would have been spared, leaving undiagnosed only 1 patient with clinically significant cancer -Gleason score>7 (4+3)-. The positive and negative predictive values for the set of variables were higher than for each one separately (PPV: 66/NPV: 63). The cost of both determinations was 82 euros. Our results suggest that measuring IGF-1 could significantly decrease the number of unnecessary rebiopsies in an inexpensive and safe manner. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. PSA predicts development of incident lower urinary tract symptoms: results from the REDUCE study.

    PubMed

    Patel, Devin N; Feng, Tom; Simon, Ross M; Howard, Lauren E; Vidal, Adriana C; Moreira, Daniel M; Castro-Santamaria, Ramiro; Roehrborn, Claus; Andriole, Gerald L; Freedland, Stephen J

    2018-05-23

    The relationship between baseline prostate-specific antigen (PSA) and development of lower urinary tract symptoms (LUTS) in asymptomatic and mildly symptomatic men is unclear. We sought to determine if PSA predicts incident LUTS in these men. A post-hoc analysis of the 4-year REDUCE study was performed to assess for incident LUTS in 1534 men with mild to no LUTS at baseline. The primary aim was to determine whether PSA independently predicted incident LUTS after adjusting for the key clinical variables of age, prostate size, and baseline International prostate symptom score (IPSS). Incident LUTS was defined as the first report of medical treatment, surgery, or sustained clinically significant symptoms (two IPSS >14). Cox proportional hazards, cumulative incidence curves, and the log-rank test were used to test our hypothesis. A total of 1534 men with baseline IPSS <8 were included in the study cohort. At baseline, there were 335 men with PSA 2.5-4 ng/mL, 589 with PSA 4.1-6 ng/mL, and 610 with PSA 6-10 ng/mL. During the 4-year study, 196 men progressed to incident LUTS (50.5% medical treatment, 9% surgery, and 40.5% new symptoms). As a continuous variable, higher PSA was associated with increased incident LUTS on univariable (HR 1.09, p = 0.019) and multivariable (HR 1.08, p = 0.040) analysis. Likewise, baseline PSA 6-10 ng/mL was associated with increased incident LUTS vs. PSA 2.5-4 ng/mL in adjusted models (HR 1.68, p = 0.016). This association was also observed in men with PSA 4.1-6 ng/mL vs. PSA 2.5-4 ng/mL (HR 1.60, p = 0.032). Men with mild to no LUTS but increased baseline PSA are at increased risk of developing incident LUTS presumed due to benign prostatic hyperplasia.

  4. Prospective validation of %p2PSA and the Prostate Health Index, in prostate cancer detection in initial prostate biopsies of Asian men, with total PSA 4-10 ng ml-1.

    PubMed

    Tan, Lincoln Gl; Tan, Yung Khan; Tai, Bee Choo; Tan, Karen Ml; Gauhar, Vineet; Tiong, Ho Yee; Hawkins, Robert Cw; Thamboo, Thomas P; Hong, Felicia Sk; Chiong, Edmund

    2017-01-01

    Despite its widespread use for prostate cancer screening, low specificity makes PSA a suboptimal biomarker, especially in the diagnostic "gray zone" of 4-10 ng ml-1 . False-positives lead to unnecessary biopsies with attendant morbidities. This is the first prospective validation study of %p2PSA and the Prostate Health Index (PHI) in Asian men presenting with a total PSA between 4.0 and 10 ng ml-1 . We studied 157 Asian men between 50 and 75 years old, with normal per rectal prostate examinations, undergoing their first prostate biopsy, using a standardized biopsy protocol, for PSA levels of 4-10 ng ml-1 . Thirty (19.1%) were found to have prostate cancer on biopsy. Statistically significant differences between patients with and without prostate cancer were found for total PSA, p2PSA, %p2PSA, and PHI. The areas under the curve of the receiver operating characteristic curve for total PSA, %fPSA, %p2PSA, and PHI were 0.479, 0.420, 0.695, and 0.794, respectively. PHI predicts prostatic biopsies results best. At a sensitivity of 90%, the specificity (95% CI) of PHI was 58.3%, more than triple the specificity of total PSA at 17.3%, potentially avoiding 77 (49%) unnecessary biopsies. Similar to studies in mainly Caucasian populations, we have prospectively shown that %p2PSA and PHI greatly outperform total and free to total PSA ratio, in the detection of prostate cancer at first biopsy. Higher PHI levels also correspond to increasing the risk of detecting GS ≥7 cancers. We have validated the use of PHI to aid decision-making regarding prostate biopsies in Asian men with serum PSA between 4 and 10 ng ml-1 .

  5. Age-Specific Cutoff Value for the Application of Percent Free Prostate-Specific Antigen (PSA) in Chinese Men with Serum PSA Levels of 4.0–10.0 ng/ml

    PubMed Central

    Xie, Liping; He, Dalin; Zhou, Liqun; Xu, Chuanliang; Gao, Xu; Ren, Shancheng; Wang, Fubo; Ma, Lulin; Wei, Qiang; Yin, Changjun; Tian, Ye; Sun, Zhongquan; Fu, Qiang; Ding, Qiang; Zheng, Junhua; Ye, Zhangqun; Ye, Dingwei; Xu, Danfeng; Hou, Jianquan; Xu, Kexin; Yuan, Jianlin; Gao, Xin; Liu, Chunxiao; Pan, Tiejun; Sun, Yinghao

    2015-01-01

    Objective The influence of age on the performance of percent free prostate-specific antigen (%fPSA) in diagnosing prostate cancer (PCa) in East Asians is controversial. We tested the diagnostic performance of %fPSA in a multi-center biopsy cohort in China and identified the proper age-specific cutoff values to avoid unnecessary biopsies. Methods Consecutive patients with a prostate-specific antigen (PSA) level of 4.0–10.0 ng/ml or 10.1–20.0 ng/ml who underwent transrectal ultrasound-guided or transperineal prostate biopsy were enrolled from 22 Chinese medical centers from Jan 1, 2010 to Dec 31, 2013. The diagnostic accuracy of PSA and %fPSA was determined using the area under the receiver operating characteristic (ROC) curve (AUC). Age-specific cutoff values were calculated using ROC curve analysis. Results The median %fPSA was much lower in younger patients compared with older patients with a PSA level of 4.0–10.0 ng/ml or 10.1–20.0 ng/ml. The AUC of %fPSA was higher than PSA only in older patients. In patients aged 50 to 59 years, %fPSA failed to improve the diagnosis compared with PSA in these two PSA ranges. Age-specific cutoff values were 24%, 27% and 32% for patients aged 60–69, 70–79 and ≥80 years, respectively, to reduce unnecessary biopsies in men with PSA levels of 4.0–10.0 ng/ml to detect 90% of all PCa. Conclusions The effectiveness of %fPSA is correlated with age in the Chinese population. Age-specific cutoff values would help avoid unnecessary biopsies in the Chinese population. PMID:26091007

  6. Age-Specific Cutoff Value for the Application of Percent Free Prostate-Specific Antigen (PSA) in Chinese Men with Serum PSA Levels of 4.0-10.0 ng/ml.

    PubMed

    Chen, Rui; Huang, Yiran; Cai, Xiaobing; Xie, Liping; He, Dalin; Zhou, Liqun; Xu, Chuanliang; Gao, Xu; Ren, Shancheng; Wang, Fubo; Ma, Lulin; Wei, Qiang; Yin, Changjun; Tian, Ye; Sun, Zhongquan; Fu, Qiang; Ding, Qiang; Zheng, Junhua; Ye, Zhangqun; Ye, Dingwei; Xu, Danfeng; Hou, Jianquan; Xu, Kexin; Yuan, Jianlin; Gao, Xin; Liu, Chunxiao; Pan, Tiejun; Sun, Yinghao

    2015-01-01

    The influence of age on the performance of percent free prostate-specific antigen (%fPSA) in diagnosing prostate cancer (PCa) in East Asians is controversial. We tested the diagnostic performance of %fPSA in a multi-center biopsy cohort in China and identified the proper age-specific cutoff values to avoid unnecessary biopsies. Consecutive patients with a prostate-specific antigen (PSA) level of 4.0-10.0 ng/ml or 10.1-20.0 ng/ml who underwent transrectal ultrasound-guided or transperineal prostate biopsy were enrolled from 22 Chinese medical centers from Jan 1, 2010 to Dec 31, 2013. The diagnostic accuracy of PSA and %fPSA was determined using the area under the receiver operating characteristic (ROC) curve (AUC). Age-specific cutoff values were calculated using ROC curve analysis. The median %fPSA was much lower in younger patients compared with older patients with a PSA level of 4.0-10.0 ng/ml or 10.1-20.0 ng/ml. The AUC of %fPSA was higher than PSA only in older patients. In patients aged 50 to 59 years, %fPSA failed to improve the diagnosis compared with PSA in these two PSA ranges. Age-specific cutoff values were 24%, 27% and 32% for patients aged 60-69, 70-79 and ≥80 years, respectively, to reduce unnecessary biopsies in men with PSA levels of 4.0-10.0 ng/ml to detect 90% of all PCa. The effectiveness of %fPSA is correlated with age in the Chinese population. Age-specific cutoff values would help avoid unnecessary biopsies in the Chinese population.

  7. Accuracy of PSA Self-Reports among Low-Income Men with Prostate Cancer after a Public Health Nursing Intervention.

    PubMed

    Zavala, Mary Wassel; Yule, Arthur; Kwan, Lorna; Lambrechts, Sylvia; Maliski, Sally L; Litwin, Mark S

    2016-11-01

    To examine accuracy of patient-reported prostate-specific antigen (PSA) levels among indigent, uninsured men in a state-funded prostate cancer treatment program that provides case management, care coordination, and health education. Program evaluation. About 114 men with matched self- and lab-reported PSA levels at program enrollment and another time point within 18 months. Abstraction of self- and lab-reported PSA levels to determine self-report as "accurate" or "inaccurate," and evaluate accuracy change over time, before and after nursing interventions. Chi-square tests compared patients with accurate versus inaccurate PSA values. Nonlinear multivariate analyses explored trends in self-reported accuracy over time. Program enrollees receive prostate cancer education from a Nurse Case Manager (NCM), including significance of PSA levels. Men self-report PSA results to their NCM following lab draws and appointments. The NCM provides ongoing education about PSA levels. Of the sample, 46% (n = 53) accurately reported PSA levels. Accuracy of PSA self-reports improved with increasing time since program enrollment. Compared with men at public facilities, those treated at private facilities showed increasing accuracy in self-reported PSA (p = .038). A targeted nursing intervention may increase specific knowledge of PSA levels. Additionally, the provider/treatment setting significantly impacts a patient's disease education and knowledge. © 2016 Wiley Periodicals, Inc.

  8. Phase I/II trial of dendritic cell-based active cellular immunotherapy with DCVAC/PCa in patients with rising PSA after primary prostatectomy or salvage radiotherapy for the treatment of prostate cancer.

    PubMed

    Fucikova, Jitka; Podrazil, Michal; Jarolim, Ladislav; Bilkova, Pavla; Hensler, Michal; Becht, Etienne; Gasova, Zdenka; Klouckova, Jana; Kayserova, Jana; Horvath, Rudolf; Fialova, Anna; Vavrova, Katerina; Sochorova, Klara; Rozkova, Daniela; Spisek, Radek; Bartunkova, Jirina

    2018-01-01

    Immunotherapy of cancer has the potential to be effective mostly in patients with a low tumour burden. Rising PSA (prostate-specific antigen) levels in patients with prostate cancer represents such a situation. We performed the present clinical study with dendritic cell (DC)-based immunotherapy in this patient population. The single-arm phase I/II trial registered as EudraCT 2009-017259-91 involved 27 patients with rising PSA levels. The study medication consisted of autologous DCs pulsed with the killed LNCaP cell line (DCVAC/PCa). Twelve patients with a favourable PSA response continued with the second cycle of immunotherapy. The primary and secondary objectives of the study were to assess the safety and determine the PSA doubling time (PSADT), respectively. No significant side effects were recorded. The median PSADT in all treated patients increased from 5.67 months prior to immunotherapy to 18.85 months after 12 doses (p < 0.0018). Twelve patients who continued immunotherapy with the second cycle had a median PSADT of 58 months that remained stable after the second cycle. In the peripheral blood, specific PSA-reacting T lymphocytes were increased significantly already after the fourth dose, and a stable frequency was detected throughout the remainder of DCVAC/PCa treatment. Long-term immunotherapy of prostate cancer patients experiencing early signs of PSA recurrence using DCVAC/PCa was safe, induced an immune response and led to the significant prolongation of PSADT. Long-term follow-up may show whether the changes in PSADT might improve the clinical outcome in patients with biochemical recurrence of the prostate cancer.

  9. Prostate Cancer Detection and Prognosis: From Prostate Specific Antigen (PSA) to Exosomal Biomarkers.

    PubMed

    Filella, Xavier; Foj, Laura

    2016-10-26

    Prostate specific antigen (PSA) remains the most used biomarker in the management of early prostate cancer (PCa), in spite of the problems related to false positive results and overdiagnosis. New biomarkers have been proposed in recent years with the aim of increasing specificity and distinguishing aggressive from non-aggressive PCa. The emerging role of the prostate health index and the 4Kscore is reviewed in this article. Both are blood-based tests related to the aggressiveness of the tumor, which provide the risk of suffering PCa and avoiding negative biopsies. Furthermore, the use of urine has emerged as a non-invasive way to identify new biomarkers in recent years, including the PCA3 and TMPRSS2:ERG fusion gene. Available results about the PCA3 score showed its usefulness to decide the repetition of biopsy in patients with a previous negative result, although its relationship with the aggressiveness of the tumor is controversial. More recently, aberrant microRNA expression in PCa has been reported by different authors. Preliminary results suggest the utility of circulating and urinary microRNAs in the detection and prognosis of PCa. Although several of these new biomarkers have been recommended by different guidelines, large prospective and comparative studies are necessary to establish their value in PCa detection and prognosis.

  10. Prostate Cancer Detection and Prognosis: From Prostate Specific Antigen (PSA) to Exosomal Biomarkers

    PubMed Central

    Filella, Xavier; Foj, Laura

    2016-01-01

    Prostate specific antigen (PSA) remains the most used biomarker in the management of early prostate cancer (PCa), in spite of the problems related to false positive results and overdiagnosis. New biomarkers have been proposed in recent years with the aim of increasing specificity and distinguishing aggressive from non-aggressive PCa. The emerging role of the prostate health index and the 4Kscore is reviewed in this article. Both are blood-based tests related to the aggressiveness of the tumor, which provide the risk of suffering PCa and avoiding negative biopsies. Furthermore, the use of urine has emerged as a non-invasive way to identify new biomarkers in recent years, including the PCA3 and TMPRSS2:ERG fusion gene. Available results about the PCA3 score showed its usefulness to decide the repetition of biopsy in patients with a previous negative result, although its relationship with the aggressiveness of the tumor is controversial. More recently, aberrant microRNA expression in PCa has been reported by different authors. Preliminary results suggest the utility of circulating and urinary microRNAs in the detection and prognosis of PCa. Although several of these new biomarkers have been recommended by different guidelines, large prospective and comparative studies are necessary to establish their value in PCa detection and prognosis. PMID:27792187

  11. Cytokine profiling identifies an interaction of IL-6 and IL-1α to drive PSMA-PSA prostate clones.

    PubMed

    Jemaa, Awatef Ben; Bouraoui, Yosra; Rais, Nawfel Ben; Nouira, Yassine; Oueslati, Ridha

    2016-12-01

    Several PSMA-PSA prostate clones have been identified during prostate cancer progression; however, until now, their in situ inflammatory characteristics have remained unclear. We therefore investigated the interplay between proinflammatory cytokines and (PSMA,PSA) sub-groups. 27 benign prostate hyperplasia (BPH) and 18 prostate cancers (PC) were enrolled in this study. Immunohistochemical analysis was performed. Serum levels of PSA were assayed by Immulite autoanalyser. In BPH and PC patients with elevated serum PSA levels, IL-1α was the most proinflammatory cytokine expressed in (PSMA+,PSA-) subgroup. However, most samples of (PSMA+,PSA+) subgroup had positive immunoreaction to IL-6. In samples of PC with PSA serum levels of 4-20ng/mL or >20ng/mL, immunoreaction to TNF-α was seen only in (PSMA+,PSA+) subgroup. Interestingly, several combinations of proinflammatory cytokines (IL-6, IL-1α and TNF-α) showed that coexpression of tissue PSMA and PSA was concomitant with high immunoreactions to (IL-6+,TNF-α-), (IL-6+,IL-1α+) and (IL-1α+,TNFα-) in BPH and PC patients. (PSMA,PSA) subgroup lacking tissue PSA expression showed a high immunoexpression of the profile (IL-6+,TNF-α-). The combinations of (IL-6-, TNF-α-) and (IL-6-, IL-1α-) were absent in (PSMA+,PSA-) and (PSMA+,PSA+) BPH sub-groups. Collectively, these findings underscore the importance of TNF-α and highlight the interaction between IL-6 and IL-1α to generate an inflammatory microenvironment in driving (PSMA,PSA) prostate clones. Copyright © 2016 Elsevier GmbH. All rights reserved.

  12. Low percentage of free prostate-specific antigen (PSA) is a strong predictor of later detection of prostate cancer among Japanese men with serum levels of total PSA of 4.0 ng/mL or less.

    PubMed

    Sasaki, Mitsuharu; Ishidoya, Shigeto; Ito, Akihiro; Saito, Hideo; Yamada, Shigeyuki; Mitsuzuka, Koji; Kaiho, Yasuhiro; Shibuya, Daisuke; Yamaguchi, Takuhiro; Arai, Yoichi

    2014-11-01

    To investigate the effect of the percentage of free prostate-specific antigen (%fPSA) on future prostate cancer risk. We examined serum total PSA (tPSA) and %fPSA annually in a prostate cancer-screening cohort between July 2001 and June 2011. Men with tPSA >4.0 ng/mL or tPSA of 2.0-4.0 ng/mL with %fPSA ≤12% were screened as positive and were recommended to undergo a biopsy. The study population consisted of 6368 men, aged 40-79 years, who had tPSA ≤4.0 ng/mL at initial screening and who subsequently underwent 1 or more screenings. We calculated the cumulative risk and hazard ratio of prostate cancer stratified by the initial %fPSA groups as quartiles of prostate cancer patients. During a median follow-up of 36 months, 119 men were diagnosed with prostate cancer. The lowest quartile of %fPSA (<13.3%) was associated with a 21.2-fold higher risk of having prostate cancer compared with the highest quartile (>22.2%). For the subset with an initial tPSA ≤1.0 ng/mL, all men diagnosed with cancer had an initial %fPSA ≤33.3% (median). For the subset with tPSA >1.0 ng/mL, men with %fPSA ≤23.0% (median) had significantly higher risk for cancer than those with %fPSA >23.0% (P <.0001). Of the 114 men with prostate cancer in whom pathologic findings were available, 79 (69.3%) had a Gleason score ≥3 + 4 = 7. A low %fPSA is a strong predictor of a subsequent diagnosis of prostate cancer among men with tPSA levels ≤4.0 ng/mL. Measurement of %fPSA might enhance the detection of high-grade cancer that warrants aggressive treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Role of PSA density in diagnosis of prostate cancer in obese men.

    PubMed

    Chiu, Peter Ka-Fung; Teoh, Jeremy Yuen-Chun; Chan, Samson Yun-Sang; Chu, Peggy Sau-Kwan; Man, Chi-Wai; Hou, See-Ming; Ng, Chi-Fai

    2014-12-01

    To compare the performance of prostate-specific antigen (PSA) density in the diagnosis of prostate cancer in obese and non-obese Chinese men. The results of transrectal ultrasound-guided (TRUS) prostate biopsies of Chinese men with PSA <20 ng/mL were reviewed. Parameters including age, body mass index (BMI), TRUS prostate volume, and TRUS biopsy results were recorded. The diagnostic yields of PSA density (>0.15 ng/mL as positive) in obese and non-obese men with PSA <20 ng/mL were compared. Obesity was defined as BMI ≥ 27 kg/m(2) according to WHO recommendation for Hong Kong Chinese. TRUS biopsy, BMI, and PSA density data were available for 854 men (mean age 65.9 ± 7.3). The mean PSA values for the obese and non-obese patients were 7.9 ± 3.7 and 8.2 ± 4.1 ng/mL, respectively (p = 0.416). TRUS volumes in obese and non-obese men were 63.2 ml and 51.6 ml, respectively (t test, p < 0.001), and PSA density was significantly lower in obese men (0.145 vs. 0.188, p < 0.001). For obese men, positive PSA density was associated with four times (41.1 vs. 9.5 %, p < 0.001) the risk of prostate cancer, compared to only twice the risk (18.8 vs. 9.7 %, p = 0.001) in non-obese men. The specificity and area under the curve of PSA density were 74.2 % and 0.731, respectively, for obese men, and 51.4 % and 0.653, respectively, for non-obese men. Among patients with a diagnosis of prostate cancer, the obese patient group had a significantly higher proportion of patients with Gleason 7-10 prostate cancer than the non-obese patient group (48.9 vs. 32.7 %, Chi-square test, p = 0.035), and a trend toward a higher proportion of bilateral lobe involvement. PSA density had better performance in obese men. Positive PSA density in obese men was associated with four times the risk of prostate cancer.

  14. Predictive value of [-2]propsa (p2psa) and its derivatives for the prostate cancer detection in the 2.0 to 10.0ng/mL PSA range.

    PubMed

    Vukovic, I; Djordjevic, D; Bojanic, N; Babic, U; Soldatovic, I

    2017-01-01

    To assess predictive value of new tumor markers, precursor of prostate specific antigen (p2PSA) and its derivates-%p2PSA and prostate health index (PHI) in detection of patients with indolent and aggressive prostate cancer (PC) in a subcohort of man whose total PSA ranged from 2 to 10ng/mL. This cross-sectional study included 129 consecutive male patients aged over 50 years, with no previous history of PC and with normal digital rectal examination findings, but with serum PSA in interval between 2 and 10ng/mL. All patients underwent standard transrectal ultrasonography guided prostate biopsy for the first time. For all patients, serum PSA, free PSA (fPSA) and p2PSA were measured and PHI and %p2PSA were calculated. PHI and %p2PSA levels were significanlty higher in patients with PC compared to those without this malignancy. The same findings have been observed in group of patients with Gleason score ≥7 compared to those with Gleason score <7. ROC analysis reveled the highest area under the curve with these two markers. Multivariate logistic regression showed significant improvement in PC detection and its agressive form (assumed as Gleason score ≥7). New markers, derivates of p2PSA (especially %p2PSA and PHI), represente potentially very important clinical tool for predicting presence of PC, and even more important, to discriminate patients with Gleason score <7 from those with Gleason score ≥7 with total PSA in range from 2 to 10ng/mL. Copyright® by the International Brazilian Journal of Urology.

  15. Literacy, race, and PSA level among low-income men newly diagnosed with prostate cancer.

    PubMed

    Wolf, Michael S; Knight, Sara J; Lyons, E Allison; Durazo-Arvizu, Ramón; Pickard, Simon A; Arseven, Adnan; Arozullah, Ahsan; Colella, Kathleen; Ray, Paul; Bennett, Charles L

    2006-07-01

    Among men with newly diagnosed prostate cancer, prostate-specific antigen (PSA) levels are higher and the cancer stage more advanced for African Americans than for whites. An earlier study found that after adjustment for literacy, race was no longer a significant predictor of advanced stage at presentation. We investigated whether, after adjusting for literacy, race was a significant independent predictor of greater PSA levels among men with newly diagnosed prostate cancer. Consecutive patients with newly diagnosed prostate cancer from four outpatient care facilities in Chicago were interviewed and given a literacy assessment (n = 308). The PSA level at diagnosis was obtained from the medical charts. Logistic regression models were used to identify predictors of high PSA levels (greater than 20 ng/mL) at presentation. African-American men were three times more likely to have low literacy skills (sixth grade or less: 22.9% versus 7.1%; P <0.001) than were white men. In turn, men with low literacy skills were more than twice as likely to have a PSA level greater than 20 ng/mL at diagnosis (33.3% versus 13.5%; P = 0.009). On multivariate analyses, significant predictors of high PSA levels included low literacy (adjusted odds ratio 2.5, 95% confidence interval 1.5 to 4.2) and older age (age 65 to 74 years, adjusted odds ratio 2.6, 95% confidence interval 2.1 to 3.1 versus older than 74 years, adjusted odds ratio 3.4, 95% confidence interval 1.8 to 6.6), but not African-American race. In the current era in which PSA testing is common, low literacy may be an important and potentially overlooked factor associated with higher PSA levels at prostate cancer diagnosis among African-American and white men.

  16. The PSA testing dilemma: GPs' reports of consultations with asymptomatic men: a qualitative study.

    PubMed

    Clements, Alison; Watson, Eila; Rai, Tanvi; Bukach, Colleen; Shine, Brian; Austoker, Joan

    2007-06-25

    The National Health Service Prostate Cancer Risk Management Programme (PCRMP) has recommended that screening for prostate cancer is available for asymptomatic men, on the understanding that they have been provided with full and balanced information about the advantages and limitations of the prostate-specific antigen (PSA) test. Guidance has been distributed to all GPs in England and Wales to assist in the provision of information to men. This study aimed to elicit GPs' accounts of their discussions with asymptomatic men who consult with concerns about prostate cancer in order to identify the degree to which the PCRMP guidance was reflected in these consultations. Qualitative interview study. Semi-structured telephone interviews with 21 GPs from 18 GP practices in Oxfordshire. All GPs reported undertaking some discussion with asymptomatic men about the PSA test. They described focussing most of the discussion on the false-positive and false-negative rates of the test, and the risks associated with a prostate biopsy. They reported less discussion of the potential for diagnosing indolent cancers, the dilemmas regarding treatment options for localised prostate cancer and the potential benefits of testing. Considerable variation existed between GPs in their accounts of the degree of detail given, and GP's presentation of information appeared to be affected by their personal views of the PSA test. The GPs in this study appear to recognise the importance of discussions regarding PSA testing; however, a full and balanced picture of the associated advantages and limitations does not seem to be consistently conveyed. Factors specific to PSA testing which appeared to have an impact on the GPs' discussions were the GP's personal opinions of the PSA test, and the need to counter men's primarily positive views of the benefits of PSA testing. Awareness of the impact of their views on the consultations may help GPs give men a more balanced presentation of the benefits and

  17. The influence of stress, depression, and anxiety on PSA screening rates in a nationally representative sample.

    PubMed

    Kotwal, Ashwin A; Schumm, Phil; Mohile, Supriya G; Dale, William

    2012-12-01

    Prostate-specific antigen (PSA) testing for prostate cancer is controversial, with concerning rates of both overscreening and underscreening. The reasons for the observed rates of screening are unknown, and few studies have examined the relationship of psychological health to PSA screening rates. Understanding this relationship can help guide interventions to improve informed decision-making for screening. A nationally representative sample of men 57-85 years old without prostate cancer (N = 1169) from the National Social life, Health and Aging Project was analyzed. The independent relationship of validated psychological health scales measuring stress, anxiety, and depression to PSA testing rates was assessed using multivariable logistic regression analyses. PSA screening rates were significantly lower for men with higher perceived stress [odds ratio (OR) = 0.76, P = 0.006], but not for higher depressive symptoms (OR = 0.89, P = 0.22) when accounting for stress. Anxiety influences PSA screening through an interaction with number of doctor visits (P = 0.02). Among the men who visited the doctor once those with higher anxiety were less likely to be screened (OR = 0.65, P = 0.04). Conversely, those who visited the doctor 10+ times with higher anxiety were more likely to be screened (OR = 1.71, P = 0.04). Perceived stress significantly lowers PSA screening likelihood, and it seems to partly mediate the negative relationship of depression with screening likelihood. Anxiety affects PSA screening rates differently for men with different numbers of doctor visits. Interventions to influence PSA screening rates should recognize the role of the patients' psychological state to improve their likelihood of making informed decisions and improve screening appropriateness.

  18. Simultaneous silencing of isoamylases ISA1, ISA2 and ISA3 by multi-target RNAi in potato tubers leads to decreased starch content and an early sprouting phenotype

    PubMed Central

    Ferreira, Stephanus J.; Senning, Melanie; Fischer-Stettler, Michaela; Streb, Sebastian; Ast, Michelle; Neuhaus, H. Ekkehard; Zeeman, Samuel C.; Sonnewald, Sophia

    2017-01-01

    Isoamylases hydrolyse (1–6)-alpha-D-glucosidic linkages in starch and are involved in both starch granule formation and starch degradation. In plants, three isoamylase isoforms with distinct functions in starch synthesis (ISA1 and ISA2) and degradation (ISA3) have been described. Here, we created transgenic potato plants with simultaneously decreased expression of all three isoamylases using a chimeric RNAi construct targeting all three isoforms. Constitutive expression of the hairpin RNA using the 35S CaMV promoter resulted in efficient silencing of all three isoforms in leaves, growing tubers, and sprouting tubers. Neither plant growth nor tuber yield was effected in isoamylase-deficient potato lines. Interestingly, starch metabolism was found to be impaired in a tissue-specific manner. While leaf starch content was unaffected, tuber starch was significantly reduced. The reduction in tuber starch content in the transgenic plants was accompanied by a decrease in starch granules size, an increased sucrose content and decreased hexose levels. Despite the effects on granule size, only little changes in chain length composition of soluble and insoluble glucose polymers were detected. The transgenic tubers displayed an early sprouting phenotype that was accompanied by an increased level of sucrose in parenchyma cells below the outgrowing bud. Since high sucrose levels promote sprouting, we propose that the increased number of small starch granules may cause an accelerated turnover of glucan chains and hence a more rapid synthesis of sucrose. This observation links alterations in starch structure/degradation with developmental processes like meristem activation and sprout outgrowth in potato tubers. PMID:28708852

  19. High-sensitivity detection of PSA by time-resolved fluorometry with Europium chelate

    NASA Astrophysics Data System (ADS)

    Nahm, Kie B.; Jeong, Jin H.; Kim, Byoung C.; Kim, Jae H.; Kim, Young M.; Jeong, Dong S.; Oh, Sang W.; Choi, Eui Y.; Ko, Dong S.

    2006-01-01

    Prostate-specific antigen (PSA) is an androgen-dependent glycoprotein protease (M.W. 33 kDa) and a member of kallikrein super-family of serine protease, and has chymotrypsin-like enzymatic activity. It is synthesized by the prostate epithelial cells and found in the prostate gland and seminal plasma as a major protein. It is widely used as a clinical marker for diagnosis, screening, monitoring and prognosis of prostate cancer. In normal male adults, the concentration of PSA in the blood is below 4 ng/ml and this value increases in patients with the prostate cancer or the benign prostatic hyperplasia (BPH) due to its leakage into the circulatory system. As such, systematic monitoring of the PSA level in the blood can provide critical information about the progress of the prostatic disease. We have fabricated a bread-board time resolved fluorescence system that could detect a concentration of Prostate Specific Antigen t-PSA) at clinically meaningful level in plasma as well as in whole blood sample. We chose Europium chelates as the fluorescence markers to attach to the PSA for its long decay lifetime and relative photostability. We have simplified the electronic circuits considerably by employing a MCS. With this setup, we have successfully proved that PSA concentration of 4pg/mL can be detected with acceptable reliability.

  20. CCR study: evidence for benefit of TARP vaccine for men with early stage prostate cancer | Center for Cancer Research

    Cancer.gov

    Results from a pilot clinical trial found that TARP, or T-cell receptor gamma chain alternate reading frame protein, vaccination slowed prostate-specific antigen (PSA) rise in the majority of patients with early stage prostate cancer.

  1. Association between PSA Levels and Biomarkers of Subclinical Systemic Inflammation in Middle-Aged Healthy Men from the General Population.

    PubMed

    Elzanaty, Saad; Rezanezhad, Babak; Borgquist, Rasmus

    2016-10-01

    This study was aimed to determine the association between PSA levels and biomarkers of subclinical systemic inflammation based on data from 119 middle-aged healthy men from the general population. Serum levels of PSA and biomarkers of systemic inflammation (CRP and fibrinogen) were measured. Demographic data were also collected. Subjects were divided into two groups according to PSA levels; < 2 ng/ml and ≥ 2 ng/ml. The mean (SD) age of men was 55 ± 4.0 years. We found a positive significant correlation between PSA and fibrinogen levels (r = 0.20, p = 0.04), and between CRP and fibrinogen levels (r = 0.60, p = 0.01). On the other hand, no significant correlation between PSA and CRP levels was found. Men with PSA values ≥ 2 ng/ml had significantly higher levels of fibrinogen as compared to those with PSA < 2 ng/ml (2.9 ng/ml vs. 2.4 ng/ml, p = 0.01). In a multivariate regression analysis model adjusted for the age of subjects, BMI, marital status, smoking, snuff, and alcohol intake with serum levels of PSA as a dependent variable, serum level of fibrinogen predicted higher PSA-values (odds ratio = 3.30, 95% CI = 1.05-10.20, p = 0.042). The present results indicate that serum fibrinogen is a biomarker of subclinical systemic inflammation associated with PSA elevation among middle-aged healthy men from the general population.

  2. Ethnicity Is an Independent Determinant of Age-Specific PSA Level: Findings from a Multiethnic Asian Setting

    PubMed Central

    Sothilingam, Selvalingam; Malek, Rohan; Sundram, Murali; Hisham Bahadzor, Badrul; Ong, Teng Aik; Ng, Keng Lim; Sivalingam, Sivaprakasam; Razack, Azad Hassan Abdul

    2014-01-01

    Objectives To study the baseline PSA profile and determine the factors influencing the PSA levels within a multiethnic Asian setting. Materials and Methods We conducted a cross-sectional study of 1054 men with no clinical evidence of prostate cancer, prostate surgery or 5α-reductase inhibitor treatment of known prostate conditions. The serum PSA concentration of each subject was assayed. Potential factors associated with PSA level including age, ethnicity, height, weight, family history of prostate cancer, lower urinary tract voiding symptoms (LUTS), prostate volume and digital rectal examination (DRE) were evaluated using univariable and multivariable analysis. Results There were 38 men (3.6%) found to have a PSA level above 4 ng/ml and 1016 (96.4%) with a healthy PSA (≤4 ng/ml). The median PSA level of Malay, Chinese and Indian men was 1.00 ng/ml, 1.16 ng/ml and 0.83 ng/ml, respectively. Indians had a relatively lower median PSA level and prostate volume than Malays and Chinese, who shared a comparable median PSA value across all 10-years age groups. The PSA density was fairly similar amongst all ethnicities. Further analysis showed that ethnicity, weight and prostate volume were independent factors associated with age specific PSA level in the multivariable analysis (p<0.05). Conclusion These findings support the concept that the baseline PSA level varies between different ethnicities across all age groups. In addition to age and prostate volume, ethnicity may also need to be taken into account when investigating serum PSA concentrations in the multiethnic Asian population. PMID:25111507

  3. Exploring the potential of [11C]choline-PET/CT as a novel imaging biomarker for predicting early treatment response in prostate cancer.

    PubMed

    Challapalli, Amarnath; Barwick, Tara; Tomasi, Giampaolo; O' Doherty, Michael; Contractor, Kaiyumars; Stewart, Simon; Al-Nahhas, Adil; Behan, Kevin; Coombes, Charles; Aboagye, Eric O; Mangar, Stephen

    2014-01-01

    The aim of the study was to assess the effects of neoadjuvant androgen deprivation (NAD) and radical prostate radiotherapy with concurrent androgen deprivation (RT-CAD) on prostatic [C]choline kinetics and thus develop methodology for the use of [C]choline-PET/computed tomography (CT) as an early imaging biomarker. Ten patients with histologically confirmed prostate cancer underwent three sequential dynamic [C]choline-PET/CT pelvic scans: at baseline, after NAD and 4 months after RT-CAD. [C]Choline uptake was quantified using the average and maximum standardized uptake values at 60 min (SUV60,ave and SUV60,max), the tumour-to-muscle ratios (TMR60,max) and net irreversible retention of [C]choline at steady state (Kimod-pat). The combination of NAD and RT-CAD significantly decreased tumour [C]choline uptake (SUV60,ave, SUV60,max, TMR60,max or Kimod-pat) and prostate-specific antigen (PSA) levels (analysis of variance, P<0.001 for all variables). Although the magnitude of reduction in the variables was larger after NAD, there was a smaller additional reduction after RT-CAD. A wide range of reduction in tumour SUV60,ave (38-83.7%) and SUV60,max (22.2-85.3%) was seen with combined NAD and RT-CAD despite patients universally achieving PSA suppression (narrow range of 93.5-99.7%). There was good association between baseline SUV60,max and initial PSA levels (Pearson's r=0.7, P=0.04). The reduction in tumour SUV60,ave after NAD was associated with PSA reduction (r=0.7, P=0.04). This association occurred despite the larger reduction in PSA (94%) compared with SUV60,ave (58%). This feasibility study shows that [C]choline-PET/CT detects metabolic changes within tumours following NAD and RT-CAD to the prostate. A differential reduction in [C]choline uptake despite a global reduction in PSA following NAD and RT-CAD could provide prognostic information and warrants further evaluation as an imaging biomarker in this setting.

  4. Prostate-Specific Antigen (PSA)–Based Population Screening for Prostate Cancer: An Economic Analysis

    PubMed Central

    Tawfik, A

    2015-01-01

    Background The prostate-specific antigen (PSA) blood test has become widely used in Canada to test for prostate cancer (PC), the most common cancer among Canadian men. Data suggest that population-based PSA screening may not improve overall survival. Objectives This analysis aimed to review existing economic evaluations of population-based PSA screening, determine current spending on opportunistic PSA screening in Ontario, and estimate the cost of introducing a population-based PSA screening program in the province. Methods A systematic literature search was performed to identify economic evaluations of population-based PSA screening strategies published from 1998 to 2013. Studies were assessed for their methodological quality and applicability to the Ontario setting. An original cost analysis was also performed, using data from Ontario administrative sources and from the published literature. One-year costs were estimated for 4 strategies: no screening, current (opportunistic) screening of men aged 40 years and older, current (opportunistic) screening of men aged 50 to 74 years, and population-based screening of men aged 50 to 74 years. The analysis was conducted from the payer perspective. Results The literature review demonstrated that, overall, population-based PSA screening is costly and cost-ineffective but may be cost-effective in specific populations. Only 1 Canadian study, published 15 years ago, was identified. Approximately $119.2 million is being spent annually on PSA screening of men aged 40 years and older in Ontario, including close to $22 million to screen men younger than 50 and older than 74 years of age (i.e., outside the target age range for a population-based program). A population-based screening program in Ontario would cost approximately $149.4 million in the first year. Limitations Estimates were based on the synthesis of data from a variety of sources, requiring several assumptions and causing uncertainty in the results. For example, where

  5. Effects of increasing the PSA cutoff to perform additional biomarker tests before prostate biopsy.

    PubMed

    Nordström, Tobias; Adolfsson, Jan; Grönberg, Henrik; Eklund, Martin

    2017-10-03

    Multi-step testing might enhance performance of the prostate cancer diagnostic pipeline. Using PSA >1 ng/ml for first-line risk stratification and the Stockholm 3 Model (S3M) blood-test >10% risk of Gleason Score > 7 prostate cancer to inform biopsy decisions has been suggested. We aimed to determine the effects of changing the PSA cutoff to perform reflex testing with S3M and the subsequent S3M cutoff to recommend prostate biopsy while maintaining the sensitivity to detect Gleason Score ≥ 7 prostate cancer. We used data from the prospective, population-based, paired, diagnostic Stockholm 3 (STHLM3) study with participants invited by date of birth from the Swedish Population Register during 2012-2014. All participants underwent testing with PSA and S3M (a combination of plasma protein biomarkers [PSA, free PSA, intact PSA, hK2, MSMB, MIC1], genetic polymorphisms, and clinical variables [age, family, history, previous prostate biopsy, prostate exam]). Of 47,688 men in the STHLM3 main study, we used data from 3133 men with S3M >10% and prostate biopsy data. Logistic regression models were used to calculate prostate cancer detection rates and proportion saved biopsies. 44.2%, 62.5% and 67.9% of the participants had PSA <1, <1.5 and <1.7 ng/ml, respectively. Increasing the PSA cut-off for additional work-up from 1 ng/ml to 1.5 ng/ml would thus save 18.3% of the performed tests, 4.9% of the biopsies and 1.3% (10/765) of Gleason Grade ≥ 7 cancers would be un-detected. By lowering the S3M cutoff to recommend biopsy, sensitivity to high-grade prostate cancer can be restored, to the cost of increasing the number of performed biopsies modestly. The sensitivity to detect prostate cancer can be maintained when using different PSA cutoffs to perform additional testing. Biomarker cut-offs have implications on number of tests and prostate biopsies performed. A PSA cutoff of 1.5 ng/ml to perform additional testing such as the S3M test might be considered. ISRCTN

  6. Assessing the Clinical Role of Genetic Markers of Early-Onset Prostate Cancer Among High-Risk Men Enrolled in Prostate Cancer Early Detection

    PubMed Central

    Hughes, Lucinda; Zhu, Fang; Ross, Eric; Gross, Laura; Uzzo, Robert G.; Chen, David Y. T.; Viterbo, Rosalia; Rebbeck, Timothy R.; Giri, Veda N.

    2011-01-01

    Background Men with familial prostate cancer (PCA) and African American men are at risk for developing PCA at younger ages. Genetic markers predicting early-onset PCA may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset PCA in a longitudinal cohort of high-risk men enrolled in PCA early detection with significant African American participation. Methods Eligibility criteria include ages 35–69 with a family history of PCA or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset PCA (rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)) were genotyped. Cox models were used to evaluate time to PCA diagnosis and PSA prediction for PCA by genotype. Harrell’s concordance index was used to evaluate predictive accuracy for PCA by PSA and genetic markers. Results 460 participants with complete data and ≥1 follow-up visit were included. 56% were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to PCA diagnosis (p=0.005) and influenced prediction for PCA by the PSA (p<0.001). When combined with PSA, rs6983561 improved predictive accuracy for PCA compared to PSA alone among African American men (PSA= 0.57 vs. PSA+rs6983561=0.75, p=0.03). Conclusions Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing PCA risk assessment. Further study is warranted to validate these findings. Impact Genetic markers of early-onset PCA have potential to refine and personalize PCA early detection for high-risk men. PMID:22144497

  7. Patterns of clinical response to PSA elevation in American Indian/Alaska Native men: a multi-center pilot study.

    PubMed

    Tilburt, Jon C; Koller, Kathryn; Tiesinga, James J; Wilson, Robin T; Trinh, Anne C; Hill, Kristin; Hall, Ingrid J; Smith, Judith Lee; Ekwueme, Donatus U; Petersen, Wesley O

    2013-11-01

    To assess clinical treatment patterns and response times among American Indian/Alaska Native men with a newly elevated PSA. We retrospectively identified men ages 50-80 receiving care in one of three tribally-operated clinics in Northern Minnesota, one medical center in Alaska, and who had an incident PSA elevation (> 4 ng/ml) in a specified time period. A clinical response was considered timely if it was documented as occurring within 90 days of the incident PSA elevation. Among 82 AI/AN men identified from medical records with an incident PSA elevation, 49 (60%) received a timely clinical response, while 18 (22%) had no documented clinical response. One in five AI/AN men in our study had no documented clinical action following an incident PSA elevation. Although a pilot study, these findings suggest the need to improve the documentation, notification, and care following an elevated PSA at clinics serving AI/AN men.

  8. Percentage of free prostate-specific antigen (PSA) is a useful method in deciding to perform prostate biopsy with higher core numbers in patients with low PSA cut-off values.

    PubMed

    Yilmaz, Hasan; Ciftci, Seyfettin; Yavuz, Ufuk; Ustuner, Murat; Saribacak, Ali; Dillioglugil, Ozdal

    2015-06-01

    The aim of this study was to evaluate the predictive role of percentage of free prostate-specific antigen (%fPSA) cut-points in prostate cancer (PCa) detection in patients with total PSA (tPSA) levels between 2.5 ng/mL and 10.0 ng/mL. In total, 1321 consecutive initial transrectal ultrasound (TRUS)-guided 12-core biopsies performed between 2005 and 2011 were evaluated retrospectively. Benign pathologies, high-grade prostatic intraepithelial neoplasia, and atypical small acinary proliferations were categorized as noncancerous (benign), and prostate adenocarcinomas were categorized as cancerous (malignant). The patients were categorized according to: Catalona's published %fPSA categories (<10%, 10-15%, 15-20%, 20-25%, or > 25%); digital rectal examination (DRE) results [benign (negative) or suspicious of malignancy (positive)]. There was a significant relationship between the %fPSA cut-points and detection of PCa in DRE-negative patients. The presence of a 10% cut-point increased the probability of PCa threefold. The %fPSA was significantly more related to PCa than the tPSA value in receiver operating characteristic (ROC) curve analyses (p = 0.001). Based on our findings, a lower %fPSA, especially <10%, is an important parameter when deciding whether to perform a biopsy on patients with a tPSA between 2.5 ng/mL and 10 ng/mL. Copyright © 2015. Published by Elsevier Taiwan.

  9. Investigative clinical study on prostate cancer part III: exploring total PSA and free testosterone distributions and linear correlations in groups and subgroups of operated prostate cancer patients according to the total PSA/FT ratio.

    PubMed

    Porcaro, Antonio B; Petrozziello, Aldo; Romano, Mario; Sava, Teodoro; Ghimenton, Claudio; Caruso, Beatrice; Migliorini, Filippo; Zecchini Antoniolli, Stefano; Rubilotta, Emanuele; Lacola, Vincenzo; Monaco, Carmelo; Comunale, Luigi

    2010-01-01

    Prostate cancer is an interesting tumor for endocrine investigation. The prostate-specific antigen/free testosterone (PSA/FT) ratio has been shown to be effective in clustering patients in prognostic groups as follows: low risk (PSA/FT ≤0.20), intermediate risk (PSA/FT >0.20 and ≤0.40) and high risk (PSA/FT >0.40 and ≤1.5). In the present study we explored the total PSA and FT distributions, and linear regression of FT predicting PSA in the different groups (PSA/FT, pT and pG) and subgroups (pT and pG) of patients according to the prognostic PSA/FT ratio. The study included 128 operated prostate cancer patients. Pretreatment simultaneous serum samples were obtained for measuring free testosterone (FT) and total PSA levels. Patients were grouped according to the total PSA/FT ratio prognostic clusters (≤0.20, >0.20 and ≤0.40, >0.40), pT (2, 3a and 3b+4) and pathological Gleason score (pG) (≤6, = 7 >3 + 4, ≥7 >4 + 3). The pT and pG sets were subgrouped according to the prognostic PSA/FT ratio. Linear regression analysis of FT predicting total PSA was computed according to the different PSA/FT prognostic clusters for the: (1) total sample population, (2) pT and pG groups, (3) intraprostatic (pT2) and extraprostatic disease (pT3a/3b/4), and (4) low-intermediate grade (pG ≤6) and high-grade (pG ≥7) prostate cancer. Analysis of variance always showed highly significant different PSA distributions for (1) the different PSA/FT, pT and pG groups; and (2) the pT and pG prognostic subgroups. Significant FT distributions were detected for the (1) PSA/FT and pT groups; and (2) the pT2, pT3a and pG ≤6 prognostic PSA/FT subgroups. Correlation, variance and linear regression analysis of FT predicting total PSA was significant for (1) the PSA/FT prognostic clusters, (2) all the pT2 and pT3a subgroups, and (3) the pT3b/4 subgroup with PSA/FT >0.20 and ≤0.40, and (4) all the pG subsets. Linear regression analysis showed that the slopes of the predicting variable

  10. The new Planetary Science Archive (PSA): Exploration and discovery of scientific datasets from ESA's planetary missions

    NASA Astrophysics Data System (ADS)

    Martinez, Santa; Besse, Sebastien; Heather, Dave; Barbarisi, Isa; Arviset, Christophe; De Marchi, Guido; Barthelemy, Maud; Docasal, Ruben; Fraga, Diego; Grotheer, Emmanuel; Lim, Tanya; Macfarlane, Alan; Rios, Carlos; Vallejo, Fran; Saiz, Jaime; ESDC (European Space Data Centre) Team

    2016-10-01

    The Planetary Science Archive (PSA) is the European Space Agency's (ESA) repository of science data from all planetary science and exploration missions. The PSA provides access to scientific datasets through various interfaces at http://archives.esac.esa.int/psa. All datasets are scientifically peer-reviewed by independent scientists, and are compliant with the Planetary Data System (PDS) standards. The PSA is currently implementing a number of significant improvements, mostly driven by the evolution of the PDS standard, and the growing need for better interfaces and advanced applications to support science exploitation. The newly designed PSA will enhance the user experience and will significantly reduce the complexity for users to find their data promoting one-click access to the scientific datasets with more specialised views when needed. This includes a better integration with Planetary GIS analysis tools and Planetary interoperability services (search and retrieve data, supporting e.g. PDAP, EPN-TAP). It will be also up-to-date with versions 3 and 4 of the PDS standards, as PDS4 will be used for ESA's ExoMars and upcoming BepiColombo missions. Users will have direct access to documentation, information and tools that are relevant to the scientific use of the dataset, including ancillary datasets, Software Interface Specification (SIS) documents, and any tools/help that the PSA team can provide. A login mechanism will provide additional functionalities to the users to aid / ease their searches (e.g. saving queries, managing default views). This contribution will introduce the new PSA, its key features and access interfaces.

  11. [PSA testing, biopsy and cancer and benign prostate hyperplasia in France].

    PubMed

    Tuppin, P; Samson, S; Fagot-Campagna, A; Lukacs, B; Alla, F; Allemand, H; Paccaud, F; Thalabard, J-C; Vicaut, E; Vidaud, M; Millat, B

    2014-07-01

    Prostate-specific antigen (PSA) testing is high in France. The aim of this study was to estimate their frequency and those of biopsy and newly diagnosed cancer (PCa) according to the presence or absence of treated benign prostatic hyperplasia (BPH). This study concerned men 40 years and older covered by the main French national health insurance scheme (73 % of all men of this age). Data were collected from the national health insurance information system (SNIIRAM). This database comprehensively records all of the outpatient prescriptions and healthcare services reimbursed. This information are linked to data collected during hospitalisations. The frequency of men without diagnosed PCa (10.9 millions) with at least one PSA test was very high in 2011 (men aged 40 years and older: 30 %, 70-74 years: 56 %, 85 years and older: 33 % and without HBP: 25 %, 41 % and 19 %). Men with treated BPH totalized 9 % of the study population, but 18 % of the men with at least one PSA test, 44 % of those with at least one prostate biopsy and 40 % of those with newly managed PCa. Over a 3-year period, excluding men with PCa, 88 % of men with BPH had at least one PSA test and 52 % had three or more PSA tests versus 52 % and 15 % for men without BPH. One year after PSA testing, men of 55-69 years with BPH more frequently underwent prostate biopsy than those without BPH (5.4 % vs 1.8 %) and presented PCa (1.9 % vs 0.9 %). PSA testing frequencies in France are very high even after exclusion of men with BPH, who can be a group with more frequent managed PCa. 4. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. Association of Reported Prostate Cancer Risk Alleles With PSA Levels Among Men Without a Diagnosis of Prostate Cancer

    PubMed Central

    Wiklund, Fredrik; Zheng, S. Lilly; Sun, Jielin; Adami, Hans-Olov; Lilja, Hans; Hsu, Fang-Chi; Stattin, Pär; Adolfsson, Jan; Cramer, Scott D.; Duggan, David; Carpten, John D.; Chang, Bao-Li; Isaacs, William B.; Grönberg, Henrik; Xu, Jianfeng

    2012-01-01

    BACKGROUND Prostate specific antigen (PSA) is widely used for prostate cancer screening but its levels are influenced by many non cancer-related factors. The goal of the study is to estimate the effect of genetic variants on PSA levels. METHODS We evaluated the association of SNPs that were reported to be associated with prostate cancer risk in recent genome-wide association studies with plasma PSA levels in a Swedish study population, including 1,722 control subjects without a diagnosis of prostate cancer. RESULTS Of the 16 SNPs analyzed in control subjects, significant associations with PSA levels (P≤0.05) were found for six SNPs. These six SNPs had a cumulative effect on PSA levels; the mean PSA levels in men were almost twofold increased across increasing quintile of number of PSA associated alleles, P-trend=3.4×10−14. In this Swedish study population risk allele frequencies were similar among T1c case patients (cancer detected by elevated PSA levels alone) as compared to T2 and above prostate cancer case patients. CONCLUSIONS Results from this study may have two important clinical implications. The cumulative effect of six SNPs on PSA levels suggests genetic-specific PSA cutoff values may be used to improve the discriminatory performance of this test for prostate cancer; and the dual associations of these SNPs with PSA levels and prostate cancer risk raise a concern that some of reported prostate cancer risk-associated SNPs may be confounded by the prevalent use of PSA screening. PMID:19116992

  13. Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL

    PubMed Central

    Bryce, A H; Alumkal, J J; Armstrong, A; Higano, C S; Iversen, P; Sternberg, C N; Rathkopf, D; Loriot, Y; de Bono, J; Tombal, B; Abhyankar, S; Lin, P; Krivoshik, A; Phung, D; Beer, T M

    2017-01-01

    Background: Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested. Methods: Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups. Results: Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26–2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar. Conclusions: Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression. PMID:28117385

  14. Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL.

    PubMed

    Bryce, A H; Alumkal, J J; Armstrong, A; Higano, C S; Iversen, P; Sternberg, C N; Rathkopf, D; Loriot, Y; de Bono, J; Tombal, B; Abhyankar, S; Lin, P; Krivoshik, A; Phung, D; Beer, T M

    2017-06-01

    Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested. Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups. Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26-2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar. Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression.

  15. The value of multimodality imaging in the investigation of a PSA recurrence after radical prostatectomy in the Irish hospital setting.

    PubMed

    McLoughlin, L C; Inder, S; Moran, D; O'Rourke, C; Manecksha, R P; Lynch, T H

    2018-02-01

    The diagnostic evaluation of a PSA recurrence after RP in the Irish hospital setting involves multimodality imaging with MRI, CT, and bone scanning, despite the low diagnostic yield from imaging at low PSA levels. We aim to investigate the value of multimodality imaging in PC patients after RP with a PSA recurrence. Forty-eight patients with a PSA recurrence after RP who underwent multimodality imaging were evaluated. Demographic data, postoperative PSA levels, and imaging studies performed at those levels were evaluated. Eight (21%) MRIs, 6 (33%) CTs, and 4 (9%) bone scans had PCa-specific findings. Three (12%) patients had a positive MRI with a PSA <1.0 ng/ml, while 5 (56%) were positive at PSA ≥1.1 ng/ml (p = 0.05). Zero patient had a positive CT TAP at a PSA level <1.0 ng/ml, while 5 (56%) were positive at levels ≥1.1 ng/ml (p = 0.03). Zero patient had a positive bone at PSA levels <1.0 ng/ml, while 4 (27%) were positive at levels ≥1.1 ng/ml (p = 0.01). The diagnostic yield from multimodality imaging, and isotope bone scanning in particular, in PSA levels <1.0 ng/ml, is low. There is a statistically significant increase in the frequency of positive findings on CT and bone scanning at PSA levels ≥1.1 ng/ml. MRI alone is of investigative value at PSA <1.0 ng/ml. The indication for CT, MRI, or isotope bone scanning should be carefully correlated with the clinical question and how it will affect further management.

  16. Correlation of serum androgens and pituitary hormone levels with serum PSA less than 2.5 ng/ml.

    PubMed

    Sofikerim, Mustafa; Oruç, Ozgür; Eskicorapci, Sadettin; Guliyev, Fuat; Ozen, Haluk

    2007-07-27

    The aim of this clinical study was to determine whether there is a relationship between total serum testosterone, free testosterone, FSH (Follicle-Stimulating Hormone), LH (Luteinizing Hormone) and serum prostate specific antigen (PSA) levels. We postulated that such a correlation existed then the use of hormone specific reference ranges might enhance the usefullness of PSA concentrations <2.5 ng/mL as a marker for prostate cancer. Prior to digital rectal examination, serum was obtained from all patients between 8.30-10:00 AM for hormone and PSA concentrations. The study was performed on 210 male patients >40 years of age visiting our urology outpatient clinics. PSA was correlated to age (r = 0.23, p = 0.019), but there none between serum testosterone and age. No significant correlation was noted between testosterone or free testosterone and serum PSA levels, and none between serum FSH or LH and PSA. In age specific reference groups (41-49; 50-59; 60-69 years), we found no significant correlation between PSA and hormone concentrations. In this population of eugonadal men with serum PSA values less than 2.5 ng/ml, serum androgens and pituitary hormones do not appear to correlate with serum PSA.

  17. The New Planetary Science Archive (PSA): Exploration and Discovery of Scientific Datasets from ESA's Planetary Missions

    NASA Astrophysics Data System (ADS)

    Heather, David; Besse, Sebastien; Vallat, Claire; Barbarisi, Isa; Arviset, Christophe; De Marchi, Guido; Barthelemy, Maud; Coia, Daniela; Costa, Marc; Docasal, Ruben; Fraga, Diego; Grotheer, Emmanuel; Lim, Tanya; MacFarlane, Alan; Martinez, Santa; Rios, Carlos; Vallejo, Fran; Saiz, Jaime

    2017-04-01

    The Planetary Science Archive (PSA) is the European Space Agency's (ESA) repository of science data from all planetary science and exploration missions. The PSA provides access to scientific datasets through various interfaces at http://psa.esa.int. All datasets are scientifically peer-reviewed by independent scientists, and are compliant with the Planetary Data System (PDS) standards. The PSA is currently implementing a number of significant improvements, mostly driven by the evolution of the PDS standard, and the growing need for better interfaces and advanced applications to support science exploitation. As of the end of 2016, the PSA is hosting data from all of ESA's planetary missions. This includes ESA's first planetary mission Giotto that encountered comet 1P/Halley in 1986 with a flyby at 800km. Science data from Venus Express, Mars Express, Huygens and the SMART-1 mission are also all available at the PSA. The PSA also contains all science data from Rosetta, which explored comet 67P/Churyumov-Gerasimenko and asteroids Steins and Lutetia. The year 2016 has seen the arrival of the ExoMars 2016 data in the archive. In the upcoming years, at least three new projects are foreseen to be fully archived at the PSA. The BepiColombo mission is scheduled for launch in 2018. Following that, the ExoMars Rover Surface Platform (RSP) in 2020, and then the JUpiter ICy moon Explorer (JUICE). All of these will archive their data in the PSA. In addition, a few ground-based support programmes are also available, especially for the Venus Express and Rosetta missions. The newly designed PSA will enhance the user experience and will significantly reduce the complexity for users to find their data promoting one-click access to the scientific datasets with more customized views when needed. This includes a better integration with Planetary GIS analysis tools and Planetary interoperability services (search and retrieve data, supporting e.g. PDAP, EPN-TAP). It will also be up

  18. Applying strategies from libertarian paternalism to decision making for prostate specific antigen (PSA) screening

    PubMed Central

    2011-01-01

    Background Despite the recent publication of results from two randomized clinical trials, prostate specific antigen (PSA) screening for prostate cancer remains a controversial issue. There is lack of agreement across studies that PSA screening significantly reduces prostate cancer mortality. In spite of these facts, the widespread use of PSA testing in the United States leads to overdetection and overtreatment of clinically indolent prostate cancer, and its associated harms of incontinence and impotence. Discussion Given the inconclusive results from clinical trials and incongruent PSA screening guidelines, the decision to screen for prostate cancer with PSA testing is an uncertain one for patients and health care providers. Screening guidelines from some health organizations recommend an informed decision making (IDM) or shared decision making (SDM) approach for deciding on PSA screening. These approaches aim to empower patients to choose among the available options by making them active participants in the decision making process. By increasing involvement of patients in the clinical decision-making process, IDM/SDM places more of the responsibility for a complex decision on the patient. Research suggests, however, that patients are not well-informed of the harms and benefits associated with prostate cancer screening and are also subject to an assortment of biases, emotion, fears, and irrational thought that interferes with making an informed decision. In response, the IDM/SDM approaches can be augmented with strategies from the philosophy of libertarian paternalism (LP) to improve decision making. LP uses the insights of behavioural economics to help people better make better choices. Some of the main strategies of LP applicable to PSA decision making are a default decision rule, framing of decision aids, and timing of the decision. In this paper, we propose that applying strategies from libertarian paternalism can help with PSA screening decision

  19. Applying strategies from libertarian paternalism to decision making for prostate specific antigen (PSA) screening.

    PubMed

    Wheeler, David C; Szymanski, Konrad M; Black, Amanda; Nelson, David E

    2011-04-21

    Despite the recent publication of results from two randomized clinical trials, prostate specific antigen (PSA) screening for prostate cancer remains a controversial issue. There is lack of agreement across studies that PSA screening significantly reduces prostate cancer mortality. In spite of these facts, the widespread use of PSA testing in the United States leads to overdetection and overtreatment of clinically indolent prostate cancer, and its associated harms of incontinence and impotence. Given the inconclusive results from clinical trials and incongruent PSA screening guidelines, the decision to screen for prostate cancer with PSA testing is an uncertain one for patients and health care providers. Screening guidelines from some health organizations recommend an informed decision making (IDM) or shared decision making (SDM) approach for deciding on PSA screening. These approaches aim to empower patients to choose among the available options by making them active participants in the decision making process. By increasing involvement of patients in the clinical decision-making process, IDM/SDM places more of the responsibility for a complex decision on the patient. Research suggests, however, that patients are not well-informed of the harms and benefits associated with prostate cancer screening and are also subject to an assortment of biases, emotion, fears, and irrational thought that interferes with making an informed decision. In response, the IDM/SDM approaches can be augmented with strategies from the philosophy of libertarian paternalism (LP) to improve decision making. LP uses the insights of behavioural economics to help people better make better choices. Some of the main strategies of LP applicable to PSA decision making are a default decision rule, framing of decision aids, and timing of the decision. In this paper, we propose that applying strategies from libertarian paternalism can help with PSA screening decision-making. Our proposal to augment IDM

  20. Proteins Annexin A2 and PSA in Prostate Cancer Biopsies Do Not Predict Biochemical Failure.

    PubMed

    Lamb, David S; Sondhauss, Sven; Dunne, Jonathan C; Woods, Lisa; Delahunt, Brett; Ferguson, Peter; Murray, Judith; Nacey, John N; Denham, James W; Jordan, T William

    2017-12-01

    We previously reported the use of mass spectrometry and western blotting to identify proteins from tumour regions of formalin-fixed paraffin-embedded biopsies from 16 men who presented with apparently localized prostate cancer, and found that annexin A2 (ANXA2) appeared to be a better predictor of subsequent biochemical failure than prostate-specific antigen (PSA). In this follow-up study, ANXA2 and PSA were measured using western blotting of proteins extracted from biopsies from 37 men from a subsequent prostate cancer trial. No significant differences in ANXA2 and PSA levels were observed between men with and without biochemical failure. The statistical effect sizes were small, d=0.116 for ANXA2, and 0.266 for PSA. ANXA2 and PSA proteins measured from biopsy tumour regions are unlikely to be good biomarkers for prediction of the clinical outcome of prostate cancer presenting with apparently localized disease. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. Abnormal neural precursor cell regulation in the early postnatal Fragile X mouse hippocampus.

    PubMed

    Sourial, Mary; Doering, Laurie C

    2017-07-01

    The regulation of neural precursor cells (NPCs) is indispensable for a properly functioning brain. Abnormalities in NPC proliferation, differentiation, survival, or integration have been linked to various neurological diseases including Fragile X syndrome. Yet, no studies have examined NPCs from the early postnatal Fragile X mouse hippocampus despite the importance of this developmental time point, which marks the highest expression level of FMRP, the protein missing in Fragile X, in the rodent hippocampus and is when hippocampal NPCs have migrated to the dentate gyrus (DG) to give rise to lifelong neurogenesis. In this study, we examined NPCs from the early postnatal hippocampus and DG of Fragile X mice (Fmr1-KO). Immunocytochemistry on neurospheres showed increased Nestin expression and decreased Ki67 expression, which collectively indicated aberrant NPC biology. Intriguingly, flow cytometric analysis of the expression of the antigens CD15, CD24, CD133, GLAST, and PSA-NCAM showed a decreased proportion of neural stem cells (GLAST + CD15 + CD133 + ) and an increased proportion of neuroblasts (PSA-NCAM + CD15 + ) in the DG of P7 Fmr1-KO mice. This was mirrored by lower expression levels of Nestin and the mitotic marker phospho-histone H3 in vivo in the P9 hippocampus, as well as a decreased proportion of cells in the G 2 /M phases of the P7 DG. Thus, the absence of FMRP leads to fewer actively cycling NPCs, coinciding with a decrease in neural stem cells and an increase in neuroblasts. Together, these results show the importance of FMRP in the developing hippocampal formation and suggest abnormalities in cell cycle regulation in Fragile X. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  2. Decreased expression of CD69 in chronic fatigue syndrome in relation to inflammatory markers: evidence for a severe disorder in the early activation of T lymphocytes and natural killer cells.

    PubMed

    Mihaylova, Ivana; DeRuyter, Marcel; Rummens, Jean-Luc; Bosmans, Eugene; Maes, Michael

    2007-08-01

    There is some evidence that patients with chronic fatigue syndrome (CFS) suffer from immune abnormalities, such as immune activation and decreased immune cell responsivity upon polyclonal stimili. This study was designed to evaluate lymphocyte activation in CFS by using a CD69 expression assay. CD69 acts as a costimulatory molecule for T- and natural killer (NK) cell activation. We collected whole blood from CFS patients, who met CDC criteria, and healthy volunteers. The blood samples were stimulated with mitogens during 18 h and the levels of activated T and NK cells expressing CD69 were measured on a Coulter Epics flow cytometer using a three color immunofluorescence staining protocol. The expression of the CD69 activation marker on T cells (CD3+, CD3+CD4+, and CD3+CD8+) and on NK cells (CD45+CD56+) was significantly lower in CFS patients than in healthy subjects. These differences were significant to the extent that a significant diagnostic performance was obtained, i.e. the area under the ROC curve was around 89%. No differences either in the number of leukocytes or in the number or percentage of lymphocytes, i.e. CD3, CD4, CD8 and CD19, could be found between CFS patients and the controls. Patients with CFS show defects in T- and NK cell activation. Since induction of CD69 surface expression is dependent on the activation of the protein kinase C (PKC) activation pathway, it is suggested that in CFS there is a disorder in the early activation of the immune system involving PKC.

  3. The Degree of Early Life Stress Predicts Decreased Medial Prefrontal Activations and the Shift from Internally to Externally Guided Decision Making: An Exploratory NIRS Study during Resting State and Self-Oriented Task

    PubMed Central

    Nakao, Takashi; Matsumoto, Tomoya; Morita, Machiko; Shimizu, Daisuke; Yoshimura, Shinpei; Northoff, Georg; Morinobu, Shigeru; Okamoto, Yasumasa; Yamawaki, Shigeto

    2013-01-01

    Early life stress (ELS), an important risk factor for psychopathology in mental disorders, is associated neuronally with decreased functional connectivity within the default mode network (DMN) in the resting state. Moreover, it is linked with greater deactivation in DMN during a working memory task. Although DMN shows large amplitudes of very low-frequency oscillations (VLFO) and strong involvement during self-oriented tasks, these features’ relation to ELS remains unclear. Therefore, our preliminary study investigated the relationship between ELS and the degree of frontal activations during a resting state and self-oriented task using near-infrared spectroscopy (NIRS). From 22 healthy participants, regional hemodynamic changes in 43 front-temporal channels were recorded during 5 min resting states, and execution of a self-oriented task (color-preference judgment) and a control task (color-similarity judgment). Using a child abuse and trauma scale, ELS was quantified. We observed that ELS showed a negative correlation with medial prefrontal cortex (MPFC) activation during both resting state and color-preference judgment. In contrast, no significant correlation was found between ELS and MPFC activation during color-similarity judgment. Additionally, we observed that ELS and the MPFC activation during color-preference judgment were associated behaviorally with the rate of similar color choice in preference judgment, which suggests that, for participants with higher ELS, decisions in the color-preference judgment were based on an external criterion (color similarity) rather than an internal criterion (subjective preference). Taken together, our neuronal and behavioral findings show that high ELS is related to lower MPFC activation during both rest and self-oriented tasks. This is behaviorally manifest in an abnormal shift from internally to externally guided decision making, even under circumstances where internal guidance is required. PMID:23840186

  4. Elevated Serum PSA is Associated With Human Herpesvirus 8 Infection and Increased Circulating Cytokine Levels in Men From Tobago.

    PubMed

    Henning, Jill D; Karamchandani, Jaideep M; Bonachea, Luis A; Bunker, Clareann H; Patrick, Alan L; Jenkins, Frank J

    2017-05-01

    Serum-prostate specific antigen (PSA) levels have been used for many years as a biomarker for prostate cancer. This usage is under scrutiny due to the fact that elevated PSA levels can be caused by other conditions such as benign prostatic hyperplasia and infections of or injury to the prostate. As a result, the identification of specific pathogens capable of increasing serum levels of PSA is important. A potential candidate responsible for elevated PSA is human herpesvirus 8 (HHV-8). We have reported previously that HHV-8 is capable of infecting and establishing a latent infection in the prostate. In this current study we test the hypothesis that HHV-8 infection is associated with elevated PSA levels. Circulating cytokine levels between men with elevated PSA and controls are also compared. HHV-8 serostatus was determined among men with elevated serum PSA (≥4 ng/ml; n = 168, no prostate cancer on biopsy) and age-matched controls (PSA <4 ng/ml; n = 234), Circulating cytokine levels were determined among a subset of each group (116 with elevated PSA and 85 controls). Men with an elevated serum PSA were significantly more likely to be HHV-8 seropositive (42.9%) than the age-matched cancer-free men (22.2%; OR 2.51; 95%CI 1.48-4.29, P = 00001). Comparison of circulating cytokine levels between men with elevated serum PSA and controls indicated that elevated serum PSA is associated with a pro-inflammatory response with a mixed Th1/Th2 response while HHV-8 infection was associated with significantly higher levels of IL12p70, IL-10, and IL-13 indicating a Th2 immune response. We found a significant association between HHV-8 infection and increased levels of serum PSA. In an age of patient-centered medicine, men with an elevated serum PSA should be considered for HHV-8 serology testing to determine if HHV-8 is responsible for the elevated PSA. Prostate 77: 617-624, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. Treatment strategy for metastatic prostate cancer with extremely high PSA level: reconsidering the value of vintage therapy.

    PubMed

    Yamada, Yasutaka; Sakamoto, Shinichi; Amiya, Yoshiyasu; Sasaki, Makoto; Shima, Takayuki; Komiya, Akira; Suzuki, Noriyuki; Akakura, Koichiro; Ichikawa, Tomohiko; Nakatsu, Hiroomi

    2018-05-04

    The prognostic significance of initial prostate-specific antigen (PSA) level for metastatic prostate cancer remains uncertain. We investigated the differences in prognosis and response to hormonal therapies of metastatic prostate cancer patients according to initial PSA levels. We analyzed 184 patients diagnosed with metastatic prostate cancer and divided them into three PSA level groups as follows: low (<100 ng ml -1 ), intermediate (100-999 ng ml -1 ), and high (≥1000 ng ml -1 ). All patients received androgen deprivation therapy (ADT) immediately. We investigated PSA progression-free survival (PFS) for first-line ADT and overall survival (OS) within each of the three groups. Furthermore, we analyzed response to antiandrogen withdrawal (AW) and alternative antiandrogen (AA) therapies after development of castration-resistant prostate cancer (CRPC). No significant differences in OS were observed among the three groups (P = 0.654). Patients with high PSA levels had significantly short PFS for first-line ADT (P = 0.037). Conversely, patients in the high PSA level group had significantly longer PFS when treated with AW than those in the low PSA level group (P = 0.047). Furthermore, patients with high PSA levels had significantly longer PFS when provided with AA therapy (P = 0.049). PSA responders to AW and AA therapies had significantly longer survival after CRPC development than nonresponders (P = 0.011 and P < 0.001, respectively). Thus, extremely high PSA level predicted favorable response to vintage sequential ADT and AW. The current data suggest a novel aspect of extremely high PSA value as a favorable prognostic marker after development of CRPC.

  6. Performance of serum prostate-specific antigen isoform [-2]proPSA (p2PSA) and the prostate health index (PHI) in a Chinese hospital-based biopsy population.

    PubMed

    Na, Rong; Ye, Dingwei; Liu, Fang; Chen, Haitao; Qi, Jun; Wu, Yishuo; Zhang, Guiming; Wang, Meilin; Wang, Wenying; Sun, Jielin; Yu, Guopeng; Zhu, Yao; Ren, Shancheng; Zheng, S Lilly; Jiang, Haowen; Sun, Yinghao; Ding, Qiang; Xu, Jianfeng

    2014-11-01

    The use of serum [-2]proPSA (p2PSA) and its derivative, the prostate health index (PHI), in detecting prostate cancer (PCa) have been consistently shown to have better performance than total prostate-specific antigen (tPSA) in discriminating biopsy outcomes in western countries. However, little is known about their performance in Chinese men. Our objective is to test the performance of p2PSA and PHI and their added value to tPSA in discriminating biopsy outcomes in Chinese men. Consecutive patients who underwent prostate biopsy in three tertiary hospitals in Shanghai, China during 2012-2013 were recruited. Serum tPSA, free PSA (fPSA), and p2PSA were measured centrally using Beckman Coulter's DxI 800 Immunoassay System. The primary outcome is PCa and the secondary outcome is high-grade PCa (Gleason Score of 4 + 3 or worse). Discriminative performance was assessed using the area under the receiver operating characteristic curve (AUC), detection rate and Decision Curve Analysis (DCA). Among 636 patients who underwent prostate biopsy, PHI was a significant predictor of biopsy outcomes, independent of other clinical variables. The AUC in discriminating PCa from non-PCa was consistently higher for PHI than tPSA in the entire cohort (0.88 vs. 0.81) as well as in patients with tPSA at 2-10 ng/ml (0.73 vs. 0.53), at 10.1-20 ng/ml (0.81 vs. 0.58), and at tPSA >20 ng/ml (0.90 vs. 0.80). The differences were statistically significant in all comparisons, P < 0.01. To detect 90% of all PCa in the cohort, 362 and 457 patients would need to be biopsied based on PHI and tPSA cutoff, respectively, a 21% reduction for PHI. Similar results were found for discriminating high-grade PCa. PHI provides added value over tPSA in discriminating PCa and high-grade PCa in patients who underwent prostate biopsy in China. © 2014 Wiley Periodicals, Inc.

  7. A comparison of US and Australian men's values and preferences for PSA screening.

    PubMed

    Howard, Kirsten; Brenner, Alison T; Lewis, Carmen; Sheridan, Stacey; Crutchfield, Trisha; Hawley, Sarah; Nielsen, Matthew E; Pignone, Michael P

    2013-10-05

    Patient preferences derived from an assessment of values can help inform the design of screening programs, but how best to do so, and whether such preferences differ cross-nationally, has not been well-examined. The objective of this study was to compare the values and preferences of Australian and US men for PSA (prostate specific antigen) screening. We used an internet based survey of men aged 50-75 with no personal or family history of prostate cancer recruited from on-line panels of a survey research organization in the US and Australia. Participants viewed information on prostate cancer and prostate cancer screening with PSA testing then completed a values clarification task that included information on 4 key attributes: chance of 1) being diagnosed with prostate cancer, 2) dying from prostate cancer, 3) requiring a biopsy as a result of screening, and 4) developing impotence or incontinence as a result of screening. The outcome measures were self reported most important attribute, unlabelled screening test choice, and labelled screening intent, assessed on post-task questionnaires. We enrolled 911 participants (US:456; AU:455), mean age was 59.7; 88.0% were white; 36.4% had completed at least a Bachelors' degree; 42.0% reported a PSA test in the past 12 months. Australian men were more likely to be white and to have had recent screening. For both US and Australian men, the most important attribute was the chance of dying from prostate cancer. Unlabelled post-task preference for the PSA screening-like option was greater for Australian (39.1%) compared to US (26.3%) participants (adjusted OR 1.68 (1.28-2.22)). Labelled intent for screening was high for both countries: US:73.7%, AUS:78.0% (p = 0.308). There was high intent for PSA screening in both US and Australian men; fewer men in each country chose the PSA-like option on the unlabelled question. Australian men were somewhat more likely to prefer PSA screening. Men in both countries did not view the

  8. Vaginal Prostate Specific Antigen (PSA) Is a Useful Biomarker of Semen Exposure Among HIV-Infected Ugandan Women.

    PubMed

    Woolf-King, Sarah E; Muyindike, Winnie; Hobbs, Marcia M; Kusasira, Adrine; Fatch, Robin; Emenyonu, Nneka; Johnson, Mallory O; Hahn, Judith A

    2017-07-01

    The practical feasibility of using prostate specific antigen (PSA) as a biomarker of semen exposure was examined among HIV-infected Ugandan women. Vaginal fluids were obtained with self-collected swabs and a qualitative rapid test (ABAcard ® p30) was used to detect PSA. Trained laboratory technicians processed samples on-site and positive PSA tests were compared to self-reported unprotected vaginal sex (UVS) in the last 48 h. A total of 77 women submitted 126 samples for PSA testing at up to three study visits. Of these samples, 31 % (n = 39/126) were PSA positive, and 64 % (n = 25/39) of the positive PSA samples were accompanied by self-report of no UVS at the study visit the PSA was collected. There were no reported difficulties with specimen collection, storage, or processing. These findings provide preliminary data on high levels of misreported UVS among HIV-infected Ugandan women using practically feasible methods for PSA collection and processing.

  9. Presence of PSA auto-antibodies in men with prostate abnormalities (prostate cancer/benign prostatic hyperplasia/prostatitis).

    PubMed

    Lokant, M T; Naz, R K

    2015-04-01

    Prostate-specific antigen (PSA), produced by the prostate, liquefies post-ejaculate semen. PSA is detected in semen and blood. Increased circulating PSA levels indicate prostate abnormality [prostate cancer (PC), benign prostatic hyperplasia (BPH), prostatitis (PTIS)], with variance among individuals. As the prostate has been proposed as an immune organ, we hypothesise that variation in PSA levels among men may be due to presence of auto-antibodies against PSA. Sera from healthy men (n = 28) and men having prostatitis (n = 25), BPH (n = 30) or PC (n = 29) were tested for PSA antibody presence using enzyme-linked immunosorbent assay (ELISA) values converted to standard deviation (SD) units, and Western blotting. Taking ≥2 SD units as cut-off for positive immunoreactivity, 0% of normal men, 0% with prostatitis, 33% with BPH and 3.45% with PC demonstrated PSA antibodies. One-way analysis of variance (anova) performed on the mean absorbance values and SD units of each group showed BPH as significantly different (P < 0.01) compared with PC and prostatitis. All others were nonsignificant (P < 0.05). Men (33%) with BPH had PSA antibodies by ELISA and Western blot. These discoveries may find clinical application in differential diagnosis among prostate abnormalities, especially differentiating BPH from prostate cancer and prostatitis. © 2014 Blackwell Verlag GmbH.

  10. Men presenting with prostate-specific antigen (PSA) values of over 100 ng/mL.

    PubMed

    Ang, Mann; Rajcic, Branimir; Foreman, Darren; Moretti, Kim; O'Callaghan, Michael E

    2016-04-01

    To investigate overall survival and prostate cancer-specific mortality in men with prostate cancer presenting with a PSA level <100 ng/mL at the time of diagnosis. Five-thousand seven hundred and sixteen patients with prostate cancer and a recorded diagnostic PSA level extracted from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC) database. Men included were diagnosed between January 1998 and August 2013. Patients were divided into groups according to diagnostic PSA level: <20, 20-≤100, 100-≤200 ng/mL, 200-≤500 ng/mL, and >500 ng/mL. Outcomes measured include overall survival and prostate cancer-specific mortality. Clinical stage, Gleason score and the presence of bony metastasis was evaluated to determine if they were prognostic factors in patients with PSA over 100 at diagnosis. Cox proportional hazards and competing risks regression were used to model overall survival and prostate cancer-specific mortality outcomes respectively. Of this cohort, 241 patients (4.2%) had a diagnostic PSA level >100 ng/mL. Patients with PSA >100 ng/mL have a significant reduction in five (29.1% vs 62.5% vs 87%) and ten-year (18.2% vs 36.7% vs 70.7%) overall survival when compared to men with diagnostic PSA 20-100 and <20 ng/mL respectively. In this group, prostate cancer-specific mortality was associated with Gleason score and metastases, but not PSA level at diagnosis. Overall survival was associated with PSA level, Gleason score and age. There was a linear increase in risk (overall survival) as PSA increased until 200 and no association thereafter. Models of overall survival and prostate cancer-specific mortality incorporating a risk stratification developed by Izumi et al. predicted overall survival but not prostate cancer-specific mortality. The use of this stratification did not improve model accuracy. Only a small number of men (4.2%) with prostate cancer present with PSA >100 ng/mL at diagnosis. Overall survival at five and ten

  11. Do Men Receive Information Required for Shared Decision Making About PSA Testing? Results from a National Survey.

    PubMed

    Leyva, Bryan; Persoskie, Alexander; Ottenbacher, Allison; Hamilton, Jada G; Allen, Jennifer D; Kobrin, Sarah C; Taplin, Stephen H

    2016-12-01

    Most professional organizations, including the American College of Physicians and U.S. Preventive Services Task Force, emphasize that screening for prostate cancer with the prostate-specific antigen (PSA) test should only occur after a detailed discussion between the health-care provider and patient about the known risks and potential benefits of the test. In fact, guidelines strongly advise health-care providers to involve patients, particularly those at elevated risk of prostate cancer, in a "shared decision making" (SDM) process about PSA testing. We analyzed data from the National Cancer Institute's Health Information National Trends Survey 2011-2012-a nationally representative, cross-sectional survey-to examine the extent to which health professionals provided men with information critical to SDM prior to PSA testing, including (1) that patients had a choice about whether or not to undergo PSA testing, (2) that not all doctors recommend PSA testing, and (3) that no one is sure if PSA testing saves lives. Over half (55 %) of men between the ages of 50 and 74 reported ever having had a PSA test. However, only 10 % of men, regardless of screening status, reported receiving all three pieces of information: 55 % reported being informed that they could choose whether or not to undergo testing, 22 % reported being informed that some doctors recommend PSA testing and others do not, and 14 % reported being informed that no one is sure if PSA testing actually saves lives. Black men and men with lower levels of education were less likely to be provided this information. There is a need to improve patient-provider communication about the uncertainties associated with the PSA test. Interventions directed at patients, providers, and practice settings should be considered.

  12. PSA and Prostate Health Index based prostate cancer screening in a hereditary migration complicated population: implications in precision diagnosis.

    PubMed

    Akizhanova, Mariyam; Iskakova, Elzira E; Kim, Valdemir; Wang, Xiao; Kogay, Roman; Turebayeva, Aiym; Sun, Qinglei; Zheng, Ting; Wu, Shenghui; Miao, Lixia; Xie, Yingqiu

    2017-01-01

    Precision diagnosis requires specific markers for differential ethnic populations. Prostate-Specific Antigen (PSA) level (threshold of 4ng/ml) has been widely used to screen prostate cancer and as reference of pro-biopsy but false diagnosis frequently occurs. Prostate health Index (PHI) is a new diagnosis marker which combines PSA, free PSA and p2PSA4. Overall the PCa screening database is lacking in Kazakhstani patients. We analyzed the PSA levels and Gleason scores of 222 biopsies collected in 2015 in Almaty area, Kazakhstan approved by institutional ethics board. We found using PSA of 4ng/ml as threshold, only 25.68% of patients have cancer with Gleason score ranged 6-8 and 65.77% of patients have no character of cancer. Moreover, there is no significant correlation between PSA and cancerous (P=0.266) or Gleason grade (P=0.3046) based on pathological biopsy. In addition, PHI is not correlated to prostate cancer (P=0.4301). Our data suggest that false-positive rate is much higher than the correct-positive diagnosis when using PSA as the first screening. Thus in this cohort study, most patients can not get benefit from the PSA screening for precision PCa diagnosis. As Kazakhstani family trees are unique and complicated because of history and migration, the high rate of over diagnosis might be due to the hyperexpression of PSA via heterosis in Eurasian men. Therefore we should be cautious when using pro-biopsy in precision diagnosis for Eurasian prostate cancer patients.

  13. Urine output - decreased

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003147.htm Urine output - decreased To use the sharing features on this page, please enable JavaScript. Decreased urine output means that you produce less urine than ...

  14. Two-year survival rates of anti-TNF-α therapy in psoriatic arthritis (PsA) patients with either polyarticular or oligoarticular PsA.

    PubMed

    Iannone, F; Lopriore, S; Bucci, R; Scioscia, C; Anelli, M G; Notarnicola, A; Lapadula, G

    2015-05-01

    To evaluate the 2-year drug survival rates of the tumour necrosis factor (TNF)-α blockers adalimumab, etanercept, and infliximab in psoriatic arthritis (PsA) patients with either oligoarticular (oligo-PsA) or polyarticular PsA (poly-PsA). We studied a prospective cohort of 328 PsA patients with peripheral arthritis (213 with poly-PsA and 115 with oligo-PsA), beginning their first ever anti-TNF-α treatment with adalimumab, etanercept, or infliximab. The aim of the study was to evaluate the drug survival rates and possible baseline predictors at 2 years. After 24 months, persistence in therapy with the first anti-TNF-α blocker was not statistically different in the oligo-PsA (70.4%) and poly-PsA (65.7%) subsets. Predictors of drug discontinuation were female sex [hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.00-2.68, p = 0.04] and starting the therapy in years 2003-8 (HR 0.51, 95% CI 0.33-0.80, p = 0.003). In poly-PsA, the persistence of etanercept (68.3%) was significantly higher than that of adalimumab (51.9%, p = 0.01), whereas in oligo-PsA no significant difference was detected. In poly-PsA, the period 2003-8 was a negative predictor (HR 0.36, 95% CI 0.21-0.62, p = 0.0001) whereas in oligo-PsA female gender was a positive predictor of drug discontinuation (HR 2.08, 95% CI 1.02-4.24, p = 0.04). With regard to clinical outcomes, the best responses in terms of European League Against Rheumatism (EULAR) 'good' response or Disease Activity Score (DAS28) remission, crude or adjusted according to the LUND Efficacy indeX (LUNDEX), were seen in patients on etanercept or infliximab. Our study provides some evidence that anti-TNF-α drugs may perform differently in PsA, and that the analysis of clinical disease subsets may improve our knowledge and promote better management of PsA.

  15. Student-Designed Public Service Announcement (PSA) Videos to Enhance Motivation and Engagement

    ERIC Educational Resources Information Center

    Abrams, Kenneth

    2012-01-01

    Educators often focus on enhancing student motivation and engagement. This article describes an activity with these aims, in which undergraduates (a) learn about theories and research on means of persuasion and (b) in small groups design and record a public service announcement (PSA) video, write a brief paper that outlines the theories used to…

  16. PSA discriminator influence on (222)Rn efficiency detection in waters by liquid scintillation counting.

    PubMed

    Stojković, Ivana; Todorović, Nataša; Nikolov, Jovana; Tenjović, Branislava

    2016-06-01

    A procedure for the (222)Rn determination in aqueous samples using liquid scintillation counting (LSC) was evaluated and optimized. Measurements were performed by ultra-low background spectrometer Quantulus 1220™ equipped with PSA (Pulse Shape Analysis) circuit which discriminates alpha/beta spectra. Since calibration procedure is carried out with (226)Ra standard, which has both alpha and beta progenies, it is clear that PSA discriminator has vital importance in order to provide precise spectra separation. Improvement of calibration procedure was done through investigation of PSA discriminator level and, consequentially, the activity of (226)Ra calibration standard influence on (222)Rn efficiency detection. Quench effects on generated spectra i.e. determination of radon efficiency detection were also investigated with quench calibration curve obtained. Radon determination in waters based on modified procedure according to the activity of (226)Ra standard used, dependent on PSA setup, was evaluated with prepared (226)Ra solution samples and drinking water samples with assessment of measurement uncertainty variation included. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. A Microfluidic Love-Wave Biosensing Device for PSA Detection Based on an Aptamer Beacon Probe.

    PubMed

    Zhang, Feng; Li, Shuangming; Cao, Kang; Wang, Pengjuan; Su, Yan; Zhu, Xinhua; Wan, Ying

    2015-06-11

    A label-free and selective aptamer beacon-based Love-wave biosensing device was developed for prostate specific antigen (PSA) detection. The device consists of the following parts: LiTaO3 substrate with SiO2 film as wave guide layer, two set of inter-digital transducers (IDT), gold film for immobilization of the biorecongniton layer and a polydimethylsiloxane (PDMS) microfluidic channels. DNA aptamer, or "artificial antibody", was used as the specific biorecognition probe for PSA capture. Some nucleotides were added to the 3'-end of the aptamer to form a duplex with the 3'-end, turning the aptamer into an aptamer-beacon. Taking advantage of the selective target-induced assembly changes arising from the "aptamer beacon", highly selective and specific detection of PSA was achieved. Furthermore, PDMS microfluidic channels were designed and fabricated to realize automated quantitative sample injection. After optimization of the experimental conditions, the established device showed good performance for PSA detection between 10 ng/mL to 1 μg/mL, with a detection limit of 10 ng/mL. The proposed sensor might be a promising alternative for point of care diagnostics.

  18. A Diet, Physical Activity, and Meditation Intervention in Men With Rising Prostate-Specific Antigen (PSA)

    DTIC Science & Technology

    2006-05-01

    AD_________________ Award Number: DAMD17-03-1-0139 TITLE: A Diet , Physical Activity, and...A Diet , Physical Activity, and Meditation Intervention in Men With Rising Prostate- 5a. CONTRACT NUMBER Specific Antigen (PSA...favorably affected by an intensive, vegetable-based diet , plus physical activity and mindfulness-based stress reduction. This randomized trial will

  19. Nuclear power and probabilistic safety assessment (PSA): past through future applications

    NASA Astrophysics Data System (ADS)

    Stamatelatos, M. G.; Moieni, P.; Everline, C. J.

    1995-03-01

    Nuclear power reactor safety in the United States is about to enter a new era -- an era of risk- based management and risk-based regulation. First, there was the age of `prescribed safety assessment,' during which a series of design-basis accidents in eight categories of severity, or classes, were postulated and analyzed. Toward the end of that era, it was recognized that `Class 9,' or `beyond design basis,' accidents would need special attention because of the potentially severe health and financial consequences of these accidents. The accident at Three Mile Island showed that sequences of low-consequence, high-frequency events and human errors can be much more risk dominant than the Class 9 accidents. A different form of safety assessment, PSA, emerged and began to gain ground against the deterministic safety establishment. Eventually, this led to the current regulatory requirements for individual plant examinations (IPEs). The IPEs can serve as a basis for risk-based regulation and management, a concept that may ultimately transform the U.S. regulatory process from its traditional deterministic foundations to a process predicated upon PSA. Beyond the possibility of a regulatory environment predicated upon PSA lies the possibility of using PSA as the foundation for managing daily nuclear power plant operations.

  20. Antibiotics may not decrease prostate-specific antigen levels or prevent unnecessary prostate biopsy in patients with moderately increased prostate-specific antigen levels: A meta-analysis.

    PubMed

    Yang, Lu; Zhu, Yuchun; Tang, Zhuang; Chen, Yongji; Gao, Liang; Liu, Liangren; Han, Ping; Li, Xiang; Wei, Qiang

    2015-05-01

    To evaluate the effect of empiric antibiotics on decreasing prostate-specific antigen (PSA) levels and the possibility of avoiding unnecessary prostate biopsies (PBs). A systematic search of PubMed, Embase, and the Cochrane Library was performed to identify all randomized controlled trials (RCTs) that compared effects of empiric antibiotics with no treatment or placebo on lowering PSA levels and minimizing unnecessary PBs in patients with moderately increased PSA levels. The Cochrane Collaboration Review Manager software (RevMan 5.1.4) was used for statistical analysis. The inclusion criteria for the study were met by 6 RCTs (1 placebo controlled and 5 no treatment controlled) involving 656 patients. The synthesized data from these RCTs indicated that there were no significant differences between the antibiotic and control groups in the PSA levels after treatment (mean difference [MD] = 0.15, 95% CI:-0.50 to 0.81, P = 0.65], number of patients with decreased PSA levels after treatment (relative risk [RR] = 1.22, 95% CI: 0.90-1.65, P = 0.20], prostate-specific antigen density levels after treatment (MD =-0.04, 95% CI:-0.15 to 0.07, P = 0.47), f/t% PSA after treatment (MD =-1.47, 95% CI:-4.65 to 1.71, P = 0.37), number of patients with responsive PSA (RR = 1.02, 95% CI: 0.58-1.81, P = 0.94), and individual Pca-positiverate in these patients (RR = 1.07, 95% CI: 0.53-2.16, P = 0.86), and Pca-positiverates (RR = 0.85, 95% CI: 0.48-1.50, P = 0.57). However, the antibiotic group had a significant change in the net PSA decrease after treatment compared with the control group (MD = 1.44, 95% CI: 0.70-2.17, P = 0.0001). The use of empiric antibiotics may not significantly decrease PSA levels or avoid unnecessary PBs. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. PSA-alpha-2-macroglobulin complex is enzymatically active in the serum of patients with advanced prostate cancer and can degrade circulating peptide hormones.

    PubMed

    Kostova, Maya B; Brennen, William Nathaniel; Lopez, David; Anthony, Lizamma; Wang, Hao; Platz, Elizabeth; Denmeade, Samuel R

    2018-08-01

    Prostate cancer cells produce high levels of the serine protease Prostate-Specific Antigen (PSA). PSA is enzymatically active in the tumor microenvironment but is presumed to be enzymatically inactive in the blood due to complex formation with serum protease inhibitors α-1-antichymotrypsin and α-2-macroglobulin (A2M). PSA-A2M complexes cannot be measured by standard ELISA assays and are also rapidly cleared from the circulation. Thus the exact magnitude of PSA production by prostate cancer cells is not easily measured. The PSA complexed to A2M is unable to cleave proteins but maintains the ability to cleave small peptide substrates. Thus, in advanced prostate cancer, sufficient PSA-A2M may be in circulation to effect total A2M levels, levels of cytokines bound to A2M and hydrolyze small circulating peptide hormones. Total A2M levels in men with advanced prostate cancer and PSA levels above 1000 ng/mL were measured by ELISA and compared to controls. Additional ELISA assays were used to measure levels of IL-6 and TGF-beta which can bind to A2M. The ability of PSA-A2M complexes to hydrolyze protein and peptide substrates was analyzed ± PSA inhibitor. Enzymatic activity of PSA-A2M in serum of men with high PSA levels was also assayed. Serum A2M levels are inversely correlated with PSA levels in men with advanced prostate cancer. Il-6 Levels are significantly elevated in men with PSA >1000 ng/mL compared to controls with PSA <0.1 ng/mL. PSA-A2M complex in serum of men with PSA levels >1000 ng/mL can hydrolyze small fluorescently labeled peptide substrates but not large proteins that are PSA substrates. PSA can hydrolyze small peptide hormones like PTHrP and osteocalcin. PSA complexed to A2M retains the ability to degrade PTHrP. In advanced prostate cancer with PSA levels >1000 ng/mL, sufficient PSA-A2M is present in circulation to produce enzymatic activity against circulating small peptide hormones. Sufficient PSA is produced in advanced prostate

  2. Prostate-Specific Antigen (PSA) Screening and New Biomarkers for Prostate Cancer (PCa)

    PubMed Central

    Rittenhouse, Harry; Hu, Xinhai; Cammann, Henning; Jung, Klaus

    2014-01-01

    Abstract PSA screening reduces PCa-mortality but the disadvantages overdiagnosis and overtreatment require multivariable risk-prediction tools to select appropriate treatment or active surveillance. This review explains the differences between the two largest screening trials and discusses the drawbacks of screening and its meta-analysisxs. The current American and European screening strategies are described. Nonetheless, PSA is one of the most widely used tumor markers and strongly correlates with the risk of harboring PCa. However, while PSA has limitations for PCa detection with its low specificity there are several potential biomarkers presented in this review with utility for PCa currently being studied. There is an urgent need for new biomarkers especially to detect clinically significant and aggressive PCa. From all PSA-based markers, the FDA-approved prostate health index (phi) shows improved specificity over percent free and total PSA. Another kallikrein panel, 4K, which includes KLK2 has recently shown promise in clinical research studies but has not yet undergone formal validation studies. In urine, prostate cancer gene 3 (PCA3) has also been validated and approved by the FDA for its utility to detect PCa. The potential correlation of PCA3 with cancer aggressiveness requires more clinical studies. The detection of the fusion of androgen-regulated genes with genes of the regulatory transcription factors in tissue of ~50% of all PCa-patients is a milestone in PCa research. A combination of the urinary assays for TMPRSS2:ERG gene fusion and PCA3 shows an improved accuracy for PCa detection. Overall, the field of PCa biomarker discovery is very exciting and prospective. PMID:27683457

  3. Mutations in the prostate specific antigen (PSA/KLK3) correlate with male infertility.

    PubMed

    Gupta, Nishi; Sudhakar, Digumarthi V S; Gangwar, Pravin Kumar; Sankhwar, Satya Narayan; Gupta, Nalini J; Chakraborty, Baidyanath; Thangaraj, Kumarasamy; Gupta, Gopal; Rajender, Singh

    2017-09-11

    Prostate specific antigen (PSA/KLK3) is known to be the chief executor of the fragmentation of semenogelins, dissolution of semen coagulum, thereby releasing sperm for active motility. Recent research has found that semenogelins also play significant roles in sperm fertility by affecting hyaluronidase activity, capacitation and motility, thereby making PSA important for sperm fertility beyond simple semen liquefaction. PSA level in semen has been shown to correlate with sperm motility, suggesting that PSA level/activity can affect fertility. However, no study investigating the genetic variations in the KLK3/PSA gene in male fertility has been undertaken. We analyzed the complete coding region of the KLK3 gene in ethnically matched 875 infertile and 290 fertile men to find if genetic variations in KLK3 correlate with infertility. Interestingly, this study identified 28 substitutions, of which 8 were novel (not available in public databases). Statistical comparison of the genotype frequencies showed that five SNPs, rs266881 (OR = 2.92, P < 0.0001), rs174776 (OR = 1.91, P < 0.0001), rs266875 (OR = 1.44, P = 0.016), rs35192866 (OR = 4.48, P = 0.025) and rs1810020 (OR = 2.08, P = 0.034) correlated with an increased risk of infertility. On the other hand, c.206 + 235 T > C, was more freuqent in the control group, showing protective association. Our findings suggest that polymorphisms in the KLK3 gene correlate with infertility risk.

  4. Deciding on PSA-screening - Quality of current consumer information on the Internet.

    PubMed

    Korfage, Ida J; van den Bergh, Roderick C N; Essink-Bot, Marie-Louise

    2010-11-01

    Given that screening for prostate cancer has the potential to reduce prostate cancer mortality at the expense of considerable overdiagnosis and overtreatment, the availability of core consumer information - correct, balanced and supportive of autonomous decision-making - is a must. We assessed the quality of consumer information available through the Internet per November 2009 and its possible contribution to informed decision-making by potential screenees. Consumer information on PSA-screening was sought through the Internet in November 2009. Materials had to be targeted at potential consumers, offered by not-for-profit organisations, released in 2005 or after, in English or Dutch. Per material 2 of the authors assessed independently from each other whether standardised pre-defined topics were addressed, whether the content was correct and which approach was taken towards the decision-making process about uptake. Twenty-three materials were included, of which 11 were released (shortly) after the results of 2 large randomized-controlled trials (RCTs) that evaluated the effectiveness of screening for prostate cancer had been published in March 2009. That a PSA-test result can be abnormal because of non-cancerous conditions (false positive) and that it may miss prostate cancer (false negative) was not addressed in 2/23 and 8/23 materials, respectively. The risk of overdiagnosis and overtreatment was not mentioned in 6 out of 23. PSA-screening was presented as a usual thing to do in some materials, whereas other materials emphasised the voluntary nature of PSA-screening ('it is your decision'). The content of 19/23 materials was considered sufficiently informative according to the pre-defined criteria, 12/23 materials were considered supportive of informed decision-making by men. Most materials of not-for-profit organizations supplied adequate information about PSA-screening, whilst the degree of persuasion towards uptake reflected variations in opinions on men

  5. Evaluation of a rapid quantitative determination method of PSA concentration with gold immunochromatographic strips.

    PubMed

    Wu, Cheng-Ching; Lin, Hung-Yu; Wang, Chao-Ping; Lu, Li-Fen; Yu, Teng-Hung; Hung, Wei-Chin; Houng, Jer-Yiing; Chung, Fu-Mei; Lee, Yau-Jiunn; Hu, Jin-Jia

    2015-11-03

    Prostate cancer remains the most common cancer in men. Qualitative or semi-quantitative immunochromatographic measurements of prostate specific antigen (PSA) have been shown to be simple, noninvasive and feasible. The aim of this study was to evaluate an optimized gold immunochromatographic strip device for the detection of PSA, in which the results can be analysed using a Chromogenic Rapid Test Reader to quantitatively assess the test results. This reader measures the reflectance of the signal line via a charge-coupled device camera. For quantitative analysis, PSA concentration was computed via a calibration equation. Capillary blood samples from 305 men were evaluated, and two independent observers interpreted the test results after 12 min. Blood samples were also collected and tested with a conventional quantitative assay. Sensitivity, specificity, positive and negative predictive values, and accuracy of the PSA rapid quantitative test system were 100, 96.6, 89.5, 100, and 97.4 %, respectively. Reproducibility of the test was 99.2, and interobserver variation was 8 % with a false positive rate of 3.4 %. The correlation coefficient between the ordinary quantitative assay and the rapid quantitative test was 0.960. The PSA rapid quantitative test system provided results quickly and was easy to use, so that tests using this system can be easily performed at outpatient clinics or elsewhere. This system may also be useful for initial cancer screening and for point-of-care testing, because results can be obtained within 12 min and at a cost lower than that of conventional quantitative assays.

  6. Extent of disease in recurrent prostate cancer determined by [(68)Ga]PSMA-HBED-CC PET/CT in relation to PSA levels, PSA doubling time and Gleason score.

    PubMed

    Verburg, Frederik A; Pfister, David; Heidenreich, Axel; Vogg, Andreas; Drude, Natascha I; Vöö, Stefan; Mottaghy, Felix M; Behrendt, Florian F

    2016-03-01

    To examine the relationship between the extent of disease determined by [(68)Ga]PSMA-HBED-CC-PET/CT and the important clinical measures prostate-specific antigen (PSA), PSA doubling time (PSAdt) and Gleason score. We retrospectively studied the first 155 patients with recurrent prostate cancer (PCA) referred to our university hospital for [(68)Ga]PSMA-HBED-CC PET/CT. PET/CT was positive in 44%, 79% and 89% of patients with PSA levels of ≤1, 1-2 and ≥2 ng/ml, respectively. Patients with high PSA levels showed higher rates of local prostate tumours (p < 0.001), and extrapelvic lymph node (p = 0.037) and bone metastases (p = 0.013). A shorter PSAdt was significantly associated with pelvic lymph node (p = 0.026), extrapelvic lymph node (p = 0.001), bone (p < 0.001) and visceral (p = 0.041) metastases. A high Gleason score was associated with more frequent pelvic lymph node metastases (p = 0.039). In multivariate analysis, both PSA and PSAdt were independent determinants of scan positivity and of extrapelvic lymph node metastases. PSAdt was the only independent marker of bone metastases (p = 0.001). Of 20 patients with a PSAdt <6 months and a PSA ≥2 ng/ml, 19 (95%) had a positive scan and 12 (60%) had M1a disease. Of 14 patients with PSA <1 ng/ml and PSAdt >6 months, only 5 (36%) had a positive scan and 1 (7%) had M1a disease. [(68)Ga]PSMA-HBED-CC PET/CT will identify PCA lesions even in patients with very low PSA levels. Higher PSA levels and shorter PSAdt are independently associated with scan positivity and extrapelvic metastases, and can be used for patient selection for [(68)Ga]PSMA-HBED-CC PET/CT.

  7. Prostate-specific Antigen (PSA) Density and Free to Total PSA Ratio in Diagnosing Prostate Cancer with Prostate-Specific Antigen Levels of 4.0 ng/ml or Less.

    PubMed

    Liu, Xin; Tang, Jie; Fei, Xiang; Li, Qiu-Yang

    2015-11-01

    We aimed to value the usefulness of free to total prostate-specific antigen and Prostate-specific antigen (PSA) density for prostate cancer in the patients with PSA levels of 4.0 ng/ml or less. A total of 343 subjects with PSA levels of 4.0 ng/ml or less were biopsied. All patients were divided into four groups according to the PSA levels: 0 to 1.0 ng/ml, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml, and 3.1 to 4.0 ng/ml. The reliability of cancer detection in relation to the f/t PSA ratio and PSAD were estimated. Overall, 65 people were diagnosed with prostate cancer. The detection rate was 16.28%、17.17%, 21.82%, 25.00% in subjects with PSA levels of 0 to 1.0 ng/ml, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml, and 3.1 to 4.0 ng/ml, respectively. The f/t PSA ratio was significantly lower in patients with prostate cancer and PSA levels of 2.1 to 4.0 ng/ml (P<0.05). The PSAD had no statistical significance between the two groups. Routine prostate biopsy should be undertaken if the f/t PSA ratio less than 15% with /without abnormal DRE/TRUS findings.

  8. Porous Silicon Antibody Microarrays for Quantitative Analysis: Measurement of Free and Total PSA in Clinical Plasma Samples

    PubMed Central

    Tojo, Axel; Malm, Johan; Marko-Varga, György; Lilja, Hans; Laurell, Thomas

    2014-01-01

    The antibody microarrays have become widespread, but their use for quantitative analyses in clinical samples has not yet been established. We investigated an immunoassay based on nanoporous silicon antibody microarrays for quantification of total prostate-specific-antigen (PSA) in 80 clinical plasma samples, and provide quantitative data from a duplex microarray assay that simultaneously quantifies free and total PSA in plasma. To further develop the assay the porous silicon chips was placed into a standard 96-well microtiter plate for higher throughput analysis. The samples analyzed by this quantitative microarray were 80 plasma samples obtained from men undergoing clinical PSA testing (dynamic range: 0.14-44ng/ml, LOD: 0.14ng/ml). The second dataset, measuring free PSA (dynamic range: 0.40-74.9ng/ml, LOD: 0.47ng/ml) and total PSA (dynamic range: 0.87-295ng/ml, LOD: 0.76ng/ml), was also obtained from the clinical routine. The reference for the quantification was a commercially available assay, the ProStatus PSA Free/Total DELFIA. In an analysis of 80 plasma samples the microarray platform performs well across the range of total PSA levels. This assay might have the potential to substitute for the large-scale microtiter plate format in diagnostic applications. The duplex assay paves the way for a future quantitative multiplex assay, which analyses several prostate cancer biomarkers simultaneously. PMID:22921878

  9. Decision-making Processes among Prostate Cancer Survivors with Rising PSA Levels: Results from a Qualitative Analysis.

    PubMed

    Shen, Megan Johnson; Nelson, Christian J; Peters, Ellen; Slovin, Susan F; Hall, Simon J; Hall, Matt; Herrera, Phapichaya Chaoprang; Leventhal, Elaine A; Leventhal, Howard; Diefenbach, Michael A

    2015-05-01

    Prostate cancer survivors with a rising prostate-specific antigen (PSA) level have few treatment options, experience a heightened state of uncertainty about their disease trajectory that might include the possibility of cancer metastasis and death, and often experience elevated levels of distress as they have to deal with a disease they thought they had conquered. Guided by self-regulation theory, the present study examined the cognitive and affective processes involved in shared decision making between physicians and patients who experience a rising PSA after definitive treatment for prostate cancer. In-depth interviews were conducted with 34 prostate cancer survivors who had been diagnosed with a rising PSA (i.e., biochemical failure) within the past 12 months. Survivors were asked about their experiences and affective responses after being diagnosed with a rising PSA and while weighing potential treatment options. In addition, patients were asked about their decision-making process for the initial prostate cancer treatment. Compared with the initial diagnosis, survivors with a rising PSA reported increased negative affect following their diagnosis, concern about the treatability of their disease, increased planning and health behavior change, heightened levels of worry preceding doctor appointments (especially prior to the discussion of PSA testing results), and a strong reliance on physicians' treatment recommendations. Prostate cancer survivors' decision-making processes for the treatment of a rising PSA are markedly different from those of the initial diagnosis of prostate cancer. Because patients experience heightened distress and rely more heavily on their physicians' recommendations with a rising PSA, interactions with the health care provider provide an excellent opportunity to address and assist patients with managing the uncertainty and distress inherent with rising PSA levels. © The Author(s) 2014.

  10. Association of GPs’ risk attitudes, level of empathy, and burnout status with PSA testing in primary care

    PubMed Central

    Pedersen, Anette F; Carlsen, Anders H; Vedsted, Peter

    2015-01-01

    Background Rates of prostate specific antigen (PSA) test ordering vary among GPs. Aim To examine whether GPs’ risk attitude, level of empathy, and burnout status are associated with PSA testing. Design and setting Register and questionnaire study including 129 solo GPs (active in the Central Denmark Region) and 76 672 of their adult male patients with no history of or current prostate cancer diagnosis. Method PSA tests from 2012 were retrieved from a register and classified as incident (that is, the first PSA test within 24 months), repeated normal, or repeated raised tests. This was merged with information on GPs’ risk attitudes, empathy, and burnout status from a 2012 survey. Results Patients registered with a GP with a high score on anxiety caused by uncertainty (odds ratio [OR] 1.03, 95% confidence interval [CI] = 1.00 to 1.06, P = 0.025) or concern about bad outcomes (OR 1.04; 95% CI = 1.00 to 1.08, P = 0.034) were more likely to have an incident PSA test, whereas those registered with a GP with increased tolerance for ambiguity were less likely (OR 0.98, 95% CI = 0.96 to 1.00, P = 0.025). Patients registered with a GP reporting high tolerance for ambiguity (OR 0.96, 95% CI = 0.94 to 0.99, P = 0.009) or high propensity to risk-taking (OR 0.97, 95% CI = 0.93 to 1.00, P = 0.047) were less likely to have a repeated normal PSA test. Conclusion Various aspects of GPs’ risk-taking attitudes were associated with patients’ probability of having an incident and a repeated normal PSA test. The probability of having a repeated raised PSA test was not influenced by any of the psychological factors. Burnout and empathy were not associated with PSA testing. PMID:26541183

  11. Building an information model (with the help of PSL/PSA). [Problem Statement Language/Problem Statement Analyzer

    NASA Technical Reports Server (NTRS)

    Callender, E. D.; Farny, A. M.

    1983-01-01

    Problem Statement Language/Problem Statement Analyzer (PSL/PSA) applications, which were once a one-step process in which product system information was immediately translated into PSL statements, have in light of experience been shown to result in inconsistent representations. These shortcomings have prompted the development of an intermediate step, designated the Product System Information Model (PSIM), which provides a basis for the mutual understanding of customer terminology and the formal, conceptual representation of that product system in a PSA data base. The PSIM is initially captured as a paper diagram, followed by formal capture in the PSL/PSA data base.

  12. Long-term prognostic significance of rising PSA levels following radiotherapy for localized prostate cancer - focus on overall survival.

    PubMed

    Freiberger, Carla; Berneking, Vanessa; Vögeli, Thomas-Alexander; Kirschner-Hermanns, Ruth; Eble, Michael J; Pinkawa, Michael

    2017-06-14

    The aim of this study was to evaluate the long-term prognostic significance of rising PSA levels, particularly focussing on overall survival. Two hundred ninety-five patients with localized prostate cancer were either treated with low-dose-rate (LDR) brachytherapy with I-125 seeds as monotherapy (n = 94; 145Gy), high-dose-rate (HDR) brachytherapy with Ir-192 as a boost to external beam RT (n = 66; 50.4Gy in 1.8Gy fractions EBRT + 18Gy in 9Gy fractions HDR) or EBRT alone (70.2Gy in 1.8Gy fractions; n = 135). "PSA bounce" was defined as an increase of at least 0.2 ng/ml followed by spontaneous return to pre-bounce level or lower, biochemical failure was defined according to the Phoenix definition. Median follow-up after the end of radiotherapy was 108 months. A PSA bounce showed to be a significant factor for biochemical control (BC) and overall survival (OS) after ten years (BC10 of 83% with bounce vs. 34% without, p < 0.01; OS10 of 82% with bounce vs. 59% without bounce, p < 0.01). The occurrence of a bounce, a high nadir and the therapy modality (LDR-BT vs. EBRT and HDR-BT + EBRT vs. EBRT) proved to be independent factors for PSA recurrence in multivariate Cox regression analysis. A bounce was detected significantly earlier than a PSA recurrence (median 20 months vs. 32 months after RT; p < 0.01; median PSA doubling time 5.5 vs. 5.0 months, not significant). PSA doubling time was prognostically significant in case of PSA recurrence (OS10 of 72% vs. 36% with PSA doubling time ˃ 5 months vs. ≤ 5 months; p < 0.01). Rising PSA levels within the first two years can usually be classified as a benign PSA bounce, with favourable recurrence-free and overall survival rates. PSA doubling time is an important predictor for overall survival following the diagnosis of a recurrence.

  13. Survival benefit of local versus no local treatment for metastatic prostate cancer-Impact of baseline PSA and metastatic substages.

    PubMed

    Pompe, Raisa S; Tilki, Derya; Preisser, Felix; Leyh-Bannurah, Sami-Ramzi; Bandini, Marco; Marchioni, Michele; Gild, Philipp; Tian, Zhe; Fossati, Nicola; Cindolo, Luca; Shariat, Shahrokh F; Huland, Hartwig; Graefen, Markus; Briganti, Alberto; Karakiewicz, Pierre I

    2018-07-01

    To test whether local treatment (LT), namely radical prostatectomy (RP) or brachytherapy (BT) still confers a survival benefit versus no local treatment (NLT), when adjusted for baseline PSA (bPSA). To further examine whether the effect of LT might be modulated according to bPSA and M1 substages. Of 13 906 mPCa patients within the SEER (2004-2014), 375 underwent RP, 175 BT, and 13 356 NLT. Multivariable competing risks regression (MVA CRR) analyses after 1:2 propensity score matching assessed the impact of LT versus NLT on cancer specific mortality (CSM). Interaction analyses tested the association between treatment type and bPSA within different M1 substages. MVA CRR analyses revealed lower CSM rates for LT (RP [HR: 0.55, CI: 0.44-0.70, P < 0.001] and BT [HR: 0.63, CI: 0.49-0.83, P < 0.001]) compared to NLT. A significant interaction existed between bPSA and treatment type, in M1b patients only. Here, LT conferred a survival benefit when bPSA was <60 ng/mL with maximum benefit when bPSA was <40 ng/mL. No survival benefit existed for M1b patients above the 60 ng/mL bPSA threshold and for M1c patients, regardless of bPSA. For M1a patients, LT conferred a survival benefit compared to NLT. However, dose-response according to bPSA could not be tested, due to insufficient sample size. Our observations provide new insight regarding the pivotal effect of bPSA and M1 substages on CSM, when LT is contemplated. While M1a patients benefited from LT, the survival benefit was modulated by bPSA in M1b patients and no survival benefit existed in M1c patients. © 2018 Wiley Periodicals, Inc.

  14. First Prototype of a Web Map Interface for ESA's Planetary Science Archive (PSA)

    NASA Astrophysics Data System (ADS)

    Manaud, N.; Gonzalez, J.

    2014-04-01

    We present a first prototype of a Web Map Interface that will serve as a proof of concept and design for ESA's future fully web-based Planetary Science Archive (PSA) User Interface. The PSA is ESA's planetary science archiving authority and central repository for all scientific and engineering data returned by ESA's Solar System missions [1]. All data are compliant with NASA's Planetary Data System (PDS) Standards and are accessible through several interfaces [2]: in addition to serving all public data via FTP and the Planetary Data Access Protocol (PDAP), a Java-based User Interface provides advanced search, preview, download, notification and delivery-basket functionality. It allows the user to query and visualise instrument observations footprints using a map-based interface (currently only available for Mars Express HRSC and OMEGA instruments). During the last decade, the planetary mapping science community has increasingly been adopting Geographic Information System (GIS) tools and standards, originally developed for and used in Earth science. There is an ongoing effort to produce and share cartographic products through Open Geospatial Consortium (OGC) Web Services, or as standalone data sets, so that they can be readily used in existing GIS applications [3,4,5]. Previous studies conducted at ESAC [6,7] have helped identify the needs of Planetary GIS users, and define key areas of improvement for the future Web PSA User Interface. Its web map interface shall will provide access to the full geospatial content of the PSA, including (1) observation geometry footprints of all remote sensing instruments, and (2) all georeferenced cartographic products, such as HRSC map-projected data or OMEGA global maps from Mars Express. It shall aim to provide a rich user experience for search and visualisation of this content using modern and interactive web mapping technology. A comprehensive set of built-in context maps from external sources, such as MOLA topography, TES

  15. Simulation of Unique Pressure Changing Steps and Situations in Psa Processes

    NASA Technical Reports Server (NTRS)

    Ebner, Armin D.; Mehrotra, Amal; Knox, James C.; LeVan, Douglas; Ritter, James A.

    2007-01-01

    A more rigorous cyclic adsorption process simulator is being developed for use in the development and understanding of new and existing PSA processes. Unique features of this new version of the simulator that Ritter and co-workers have been developing for the past decade or so include: multiple absorbent layers in each bed, pressure drop in the column, valves for entering and exiting flows and predicting real-time pressurization and depressurization rates, ability to account for choked flow conditions, ability to pressurize and depressurize simultaneously from both ends of the columns, ability to equalize between multiple pairs of columns, ability to equalize simultaneously from both ends of pairs of columns, and ability to handle very large pressure ratios and hence velocities associated with deep vacuum systems. These changes to the simulator now provide for unique opportunities to study the effects of novel pressure changing steps and extreme process conditions on the performance of virtually any commercial or developmental PSA process. This presentation will provide an overview of the cyclic adsorption process simulator equations and algorithms used in the new adaptation. It will focus primarily on the novel pressure changing steps and their effects on the performance of a PSA system that epitomizes the extremes of PSA process design and operation. This PSA process is a sorbent-based atmosphere revitalization (SBAR) system that NASA is developing for new manned exploration vehicles. This SBAR system consists of a 2-bed 3-step 3-layer system that operates between atmospheric pressure and the vacuum of space, evacuates from both ends of the column simultaneously, experiences choked flow conditions during pressure changing steps, and experiences a continuously changing feed composition, as it removes metabolic CO2 and H20 from a closed and fixed volume, i.e., the spacecraft cabin. Important process performance indicators of this SBAR system are size, and the

  16. Enhanced detection sensitivity of prostate-specific antigen via PSA-conjugated gold nanoparticles based on localized surface plasmon resonance: GNP-coated anti-PSA/LSPR as a novel approach for the identification of prostate anomalies.

    PubMed

    Jazayeri, M H; Amani, H; Pourfatollah, A A; Avan, A; Ferns, G A; Pazoki-Toroudi, H

    2016-10-01

    Prostate-specific antigen (PSA) is used to screen for prostate disease, although it has several limitations in its application as an organ-specific or cancer-specific marker. Furthermore, a highly specific/sensitive and/or label-free identification of PSA still remains a challenge in the diagnosis of prostate anomalies. We aimed to develop a gold nanoparticle (GNP)-conjugated anti-PSA antibody-based localized surface plasmon resonance (LSPR) as a novel approach to detect prostatic disease. A total of 25 nm colloidal gold particles were prepared followed by conjugation with anti-PSA pAb (GNPs-PSA pAb). LSPR was used to monitor the absorption changes of the aggregation of the particles. The size, shape and stability of the GNP-anti-PSA were evaluated by dynamic light scattering transmission electron microscopy (TEM) and zetasizer. The GNPs-conjugated PSA-pAb was successfully synthesized and subsequently characterized using ultraviolet absorption spectroscopy and TEM to determine the size distribution, crystallinity and stability of the particles (for example, stability of GNP: 443 mV). To increase the stability of the particles, we pegylated GNPs using an N-(3-dimethylaminopropyl)-N*-ethylcarbodiimide hydrochloride (EDC)/N-hydroxylsuccinimide (NHS) linker (for example, stability of GNP after pegylation: 272 mV). We found a significant increase in the absorbance and intensity of the particles with extinction peak at 545/2 nm, which was shifted by ~1 nm after conjugation. To illustrate the potential of the GNPs-PSA pAb to bind specifically to PSA, LSPR was used. We found that the extinction peak shifted 3 nm for a solution of 100 nM unlabeled antigen. In summary, we have established a novel approach for improving the efficacy/sensitivity of PSA in the assessment of prostate disease, supporting further investigation on the diagnostic value of GNP-conjugated anti-PSA/LSPR for the detection of prostate cancer.

  17. Prostatic specific antigen. From its early days until becoming a prostate cancer biomarker.

    PubMed

    Dellavedova, T

    2016-01-01

    Prostate-specific antigen (PSA) has been since the mid 80's the most commonly used biomarker for measuring current and future risk of prostate cancer, for its early detection and to measure response to treatments and detecting recurrence in all stages of the disease. PSA's early development came along with progress in the field of immunology, which allowed detection and study of antigens from different tissues and fluids when injecting them into rabbits to promote immune response. Rubin Flocks in 1960 was the first to investigate and discover prostate-specific antigens in benign and malignant tissue. Some years later, Hara, a Japanese forensic investigator, found 'gamma seminoprotein', that he used to detect human semen in rape cases. However, his work published in Japanese did not reach the Englishspeaking scientific community. In 1970 Ablin discovered both in prostatic fluid and tissue what he called "prostate-specific antigen", but he didn't characterize or describe it. Investigators Li and Beling, and Sensabaugh, approached the current PSA, but they were limited by available technology at that time. Dr T Ming Chu led a research team on prostate cancer in New York, USA and published their results in 1979. He finally received the patent for the discovery of "human purified prostate antigen" in 1984. Due to this work, the Food and Drug Administration (FDA), in USA, approved the use of PSA for monitoring recurrence after treatment. It was later known that PSA was not prostate-specific since it was produced in other tissues and fluids, but it was recognized that it was human species-specific. Works by Papsidero and Stamey showed new indications and utilities for PSA, but it was Catalona who first used it as a marker for prostate cancer in 1991. Thanks to these advances FDA authorized in 1994 the clinical use of PSA for early detection of prostate cancer.

  18. Is there subclinical enthesitis in early psoriatic arthritis? A clinical comparison with power doppler ultrasound.

    PubMed

    Freeston, J E; Coates, L C; Helliwell, P S; Hensor, E M A; Wakefield, R J; Emery, P; Conaghan, P G

    2012-10-01

    Enthesitis is a recognized feature of spondylarthritides (SpA), including psoriatic arthritis (PsA). Previously, ultrasound imaging has highlighted the presence of subclinical enthesitis in established SpA, but there are little data on ultrasound findings in early PsA. The aim of our study was to compare ultrasound and clinical examination (CE) for the detection of entheseal abnormalities in an early PsA cohort. Forty-two patients with new-onset PsA and 10 control subjects underwent CE of entheses for tenderness and swelling, as well as gray-scale (GS) and power Doppler (PD) ultrasound of a standard set of entheses. Bilateral elbow lateral epicondyles, Achilles tendons, and plantar fascia were assessed by both CE and ultrasound, the latter scored using a semiquantitative (SQ) scale. Inferior patellar tendons were assessed by ultrasound alone. A GS SQ score of >1 and/or a PD score of >0 was used to describe significant ultrasound entheseal abnormality. A total of 24 (57.1%) of 42 patients in the PsA group and 0 (0%) of 10 controls had clinical evidence of at least 1 tender enthesis. In the PsA group, for sites assessed by both CE and ultrasound, 4% (7 of 177) of nontender entheses had a GS score >1 and/or a PD score >0 compared to 24% (9 of 37) of tender entheses. CE overestimated activity in 28 (13%) of 214 of entheses. All the nontender ultrasound-abnormal entheses were in the lower extremity. The prevalence of subclinical enthesitis in this early PsA cohort was low. CE may overestimate active enthesitis. The few subclinically inflamed entheses were in the lower extremity, where mechanical stress is likely to be more significant. Copyright © 2012 by the American College of Rheumatology.

  19. Independent association between time to prostate-specific antigen (PSA) nadir and PSA progression-free survival in patients with docetaxel-naïve, metastatic castration-resistant prostate cancer receiving abiraterone acetate, but not enzalutamide.

    PubMed

    Miyake, Hideaki; Hara, Takuto; Tamura, Keita; Sugiyama, Takayuki; Furuse, Hiroshi; Ozono, Seiichiro; Fujisawa, Masato

    2017-06-01

    The objective of this study was to compare the prognostic effect of time to prostate-specific antigen (PSA) nadir (TTPN) after treatment with abiraterone acetate (AA) and enzalutamide (Enz) in patients with docetaxel-naïve, metastatic castration-resistant prostate cancer (mCRPC). This study included a total of 297 consecutive patients with mCRPC, of whom 125 and 172 received AA and Enz, respectively, without previous treatment with docetaxel and subsequently achieved any degree of PSA reduction after the administration of either agent. The mean values of TTPN in the AA and Enz groups were 19 and 14 weeks, respectively. Despite the lack of significant differences in several parameters according to the mean TTPN in the Enz group, patients with TTPN>19 weeks were characterized by longer duration of androgen deprivation therapy, better performance status, lower incidence of bone metastasis, lower value of nadir PSA, and higher incidence of PSA response than those with TTPN ≤19 weeks in the AA group. The PSA progression-free survival (PFS) in patients with TTPN >19 weeks was significantly superior when compared with TTPN ≤19 weeks in the AA group; however, there was no significant effect of the mean TTPN on the PSA-PFS in the Enz group. Furthermore, TTPN was identified as one of the independent predictors of PSA-PFS in the AA group but not in Enz group. A longer time to reach a PSA nadir after treatment with AA, but not Enz, appeared to be associated with favorable disease control in patients with docetaxel-naïve mCRPC. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Prostate cancer screening by prostate-specific antigen (PSA); a relevant approach for the small population of the Cayman Islands.

    PubMed

    Jyoti, Shravana Kumar; Blacke, Camille; Patil, Pallavi; Amblihalli, Vibha P; Nicholson, Amanda

    2018-01-01

    The common tool for diagnosing prostate cancer is prostate-specific antigen (PSA), but the high sensitivity and low specificity of PSA testing are the problems in clinical practice. There are no proper guidelines to investigate the suspected prostate cancer in the Cayman Islands. We correlated PSA levels with the incidence of prostate cancers by tissue diagnosis and proposed logical protocol for prostate screening by using PSA test in this small population. A total of 165 Afro Caribbean individuals who had prostate biopsy done after the investigations for PSA levels from year 2005 to 2015 were studied retrospectively. The patients were divided into subgroups by baseline PSA levels as follows: <4, 4.1-10, 10.1-20, 20.1-50, 50.1-100, and >100 ng/mL and were correlated to the age and presence of cancer. Benign lesions had lower PSA levels compared to cancer which generally had higher values. Only three cases that had less than 4 ng/mg were turned out to be malignant. When PSA value was more than 100 ng/mL, all the cases were malignant. Between PSA values of 4-100 ng/mL, the probability of cancer diagnosis was 56.71% (76 cancers out of 134 in this range). Limitation of PSA testing has the risk of over diagnosis and the resultant negative biopsies owing to poor specificity. Whereas the cutoff limit for cancer diagnosis still remains 4 ng/mL from our study, most of the patients can be assured of benign lesion below this level and thus morbidity associated with the biopsy can be prevented. When the PSA value is greater than 100 ng, biopsy procedure was mandatory as there were 100% cancers above this level. On the background of vast literature linking PSA to prostate cancer and its difficulty in implementing in clinical practice, we studied literature of this conflicting and complex topic and tried to bring relevant protocols to the small population of Cayman Islands for the screening of prostate cancer. In this study, a total of 165 Afro Caribbean individuals who

  1. Predictive simulations and optimization of nanowire field-effect PSA sensors including screening

    NASA Astrophysics Data System (ADS)

    Baumgartner, Stefan; Heitzinger, Clemens; Vacic, Aleksandar; Reed, Mark A.

    2013-06-01

    We apply our self-consistent PDE model for the electrical response of field-effect sensors to the 3D simulation of nanowire PSA (prostate-specific antigen) sensors. The charge concentration in the biofunctionalized boundary layer at the semiconductor-electrolyte interface is calculated using the propka algorithm, and the screening of the biomolecules by the free ions in the liquid is modeled by a sensitivity factor. This comprehensive approach yields excellent agreement with experimental current-voltage characteristics without any fitting parameters. Having verified the numerical model in this manner, we study the sensitivity of nanowire PSA sensors by changing device parameters, making it possible to optimize the devices and revealing the attributes of the optimal field-effect sensor.

  2. PSA Response After Short-Term Hormonal Therapy Plus External Beam Radiotherapy and Outcome in Patients Treated on RTOG 9413

    PubMed Central

    Cury, Fabio L.; Hunt, Daniel; Roach, Mack; Shipley, William; Gore, Elizabeht; Hsu, I-Chow; Krisch, Robert E.; Seider, Michael J.; Sandler, Howard; Lawton, Colleen

    2013-01-01

    Purpose Assess the impact of PSA-complete response (PSA-CR), measured at the end of external beam radiotherapy (EBRT) and short-term hormonal therapy (STHT), on treatment outcomes. Design The Phase III RTOG-9413 trial had as part of its original protocol the assessment of PSA-CR, i.e. PSA≤0.3ng/ml, at the end of STHT as a secondary endpoint. STHT consisted of flutamide plus an LHRH-agonist for 4 months. Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival (DFS). Cumulative incidence was used to estimate biochemical failure (BF), distant metastasis (DM), and disease-specific survival (DSS). Univariate and multivariate analyses were performed to correlate PSA-CR after STHT with all endpoints, and the following variables were considered for analysis: PSA at baseline, Gleason score, treatment arm, age, and baseline testosterone. Phoenix-consensus was used to define PSA failure. Results For 1070 evaluable patients, the median PSA at the end of STHT was 0.2ng/mL. A total of 744 patients (70%) had PSA-CR. With median follow-up of 7.2 years, failure to obtain PSA-CR was significantly associated with worse DSS (p=0.0003; hazard ratio, 2.03[95%CI, 1.38–2.97]) and DFS (p=0.003; 1.28[1.09–1.50]), as well as with a higher incidence of DM (p=0.0002; 1.92[1.37–2.69]) and BF (p<0.0001; 1.57[1.29–1.91]). The other factors associated with worse DSS were Gleason score 8–10 (p=0.0002; 3.06[1.71–5.47]) and PSA>20ng/mL (p=0.04; 1.55[1.02–2.30]). Conclusion Failure to obtain a post STHT and EBRT PSA-CR (≤0.3ng/mL) appears to be an independent predictor of unfavorable outcomes, and may help identify patients who could benefit from the addition of long-term androgen ablation. PMID:23504930

  3. A three-gene panel on urine increases PSA specificity in the detection of prostate cancer.

    PubMed

    Rigau, Marina; Ortega, Israel; Mir, Maria Carmen; Ballesteros, Carlos; Garcia, Marta; Llauradó, Marta; Colás, Eva; Pedrola, Núria; Montes, Melania; Sequeiros, Tamara; Ertekin, Tugce; Majem, Blanca; Planas, Jacques; Ruiz, Anna; Abal, Miguel; Sánchez, Alex; Morote, Juan; Reventós, Jaume; Doll, Andreas

    2011-12-01

    Several studies have demonstrated the usefulness of monitoring an RNA transcript, such as PCA3, in post-prostate massage (PM) urine for increasing the specificity of prostate-specific antigen (PSA) in the detection of prostate cancer (PCa). However, a single marker may not necessarily reflect the multifactorial nature of PCa. We analyzed post-PM urine samples from 154 consecutive patients, who presented for prostate biopsies because of elevated serum PSA (>4 ng/ml) and/or abnormal digital rectal exam. We tested whether the putative PCa biomarkers PSMA, PSGR, and PCA3 could be detected by quantitative real-time PCR in post-PM urine sediment. We combined these findings to test if a combination of these biomarkers could improve the specificity of actual diagnosis. Afterwards, we specifically tested our model for clinical usefulness in the PSA diagnostic "gray zone" (4-10 ng/ml) on a target subset of 82 men with no prior biopsy. By univariate analysis, we found that the PSMA, PSGR, and PCA3 scores were significant predictors of PCa. Using a multiplex model, the area under the multi receiver-operating characteristic curve was 0.74 versus 0.82 in the diagnostic "gray zone." Fixing the sensitivity at 96%, we obtained a specificity of 34% and 50% in the gray zone. Taken together, these results provide a strategy for the development of a more accurate model for PCa diagnosis. In the future, a multiplexed, urine-based diagnostic test for PCa with a higher specificity, but the same sensitivity as the serum-PSA test, could be used to determine better which patients should undergo biopsy. Copyright © 2011 Wiley Periodicals, Inc.

  4. PSA-Based Screening Outcomes, Dietary Heterocyclic Amine Exposure, and Prostate Cancer Risk in African Americans

    DTIC Science & Technology

    2008-06-01

    al., 1993; Kaderlik et al., 1994a-b; Takahashi et al., 1998; Schut and Snyderwine, 1999; Gooderham et al., 2002). In male lacI trangenic rats, a diet ...Detailed data on diet and meat consumption continue to be obtained by in-person interviews using established questionnaires, each followed by PSA...questionnaire for use in diet and cancer studies. J. Am. Dietetic Assoc. 107, 1356-62. [see Appendix of this report] Bogen KT, GA Keating II, JM

  5. A Diet, Physical Activity, and Meditation Intervention in Men With Rising Prostate-Specific Antigen (PSA)

    DTIC Science & Technology

    2007-05-01

    AD_________________ Award Number: DAMD17-03-1-0139 TITLE: A Diet , Physical Activity, and...To) 1 May 2003 – 30 Apr 2007 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A Diet , Physical Activity, and Meditation Intervention in Men with...asymptomatic men with biochemically recurrent PrCA, as reflected by the PSA rise, is favorably affected by an intensive, vegetable-based diet , plus

  6. Co-delivery of PSA and PSMA DNA vaccines with electroporation induces potent immune responses.

    PubMed

    Ferraro, Bernadette; Cisper, Neil J; Talbott, Kendra T; Philipson-Weiner, Lindsey; Lucke, Colleen E; Khan, Amir S; Sardesai, Niranjan Y; Weiner, David B

    2011-01-01

    Prostate cancer (PCa) remains a significant public health problem. Current treatment modalities for PCa can be useful, but may be accompanied by deleterious side effects and often do not confer long-term control. Accordingly, additional modalities, such as immunotherapy, may represent an important approach for PCa treatment. The identification of tissue-specific antigens engenders PCa an attractive target for immunotherapeutic approaches. Delivery of DNA vaccines with electroporation has shown promising results for prophylactic and therapeutic targets in a variety of species including humans. Application of this technology for PCa immunotherapy strategies has been limited to single antigen and epitope targets. We sought to test the hypothesis that a broader collection of antigens would improve the breadth and effectiveness of a PCa immune therapy approach. We therefore developed highly optimized DNA vaccines encoding prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) as a dual antigen approach to immune therapy of PCa. PSA-and PSMA-specific cellular immunogenicity was evaluated in a mouse model for co-delivery and single antigen vaccination. Mice received 2 immunizations spaced 2 weeks apart and immunogenicity was evaluated 1 week after the second vaccination. Both the PSA and PSMA vaccines induced robust antigen-specific IFNγ responses by ELISpot. Further characterization of cellular immunogenicity by flow cytometry indicated strong antigen-specific TNFα production by CD4+ T cells and IFNγ and IL-2 secretion by both CD4+ and CD8+ T cells. There was also a strong humoral response as determined by PSA-specific seroconversion. These data support further study of this novel approach to immune therapy of PCa.

  7. Prostate-specific antigen (PSA) testing of men in UK general practice: a 10-year longitudinal cohort study

    PubMed Central

    Young, Grace J; Harrison, Sean; Turner, Emma L; Walsh, Eleanor I; Oliver, Steven E; Ben-Shlomo, Yoav; Evans, Simon; Lane, J Athene; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Martin, Richard M; Metcalfe, Chris

    2017-01-01

    Objectives Cross-sectional studies suggest that around 6% of men undergo prostate-specific antigen (PSA) testing each year in UK general practice (GP). This longitudinal study aims to determine the cumulative testing pattern of men over a 10-year period and whether this testing can be considered equivalent to screening for prostate cancer (PCa). Setting, participants and outcome measures Patient-level data on PSA tests, biopsies and PCa diagnoses were obtained from the UK Clinical Practice Research Datalink (CPRD) for the years 2002 to 2011. The cumulative risks of PSA testing and of being diagnosed with PCa were estimated for the 10-year study period. Associations of a man’s age, region and index of multiple deprivation with the cumulative risk of PSA testing and PCa diagnosis were investigated. Rates of biopsy and diagnosis, following a high test result, were compared with those from the programme of PSA testing in the Prostate Testing for Cancer and Treatment (ProtecT) study. Results The 10-year risk of exposure to at least one PSA test in men aged 45 to 69 years in UK GP was 39.2% (95% CI 39.0 to 39.4%). The age-specific risks ranged from 25.2% for men aged 45–49 years to 53.0% for men aged 65–69 years (p for trend <0.001). For those with a PSA level ≥3, a test in UK GP was less likely to result in a biopsy (6%) and/or diagnosis of PCa (15%) compared with ProtecT study participants (85% and 34%, respectively). Conclusion A high proportion of men aged 45–69 years undergo PSA tests in UK GP: 39% over a 10-year period. A high proportion of these tests appear to be for the investigation of lower urinary tract symptoms and not screening for PCa. Trial registration number ISRCTN20141297, NCT02044172. PMID:29084797

  8. Multiple external hazards compound level 3 PSA methods research of nuclear power plant

    NASA Astrophysics Data System (ADS)

    Wang, Handing; Liang, Xiaoyu; Zhang, Xiaoming; Yang, Jianfeng; Liu, Weidong; Lei, Dina

    2017-01-01

    2011 Fukushima nuclear power plant severe accident was caused by both earthquake and tsunami, which results in large amount of radioactive nuclides release. That accident has caused the radioactive contamination on the surrounding environment. Although this accident probability is extremely small, once such an accident happens that is likely to release a lot of radioactive materials into the environment, and cause radiation contamination. Therefore, studying accidents consequences is important and essential to improve nuclear power plant design and management. Level 3 PSA methods of nuclear power plant can be used to analyze radiological consequences, and quantify risk to the public health effects around nuclear power plants. Based on multiple external hazards compound level 3 PSA methods studies of nuclear power plant, and the description of the multiple external hazards compound level 3 PSA technology roadmap and important technical elements, as well as taking a coastal nuclear power plant as the reference site, we analyzed the impact of off-site consequences of nuclear power plant severe accidents caused by multiple external hazards. At last we discussed the impact of off-site consequences probabilistic risk studies and its applications under multiple external hazards compound conditions, and explained feasibility and reasonableness of emergency plans implementation.

  9. PERFORMANCE AND DURABILITY OF THE PSA PEUGEOT CITROEN'S DPF SYSTEM ON A TAXI FLEET IN THE PARIS AREA

    SciTech Connect

    COROLLER, P; PLASSAT, G

    The use of Diesel engines has strongly increased during the last years and now represents 40% of the sales in Europe and up to 50% of the number of cars in circulation for some countries. This success is linked not only to the economical aspect of the use of such vehicles, but also to the recent technological improvements of these engines. The new technical solutions (high pressure direct injection, turbocharger) have indeed allowed the increase of these engine performances while decreasing their fuel consumption, pollutant emissions and noise level. From an environment point of view, Diesel engines are nevertheless penalizedmore » by their particulates and NOx emissions. The study and the treatment of the particulate, highly criticized for their potential impact on health, are the subject of numerous works of characterizations and developments. PSA Peugeot Citroen has recently (2000) launched its particulate filter technology on several types of vehicles (500,000 vehicles with DPF have been sold today). In order to evaluate the durability of this technology over a long period of time, a study program has been set-up by ADEME (French Environmental Agency), IFP Powertrain, PSA Peugeot Citroen and Taxis G7 (a Parisian taxis Company). The objective is to study the evolution of five taxis and their after-treatment system performances over 80,000km mileage--which corresponds to the recommended mileage before the first DPF maintenance--in hard urban driving conditions, as well over 120,000km, after the DPF maintenance and remanufacturing. More specifically, the following evaluations are being performed at regular intervals (around 20,000km): regulated gaseous pollutant emissions on NEDC cycle, particulate emissions and unregulated pollutant emissions. The results obtained until now have not shown any degradation of the particulate filter efficiency (more than 90%). This paper presents the methodology set-up, and the explanation of the first results obtained. Indeed, a

  10. Association between Serum Testosterone and PSA Levels in Middle-Aged Healthy Men from the General Population.

    PubMed

    Elzanaty, Saad; Rezanezhad, Babak; Dohle, Gert

    2017-04-01

    The aim of the present study was to evaluate the association between serum testosterone and PSA levels in middle-aged healthy men from the general population. Based on 119 healthy men from the general population, total testosterone and PSA levels were measured. Demographic data regarding BMI, waist-to-hip ratio, smoking, and alcohol consumption were also collected. Men were classified into two groups according to testosterone levels; hypogonadal (testosterone ≤ 12 nmol/l), and eugonadal (testosterone > 12 nmol/l). The mean age of the subjects was 55 years (range 46-60 years). No significant correlation between serum testosterone and PSA levels was found (p = 0.60). PSA levels were similar when compared between hypogonadal and eugonadal men (1.4 µg/l vs. 1.4 µg/l, p = 0.90). When using a multivariate analysis model adjusted for the age of the subjects, BMI, waist-to-hip ratio, smoking, and alcohol consumption, a positive significant association between testosterone and PSA levels was found (β = 0.03, 95 % CI = 0.003-0.062, p = 0.03). Only after adjusted multivariate analysis, our results indicated that testosterone was associated with PSA levels in middle-aged healthy men.

  11. Analysis of Serum Total and Free PSA Using Immunoaffinity Depletion Coupled to SRM: Correlation with Clinical Immunoassay Tests

    PubMed Central

    Liu, Tao; Hossain, Mahmud; Schepmoes, Athena A.; Fillmore, Thomas L.; Sokoll, Lori J.; Kronewitter, Scott R.; Izmirlian, Grant; Shi, Tujin; Qian, Wei-Jun; Leach, Robin J.; Thompson, Ian M.; Chan, Daniel W.; Smith, Richard D.; Kagan, Jacob; Srivastava, Sudhir; Rodland, Karin D.; Camp, David G.

    2012-01-01

    Recently, selected reaction monitoring mass spectrometry (SRM-MS) has been more frequently applied to measure low abundance biomarker candidates in tissues and biofluids, owing to its high sensitivity and specificity, simplicity of assay configuration, and exceptional multiplexing capability. In this study, we report for the first time the development of immunoaffinity depletion-based workflows and SRM-MS assays that enable sensitive and accurate quantification of total and free prostate-specific antigen (PSA) in serum without the requirement for specific PSA antibodies. Low ng/mL level detection of both total and free PSA was consistently achieved in both PSA-spiked female serum samples and actual patient serum samples. Moreover, comparison of the results obtained when SRM PSA assays and conventional immunoassays were applied to the same samples showed good correlation in several independent clinical serum sample sets. These results demonstrate that the workflows and SRM assays developed here provide an attractive alternative for reliably measuring candidate biomarkers in human blood, without the need to develop affinity reagents. Furthermore, the simultaneous measurement of multiple biomarkers, including the free and bound forms of PSA, can be performed in a single multiplexed analysis using high-resolution liquid chromatographic separation coupled with SRM-MS. PMID:22846433

  12. Correlation of pretreatment clinical parameters and PSA nadir after high-intensity focused ultrasound (HIFU) for localised prostate cancer.

    PubMed

    Ganzer, Roman; Bründl, Johannes; Koch, Daniel; Wieland, Wolf F; Burger, Maximilian; Blana, Andreas

    2015-01-01

    To determine which pretreatment clinical parameters were predictive of a low prostate-specific antigen (PSA) nadir following high-intensity focused ultrasound (HIFU) treatment. Retrospective study of patients with clinically localised prostate cancer undergoing HIFU at a single centre between December 1997 and September 2009. Whole-gland treatment was applied. Patients also included if they had previously undergone transurethral resection of the prostate (TURP). TURP was also conducted simultaneously to HIFU. Biochemical failure based on Phoenix definition (PSA nadir + 2). Univariate and multivariate analysis of pretreatment clinical parameters conducted to assess those factors predictive of a PSA nadir ≤0.2 and >0.2 ng/ml. Mean (SD) follow-up was 6.2 (2.8) years; median (range) was 6.3 (1.1-12.2) years. Kaplan-Meier estimate of biochemical disease-free survival rate at 8 years was 83 and 48 % for patients achieving a PSA nadir of ≤0.2 and >0.2 ng/ml, respectively. Prostate volume and incidental finding of cancer were significant predictors of low PSA nadir (≤0.2 ng/ml). Prostate volume and incidental finding of cancer could be predictors for oncologic success of HIFU based on post-treatment PSA nadir.

  13. Assessing the Optimal Timing for Early Salvage Radiation Therapy in Patients with Prostate-specific Antigen Rise After Radical Prostatectomy.

    PubMed

    Fossati, Nicola; Karnes, R Jeffrey; Cozzarini, Cesare; Fiorino, Claudio; Gandaglia, Giorgio; Joniau, Steven; Boorjian, Stephen A; Goldner, Gregor; Hinkelbein, Wolfgang; Haustermans, Karin; Tombal, Bertrand; Shariat, Shahrokh; Karakiewicz, Pierre I; Montorsi, Francesco; Van Poppel, Hein; Wiegel, Thomas; Briganti, Alberto

    2016-04-01

    Early salvage radiation therapy (eSRT) represents a treatment option for patients who experience a prostate-specific antigen (PSA) rise after radical prostatectomy (RP); however, the optimal PSA level for eSRT administration is still unclear. To test the impact of PSA level on cancer control after eSRT according to pathologic tumour characteristics. The study included 716 node-negative patients with undetectable postoperative PSA who experienced a PSA rise after RP. All patients received eSRT, defined as local radiation to the prostate and seminal vesicle bed, delivered at PSA ≤ 0.5 ng/ml. Biochemical recurrence (BCR) after eSRT was defined as two consecutive PSA values ≥ 0.2 ng/ml. Multivariable Cox regression analysis tested the association between pre-eSRT PSA level and BCR after eSRT. Covariates consisted of pathologic stage (pT2 vs pT3a vs pT3b or higher), pathologic Gleason score (≤ 6, 7, or ≥ 8), and surgical margin status (negative vs positive). We tested an interaction with PSA level and baseline pathologic risk for the hypothesis that BCR-free survival differed by pre-eSRT PSA level. Three pathologic risk factors were identified: pathologic stage pT3b or higher, pathologic Gleason score ≥ 8, and negative surgical margins. Median follow-up among patients who did not experience BCR after eSRT was 57 mo (interquartile range: 27-105). At 5 yr after eSRT, BCR-free survival rate was 82% (95% confidence interval [CI], 78-85). At multivariable Cox regression analysis, pre-eSRT PSA level was significantly associated with BCR after eSRT (hazard ratio: 4.89; 95% CI, 1.40-22.9; p < 0.0001). When patients were stratified according to the number of risk factors at final pathology, patients with at least two pathologic risk factors showed an increased risk of 5-yr BCR as high as 10% per 0.1 ng/ml of PSA level compared with only 1.5% in patients with one or no pathologic risk factors. In this retrospective study, cancer control after eSRT greatly depended on

  14. A comparative Study of Aptasensor Vs Immunosensor for Label-Free PSA Cancer Detection on GQDs-AuNRs Modified Screen-Printed Electrodes.

    PubMed

    Srivastava, Monika; Nirala, Narsingh R; Srivastava, S K; Prakash, Rajiv

    2018-01-31

    Label-free and sensitive detection of PSA (Prostate Specific Antigen) is still a big challenge in the arena of prostate cancer diagnosis in males. We present a comparative study for label-free PSA aptasensor and PSA immunosensor for the PSA-specific monoclonal antibody, based on graphene quantum dots-gold nanorods (GQDs-AuNRs) modified screen-printed electrodes. GQDs-AuNRs composite has been synthesized and used as an electro-active material, which shows fast electron transfer and catalytic property. Aptamer or anti-PSA has immobilized onto the surface of modified screen printed electrodes. Three techniques are used simultaneously, viz. cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedence spectroscopy (EIS) to investigate the analytical performance of both PSA aptasensor and PSA immunosensor with its corresponding PSA antigen. Under optimum conditions, both sensors show comparable results with an almost same limit of detection (LOD) of 0.14 ng mL -1 . The results developed with aptasensor and anti-PSA is also checked through the detection of PSA in real samples with acceptable results. Our study suggests some advantages of aptasensor in terms of better stability, simplicity and cost effectiveness. Further our present work shows enormous potential of our developed sensors for real application using voltammetric and EIS techniques simultaneous to get reliable detection of the disease.

  15. Increasing Fractional Doses Increases the Probability of Benign PSA Bounce in Patients Undergoing Definitive HDR Brachytherapy for Prostate Cancer

    SciTech Connect

    Hauck, Carlin R.; Ye, Hong; Chen, Peter Y.

    Purpose: Prostate-specific antigen (PSA) bounce is a temporary elevation of the PSA level above a prior nadir. The purpose of this study was to determine whether the frequency of a PSA bounce following high-dose-rate (HDR) interstitial brachytherapy for the treatment of prostate cancer is associated with individual treatment fraction size. Methods and Materials: Between 1999 and 2014, 554 patients underwent treatment of low- or intermediate-risk prostate cancer with definitive HDR brachytherapy as monotherapy and had ≥3 subsequent PSA measurements. Four different fraction sizes were used: 950 cGy × 4 fractions, 1200 cGy × 2 fractions, 1350 cGy × 2 fractions, 1900 cGy × 1more » fraction. Four definitions of PSA bounce were applied: ≥0.2, ≥0.5, ≥1.0, and ≥2.0 ng/mL above the prior nadir with a subsequent return to the nadir. Results: The median follow-up period was 3.7 years. The actuarial 3-year rate of PSA bounce for the entire cohort was 41.3%, 28.4%, 17.4%, and 6.8% for nadir +0.2, +0.5, +1.0, and +2.0 ng/mL, respectively. The 3-year rate of PSA bounce >0.2 ng/mL was 42.2%, 32.1%, 41.0%, and 59.1% for the 950-, 1200-, 1350-, and 1900-cGy/fraction levels, respectively (P=.002). The hazard ratio for bounce >0.2 ng/mL for patients receiving a single fraction of 1900 cGy compared with those receiving treatment in multiple fractions was 1.786 (P=.024). For patients treated with a single 1900-cGy fraction, the 1-, 2-, and 3-year rates of PSA bounce exceeding the Phoenix biochemical failure definition (nadir +2 ng/mL) were 4.5%, 18.7%, and 18.7%, respectively, higher than the rates for all other administered dose levels (P=.025). Conclusions: The incidence of PSA bounce increases with single-fraction HDR treatment. Knowledge of posttreatment PSA kinetics may aid in decision making regarding management of potential biochemical failures.« less

  16. Increasing Fractional Doses Increases the Probability of Benign PSA Bounce in Patients Undergoing Definitive HDR Brachytherapy for Prostate Cancer.

    PubMed

    Hauck, Carlin R; Ye, Hong; Chen, Peter Y; Gustafson, Gary S; Limbacher, Amy; Krauss, Daniel J

    2017-05-01

    Prostate-specific antigen (PSA) bounce is a temporary elevation of the PSA level above a prior nadir. The purpose of this study was to determine whether the frequency of a PSA bounce following high-dose-rate (HDR) interstitial brachytherapy for the treatment of prostate cancer is associated with individual treatment fraction size. Between 1999 and 2014, 554 patients underwent treatment of low- or intermediate-risk prostate cancer with definitive HDR brachytherapy as monotherapy and had ≥3 subsequent PSA measurements. Four different fraction sizes were used: 950 cGy × 4 fractions, 1200 cGy × 2 fractions, 1350 cGy × 2 fractions, 1900 cGy × 1 fraction. Four definitions of PSA bounce were applied: ≥0.2, ≥0.5, ≥1.0, and ≥2.0 ng/mL above the prior nadir with a subsequent return to the nadir. The median follow-up period was 3.7 years. The actuarial 3-year rate of PSA bounce for the entire cohort was 41.3%, 28.4%, 17.4%, and 6.8% for nadir +0.2, +0.5, +1.0, and +2.0 ng/mL, respectively. The 3-year rate of PSA bounce >0.2 ng/mL was 42.2%, 32.1%, 41.0%, and 59.1% for the 950-, 1200-, 1350-, and 1900-cGy/fraction levels, respectively (P=.002). The hazard ratio for bounce >0.2 ng/mL for patients receiving a single fraction of 1900 cGy compared with those receiving treatment in multiple fractions was 1.786 (P=.024). For patients treated with a single 1900-cGy fraction, the 1-, 2-, and 3-year rates of PSA bounce exceeding the Phoenix biochemical failure definition (nadir +2 ng/mL) were 4.5%, 18.7%, and 18.7%, respectively, higher than the rates for all other administered dose levels (P=.025). The incidence of PSA bounce increases with single-fraction HDR treatment. Knowledge of posttreatment PSA kinetics may aid in decision making regarding management of potential biochemical failures. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Circulating total testosterone and PSA concentrations in a nationally representative sample of men without a diagnosis of prostate cancer.

    PubMed

    Peskoe, Sarah B; Joshu, Corinne E; Rohrmann, Sabine; McGlynn, Katherine A; Nyante, Sarah J; Bradwin, Gary; Dobs, Adrian S; Kanarek, Norma; Nelson, William G; Platz, Elizabeth A

    2015-08-01

    The association between serum sex steroid hormones and PSA in a general population has not been described. Included were 378 men aged 40-85 years who participated in the National Health and Nutrition Examination Survey in 2001-2004, who did not have a prostate cancer diagnosis, and had not had a recent biopsy, rectal examination, cystoscopy, or prostate infection or inflammation. Serum total PSA, total testosterone, androstanediol glucuronide (3α-diol-G), estradiol, and sex hormone binding globulin (SHBG) concentrations were previously measured. Free testosterone was estimated by mass action. We applied sampling weights and calculated geometric mean PSA concentration by hormone quintiles adjusting for age and race/ethnicity, and also for body mass index, waist circumference, smoking, diabetes, and mutually for hormones. We estimated the OR of PSA ≥2.5 ng/ml per hormone quintile using logistic regression. Geometric mean PSA increased across testosterone quintiles after age and race/ethnicity (Q1: 0.80, Q5: 1.14 ng/ml; P-trend = 0.002) and multivariable (Q1: 0.79, Q5: 1.16 ng/ml; P-trend = 0.02) adjustment; patterns were similar for free testosterone and 3α-diol-G. SHBG was inversely associated with PSA only after multivariable adjustment (Q1: 1.32, Q5: 0.82 nmol/L; P-trend = 0.01). Estradiol and PSA were not associated. The OR of PSA ≥2.5 ng/ml was 1.54 (95% CI 1.18-2.01) per testosterone quintile after age and race/ethnicity adjustment, and 1.78 (95% CI 1.16-2.73) after multivariable adjustment. In this nationally representative sample, men with higher testosterone had higher PSA even after taking into account other hormones and modifiable factors. Men with higher SHBG had lower PSA, but only after multivariable adjustment. © 2015 Wiley Periodicals, Inc.

  18. Statins and Metformin Use Is Associated with Lower PSA Levels in Prostate Cancer Patients Presenting for Radiation Therapy.

    PubMed

    Liu, Xiaonan; Li, Jing; Schild, Steven E; Schild, Michael H; Wong, William; Vora, Sujay; Herman, Michael G; Fatyga, Mirek

    2017-02-01

    A possible association between the level of prostate specific antigen (PSA) and the use of some commonly prescribed medications has been reported in recent studies. Most of these studies were carried out in general populations of men who were screened for prostate cancer using the PSA test. We reported on the association between the initial PSA level and the use of statins, metformin and alpha-blockers in patients who were diagnosed with prostate cancer and presented for radiation therapy. Three hundred and eighty one patients treated between the years of 2000-2005 and 2009-2012 were included in this retrospective study. The information about statin, metformin and alpha-blockers use was recorded immediately prior to treatment. Differences in PSA levels prior to treatment by medication status were estimated using univa-riate and multivariate linear regression on log PSA values. Compared with men who were not on these medications, the PSA level at presentation was 20% lower for statin users (p = 0.002) and 33% lower for metformin users (p = 0.004). We did not observe statistically significant associations between the use of statins or metformin and cancer stage, National Comprehensive Cancer Network (NCCN) risk score, or therapy outcome. A statistically significant association between the NCCN risk score and the use of alpha-blockers was observed (p = 0.002). We found that statins and metformin were associated with lower PSA levels in prostate cancer patients to an extent that could influence management decisions. We found no statistically significant associations between the use of these medications and treatment outcomes.

  19. Analysis of Serum Total and Free PSA Using Immunoaffinity Depletion Coupled to SRM: Correlation with Clinical Immunoassay Tests

    SciTech Connect

    Liu, Tao; Hossain, Mahmud; Schepmoes, Athena A.

    2012-08-03

    Sandwich immunoassay is the standard technique used in clinical labs for quantifying protein biomarkers for disease detection, monitoring and therapeutic intervention. Albeit highly sensitive, the development of a specific immunoassay is rather time-consuming and associated with extremely high cost due to the requirement for paired immunoaffinity reagents of high specificity. Recently, mass spectrometry-based methods, specifically selected reaction monitoring mass spectrometry (SRM-MS), have been increasingly applied to measure low abundance biomarker candidates in tissue and biofluids, owing to high sensitivity and specificity, simplicity of assay configuration, and great multiplexing capability. In this study, we report for the first time the developmentmore » of immunoaffinity depletion-based workflows and SRM-MS assays that enable sensitive and accurate quantification of total and free prostate-specific antigen (PSA) in serum without the requirement for specific PSA antibodies. With stable isotope dilution and external calibration, low ng/mL level detection of both total and free PSA was consistently achieved in both PSA-spiked female serum samples and actual patient serum samples. Moreover, comparison of the results obtained when SRM PSA assays and conventional immunoassays were applied to the same samples showed very good correlation (R2 values ranging from 0.90 to 0.99) in several independent clinical serum sample sets, including a set of 33 samples assayed in a blinded test. These results demonstrate that the workflows and SRM assays developed here provide an attractive alternative for reliably measuring total and free PSA in human blood. Furthermore, simultaneous measurement of free and total PSA and many other biomarkers can be performed in a single analysis using high-resolution liquid chromatographic separation coupled with SRM-MS.« less

  20. The Low Molecular Weight Protein PsaI Stabilizes the Light-Harvesting Complex II Docking Site of Photosystem I.

    PubMed

    Plöchinger, Magdalena; Torabi, Salar; Rantala, Marjaana; Tikkanen, Mikko; Suorsa, Marjaana; Jensen, Poul-Erik; Aro, Eva Mari; Meurer, Jörg

    2016-09-01

    PsaI represents one of three low molecular weight peptides of PSI. Targeted inactivation of the plastid PsaI gene in Nicotiana tabacum has no measurable effect on photosynthetic electron transport around PSI or on accumulation of proteins involved in photosynthesis. Instead, the lack of PsaI destabilizes the association of PsaL and PsaH to PSI, both forming the light-harvesting complex (LHC)II docking site of PSI. These alterations at the LHCII binding site surprisingly did not prevent state transition but led to an increased incidence of PSI-LHCII complexes, coinciding with an elevated phosphorylation level of the LHCII under normal growth light conditions. Remarkably, LHCII was rapidly phosphorylated in ΔpsaI in darkness even after illumination with far-red light. We found that this dark phosphorylation also occurs in previously described mutants impaired in PSI function or state transition. A prompt shift of the plastoquinone (PQ) pool into a more reduced redox state in the dark caused an enhanced LHCII phosphorylation in ΔpsaI Since the redox status of the PQ pool is functionally connected to a series of physiological, biochemical, and gene expression reactions, we propose that the shift of mutant plants into state 2 in darkness represents a compensatory and/or protective metabolic mechanism. This involves an increased reduction and/or reduced oxidation of the PQ pool, presumably to sustain a balanced excitation of both photosystems upon the onset of light. © 2016 American Society of Plant Biologists. All rights reserved.

  1. The Effect of Increasing Doses of Saw Palmetto Fruit Extract on Serum PSA Levels: Analysis of the CAMUS Randomized Trial

    PubMed Central

    Andriole, Gerald L.; McCullum-Hill, Christie; Sandhu, Gurdarshan S.; Crawford, E. David; Barry, Michael J.; Cantor, Alan

    2014-01-01

    Purpose Saw palmetto extracts are used for treating lower urinary tract symptoms in men despite level I evidence concluding that saw palmetto was ineffective in reducing lower urinary symptoms. We sought to determine whether higher doses of saw palmetto as studied in CAMUS affect serum PSA levels. Materials and Methods The CAMUS trial was a randomized, placebo-controlled double blind multi-centered North American trial conducted between June 5, 2008 and October 10, 2012 in which 369 men >45 years of age with AUA symptom score ≥ 8 and ≤ 24 were randomly assigned to placebo or dose escalation saw palmetto, which consisted of 320mg for first 24 weeks to 640mg for next 24 weeks to 960mg for last 24 weeks of this 72 week trial. Serum PSA levels (Beckman-Coulter) were obtained at baseline and at weeks 24, 48 and 72 and were compared between treatment groups using the pooled t and Fisher's exact tests. Results Serum PSA levels were similar at baseline for the placebo (1.93 ± 1.59 ng/ml) and saw palmetto groups (2.20 ± 1.95, p = 0.16). Changes in PSA levels over the course of the study were similar: placebo group mean change 0.16 ± 1.08 ng/ml and saw palmetto group mean change 0.23 ± 0.83 ng/ml (p value 0.50). Additionally, no differential effect on serum PSA levels was observed between treatment arms when groups were stratified by baseline PSA values. Conclusions Saw palmetto extract does not affect serum PSA levels more than placebo even at relatively high doses. PMID:23253958

  2. [The value of PHI/PCA3 in the early diagnosis of prostate cancer].

    PubMed

    Tan, S J; Xu, L W; Xu, Z; Wu, J P; Liang, K; Jia, R P

    2016-01-12

    To investigate the value of prostate health index (PHI) and prostate cancer gene 3 (PCA3) in the early diagnosis of prostate cancer (PCa). A total of 190 patients with abnormal serum prostate specific antigen (PSA) or abnormal digital rectal examination were enrolled. They were all underwent initial biopsy and 11 of them were also underwent repeated biopsy. In addition, 25 healthy cases (with normal digital rectal examination and PSA<4 ng/ml) were the control group.The PHI and PCA3 were detected by using immunofluorescence and Loop-Mediated Isothermal Amplification (LAMP). The sensitivity and specificity of diagnosis were determined by ROC curve.In addition, the relationship between PHI/PSA and the Gleason score and clinical stage were analyzed. A total of 89 patients were confirmed PCa by Pathological diagnosis. The other 101 patients were diagnosed as benign prostatic hyperplasia (BPH). The sensitivity and specificity of PCA3 test were 85.4% was 92.1%. Area under curve (AUC) of PHI is higher than AUC of PSA (0.727>0.699). The PHI in peripheral blood was positively correlated with Gleason score and clinical stage. The detection of PCA3 and PHI shows excellent detecting effectiveness. Compared with single PSA, the combined detection of PHI and PCA3 improved the diagnostic specificity. It can provide a new method for the early diagnosis in prostate cancer and avoid unnecessary biopsies.

  3. Evaluation of [-2] proPSA and Prostate Health Index (phi) for the detection of prostate cancer: a systematic review and meta-analysis.

    PubMed

    Filella, Xavier; Giménez, Nuria

    2013-04-01

    The usefulness of %[-2] proPSA and Prostate Health Index (phi) in the detection of prostate cancer are currently unknown. It has been suggested that these tests can distinguish prostate cancer from benign prostatic diseases better than PSA or %fPSA. We performed a systematic review and meta-analysis of the available scientific evidence to evaluate the clinical usefulness of %[-2] proPSA and phi. Relevant published papers were identified by searching computerized bibliographic systems. Data on sensitivity and specificity were extracted from 12 studies: 10 studies about %[-2] proPSA (3928 patients in total, including 1762 with confirmed prostate cancer) and eight studies about phi (2919 patients in total, including 1515 with confirmed prostate cancer). The sensitivity for the detection of prostate cancer was 90% for %[-2] proPSA and phi, while the pooled specificity was 32.5% (95% CI 30.6-34.5) and 31.6% (95% CI 29.2-34.0) for %[-2] proPSA and phi, respectively. The measurement of %[-2] proPSA improves the accuracy of prostate cancer detection in comparison with PSA or %fPSA, particularly in the group of patients with PSA between 2 μg/L and 10 μg/L. Similar results were obtained measuring phi. Using these tests, it is possible to reduce the number of unnecessary biopsies, maintaining a high cancer detection rate. Published results also showed that %[-2] proPSA and phi are related to the aggressiveness of the tumor.

  4. The combination of ovarian volume and outline has better diagnostic accuracy than prostate-specific antigen (PSA) concentrations in women with polycystic ovarian syndrome (PCOs).

    PubMed

    Bili, Eleni; Bili, Authors Eleni; Dampala, Kaliopi; Iakovou, Ioannis; Tsolakidis, Dimitrios; Giannakou, Anastasia; Tarlatzis, Basil C

    2014-08-01

    The aim of this study was to determine the performance of prostate specific antigen (PSA) and ultrasound parameters, such as ovarian volume and outline, in the diagnosis of polycystic ovary syndrome (PCOS). This prospective, observational, case-controlled study included 43 women with PCOS, and 40 controls. Between day 3 and 5 of the menstrual cycle, fasting serum samples were collected and transvaginal ultrasound was performed. The diagnostic performance of each parameter [total PSA (tPSA), total-to-free PSA ratio (tPSA:fPSA), ovarian volume, ovarian outline] was estimated by means of receiver operating characteristic (ROC) analysis, along with area under the curve (AUC), threshold, sensitivity, specificity as well as positive (+) and negative (-) likelihood ratios (LRs). Multivariate logistical regression models, using ovarian volume and ovarian outline, were constructed. The tPSA and tPSA:fPSA ratio resulted in AUC of 0.74 and 0.70, respectively, with moderate specificity/sensitivity and insufficient LR+/- values. In the multivariate logistic regression model, the combination of ovarian volume and outline had a sensitivity of 97.7% and a specificity of 97.5% in the diagnosis of PCOS, with +LR and -LR values of 39.1 and 0.02, respectively. In women with PCOS, tPSA and tPSA:fPSA ratio have similar diagnostic performance. The use of a multivariate logistic regression model, incorporating ovarian volume and outline, offers very good diagnostic accuracy in distinguishing women with PCOS patients from controls. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Impact of PSA density of transition zone as a potential parameter in reducing the number of unnecessary prostate biopsies in patients with psa levels between 2.6 and 10.0 ng/mL.

    PubMed

    Castro, Hugo A Socrates; Iared, Wagner; Santos, José Eduardo Mourão; Solha, Raphael Sandes; Shigueoka, David Carlos; Ajzen, Sergio Aron

    2018-04-10

    To assess the accuracy of prostate-specific antigen (PSA) adjusted for the transition zone volume (PSATZ) in predicting prostate cancer by comparing the ability of several PSA parameters in predicting prostate cancer in men with intermediate PSA levels of 2.6 - 10.0 ng/mL and its ability to reduce unnecessary biopsies. This study included 656 patients referred for prostate biopsy who had a serum PSA of 2.6 - 10.0 ng/mL. Total prostate and transition zone volumes were measured by transrectal ultrasound using the prolate ellipsoid method. The clinical values of PSA, free-to-total (F/T) ratio, PSA density (PSAD) and PSATZ for the detection of prostate cancer were calculated and statistical comparisons between biopsy-positive (cancer) and biopsy-negative (benign) were conducted. Cancer was detected in 172 patients (26.2%). Mean PSA, PSATZ, PSAD and F/T ratio were 7.5 ng/mL, 0.68 ng/mL/cc. 0.25 ng/mL/cc and 0.14 in patients with prostate cancer and 6.29 ng/mL, 0.30 ng/mL/cc, 0.16 ng/mL/cc and 0.22 in patients with benign biopsies, respectively. ROC curves analysis demonstrated that PSATZ had a higher area under curve (0,838) than F/T ratio (0,806) (P<0.001) and PSAD (0,806) (P<0.001). With a cut-off value of 0.22 ng/mL/cc, PSATZ had 100% of sensitivity and could have prevented 24% of unnecessary biopsies. PSATZ may be useful in enhancing the specificity of serum PSA. Compared to other PSA related parameters, it was better in differentiating between prostate cancer and benign prostatic enlargement. Also, PSATZ could reduce a significant number of unnecessary biopsies. Copyright® by the International Brazilian Journal of Urology.

  6. Phosphorylcholine Decreases Early Inflammation and Promotes the Establishment of Stable Biofilm Communities of Nontypeable Haemophilus influenzae Strain 86-028NP in a Chinchilla Model of Otitis Media▿ †

    PubMed Central

    Hong, Wenzhou; Mason, Kevin; Jurcisek, Joseph; Novotny, Laura; Bakaletz, Lauren O.; Swords, W. Edward

    2007-01-01

    Nontypeable Haemophilus influenzae (NTHi) is a leading causative agent of otitis media. Much of the inflammation occurring during NTHi disease is initiated by lipooligosaccharides (LOS) on the bacterial surface. Phosphorylcholine (PCho) is added to some LOS forms in a phase-variable manner, and these PCho+ variants predominate in vivo. Thus, we asked whether this modification confers some advantage during infection. Virulence of an otitis media isolate (NTHi strain 86-028NP) was compared with that of an isogenic PCho transferase (licD) mutant using a chinchilla (Chinchilla lanigera) model of otitis media. Animals infected with NTHi 86-028NP licD demonstrated increased early inflammation and a delayed increase in bacterial counts compared to animals infected with NTHi 86-028NP. LOS purified from chinchilla-passed NTHi 86-028NP had increased PCho content compared to LOS purified from the inoculum. Both strains were recovered from middle ear fluids as long as 14 days postinfection. Biofilms were macroscopically visible in the middle ears of euthanized animals infected with NTHi 86-028NP 7 days and 14 days postchallenge. Conversely, less dense biofilms were observed in animals infected with NTHi 86-028NP licD 7 days postinfection, and none of the animals infected with NTHi 86-028NP licD had a visible biofilm by 14 days. Fluorescent antibody staining revealed PCho+ variants within biofilms, similar to our prior results with tissue culture cells in vitro (S. L. West-Barnette, A. Rockel, and W. E. Swords, Infect. Immun. 74:1828-1836, 2006). Animals coinfected with equal proportions of both strains had equal persistence of each strain and somewhat greater severity of disease. We thus conclude that PCho promotes NTHi infection and persistence by reducing the host inflammatory response and by promoting formation of stable biofilm communities. PMID:17130253

  7. Pre- and postnatal exposure of mice to concentrated urban PM2.5 decreases the number of alveoli and leads to altered lung function at an early stage of life.

    PubMed

    de Barros Mendes Lopes, Thais; Groth, Espen E; Veras, Mariana; Furuya, Tatiane K; de Souza Xavier Costa, Natalia; Ribeiro Júnior, Gabriel; Lopes, Fernanda Degobbi; de Almeida, Francine M; Cardoso, Wellington V; Saldiva, Paulo Hilario Nascimento; Chammas, Roger; Mauad, Thais

    2018-06-04

    Gestational exposure to air pollution is associated with negative outcomes in newborns and children. In a previous study, we demonstrated a synergistic negative effect of pre- and postnatal exposure to PM 2.5 on lung development in mice. However, the means by which air pollution affects development of the lung have not yet been identified. In this study, we exposed pregnant BALB/c mice and their offspring to concentrated urban PM 2.5 (from São Paulo, Brazil; target dose 600 μg/m 3 for 1 h daily). Exposure was started on embryonic day 5.5 (E5.5, time of placental implantation). Lung tissue of fetuses and offspring was submitted to stereological and transcriptomic analyses at E14.5 (pseudoglandular stage of lung development), E18.5 (saccular stage) and P40 (postnatal day 40, alveolarized lung). Additionally, lung function and cellularity of bronchoalveolar lavage (BAL) fluid were studied in offspring animals at P40. Compared to control animals that were exposed to filtered air throughout gestation and postnatal life, PM-exposed mice exhibited higher lung elastance and a lower alveolar number at P40 whilst the total lung volume and cellularity of BAL fluid were not affected. Glandular and saccular structures of fetal lungs were not altered upon gestational exposure; transcriptomic signatures, however, showed changes related to DNA damage and its regulation, inflammation and regulation of cell proliferation. A differential expression was validated at E14.5 for the candidates Sox8, Angptl4 and Gas1. Our data substantiate the in utero biomolecular effect of gestational exposure to air pollution and provide first-time stereological evidence that pre- and early life-postnatal exposure compromise lung development, leading to a reduced number of alveoli and an impairment of lung function in the adult mouse. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Measurement of serum isoform [-2]proPSA derivatives shows superior accuracy to magnetic resonance imaging in the diagnosis of prostate cancer in patients with a total prostate-specific antigen level of 2-10 ng/ml.

    PubMed

    Furuya, Kazuhiro; Kawahara, Takashi; Narahara, Masaki; Tokita, Takashi; Fukui, Sachi; Imano, Masashi; Mitome, Taku; Ito, Yusuke; Izumi, Koji; Osaka, Kimito; Yokomizo, Yumiko; Hayashi, Narihiko; Hasumi, Hisashi; Nawata, Shintaro; Kawano, Tsuyoshi; Yao, Masahiro; Uemura, Hiroji

    2017-08-01

    More accurate diagnostic procedures for prostate cancer are needed to avoid unnecessary biopsy due to the low specificity of prostate-specific antigen (PSA). Recent studies showed that the percentage of serum isoform [-2]proPSA (p2PSA) to free PSA (%p2PSA), the Prostate Health Index (PHI) and magnetic resonance imaging (MRI) were more accurate than PSA. The aim of this study was to test the accuracy of %p2PSA, PHI and MRI in discriminating patients with and without prostate cancer. The subjects were 50 consecutive men with a PSA level of 2.0-10.0 ng/ml, who underwent prostate biopsy from October 2012 to July 2014. These patients underwent multiparametric MRI before biopsy, and their serum samples were measured for PSA, free PSA and p2PSA. The sensitivity, specificity and accuracy of PHI, %p2PSA and MRI were compared with PSA in the diagnosis of biopsy-confirmed prostate cancer. In a univariate analysis, %p2PSA [area under the curve (AUC): 0.811] and PHI (AUC 0.795) were more accurate than MRI (AUC: 0.583) and PSA (AUC: 0.554) for prostate cancer detection. At 60% sensitivity, the specificity of PHI (76.5%) was higher than that of MRI (52.9%). For significant cancer detection, %p2PSA (AUC: 0.745), PHI (AUC: 0.791) and MRI (AUC: 0.739) were marginally more accurate than PSA (AUC: 0.696). At 85% sensitivity, the specificity of MRI (62.1%) was higher than that of PHI (34.5%). PHI and %p2PSA can be used for screening the general population and MRI can be used for detection of significant cancer in patients suspected, from screening tests, of having prostate cancer.

  9. First postoperative PSA is associated with outcomes in patients with node positive prostate cancer: Results from the SEARCH database.

    PubMed

    McDonald, Michelle L; Howard, Lauren E; Aronson, William J; Terris, Martha K; Cooperberg, Matthew R; Amling, Christopher L; Freedland, Stephen J; Kane, Christopher J

    2018-05-01

    To analyze factors associated with metastases, prostate cancer-specific mortality, and all-cause mortality in pN1 patients. We analyzed 3,642 radical prostatectomy patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Pathologic Gleason grade, number of lymph nodes (LN) removed, and first postoperative prostate-specific antigen (PSA) (<0.2 ng/ml or ≥0.2 ng/ml) were among covariates assessed. Cox regression was used to analyze the association between characteristics and survival outcomes. Kaplan-Meier was used to estimate survival in pN1 patients stratified by first postoperative PSA. Of 3,642 patients, 124 (3.4%) had pN1. There were 71 (60%) patients with 1 positive LN, 32 (27%) with 2 positive LNs, and 15 (13%) with ≥3. Among men with pN1, first postoperative PSA was<0.2ng/ml in 46 patients (51%) and ≥0.2ng/ml in 44 patients (49%). Univariable Cox regression determined pathological Gleason grade (P = 0.021), seminal vesicle invasion (P = 0.010), and first postoperative PSA ≥0.2 ng/ml (P = 0.005) were associated with metastases. First postoperative PSA ≥0.2ng/ml was associated with metastasis on multivariable analysis (P = 0.046). Log-rank analysis revealed a more favorable metastases-free survival in patients with a first postoperative PSA<0.2ng/ml (P = 0.001). Estimated 5-year metastases-free survival rate was 99% for patients with a first postoperative PSA<0.2ng/ml and 87% for ≥0.2ng/ml. pN1 patients with a first postoperative PSA ≥0.2ng/ml were more likely to develop metastases. First postoperative PSA may be useful in identifying pN1 patients who harbor distant disease and aid in secondary treatment decisions. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).

    PubMed

    Turner, E L; Metcalfe, C; Donovan, J L; Noble, S; Sterne, J A C; Lane, J A; Avery, K N; Down, L; Walsh, E; Davis, M; Ben-Shlomo, Y; Oliver, S E; Evans, S; Brindle, P; Williams, N J; Hughes, L J; Hill, E M; Davies, C; Ng, S Y; Neal, D E; Hamdy, F C; Martin, R M

    2014-06-10

    Screening for prostate cancer continues to generate controversy because of concerns about over-diagnosis and unnecessary treatment. We describe the rationale, design and recruitment of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) trial, a UK-wide cluster randomised controlled trial investigating the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing. Seven hundred and eighty-five general practitioner (GP) practices in England and Wales were randomised to a population-based PSA testing or standard care and then approached for consent to participate. In the intervention arm, men aged 50-69 years were invited to undergo PSA testing, and those diagnosed with localised prostate cancer were invited into a treatment trial. Control arm practices undertook standard UK management. All men were flagged with the Health and Social Care Information Centre for deaths and cancer registrations. The primary outcome is prostate cancer mortality at a median 10-year-follow-up. Among randomised practices, 271 (68%) in the intervention arm (198,114 men) and 302 (78%) in the control arm (221,929 men) consented to participate, meeting pre-specified power requirements. There was little evidence of differences between trial arms in measured baseline characteristics of the consenting GP practices (or men within those practices). The CAP trial successfully met its recruitment targets and will make an important contribution to international understanding of PSA-based prostate cancer screening.

  11. Simulation optimization of PSA-threshold based prostate cancer screening policies

    PubMed Central

    Zhang, Jingyu; Denton, Brian T.; Shah, Nilay D.; Inman, Brant A.

    2013-01-01

    We describe a simulation optimization method to design PSA screening policies based on expected quality adjusted life years (QALYs). Our method integrates a simulation model in a genetic algorithm which uses a probabilistic method for selection of the best policy. We present computational results about the efficiency of our algorithm. The best policy generated by our algorithm is compared to previously recommended screening policies. Using the policies determined by our model, we present evidence that patients should be screened more aggressively but for a shorter length of time than previously published guidelines recommend. PMID:22302420

  12. ONC201 Targets AR and AR-V7 Signaling, Reduces PSA, and Synergizes with Everolimus in Prostate Cancer.

    PubMed

    Lev, Avital; Lulla, Amriti R; Ross, Brian C; Ralff, Marie D; Makhov, Petr B; Dicker, David T; El-Deiry, Wafik S

    2018-05-01

    Androgen receptor (AR) signaling plays a key role in prostate cancer progression, and androgen deprivation therapy (ADT) is a mainstay clinical treatment regimen for patients with advanced disease. Unfortunately, most prostate cancers eventually become androgen-independent and resistant to ADT with patients progressing to metastatic castration-resistant prostate cancer (mCRPC). Constitutively activated AR variants (AR-V) have emerged as mediators of resistance to AR-targeted therapy and the progression of mCRPC, and they represent an important therapeutic target. Out of at least 15 AR-Vs described thus far, AR-V7 is the most abundant, and its expression correlates with ADT resistance. ONC201/TIC10 is the founding member of the imipridone class of small molecules and has shown anticancer activity in a broad range of tumor types. ONC201 is currently being tested in phase I/II clinical trials for advanced solid tumors, including mCRPC, and hematologic malignancies. There has been promising activity observed in patients in early clinical testing. This study demonstrates preclinical single-agent efficacy of ONC201 using in vitro and in vivo models of prostate cancer. ONC201 has potent antiproliferative and proapoptotic effects in both castration-resistant and -sensitive prostate cancer cells. Furthermore, the data demonstrate that ONC201 downregulates the expression of key drivers of prostate cancer such as AR-V7 and downstream target genes including the clinically used biomarker PSA (KLK3). Finally, the data also provide a preclinical rationale for combination of ONC201 with approved therapeutics for prostate cancer such as enzalutamide, everolimus (mTOR inhibitor), or docetaxel. Implications: The preclinical efficacy of ONC201 as a single agent or in combination, in hormone-sensitive or castration-resistant prostate cancer, suggests the potential for immediate clinical translation. Mol Cancer Res; 16(5); 754-66. ©2018 AACR . ©2018 American Association for Cancer

  13. Association between PSA kinetics and cancer-specific mortality in patients with localised prostate cancer: analysis of the placebo arm of the SPCG-6 study.

    PubMed

    Thomsen, F B; Brasso, K; Berg, K D; Gerds, T A; Johansson, J-E; Angelsen, A; Tammela, T L J; Iversen, P

    2016-03-01

    The prognostic value of prostate-specific antigen (PSA) kinetics in untreated prostate cancer (PCa) patients is debatable. We investigated the association between PSA doubling time (PSAdt), PSA velocity (PSAvel) and PSAvel risk count (PSAvRC) and PCa mortality in a cohort of patients with localised PCa managed on watchful waiting. Patients with clinically localised PCa managed observationally, who were randomised to and remained on placebo for minimum 18 months in the SPCG-6 study, were included. All patients survived at least 2 years and had a minimum of three PSA determinations available. The prognostic value of PSA kinetics was analysed and patients were stratified according to their PSA at consent: ≤10, 10.1-25, and >25 ng/ml. Cumulative incidences of PCa-specific mortality were estimated with the Aalen-Johansen method. Two hundred and sixty-three patients were included of which 116, 76 and 71 had a PSA at consent ≤10, 10.1-25, and >25 ng/ml, respectively. Median follow-up was 13.6 years. For patients with PSA at consent between 10.1 and 25 ng/ml, the 13-year risks of PCa mortality were associated with PSA kinetics: PSAdt ≤3 years: 62.0% versus PSAdt >3 years: 16.3% (Gray's test: P < 0.0001), PSAvel ≥2 ng/ml/year: 48.0% versus PSAvel <2 ng/ml/year: 11.0% (Gray's test: P = 0.0008), and PSAvRC 2: 45.0% versus 0-1: 3.8% (Gray's test: P = 0.001). In contrast, none of the PSA kinetics were significantly associated with changes of 13-year risks of PCa mortality in patients with PSA at consent ≤10 or >25 ng/ml. We found that magnitude changes in 13-year risks of PCa mortality that can be indicated by PSA kinetics depend on PSA level in patients with localised PCa who were managed observationally. Our results question PSA kinetics as surrogate marker for PCa mortality in patients with low and high PSA values. NCT00672282. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For

  14. Prostate health index significantly reduced unnecessary prostate biopsies in patients with PSA 2-10 ng/mL and PSA >10 ng/mL: Results from a Multicenter Study in China.

    PubMed

    Na, Rong; Ye, Dingwei; Qi, Jun; Liu, Fang; Helfand, Brian T; Brendler, Charles B; Conran, Carly A; Packiam, Vignesh; Gong, Jian; Wu, Yishuo; Zheng, Siqun L; Mo, Zengnan; Ding, Qiang; Sun, Yinghao; Xu, Jianfeng

    2017-08-01

    The performance of prostate health index (phi) in predicting prostate biopsy outcomes has been well established for patients with prostate-specific antigen (PSA) values between 2 and 10 ng/mL. However, the performance of phi remains unknown in patients with PSA >10 ng/mL, the vast majority in Chinese biopsy patients. We aimed to assess the ability of phi to predict prostate cancer (PCa) and high-grade disease (Gleason Score ≥7) on biopsy in a Chinese population. This is a prospective, observational, multi-center study of consecutive patients who underwent a transrectal ultrasound guided prostate biopsy at four hospitals in Shanghai, China from August 2013 to December 2014. In the cohort of 1538 patients, the detection rate of PCa was 40.2%. phi had a significantly better predictive performance for PCa than total PSA (tPSA). The areas under the receiver operating characteristic curve (AUC) were 0.90 and 0.79 for phi and tPSA, respectively, P < 0.0001. A considerable proportion of patients in the cohort had PSAs >10 ng/mL (N = 838, 54.5%). The detection rates of PCa were 35.9% and 57.7% in patients with tPSA 10.1-20 and 20.1-50 ng/mL, respectively. The AUCs of phi (0.79 and 0.89, for these two groups, respectively) were also significantly higher than tPSA (0.57 and 0.63, respectively), both P < 0.0001. If a phi ≤35 was used as the cutoff, 599/1538 (39%) biopsies could have been avoided at a cost of missing small numbers of PCa patients: 49 (7.93%) PCa patients, including 18 (3.69%) high-grade tumors. Results from this study suggest that phi can be used to predict PCa and high-grade disease in Chinese men with high PSA levels (>10 ng/mL). © 2017 Wiley Periodicals, Inc.

  15. Formulation of the bivalent prostate cancer vaccine with surgifoam elicits antigen-specific effector T cells in PSA-transgenic mice.

    PubMed

    Karan, Dev

    2017-10-13

    We previously developed and characterized an adenoviral-based prostate cancer vaccine for simultaneous targeting of prostate-specific antigen (PSA) and prostate stem cell antigen (PSCA). We also demonstrated that immunization of mice with the bivalent vaccine (Ad 5 -PSA+PSCA) inhibited the growth of established prostate tumors. However, there are multiple challenges hindering the success of immunological therapies in the clinic. One of the prime concerns has been to overcome the immunological tolerance and maintenance of long-term effector T cells. In this study, we further characterized the use of the bivalent vaccine (Ad 5 -PSA+PSCA) in a transgenic mouse model expressing human PSA in the mouse prostate. We demonstrated the expression of PSA analyzed at the mRNA level (by RT-PCR) and protein level (by immunohistochemistry) in the prostate lobes harvested from the PSA-transgenic (PSA-Tg) mice. We established that the administration of the bivalent vaccine in surgifoam to the PSA-Tg mice induces strong PSA-specific effector CD8 + T cells as measured by IFN-γ secretion and in vitro cytotoxic T-cell assay. Furthermore, the use of surgifoam with Ad 5 -PSA+PSCA vaccine allows multiple boosting vaccinations with a significant increase in antigen-specific CD8 + T cells. These observations suggest that the formulation of the bivalent prostate cancer vaccine (Ad 5 -PSA+PSCA) with surgifoam bypasses the neutralizing antibody response, thus allowing multiple boosting. This formulation is also helpful for inducing an antigen-specific immune response in the presence of self-antigen, and maintains long-term effector CD8 + T cells. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  16. Verna Wright Lecture: Psoriatic Arthritis: The Need for Early Intervention.

    PubMed

    McHugh, Neil J

    2015-11-01

    About 30% of individuals with skin psoriasis will develop an inflammatory disease of the peripheral or axial skeleton involving synovial and/or entheseal tissue termed psoriatic arthritis (PsA). In most cases psoriasis will precede PsA by several years. Hence skin psoriasis provides an opportune model to investigate genetic and environmental factors that interact and contribute to the development of a common form of inflammatory arthritis. Further, the preexisting presence of psoriasis represents a unique opportunity for the early detection of arthritis and the potential for more effective intervention. However, despite the presence of psoriasis, there may be delay in the diagnosis of PsA that is associated with adverse longterm outcome. Undiagnosed disease is not uncommon, as demonstrated by studies applying screening questionnaires to primary care and dermatology clinic populations. Other potential risk factors, such as obesity and smoking, the presence of certain genetic and biomarker profiles, combined with accurate imaging modalities, offer the potential for more targeted screening. So in future it should be possible to detect PsA at a much earlier stage and prevent significant joint damage and associated disability before it happens.

  17. Percent free prostate-specific antigen for prostate cancer diagnosis in Chinese men with a PSA of 4.0-10.0 ng/mL: Results from the Chinese Prostate Cancer Consortium.

    PubMed

    Chen, Rui; Xie, Liping; Cai, Xiaobing; Huang, Yiran; Zhou, Liqun; Ma, Lulin; Gao, Xu; Xu, Chuanliang; Ren, Shancheng; Shao, Pengfei; Xu, Danfeng; Xu, Kexin; Ye, Zhangqun; Liu, Chunxiao; Ye, Dingwei; Lu, Li; Fu, Qiang; Hou, Jianquan; Yuan, Jianlin; He, Dalin; Zhou, Tie; Wang, Fubo; He, Biming; Sun, Yinghao

    2015-04-01

    To test the diagnostic performance of percent free prostate-specific antigen (%fPSA) in predicting any prostate cancer (PCa) and high-grade prostate cancer (HGPCa) in a retrospective multi-center biopsy cohort with a PSA level of 4.0-10.0 ng/mL in China. Consecutive patients with a PSA of 4.0-10.0 ng/mL who underwent transrectal ultrasound-guided biopsy were enrolled at 16 Chinese medical centers from January 1st, 2010 to December 31st, 2013. Total and free serum PSA determinations were performed using three types of electro-chemiluminescence immunoassays recalibrated to the World Health Organization (WHO) standard. The diagnostic accuracy of PSA, %fPSA, and %fPSA in combination with PSA (%fPSA + PSA) was determined using the area under the receiver operating characteristic (ROC) curve (AUC). A total of 2310 consecutive men with PSA levels between 4.0 and 10.0 ng/mL were included, and the detection rate of PCa was 25.1%. The AUC of %fPSA and %fPSA + PSA in predicting any PCa was superior to PSA alone in men aged ≥60 years (0.623 vs. 0.534, p  < 0.0001) but not in men aged 40-59 years (0.517 vs. 0.518, p  = 0.939). Similar result was yield in predicting HGPCa. In a clinical setting of Chinese men with 4.0-10.0 ng/mL PSA undergoing initial prostate biopsy, adding %fPSA to PSA can moderately improve the diagnostic accuracy for any PCa and HGPCa compared with PSA alone in patients ≥60 but not in patients aged 40-59 years.

  18. Prostate-specific antigen (PSA) testing of men in UK general practice: a 10-year longitudinal cohort study.

    PubMed

    Young, Grace J; Harrison, Sean; Turner, Emma L; Walsh, Eleanor I; Oliver, Steven E; Ben-Shlomo, Yoav; Evans, Simon; Lane, J Athene; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Martin, Richard M; Metcalfe, Chris

    2017-10-30

    Cross-sectional studies suggest that around 6% of men undergo prostate-specific antigen (PSA) testing each year in UK general practice (GP). This longitudinal study aims to determine the cumulative testing pattern of men over a 10-year period and whether this testing can be considered equivalent to screening for prostate cancer (PCa). Patient-level data on PSA tests, biopsies and PCa diagnoses were obtained from the UK Clinical Practice Research Datalink (CPRD) for the years 2002 to 2011. The cumulative risks of PSA testing and of being diagnosed with PCa were estimated for the 10-year study period. Associations of a man's age, region and index of multiple deprivation with the cumulative risk of PSA testing and PCa diagnosis were investigated. Rates of biopsy and diagnosis, following a high test result, were compared with those from the programme of PSA testing in the Prostate Testing for Cancer and Treatment (ProtecT) study. The 10-year risk of exposure to at least one PSA test in men aged 45 to 69 years in UK GP was 39.2% (95% CI 39.0 to 39.4%). The age-specific risks ranged from 25.2% for men aged 45-49 years to 53.0% for men aged 65-69 years (p for trend <0.001). For those with a PSA level ≥3, a test in UK GP was less likely to result in a biopsy (6%) and/or diagnosis of PCa (15%) compared with ProtecT study participants (85% and 34%, respectively). A high proportion of men aged 45-69 years undergo PSA tests in UK GP: 39% over a 10-year period. A high proportion of these tests appear to be for the investigation of lower urinary tract symptoms and not screening for PCa. ISRCTN20141297,NCT02044172. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Validation of Association of Genetic Variants at 10q with PSA Levels in Men at High Risk for Prostate Cancer

    PubMed Central

    Chang, Bao-Li; Hughes, Lucinda; Chen, David Y. T.; Gross, Laura; Ruth, Karen; Giri, Veda N.

    2013-01-01

    Objectives Men with a family history of prostate cancer and African American men are at increased risk for prostate cancer and stand to benefit from individualized interpretation of PSA to guide screening strategies. The purpose of this study was to validate six previously identified markers among high-risk men enrolled in the Prostate Cancer Risk Assessment Program - a prostate cancer screening study. Patients and Methods Eligibility for PRAP includes men ages 35–69 years with a family history of prostate cancer, any African American male regardless of family history, and men with known BRCA gene mutations. GWAS markers assessed included rs2736098 (5p15.33), rs10993994 (10q11), rs10788160 (10q26), rs11067228 (12q24), rs4430796 (17q12), and rs17632542 (19q13.33). Genotyping methods included either Taqman® SNP Genotyping Assay (Applied Biosystems) or pyrosequencing. Linear regression models were used to evaluate the association between individual markers and log-transformed baseline PSA levels, while adjusting for potential confounders. Results 707 participants (37% Caucasian, 63% African American) with clinical and genotype data were included in the analysis. Rs10788160 (10q26) strongly associated with PSA levels among high-risk Caucasian participants (p<0.01), with a 33.2% increase in PSA level with each A-allele carried. Furthermore, rs10993994 (10q11) demonstrated an association to PSA level (p=0.03) in high-risk Caucasian men, with a 15% increase in PSA with each T-allele carried. A PSA adjustment model based on allele carrier status at rs10788160 and rs10993994 is proposed specific to high-risk Caucasian men. Conclusion Genetic variation at 10q may be particularly important in personalizing interpretation of PSA for high-risk Caucasian men. Such information may have clinical relevance in shared decision-making and individualized prostate cancer screening strategies for high-risk Caucasian men. Further study is warranted. PMID:23937305

  20. Effect of a Low-Intensity PSA-Based Screening Intervention on Prostate Cancer Mortality: The CAP Randomized Clinical Trial.

    PubMed

    Martin, Richard M; Donovan, Jenny L; Turner, Emma L; Metcalfe, Chris; Young, Grace J; Walsh, Eleanor I; Lane, J Athene; Noble, Sian; Oliver, Steven E; Evans, Simon; Sterne, Jonathan A C; Holding, Peter; Ben-Shlomo, Yoav; Brindle, Peter; Williams, Naomi J; Hill, Elizabeth M; Ng, Siaw Yein; Toole, Jessica; Tazewell, Marta K; Hughes, Laura J; Davies, Charlotte F; Thorn, Joanna C; Down, Elizabeth; Davey Smith, George; Neal, David E; Hamdy, Freddie C

    2018-03-06

    Prostate cancer screening remains controversial because potential mortality or quality-of-life benefits may be outweighed by harms from overdetection and overtreatment. To evaluate the effect of a single prostate-specific antigen (PSA) screening intervention and standardized diagnostic pathway on prostate cancer-specific mortality. The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) included 419 582 men aged 50 to 69 years and was conducted at 573 primary care practices across the United Kingdom. Randomization and recruitment of the practices occurred between 2001 and 2009; patient follow-up ended on March 31, 2016. An invitation to attend a PSA testing clinic and receive a single PSA test vs standard (unscreened) practice. Primary outcome: prostate cancer-specific mortality at a median follow-up of 10 years. Prespecified secondary outcomes: diagnostic cancer stage and Gleason grade (range, 2-10; higher scores indicate a poorer prognosis) of prostate cancers identified, all-cause mortality, and an instrumental variable analysis estimating the causal effect of attending the PSA screening clinic. Among 415 357 randomized men (mean [SD] age, 59.0 [5.6] years), 189 386 in the intervention group and 219 439 in the control group were included in the analysis (n = 408 825; 98%). In the intervention group, 75 707 (40%) attended the PSA testing clinic and 67 313 (36%) underwent PSA testing. Of 64 436 with a valid PSA test result, 6857 (11%) had a PSA level between 3 ng/mL and 19.9 ng/mL, of whom 5850 (85%) had a prostate biopsy. After a median follow-up of 10 years, 549 (0.30 per 1000 person-years) died of prostate cancer in the intervention group vs 647 (0.31 per 1000 person-years) in the control group (rate difference, -0.013 per 1000 person-years [95% CI, -0.047 to 0.022]; rate ratio [RR], 0.96 [95% CI, 0.85 to 1.08]; P = .50). The number diagnosed with prostate cancer was higher in the intervention group (n = 8054; 4

  1. Identification of the psaA Gene, Coding for Pneumococcal Surface Adhesin A, in Viridans Group Streptococci other than Streptococcus pneumoniae

    PubMed Central

    Jado, Isabel; Fenoll, Asunción; Casal, Julio; Pérez, Amalia

    2001-01-01

    The gene encoding the pneumococcal surface adhesin A (PsaA) protein has been identified in three different viridans group streptococcal species. Comparative studies of the psaA gene identified in different pneumococcal isolates by sequencing PCR products showed a high degree of conservation among these strains. PsaA is encoded by an open reading frame of 930 bp. The analysis of this fragment in Streptococcus mitis, Streptococcus oralis, and Streptococcus anginosus strains revealed a sequence identity of 95, 94, and 90%, respectively, to the corresponding open reading frame of the previously reported Streptococcus pneumoniae serotype 6B strain. Our results confirm that psaA is present and detectable in heterologous bacterial species. The possible implications of these results for the suitability and potential use of PsaA in the identification and diagnosis of pneumococcal diseases are discussed. PMID:11527799

  2. Positive communication paradigm decreases early