Impact of nucleic acid testing relative to antigen/antibody combination immunoassay on the detection of acute HIV infection.

PubMed

De Souza, Mark S; Phanuphak, Nittaya; Pinyakorn, Suteeraporn; Trichavaroj, Rapee; Pattanachaiwit, Supanit; Chomchey, Nitiya; Fletcher, James L; Kroon, Eugene D; Michael, Nelson L; Phanuphak, Praphan; Kim, Jerome H; Ananworanich, Jintanat

2015-04-24

To assess the addition of HIV nucleic acid testing (NAT) to fourth-generation (4thG) HIV antigen/antibody combination immunoassay in improving detection of acute HIV infection (AHI). Participants attending a major voluntary counseling and testing site in Thailand were screened for AHI using 4thG HIV antigen/antibody immunoassay and sequential less sensitive HIV antibody immunoassay. Samples nonreactive by 4thG antigen/antibody immunoassay were further screened using pooled NAT to identify additional AHI. HIV infection status was verified following enrollment into an AHI study with follow-up visits and additional diagnostic tests. Among 74 334 clients screened for HIV infection, HIV prevalence was 10.9% and the overall incidence of AHI (N = 112) was 2.2 per 100 person-years. The inclusion of pooled NAT in the testing algorithm increased the number of acutely infected patients detected, from 81 to 112 (38%), relative to 4thG HIV antigen/antibody immunoassay. Follow-up testing within 5 days of screening marginally improved the 4thG immunoassay detection rate (26%). The median CD4 T-cell count at the enrollment visit was 353 cells/μl and HIV plasma viral load was 598 289 copies/ml. The incorporation of pooled NAT into the HIV testing algorithm in high-risk populations may be beneficial in the long term. The addition of pooled NAT testing resulted in an increase in screening costs of 22% to identify AHI: from $8.33 per screened patient to $10.16. Risk factors of the testing population should be considered prior to NAT implementation given the additional testing complexity and costs.

Internalizing the threat of risk-a qualitative study about adolescents’ experience living with screening-detected celiac disease 5 years after diagnosis

PubMed Central

2014-01-01

Background Mass screening could identify those with unrecognized celiac disease (CD), but the experience of being detected through screening and living with screening-detected CD should be explored before considering this as acceptable intervention. For this study we invited screening-detected adolescents to describe their experience living with screening-detected CD five years after diagnosis with the aim to explore how their perceptions, practices, and beliefs evolved. Methods Adolescents who were diagnosed through a population-based CD screening were invited to write narratives after being diagnosed. Of 153 adolescents who were eventually diagnosed through the screening, 91 wrote narratives one year after diagnosis and 72 five years after diagnosis. A qualitative content analysis resulted in a theme and categories that describe the experience living with screening-detected CD five years after diagnosis. Results The overall theme – Internalizing the threat of risk – illustrates that being detected through screening and the internalized threat of future health complications have impacted how these adolescents felt about the diagnosis, coped with the gluten-free diet (GFD), and thought about CD screening. This theme is supported by four categories: maintaining an imposed disease identity describes how they continued to define their diagnosis in relation to the screening. They also expressed moving from forced food changes to adapted diet routines by describing habits, routines, coping strategies, and the financial burden of the GFD. They had enduring beliefs of being spared negative consequences, however, even after five years, some doubted they had CD and worried that being detected and eating a GFD might not be beneficial, i.e. continuing to fear it is “all in vain”. Conclusions There was maintenance and evolution in the perceptions, practices, and beliefs of the adolescents after five years. Some have adjusted to the disease and adapted new habits and coping strategies to deal with the GFD, while others still doubt they have CD or that being detected was beneficial. The transition to adapting to the disease and GFD is ongoing, illustrating the importance of providing ongoing support for those with screening-detected CD as they adjust to this chronic disease and the GFD. PMID:24915870

Patterns of repeated anal cytology results among HIV-positive and HIV-negative men who have sex with men.

PubMed

Robbins, Hilary A; Wiley, Dorothy J; Ho, Ken; Plankey, Michael; Reddy, Susheel; Joste, Nancy; Darragh, Teresa M; Breen, Elizabeth C; Young, Stephen; D'Souza, Gypsyamber

2018-06-01

Men who have sex with men (MSM) are at increased risk for anal cancer. In cervical cancer screening, patterns of repeated cytology results are used to identify low- and high-risk women, but little is known about these patterns for anal cytology among MSM. We analyzed Multicenter AIDS Cohort Study (MACS) data for MSM who were offered anal cytology testing annually (HIV-positive) or every 2 years (HIV-negative) for 4 years. Following an initial negative (normal) cytology, the frequency of a second negative cytology was lower among HIV-positive MSM with CD4 ≥ 500 (74%) or CD4 < 500 (68%) than HIV-negative MSM (83%) (p < 0.001). After an initial abnormal cytology, the frequency of a second abnormal cytology was highest among HIV-positive MSM with CD4 < 500 (70%) compared to CD4 ≥ 500 (53%) or HIV-negative MSM (46%) (p = 0.003). Among HIV-positive MSM with at least three results, 37% had 3 consecutive negative results; 3 consecutive abnormal results were more frequent among CD4 < 500 (22%) than CD4 ≥ 500 (10%) (p = 0.008). More than one-third of HIV-positive MSM have consistently negative anal cytology over three years. Following abnormal anal cytology, a repeated cytology is commonly negative in HIV-negative or immunocompetent HIV-positive men, while persistent cytological abnormality is more likely among HIV-positive men with CD4 < 500. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

A Multiplex Immunoassay Using the Guthrie Specimen to Detect T-Cell Deficiencies Including Severe Combined Immunodeficiency Disease

PubMed Central

Janik, David K.; Lindau-Shepard, Barbara; Comeau, Anne Marie; Pass, Kenneth A.

2011-01-01

BACKGROUND Severe combined immunodeficiency (SCID) fulfills many of the requirements for addition to a newborn screening panel. Two newborn screening SCID pilot studies are now underway using the T-cell receptor excision circle (TREC) assay, a molecular technique. Here we describe an immunoassay with CD3 as a marker for T cells and CD45 as a marker for total leukocytes that can be used with the Guthrie specimen. METHODS The multiplexing capabilities of the Luminex platform were used. Antibody pairs were used to capture and detect CD3 and CD45 from a single 3-mm punch of the Guthrie specimen. The assay for each bio-marker was developed separately in identical buffers and then combined to create a multiplex assay. RESULTS Using calibrators made from known amounts of leukocytes, a detection limit of 0.25 × 106 cells/mL for CD3 and 0.125 × 106 cells/mL for CD45 was obtained. Affinity tests showed no cross-reactivity between the antibodies to CD3 and CD45. The multiplex assay was validated against 8 coded specimens of known clinical status and linked to results from the TREC assay that had identified them. All were correctly identified by the CD345 assay. CONCLUSIONS The performance parameters of the CD345 assay met the performance characteristics generally accepted for immunoassays. Our assay classifications of positive specimens concur with previous TREC results. This CD345 assay warrants evaluation as a viable alternative or complement to the TREC assay as a primary screening tool for detecting T-cell immunodeficiencies, including SCID, in Guthrie specimens. PMID:20660143

Asymptomatic cryptococcal antigen prevalence detected by lateral flow assay in hospitalised HIV-infected patients in São Paulo, Brazil.

PubMed

Vidal, José E; Toniolo, Carolina; Paulino, Adriana; Colombo, Arnaldo; Dos Anjos Martins, Marilena; da Silva Meira, Cristina; Pereira-Chioccola, Vera Lucia; Figueiredo-Mello, Claudia; Barros, Tiago; Duarte, Jequelie; Fonseca, Fernanda; Alves Cunha, Mirella; Mendes, Clara; Ribero, Taiana; Dos Santos Lazera, Marcia; Rajasingham, Radha; Boulware, David R

2016-12-01

To determine the prevalence of asymptomatic cryptococcal antigen (CRAG) using lateral flow assay (LFA) in hospitalised HIV-infected patients with CD4 counts <200 cells/μl. Hospitalised HIV-infected patients were prospectively recruited at Instituto de Infectologia Emilio Ribas, a tertiary referral hospital to HIV-infected patients serving the São Paulo State, Brazil. All patients were >18 years old without prior cryptococcal meningitis, without clinical suspicion of cryptococcal meningitis, regardless of antiretroviral (ART) status, and with CD4 counts <200 cells/μl. Serum CRAG was tested by LFA in all patients, and whole blood CRAG was tested by LFA in positive cases. We enrolled 163 participants of whom 61% were men. The duration of HIV diagnosis was a median of 8 (range, 1-29) years. 26% were antiretroviral (ART)-naïve, and 74% were ART-experienced. The median CD4 cell count was 25 (range, 1-192) cells/μl. Five patients (3.1%; 95%CI, 1.0-7.0%) were asymptomatic CRAG-positive. Positive results cases were cross-verified by performing LFA in whole blood. 3.1% of HIV-infected inpatients with CD4 <200 cells/μl without symptomatic meningitis had cryptococcal antigenemia in São Paulo, suggesting that routine CRAG screening may be beneficial in similar settings in South America. Our study reveals another targeted population for CRAG screening: hospitalised HIV-infected patients with CD4 <200 cells/μl, regardless of ART status. Whole blood CRAG LFA screening seems to be a simple strategy to prevention of symptomatic meningitis. © 2016 John Wiley & Sons Ltd.

Estimated Prevalence of Cryptococcus Antigenemia (CrAg) among HIV-Infected Adults with Advanced Immunosuppression in Namibia Justifies Routine Screening and Preemptive Treatment.

PubMed

Sawadogo, Souleymane; Makumbi, Boniface; Purfield, Anne; Ndjavera, Christophine; Mutandi, Gram; Maher, Andrew; Kaindjee-Tjituka, Francina; Kaplan, Jonathan E; Park, Benjamin J; Lowrance, David W

2016-01-01

Cryptococcal meningitis is common and associated with high mortality among HIV infected persons. The World Health Organization recommends that routine Cryptococcal antigen (CrAg) screening in ART-naïve adults with a CD4+ count <100 cells/μL followed by pre-emptive antifungal therapy for CrAg-positive patients be considered where CrAg prevalence is ≥3%. The prevalence of CrAg among HIV adults in Namibia is unknown. We estimated CrAg prevalence among HIV-infected adults receiving care in Namibia for the purpose of informing routine screening strategies. The study design was cross-sectional. De-identified plasma specimens collected for routine CD4+ testing from HIV-infected adults enrolled in HIV care at 181 public health facilities from November 2013 to January 2014 were identified at the national reference laboratory. Remnant plasma from specimens with CD4+ counts <200 cells/μL were sampled and tested for CrAg using the IMMY® Lateral Flow Assay. CrAg prevalence was estimated and assessed for associations with age, sex, and CD4+ count. A total of 825 specimens were tested for CrAg. The median (IQR) age of patients from whom specimens were collected was 38 (32-46) years, 45.9% were female and 62.9% of the specimens had CD4 <100 cells/μL. CrAg prevalence was 3.3% overall and 3.9% and 2.3% among samples with CD4+ counts of CD4+<100 cells/μL and 100-200 cells/μL, respectively. CrAg positivity was significantly higher among patients with CD4+ cells/μL < 50 (7.2%, P = 0.001) relative to those with CD4 cells/μL 50-200 (2.2%). This is the first study to estimate CrAg prevalence among HIV-infected patients in Namibia. CrAg prevalence of ≥3.0% among patients with CD4+<100 cells/μL justifies routine CrAg screening and preemptive treatment among HIV-infected in Namibia in line with WHO recommendations. Patients with CD4+<100 cells/μL have a significantly greater risk for CrAg positivity. Revised guidelines for ART in Namibia now recommend routine screening for CrAg.

The Clinical Significance of the MIF Homolog D-Dopachrome Tautomerase (MIF-2) and its Circulating Receptor (sCD74) in Burn Injury

PubMed Central

Kim, Bong-Sung; Stoppe, Christian; Grieb, Gerrit; Leng, Lin; Sauler, Maor; Assis, David; Simons, David; Boecker, Arne Hendrick; Schulte, Wibke; Piecychna, Marta; Hager, Stephan; Bernhagen, Jürgen; Pallua, Norbert; Bucala, Richard

2016-01-01

Background We reported earlier that the cytokine macrophage migration inhibitory factor (MIF) is a potential biomarker in burn injury. In the present study, we investigated the clinical significance in severely burned patients of expression levels the newly discovered MIF family member D-dopachrome tautomerase (DDT or MIF-2) and their common soluble receptor CD74 (sCD74). Methods DDT and sCD74 serum levels were measured 20 severely burned patients and 20 controls. Serum levels were correlated to the abbreviated burn severity index (ABSI) and TBSA followed by receiver operating characteristic (ROC) analysis. Data were supported by gene expression dataset analysis of 31 burn patients and 28 healthy controls. Results CD74 and DDT were increased in burn patients. Furthermore, CD74 and DDT also were elevated in septic non-survivors when compared to survivors. Serum levels of DDT showed a positive correlation with the ABSI and TBSA in the early stage after burn injury, and the predictive character of DDT was strongest at 24 hrs. Serum levels of CD74 only correlated with the ABSI five days post-injury. Conclusions DDT may assist in the monitoring of clinical outcome and prediction of sepsis during the early post-burn period. sCD74 and MIF, by contrast, have limited value as an early predictor of death due to their delayed response to burn injury. PMID:27209369

Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation.

PubMed

Zhyvoloup, Alexander; Melamed, Anat; Anderson, Ian; Planas, Delphine; Lee, Chen-Hsuin; Kriston-Vizi, Janos; Ketteler, Robin; Merritt, Andy; Routy, Jean-Pierre; Ancuta, Petronela; Bangham, Charles R M; Fassati, Ariberto

2017-07-01

HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism. Analysis of >400,000 unique integration sites showed that WT virus integrated more frequently than N74D mutant within or near genes susceptible to repression by digoxin and involved in T-cell activation and cell metabolism. Two main gene networks down-regulated by the drug were CD40L and CD38. Blocking CD40L by neutralizing antibodies selectively inhibited WT virus infection, phenocopying digoxin. Thus the selectivity of digoxin depends on a combination of integration targeting and repression of specific gene networks. The drug unmasked a functional connection between HIV-1 integration and T-cell activation. Our results suggest that HIV-1 evolved integration site selection to couple its early gene expression with the status of target CD4+ T-cells, which may affect latency and viral reactivation.

Impact of Urban Neighborhood Disadvantage on Late Stage Breast Cancer Diagnosis in Virginia.

PubMed

DeGuzman, Pam Baker; Cohn, Wendy F; Camacho, Fabian; Edwards, Brandy L; Sturz, Vanessa N; Schroen, Anneke T

2017-04-01

Research suggests that residents of inner-city urban neighborhoods have higher rates of late stage cancer diagnosis. Identifying urban neighborhoods with high rates of both concentrated disadvantage and late stage cancer diagnosis may assist health care providers to target screening interventions to reduce disparities. The purposes of this study were to (1) create an index to evaluate concentrated disadvantage (CD) using non-racial measures of poverty, (2) determine the impact of neighborhood CD on late stage breast cancer diagnosis in US cities, and (3) to understand the role of obesity on this relationship. We used census block group- (CBG) level poverty indicators from five Virginia cities to develop the index. Breast cancer cases of women aged 18-65 who lived in the five cities were identified from the 2000-2012 Virginia Cancer Registry. A logistic regression model with random intercept was used to evaluate the impact of disadvantage on late stage breast cancer diagnosis. CBG-level maps were developed to geographically identify neighborhoods with both high rates of CD and late breast cancer staging. Over 900 CBGs and 6000 breast cases were included. Global fit of the concentrated disadvantage model was acceptable. The effect of disadvantage on late stage was significant (OR = 1.0083, p = 0.032). Inner-city poverty impacts risk of late stage breast cancer diagnosis. Area-level obesity is highly correlated with neighborhood poverty (ρ = 0.74, p < 0.0001) but the mediating direct and indirect effects are non-significant. Intervening in these high poverty neighborhoods may help combat disparities in late stage diagnosis for urban poor and for minorities living in these underserved neighborhoods, but more study is needed to understanding the complex relationship between concentrated neighborhood poverty, obesity, and late stage diagnosis.

Anti-CD74 antibodies have no diagnostic value in early axial spondyloarthritis: data from the spondyloarthritis caught early (SPACE) cohort.

PubMed

de Winter, Janneke J; van de Sande, Marleen G; Baerlecken, Niklas; Berg, Inger; Ramonda, Roberta; van der Heijde, Désirée; van Gaalen, Floris A; Witte, Torsten; Baeten, Dominique L

2018-03-01

Anti-CD74 IgG antibodies are reported to be elevated in patients with axial spondyloarthritis (axSpA). This study assessed the diagnostic value of anti-CD74 antibodies in patients with early axSpA. Anti-CD74 IgG and IgA antibodies were first measured in an exploratory cohort of patients with radiographic axSpA (138 patients with ankylosing spondyloarthritis (AS)) and 57 healthy controls and then were measured in patients with early axSpA (n = 274) and with non-SpA chronic back pain (CBP) (n = 319), participating in the spondyloarthritis caught early (SPACE) prospective cohort study of patients under 45 years old with early back pain (for ≥ 3 months, but ≤ 2 years). In the exploratory cohort, anti-CD74 IgG antibodies were present in 79.7% of patients with AS vs. 43.9% of healthy controls (p < 0.001). Anti-CD74 IgA antibodies were present in 28.5% of patients with AS vs. 5.3% of healthy controls (p < 0.001). In the SPACE cohort, anti-CD74 IgG antibody levels were present in 46.4% of the patients with axSpA vs. 47.9% of the patients with CBP (p = 0.71). Anti-CD74 IgA antibodies were present in 54.7% of the patients with axSpA and 37.0% of the patients with CBP (p < 0.001). This resulted in a positive predictive value of 58.8% (compared to a prior probability of 46.2%) and a negative predictive value of 59.1% (compared to a prior probability of 53.8%). In a regression model, total serum IgA was associated with axSpA odds ratio (OR) 1.19, p < 0.001) whereas anti-CD74 IgA was not (OR) 1.01, p = 0.33). Furthermore, anti-CD74 IgA was associated with sacroiliitis on magnetic resonance imaging (MRI) (OR) = 2.50, p = 0.005) and heel enthesitis (OR) = 2.56, p = 0.002). Albeit anti-CD74 IgA is elevated in patients with early axSpA, this elevation is not sufficiently specific to yield significant diagnostic value in patients under 45 years old presenting with early back pain.

Screening HIV-Infected Patients with Low CD4 Counts for Cryptococcal Antigenemia prior to Initiation of Antiretroviral Therapy: Cost Effectiveness of Alternative Screening Strategies in South Africa.

PubMed

Larson, Bruce A; Rockers, Peter C; Bonawitz, Rachael; Sriruttan, Charlotte; Glencross, Deborah K; Cassim, Naseem; Coetzee, Lindi M; Greene, Gregory S; Chiller, Tom M; Vallabhaneni, Snigdha; Long, Lawrence; van Rensburg, Craig; Govender, Nelesh P

2016-01-01

In 2015 South Africa established a national cryptococcal antigenemia (CrAg) screening policy targeted at HIV-infected patients with CD4+ T-lymphocyte (CD4) counts <100 cells/ μl who are not yet on antiretroviral treatment (ART). Two screening strategies are included in national guidelines: reflex screening, where a CrAg test is performed on remnant blood samples from CD4 testing; and provider-initiated screening, where providers order a CrAg test after a patient returns for CD4 test results. The objective of this study was to compare costs and effectiveness of these two screening strategies. We developed a decision analytic model to compare reflex and provider-initiated screening in terms of programmatic and health outcomes (number screened, number identified for preemptive treatment, lives saved, and discounted years of life saved) and screening and treatment costs (2015 USD). We estimated a base case with prevalence and other parameters based on data collected during CrAg screening pilot projects integrated into routine HIV care in Gauteng, Free State, and Western Cape Provinces. We conducted sensitivity analyses to explore how results change with underlying parameter assumptions. In the base case, for each 100,000 CD4 tests, the reflex strategy compared to the provider-initiated strategy has higher screening costs ($37,536 higher) but lower treatment costs ($55,165 lower), so overall costs of screening and treatment are $17,629 less with the reflex strategy. The reflex strategy saves more lives (30 lives, 647 additional years of life saved). Sensitivity analyses suggest that reflex screening dominates provider-initiated screening (lower total costs and more lives saved) or saves additional lives for small additional costs (< $125 per life year) across a wide range of conditions (CrAg prevalence, patient and provider behavior, patient survival without treatment, and effectiveness of preemptive fluconazole treatment). In countries with substantial numbers of people with untreated, advanced HIV disease such as South Africa, CrAg screening before initiation of ART has the potential to reduce cryptococcal meningitis and save lives. Reflex screening compared to provider-initiated screening saves more lives and is likely to be cost saving or have low additional costs per additional year of life saved.

Screening HIV-Infected Patients with Low CD4 Counts for Cryptococcal Antigenemia prior to Initiation of Antiretroviral Therapy: Cost Effectiveness of Alternative Screening Strategies in South Africa

PubMed Central

Rockers, Peter C.; Bonawitz, Rachael; Sriruttan, Charlotte; Glencross, Deborah K.; Cassim, Naseem; Coetzee, Lindi M.; Greene, Gregory S.; Chiller, Tom M.; Vallabhaneni, Snigdha; Long, Lawrence; van Rensburg, Craig; Govender, Nelesh P.

2016-01-01

Background In 2015 South Africa established a national cryptococcal antigenemia (CrAg) screening policy targeted at HIV-infected patients with CD4+ T-lymphocyte (CD4) counts <100 cells/ μl who are not yet on antiretroviral treatment (ART). Two screening strategies are included in national guidelines: reflex screening, where a CrAg test is performed on remnant blood samples from CD4 testing; and provider-initiated screening, where providers order a CrAg test after a patient returns for CD4 test results. The objective of this study was to compare costs and effectiveness of these two screening strategies. Methods We developed a decision analytic model to compare reflex and provider-initiated screening in terms of programmatic and health outcomes (number screened, number identified for preemptive treatment, lives saved, and discounted years of life saved) and screening and treatment costs (2015 USD). We estimated a base case with prevalence and other parameters based on data collected during CrAg screening pilot projects integrated into routine HIV care in Gauteng, Free State, and Western Cape Provinces. We conducted sensitivity analyses to explore how results change with underlying parameter assumptions. Results In the base case, for each 100,000 CD4 tests, the reflex strategy compared to the provider-initiated strategy has higher screening costs ($37,536 higher) but lower treatment costs ($55,165 lower), so overall costs of screening and treatment are $17,629 less with the reflex strategy. The reflex strategy saves more lives (30 lives, 647 additional years of life saved). Sensitivity analyses suggest that reflex screening dominates provider-initiated screening (lower total costs and more lives saved) or saves additional lives for small additional costs (< $125 per life year) across a wide range of conditions (CrAg prevalence, patient and provider behavior, patient survival without treatment, and effectiveness of preemptive fluconazole treatment). Conclusions In countries with substantial numbers of people with untreated, advanced HIV disease such as South Africa, CrAg screening before initiation of ART has the potential to reduce cryptococcal meningitis and save lives. Reflex screening compared to provider-initiated screening saves more lives and is likely to be cost saving or have low additional costs per additional year of life saved. PMID:27390864

Milatuzumab-SN-38 conjugates for the treatment of CD74+ cancers.

PubMed

Govindan, Serengulam V; Cardillo, Thomas M; Sharkey, Robert M; Tat, Fatma; Gold, David V; Goldenberg, David M

2013-06-01

CD74 is an attractive target for antibody-drug conjugates (ADC), because it internalizes and recycles after antibody binding. CD74 mostly is associated with hematologic tumors but is expressed also in solid cancers. Therefore, ADCs of the humanized anti-CD74 antibody, milatuzumab, were examined for the therapy of CD74-expressing solid tumors. Milatuzumab-doxorubicin and two milatuzumab-SN-38 conjugates with cleavable linkers, differing in their stability in serum and how they release SN-38 in the lysosome, were prepared. CD74 expression was determined by flow cytometry and immunohistology. In vitro cytotoxicity and in vivo therapeutic studies were conducted in the human cancer cell lines A-375 (melanoma), HuH-7 and Hep-G2 (hepatoma), Capan-1 (pancreatic), NCI-N87 (gastric), and Raji Burkitt lymphoma. The milatuzumab-SN-38 ADC was compared with SN-38 ADCs prepared with anti-Trop-2 and anti-CEACAM6 antibodies in xenografts expressing their target antigens. Milatuzumab-doxorubicin was most effective in the lymphoma model, whereas in A-375 and Capan-1 solid tumors, only milatuzumab-SN-38 showed a therapeutic benefit. Despite much lower surface expression of CD74 than Trop-2 or CEACAM6, milatuzumab-SN-38 had similar efficacy in Capan-1 as anti-Trop-2-SN-38, but in NCI-N87, anti-CEACAM6 and anti-Trop-2 conjugates were superior. Studies in two hepatoma lines at a single dose level showed significant benefit over saline controls but not against an irrelevant immunoglobulin G conjugate. CD74 is a suitable target for ADCs in some solid tumor xenografts, with efficacy largely influenced by uniformity of CD74 expression and with SN-38 conjugates providing the best therapeutic responses; SN-38 conjugates were preferable in solid cancers, whereas doxorubicin ADC was better in lymphoma tested. ©2013 AACR

[Key effect genes responding to nerve injury identified by gene ontology and computer pattern recognition].

PubMed

Pan, Qian; Peng, Jin; Zhou, Xue; Yang, Hao; Zhang, Wei

2012-07-01

In order to screen out important genes from large gene data of gene microarray after nerve injury, we combine gene ontology (GO) method and computer pattern recognition technology to find key genes responding to nerve injury, and then verify one of these screened-out genes. Data mining and gene ontology analysis of gene chip data GSE26350 was carried out through MATLAB software. Cd44 was selected from screened-out key gene molecular spectrum by comparing genes' different GO terms and positions on score map of principal component. Function interferences were employed to influence the normal binding of Cd44 and one of its ligands, chondroitin sulfate C (CSC), to observe neurite extension. Gene ontology analysis showed that the first genes on score map (marked by red *) mainly distributed in molecular transducer activity, receptor activity, protein binding et al molecular function GO terms. Cd44 is one of six effector protein genes, and attracted us with its function diversity. After adding different reagents into the medium to interfere the normal binding of CSC and Cd44, varying-degree remissions of CSC's inhibition on neurite extension were observed. CSC can inhibit neurite extension through binding Cd44 on the neuron membrane. This verifies that important genes in given physiological processes can be identified by gene ontology analysis of gene chip data.

Reduced Expression of CD45 Protein-tyrosine Phosphatase Provides Protection against Anthrax Pathogenesis*S⃞

PubMed Central

Panchal, Rekha G.; Ulrich, Ricky L.; Bradfute, Steven B.; Lane, Douglas; Ruthel, Gordon; Kenny, Tara A.; Iversen, Patrick L.; Anderson, Arthur O.; Gussio, Rick; Raschke, William C.; Bavari, Sina

2009-01-01

The modulation of cellular processes by small molecule inhibitors, gene inactivation, or targeted knockdown strategies combined with phenotypic screens are powerful approaches to delineate complex cellular pathways and to identify key players involved in disease pathogenesis. Using chemical genetic screening, we tested a library of known phosphatase inhibitors and identified several compounds that protected Bacillus anthracis infected macrophages from cell death. The most potent compound was assayed against a panel of sixteen different phosphatases of which CD45 was found to be most sensitive to inhibition. Testing of a known CD45 inhibitor and antisense phosphorodiamidate morpholino oligomers targeting CD45 also protected B. anthracis-infected macrophages from cell death. However, reduced CD45 expression did not protect anthrax lethal toxin (LT) treated macrophages, suggesting that the pathogen and independently added LT may signal through distinct pathways. Subsequent, in vivo studies with both gene-targeted knockdown of CD45 and genetically engineered mice expressing reduced levels of CD45 resulted in protection of mice after infection with the virulent Ames B. anthracis. Intermediate levels of CD45 expression were critical for the protection, as mice expressing normal levels of CD45 or disrupted CD45 phosphatase activity or no CD45 all succumbed to this pathogen. Mechanism-based studies suggest that the protection provided by reduced CD45 levels results from regulated immune cell homeostasis that may diminish the impact of apoptosis during the infection. To date, this is the first report demonstrating that reduced levels of host phosphatase CD45 modulate anthrax pathogenesis. PMID:19269962

Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation

PubMed Central

Planas, Delphine; Merritt, Andy; Routy, Jean-Pierre; Ancuta, Petronela; Bangham, Charles R. M.

2017-01-01

HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism. Analysis of >400,000 unique integration sites showed that WT virus integrated more frequently than N74D mutant within or near genes susceptible to repression by digoxin and involved in T-cell activation and cell metabolism. Two main gene networks down-regulated by the drug were CD40L and CD38. Blocking CD40L by neutralizing antibodies selectively inhibited WT virus infection, phenocopying digoxin. Thus the selectivity of digoxin depends on a combination of integration targeting and repression of specific gene networks. The drug unmasked a functional connection between HIV-1 integration and T-cell activation. Our results suggest that HIV-1 evolved integration site selection to couple its early gene expression with the status of target CD4+ T-cells, which may affect latency and viral reactivation. PMID:28727807

Gene Deletions in Mycobacterium bovis BCG Stimulate Increased CD8+ T Cell Responses

PubMed Central

Panas, Michael W.; Sixsmith, Jaimie D.; White, KeriAnn; Korioth-Schmitz, Birgit; Shields, Shana T.; Moy, Brian T.; Lee, Sunhee; Schmitz, Joern E.; Jacobs, William R.; Porcelli, Steven A.; Haynes, Barton F.; Letvin, Norman L.

2014-01-01

Mycobacteria, the etiological agents of tuberculosis and leprosy, have coevolved with mammals for millions of years and have numerous ways of suppressing their host's immune response. It has been suggested that mycobacteria may contain genes that reduce the host's ability to elicit CD8+ T cell responses. We screened 3,290 mutant Mycobacterium bovis bacillus Calmette Guerin (BCG) strains to identify genes that decrease major histocompatibility complex (MHC) class I presentation of mycobacterium-encoded epitope peptides. Through our analysis, we identified 16 mutant BCG strains that generated increased transgene product-specific CD8+ T cell responses. The genes disrupted in these mutant strains had disparate predicted functions. Reconstruction of strains via targeted deletion of genes identified in the screen recapitulated the enhanced immunogenicity phenotype of the original mutant strains. When we introduced the simian immunodeficiency virus (SIV) gag gene into several of these novel BCG strains, we observed enhanced SIV Gag-specific CD8+ T cell responses in vivo. This study demonstrates that mycobacteria carry numerous genes that act to dampen CD8+ T cell responses and suggests that genetic modification of these genes may generate a novel group of recombinant BCG strains capable of serving as more effective and immunogenic vaccine vectors. PMID:25287928

Gene deletions in Mycobacterium bovis BCG stimulate increased CD8+ T cell responses.

PubMed

Panas, Michael W; Sixsmith, Jaimie D; White, KeriAnn; Korioth-Schmitz, Birgit; Shields, Shana T; Moy, Brian T; Lee, Sunhee; Schmitz, Joern E; Jacobs, William R; Porcelli, Steven A; Haynes, Barton F; Letvin, Norman L; Gillard, Geoffrey O

2014-12-01

Mycobacteria, the etiological agents of tuberculosis and leprosy, have coevolved with mammals for millions of years and have numerous ways of suppressing their host's immune response. It has been suggested that mycobacteria may contain genes that reduce the host's ability to elicit CD8(+) T cell responses. We screened 3,290 mutant Mycobacterium bovis bacillus Calmette Guerin (BCG) strains to identify genes that decrease major histocompatibility complex (MHC) class I presentation of mycobacterium-encoded epitope peptides. Through our analysis, we identified 16 mutant BCG strains that generated increased transgene product-specific CD8(+) T cell responses. The genes disrupted in these mutant strains had disparate predicted functions. Reconstruction of strains via targeted deletion of genes identified in the screen recapitulated the enhanced immunogenicity phenotype of the original mutant strains. When we introduced the simian immunodeficiency virus (SIV) gag gene into several of these novel BCG strains, we observed enhanced SIV Gag-specific CD8(+) T cell responses in vivo. This study demonstrates that mycobacteria carry numerous genes that act to dampen CD8(+) T cell responses and suggests that genetic modification of these genes may generate a novel group of recombinant BCG strains capable of serving as more effective and immunogenic vaccine vectors. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Identification of cadmium-excluding Welsh onion (Allium fistulosum L.) cultivars and their mechanisms of low cadmium accumulation.

PubMed

Li, Xuhui; Zhou, Qixing; Wei, Shuhe; Ren, Wenjie

2012-06-01

Screening out cadmium (Cd) excluding cultivars of a crop in agricultural production is an effective way to prohibit Cd entering into food chain. A judging criterion for Cd-excluding cultivars based on food safety was suggested and used in the identification of Cd-excluding welsh onion (Allium fistulosum L.) cultivars. A pot culture experiment was carried out to screen out Cd-excluding cultivars, of which the results were confirmed by plot experiments. The relevant factors of Cd accumulation in the pseudostem were analyzed and used in the correlation analysis aiming to study the low Cd accumulation mechanisms. The concentration of Cd in the pseudostem of welsh onions was 0.08-0.20, 0.18-0.41, and 0.26-0.61 mg/kg fresh weight (FW) under three treatments (1.0, 2.5, and 5.0 mg/kg), respectively. The significant (p < 0.05) difference in the concentration of Cd in the pseudostem was observed among 25 welsh onion cultivars, but Cd contamination in soil had little influence on biomass and the contents of soluble sugar, NO(3)(-)-N, and eight other elements in the tested welsh onion cultivars. Two cultivars were identified as Cd-excluding cultivars, mainly because the accumulation of Cd in their pseudostem was only 0.041 ± 0.003 and 0.046 ± 0.002 mg/kg FW, and 0.054 ± 0.001 and 0.066 ± 0.011 mg/kg FW, when growing in plots with Cd concentration of 0.49 and 0.99 mg/kg, respectively. Ribentiegancongwang and Wuyeqi could be identified as Cd-excluding cultivars. Low bioaccumulation factor of the roots was the main mechanism of Cd-excluding welsh onion cultivars.

Node-pore sensing enables label-free surface-marker profiling of single cells.

PubMed

Balakrishnan, Karthik R; Whang, Jeremy C; Hwang, Richard; Hack, James H; Godley, Lucy A; Sohn, Lydia L

2015-03-03

Flow cytometry is a ubiquitous, multiparametric method for characterizing cellular populations. However, this method can grow increasingly complex with the number of proteins that need to be screened simultaneously: spectral emission overlap of fluorophores and the subsequent need for compensation, lengthy sample preparation, and multiple control tests that need to be performed separately must all be considered. These factors lead to increased costs, and consequently, flow cytometry is performed in core facilities with a dedicated technician operating the instrument. Here, we describe a low-cost, label-free microfluidic method that can determine the phenotypic profiles of single cells. Our method employs Node-Pore Sensing to measure the transit times of cells as they interact with a series of different antibodies, each corresponding to a specific cell-surface antigen, that have been functionalized in a single microfluidic channel. We demonstrate the capabilities of our method not only by screening two acute promyelocytic leukemia human cells lines (NB4 and AP-1060) for myeloid antigens, CD13, CD14, CD15, and CD33, simultaneously, but also by distinguishing a mixture of cells of similar size—AP-1060 and NALM-1—based on surface markers CD13 and HLA-DR. Furthermore, we show that our method can screen complex subpopulations in clinical samples: we successfully identified the blast population in primary human bone marrow samples from patients with acute myeloid leukemia and screened these cells for CD13, CD34, and HLA-DR. We show that our label-free method is an affordable, highly sensitive, and user-friendly technology that has the potential to transform cellular screening at the benchside.

Relevance and acceptability of using the Quantiferon gold test (QGIT) to screen CD4 blood draws for latent TB infection among PLHIV in South Africa: formative qualitative research findings from the TEKO trial.

PubMed

Kerrigan, Deanna; Tudor, Carrie; Motlhaoleng, Katlego; Lebina, Limakatso; Qomfu, Cokiswa; Variava, Ebrahim; Chon, Sandy; Martinson, Neil; Golub, Jonathan E

2018-04-16

Tuberculosis (TB) is the leading cause of mortality among people living with HIV (PLHIV), despite the availability of effective preventive therapy. The TEKO trial is assessing the impact of using a blood test, Quantiferon-TB Gold In-Tube Test (QGIT), to screen for latent TB compared to the Tuberculin Screening Test (TST) among PLHIV in South Africa. Fifty-six qualitative interviews were conducted with PLHIV and clinical providers participating in the TEKO trial. We explored TB screening, diagnosis, and treatment guidelines and processes and the use of the QGIT to screen for latent TB infection at the time of CD4 blood draw. Thematic content analysis was conducted. Considerable variability in TB screening procedures was documented due to lack of personnel and clarity regarding current national TB guidelines for PLHIV. Few clinics had started using the TST per national guidelines and many patients had never heard of isoniazid preventive therapy (IPT). Nearly all participants supported the idea of latent TB screening using routine blood drawn for CD4 counts. Findings indicate that screening for latent TB infection using QGIT from blood drawn for CD4 counts among PLHIV is an acceptable approach to increase latent TB detection given the challenges associated with ensuring systematic latent TB screening in overburdened public clinics. The results presented here were from formative research related to the TEKO trial (Identifier NCT02119130 , registered 10 April 2014).

Mass Screening for Celiac Disease Among School-aged Children: Toward Exploring Celiac Iceberg in Saudi Arabia.

PubMed

Al-Hussaini, Abdulrahman; Troncone, Riccardo; Khormi, Musa; AlTuraiki, Muath; Alkhamis, Wahid; Alrajhi, Mona; Halal, Thana; Fagih, Mosa; Alharbi, Sahar; Bashir, Muhammed Salman; Chentoufi, Aziz Alami

2017-12-01

We conducted this mass screening study to determine the prevalence of celiac disease (CD) and characterize the celiac iceberg among Saudi pediatric population in Riyadh, the capital city of Saudi Arabia. During the study period (January 2014-June 2016), we have conducted a cross-sectional, mass screening, immunoglobulin A-tissue transglutaminase (TTG-IgA)-based study on 7930 Saudi students from primary and intermediate schools in Riyadh. Students with positive TTG-IgA (>20 U/L) were called in the hospital to undergo a repeat of TTG-IgA; in those with borderline positive TTG-IgA (20-60 U/L), IgA-endomyseal antibody (EMA-IgA) test was performed. Children with TTG-IgA >60 U/L and children with borderline positive TTG-IgA and positive EMA-IgA were advised to undergo upper endoscopy and intestinal biopsies. We identified 221 students with positive TTG-IgA (2.8%). CD was diagnosed in 119 cases (1.5%, 1:67 Saudi children) (mean age 11.5 ± 2.62 years; girls 81 [68%]). Another 51 children had persistently borderline positive TTG-IgA but negative EMA (0.64%) and the remaining 51 had transiently positive TTG-IgA. We have identified 3 clinical patterns in the screening-identified cases with CD: a silent form (37%), a mild symptomatic form characterized by gastrointestinal symptoms in presence of normal growth or overweight/obesity (48%), and gastrointestinal symptoms associated with impaired growth in 15%. Our study provided evidence of a high prevalence of CD among Saudi children (1.5%), a rate that is at least twice the average prevalence rate in Europe and North America.

Cost-effectiveness of digital mammography screening before the age of 50 in The Netherlands.

PubMed

Sankatsing, Valérie D V; Heijnsdijk, Eveline A M; van Luijt, Paula A; van Ravesteyn, Nicolien T; Fracheboud, Jacques; de Koning, Harry J

2015-10-15

In the Netherlands, routine mammography screening starts at age 50. This starting age may have to be reconsidered because of the increasing breast cancer incidence among women aged 40 to 49 and the recent implementation of digital mammography. We assessed the cost-effectiveness of digital mammography screening that starts between age 40 and 49, using a microsimulation model. Women were screened before age 50, in addition to the current programme (biennial 50-74). Screening strategies varied in starting age (between 40 and 50) and frequency (annual or biennial). The numbers of breast cancers diagnosed, life-years gained (LYG) and breast cancer deaths averted were predicted and incremental cost-effectiveness ratios (ICERs) were calculated to compare screening scenarios. Biennial screening from age 50 to 74 (current strategy) was estimated to gain 157 life years per 1,000 women with lifelong follow-up, compared to a situation without screening, and cost €3,376/LYG (3.5% discounted). Additional screening increased the number of LYG, compared to no screening, ranging from 168 to 242. The costs to generate one additional LYG (i.e., ICER), comparing a screening strategy to the less intensive alternative, were estimated at €5,329 (biennial 48-74 vs. current strategy), €7,628 (biennial 45-74 vs. biennial 48-74), €10,826 (biennial 40-74 vs. biennial 45-74) and €18,759 (annual 40-49 + biennial 50-74 vs. biennial 40-74). Other strategies (49 + biennial 50-74 and annual 45-49 + biennial 50-74) resulted in less favourable ICERs. These findings show that extending the Dutch screening programme by screening between age 40 and 49 is cost-effective, particularly for biennial strategies. © 2015 UICC.

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 Ontario-specific data were unavailable, data from the United States were used. Conclusions PSA screening is associated with significant costs to the health care system when the cost of the PSA test itself is considered in addition to the costs of diagnosis, staging, and treatment of screen-detected PCs. PMID:26366237

Genotype variations in cadmium and lead accumulations of leafy lettuce (Lactuca sativa L.) and screening for pollution-safe cultivars for food safety.

PubMed

Zhang, Kun; Yuan, Jiangang; Kong, Wei; Yang, Zhongyi

2013-06-01

Heavy-metals in polluted soils can accumulate in plants and threaten crop safety. To evaluate the risk of heavy-metal pollution in leafy lettuce (Lactuca sativa L.), two pot experiments were conducted to investigate Cd and Pb accumulation and transfer potential in 28 cultivars of lettuce and to screen for low-Cd and low-Pb accumulative cultivars. In the three treatments, 5.2-fold, 4.8-fold and 4.8-fold differences in the shoot Cd concentration were observed between the cultivars with the highest and the lowest Cd concentrations, respectively. This genotype variation was sufficiently large to identify low-Cd accumulative genotypes to reduce Cd contamination in food. Cadmium accumulation in the low-Cd accumulative genotypes was significantly positively correlated with Pb accumulation. At the cultivar level, Cd and Pb accumulation in lettuce was stable and genotype-dependent. High Pb soil levels did not affect shoot Cd accumulation in lettuce. Lettuce was concluded to be at high risk for Cd pollution and low risk for Pb pollution. Among the tested cultivars, cvs. SJGT, YLGC, N518, and KR17 had the lowest Cd and Pb accumulation abilities in shoots and are thus important parental material for breeding pollution-safe cultivars to minimize Cd and Pb accumulation.

Cadmium biosorption by Streptomyces sp. F4 isolated from former uranium mine.

PubMed

Siñeriz, Manuel Louis; Kothe, Erika; Abate, Carlos Mauricio

2009-09-01

46 actinomycetes were isolated from two polluted sites and one unpolluted site. One strain, F4, was selected through primary qualitative screening assays because of its cadmium resistance, and physiologically and taxonomically characterized. F4 was able to grow at 7.5% NaCl and 100 microg/ml lysozyme and at a pH between 6 and 10. 16S rDNA sequence analysis showed that F4 was closely related to Streptomyces tendae. Growth of Streptomyces sp. F4 on culture medium with 8 mg/l Cd(2+) for 8 days showed 80% inhibition. Maximum specific biosorption was 41.7 mg Cd(2+)/g dry weight after 7 days of growth and highest Cd(2+ )concentration was found in the cell wall (41.2%). The exopolysaccharide layer only contained 7.4%, whereas 39.4% of Cd(2+) was found in the cytosolic fraction. Twelve % was found in the ribosomes and membrane fraction. This was verified with TEM, showing Streptomyces sp. F4 cytoplasm with dark granulate appearance. This study could present the potential capacity of Streptomyces sp. F4 for Cd(2+) bioremediation. Copyright 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preparation of Microkernel-Based Mesoporous (SiO2-CdTe-SiO2)@SiO2 Fluorescent Nanoparticles for Imaging Screening and Enrichment of Heat Shock Protein 90 Inhibitors from Tripterygium Wilfordii.

PubMed

Hu, Yue; Miao, Zhao-Yi; Zhang, Xiao-Jing; Yang, Xiao-Tong; Tang, Ying-Ying; Yu, Sheng; Shan, Chen-Xiao; Wen, Hong-Mei; Zhu, Dong

2018-05-01

The currently utilized ligand fishing for bioactive molecular screening from complex matrixes cannot perform imaging screening. Here, we developed a new solid-phase ligand fishing coupled with an in situ imaging protocol for the specific enrichment and identification of heat shock protein 90 (Hsp 90) inhibitors from Tripterygium wilfordii, utilizing a multiple-layer and microkernel-based mesoporous nanostructure composed of a protective silica coating CdTe quantum dot (QD) core and a mesoporous silica shell, i.e., microkernel-based mesoporous (SiO 2 -CdTe-SiO 2 )@SiO 2 fluorescent nanoparticles (MMFNPs) as extracting carries and fluorescent probes. The prepared MMFNPs showed a highly uniform spherical morphology, retention of fluorescence emission, and great chemical stability. The fished ligands by Hsp 90α-MMFNPs were evaluated via the preliminary bioactivity based on real-time cellular morphology imaging by confocal laser scanning microscopy (CLSM) and then identified by mass spectrometry (MS). Celastrol was successfully isolated as an Hsp 90 inhibitor, and two other specific components screened by Hsp 90α-MMFNPs, i.e., demecolcine and wilforine, were preliminarily identified as potential Hsp 90 inhibitors through the verification of strong affinity to Hsp 90 and antitumor bioactivity. The approach based on the MMFNPs provides a strong platform for imaging screening and discovery of plant-derived biologically active molecules with high efficiency and selectivity.

Phytoremediation of Metal Contaminated Soil Using Willow: Exploiting Plant-Associated Bacteria to Improve Biomass Production and Metal Uptake.

PubMed

Janssen, Jolien; Weyens, Nele; Croes, Sarah; Beckers, Bram; Meiresonne, Linda; Van Peteghem, Pierre; Carleer, Robert; Vangronsveld, Jaco

2015-01-01

Short rotation coppice (SRC) of willow and poplar is proposed for economic valorization and concurrently as remediation strategy for metal contaminated land in northeast-Belgium. However, metal phytoextraction appears insufficient to effectuate rapid reduction of soil metal contents. To increase both biomass production and metal accumulation of SRC, two strategies are proposed: (i) in situ selection of the best performing clones and (ii) bioaugmentation of these clones with beneficial plant-associated bacteria. Based on field data, two experimental willow clones, a Salix viminalis and a Salix alba x alba clone, were selected. Compared to the best performing commercial clones, considerable increases in stem metal extraction were achieved (up to 74% for Cd and 91% for Zn). From the selected clones, plant-associated bacteria were isolated and identified. All strains were subsequently screened for their plant growth-promoting and metal uptake enhancing traits. Five strains were selected for a greenhouse inoculation experiment with the selected clones planted in Cd-Zn-Pb contaminated soil. Extraction potential tended to increase after inoculation of S. viminalis plants with a Rahnella sp. strain due to a significantly increased twig biomass. However, although bacterial strains showing beneficial traits in vitro were used for inoculation, increments in extraction potential were not always observed.

Mycobacterium tuberculosis genome-wide screen exposes multiple CD8+ T cell epitopes

PubMed Central

Hammond, A S; Klein, M R; Corrah, T; Fox, A; Jaye, A; McAdam, K P; Brookes, R H

2005-01-01

Mounting evidence suggests human leucocyte antigen (HLA) class I-restricted CD8+ T cells play a role in protective immunity against tuberculosis yet relatively few epitopes specific for the causative organism, Mycobacterium tuberculosis, are reported. Here a total genome-wide screen of M. tuberculosis was used to identify putative HLA-B*3501 T cell epitopes. Of 479 predicted epitopes, 13 with the highest score were synthesized and used to restimulate lymphocytes from naturally exposed HLA-B*3501 healthy individuals in cultured and ex vivo enzyme-linked immunospot (ELISPOT) assays for interferon (IFN)-γ. All 13 peptides elicited a response that varied considerably between individuals. For three peptides CD8+ T cell lines were expanded and four of the 13 were recognized permissively through the HLA-B7 supertype family. Although further testing is required we show the genome-wide screen to be feasible for the identification of unknown mycobacterial antigens involved in immunity against natural infection. While the mechanisms of protective immunity against M. tuberculosis infection remain unclear, conventional class I-restricted CD8+ T cell responses appear to be widespread throughout the genome. PMID:15762882

Coeliac disease screening is suboptimal in a tertiary gastroenterology setting.

PubMed

Iskandar, Heba; Gray, Darrell M; Vu, Hongha; Mirza, Faiz; Rude, Mary Katherine; Regan, Kara; Abdalla, Adil; Gaddam, Srinivas; Almaskeen, Sami; Mello, Michael; Marquez, Evelyn; Meyer, Claire; Bolkhir, Ahmed; Kanuri, Navya; Sayuk, Gregory; Gyawali, C Prakash

2017-08-01

Coeliac disease (CD) is widely prevalent in North America, but case-finding techniques currently used may not be adequate for patient identification. We aimed to determine the adequacy of CD screening in an academic gastroenterology (GI) practice. Consecutive initial visits to a tertiary academic GI practice were surveyed over a 3-month period as a fellow-initiated quality improvement project. All electronic records were reviewed to look for indications for CD screening according to published guidelines. The timing of screening was noted (before or after referral), as well as the screening method (serology or biopsy). Data were analysed to compare CD screening practices across subspecialty clinics. 616 consecutive patients (49±0.6 years, range 16-87 years, 58.5% females, 94% Caucasian) fulfilled inclusion criteria. CD testing was indicated in 336 (54.5%), but performed in only 145 (43.2%). The need for CD screening was highest in luminal GI and inflammatory bowel disease clinics, followed by biliary and hepatology clinics (p<0.0001); CD screening rate was highest in the luminal GI clinic (p=0.002). Of 145 patients screened, 4 patients (2.4%) had serology consistent with CD, of which 2 were proven by duodenal biopsy. Using this proportion, an additional 5 patients might have been diagnosed in 191 untested patients with indications for CD screening. More than 50% of patients in a tertiary GI clinic have indications for CD screening, but <50% of indicated cases are screened. Case-finding techniques therefore are suboptimal, constituting a gap in patient care and an important target for future quality improvement initiatives. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Comparative transcriptome analysis of duckweed (Landoltia punctata) in response to cadmium provides insights into molecular mechanisms underlying hyperaccumulation.

PubMed

Xu, Hua; Yu, Changjiang; Xia, Xinli; Li, Mingliang; Li, Huiguang; Wang, Yu; Wang, Shumin; Wang, Congpeng; Ma, Yubin; Zhou, Gongke

2018-01-01

Cadmium (Cd) is a detrimental environmental pollutant. Duckweeds have been considered promising candidates for Cd phytoremediation. Although many physiological studies have been conducted, the molecular mechanisms underlying Cd hyperaccumulation in duckweeds are largely unknown. In this study, clone 6001 of Landoltia punctata, which showed high Cd tolerance, was obtained by large-scale screening of over 200 duckweed clones. Subsequently, its growth, Cd flux, Cd accumulation, and Cd distribution characteristics were investigated. To further explore the global molecular mechanism, a comprehensive transcriptome analysis was performed. For RNA-Seq, samples were treated with 20 μM CdCl 2 for 0, 1, 3, and 6 days. In total, 9,461, 9,847, and 9615 differentially expressed unigenes (DEGs) were discovered between Cd-treated and control (0 day) samples. DEG clustering and enrichment analysis identified several biological processes for coping with Cd stress. Genes involved in DNA repair acted as an early response to Cd, while RNA and protein metabolism would be likely to respond as well. Furthermore, the carbohydrate metabolic flux tended to be modulated in response to Cd stress, and upregulated genes involved in sulfur and ROS metabolism might cause high Cd tolerance. Vacuolar sequestration most likely played an important role in Cd detoxification in L. punctata 6001. These novel findings provided important clues for molecular assisted screening and breeding of Cd hyperaccumulating cultivars for phytoremediation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Expression of MIF and CD74 in leukemic cell lines: correlation to DR expression destiny.

PubMed

Georgouli, Mirella; Papadimitriou, Lina; Glymenaki, Maria; Patsaki, Valia; Athanassakis, Irene

2016-06-01

Invariant chain (Ii) or CD74 is a non-polymorphic glycoprotein, which apart from its role as a chaperone dedicated to MHCII molecules, is known to be a high-affinity receptor for macrophage migration inhibitory factor (MIF). The present study aimed to define the roles of CD74 and MIF in the immune surveillance escape process. Towards this direction, the cell lines HL-60, Raji, K562 and primary pre-B leukemic cells were examined for expression and secretion of MIF. Flow cytometry analysis detected high levels of MIF and intracellular/membrane CD74 expression in all leukemic cells tested, while MIF secretion was shown to be inversely proportional to intracellular HLA-DR (DR) expression. In the MHCII-negative cells, IFN-γ increased MIF expression and induced its secretion in HL-60 and K562 cells, respectively. In K562 cells, CD74 (Iip33Iip35) was shown to co-precipitate with HLA-DOβ (DOβ), inhibiting thus MIF or DR binding. Induced expression of DOα in K562 (DOα-DOβ+) cells in different transfection combinations decreased MIF expression and secretion, while increasing surface DR expression. Thus, MIF could indeed be part of the antigen presentation process.

Both host and parasite MIF molecules bind to chicken macrophages via CD74 surface receptor

USDA-ARS?s Scientific Manuscript database

Macrophage migration inhibitory factor (MIF) is recognized as a soluble factor that inhibits the random migration of macrophages and plays a pivotal immunoregulatory function in innate and adaptive immunity. Our group has identified both chicken and Eimeria MIFs, and characterized their function in...

Establishment of CMab-43, a Sensitive and Specific Anti-CD133 Monoclonal Antibody, for Immunohistochemistry.

PubMed

Itai, Shunsuke; Fujii, Yuki; Nakamura, Takuro; Chang, Yao-Wen; Yanaka, Miyuki; Saidoh, Noriko; Handa, Saori; Suzuki, Hiroyoshi; Harada, Hiroyuki; Yamada, Shinji; Kaneko, Mika K; Kato, Yukinari

2017-10-01

CD133, also known as prominin-1, was first described as a cell surface marker on early progenitor and hematopoietic stem cells. It is a five-domain transmembrane protein composed of an N-terminal extracellular tail, two small cytoplasmic loops, two large extracellular loops containing seven potential glycosylation sites, and a short C-terminal intracellular tail. CD133 has been used as a marker to identify cancer stem cells derived from primary solid tumors and as a prognostic marker of gliomas. Herein, we developed novel anti-CD133 monoclonal antibodies (mAbs) and characterized their efficacy in flow cytometry, Western blot, and immunohistochemical analyses. We expressed the full length of CD133 in LN229 glioblastoma cells, immunized mice with LN229/CD133 cells, and performed the first screening using flow cytometry. After limiting dilution, we established 100 anti-CD133 mAbs, reacting with LN229/CD133 cells but not with LN229 cells. Subsequently, we performed the second and third screening with Western blot and immunohistochemical analyses, respectively. Among 100 mAbs, 11 strongly reacted with CD133 in Western blot analysis. One of 11 clones, CMab-43 (IgG 2a , kappa), showed a sensitive and specific reaction against colon cancer cells, warranting the use of CMab-43 in detecting CD133 in pathological analyses of CD133-expressing cancers.

Effectiveness of anti-tumour necrosis factor-α therapy in Danish patients with inflammatory bowel diseases.

PubMed

Bank, Steffen; Andersen, Paal Skytt; Burisch, Johan; Pedersen, Natalia; Roug, Stine; Galsgaard, Julie; Turino, Stine Ydegaard; Brodersen, Jacob Broder; Rashid, Shaista; Avlund, Sara; Olesen, Thomas Bastholm; Green, Anders; Hoffmann, Hans Jürgen; Thomsen, Marianne Kragh; Thomsen, Vibeke Østergaard; Nexø, Bjørn Andersen; Vogel, Ulla; Andersen, Vibeke

2015-03-01

The objective of this study was to evaluate the outcome of anti-tumour necrosis factor-α (anti-TNF) treatment in a large cohort of patients with inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC) in clinical practice and to establish a cohort for future studies of genetic markers associated with treatment response. A national, clinically based cohort of previously naïve anti-TNF treated patients from 18 medical departments was established. The patients were screened for tuberculosis prior to treatment initiation. By combining the unique personal identification number of Danish citizens (the CPR number) from blood samples with data from the National Patient Registry, patients with International Classification of Diseases, Version 10 (ICD-10) codes K50-K63 were identified. Treatment efficacy reflected the maximum response within 22 weeks. Among 492 patients with CD and 267 patients with UC, 74%/13%/14% and 65%/12%/24% were responders, partial responders and non-responders to anti-TNF therapy, respectively. More patients with UC than with CD were non-responders (odds ratio (OR) = 1.96, 95% confidence interval (CI): 1.34-2.87, p = 0.001). Young age was associated with a beneficial response (p = 0.03), whereas smoking ≥ 10 cigarettes/day was associated with non-response among patients with CD (OR = 2.33, 95% CI: 1.13-4.81, p = 0.03). In this clinically based cohort of Danish patients with IBD treated with anti-TNF, high response rates were found. Heavy smoking was associated with non-response, whereas young age at treatment initiation was associated with a beneficial response among patients with CD. Thus, the results obtained in this cohort recruited from clinical practice were similar to those previously obtained in clinical trials. The work was funded by Health Research Fund of Central Denmark Region, Colitis-Crohn Foreningen and the University of Aarhus (PhD grant). Clinicaltrials NCT02322008.

Identifying a Small Molecule Blocking Antigen Presentation in Autoimmune Thyroiditis.

PubMed

Li, Cheuk Wun; Menconi, Francesca; Osman, Roman; Mezei, Mihaly; Jacobson, Eric M; Concepcion, Erlinda; David, Chella S; Kastrinsky, David B; Ohlmeyer, Michael; Tomer, Yaron

2016-02-19

We previously showed that an HLA-DR variant containing arginine at position 74 of the DRβ1 chain (DRβ1-Arg74) is the specific HLA class II variant conferring risk for autoimmune thyroid diseases (AITD). We also identified 5 thyroglobulin (Tg) peptides that bound to DRβ1-Arg74. We hypothesized that blocking the binding of these peptides to DRβ1-Arg74 could block the continuous T-cell activation in thyroiditis needed to maintain the autoimmune response to the thyroid. The aim of the current study was to identify small molecules that can block T-cell activation by Tg peptides presented within DRβ1-Arg74 pockets. We screened a large and diverse library of compounds and identified one compound, cepharanthine that was able to block peptide binding to DRβ1-Arg74. We then showed that Tg.2098 is the dominant peptide when inducing experimental autoimmune thyroiditis (EAT) in NOD mice expressing human DRβ1-Arg74. Furthermore, cepharanthine blocked T-cell activation by thyroglobulin peptides, in particular Tg.2098 in mice that were induced with EAT. For the first time we identified a small molecule that can block Tg peptide binding and presentation to T-cells in autoimmune thyroiditis. If confirmed cepharanthine could potentially have a role in treating human AITD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Comprehensive definition of human immunodominant CD8 antigens in tuberculosis.

PubMed

Lewinsohn, Deborah A; Swarbrick, Gwendolyn M; Park, Byung; Cansler, Meghan E; Null, Megan D; Toren, Katelynne G; Baseke, Joy; Zalwango, Sarah; Mayanja-Kizza, Harriet; Malone, LaShaunda L; Nyendak, Melissa; Wu, Guanming; Guinn, Kristi; McWeeney, Shannon; Mori, Tomi; Chervenak, Keith A; Sherman, David R; Boom, W Henry; Lewinsohn, David M

2017-01-01

Despite widespread use of the Bacillus Calmette-Guerin vaccine, tuberculosis, caused by infection with Mycobacterium tuberculosis , remains a leading cause of morbidity and mortality worldwide. As CD8 + T cells are critical to tuberculosis host defense and a phase 2b vaccine trial of modified vaccinia Ankara expressing Ag85a that failed to demonstrate efficacy, also failed to induce a CD8 + T cell response, an effective tuberculosis vaccine may need to induce CD8 + T cells. However, little is known about CD8, as compared to CD4, antigens in tuberculosis. Herein, we report the results of the first ever HLA allele independent genome-wide CD8 antigen discovery program. Using CD8 + T cells derived from humans with latent tuberculosis infection or tuberculosis and an interferon-γ ELISPOT assay, we screened a synthetic peptide library representing 10% of the Mycobacterium tuberculosis proteome, selected to be enriched for Mycobacterium tuberculosis antigens. We defined a set of immunodominant CD8 antigens including part or all of 74 Mycobacterium tuberculosis proteins, only 16 of which are previously known CD8 antigens. Immunogenicity was associated with the degree of expression of mRNA and protein. Immunodominant antigens were enriched in cell wall proteins with preferential recognition of Esx protein family members, and within proteins comprising the Mycobacterium tuberculosis secretome. A validation study of immunodominant antigens demonstrated that these antigens were strongly recognized in Mycobacterium tuberculosis -infected individuals from a tuberculosis endemic region in Africa. The tuberculosis vaccine field will likely benefit from this greatly increased known repertoire of CD8 immunodominant antigens and definition of properties of Mycobacterium tuberculosis proteins important for CD8 antigenicity.

Phage display discovery of novel molecular targets in glioblastoma-initiating cells.

PubMed

Liu, J K; Lubelski, D; Schonberg, D L; Wu, Q; Hale, J S; Flavahan, W A; Mulkearns-Hubert, E E; Man, J; Hjelmeland, A B; Yu, J; Lathia, J D; Rich, J N

2014-08-01

Glioblastoma is the most common primary intrinsic brain tumor and remains incurable despite maximal therapy. Glioblastomas display cellular hierarchies with self-renewing glioma-initiating cells (GICs) at the apex. To discover new GIC targets, we used in vivo delivery of phage display technology to screen for molecules selectively binding GICs that may be amenable for targeting. Phage display leverages large, diverse peptide libraries to identify interactions with molecules in their native conformation. We delivered a bacteriophage peptide library intravenously to a glioblastoma xenograft in vivo then derived GICs. Phage peptides bound to GICs were analyzed for their corresponding proteins and ranked based on prognostic value, identifying VAV3, a Rho guanine exchange factor involved tumor invasion, and CD97 (cluster of differentiation marker 97), an adhesion G-protein-coupled-receptor upstream of Rho, as potentially enriched in GICs. We confirmed that both VAV3 and CD97 were preferentially expressed by tumor cells expressing GIC markers. VAV3 expression correlated with increased activity of its downstream mediator, Rac1 (ras-related C3 botulinum toxin substrate 1), in GICs. Furthermore, targeting VAV3 by ribonucleic acid interference decreased GIC growth, migration, invasion and in vivo tumorigenesis. As CD97 is a cell surface protein, CD97 selection enriched for sphere formation, a surrogate of self-renewal. In silico analysis demonstrated VAV3 and CD97 are highly expressed in tumors and inform poor survival and tumor grade, and more common with epidermal growth factor receptor mutations. Finally, a VAV3 peptide sequence identified on phage display specifically internalized into GICs. These results show a novel screening method for identifying oncogenic pathways preferentially activated within the tumor hierarchy, offering a new strategy for developing glioblastoma therapies.

Phage display discovery of novel molecular targets in glioblastoma-initiating cells

PubMed Central

Liu, J K; Lubelski, D; Schonberg, D L; Wu, Q; Hale, J S; Flavahan, W A; Mulkearns-Hubert, E E; Man, J; Hjelmeland, A B; Yu, J; Lathia, J D; Rich, J N

2014-01-01

Glioblastoma is the most common primary intrinsic brain tumor and remains incurable despite maximal therapy. Glioblastomas display cellular hierarchies with self-renewing glioma-initiating cells (GICs) at the apex. To discover new GIC targets, we used in vivo delivery of phage display technology to screen for molecules selectively binding GICs that may be amenable for targeting. Phage display leverages large, diverse peptide libraries to identify interactions with molecules in their native conformation. We delivered a bacteriophage peptide library intravenously to a glioblastoma xenograft in vivo then derived GICs. Phage peptides bound to GICs were analyzed for their corresponding proteins and ranked based on prognostic value, identifying VAV3, a Rho guanine exchange factor involved tumor invasion, and CD97 (cluster of differentiation marker 97), an adhesion G-protein-coupled-receptor upstream of Rho, as potentially enriched in GICs. We confirmed that both VAV3 and CD97 were preferentially expressed by tumor cells expressing GIC markers. VAV3 expression correlated with increased activity of its downstream mediator, Rac1 (ras-related C3 botulinum toxin substrate 1), in GICs. Furthermore, targeting VAV3 by ribonucleic acid interference decreased GIC growth, migration, invasion and in vivo tumorigenesis. As CD97 is a cell surface protein, CD97 selection enriched for sphere formation, a surrogate of self-renewal. In silico analysis demonstrated VAV3 and CD97 are highly expressed in tumors and inform poor survival and tumor grade, and more common with epidermal growth factor receptor mutations. Finally, a VAV3 peptide sequence identified on phage display specifically internalized into GICs. These results show a novel screening method for identifying oncogenic pathways preferentially activated within the tumor hierarchy, offering a new strategy for developing glioblastoma therapies. PMID:24832468

Screening mammography among nursing home residents in the United States: Current guidelines and practice.

PubMed

Mack, Deborah S; Epstein, Mara M; Dubé, Catherine; Clark, Robin E; Lapane, Kate L

2018-06-04

United States (US) guidelines regarding when to stop routine breast cancer screening remain unclear. No national studies to-date have evaluated the use of screening mammography among US long-stay nursing home residents. This cross-sectional study was designed to identify prevalence, predictors, and geographic variation of screening mammography among that population in the context of current US guidelines. Screening mammography prevalence, identified with Physician/Supplier Part B claims and stratified by guideline age classification (65-74, ≥75 years), was estimated for all women aged ≥65 years residing in US Medicare- and Medicaid- certified nursing homes (≥1 year) with an annual Minimum Data Set (MDS) 3.0 assessment, continuous Medicare Part B enrollment, and no clinical indication for screening mammography as of 2011 (n = 389,821). The associations between resident- and regional- level factors, and screening mammography, were estimated by crude and adjusted prevalence ratios from robust Poisson regressions clustered by facility. Women on average were 85.4 (standard deviation ±8.1) years old, 77.9% were disabled, and 76.3% cognitively impaired. Screening mammography prevalence was 7.1% among those aged 65-74 years (95% Confidence Interval (CI): 6.8%-7.3%) and 1.7% among those ≥75 years (95% CI, 1.7%-1.8%), with geographic variation observed. Predictors of screening in both age groups included race, cognitive impairment, frailty, hospice, and some comorbidities. These results shed light on the current screening mammography practices in US nursing homes. Thoughtful consideration about individual screening recommendations and the implementation of more clear guidelines for this special population are warranted to prevent overscreening. Copyright © 2018 Elsevier Inc. All rights reserved.

The efficacy and cost of alternative strategies for systematic screening for type 2 diabetes in the U.S. population 45-74 years of age.

PubMed

Johnson, Susan L; Tabaei, Bahman P; Herman, William H

2005-02-01

To simulate the outcomes of alternative strategies for screening the U.S. population 45-74 years of age for type 2 diabetes. We simulated screening with random plasma glucose (RPG) and cut points of 100, 130, and 160 mg/dl and a multivariate equation including RPG and other variables. Over 15 years, we simulated screening at intervals of 1, 3, and 5 years. All positive screening tests were followed by a diagnostic fasting plasma glucose or an oral glucose tolerance test. Outcomes include the numbers of false-negative, true-positive, and false-positive screening tests and the direct and indirect costs. At year 15, screening every 3 years with an RPG cut point of 100 mg/dl left 0.2 million false negatives, an RPG of 130 mg/dl or the equation left 1.3 million false negatives, and an RPG of 160 mg/dl left 2.8 million false negatives. Over 15 years, the absolute difference between the most sensitive and most specific screening strategy was 4.5 million true positives and 476 million false-positives. Strategies using RPG cut points of 130 mg/dl or the multivariate equation every 3 years identified 17.3 million true positives; however, the equation identified fewer false-positives. The total cost of the most sensitive screening strategy was $42.7 billion and that of the most specific strategy was $6.9 billion. Screening for type 2 diabetes every 3 years with an RPG cut point of 130 mg/dl or the multivariate equation provides good yield and minimizes false-positive screening tests and costs.

Exome sequencing identifies novel compound heterozygous IFNA4 and IFNA10 mutations as a cause of impaired function in Crohn’s disease patients

PubMed Central

Xiao, Chuan-Xing; Xiao, Jing-Jing; Xu, Hong-Zhi; Wang, Huan-Huan; Chen, Xu; Liu, Yuan-Sheng; Li, Ping; Shi, Ying; Nie, Yong-Zhan; Li, Shao; Wu, Kai-Chun; Liu, Zhan-Ju; Ren, Jian-Lin; Guleng, Bayasi

2015-01-01

Previous studies have highlighted the role of genetic predispositions in disease, and several genes had been identified as important in Crohn’s disease (CD). However, many of these genes are likely rare and not associated with susceptibility in Chinese CD patients. We found 294 shared identical variants in the CD patients of which 26 were validated by Sanger sequencing. Two heterozygous IFN variants (IFNA10 c.60 T > A; IFNA4 c.60 A > T) were identified as significantly associated with CD susceptibility. The single-nucleotide changes alter a cysteine situated before the signal peptide cleavage site to a stop code (TGA) in IFNA10 result in the serum levels of IFNA10 were significantly decreased in the CD patients compared to the controls. Furthermore, the IFNA10 and IFNA4 mutants resulted in an impairment of the suppression of HCV RNA replication in HuH7 cells, and the administration of the recombinant IFN subtypes restored DSS-induced colonic inflammation through the upregulation of CD4+ Treg cells. We identified heterozygous IFNA10 and IFNA4 variants as a cause of impaired function and CD susceptibility genes in Chinese patients from multiple center based study. These findings might provide clues in the understanding of the genetic heterogeneity of CD and lead to better screening and improved treatment. PMID:26000985

Acquired Resistance to Crizotinib from a Mutation in CD74–ROS1

PubMed Central

Awad, Mark M.; Katayama, Ryohei; McTigue, Michele; Liu, Wei; Deng, Ya-Li; Brooun, Alexei; Friboulet, Luc; Huang, Donghui; Falk, Matthew D.; Timofeevski, Sergei; Wilner, Keith D.; Lockerman, Elizabeth L.; Khan, Tahsin M.; Mahmood, Sidra; Gainor, Justin F.; Digumarthy, Subba R.; Stone, James R.; Mino-Kenudson, Mari; Christensen, James G.; Iafrate, A. John; Engelman, Jeffrey A.; Shaw, Alice T.

2013-01-01

Summary Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), has also recently shown efficacy in the treatment of lung cancers with ROS1 translocations. Resistance to crizotinib developed in a patient with metastatic lung adenocarcinoma harboring a CD74–ROS1 rearrangement who had initially shown a dramatic response to treatment. We performed a biopsy of a resistant tumor and identified an acquired mutation leading to a glycine-to-arginine substitution at codon 2032 in the ROS1 kinase domain. Although this mutation does not lie at the gatekeeper residue, it confers resistance to ROS1 kinase inhibition through steric interference with drug binding. The same resistance mutation was observed at all the meta-static sites that were examined at autopsy, suggesting that this mutation was an early event in the clonal evolution of resistance. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00585195.) PMID:23724914

Transcultural validation of the ALS-CBS Cognitive Section for the Brazilian population.

PubMed

Branco, Lucas M T; Zanao, Tamires; De Rezende, Thiago J; Casseb, Raphael F; Balthazar, Marcio F; Woolley, Susan C; França, Marcondes C

2017-02-01

Cognitive decline (CD) is common but often under-recognized in ALS due to the scarcity of adequate cognitive screening methods. In this scenario, the Amyotrophic Lateral Sclerosis Cognitive Behavioural Screen (ALS-CBS) is the most investigated instrument and presents high sensitivity to identify CD. Currently, there are no validated cognitive screening tools for ALS patients in the Brazilian population and little is known about the frequency of ALS related CD in the country. We assessed the accuracy of the Brazilian Portuguese version of ALS-CBS Cognitive Section (ALS-CBS-Br) for classifying the cognitive status of Brazilian patients compared to a standard neuropsychological battery, and estimated the prevalence of CD in the Brazilian ALS population. Among 73 initially recruited ALS patients, 49 were included. Twenty-four patients were excluded due to severe motor disability, FTD diagnosis or non-acceptance. Ten healthy controls were also included. Ten ALS patients (20%) were diagnosed with executive dysfunction (ALSci) based on the battery results. ALS-CBS-Br scores were significantly lower in the ALSci group (p < 0.001). The scale accuracy in detecting executive dysfunction was 0.906. Optimal cut-off score was 10/20 (specificity 0.872 and sensitivity 0.900). In conclusion, the ALS-CBS-Br may facilitate the recognition of CD in routine clinical care and complement future studies in our population.

Involvement of macrophage migration inhibitory factor and its receptor (CD74) in human breast cancer.

PubMed

Richard, Vincent; Kindt, Nadège; Decaestecker, Christine; Gabius, Hans-Joachim; Laurent, Guy; Noël, Jean-Christophe; Saussez, Sven

2014-08-01

Macrophage migration inhibitory factor (MIF) and its receptor CD74 appear to be involved in tumorigenesis. We evaluated, by immunohistochemical staining, the tissue expression and distribution of MIF and CD74 in serial sections of human invasive breast cancer tumor specimens. The serum MIF level was also determined in breast cancer patients. We showed a significant increase in serum MIF average levels in breast cancer patients compared to healthy individuals. MIF tissue expression, quantified by a modified Allred score, was strongly increased in carcinoma compared to tumor-free specimens, in the cancer cells and in the peritumoral stroma, with fibroblasts the most intensely stained. We did not find any significant correlation with histoprognostic factors, except for a significant inverse correlation between tumor size and MIF stromal positivity. CD74 staining was heterogeneous and significantly decreased in cancer cells but increased in the surrounding stroma, namely in lymphocytes, macrophages and vessel endothelium. There was no significant variation according to classical histoprognostic factors, except that CD74 stromal expression was significantly correlated with triple-negative receptor (TRN) status and the absence of estrogen receptors. In conclusion, our data support the concept of a functional role of MIF in human breast cancer. In addition to auto- and paracrine effects on cancer cells, MIF could contribute to shape the tumor microenvironment leading to immunomodulation and angiogenesis. Interfering with MIF effects in breast tumors in a therapeutic perspective remains an attractive but complex challenge. Level of co-expression of MIF and CD74 could be a surrogate marker for efficacy of anti-angiogenic drugs, particularly in TRN breast cancer tumor.

Association of New Putative Epitopes of Myelin Proteolipid Protein (58-74) with Pathogenesis of Multiple Sclerosis.

PubMed

Zamanzadeh, Zahra; Ahangari, Ghasem; Ataei, Mitra; Pouragahi, Samie; Nabavi, Seyed Massood; Sadeghi, Mehdi; Sanati, Mohammad Hossein

2016-10-01

Multiple sclerosis (MS) is an autoimmune disease in which auto-reactive T cells react with self-antigens expressed in the central nervous system (CNS). The main cause of MS is unknown. Nonetheless, the most probable theory is based on molecular mimicry, which suggests that some infections can activate T cells against brain auto-antigens like myelin proteolipid protein (PLP) and initiate the disease cascade. This study is conducted to evaluate the activatory effects of PLP58-74 on T lymphocytes and humoral immunity. PLP58-74 was considered as an immunodominant epitope candidate of PLP using bioinformatics tools. Patients and healthy individuals' peripheral blood mononuclear cells (PBMCs) were treated with PLP58-74 and its proliferative effects were evaluated through assessing proliferating cell nuclear antigen (PCNA) gene expression changes by real time PCR and immunocytochemistry assay. Finally, the rate of CD4+ and CD8+ T cells were assessed by flowcytometry. ELISA was also performed to measure anti PLP58-74 antibody in patients' serum. PLP58-74 induced proliferation in patients' PBMCs while it did not influence PBMCs of healthy individuals. CD4+ T cells were the main activated cells in reaction to PLP58-74 which increased from 22% to 39.91%. In addition, immune assay showed threefold increase in specific anti PLP58-74 IgG in patients compared to healthy controls. Results showed that PLP58-74 can stimulate CD4+ T cells and humoral immunity. Therefore it seems that the epitopes of some microorganisms mimicking PLP such as PLP58-74 might have a potential role in the initiation of MS.

Developmental Changes in Soluble CD40 Ligand

PubMed Central

Cholette, Jill M.; Blumberg, Neil; Phipps, Richard P.; McDermott, Michael P.; Gettings, Kelly F.; Lerner, Norma B.

2008-01-01

Objectives To determine if soluble CD40 ligand (sCD40L; formally CD154) levels vary with age and to identify age-dependent ranges in healthy pediatric and adult populations. Study design sCD40L was measured in 25 neonates, 74 children (3 months –15 years) and 20 adults using an enzyme-linked immunosorbent assay. For age group comparisons, Mann-Whitney tests were performed. Correlation coefficients assessed relationships between plasma and serum sCD40L. Results Plasma sCD40L levels were higher in neonates than in all other age groups, (p<0.001). All grouped pediatric plasma levels were significantly higher than in adults (p<0.0001). There were no significant differences in plasma sCD40L between pediatric age groups. Serum levels were significantly higher in neonates than in any other age group (p <0.0001). Pediatric and adult serum sCD40L levels were not significantly different. Conclusions Plasma sCD40L levels are highest at birth and remain higher than those in adults throughout childhood. Reasons for such developmental changes remain to be investigated. Age appropriate reference ranges should be used when sCD40L is being evaluated in pediatric disorders. PMID:18154898

Parasite Manipulation of the Invariant Chain and the Peptide Editor H2-DM Affects Major Histocompatibility Complex Class II Antigen Presentation during Toxoplasma gondii Infection

PubMed Central

Nishi, Manami; El-Hage, Sandy; Fox, Barbara A.; Bzik, David J.

2015-01-01

Toxoplasma gondii is an obligate intracellular protozoan parasite. This apicomplexan is the causative agent of toxoplasmosis, a leading cause of central nervous system disease in AIDS. It has long been known that T. gondii interferes with major histocompatibility complex class II (MHC-II) antigen presentation to attenuate CD4+ T cell responses and establish persisting infections. Transcriptional downregulation of MHC-II genes by T. gondii was previously established, but the precise mechanisms inhibiting MHC-II function are currently unknown. Here, we show that, in addition to transcriptional regulation of MHC-II, the parasite modulates the expression of key components of the MHC-II antigen presentation pathway, namely, the MHC-II-associated invariant chain (Ii or CD74) and the peptide editor H2-DM, in professional antigen-presenting cells (pAPCs). Genetic deletion of CD74 restored the ability of infected dendritic cells to present a parasite antigen in the context of MHC-II in vitro. CD74 mRNA and protein levels were, surprisingly, elevated in infected cells, whereas MHC-II and H2-DM expression was inhibited. CD74 accumulated mainly in the endoplasmic reticulum (ER), and this phenotype required live parasites, but not active replication. Finally, we compared the impacts of genetic deletion of CD74 and H2-DM genes on parasite dissemination toward lymphoid organs in mice, as well as activation of CD4+ T cells and interferon gamma (IFN-γ) levels during acute infection. Cyst burdens and survival during the chronic phase of infection were also evaluated in wild-type and knockout mice. These results highlight the fact that the infection is influenced by multiple levels of parasite manipulation of the MHC-II antigen presentation pathway. PMID:26195549

Entirely screen printed CdS/CdTe solar cell

NASA Astrophysics Data System (ADS)

Ikegami, S.; Matsumoto, H.; Uda, H.; Komatsu, Y.; Nakano, A.; Kuribayashi, K.

An entirely screen printed CdS/CdTe solar cell has been manufactured on a borosilicate glass substrate by successively repeating screen printing and heating in a belt furnace of each paste of CdS, Cd+Te, C, Ag+In and Ag. In a small cell with 0.78 sq cm area, the intrinsic conversion efficiency of 12.8 percent has been obtained; this value is the highest in the thin film type solar cells. On a large glass substrate of 30 x 30 sq cm, 28 unit solar cells connected in series have been constructed by this printing technique, their intrinsic efficiency being 8.5 percent. Under the roof top condition, no change in output power is observed in the present solar cells encapsulated over 206 days. Thus, the entirely screen printed CdS/CdTe solar cells can be expected as low cost, highly efficient, and stable solar cells.

Short Communication: Viral Suppression Is Associated with Increased Likelihood of Colorectal Cancer Screening Among Persons Living with HIV/AIDS.

PubMed

Burkholder, Greer A; Tamhane, Ashutosh R; Appell, Lauren E; Willig, James H; Saag, Michael S; Raper, James L; Westfall, Andrew O; Mugavero, Michael J

2015-05-01

With improved survival and aging, more persons living with HIV/AIDS (PLWHA) are at risk for colorectal cancer (CRC). This retrospective longitudinal study evaluated patient characteristics associated with CRC screening in our HIV cohort. Patients were followed beginning at age 50 years during a study period from January 1, 2003 to December 31, 2010 (n=265). During a median follow-up time of 1.7 years, only 30% of patients underwent CRC screening. The majority of screened patients received endoscopic screening (colonoscopy, 86%; sigmoidoscopy, 8%); among these patients, results were available for 68/75, and adenomatous polyps were found in 13%. No cases of CRC were reported. Among unscreened patients, only 23% had an external primary care provider, indicating an HIV provider was the expected source for CRC screening referral in the majority. Patients with time-varying suppressed HIV viral load were more likely to receive screening (HRadjusted=1.74; 95% CI: 1.05-2.87), independent of CD4 count. Our findings suggest HIV providers are more likely to address non-HIV-related healthcare maintenance when HIV is controlled. In addition, a significant number of neoplastic lesions are likely being missed in PLWHA who have not been screened for CRC. Provision of evidence-based preventive care in addition to HIV care is required for the aging population of PLWHA.

Characterisation of monoclonal antibodies specific for hamster leukocyte differentiation molecules.

PubMed

Rees, Jennifer; Haig, David; Mack, Victoria; Davis, William C

2017-01-01

Flow cytometry was used to identify mAbs that recognize conserved epitopes on hamster leukocyte differentiation molecules (hLDM) and also to characterize mAbs developed against hLDM. Initial screening of mAbs developed against LDMs in other species yielded mAbs specific for the major histocompatibility (MHC) II molecule, CD4 and CD18. Screening of sets of mAbs developed against hLDM yielded 22 new mAbs, including additional mAbs to MHC II molecules and mAbs that recognize LDMs expressed on all leukocytes, granulocytes, all lymphocytes, all T cells, a subset of T cells, or on all B cells. Based on comparison of the pattern of expression of LDMs expressed on all hamster leukocytes with the patterns of expression of known LDMs in other species, as detected by flow cytometry (FC), four mAbs are predicted to recognize CD11a, CD44, and CD45. Cross comparison of mAbs specific for a subset of hamster T cells with a cross reactive mAb known to recognize CD4 in mice and one recognising CD8 revealed they recognize CD4. The characterization of these mAbs expands opportunities to use hamsters as an additional model species to investigate the mechanisms of immunopathogenesis of infectious diseases. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Tetraspanin CD9 and ectonucleotidase CD73 identify an osteochondroprogenitor population with elevated osteogenic properties.

PubMed

Singh, Anju; Lester, Chantel; Drapp, Rebecca; Hu, Dorothy Z; Glimcher, Laurie H; Jones, Dallas

2015-02-01

Cell-based bone regeneration strategies offer promise for traumatic bone injuries, congenital defects, non-union fractures and other skeletal pathologies. Postnatal bone remodeling and fracture healing provide evidence that an osteochondroprogenitor cell is present in adult life that can differentiate to remodel or repair the fractured bone. However, cell-based skeletal repair in the clinic is still in its infancy, mostly due to poor characterization of progenitor cells and lack of knowledge about their in vivo behavior. Here, we took a combined approach of high-throughput screening, flow-based cell sorting and in vivo transplantation to isolate markers that identify osteochondroprogenitor cells. We show that the presence of tetraspanin CD9 enriches for osteochondroprogenitors within CD105(+) mesenchymal cells and that these cells readily form bone upon transplantation. In addition, we have used Thy1.2 and the ectonucleotidase CD73 to identify subsets within the CD9(+) population that lead to endochondral or intramembranous-like bone formation. Utilization of this unique cell surface phenotype to enrich for osteochondroprogenitor cells will allow for further characterization of the molecular mechanisms that regulate their osteogenic properties. © 2015. Published by The Company of Biologists Ltd.

c-Met and its ligand hepatocyte growth factor/scatter factor regulate mature B cell survival in a pathway induced by CD74.

PubMed

Gordin, Maya; Tesio, Melania; Cohen, Sivan; Gore, Yael; Lantner, Frida; Leng, Lin; Bucala, Richard; Shachar, Idit

2010-08-15

The signals regulating the survival of mature splenic B cells have become a major focus in recent studies of B cell immunology. Durable B cell persistence in the periphery is dependent on survival signals that are transduced by cell surface receptors. In this study, we describe a novel biological mechanism involved in mature B cell homeostasis, the hepatocyte growth factor/scatter factor (HGF)/c-Met pathway. We demonstrate that c-Met activation by HGF leads to a survival cascade, whereas its blockade results in induction of mature B cell death. Our results emphasize a unique and critical function for c-Met signaling in the previously described macrophage migration inhibitory factor/CD74-induced survival pathway. Macrophage migration inhibitory factor recruits c-Met to the CD74/CD44 complex and thereby enables the induction of a signaling cascade within the cell. This signal results in HGF secretion, which stimulates the survival of the mature B cell population in an autocrine manner. Thus, the CD74-HGF/c-Met axis defines a novel physiologic survival pathway in mature B cells, resulting in the control of the humoral immune response.

Vaccine-associated varicella and rubella infections in severe combined immunodeficiency with isolated CD4 lymphocytopenia and mutations in IL7R detected by tandem whole exome sequencing and chromosomal microarray

PubMed Central

Bayer, D K; Martinez, C A; Sorte, H S; Forbes, L R; Demmler-Harrison, G J; Hanson, I C; Pearson, N M; Noroski, L M; Zaki, S R; Bellini, W J; Leduc, M S; Yang, Y; Eng, C M; Patel, A; Rodningen, O K; Muzny, D M; Gibbs, R A; Campbell, I M; Shaw, C A; Baker, M W; Zhang, V; Lupski, J R; Orange, J S; Seeborg, F O; Stray-Pedersen, A

2014-01-01

In areas without newborn screening for severe combined immunodeficiency (SCID), disease-defining infections may lead to diagnosis, and in some cases, may not be identified prior to the first year of life. We describe a female infant who presented with disseminated vaccine-acquired varicella (VZV) and vaccine-acquired rubella infections at 13 months of age. Immunological evaluations demonstrated neutropenia, isolated CD4 lymphocytopenia, the presence of CD8+ T cells, poor lymphocyte proliferation, hypergammaglobulinaemia and poor specific antibody production to VZV infection and routine immunizations. A combination of whole exome sequencing and custom-designed chromosomal microarray with exon coverage of primary immunodeficiency genes detected compound heterozygous mutations (one single nucleotide variant and one intragenic copy number variant involving one exon) within the IL7R gene. Mosaicism for wild-type allele (20–30%) was detected in pretransplant blood and buccal DNA and maternal engraftment (5–10%) demonstrated in pretransplant blood DNA. This may be responsible for the patient's unusual immunological phenotype compared to classical interleukin (IL)-7Rα deficiency. Disseminated VZV was controlled with anti-viral and immune-based therapy, and umbilical cord blood stem cell transplantation was successful. Retrospectively performed T cell receptor excision circle (TREC) analyses completed on neonatal Guthrie cards identified absent TREC. This case emphasizes the danger of live viral vaccination in severe combined immunodeficiency (SCID) patients and the importance of newborn screening to identify patients prior to high-risk exposures. It also illustrates the value of aggressive pathogen identification and treatment, the influence newborn screening can have on morbidity and mortality and the significant impact of newer genomic diagnostic tools in identifying the underlying genetic aetiology for SCID patients. PMID:25046553

Cadmium Accumulation Characteristics in Turnip Landraces from China and Assessment of Their Phytoremediation Potential for Contaminated Soils.

PubMed

Li, Xiong; Zhang, Xiaoming; Yang, Ya; Li, Boqun; Wu, Yuansheng; Sun, Hang; Yang, Yongping

2016-01-01

Heavy metal (HM) pollution is a global environmental problem that threatens ecosystem and human health. Cadmium (Cd) pollution is the most prominent HM pollution type because of its high toxicity, strong migration, and the large polluted area globally. Phytoremediation of contaminated soil is frequently practiced because of its cost-effectiveness and operability and because it has no associated secondary pollution. High-accumulation plants, including those identified as hyperaccumulators, play an important role in phytoremediation. Therefore, screening of plants to identify hyperaccumulators is important for continued phytoremediation. In the present study, we investigated the Cd tolerance and accumulation capabilities of 18 turnip landraces from China under a soil experiment with known Cd level. The results indicated that turnip has a high capacity for Cd accumulation. Furthermore, significant differences in Cd tolerance and accumulation characteristics were found among different landraces when they grew at 50 mg kg -1 (dry weight) Cd concentration. Among the studied landraces, five turnip landraces met the requirements of Cd hyperaccumulators and three landraces were identified as potential candidates. However, the total Cd content accumulated by individual plant of different turnip landraces was dependent on both the Cd accumulation capacity and plant biomass. Compared with some reported Cd hyperaccumulators, turnip not only shows a high Cd-accumulation capacity but also has rapid growth and a wide distribution area. These advantages indicate that turnip may have considerable potential for phytoremediation of Cd-contaminated soil. Furthermore, the study also indicates that it is not advisable to consume turnip cultivated in an environment that exceeds safe Cd levels.

Baseline and annual repeat rounds of screening: implications for optimal regimens of screening.

PubMed

Henschke, Claudia I; Salvatore, Mary; Cham, Matthew; Powell, Charles A; DiFabrizio, Larry; Flores, Raja; Kaufman, Andrew; Eber, Corey; Yip, Rowena; Yankelevitz, David F

2018-03-01

Differences in results of baseline and subsequent annual repeat rounds provide important information for optimising the regimen of screening. A prospective cohort study of 65,374 was reviewed to examine the frequency/percentages of the largest noncalcified nodule (NCN), lung cancer cell types and Kaplan-Meier (K-M) survival rates, separately for baseline and annual rounds. Of 65,374 baseline screenings, NCNs were identified in 28,279 (43.3%); lung cancer in 737 (1.1%). Of 74,482 annual repeat screenings, new NCNs were identified in 4959 (7%); lung cancer in 179 (0.24%). Only adenocarcinoma was diagnosed in subsolid NCNs. Percentages of lung cancers by cell type were significantly different (p < 0.0001) in the baseline round compared with annual rounds, reflecting length bias, as were the ratios, reflecting lead times. Long-term K-M survival rate was 100% for typical carcinoids and for adenocarcinomas manifesting as subsolid NCNs; 85% (95% CI 81-89%) for adenocarcinoma, 74% (95% CI 63-85%) for squamous cell, 48% (95% CI 34-62%) for small cell. The rank ordering by lead time was the same as the rank ordering by survival rates. The significant differences in the frequency of NCNs and frequency and aggressiveness of diagnosed cancers in baseline and annual repeat need to be recognised for an optimal regimen of screening. • Lung cancer aggressiveness varies considerably by cell type and nodule consistency. • Kaplan-Meier survival rates varied by cell type between 100% and 48%. • The percentages of lung cancers by cell type in screening rounds reflect screening biases. • Rank ordering by cell type survival is consistent with that by lead times. • Empirical evidence provides critical information for the regimen of screening.

Costs and cost-effectiveness of full implementation of a biennial faecal occult blood test screening program for bowel cancer in Australia.

PubMed

Pignone, Michael P; Flitcroft, Kathy L; Howard, Kirsten; Trevena, Lyndal J; Salkeld, Glenn P; St John, D James B

2011-02-21

To examine the costs and cost-effectiveness of full implementation of biennial bowel cancer screening for Australian residents aged 50-74 years. Identification of existing economic models from 1993 to 2010 through searches of PubMed and economic analysis databases, and by seeking expert advice; and additional modelling to determine the costs and cost-effectiveness of full implementation of biennial faecal occult blood test screening for the five million adults in Australia aged 50-74 years. Estimated number of deaths from bowel cancer prevented, costs, and cost-effectiveness (cost per life-year gained [LYG]) of biennial bowel cancer screening. We identified six relevant economic analyses, all of which found colorectal cancer (CRC) screening to be very cost-effective, with costs per LYG under $55,000 per year in 2010 Australian dollars. Based on our additional modelling, we conservatively estimate that full implementation of biennial screening for people aged 50-74 years would have gross costs of $150 million, reduce CRC mortality by 15%-25%, prevent 300-500 deaths from bowel cancer, and save 3600-6000 life-years annually, for an undiscounted cost per LYG of $25,000-$41,667, compared with no screening, and not taking cost savings as a result of treatment into consideration. The additional expenditure required, after accounting for reductions in CRC incidence, savings in CRC treatment costs, and existing ad-hoc colonoscopy use, is likely to be less than $50 million annually. Full implementation of biennial faecal occult blood test screening in Australia can reduce bowel cancer mortality, and is an efficient use of health resources that would require modest additional government investment.

Age at gluten introduction and risk of celiac disease.

PubMed

Aronsson, Carin Andrén; Lee, Hye-Seung; Liu, Edwin; Uusitalo, Ulla; Hummel, Sandra; Yang, Jimin; Hummel, Michael; Rewers, Marian; She, Jin-Xiong; Simell, Olli; Toppari, Jorma; Ziegler, Anette-G; Krischer, Jeffrey; Virtanen, Suvi M; Norris, Jill M; Agardh, Daniel

2015-02-01

The goal of this study was to determine whether age at introduction to gluten was associated with risk for celiac disease (CD) in genetically predisposed children. TEDDY (The Environmental Determinants of Diabetes in the Young) is a prospective birth cohort study. Newborn infants (N = 6436) screened for high-risk HLA-genotypes for CD were followed up in Finland, Germany, Sweden, and the United States. Information about infant feeding was collected at clinical visits every third month. The first outcome was persistent positive for tissue transglutaminase autoantibodies (tTGA), the marker for CD. The second outcome was CD, defined as either a diagnosis based on intestinal biopsy results or on persistently high levels of tTGA. Swedish children were introduced to gluten earlier (median: 21.7 weeks) compared with children from Finland (median: 26.1 weeks), Germany, and the United States (both median: 30.4 weeks) (P < .0001). During a median follow-up of 5.0 years (range: 1.7-8.8 years), 773 (12%) children developed tTGA and 307 (5%) developed CD. Swedish children were at increased risk for tTGA (hazard ratio: 1.74 [95% CI: 1.47-2.06]) and CD (hazard ratio: 1.76 [95% CI: 1.34-2.24]) compared with US children, respectively (P < .0001).Gluten introduction before 17 weeks or later than 26 weeks was not associated with increased risk for tTGA or CD, adjusted for country, HLA, gender, and family history of CD, neither in the overall analysis nor on a country-level comparison. In TEDDY, the time to first introduction to gluten introduction was not an independent risk factor for developing CD. Copyright © 2015 by the American Academy of Pediatrics.

Screening of carcinoma metastasis by flow cytometry: A study of 238 cases.

PubMed

Acosta, Maria; Pereira, José; Arroz, Maria

2016-05-01

Malignant epithelial cells may be detected in different specimens, by immunophenotyping using flow cytometry (FCM). CD326 (epithelial-specific antigen, clone Ber-Ep4) was used to identify epithelial cells, CD45 to discriminate between leucocytes (positive for this antigen) and non-hematological cells (negative for this antigen), and CD33 to identify monocytes/macrophages. This combination is particularly useful in effusions to characterize large cells and distinguish between monocyte/macrophages (CD45+ CD33+ CD326-), mesothelial cells (CD45 ± (dim) CD33 - CD326-) and epithelial cells (CD45 - CD33 - CD326 +). We evaluated the efficiency of flow cytometry to detect malignant epithelial cells in 238 fresh samples, including effusions, lymph node biopsies, fine needle aspirates, bone marrow aspirates, cerebrospinal fluid, among others. These are specimens expected to lack epithelial cells. FCM results were then compared to the results of smear and cell block morphology, as well as immunocytochemistry on paraffin wax embedded cell blocks, when available. Final diagnosis was the gold standard and a very good sensitivity (96.7%) and specificity (99.3%) were obtained. We concluded that the detection of CD326 positive cells using FCM is strongly indicative of the presence of carcinoma cells. © 2015 International Clinical Cytometry Society. © 2015 International Clinical Cytometry Society.

The Expenditures for Academic Inpatient Care of Inflammatory Bowel Disease Patients Are Almost Double Compared with Average Academic Gastroenterology and Hepatology Cases and Not Fully Recovered by Diagnosis-Related Group (DRG) Proceeds.

PubMed

Baumgart, Daniel C; le Claire, Marie

2016-01-01

Crohn's disease (CD) and ulcerative colitis (UC) challenge economies worldwide. Detailed health economic data of DRG based academic inpatient care for inflammatory bowel disease (IBD) patients in Europe is unavailable. IBD was identified through ICD-10 K50 and K51 code groups. We took an actual costing approach, compared expenditures to G-DRG and non-DRG proceeds and performed detailed cost center and type accounting to identify coverage determinants. Of all 3093 hospitalized cases at our department, 164 were CD and 157 UC inpatients in 2012. On average, they were 44.1 (CD 44.9 UC 43.3 all 58) years old, stayed 10.1 (CD 11.8 UC 8.4 vs. all 8) days, carried 5.8 (CD 6.4 UC 5.2 vs. all 6.8) secondary diagnoses, received 7.4 (CD 7.7 UC 7 vs. all 6.2) procedures, had a higher cost weight (CD 2.8 UC 2.4 vs. all 1.6) and required more intense nursing. Their care was more costly (means: total cost IBD 8477€ CD 9051€ UC 7903€ vs. all 5078€). However, expenditures were not fully recovered by DRG proceeds (means: IBD 7413€, CD 8441€, UC 6384€ vs all 4758€). We discovered substantial disease specific mismatches in cost centers and types and identified the medical ward personnel and materials budgets to be most imbalanced. Non-DRG proceeds were almost double (IBD 16.1% vs. all 8.2%), but did not balance deficits at total coverage analysis, that found medications (antimicrobials, biologics and blood products), medical materials (mostly endoscopy items) to contribute most to the deficit. DRGs challenge sophisticated IBD care.

Health literacy in the eHealth era: A systematic review of the literature.

PubMed

Kim, Henna; Xie, Bo

2017-06-01

This study aimed to identify studies on online health service use by people with limited health literacy, as the findings could provide insights into how health literacy has been, and should be, addressed in the eHealth era. To identify the relevant literature published since 2010, we performed four rounds of selection-database selection, keyword search, screening of the titles and abstracts, and screening of full texts. This process produced a final of 74 publications. The themes addressed in the 74 publications fell into five categories: evaluation of health-related content, development and evaluation of eHealth services, development and evaluation of health literacy measurement tools, interventions to improve health literacy, and online health information seeking behavior. Barriers to access to and use of online health information can result from the readability of content and poor usability of eHealth services. We need new health literacy screening tools to identify skills for adequate use of eHealth services. Mobile apps hold great potential for eHealth and mHealth services tailored to people with low health literacy. Efforts should be made to make eHealth services easily accessible to low-literacy individuals and to enhance individual health literacy through educational programs. Copyright © 2017 Elsevier B.V. All rights reserved.

Apolipoprotein C-II Is a Potential Serum Biomarker as a Prognostic Factor of Locally Advanced Cervical Cancer After Chemoradiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harima, Yoko, E-mail: harima@takii.kmu.ac.jp; Ikeda, Koshi; Utsunomiya, Keita

Purpose: To determine pretreatment serum protein levels for generally applicable measurement to predict chemoradiation treatment outcomes in patients with locally advanced squamous cell cervical carcinoma (CC). Methods and Materials: In a screening study, measurements were conducted twice. At first, 6 serum samples from CC patients (3 with no evidence of disease [NED] and 3 with cancer-caused death [CD]) and 2 from healthy controls were tested. Next, 12 serum samples from different CC patients (8 NED, 4 CD) and 4 from healthy controls were examined. Subsequently, 28 different CC patients (18 NED, 10 CD) and 9 controls were analyzed in themore » validation study. Protein chips were treated with the sample sera, and the serum protein pattern was detected by surface-enhanced laser desorption and ionization–time-of-flight mass spectrometry (SELDI-TOF MS). Then, single MS-based peptide mass fingerprinting (PMF) and tandem MS (MS/MS)-based peptide/protein identification methods, were used to identify protein corresponding to the detected peak. And then, turbidimetric assay was used to measure the levels of a protein that indicated the best match with this peptide peak. Results: The same peak 8918 m/z was identified in both screening studies. Neither the screening study nor the validation study had significant differences in the appearance of this peak in the controls and NED. However, the intensity of the peak in CD was significantly lower than that of controls and NED in both pilot studies (P=.02, P=.04) and validation study (P=.01, P=.001). The protein indicated the best match with this peptide peak at 8918 m/z was identified as apolipoprotein C-II (ApoC-II) using PMF and MS/MS methods. Turbidimetric assay showed that the mean serum levels of ApoC-II tended to decrease in CD group when compared with NED group (P=.078). Conclusion: ApoC-II could be used as a biomarker for detection in predicting and estimating the radiation treatment outcome of patients with CC.« less

New use of an old drug: inhibition of breast cancer stem cells by benztropine mesylate.

PubMed

Cui, Jihong; Hollmén, Maija; Li, Lina; Chen, Yong; Proulx, Steven T; Reker, Daniel; Schneider, Gisbert; Detmar, Michael

2017-01-03

Cancer stem cells (CSCs) play major roles in cancer initiation, metastasis, recurrence and therapeutic resistance. Targeting CSCs represents a promising strategy for cancer treatment. The purpose of this study was to identify selective inhibitors of breast CSCs (BCSCs). We carried out a cell-based phenotypic screening with cell viability as a primary endpoint, using a collection of 2,546 FDA-approved drugs and drug-like molecules in spheres formed by malignant human breast gland-derived cells (HMLER-shEcad cells, representing BCSCs) and control immortalized non-tumorigenic human mammary cells (HMLE cells, representing normal stem cells). 19 compounds were identified from screening. The chemically related molecules benztropine mesylate and deptropine citrate were selected for further validation and both potently inhibited sphere formation and self-renewal of BCSCs in vitro. Benztropine mesylate treatment decreased cell subpopulations with high ALDH activity and with a CD44+/CD24- phenotype. In vivo, benztropine mesylate inhibited tumor-initiating potential in a 4T1 mouse model. Functional studies indicated that benztropine mesylate inhibits functions of CSCs via the acetylcholine receptors, dopamine transporters/receptors, and/or histamine receptors. In summary, our findings identify benztropine mesylate as an inhibitor of BCSCs in vitro and in vivo. This study also provides a screening platform for identification of additional anti-CSC agents.

Linkage to HIV, TB and Non-Communicable Disease Care from a Mobile Testing Unit in Cape Town, South Africa

PubMed Central

Govindasamy, Darshini; Kranzer, Katharina; van Schaik, Nienke; Noubary, Farzad; Wood, Robin; Walensky, Rochelle P.; Freedberg, Kenneth A.; Bassett, Ingrid V.; Bekker, Linda-Gail

2013-01-01

Background HIV counseling and testing may serve as an entry point for non-communicable disease screening. Objectives To determine the yield of newly-diagnosed HIV, tuberculosis (TB) symptoms, diabetes and hypertension, and to assess CD4 count testing, linkage to care as well as correlates of linkage and barriers to care from a mobile testing unit. Methods A mobile unit provided screening for HIV, TB symptoms, diabetes and hypertension in Cape Town, South Africa between March 2010 and September 2011. The yield of newly-diagnosed cases of these conditions was measured and clients were followed-up between January and November 2011 to assess linkage. Linkage to care was defined as accessing care within one, three or six months post-HIV diagnosis (dependent on CD4 count) and one month post-diagnosis for other conditions. Clinical and socio-demographic correlates of linkage to care were evaluated using Poisson regression and barriers to care were determined. Results Of 9,806 clients screened, the yield of new diagnoses was: HIV (5.5%), TB suspects (10.1%), diabetes (0.8%) and hypertension (58.1%). Linkage to care for HIV-infected clients, TB suspects, diabetics and hypertensives was: 51.3%, 56.7%, 74.1% and 50.0%. Only disclosure of HIV-positive status to family members or partners (RR=2.6, 95% CI: 1.04-6.3, p=0.04) was independently associated with linkage to HIV care. The main barrier to care reported by all groups was lack of time to access a clinic. Conclusion Screening for HIV, TB symptoms and hypertension at mobile units in South Africa has a high yield but inadequate linkage. After-hours and weekend clinics may overcome a major barrier to accessing care. PMID:24236170

Prevalence of Chagas Disease in the Latin American–born Population of Los Angeles

PubMed Central

Forsyth, Colin J.; Soverow, Jonathan; Hernandez, Salvador; Sanchez, Daniel; Montgomery, Susan P.; Traina, Mahmoud

2017-01-01

Abstract Background. According to an estimate from the Centers for Disease Control and Prevention (CDC), Chagas disease (CD) may affect 1.31% of Latin American immigrants in the United States, with >300 000 cases. However, there is a lack of real-world data to support this estimate. Little is known about the actual prevalence of this neglected tropical disease in the United States, and the bulk of those infected are undiagnosed. Methods. From April 2008 to May 2014, we screened 4,755 Latin American–born residents of Los Angeles County. Blood samples were tested for serologic evidence of CD. We collected demographic data and assessed the impact of established risk factors on CD diagnosis, including sex, country of origin, housing materials, family history of CD, and awareness of CD. Results. There were 59 cases of CD, for an overall prevalence of 1.24%. Prevalence was highest among Salvadorans (3.45%). Of the 3,182 Mexican respondents, those from Oaxaca (4.65%) and Zacatecas (2.2%) had the highest CD prevalence. Salvadoran origin (aOR = 6.2; 95% CI = 2.8–13.5; P < .001), prior knowledge of CD (aOR = 2.4; 95% CI = 1.0–5.8; P = .047), and exposure to all 3 at-risk housing types (adobe, mud, and thatched roof) (aOR = 2.5; 95% CI = 1.0–6.4; P = .048) were associated with positive diagnosis. Conclusions. In the largest screening of CD in the United States to date outside of blood banks, we found a CD prevalence of 1.24%. This implies >30 000 people infected in Los Angeles County alone, making CD an important public health concern. Efficient, targeted surveillance of CD may accelerate diagnosis and identify candidates for early treatment. PMID:28329123

Empirical evaluation demonstrated importance of validating biomarkers for early detection of cancer in screening settings to limit the number of false-positive findings.

PubMed

Chen, Hongda; Knebel, Phillip; Brenner, Hermann

2016-07-01

Search for biomarkers for early detection of cancer is a very active area of research, but most studies are done in clinical rather than screening settings. We aimed to empirically evaluate the role of study setting for early detection marker identification and validation. A panel of 92 candidate cancer protein markers was measured in 35 clinically identified colorectal cancer patients and 35 colorectal cancer patients identified at screening colonoscopy. For each case group, we selected 38 controls without colorectal neoplasms at screening colonoscopy. Single-, two- and three-marker combinations discriminating cases and controls were identified in each setting and subsequently validated in the alternative setting. In all scenarios, a higher number of predictive biomarkers were initially detected in the clinical setting, but a substantially lower proportion of identified biomarkers could subsequently be confirmed in the screening setting. Confirmation rates were 50.0%, 84.5%, and 74.2% for one-, two-, and three-marker algorithms identified in the screening setting and were 42.9%, 18.6%, and 25.7% for algorithms identified in the clinical setting. Validation of early detection markers of cancer in a true screening setting is important to limit the number of false-positive findings. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

[Analysis of community colorectal cancer screening in 50-74 years old people in Guangzhou, 2015-2016].

PubMed

Li, Y; Liu, H Z; Liang, Y R; Lin, G Z; Li, K; Dong, H; Xu, H; Wang, M

2018-01-10

Objective: To analyze the effect of colorectal cancer screening in the general population in Guangzhou, and provide evidence for the for development of colorectal cancer screening policy and strategy. Methods: The data of colorectal cancer screening in Guangzhou during 2015- 2016 were collected. The participation, the positive rate of fecal occult blood test, the detection rate of colonoscopy and screening effect of colonoscopy were evaluated. Results: A total of 220 834 residents aged 50-74 years received the screening, and the positive rate of the screening was 16.77% (37 040 cases). Colonoscopy was performed for 7 821 cases (21.12%). Colorectal lesions were found in 4 126 cases (52.76%), of which 614 (7.85%) and 73 (0.93%) and 230 (2.94%) were identified as advanced adenoma, severe dysplasia lesions and colorectal cancers, respectively. The detection rates of all colorectal lesions were higher in men than in women (all P <0.01). The diagnostic rate of early lesion was 87.24%, and 99 early cancer cases were found, accounting for 46.26% of the total cases. The overall screening detection rate of colorectal cancer was 104.15/100 000, higher than the incidence rate (81.18/100 000) in colorectal cancer surveillance ( P <0.001), but age group <70 years had higher detection rate, age group ≥70 years had higher incidence rate. Conclusions: The colorectal cancer screening strategy in Guangzhou is effective in the detection of the population at high risk, increase the detection rate of colorectal lesions, early diagnosis rate of precancerous lesions and diagnosis rate of early colorectal cancer. The benefit in those aged ≤69 years was more obvious than that in those aged 70-74 years. It is necessary to improve the compliancy of colorectal cancer screening in population at high risk.

COLLABORATIVE MODELING OF THE BENEFITS AND HARMS ASSOCIATED WITH DIFFERENT U.S. BREAST CANCER SCREENING STRATEGIES

PubMed Central

Mandelblatt, Jeanne S.; Stout, Natasha K.; Schechter, Clyde B.; van den Broek, Jeroen J.; Miglioretti, Diana; Krapcho, Martin; Trentham-Dietz, Amy; Munoz, Diego; Lee, Sandra J.; Berry, Donald A.; van Ravesteyn, Nicolien T.; Alagoz, Oguzhan; Kerlikowske, Karla; Tosteson, Anna N.A.; Near, Aimee M.; Hoeffken, Amanda; Chang, Yaojen; Heijnsdijk, Eveline A.; Chisholm, Gary; Huang, Xuelin; Huang, Hui; Ergun, Mehmet Ali; Gangnon, Ronald; Sprague, Brian L.; Plevritis, Sylvia; Feuer, Eric; de Koning, Harry J.; Cronin, Kathleen A.

2016-01-01

Background Controversy persists about optimal mammography screening strategies. Objective To evaluate mammography strategies considering screening and treatment advances. Design Collaboration of six simulation models. Data Sources National data on incidence, risk, breast density, digital mammography performance, treatment effects, and other-cause mortality. Target Population An average-risk cohort. Time Horizon Lifetime. Perspective Societal. Interventions Mammograms from age 40, 45 or 50 to 74 at annual or biennial intervals, or annually from 40 or 45 to 49 then biennially to 74, assuming 100% screening and treatment adherence. Outcome Measures Screening benefits (vs. no screening) include percent breast cancer mortality reduction, deaths averted, and life-years gained. Harms include number of mammograms, false-positives, benign biopsies, and overdiagnosis. Results for Average-Risk Women Biennial strategies maintain 79.8%-81.3% (range across strategies and models: 68.3–98.9%) of annual screening benefits with almost half the false-positives and fewer overdiagnoses. Screening biennially from ages 50–74 achieves a median 25.8% (range: 24.1%-31.8%) breast cancer mortality reduction; annual screening from ages 40–74 years reduces mortality an additional 12.0% (range: 5.7%-17.2%) vs. no screening, but yields 1988 more false-positives and 7 more overdiagnoses per 1000 women screened. Annual screening from ages 50–74 had similar benefits as other strategies but more harms, so would not be recommended. Sub-population Results Annual screening starting at age 40 for women who have a two- to four-fold increase in risk has a similar balance of harms and benefits as biennial screening of average-risk women from 50–74. Limitations We do not consider other imaging technologies, polygenic risk, or non-adherence. Conclusion These results suggest that biennial screening is efficient for average-risk groups, but decisions on strategies depend on the weight given to the balance of harms and benefits. Primary Funding Source National Institutes of Health PMID:26756606

Human Uterine Leiomyoma Stem/Progenitor Cells Expressing CD34 and CD49b Initiate Tumors In Vivo

PubMed Central

Ono, Masanori; Moravek, Molly B.; Coon, John S.; Navarro, Antonia; Monsivais, Diana; Dyson, Matthew T.; Druschitz, Stacy A.; Malpani, Saurabh S.; Serna, Vanida A.; Qiang, Wenan; Chakravarti, Debabrata; Kim, J. Julie; Bulun, Serdar E.

2015-01-01

Context: Uterine leiomyoma is the most common benign tumor in reproductive-age women. Using a dye-exclusion technique, we previously identified a side population of leiomyoma cells exhibiting stem cell characteristics. However, unless mixed with mature myometrial cells, these leiomyoma side population cells did not survive or grow well in vitro or in vivo. Objective: The objective of this study was to identify cell surface markers to isolate leiomyoma stem/progenitor cells. Design: Real-time PCR screening was used to identify cell surface markers preferentially expressed in leiomyoma side population cells. In vitro colony-formation assay and in vivo tumor-regeneration assay were used to demonstrate functions of leiomyoma stem/progenitor cells. Results: We found significantly elevated CD49b and CD34 gene expression in side population cells compared with main population cells. Leiomyoma cells were sorted into three populations based on the expression of CD34 and CD49b: CD34+/CD49b+, CD34+/CD49b−, and CD34−/CD49b− cells, with the majority of the side population cells residing in the CD34+/CD49b+ fraction. Of these populations, CD34+/CD49b+ cells expressed the lowest levels of estrogen receptor-α, progesterone receptor, and α-smooth muscle actin, but the highest levels of KLF4, NANOG, SOX2, and OCT4, confirming their more undifferentiated status. The stemness of CD34+/CD49b+ cells was also demonstrated by their strongest in vitro colony-formation capacity and in vivo tumor-regeneration ability. Conclusions: CD34 and CD49b are cell surface markers that can be used to enrich a subpopulation of leiomyoma cells possessing stem/progenitor cell properties; this technique will accelerate efforts to develop new therapies for uterine leiomyoma. PMID:25658015

What happens to food choices when a gluten-free diet is required? A prospective longitudinal population-based study among Swedish adolescent with coeliac disease and their peers.

PubMed

Kautto, E; Rydén, P J; Ivarsson, A; Olsson, C; Norström, F; Högberg, L; Carlsson, A; Hagfors, L; Hörnell, A

2014-01-01

A dietary survey was performed during a large screening study in Sweden among 13-year-old adolescents. The aim was to study how the intake of food groups was affected by a screening-detected diagnosis of coeliac disease (CD) and its gluten-free (GF) treatment. Food intake was reported using a FFQ, and intake reported by the adolescents who were diagnosed with CD was compared with the intake of two same-aged referent groups: (i) adolescents diagnosed with CD prior to screening; and (ii) adolescents without CD. The food intake groups were measured at baseline before the screening-detected cases were aware of their CD, and 12-18 months later. The results showed that food intakes were affected by screen-detected CD and its dietary treatment. Many flour-based foods were reduced such as pizza, fish fingers and pastries. The results also indicated that bread intake was lower before the screened diagnosis compared with the other studied groups, but increased afterwards. Specially manufactured GF products (for example, pasta and bread) were frequently used in the screened CD group after changing to a GF diet. The present results suggest that changing to a GF diet reduces the intake of some popular foods, and the ingredients on the plate are altered, but this do not necessarily include a change of food groups. The availability of manufactured GF replacement products makes it possible for adolescents to keep many of their old food habits when diagnosed with CD in Sweden.

β-Sitosterol and flavonoids isolated from Bauhinia malabarica found during screening for Wnt signaling inhibitory activity.

PubMed

Park, Hyun Young; Toume, Kazufumi; Arai, Midori A; Koyano, Takashi; Kowithayakorn, Thaworn; Ishibashi, Masami

2014-01-01

Screening with a cell-based luciferase assay was conducted to identify bioactive natural products which inhibit Wnt signaling activity-guided separation of an MeOH extract of Bauhinia malabarica (Caesalpiniaceae) leaves yielded five compounds, which were identified as β-sitosterol (1), quercetin (2), 6,8-C-dimethyl kaempferol-3-O-rhamnopyranoside (3), hyperin (4), and 6,8-C-dimethyl kaempferol-3-methyl ether (5). The tested compounds 1, 3, and 5 exhibited Wnt signaling inhibitory activity, with IC50 values of 0.77, 0.74, and 16.6 μM, respectively.

Screening for Cryptococcal Antigenaemia in Patients Accessing an Antiretroviral Treatment Program in South Africa

PubMed Central

Jarvis, Joseph N; Lawn, Stephen D; Vogt, Monica; Bangani, Nonzwakazi; Wood, Robin; Harrison, Thomas S

2009-01-01

Background Cryptococcal meningitis is a leading cause of death in AIDS patients and contributes substantially to the high early mortality in antiretroviral treatment (ART) programs in low-resource settings. Screening for cryptococcal antigen (CRAG) in patients enrolling in ART programs may identify those at risk of cryptococcal meningitis and permit targeted use of pre-emptive therapy. Methods In this retrospective study, CRAG was measured in stored plasma samples obtained from patients as they enrolled in a well characterised ART cohort in South Africa. The predictive value of screening for CRAG prior to ART for development of microbiologically confirmed cryptococcal meningitis or death during the first year of follow-up was determined. Results Of 707 participants with a baseline median CD4 count of 97 (IQR 46-157) cells/μL, 46 (7%) had a positive CRAG. Antigenaemia was 100% sensitive for predicting development of cryptococcal meningitis during the first year of ART and in multivariate analysis was an independent predictor of mortality (AHR 3.2, 95%CI 1.5-6.6). Most (92%) cases of cryptococcal meningitis developed in patients with a CD4 count ≤100 cells/μL. In this sub-set of patients, a CRAG titre ≥1 in 8 was 100% sensitive and 96% specific for predicting incident cryptococcal meningitis during the first year of ART in those with no previous history of the disease. Conclusions CRAG screening prior to commencing ART in patients with a CD4 count ≤100 cells/μL is highly effective at identifying those at risk of cryptococcal meningitis and death and might permit implementation of a targeted pre-emptive treatment strategy. PMID:19222372

Screening for Chronic Obstructive Pulmonary Disease (COPD) in an Urban HIV Clinic: A Pilot Study

PubMed Central

Kaner, Robert J.; Glesby, Marshall J.

2015-01-01

Abstract Increased smoking and a detrimental response to tobacco smoke in the lungs of HIV/AIDS patients result in an increased risk for COPD. We aimed to determine the predictive value of a COPD screening strategy validated in the general population and to identify HIV-related factors associated with decreased lung function. Subjects at least 35 years of age at an HIV clinic in New York City completed a COPD screening questionnaire and peak flow measurement. Those with abnormal results and a random one-third of normal screens had spirometry. 235 individuals were included and 89 completed spirometry. Eleven (12%) had undiagnosed airway obstruction and 5 had COPD. A combination of a positive questionnaire and abnormal peak flow yielded a sensitivity of 20% (specificity 93%) for detection of COPD. Peak flow alone had a sensitivity of 80% (specificity 80%). Abnormal peak flow was associated with an AIDS diagnosis (p=0.04), lower nadir (p=0.001), and current CD4 counts (p=0.001). Nadir CD4 remained associated in multivariate analysis (p=0.05). Decreased FEV1 (<80% predicted) was associated with lower CD4 count nadir (p=0.04) and detectable current HIV viral load (p=0.01) in multivariate analysis. Questionnaire and peak flow together had low sensitivity, but abnormal peak flow shows potential as a screening tool for COPD in HIV/AIDS. These data suggest that lung function may be influenced by HIV-related factors. PMID:25723842

Tailoring Breast Cancer Screening Intervals by Breast Density and Risk for Women Aged 50 Years or Older: Collaborative Modeling of Screening Outcomes.

PubMed

Trentham-Dietz, Amy; Kerlikowske, Karla; Stout, Natasha K; Miglioretti, Diana L; Schechter, Clyde B; Ergun, Mehmet Ali; van den Broek, Jeroen J; Alagoz, Oguzhan; Sprague, Brian L; van Ravesteyn, Nicolien T; Near, Aimee M; Gangnon, Ronald E; Hampton, John M; Chandler, Young; de Koning, Harry J; Mandelblatt, Jeanne S; Tosteson, Anna N A

2016-11-15

Biennial screening is generally recommended for average-risk women aged 50 to 74 years, but tailored screening may provide greater benefits. To estimate outcomes for various screening intervals after age 50 years based on breast density and risk for breast cancer. Collaborative simulation modeling using national incidence, breast density, and screening performance data. United States. Women aged 50 years or older with various combinations of breast density and relative risk (RR) of 1.0, 1.3, 2.0, or 4.0. Annual, biennial, or triennial digital mammography screening from ages 50 to 74 years (vs. no screening) and ages 65 to 74 years (vs. biennial digital mammography from ages 50 to 64 years). Lifetime breast cancer deaths, life expectancy and quality-adjusted life-years (QALYs), false-positive mammograms, benign biopsy results, overdiagnosis, cost-effectiveness, and ratio of false-positive results to breast cancer deaths averted. Screening benefits and overdiagnosis increase with breast density and RR. False-positive mammograms and benign results on biopsy decrease with increasing risk. Among women with fatty breasts or scattered fibroglandular density and an RR of 1.0 or 1.3, breast cancer deaths averted were similar for triennial versus biennial screening for both age groups (50 to 74 years, median of 3.4 to 5.1 vs. 4.1 to 6.5 deaths averted; 65 to 74 years, median of 1.5 to 2.1 vs. 1.8 to 2.6 deaths averted). Breast cancer deaths averted increased with annual versus biennial screening for women aged 50 to 74 years at all levels of breast density and an RR of 4.0, and those aged 65 to 74 years with heterogeneously or extremely dense breasts and an RR of 4.0. However, harms were almost 2-fold higher. Triennial screening for the average-risk subgroup and annual screening for the highest-risk subgroup cost less than $100 000 per QALY gained. Models did not consider women younger than 50 years, those with an RR less than 1, or other imaging methods. Average-risk women with low breast density undergoing triennial screening and higher-risk women with high breast density receiving annual screening will maintain a similar or better balance of benefits and harms than average-risk women receiving biennial screening. National Cancer Institute.

Falls risk assessment outcomes and factors associated with falls for older Indigenous Australians.

PubMed

Hill, Keith D; Flicker, Leon; LoGiudice, Dina; Smith, Kate; Atkinson, David; Hyde, Zoë; Fenner, Stephen; Skeaf, Linda; Malay, Roslyn; Boyle, Eileen

2016-12-01

To describe the prevalence of falls and associated risk factors in older Indigenous Australians, and compare the accuracy of validated falls risk screening and assessment tools in this population in classifying fall status. Cross-sectional study of 289 Indigenous Australians aged ≥45 years from the Kimberley region of Western Australia who had a detailed assessment including self-reported falls in the past year (n=289), the adapted Elderly Falls Screening Tool (EFST; n=255), and the Falls Risk for Older People-Community (FROP-Com) screening tool (3 items, n=74) and FROP-Com falls assessment tool (n=74). 32% of participants had ≥1 fall in the preceding year, and 37.3% were classified high falls risk using the EFST (cut-off ≥2). In contrast, for the 74 participants assessed with the FROP-Com, only 14.9% were rated high risk, 35.8% moderate risk, and 49.3% low risk. The FROP-Com screen and assessment tools had the highest classification accuracy for identifying fallers in the preceding year (area under curve >0.85), with sensitivity/specificity highest for the FROP-Com assessment (cut-off ≥12), sensitivity=0.84 and specificity=0.73. Falls are common in older Indigenous Australians. The FROP-Com falls risk assessment tool appears useful in this population, and this research suggests changes that may improve its utility further. © 2016 Public Health Association of Australia.

CD4 Lymphocyte Count: MedlinePlus Lab Test Information

MedlinePlus

... Clinics Authority; c2017. CD4+ Count Results [updated 2017 Mar 3; cited 2017 Nov 29]; [about 7 screens]. ... Authority; c2017. CD4+ Count Test Overview [updated 2017 Mar 3; cited 2017 Nov 29]; [about 2 screens]. ...

Positive Newborn Screen for Methylmalonic Aciduria Identifies the First Mutation in TCblR/CD320, the Gene for Cellular Uptake of Transcobalamin-bound Vitamin B12

PubMed Central

Quadros, Edward V.; Lai, Shao-Chiang; Nakayama, Yasumi; Sequeira, Jeffrey M.; Hannibal, Luciana; Wang, Sihe; Jacobsen, Donald W.; Fedosov, Sergey; Wright, Erica; Gallagher, Renata C.; Anastasio, Natascia; Watkins, David; Rosenblatt, David S.

2010-01-01

Elevated methylmalonic acid in five asymptomatic newborns whose fibroblasts showed decreased uptake of transcobalamin-bound cobalamin (holo-TC), suggested a defect in the cellular uptake of cobalamin. Analysis of TCblR/CD320, the gene for the receptor for cellular uptake of holo-TC, identified a homozygous single codon deletion, c.262_264GAG (p.E88del), resulting in the loss of a glutamic acid residue in the low-density lipoprotein receptor type A-like domain. Inserting the codon by site-directed mutagenesis fully restored TCblR function. PMID:20524213

Identification of a distinct population of CD133+CXCR4+ cancer stem cells in ovarian cancer

PubMed Central

Cioffi, Michele; D’Alterio, Crescenzo; Camerlingo, Rosalba; Tirino, Virginia; Consales, Claudia; Riccio, Anna; Ieranò, Caterina; Cecere, Sabrina Chiara; Losito, Nunzia Simona; Greggi, Stefano; Pignata, Sandro; Pirozzi, Giuseppe; Scala, Stefania

2015-01-01

CD133 and CXCR4 were evaluated in the NCI-60 cell lines to identify cancer stem cell rich populations. Screening revealed that, ovarian OVCAR-3, -4 and -5 and colon cancer HT-29, HCT-116 and SW620 over expressed both proteins. We aimed to isolate cells with stem cell features sorting the cells expressing CXCR4+CD133+ within ovarian cancer cell lines. The sorted population CD133+CXCR4+ demonstrated the highest efficiency in sphere formation in OVCAR-3, OVCAR-4 and OVCAR-5 cells. Moreover OCT4, SOX2, KLF4 and NANOG were highly expressed in CD133+CXCR4+ sorted OVCAR-5 cells. Most strikingly CXCR4+CD133+ sorted OVCAR-5 and -4 cells formed the highest number of tumors when inoculated in nude mice compared to CD133−CXCR4−, CD133+CXCR4−, CD133−CXCR4+ cells. CXCR4+CD133+ OVCAR-5 cells were resistant to cisplatin, overexpressed the ABCG2 surface drug transporter and migrated toward the CXCR4 ligand, CXCL12. Moreover, when human ovarian cancer cells were isolated from 37 primary ovarian cancer, an extremely variable level of CXCR4 and CD133 expression was detected. Thus, in human ovarian cancer cells CXCR4 and CD133 expression identified a discrete population with stem cell properties that regulated tumor development and chemo resistance. This cell population represents a potential therapeutic target. PMID:26020117

A Novel Sphingomyelinase-Like Enzyme in Ixodes scapularis Tick Saliva Drives Host CD4+ T cells to Express IL-4

PubMed Central

Alarcon-Chaidez, F. J.; Boppana, V. D.; Hagymasi, A.T.; Adler, A. J.; Wikel, S. K.

2009-01-01

Tick feeding modulates host immune responses. Tick-induced skewing of host CD4+ T cells towards a Th2 cytokine profile facilitates transmission of tick-borne pathogens that would otherwise be neutralized by Th1 cytokines. Tick-derived factors that drive this Th2 response have not previously been characterized. In the current study, we examined an I. scapularis cDNA library prepared at 18-24 hours of feeding and identified and expressed a tick gene with homology to Loxosceles spider venom proteins with sphingomyelinase activity. This I. scapularis sphingomyelinase-like (IsSMase) protein is a Mg+2-dependent, neutral (pH 7.4) form of sphingomyelinase. Significantly, in an in vivo TCR transgenic adoptive transfer assay IsSMase programmed host CD4+ T cells to express the hallmark Th2 effector cytokine IL-4. IsSMase appears to directly program host CD4 T cell IL-4 expression (as opposed to its metabolic by-products) because induced IL-4 expression was not altered when enzymatic activity was neutralized. TCR transgenic CD4 T cell proliferation (CFSE-dilution) was also significantly increased by IsSMase. Furthermore, a Th2 response is superimposed onto a virally-primed Th1 response by IsSMase. Thus, IsSMase is the first identified tick molecule capable of programming host CD4+ T cells to express IL-4. PMID:19292772

Assessing the role of peripheral CD8 T cells in neurocognitive impairment in HIV-infected men who have sex with men: data from the MSM Neurocog Study.

PubMed

Rawson, T M; Dubb, S; Pozniak, A; Kelleher, W P; Mandalia, S; Gazzard, B; Barber, T J

2015-02-01

Studies have suggested CD8 lymphocytes may be a possible marker for inflammation, which is believed to be a contributing factor to neurocognitive impairment. Individuals enrolled in the MSM Neurocog Study were analysed. Those with depression, anxiety or mood disorders were excluded. Individuals with neurocognitive impairment were identified using the Brief NeuroCognitive Screen and compared to those with normal scores. CD4 and CD8 T cell values and CD4:CD8 ratios were compared between groups. In all, 144 men, aged 18-50 years, were included in the analysis. Twenty were diagnosed with neurocognitive impairment. We were unable to identify any significant difference between current, nadir or peak CD4 and CD8 counts. CD4:CD8 ratios and CD4:CD8 ratio inversion (<1) were also found to be similar between both groups. However, neurocognitive impairment subjects were 8% more likely to have inversion of CD4:CD8 ratio and higher median peak CD8 cell counts reported compared to non-impaired subjects. Analysis of data from the MSM Neurocog Study, demonstrated trends in peripheral CD8 counts and CD4:CD8 ratios. However, we are unable to demonstrate any significant benefit. Plasma biomarkers of neurocognitive impairment in HIV-infected subjects would be of great benefit over current methods of invasive CSF analysis and technical neuroimaging used in the diagnosis of neurocognitive impairment. Future, prospective, longitudinal work with large numbers of neurocognitive impairment subjects is required to further investigate the role of peripheral CD8 T cells as markers of neurocognitive impairment. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Screening of celiac disease in Down syndrome - Old and new dilemmas

PubMed Central

Pavlovic, Momcilo; Berenji, Karolina; Bukurov, Marko

2017-01-01

Celiac disease (CD) is a common and well defined autoimmune disorder caused by gliadin and related proteins of wheat, rye, and barley. Epidemiologic studies confirmed that CD is highly associated with other autoimmune diseases and with Down syndrome (DS). The symptomatic form of CD in patients with DS is more frequent than asymptomatic forms. However, growth impairment, anemia, intermittent diarrhea, and constipation are symptoms and signs typically of children with DS without CD. Late identification of the disease can lead to various complications, sometimes even very severe. Therefore, systematic screening for CD is essential in the management of children and adolescents with DS. Many medical organizations recommend screening in this group of patients. However, current policy statements vary in their recommendations for screening and there is still a need for establishing uniform diagnostic criteria. PMID:28798921

Screening of celiac disease in Down syndrome - Old and new dilemmas.

PubMed

Pavlovic, Momcilo; Berenji, Karolina; Bukurov, Marko

2017-07-16

Celiac disease (CD) is a common and well defined autoimmune disorder caused by gliadin and related proteins of wheat, rye, and barley. Epidemiologic studies confirmed that CD is highly associated with other autoimmune diseases and with Down syndrome (DS). The symptomatic form of CD in patients with DS is more frequent than asymptomatic forms. However, growth impairment, anemia, intermittent diarrhea, and constipation are symptoms and signs typically of children with DS without CD. Late identification of the disease can lead to various complications, sometimes even very severe. Therefore, systematic screening for CD is essential in the management of children and adolescents with DS. Many medical organizations recommend screening in this group of patients. However, current policy statements vary in their recommendations for screening and there is still a need for establishing uniform diagnostic criteria.

Antiretroviral therapy suppressed participants with low CD4+ T-cell counts segregate according to opposite immunological phenotypes

PubMed Central

Pérez-Santiago, Josué; Ouchi, Dan; Urrea, Victor; Carrillo, Jorge; Cabrera, Cecilia; Villà-Freixa, Jordi; Puig, Jordi; Paredes, Roger; Negredo, Eugènia; Clotet, Bonaventura; Massanella, Marta; Blanco, Julià

2016-01-01

Background: The failure to increase CD4+ T-cell counts in some antiretroviral therapy suppressed participants (immunodiscordance) has been related to perturbed CD4+ T-cell homeostasis and impacts clinical evolution. Methods: We evaluated different definitions of immunodiscordance based on CD4+ T-cell counts (cutoff) or CD4+ T-cell increases from nadir value (ΔCD4) using supervised random forest classification of 74 immunological and clinical variables from 196 antiretroviral therapy suppressed individuals. Unsupervised clustering was performed using relevant variables identified in the supervised approach from 191 individuals. Results: Cutoff definition of CD4+ cell count 400 cells/μl performed better than any other definition in segregating immunoconcordant and immunodiscordant individuals (85% accuracy), using markers of activation, nadir and death of CD4+ T cells. Unsupervised clustering of relevant variables using this definition revealed large heterogeneity between immunodiscordant individuals and segregated participants into three distinct subgroups with distinct production, programmed cell-death protein-1 (PD-1) expression, activation and death of T cells. Surprisingly, a nonnegligible number of immunodiscordant participants (22%) showed high frequency of recent thymic emigrants and low CD4+ T-cell activation and death, very similar to immunoconcordant participants. Notably, human leukocyte antigen - antigen D related (HLA-DR) PD-1 and CD45RA expression in CD4+ T cells allowed reproducing subgroup segregation (81.4% accuracy). Despite sharp immunological differences, similar and persistently low CD4+ values were maintained in these participants over time. Conclusion: A cutoff value of CD4+ T-cell count 400 cells/μl classified better immunodiscordant and immunoconcordant individuals than any ΔCD4 classification. Immunodiscordance may present several, even opposite, immunological patterns that are identified by a simple immunological follow-up. Subgroup classification may help clinicians to delineate diverse approaches that may be needed to boost CD4+ T-cell recovery. PMID:27427875

Gynecologic cancer screening and communication with health care providers in women with Lynch syndrome.

PubMed

Burton-Chase, A M; Hovick, S R; Sun, C C; Boyd-Rogers, S; Lynch, P M; Lu, K H; Peterson, S K

2014-08-01

We evaluated knowledge of gynecologic cancer screening recommendations, screening behaviors, and communication with providers among women with Lynch syndrome (LS). Women aged ≥25 years who were at risk for LS-associated cancers completed a semi-structured interview and a questionnaire. Of 74 participants (mean age 40 years), 61% knew the appropriate age to begin screening, 75-80% correctly identified the recommended screening frequency, and 84% reported no previous screening endometrial biopsy. Women initiated discussions with their providers about their LS cancer risks, but many used nonspecific terms or relied on family history. Most were not offered high-risk screening options. While many women were aware of risk-appropriate LS screening guidelines, adherence was suboptimal. Improving communication between women and their providers regarding LS-related gynecologic cancer risk and screening options may help improve adherence. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Gynecologic cancer screening and communication with health care providers in women with Lynch syndrome

PubMed Central

Burton-Chase, AM; Hovick, SR; Sun, CC; Boyd-Rogers, S; Lynch, PM; Lu, KH; Peterson, SK

2014-01-01

We evaluated knowledge of gynecologic cancer screening recommendations, screening behaviors, and communication with providers among women with Lynch syndrome (LS). Women aged ≥25 years who were at risk for LS-associated cancers completed a semi-structured interview and a questionnaire. Of 74 participants (mean age 40 years), 61% knew the appropriate age to begin screening, 75–80% correctly identified the recommended screening frequency, and 84% reported no previous screening endometrial biopsy. Women initiated discussions with their providers about their LS cancer risks, but many used nonspecific terms or relied on family history. Most were not offered high-risk screening options. While many women were aware of risk-appropriate LS screening guidelines, adherence was suboptimal. Improving communication between women and their providers regarding LS-related gynecologic cancer risk and screening options may help improve adherence. PMID:23906188

New use of an old drug: inhibition of breast cancer stem cells by benztropine mesylate

PubMed Central

Cui, Jihong; Hollmén, Maija; Li, Lina; Chen, Yong; Proulx, Steven T.; Reker, Daniel; Schneider, Gisbert; Detmar, Michael

2017-01-01

Cancer stem cells (CSCs) play major roles in cancer initiation, metastasis, recurrence and therapeutic resistance. Targeting CSCs represents a promising strategy for cancer treatment. The purpose of this study was to identify selective inhibitors of breast CSCs (BCSCs). We carried out a cell-based phenotypic screening with cell viability as a primary endpoint, using a collection of 2,546 FDA-approved drugs and drug-like molecules in spheres formed by malignant human breast gland-derived cells (HMLER-shEcad cells, representing BCSCs) and control immortalized non-tumorigenic human mammary cells (HMLE cells, representing normal stem cells). 19 compounds were identified from screening. The chemically related molecules benztropine mesylate and deptropine citrate were selected for further validation and both potently inhibited sphere formation and self-renewal of BCSCs in vitro. Benztropine mesylate treatment decreased cell subpopulations with high ALDH activity and with a CD44+/CD24− phenotype. In vivo, benztropine mesylate inhibited tumor-initiating potential in a 4T1 mouse model. Functional studies indicated that benztropine mesylate inhibits functions of CSCs via the acetylcholine receptors, dopamine transporters/receptors, and/or histamine receptors. In summary, our findings identify benztropine mesylate as an inhibitor of BCSCs in vitro and in vivo. This study also provides a screening platform for identification of additional anti-CSC agents. PMID:27894093

To screen or not to screen? Celiac antibodies in liver diseases

PubMed Central

Narciso-Schiavon, Janaína Luz; Schiavon, Leonardo Lucca

2017-01-01

Celiac disease (CD) is a systemic immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals. The typical symptoms are anemia, diarrhea, fatigue, weight loss, and abdominal pain. CD has been reported in patients with primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis, aminotransferase elevations, nonalcoholic fatty liver disease, hepatitis B, hepatitis C, portal hypertension and liver cirrhosis. We evaluate recommendations for active screening for CD in patients with liver diseases, and the effect of a gluten-free diet in these different settings. Active screening for CD is recommended in patients with liver diseases, particularly in those with autoimmune disorders, steatosis in the absence of metabolic syndrome, noncirrhotic intrahepatic portal hypertension, cryptogenic cirrhosis, and in the context of liver transplantation. In hepatitis C, diagnosis of CD can be important as a relative contraindication to interferon use. Gluten-free diet ameliorates the symptoms associated with CD; however, the associated liver disease may improve, remain the same, or progress. PMID:28223722

40 CFR 413.74 - Pretreatment standards for existing sources.

Code of Federal Regulations, 2011 CFR

2011-07-01

....5 2.7 Ni 4.1 2.6 Cr 7.0 4.0 Zn 4.2 2.6 Pb 0.6 0.4 Cd 1.2 0.7 Total metals 10.5 6.8 (d) Alternatively... days shall not exceed CN,T 74 39 Cu 176 105 Ni 160 100 Cr 273 156 Zn 164 102 Pb 23 16 Cd 47 29 Total...

40 CFR 413.74 - Pretreatment standards for existing sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

....5 2.7 Ni 4.1 2.6 Cr 7.0 4.0 Zn 4.2 2.6 Pb 0.6 0.4 Cd 1.2 0.7 Total metals 10.5 6.8 (d) Alternatively... days shall not exceed CN,T 74 39 Cu 176 105 Ni 160 100 Cr 273 156 Zn 164 102 Pb 23 16 Cd 47 29 Total...

Screening Mammography Use Among Older Women Before and After the 2009 U.S. Preventive Services Task Force Recommendations.

PubMed

Chang, Chiang-Hua; Bynum, Julie P W; Onega, Tracy; Colla, Carrie H; Lurie, Jon D; Tosteson, Anna N A

2016-10-01

It is uncertain how changes in the U.S. Preventive Services Task Force breast cancer screening recommendations (from annual to biennial mammography screening in women aged 50-74 and grading the evidence as insufficient for screening in women aged 75 and older) have affected mammography use among Medicare beneficiaries. Cohort study of 12 million Medicare fee-for-service women aged 65-74 and 75 and older to measure changes in 3-year screening use, 2007-2009 (before) and 2010-2012 (after), defined by two measures-proportion screened and frequency of screening by age, race/ethnicity, and hospital referral region. Fewer women were screened, but with similar frequency after 2009 for both age groups (after vs. before: age 65-74: 60.1% vs. 60.8% screened, 2.1 vs. 2.1 mammograms per screened woman; age 75 and older: 31.7% vs. 33.6% screened, 1.9 vs. 1.9 mammograms per screened woman; all p < 0.05). Black women were the only subgroup with an increase in screening use, and for both age groups (after vs. before: age 65-74: 55.4% vs. 54.0% screened and 2.0 vs. 1.9 mammograms per screened woman; age 75 and older: 28.5% vs. 27.9% screened and 1.8 vs. 1.8 mammograms per screened woman; all p < 0.05). Regional change patterns in screening were more similar between age groups (Pearson correlation r = 0.781 for proportion screened; r = 0.840 for frequency of screening) than between black versus nonblack women (Pearson correlation r = 0.221 for proportion screened; r = 0.212 for frequency of screening). Changes in screening mammography use for Medicare women are not fully aligned with the 2009 recommendations.

Premature cell senescence and T cell receptor-independent activation of CD8T cells in Juvenile Idiopathic Arthritis*

PubMed Central

Dvergsten, Jeffrey A.; Mueller, Robert G.; Griffin, Patricia; Abedin, Sameem; Pishko, Allyson; Michel, Joshua J.; Rosenkranz, Margalit E.; Reed, Ann M.; Kietz, Daniel A.; Vallejo, Abbe N.

2013-01-01

Objectives CD8T cells lacking CD28 were originally reported by Wedderburn and colleagues as a characteristic feature of JIA, but the relevance of these unusual cells to JIA remains to be elucidated. Because of recent evidence that CD28 loss is typical of terminally differentiated lymphocytes, we examined for functional subsets of CD8T cells in JIA. Methods Following informed consent/assent, blood and/or waste synovial fluid were collected from children with definite diagnosis of JIA (n = 98). De-identified blood (n = 33) and cord blood (n = 13) samples from healthy donors were also collected. CD8T and CD4T cells were screened for novel receptors, and where indicated, bioassays were performed to determine functional relevance of the identified receptor. Results Patients had a naïve T cell compartment with shortened telomeres, and their entire T cell pool had reduced proliferative capacity. They had an over abundance of CD31+CD28null CD8T cells, which was a significant feature of oligoarticular JIA (n = 62) compared to polyarticular JIA (n = 36). CD31+CD28null CD8T cells had limited mitotic capacity, and expressed high levels of the senescence antigens γH2Ax and/or p16. Ligation of CD31, independent of the TCR, sufficiently induced tyrosine phosphorylation, vesicle exocytosis, and production of IFN-γ and IL-10. Conclusion These data provide the first evidence for cell senescence, represented by CD31+CD28null CD8T cells, in the pathophysiology of JIA. Activation of these unusual cells in a TCR-independent manner suggests they are maladaptive, and could be potential targets for immunotherapy. PMID:23686519

Systematic review: treatment pattern and clinical effectiveness and safety of pharmaceutical therapies for Crohn’s disease in Europe

PubMed Central

Lelli, Filippo; Nuhoho, Solomon; Lee, Xin Ying; Xu, Weiwei

2016-01-01

Background Although many clinical trials have been conducted in treatments of Crohn’s disease (CD), whether the trial results were representative of daily practice needs to be supported by studies conducted in real-world settings. Aim This study aims to identify how CD is treated and what are the clinical effectiveness and safety of the pharmaceutical therapies of CD in real-world settings. Methods A systematic literature review was conducted based on Medline®, Embase®, and Cochrane. All publications were assessed for title/abstract and full-text according to a predefined study protocol. Data were extracted and reported. Results A total of 1,998 publications were identified. Fifty studies including six publications reporting treatment pattern and 44 studies reporting clinical effectiveness and safety of pharmaceutical therapies in CD management in Europe were included. 5-Aminosalicylic acid and corticosteroids were reported to be used among 14%–74% of CD patients. Immunomodulators were used by 14%–25% and 29%–31% of CD patients as an initial and follow-up treatment, respectively. Biological therapies were used by 25%–33% of CD patients. A trend toward an increasing use of immunomodulators and biological therapies in Europe has been reported in recent years. Approximately 50% of patients achieved remission on immunomodulator or biologic treatment, although a relapse rate of up to 23% has been reported. Conclusion There is a trend of treatment shift to immunomodulators and biologics in CD management. Clinical effectiveness of immunomodulators and biologics has been demonstrated, though with a lack of sustainability of the effectiveness. PMID:27785086

Systematic review: treatment pattern and clinical effectiveness and safety of pharmaceutical therapies for Crohn's disease in Europe.

PubMed

Lelli, Filippo; Nuhoho, Solomon; Lee, Xin Ying; Xu, Weiwei

2016-01-01

Although many clinical trials have been conducted in treatments of Crohn's disease (CD), whether the trial results were representative of daily practice needs to be supported by studies conducted in real-world settings. This study aims to identify how CD is treated and what are the clinical effectiveness and safety of the pharmaceutical therapies of CD in real-world settings. A systematic literature review was conducted based on Medline ® , Embase ® , and Cochrane. All publications were assessed for title/abstract and full-text according to a predefined study protocol. Data were extracted and reported. A total of 1,998 publications were identified. Fifty studies including six publications reporting treatment pattern and 44 studies reporting clinical effectiveness and safety of pharmaceutical therapies in CD management in Europe were included. 5-Aminosalicylic acid and corticosteroids were reported to be used among 14%-74% of CD patients. Immunomodulators were used by 14%-25% and 29%-31% of CD patients as an initial and follow-up treatment, respectively. Biological therapies were used by 25%-33% of CD patients. A trend toward an increasing use of immunomodulators and biological therapies in Europe has been reported in recent years. Approximately 50% of patients achieved remission on immunomodulator or biologic treatment, although a relapse rate of up to 23% has been reported. There is a trend of treatment shift to immunomodulators and biologics in CD management. Clinical effectiveness of immunomodulators and biologics has been demonstrated, though with a lack of sustainability of the effectiveness.

Collaborative Modeling of the Benefits and Harms Associated With Different U.S. Breast Cancer Screening Strategies.

PubMed

Mandelblatt, Jeanne S; Stout, Natasha K; Schechter, Clyde B; van den Broek, Jeroen J; Miglioretti, Diana L; Krapcho, Martin; Trentham-Dietz, Amy; Munoz, Diego; Lee, Sandra J; Berry, Donald A; van Ravesteyn, Nicolien T; Alagoz, Oguzhan; Kerlikowske, Karla; Tosteson, Anna N A; Near, Aimee M; Hoeffken, Amanda; Chang, Yaojen; Heijnsdijk, Eveline A; Chisholm, Gary; Huang, Xuelin; Huang, Hui; Ergun, Mehmet Ali; Gangnon, Ronald; Sprague, Brian L; Plevritis, Sylvia; Feuer, Eric; de Koning, Harry J; Cronin, Kathleen A

2016-02-16

Controversy persists about optimal mammography screening strategies. To evaluate screening outcomes, taking into account advances in mammography and treatment of breast cancer. Collaboration of 6 simulation models using national data on incidence, digital mammography performance, treatment effects, and other-cause mortality. United States. Average-risk U.S. female population and subgroups with varying risk, breast density, or comorbidity. Eight strategies differing by age at which screening starts (40, 45, or 50 years) and screening interval (annual, biennial, and hybrid [annual for women in their 40s and biennial thereafter]). All strategies assumed 100% adherence and stopped at age 74 years. Benefits (breast cancer-specific mortality reduction, breast cancer deaths averted, life-years, and quality-adjusted life-years); number of mammograms used; harms (false-positive results, benign biopsies, and overdiagnosis); and ratios of harms (or use) and benefits (efficiency) per 1000 screens. Biennial strategies were consistently the most efficient for average-risk women. Biennial screening from age 50 to 74 years avoided a median of 7 breast cancer deaths versus no screening; annual screening from age 40 to 74 years avoided an additional 3 deaths, but yielded 1988 more false-positive results and 11 more overdiagnoses per 1000 women screened. Annual screening from age 50 to 74 years was inefficient (similar benefits, but more harms than other strategies). For groups with a 2- to 4-fold increased risk, annual screening from age 40 years had similar harms and benefits as screening average-risk women biennially from 50 to 74 years. For groups with moderate or severe comorbidity, screening could stop at age 66 to 68 years. Other imaging technologies, polygenic risk, and nonadherence were not considered. Biennial screening for breast cancer is efficient for average-risk populations. Decisions about starting ages and intervals will depend on population characteristics and the decision makers' weight given to the harms and benefits of screening. National Institutes of Health.

Magnitude and kinetics of CD8+ T cell activation during hyperacute HIV infection impacts viral set point

PubMed Central

Ndhlovu, Zaza; Kamya, Philomena; Mewalal, Nikoshia; Kløverpris, Henrik N.; Nkosi, Thandeka; Pretorius, Karyn; Laher, Faatima; Ogunshola, Funsho; Chopera, Denis; Shekhar, Karthik; Ghebremichael, Musie; Ismail, Nasreen; Moodley, Amber; Malik, Amna; Leslie, Alasdair; Goulder, Philip J.R; Buus, Søren; Chakraborty, Arup; Dong, Krista; Ndung’u, Thumbi; Walker, Bruce D.

2015-01-01

Summary CD8+ T cells contribute to the control of HIV, but it is not clear whether initial immune responses modulate the viral set point. We screened high-risk uninfected women twice a week for plasma HIV RNA and identified twelve hyperacute infections. Onset of viremia elicited a massive HIV-specific CD8+ T cell response, with limited bystander activation of non-HIV memory CD8+ T cells. HIV-specific CD8+ T cells secreted little interferon-γ, underwent rapid apoptosis and failed to upregulate the interleukin 7 receptor, known to be important for T cell survival. The rapidity to peak CD8+ T cell activation and the absolute magnitude of activation induced by the exponential rise in viremia were inversely correlated with set point viremia. These data indicate that rapid, high magnitude HIV-induced CD8+ T cell responses are crucial for subsequent immune control of acute infection, which has important implications for HIV vaccine design. PMID:26362266

The Expenditures for Academic Inpatient Care of Inflammatory Bowel Disease Patients Are Almost Double Compared with Average Academic Gastroenterology and Hepatology Cases and Not Fully Recovered by Diagnosis-Related Group (DRG) Proceeds

PubMed Central

Baumgart, Daniel C.; le Claire, Marie

2016-01-01

Background Crohn’s disease (CD) and ulcerative colitis (UC) challenge economies worldwide. Detailed health economic data of DRG based academic inpatient care for inflammatory bowel disease (IBD) patients in Europe is unavailable. Methods IBD was identified through ICD-10 K50 and K51 code groups. We took an actual costing approach, compared expenditures to G-DRG and non-DRG proceeds and performed detailed cost center and type accounting to identify coverage determinants. Results Of all 3093 hospitalized cases at our department, 164 were CD and 157 UC inpatients in 2012. On average, they were 44.1 (CD 44.9 UC 43.3 all 58) years old, stayed 10.1 (CD 11.8 UC 8.4 vs. all 8) days, carried 5.8 (CD 6.4 UC 5.2 vs. all 6.8) secondary diagnoses, received 7.4 (CD 7.7 UC 7 vs. all 6.2) procedures, had a higher cost weight (CD 2.8 UC 2.4 vs. all 1.6) and required more intense nursing. Their care was more costly (means: total cost IBD 8477€ CD 9051€ UC 7903€ vs. all 5078€). However, expenditures were not fully recovered by DRG proceeds (means: IBD 7413€, CD 8441€, UC 6384€ vs all 4758€). We discovered substantial disease specific mismatches in cost centers and types and identified the medical ward personnel and materials budgets to be most imbalanced. Non-DRG proceeds were almost double (IBD 16.1% vs. all 8.2%), but did not balance deficits at total coverage analysis, that found medications (antimicrobials, biologics and blood products), medical materials (mostly endoscopy items) to contribute most to the deficit. Conclusions DRGs challenge sophisticated IBD care. PMID:26784027

CD24 Expression Identifies Teratogen-Sensitive Fetal Neural Stem Cell Subpopulations: Evidence from Developmental Ethanol Exposure and Orthotopic Cell Transfer Models

PubMed Central

Tingling, Joseph D.; Bake, Shameena; Holgate, Rhonda; Rawlings, Jeremy; Nagsuk, Phillips P.; Chandrasekharan, Jayashree; Schneider, Sarah L.; Miranda, Rajesh C.

2013-01-01

Background Ethanol is a potent teratogen. Its adverse neural effects are partly mediated by disrupting fetal neurogenesis. The teratogenic process is poorly understood, and vulnerable neurogenic stages have not been identified. Identifying these is a prerequisite for therapeutic interventions to mitigate effects of teratogen exposures. Methods We used flow cytometry and qRT-PCR to screen fetal mouse-derived neurosphere cultures for ethanol-sensitive neural stem cell (NSC) subpopulations, to study NSC renewal and differentiation. The identity of vulnerable NSC populations was validated in vivo, using a maternal ethanol exposure model. Finally, the effect of ethanol exposure on the ability of vulnerable NSC subpopulations to integrate into the fetal neurogenic environment was assessed following ultrasound guided, adoptive transfer. Results Ethanol decreased NSC mRNAs for c-kit, Musashi-1and GFAP. The CD24+ NSC population, specifically the CD24+CD15+ double-positive subpopulation, was selectively decreased by ethanol. Maternal ethanol exposure also resulted in decreased fetal forebrain CD24 expression. Ethanol pre-exposed CD24+ cells exhibited increased proliferation, and deficits in cell-autonomous and cue-directed neuronal differentiation, and following orthotopic transplantation into naïve fetuses, were unable to integrate into neurogenic niches. CD24depleted cells retained neurosphere regeneration capacity, but following ethanol exposure, generated increased numbers of CD24+ cells relative to controls. Conclusions Neuronal lineage committed CD24+ cells exhibit specific vulnerability, and ethanol exposure persistently impairs this population’s cell-autonomous differentiation capacity. CD24+ cells may additionally serve as quorum sensors within neurogenic niches; their loss, leading to compensatory NSC activation, perhaps depleting renewal capacity. These data collectively advance a mechanistic hypothesis for teratogenesis leading to microencephaly. PMID:23894503

Cost-Effectiveness of HIV Screening in STD Clinics, Emergency Departments, and Inpatient Units: A Model-Based Analysis

PubMed Central

Prabhu, Vimalanand S.; Farnham, Paul G.; Hutchinson, Angela B.; Soorapanth, Sada; Heffelfinger, James D.; Golden, Matthew R.; Brooks, John T.; Rimland, David; Sansom, Stephanie L.

2011-01-01

Background Identifying and treating persons with human immunodeficiency virus (HIV) infection early in their disease stage is considered an effective means of reducing the impact of the disease. We compared the cost-effectiveness of HIV screening in three settings, sexually transmitted disease (STD) clinics serving men who have sex with men, hospital emergency departments (EDs), settings where patients are likely to be diagnosed early, and inpatient diagnosis based on clinical manifestations. Methods and Findings We developed the Progression and Transmission of HIV/AIDS model, a health state transition model that tracks index patients and their infected partners from HIV infection to death. We used program characteristics for each setting to compare the incremental cost per quality-adjusted life year gained from early versus late diagnosis and treatment. We ran the model for 10,000 index patients for each setting, examining alternative scenarios, excluding and including transmission to partners, and assuming HAART was initiated at a CD4 count of either 350 or 500 cells/µL. Screening in STD clinics and EDs was cost-effective compared with diagnosing inpatients, even when including only the benefits to the index patients. Screening patients in STD clinics, who have less-advanced disease, was cost-effective compared with ED screening when treatment with HAART was initiated at a CD4 count of 500 cells/µL. When the benefits of reduced transmission to partners from early diagnosis were included, screening in settings with less-advanced disease stages was cost-saving compared with screening later in the course of infection. The study was limited by a small number of observations on CD4 count at diagnosis and by including transmission only to first generation partners of the index patients. Conclusions HIV prevention efforts can be advanced by screening in settings where patients present with less-advanced stages of HIV infection and by initiating treatment with HAART earlier in the course of infection. PMID:21625489

Expression of macrophage migration inhibitory factor and CD74 in the inner ear and middle ear in lipopolysaccharide-induced otitis media.

PubMed

Ishihara, Hisashi; Kariya, Shin; Okano, Mitsuhiro; Zhao, Pengfei; Maeda, Yukihide; Nishizaki, Kazunori

2016-10-01

Significant expression of macrophage migration inhibitory factor and its receptor (CD74) was observed in both the middle ear and inner ear in experimental otitis media in mice. Modulation of macrophage migration inhibitory factor and its signaling pathway might be useful in the management of inner ear inflammation due to otitis media. Inner ear dysfunction secondary to otitis media has been reported. However, the specific mechanisms involved are not clearly understood. The aim of this study is to investigate the expression of macrophage migration inhibitory factor and CD74 in the middle ear and inner ear in lipopolysaccharide-induced otitis media. BALB/c mice received a transtympanic injection of either lipopolysaccharide or phosphate-buffered saline (PBS). The mice were sacrificed 24 h after injection, and temporal bones were processed for polymerase chain reaction (PCR) analysis, histologic examination, and immunohistochemistry. PCR examination revealed that the lipopolysaccharide-injected mice showed a significant up-regulation of macrophage migration inhibitory factor in both the middle ear and inner ear as compared with the PBS-injected control mice. The immunohistochemical study showed positive reactions for macrophage migration inhibitory factor and CD74 in infiltrating inflammatory cells, middle ear mucosa, and inner ear in the lipopolysaccharide-injected mice.

Screening of Variations in CD22 Gene in Children with B-Precursor Acute Lymphoblastic Leukemia.

PubMed

Aslar Oner, Deniz; Akin, Dilara Fatma; Sipahi, Kadir; Mumcuoglu, Mine; Ezer, Ustun; Kürekci, A Emin; Akar, Nejat

2016-09-01

CD22 is expressed on the surface of B-cell lineage cells from the early progenitor stage of pro-B cell until terminal differentiation to mature B cells. It plays a role in signal transduction and as a regulator of B-cell receptor signaling in B-cell development. We aimed to screen exons 9-14 of the CD22 gene, which is a mutational hot spot region in B-precursor acute lymphoblastic leukemia (pre-B ALL) patients, to find possible genetic variants that could play role in the pathogenesis of pre-B ALL in Turkish children. This study included 109 Turkish children with pre-B ALL who were diagnosed at Losante Hospital for Children with Leukemia. Genomic DNA was extracted from both peripheral blood and bone marrow leukocytes. Gene amplification was performed with PCR, and all samples were screened for the variants by single strand conformation polymorphism. Samples showing band shifts were sequenced on an automated sequencer. In our patient group a total of 9 variants were identified in the CD22 gene by sequencing: a novel variant in intron 10 (T2199G); a missense variant in exon 12; 5 intronic variants between exon 12 and intron 13; a novel intronic variant (C2424T); and a synonymous in exon 13. Thirteen of 109 children (11.9%) carried the T2199G novel intronic variant located in intron 10, and 17 of 109 children (15.6%) carried the C2424T novel intronic variant. Novel variants in the CD22 gene in children with pre-B ALL in Turkey that are not present, in the Human Gene Mutation Database or NCBI SNP database, were found.

Screening of a new cadmium hyperaccumulator, Galinsoga parviflora, from winter farmland weeds using the artificially high soil cadmium concentration method.

PubMed

Lin, Lijin; Jin, Qian; Liu, Yingjie; Ning, Bo; Liao, Ming'an; Luo, Li

2014-11-01

A new method, the artificially high soil cadmium (Cd) concentration method, was used to screen for Cd hyperaccumulators among winter farmland weeds. Galinsoga parviflora was the most promising remedial plant among 5 Cd accumulators or hyperaccumulators. In Cd concentration gradient experiments, as soil Cd concentration increased, root and shoot biomass decreased, and their Cd contents increased. In additional concentration gradient experiments, superoxide dismutase and peroxidase activities increased with soil Cd concentrations up to 75 mg kg(-1) , while expression of their isoenzymes strengthened. Catalase (CAT) activity declined and CAT isoenzyme expression weakened at soil Cd concentrations less than 50 mg kg(-1) . The maxima of Cd contents in shoots and roots were 137.63 mg kg(-1) and 105.70 mg kg(-1) , respectively, at 100 mg kg(-1) Cd in soil. The root and shoot bioconcentration factors exceeded 1.0, as did the translocation factor. In a field experiment, total extraction of Cd by shoots was 1.35 mg m(-2) to 1.43 mg m(-2) at soil Cd levels of 2.04 mg kg(-1) to 2.89 mg kg(-1) . Therefore, the artificially high soil Cd concentration method was effective for screening Cd hyperaccumulators. Galinsoga parviflora is a Cd hyperaccumulator that could be used to efficiently remediate Cd-contaminated farmland soil. © 2014 SETAC.

Chagas disease screening among HIV-positive Latin American immigrants: an emerging problem.

PubMed

Llenas-García, J; Hernando, A; Fiorante, S; Maseda, D; Matarranz, M; Salto, E; Rubio, R; Pulido, F

2012-08-01

Chagas disease (CD) is an emergent disease in Europe that can behave as an opportunistic infection in HIV positive patients. The objective of this study was to evaluate the implementation of a CD screening programme in an HIV unit. An immunochromatography (ICT) of Trypanosoma cruzi was performed as a screening tool in HIV-positive patients born in CD endemic countries. ELISA and IFAT were used to confirm the diagnosis. A total of 155 patients, 116 males and 38 females, were included. Mean age was 36.9 years (± 8.4) and mean length of stay in Spain at the screening was 7.1 years (± 4.7). T. cruzi ICT was positive in four cases (2.6%), being confirmed (by ELISA and IFAT) in three of those (1.9%). Factors associated with confirmed positive T.cruzi serology were: Bolivia origin (p=0.016), Bolivia or Argentina origin (p=0.002), Southern Cone origin (p=0.015), rural origin (p=0.023), previously living in an adobe-made (p=0.001) or thatch-roofed house (p<0.0001), having a previous CD test (p=0.015), previous knowledge about CD (p=0.019), about vector (p=0.009) or recorded seeing vectors at home (p=0.012). Units dealing with HIV patients from endemic areas of American trypanosomiasis should implement CD screening protocols. Interviews of patients coming from endemic areas should include CD epidemiological questions.

Predictors of Subclinical Inflammatory Obesity: Plasma Levels of Leptin, Very Low-Density Lipoprotein Cholesterol and CD14 Expression of CD16+ Monocytes

PubMed Central

Leite, Fernanda; Leite, Ângela; Santos, Ana; Lima, Margarida; Barbosa, Joselina; Cosentino, Marco; Ribeiro, Laura

2017-01-01

Objective Predictors of subclinical inflammatory obesity (SIO) can be important tools for early therapeutic interventions in obesity-related comorbidities. Waist circumference (WC) and BMI have different SIO sensitivity. We aimed to i) identify SIO predictors and ii) investigate whether CD16+ monocytes are associated with BMI- (generally) or WC-defined (centrally) obesity. Methods Anthropometric and metabolic/endocrine (namely catecholamines, adrenaline and noradrenaline) parameters were evaluated, and CD16+ monocytes were studied by flow cytometry in the peripheral blood from 63 blood donors, and compared and correlated to each other. Multiple linear regression analysis was performed to identify variables that best predict SIO. Results CD16+ monocyte counts were similar in BMI and WC groups. CD16+ monocytes from centrally obese (CO) showed a more inflammatory pattern, as compared to non-CO subjects. WC was sensitive to lipidemia and, in CO subjects, lipidemia was associated with a more inflammatory phenotype of CD16+ monocytes. These differences were not noticed between BMI groups. Adrenaline was correlated with CD16+ monocyte expansion with a lower inflammatory pattern. Leptin, very low-density lipoprotein cholesterol (VLDL-C), and CD14 expression of CD16+ monocytes were found to be CO predictors. Conclusions WC-, but not BMI-defined obesity, was associated with a more inflammatory pattern of CD16+ monocytes, without monocyte expansion, suggesting that a monocyte maturation process rather than an independent arise of CD16+ monocytes occurs in CO. Thus, in a population with low cardiovascular risk, leptin, VLDL-C, and CD14 expression of CD16+ monocytes predict CO, constituting a putative tool for screening of SIO. PMID:28738359

Screening NK-, B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome.

PubMed

Curriu, Marta; Carrillo, Jorge; Massanella, Marta; Rigau, Josepa; Alegre, José; Puig, Jordi; Garcia-Quintana, Ana M; Castro-Marrero, Jesus; Negredo, Eugènia; Clotet, Bonaventura; Cabrera, Cecilia; Blanco, Julià

2013-03-20

Chronic Fatigue Syndrome (CFS) is a debilitating neuro-immune disorder of unknown etiology diagnosed by an array of clinical manifestations. Although several immunological abnormalities have been described in CFS, their heterogeneity has limited diagnostic applicability. Immunological features of CFS were screened in 22 CFS diagnosed individuals fulfilling Fukuda criteria and 30 control healthy individuals. Peripheral blood T, B and NK cell function and phenotype were analyzed by flow cytometry in both groups. CFS diagnosed individuals showed similar absolute numbers of T, B and NK cells, with minor differences in the percentage of CD4+ and CD8+ T cells. B cells showed similar subset frequencies and proliferative responses between groups. Conversely, significant differences were observed in T cell subsets. CFS individuals showed increased levels of T regulatory cells (CD25+/FOXP3+) CD4 T cells, and lower proliferative responses in vitro and in vivo. Moreover, CD8 T cells from the CFS group showed significantly lower activation and frequency of effector memory cells. No clear signs of T-cell immunosenescence were observed. NK cells from CFS individuals displayed higher expression of NKp46 and CD69 but lower expression of CD25 in all NK subsets defined. Overall, T cell and NK cell features clearly clustered CFS individuals. Our findings suggest that alterations in T-cell phenotype and proliferative response along with the specific signature of NK cell phenotype may be useful to identify CFS individuals. The striking down modulation of T cell mediated immunity may help to understand intercurrent viral infections in CFS.

Screening NK-, B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome

PubMed Central

2013-01-01

Background Chronic Fatigue Syndrome (CFS) is a debilitating neuro-immune disorder of unknown etiology diagnosed by an array of clinical manifestations. Although several immunological abnormalities have been described in CFS, their heterogeneity has limited diagnostic applicability. Methods Immunological features of CFS were screened in 22 CFS diagnosed individuals fulfilling Fukuda criteria and 30 control healthy individuals. Peripheral blood T, B and NK cell function and phenotype were analyzed by flow cytometry in both groups. Results CFS diagnosed individuals showed similar absolute numbers of T, B and NK cells, with minor differences in the percentage of CD4+ and CD8+ T cells. B cells showed similar subset frequencies and proliferative responses between groups. Conversely, significant differences were observed in T cell subsets. CFS individuals showed increased levels of T regulatory cells (CD25+/FOXP3+) CD4 T cells, and lower proliferative responses in vitro and in vivo. Moreover, CD8 T cells from the CFS group showed significantly lower activation and frequency of effector memory cells. No clear signs of T-cell immunosenescence were observed. NK cells from CFS individuals displayed higher expression of NKp46 and CD69 but lower expression of CD25 in all NK subsets defined. Overall, T cell and NK cell features clearly clustered CFS individuals. Conclusions Our findings suggest that alterations in T-cell phenotype and proliferative response along with the specific signature of NK cell phenotype may be useful to identify CFS individuals. The striking down modulation of T cell mediated immunity may help to understand intercurrent viral infections in CFS. PMID:23514202

Geographic clustering of elevated blood heavy metal levels in pregnant women.

PubMed

King, Katherine E; Darrah, Thomas H; Money, Eric; Meentemeyer, Ross; Maguire, Rachel L; Nye, Monica D; Michener, Lloyd; Murtha, Amy P; Jirtle, Randy; Murphy, Susan K; Mendez, Michelle A; Robarge, Wayne; Vengosh, Avner; Hoyo, Cathrine

2015-10-09

Cadmium (Cd), lead (Pb), mercury (Hg), and arsenic (As) exposure is ubiquitous and has been associated with higher risk of growth restriction and cardiometabolic and neurodevelopmental disorders. However, cost-efficient strategies to identify at-risk populations and potential sources of exposure to inform mitigation efforts are limited. The objective of this study was to describe the spatial distribution and identify factors associated with Cd, Pb, Hg, and As concentrations in peripheral blood of pregnant women. Heavy metals were measured in whole peripheral blood of 310 pregnant women obtained at gestational age ~12 weeks. Prenatal residential addresses were geocoded and geospatial analysis (Getis-Ord Gi* statistics) was used to determine if elevated blood concentrations were geographically clustered. Logistic regression models were used to identify factors associated with elevated blood metal levels and cluster membership. Geospatial clusters for Cd and Pb were identified with high confidence (p-value for Gi* statistic <0.01). The Cd and Pb clusters comprised 10.5 and 9.2 % of Durham County residents, respectively. Medians and interquartile ranges of blood concentrations (μg/dL) for all participants were Cd 0.02 (0.01-0.04), Hg 0.03 (0.01-0.07), Pb 0.34 (0.16-0.83), and As 0.04 (0.04-0.05). In the Cd cluster, medians and interquartile ranges of blood concentrations (μg/dL) were Cd 0.06 (0.02-0.16), Hg 0.02 (0.00-0.05), Pb 0.54 (0.23-1.23), and As 0.05 (0.04-0.05). In the Pb cluster, medians and interquartile ranges of blood concentrations (μg/dL) were Cd 0.03 (0.02-0.15), Hg 0.01 (0.01-0.05), Pb 0.39 (0.24-0.74), and As 0.04 (0.04-0.05). Co-exposure with Pb and Cd was also clustered, the p-values for the Gi* statistic for Pb and Cd was <0.01. Cluster membership was associated with lower education levels and higher pre-pregnancy BMI. Our data support that elevated blood concentrations of Cd and Pb are spatially clustered in this urban environment compared to the surrounding areas. Spatial analysis of metals concentrations in peripheral blood or urine obtained routinely during prenatal care can be useful in surveillance of heavy metal exposure.

Controlling congenital and paediatric chagas disease through a community health approach with active surveillance and promotion of paediatric awareness.

PubMed

Soriano-Arandes, Antoni; Basile, Luca; Ouaarab, Hakima; Clavería, Isabel; Gómez i Prat, Jordi; Cabezos, Juan; Ciruela, Pilar; Albajar-Viñas, Pedro; Jané, Mireia

2014-11-21

Chagas disease (CD) is endemic in countries of continental Latin America. Congenital transmission is a major concern worldwide. In 2010, the Public Health Agency of Catalonia (ASPCAT) launched a screening protocol for Trypanosoma cruzi infection in pregnant women and their newborns. In 2012, ASPCAT detected appropriate follow-up of pregnant women but incomplete information about their offspring. The PROSICS community health team carried out active surveillance and community health action in target populations. These activities included active case searches, group awareness workshops and visualization campaigns as well as investigation of all lost children born from pregnant women with CD and their families. Overall, 42/179 (23.5%) cases were included in the study: 35/42 (83.3%) children were born in Hospitalet de Llobregat (Catalonia, Spain); 4/42 (16.7%) were born in Latin America; two were miscarried and one was stillborn. The mean age of pregnant women was 31.3 years (SD 5.52; range: 21-44): 90.5% were Bolivian, of whom 74% were diagnosed with CD during pregnancy. Of the 35 newborns, 31 were recovered by community health action; 12/31 were correctly controlled at Hospitalet de Llobregat and 19/31 were controlled at a primary health centre. Of these 19 (73.7%) cases, 14 were not tested for CD by family paediatricians and were recovered by the PROSICS community health team. Finally, two (6.9%) of the 29 newborns tested with serology were positive. It is essential to implement active surveillance, education and information activities at paediatric primary care and community levels to avoid the loss of CD-infected mothers and their newborns. Training sessions addressed to paediatricians and other involved health professionals would consolidate surveillance and care reference circuits, improving the control of congenital CD.

Identification and HLA-tetramer-validation of human CD4+ and CD8+ T cell responses against HCMV proteins IE1 and IE2.

PubMed

Braendstrup, Peter; Mortensen, Bo Kok; Justesen, Sune; Osterby, Thomas; Rasmussen, Michael; Hansen, Andreas Martin; Christiansen, Claus Bohn; Hansen, Morten Bagge; Nielsen, Morten; Vindeløv, Lars; Buus, Søren; Stryhn, Anette

2014-01-01

Human cytomegalovirus (HCMV) is an important human pathogen. It is a leading cause of congenital infection and a leading infectious threat to recipients of solid organ transplants as well as of allogeneic hematopoietic cell transplants. Moreover, it has recently been suggested that HCMV may promote tumor development. Both CD4+ and CD8+ T cell responses are important for long-term control of the virus, and adoptive transfer of HCMV-specific T cells has led to protection from reactivation and HCMV disease. Identification of HCMV-specific T cell epitopes has primarily focused on CD8+ T cell responses against the pp65 phosphoprotein. In this study, we have focused on CD4+ and CD8+ T cell responses against the immediate early 1 and 2 proteins (IE1 and IE2). Using overlapping peptides spanning the entire IE1 and IE2 sequences, peripheral blood mononuclear cells from 16 healthy, HLA-typed, donors were screened by ex vivo IFN-γ ELISpot and in vitro intracellular cytokine secretion assays. The specificities of CD4+ and CD8+ T cell responses were identified and validated by HLA class II and I tetramers, respectively. Eighty-one CD4+ and 44 CD8+ T cell responses were identified representing at least seven different CD4 epitopes and 14 CD8 epitopes restricted by seven and 11 different HLA class II and I molecules, respectively, in total covering 91 and 98% of the Caucasian population, respectively. Presented in the context of several different HLA class II molecules, two epitope areas in IE1 and IE2 were recognized in about half of the analyzed donors. These data may be used to design a versatile anti-HCMV vaccine and/or immunotherapy strategy.

Identification and HLA-Tetramer-Validation of Human CD4+ and CD8+ T Cell Responses against HCMV Proteins IE1 and IE2

PubMed Central

Braendstrup, Peter; Mortensen, Bo Kok; Justesen, Sune; Østerby, Thomas; Rasmussen, Michael; Hansen, Andreas Martin; Christiansen, Claus Bohn; Hansen, Morten Bagge; Nielsen, Morten; Vindeløv, Lars; Buus, Søren; Stryhn, Anette

2014-01-01

Human cytomegalovirus (HCMV) is an important human pathogen. It is a leading cause of congenital infection and a leading infectious threat to recipients of solid organ transplants as well as of allogeneic hematopoietic cell transplants. Moreover, it has recently been suggested that HCMV may promote tumor development. Both CD4+ and CD8+ T cell responses are important for long-term control of the virus, and adoptive transfer of HCMV-specific T cells has led to protection from reactivation and HCMV disease. Identification of HCMV-specific T cell epitopes has primarily focused on CD8+ T cell responses against the pp65 phosphoprotein. In this study, we have focused on CD4+ and CD8+ T cell responses against the immediate early 1 and 2 proteins (IE1 and IE2). Using overlapping peptides spanning the entire IE1 and IE2 sequences, peripheral blood mononuclear cells from 16 healthy, HLA-typed, donors were screened by ex vivo IFN-γ ELISpot and in vitro intracellular cytokine secretion assays. The specificities of CD4+ and CD8+ T cell responses were identified and validated by HLA class II and I tetramers, respectively. Eighty-one CD4+ and 44 CD8+ T cell responses were identified representing at least seven different CD4 epitopes and 14 CD8 epitopes restricted by seven and 11 different HLA class II and I molecules, respectively, in total covering 91 and 98% of the Caucasian population, respectively. Presented in the context of several different HLA class II molecules, two epitope areas in IE1 and IE2 were recognized in about half of the analyzed donors. These data may be used to design a versatile anti-HCMV vaccine and/or immunotherapy strategy. PMID:24760079

HLA-A02:01-restricted epitopes identified from the herpes simplex virus tegument protein VP11/12 preferentially recall polyfunctional effector memory CD8+ T cells from seropositive asymptomatic individuals and protect humanized HLA-A*02:01 transgenic mice against ocular herpes.

PubMed

Srivastava, Ruchi; Khan, Arif A; Spencer, Doran; Vahed, Hawa; Lopes, Patricia P; Thai, Nhi Thi Uyen; Wang, Christine; Pham, Thanh T; Huang, Jiawei; Scarfone, Vanessa M; Nesburn, Anthony B; Wechsler, Steven L; BenMohamed, Lbachir

2015-03-01

The HSV type 1 tegument virion phosphoprotein (VP) 11/12 (VP11/12) is a major Ag targeted by CD8(+) T cells from HSV-seropositive individuals. However, whether and which VP11/12 epitope-specific CD8(+) T cells play a role in the "natural" protection seen in seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease) remain to be determined. In this study, we used multiple prediction computer-assisted algorithms to identify 10 potential HLA-A*02:01-restricted CD8(+) T cell epitopes from the 718-aa sequence of VP11/12. Three of 10 epitopes exhibited high-to-moderate binding affinity to HLA-A*02:01 molecules. In 10 sequentially studied HLA-A*02:01-positive and HSV-1-seropositive ASYMP individuals, the most frequent, robust, and polyfunctional effector CD8(+) T cell responses, as assessed by a combination of tetramer frequency, granzyme B, granzyme K, perforin, CD107(a/b) cytotoxic degranulation, IFN-γ, and multiplex cytokines assays, were predominantly directed against three epitopes: VP11/1266-74, VP11/12220-228, and VP11/12702-710. Interestingly, ASYMP individuals had a significantly higher proportion of CD45RA(low)CCR7(low)CD44(high)CD62L(low)CD27(low)CD28(low)CD8(+) effector memory CD8(+) T cells (TEMs) specific to the three epitopes, compared with symptomatic individuals (with a history of numerous episodes of recurrent ocular herpetic disease). Moreover, immunization of HLA-A*02:01 transgenic mice with the three ASYMP CD8(+) TEM cell epitopes induced robust and polyfunctional epitope-specific CD8(+) TEM cells that were associated with a strong protective immunity against ocular herpes infection and disease. Our findings outline phenotypic and functional features of protective HSV-specific CD8(+) T cells that should guide the development of an effective T cell-based herpes vaccine. Copyright © 2015 by The American Association of Immunologists, Inc.

Identification of a unique hepatocellular carcinoma line, Li-7, with CD13(+) cancer stem cells hierarchy and population change upon its differentiation during culture and effects of sorafenib.

PubMed

Yamada, Takeshi; Abei, Masato; Danjoh, Inaho; Shirota, Ryoko; Yamashita, Taro; Hyodo, Ichinosuke; Nakamura, Yukio

2015-04-11

Cancer stem cell (CSC) research has highlighted the necessity of developing drugs targeting CSCs. We investigated a hepatocellular carcinoma (HCC) cell line that not only has CSC hierarchy but also shows phenotypic changes (population changes) upon differentiation of CSC during culture and can be used for screening drugs targeting CSC. Based on a hypothesis that the CSC proportion should decrease upon its differentiation into progenitors (population change), we tested HCC cell lines (HuH-7, Li-7, PLC/PRF/5, HLF, HLE) before and after 2 months culture for several markers (CD13, EpCAM, CD133, CD44, CD90, CD24, CD166). Tumorigenicity was tested using nude mice. To evaluate the CSC hierarchy, we investigated reconstructivity, proliferation, ALDH activity, spheroid formation, chemosensitivity and microarray analysis of the cell populations sorted by FACS. Only Li-7 cells showed a population change during culture: the proportion of CD13 positive cells decreased, while that of CD166 positive cells increased. The high tumorigenicity of the Li-7 was lost after the population change. CD13(+)/CD166(-) cells showed slow growth and reconstructed the bulk Li-7 populations composed of CD13(+)/CD166(-), CD13(-)/CD166(-) and CD13(-)/CD166(+) fractions, whereas CD13(-)/CD166(+) cells showed rapid growth but could not reproduce any other population. CD13(+)/CD166(-) cells showed high ALDH activity, spheroid forming ability and resistance to 5-fluorouracil. Microarray analysis demonstrated higher expression of stemness-related genes in CD166(-) than CD166(+) fraction. These results indicated a hierarchy in Li-7 cells, in which CD13(+)/CD166(-) and CD13(-)/CD166(+) cells serve as slow growing CSCs and rapid growing progenitors, respectively. Sorafenib selectively targeted the CD166(-) fraction, including CD13(+) CSCs, which exhibited higher mRNA expression for FGF3 and FGF4, candidate biomarkers for sorafenib. 5-fluorouracil followed by sorafenib inhibited the growth of bulk Li-7 cells more effectively than the reverse sequence or either alone. We identified a unique HCC line, Li-7, which not only shows heterogeneity for a CD13(+) CSC hierarchy, but also undergoes a "population change" upon CSC differentiation. Sorafenib targeted the CSC in vitro, supporting the use of this model for screening drugs targeting the CSC. This type of "heterogeneous, unstable" cell line may prove more useful in the CSC era than conventional "homogeneous, stable" cell lines.

The CD4+/CD8+ Ratio in Pulmonary Tuberculosis: Systematic and Meta-Analysis Article.

PubMed

Yin, Yongmei; Qin, Jie; Dai, Yaping; Zeng, Fanwei; Pei, Hao; Wang, Jun

2015-02-01

The ratio of CD4+/CD8+ has been used as a clinically index to evaluate patients' immunity. Numerous researchers have studied CD4+/CD8+ ratio in pulmonary tuberculosis (PTB) patients. However, the change of CD4+/CD8+ ratio remains controversial. We present a meta-analysis of 15 case-control studies to identify the change of CD4+/CD8+ ratio in PTB patients. We assessed heterogeneity of effect estimates within each group using I(2) test. Subgroup analysis was performed to explore the potential source of heterogeneity. To investigate further the potential publication bias, we visually examined the funnel plots. For robustness of results, we performed sensitivity analysis by removing studies. Data entry and analyses were carried out with RevMan 5.2 (The Nordic Cochrane Centre). Twelve peripheral blood studies were categorized into two subgroups. Eight studies presented a significant decrease of CD4+/CD8+ ratio in PTB cases compared to healthy subjects (SMD: -0.45; 95% CI -0.65--0.25; I(2) = 7%). Other four studies researched on the newly diagnosed patients presented a more seriously and significantly decrease (SMD: -2.17; 95% CI -2.61--1.74; I(2) = 37%). The pooled analysis of bronchoalveolar lavage fluid (BALF) studies showed a significant increase of CD4+/CD8+ ratio using Flow Cytometry (FCM) (SMD: 4.75; 95% CI 3.44-6.05; I(2) =0%). The present meta-analysis indicated that there was a synthetic evidence for the reduced CD4+/CD8+ ratio in peripheral blood of PTB patients, especially newly diagnosed cases. However, the CD4+/CD8+ ratio in BALF was increased using method of FCM.

EndoU is a novel regulator of AICD during peripheral B cell selection

PubMed Central

Poe, Jonathan C.; Kountikov, Evgueni I.; Lykken, Jacquelyn M.; Natarajan, Abirami; Marchuk, Douglas A.

2014-01-01

Balanced transmembrane signals maintain a competent peripheral B cell pool limited in self-reactive B cells that may produce pathogenic autoantibodies. To identify molecules regulating peripheral B cell survival and tolerance to self-antigens (Ags), a gene modifier screen was performed with B cells from CD22-deficient C57BL/6 (CD22−/−[B6]) mice that undergo activation-induced cell death (AICD) and fail to up-regulate c-Myc expression after B cell Ag receptor ligation. Likewise, lysozyme auto-Ag–specific B cells in IgTg hen egg lysozyme (HEL) transgenic mice inhabit the spleen but undergo AICD after auto-Ag encounter. This gene modifier screen identified EndoU, a single-stranded RNA-binding protein of ancient origin, as a major regulator of B cell survival in both models. EndoU gene disruption prevents AICD and normalizes c-Myc expression. These findings reveal that EndoU is a critical regulator of an unexpected and novel RNA-dependent pathway controlling peripheral B cell survival and Ag responsiveness that may contribute to peripheral B cell tolerance. PMID:24344237

EndoU is a novel regulator of AICD during peripheral B cell selection.

PubMed

Poe, Jonathan C; Kountikov, Evgueni I; Lykken, Jacquelyn M; Natarajan, Abirami; Marchuk, Douglas A; Tedder, Thomas F

2014-01-13

Balanced transmembrane signals maintain a competent peripheral B cell pool limited in self-reactive B cells that may produce pathogenic autoantibodies. To identify molecules regulating peripheral B cell survival and tolerance to self-antigens (Ags), a gene modifier screen was performed with B cells from CD22-deficient C57BL/6 (CD22(-/-[B6])) mice that undergo activation-induced cell death (AICD) and fail to up-regulate c-Myc expression after B cell Ag receptor ligation. Likewise, lysozyme auto-Ag-specific B cells in Ig(Tg) hen egg lysozyme (HEL) transgenic mice inhabit the spleen but undergo AICD after auto-Ag encounter. This gene modifier screen identified EndoU, a single-stranded RNA-binding protein of ancient origin, as a major regulator of B cell survival in both models. EndoU gene disruption prevents AICD and normalizes c-Myc expression. These findings reveal that EndoU is a critical regulator of an unexpected and novel RNA-dependent pathway controlling peripheral B cell survival and Ag responsiveness that may contribute to peripheral B cell tolerance.

CD86 expression as a surrogate cellular biomarker for pharmacological inhibition of the histone demethylase lysine-specific demethylase 1.

PubMed

Lynch, James T; Cockerill, Mark J; Hitchin, James R; Wiseman, Daniel H; Somervaille, Tim C P

2013-11-01

There is a lack of rapid cell-based assays that read out enzymatic inhibition of the histone demethylase LSD1 (lysine-specific demethylase 1). Through transcriptome analysis of human acute myeloid leukemia THP1 cells treated with a tranylcypromine-derivative inhibitor of LSD1 active in the low nanomolar range, we identified the cell surface marker CD86 as a sensitive surrogate biomarker of LSD1 inhibition. Within 24h of enzyme inhibition, there was substantial and dose-dependent up-regulation of CD86 expression, as detected by quantitative polymerase chain reaction, flow cytometry, and enzyme-linked immunosorbent assay. Thus, the use of CD86 expression may facilitate screening of compounds with putative LSD1 inhibitory activities in cellular assays. Copyright © 2013 Elsevier Inc. All rights reserved.

Genome-wide expression profiling analysis to identify key genes in the anti-HIV mechanism of CD4+ and CD8+ T cells.

PubMed

Gao, Lijie; Wang, Yunqi; Li, Yi; Dong, Ya; Yang, Aimin; Zhang, Jie; Li, Fengying; Zhang, Rongqiang

2018-07-01

Comprehensive bioinformatics analyses were performed to explore the key biomarkers in response to HIV infection of CD4 + and CD8 + T cells. The numbers of CD4 + and CD8 + T cells of HIV infected individuals were analyzed and the GEO database (GSE6740) was screened for differentially expressed genes (DEGs) in HIV infected CD4 + and CD8 + T cells. Gene Ontology enrichment, KEGG pathway analyses, and protein-protein interaction (PPI) network were performed to identify the key pathway and core proteins in anti-HIV virus process of CD4 + and CD8 + T cells. Finally, we analyzed the expressions of key proteins in HIV-infected T cells (GSE6740 dataset) and peripheral blood mononuclear cells(PBMCs) (GSE511 dataset). 1) CD4 + T cells counts and ratio of CD4 + /CD8 + T cells decreased while CD8 + T cells counts increased in HIV positive individuals; 2) 517 DEGs were found in HIV infected CD4 + and CD8 + T cells at acute and chronic stage with the criterial of P-value <0.05 and fold change (FC) ≥2; 3) In acute HIV infection, type 1 interferon (IFN-1) pathway might played a critical role in response to HIV infection of T cells. The main biological processes of the DEGs were response to virus and defense response to virus. At chronic stage, ISG15 protein, in conjunction with IFN-1 pathway might play key roles in anti-HIV responses of CD4 + T cells; and 4) The expression of ISG15 increased in both T cells and PBMCs after HIV infection. Gene expression profile of CD4 + and CD8 + T cells changed significantly in HIV infection, in which ISG15 gene may play a central role in activating the natural antiviral process of immune cells. © 2018 Wiley Periodicals, Inc.

Serum Levels of Migration Inhibitory Factor (MIF) and In Situ Expression of MIF and Its Receptor CD74 in Lepromatous Leprosy Patients: A Preliminary Report

PubMed Central

Martinez-Guzman, Marco Alonso; Alvarado-Navarro, Anabell; Delgado-Rizo, Vidal; Garcia-Orozco, Alejandra; Mayorga-Rodríguez, Jorge Arturo; Pereira-Suarez, Ana Laura; Fafutis-Morris, Mary

2018-01-01

Leprosy is a chronic disease caused by Mycobacterium leprae that affects the skin and peripheral nerves. It may present as one of two distinct poles: the self-limiting tuberculoid leprosy and the highly infectious lepromatous leprosy (LL) characterized by M. leprae-specific absence of cellular immune response. The pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) enhance the bactericide activities of macrophages after interaction with its receptor, CD74. Importantly, MIF also possesses chemoattractant properties, and it is a key factor in situ for the activation of macrophages and in blood to promote leukocytes migration. MIF-mediated activation of macrophages is a key process for the elimination of pathogens such as Mycobacterium tuberculosis; however, its participation for the clearance of M. leprae is unclear. The aim of this study was to evaluate the serum levels of MIF as well as MIF and CD74 expression in skin lesions of LL and compare it with healthy skin (HSk) taken from subjects attending to dermatological consult. Samples of serum and skin biopsies were taken from 39 LL patients and compared with 36 serum samples of healthy subjects (HS) and 10 biopsies of HSk. Serum samples were analyzed by ELISA and skin biopsies by immunohistochemistry (IHC). IHC smears were observed in 12 100× microscopic fields, in which percentage of stained cells and staining intensity were evaluated. Both variables were used to calculate a semi-quantitative expression score that ranged from 0 to 3+. We found no differences in MIF levels between LL patients and HS in sera. In addition, MIF was observed in over 75% of cells with high intensity in the skin of patients and HSk. Although we found no differences in MIF expression between the groups, a CD74 score statistically higher was found in LL skin than HSk (p < 0.001); this was the result of a higher percentage of cells positive for CD74 (p < 0.001). As a conclusion, we found that CD74-positive cells are intensely recruited to the skin with LL lesions. In this manner, MIF signaling may be enhanced in the skin of LL patients due to increased expression of its receptor, but further studies are required. PMID:29487601

The Japanese Guidelines for Breast Cancer Screening.

PubMed

Hamashima, Chisato; Hamashima C, Chisato; Hattori, Masakazu; Honjo, Satoshi; Kasahara, Yoshio; Katayama, Takafumi; Nakai, Masahiro; Nakayama, Tomio; Morita, Takako; Ohta, Koji; Ohnuki, Koji; Sagawa, Motoyasu; Saito, Hiroshi; Sasaki, Seiju; Shimada, Tomoyuki; Sobue, Tomotaka; Suto, Akihiko

2016-05-01

The incidence of breast cancer has progressively increased, making it the leading cause of cancer deaths in Japan. Breast cancer accounts for 20.4% of all new cancers with a reported age-standardized rate of 63.6 per 100 000 women. The Japanese guidelines for breast cancer screening were developed based on a previously established method. The efficacies of mammography with and without clinical breast examination, clinical breast examination and ultrasonography with and without mammography were evaluated. Based on the balance of the benefits and harms, recommendations for population-based and opportunistic screenings were formulated. Five randomized controlled trials of mammographic screening without clinical breast examination were identified for mortality reduction from breast cancer. The overall relative risk for women aged 40-74 years was 0.75 (95% CI: 0.67-0.83). Three randomized controlled trials of mammographic screening with clinical breast examination served as eligible evidence for mortality reduction from breast cancer. The overall relative risk for women aged 40-64 years was 0.87 (95% confidence interval: 0.77-0.98). The major harms of mammographic screening were radiation exposure, false-positive cases and overdiagnosis. Although two case-control studies evaluating mortality reduction from breast cancer were found for clinical breast examination, there was no study assessing the effectiveness of ultrasonography for breast cancer screening. Mammographic screening without clinical breast examination for women aged 40-74 years and with clinical breast examination for women aged 40-64 years is recommended for population-based and opportunistic screenings. Clinical breast examination and ultrasonography are not recommended for population-based screening because of insufficient evidence regarding their effectiveness. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Photovoltaic and Impedance Spectroscopy Study of Screen-Printed TiO₂ Based CdS Quantum Dot Sensitized Solar Cells.

PubMed

Atif, M; Farooq, W A; Fatehmulla, Amanullah; Aslam, M; Ali, Syed Mansoor

2015-01-19

Cadmium sulphide (CdS) quantum dot sensitized solar cells (QDSSCs) based on screen-printed TiO₂ were assembled using a screen-printing technique. The CdS quantum dots (QDs) were grown by using the Successive Ionic Layer Adsorption and Reaction (SILAR) method. The optical properties were studied by UV-Vis absorbance spectroscopy. Photovoltaic characteristics and impedance spectroscopic measurements of CdS QDSSCs were carried out under air mass 1.5 illuminations. The experimental results of capacitance against voltage indicate a trend from positive to negative capacitance because of the injection of electrons from the Fluorine doped tin oxide (FTO) electrode into TiO₂.

HLA-A02:01-Restricted Epitopes Identified from the Herpes Simplex Virus Tegument Protein VP11/12 Preferentially Recall Polyfunctional Effector Memory CD8+ T Cells from Seropositive Asymptomatic Individuals and Protect “Humanized” HLA-A*02:01 Transgenic Mice Against Ocular Herpes

PubMed Central

Srivastava, Ruchi; Khan, Arif A.; Spencer, Doran; Vahed, Hawa; Lopes, Patricia P.; Thai, Nhi Thi Uyen; Wang, Christine; Pham, Thanh T.; Huang, Jiawei; Scarfone, Vanessa M.; Nesburn, Anthony B.; Wechsler, Steven L.; BenMohamed, Lbachir

2014-01-01

The Herpes Simplex Virus type 1 virion tegument phosphoprotein 11/12 (HSV-1 VP11/12) is a major antigen targeted by CD8+ T cells from HSV-seropositive individuals. However, whether and which VP11/12-epitope-specific CD8+ T cells play a role in the “natural” protection seen in seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease) remain to be determined. In this study, we used multiple prediction computer-assisted algorithms to identify 10 potential HLA-A*02:01-restricted CD8+ T cell epitopes from the 716 amino acids sequence of VP11/12. Three out of ten epitopes exhibited high to moderate binding affinity to HLA-A*02:01 molecules. In ten sequentially studied HLA-A*02:01 positive and HSV-1-seropositive ASYMP individuals, the most frequent, robust and polyfunctional effector CD8+ T-cell responses, as assessed by a combination of tetramer frequency, granzyme B, granzyme K, perforin, CD107a/b cytotoxic degranulation, IFN-γ and multiplex cytokines assays, were predominantly directed against three epitopes: VP11/1266–74, VP11/12220–228 and VP11/12702–710. Interestingly, ASYMP individuals had significantly higher proportion of CD45RAlowCCR7lowCD44highCD62LlowCD27lowCD28lowCD8+ effector memory T cells (TEM) specific to the three epitopes, compared to symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent ocular herpetic disease). Moreover, immunization of HLA-A*02:01 transgenic mice with the three ASYMP CD8+ TEM cell epitopes induced robust and polyfunctional epitope-specific CD8+ TEM cells that were associated with a strong protective immunity against ocular herpes infection and disease. Our findings outline phenotypic and functional features of protective HSV-specific CD8+ T cells that should guide the development of an effective T-cell-based herpes vaccine. PMID:25617474

A comprehensive screen for SNP associations on chromosome region 5q31-33 in Swedish/Norwegian celiac disease families.

PubMed

Amundsen, Silja Svanstrøm; Adamovic, Svetlana; Hellqvist, Asa; Nilsson, Staffan; Gudjónsdóttir, Audur H; Ascher, Henry; Ek, Johan; Larsson, Kristina; Wahlström, Jan; Lie, Benedicte A; Sollid, Ludvig M; Naluai, Asa Torinsson

2007-09-01

Celiac disease (CD) is a gluten-induced enteropathy, which results from the interplay between environmental and genetic factors. There is a strong human leukocyte antigen (HLA) association with the disease, and HLA-DQ alleles represent a major genetic risk factor. In addition to HLA-DQ, non-HLA genes appear to be crucial for CD development. Chromosomal region 5q31-33 has demonstrated linkage with CD in several genome-wide studies, including in our Swedish/Norwegian cohort. In a European meta-analysis 5q31-33 was the only region that reached a genome-wide level of significance except for the HLA region. To identify the genetic variant(s) responsible for this linkage signal, we performed a comprehensive single nucleotide polymorphism (SNP) association screen in 97 Swedish/Norwegian multiplex families who demonstrate linkage to the region. We selected tag SNPs from a 16 Mb region representing the 95% confidence interval of the linkage peak. A total of 1,404 SNPs were used for the association analysis. We identified several regions with SNPs demonstrating moderate single- or multipoint associations. However, the isolated association signals appeared insufficient to account for the linkage signal seen in our cohort. Collective effects of multiple risk genes within the region, incomplete genetic coverage or effects related to copy number variation are possible explanations for our findings.

An enhancer located in a CpG-island 3' to the TCR/CD3-epsilon gene confers T lymphocyte-specificity to its promoter.

PubMed Central

Clevers, H; Lonberg, N; Dunlap, S; Lacy, E; Terhorst, C

1989-01-01

The gene encoding the CD3-epsilon chain of the T cell receptor (TCR/CD3) complex is uniquely transcribed in all T lymphocyte lineage cells. The human CD3-epsilon gene, when introduced into the mouse germ line, was expressed in correct tissue-specific fashion. The gene was then screened for T lymphocyte-specific cis-acting elements in transient chloramphenicol transferase assays. The promoter (-228 to +100) functioned irrespective of cell type. A 1225 bp enhancer with strict T cell-specificity was found in a DNase I hypersensitive site downstream of the last exon, 12 kb from the promoter. This site was present in T cells only. The CD3-epsilon enhancer did not display sequence similarity with the T cell-specific enhancer of CD3-delta, a related gene co-regulated with CD3-epsilon during intrathymic differentiation. The CD3-epsilon enhancer was unusual in that it constituted a CpG island, and was hypomethylated independent of tissue type. Two HTLV I-transformed T cell lines were identified in which the CD3-epsilon gene was not expressed, and in which the enhancer was inactive. Images PMID:2583122

A novel high-throughput screening format to identify inhibitors of secreted acid sphingomyelinase.

PubMed

Mintzer, Robert J; Appell, Kenneth C; Cole, Andrew; Johns, Anthony; Pagila, Rene; Polokoff, Mark A; Tabas, Ira; Snider, R Michael; Meurer-Ogden, Janet A

2005-04-01

Secreted extracellular acid sphingomyelinase (sASM) activity has been suggested to promote atherosclerosis by enhancing subendothelial aggregation and retention of low-density lipoprotein (LDL) with resultant foam cell formation. Compounds that inhibit sASM activity, at neutral pH, may prevent lipid retention and thus would be expected to be anti-atherosclerotic. With the goal of identifying novel compounds that inhibit sASM at pH 7.4, a high-throughput screen was performed. Initial screening was run using a modification of a proven system that measures the hydrolysis of radiolabeled sphingomyelin presented in detergent micelles in a 96-well format. Separation of the radiolabeled aqueous phosphorylcholine reaction product from uncleaved sphingomyelin lipid substrate was achieved by chloroform/methanol extraction. During the screening campaign, a novel extraction procedure was developed to eliminate the use of the hazardous organic reagents. This new procedure exploited the ability of uncleaved, radiolabeled lipid substrate to interact with hydrophobic phenyl-sepharose beads. A comparison of the organic-based and the bead-based extraction sASM screening assays revealed Z' factor values ranging from 0.7 to 0.95 for both formats. In addition, both assay formats led to the identification of sub- to low micromolar inhibitors of sASM at pH 7.4 with similar IC(50) values. Subsequent studies demonstrated that both methods were also adaptable to run in a 384-well format. In contrast to the results observed at neutral pH, however, only the organic extraction assay was capable of accurately measuring sASM activity at its pH optimum of 5.0. The advantages and disadvantages of both sASM assay formats are discussed.

Phosphorylation of deoxycytidine kinase on Ser-74: impact on kinetic properties and nucleoside analog activation in cancer cells.

PubMed

Amsailale, Rachid; Van Den Neste, Eric; Arts, Angélique; Starczewska, Eliza; Bontemps, Françoise; Smal, Caroline

2012-07-01

Deoxycytidine kinase (dCK) (EC 2.7.1.74) is a key enzyme in the activation of several therapeutic nucleoside analogs (NA). Its activity can be increased in vivo by Ser-74 phosphorylation, a property that could be used for enhancing NA activation and clinical efficacy. In line with this, studies with recombinant dCK showed that mimicking Ser-74 phosphorylation by a S74E mutation increases its activity toward pyrimidine analogs. However, purine analogs had not been investigated. Here, we show that the S74E mutation increased the k(cat) for cladribine (CdA) by 8- or 3-fold, depending on whether the phosphoryl donor was ATP or UTP, for clofarabine (CAFdA) by about 2-fold with both ATP and UTP, and for fludarabine (F-Ara-A) by 2-fold, but only with UTP. However, the catalytic efficiencies (k(cat)/Km) were not, or slightly, increased. The S74E mutation also sensitized dCK to feed-back inhibition by dCTP, regardless of the phosphoryl donor. Importantly, we did not observe an increase of endogenous dCK activity toward purine analogs after in vivo-induced increase of Ser-74 phosphorylation. Accordingly, treatment of CLL cells with aphidicolin, which enhances dCK activity through Ser-74 phosphorylation, did not modify the conversion of CdA or F-Ara-A into their active triphosphate form. Nevertheless, the same treatment enhanced activation of gemcitabine (dFdC) into dFdCTP in CLL as well as in HCT-116 cells and produced synergistic cytotoxicity. We conclude that increasing phosphorylation of dCK on Ser-74 might constitute a valuable strategy to enhance the clinical efficacy of some NA, like dFdC, but not of CdA or F-Ara-A. Copyright © 2012 Elsevier Inc. All rights reserved.

Differential Susceptibility of Germ and Leydig Cells to Cadmium-Mediated Toxicity: Impact on Testis Structure, Adiponectin Levels, and Steroidogenesis

PubMed Central

Cupertino, Marli C.; Neves, Ana C.; Oliveira, Juraci A.

2017-01-01

This study investigated the relationship between germ and Leydig cell death, testosterone, and adiponectin levels in cadmium-mediated acute toxicity. Cadmium chloride was administered in a single dose to five groups of rats: G1 (0.9% NaCl) and G2 to G5 (0.67, 0.74, 0.86, and 1.1 mg Cd/kg). After 7 days, the animals were euthanized, and the testosterone and testes were analyzed. Dose-dependent Cd accumulation in the testes was identified. At 0.86 and 1.1 mg/kg, animals exhibited marked inflammatory infiltrate and disorganization of the seminiferous epithelium. While Leydig cells were morphologically resistant to Cd toxicity, massive germ cell death and DNA oxidation and fragmentation were observed. Although numerical density of Leydig cells was unchanged, testosterone levels were significantly impaired in animals exposed to 0.86 and 1.1 mg Cd/kg, occurring in parallel with the reduction in total adiponectins and the increase in high-molecular weight adiponectin levels. Our findings indicated that Leydig and germ cells exhibit differential microstructural resistance to Cd toxicity. While germ cells are a primary target of Cd-induced toxicity, Leydig cells remain resistant to death even when exposed to high doses of Cd. Despite morphological resistance, steroidogenesis was drastically impaired by Cd exposure, an event potentially related to the imbalance in adiponectin production. PMID:29422988

Elevated CD147 expression is associated with shorter overall survival in non-small cell lung cancer.

PubMed

Zhang, Xiaojun; Tian, Tian; Zhang, Xiaofeng; Liu, Changting; Fang, Xiangqun

2017-06-06

A number of studies have reported on the prognostic role of CD147 expression in non-small cell lung cancer (NSCLC); however, the results remain controversial. This study aims to investigate the impact of CD147 on the prognosis of NSCLC by means of a meta-analysis. A literature search was performed for relevant studies published before October 29, 2016. The hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated as effective measures. Sensitivity analysis and publication bias examination were also conducted. Ten eligible studies with a total of 1605 patients were included in this meta-analysis. CD147 overexpression was correlated with poor overall survival (OS) (HR=1.59, 95% CI=1.32-1.91, p<0.001). Elevated CD147 expression was associated with the presence of lymph node metastasis (OR=2.31, 95% CI=1.74-3.07, p<0.001) and advanced TNM stage (OR=3.03, 95% CI=1.24-7.39, p=0.015). However, no significant association between CD147 and sex, age, differentiation, or histology was found. No evidence of significant publication bias was identified. This meta-analysis revealed that overexpression of CD147 was associated with shorter OS, the presence of lymph node metastasis and advanced TNM stage in NSCLC. Therefore, CD147 could serve as a potential prognostic marker for NSCLC.

Elevated CD147 expression is associated with shorter overall survival in non-small cell lung cancer

PubMed Central

Zhang, Xiaojun; Tian, Tian; Zhang, Xiaofeng; Liu, Changting; Fang, Xiangqun

2017-01-01

A number of studies have reported on the prognostic role of CD147 expression in non-small cell lung cancer (NSCLC); however, the results remain controversial. This study aims to investigate the impact of CD147 on the prognosis of NSCLC by means of a meta-analysis. A literature search was performed for relevant studies published before October 29, 2016. The hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated as effective measures. Sensitivity analysis and publication bias examination were also conducted. Ten eligible studies with a total of 1605 patients were included in this meta-analysis. CD147 overexpression was correlated with poor overall survival (OS) (HR=1.59, 95% CI=1.32–1.91, p<0.001). Elevated CD147 expression was associated with the presence of lymph node metastasis (OR=2.31, 95% CI=1.74–3.07, p<0.001) and advanced TNM stage (OR=3.03, 95% CI=1.24–7.39, p=0.015). However, no significant association between CD147 and sex, age, differentiation, or histology was found. No evidence of significant publication bias was identified. This meta-analysis revealed that overexpression of CD147 was associated with shorter OS, the presence of lymph node metastasis and advanced TNM stage in NSCLC. Therefore, CD147 could serve as a potential prognostic marker for NSCLC. PMID:28445149

Virtual screening-driven repositioning of etoposide as CD44 antagonist in breast cancer cells

PubMed Central

Aguirre-Alvarado, Charmina; Segura-Cabrera, Aldo; Velázquez-Quesada, Inés; Hernández-Esquivel, Miguel A.; García-Pérez, Carlos A.; Guerrero-Rodríguez, Sandra L.; Ruiz, Angel J.; Rodríguez-Moreno, Andrea; Pérez-Tapia, Sonia M.; Velasco-Velázquez, Marco A.

2016-01-01

CD44 is a receptor for hyaluronan (HA) that promotes epithelial-to-mesenchymal transition (EMT), induces cancer stem cell (CSC) expansion, and favors metastasis. Thus, CD44 is a target for the development of antineoplastic agents. In order to repurpose drugs as CD44 antagonists, we performed consensus-docking studies using the HA-binding domain of CD44 and 11,421 molecules. Drugs that performed best in docking were examined in molecular dynamics simulations, identifying etoposide as a potential CD44 antagonist. Ligand competition and cell adhesion assays in MDA-MB-231 cells demonstrated that etoposide decreased cell binding to HA as effectively as a blocking antibody. Etoposide-treated MDA-MB-231 cells developed an epithelial morphology; increased their expression of E-cadherin; and reduced their levels of EMT-associated genes and cell migration. By gene expression analysis, etoposide reverted an EMT signature similarly to CD44 knockdown, whereas other topoisomerase II (TOP2) inhibitors did not. Moreover, etoposide decreased the proportion of CD44+/CD24− cells, lowered chemoresistance, and blocked mammosphere formation. Our data indicate that etoposide blocks CD44 activation, impairing key cellular functions that drive malignancy, thus rendering it a candidate for further translational studies and a potential lead compound in the development of new CD44 antagonists. PMID:27009862

Virtual screening-driven repositioning of etoposide as CD44 antagonist in breast cancer cells.

PubMed

Aguirre-Alvarado, Charmina; Segura-Cabrera, Aldo; Velázquez-Quesada, Inés; Hernández-Esquivel, Miguel A; García-Pérez, Carlos A; Guerrero-Rodríguez, Sandra L; Ruiz-Moreno, Angel J; Rodríguez-Moreno, Andrea; Pérez-Tapia, Sonia M; Velasco-Velázquez, Marco A

2016-04-26

CD44 is a receptor for hyaluronan (HA) that promotes epithelial-to-mesenchymal transition (EMT), induces cancer stem cell (CSC) expansion, and favors metastasis. Thus, CD44 is a target for the development of antineoplastic agents. In order to repurpose drugs as CD44 antagonists, we performed consensus-docking studies using the HA-binding domain of CD44 and 11,421 molecules. Drugs that performed best in docking were examined in molecular dynamics simulations, identifying etoposide as a potential CD44 antagonist. Ligand competition and cell adhesion assays in MDA-MB-231 cells demonstrated that etoposide decreased cell binding to HA as effectively as a blocking antibody. Etoposide-treated MDA-MB-231 cells developed an epithelial morphology; increased their expression of E-cadherin; and reduced their levels of EMT-associated genes and cell migration. By gene expression analysis, etoposide reverted an EMT signature similarly to CD44 knockdown, whereas other topoisomerase II (TOP2) inhibitors did not. Moreover, etoposide decreased the proportion of CD44+/CD24- cells, lowered chemoresistance, and blocked mammosphere formation. Our data indicate that etoposide blocks CD44 activation, impairing key cellular functions that drive malignancy, thus rendering it a candidate for further translational studies and a potential lead compound in the development of new CD44 antagonists.

In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target.

PubMed

Manguso, Robert T; Pope, Hans W; Zimmer, Margaret D; Brown, Flavian D; Yates, Kathleen B; Miller, Brian C; Collins, Natalie B; Bi, Kevin; LaFleur, Martin W; Juneja, Vikram R; Weiss, Sarah A; Lo, Jennifer; Fisher, David E; Miao, Diana; Van Allen, Eliezer; Root, David E; Sharpe, Arlene H; Doench, John G; Haining, W Nicholas

2017-07-27

Immunotherapy with PD-1 checkpoint blockade is effective in only a minority of patients with cancer, suggesting that additional treatment strategies are needed. Here we use a pooled in vivo genetic screening approach using CRISPR-Cas9 genome editing in transplantable tumours in mice treated with immunotherapy to discover previously undescribed immunotherapy targets. We tested 2,368 genes expressed by melanoma cells to identify those that synergize with or cause resistance to checkpoint blockade. We recovered the known immune evasion molecules PD-L1 and CD47, and confirmed that defects in interferon-γ signalling caused resistance to immunotherapy. Tumours were sensitized to immunotherapy by deletion of genes involved in several diverse pathways, including NF-κB signalling, antigen presentation and the unfolded protein response. In addition, deletion of the protein tyrosine phosphatase PTPN2 in tumour cells increased the efficacy of immunotherapy by enhancing interferon-γ-mediated effects on antigen presentation and growth suppression. In vivo genetic screens in tumour models can identify new immunotherapy targets in unanticipated pathways.

Validation of a Type 2 Diabetes Screening Tool in Rural Honduras

PubMed Central

Milton, Evan C.; Herman, William H.; Aiello, Allison E.; Danielson, Kris R.; Mendoza-Avelarez, Milton O.; Piette, John D.

2010-01-01

OBJECTIVE To validate a low-cost tool for identifying diabetic patients in rural areas of Latin America. RESEARCH DESIGN AND METHODS A regression equation incorporating postprandial time and a random plasma glucose was used to screen 800 adults in Honduras. Patients with a probability of diabetes of ≥20% were asked to return for a fasting plasma glucose (FPG). A random fifth of those with a screener-based probability of diabetes <20% were also asked to return for follow-up. The gold standard was an FPG ≥126 mg/dl. RESULTS The screener had very good test characteristics (area under the receiver operating characteristic curve = 0.89). Using the screening criterion of ≥0.42, the equation had a sensitivity of 74.1% and specificity of 97.2%. CONCLUSIONS This screener is a valid measure of diabetes risk in Honduras and could be used to identify diabetic patients in poor clinics in Latin America. PMID:19918008

Analysis of Exhaled Breath Volatile Organic Compounds in Inflammatory Bowel Disease: A Pilot Study.

PubMed

Hicks, Lucy C; Huang, Juzheng; Kumar, Sacheen; Powles, Sam T; Orchard, Timothy R; Hanna, George B; Williams, Horace R T

2015-09-01

Distinguishing between the inflammatory bowel diseases [IBD], Crohn's disease [CD] and ulcerative colitis [UC], is important for determining management and prognosis. Selected ion flow tube mass spectrometry [SIFT-MS] may be used to analyse volatile organic compounds [VOCs] in exhaled breath: these may be altered in disease states, and distinguishing breath VOC profiles can be identified. The aim of this pilot study was to identify, quantify, and analyse VOCs present in the breath of IBD patients and controls, potentially providing insights into disease pathogenesis and complementing current diagnostic algorithms. SIFT-MS breath profiling of 56 individuals [20 UC, 18 CD, and 18 healthy controls] was undertaken. Multivariate analysis included principal components analysis and partial least squares discriminant analysis with orthogonal signal correction [OSC-PLS-DA]. Receiver operating characteristic [ROC] analysis was performed for each comparative analysis using statistically significant VOCs. OSC-PLS-DA modelling was able to distinguish both CD and UC from healthy controls and from one other with good sensitivity and specificity. ROC analysis using combinations of statistically significant VOCs [dimethyl sulphide, hydrogen sulphide, hydrogen cyanide, ammonia, butanal, and nonanal] gave integrated areas under the curve of 0.86 [CD vs healthy controls], 0.74 [UC vs healthy controls], and 0.83 [CD vs UC]. Exhaled breath VOC profiling was able to distinguish IBD patients from controls, as well as to separate UC from CD, using both multivariate and univariate statistical techniques. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Screening and Identification of a Phage Display Derived Peptide That Specifically Binds to the CD44 Protein Region Encoded by Variable Exons.

PubMed

Zhang, Dan; Jia, Huan; Li, Weiming; Hou, Yingchun; Lu, Shaoying; He, Shuixiang

2016-01-01

CD44, especially the isoforms with variable exons (CD44v), is a promising biomarker for the detection of cancer. To develop a CD44v-specific probe, we screened a 7-mer phage peptide library against the CD44v3-v10 protein using an improved subtractive method. The consensus sequences with the highest frequency (designated CV-1) emerged after four rounds of panning. The binding affinity and specificity of the CV-1 phage and the synthesized peptide for the region of CD44 encoded by the variable exons were confirmed using enzyme-linked immunosorbent assay and competitive inhibition assays. Furthermore, the binding of the CV-1 probe to gastric cancer cells and tissues was validated using immunofluorescence and immunohistochemistry assays. CV-1 sensitively and specifically bound to CD44v on cancer cells and tissues. Thus, CV-1 has the potential to serve as a promising probe for cancer molecular imaging and target therapy. © 2015 Society for Laboratory Automation and Screening.

Depression and CD4 cell count among patients with HIV in a Nigerian University Teaching Hospital.

PubMed

Olisah, Victor Obiajulu; Adekeye, Oluwatosin; Sheikh, Taiwo Lateef

2015-01-01

Depression is common in people living with HIV/AIDS and there is some evidence that depressive symptoms may have adverse effects on immune functioning. The purpose of this study was to determine the prevalence of current depressive disorder in patients with HIV/AIDS and its association with CD4 cell count. A consecutive sample of 310 patients with HIV/AIDS attending Out-patient clinic in Ahmadu Bello University Teaching Hospital (A.B.U.T.H.), Zaria, Nigeria was assessed. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to screen for depressive symptoms, and the Schedule for Clinical Assessment in Neuropsychiatry (SCAN) was used to confirm the diagnosis of current depressive disorder. The CD4 cell counts of participants with depressive disorder were compared with those of participants without depressive disorder. Multiple regression analysis was conducted to identify socio-demographic and disease-related factors associated with depression. Among the 310 HIV-infected participants assessed for depression, 14.2% had current depressive disorder. Adjusting for age, gender, education, occupation, and marital status, patients with CD4 counts < 150 cells/μl were more likely to be depressed. Depression is common among HIV-infected persons in Nigeria and is associated with low CD4 cell counts. The screening and treatment of mental health problems such as depression should be considered an integral component of HIV care and support. © 2015, The Author(s).

The number of tumor infiltrating T-cell subsets in lymph nodes from patients with Hodgkin lymphoma is associated with the outcome after first line ABVD therapy.

PubMed

Alonso-Álvarez, Sara; Vidriales, Maria Belén; Caballero, Maria Dolores; Blanco, Oscar; Puig, Noemí; Martin, Alejandro; Peñarrubia, Maria Jesús; Zato, Esther; Galende, Josefina; Bárez, Abelardo; Alcoceba, Miguel; Orfão, Alberto; González, Marcos; García-Sanz, Ramón

2017-05-01

Prognostic factors in Hodgkin lymphoma (HL) still fail to accurately identify high-risk patients. Tumor microenvironment in HL is a current focus of research for risk definition but few studies have focused on infiltrating lymphocytes. Here, we analyzed the number of tumor infiltrating lymphocytes by flow cytometry in diagnostic biopsies from 96 HL homogeneously treated patients with ABVD with or without radiotherapy. Most lymph node cells were lymphocytes (90 ± 17), with a median T/B/NK distribution of 74%/26%/0.7%, and CD4 + T-cell predominance. The amount of CD19 + B cells, and NK cells did not show association with disease features. However, high numbers of CD8 + and CD4 + cells were associated with better and poorer outcomes, respectively. Patients with ≥15% cytotoxic CD8 + cells among the total cell population had a longer 10-year freedom from treatment failure (FFTF) (93% vs. 73%, p=.04). In turn, cases with ≥75% of CD4 + infiltrating cells showed a significantly decreased FFTF (73% vs. 96%, p=.021). Consequently, CD4/CD8 ratio ≥5 associated with a poorer 10-year FFTF (69.5% vs. 94%, p=.02). This deleterious effect was particularly prominent in advanced disease (n = 58, p=.01). In multivariate analysis, a CD4/CD8 ratio ≥5 was the only independent variable to predict for treatment failure (HR = 4.5, 95% confidence interval, 1.2-16.8). In conclusion, our study shows that high CD4 + and low CD8 + T-cells infiltrates of tumor specimens associate with poor prognosis in HL patients, and CD4/CD8 ratio might be potentially useful for tailoring therapy.

Fine Mapping and Functional Analysis of the Multiple Sclerosis Risk Gene CD6

PubMed Central

Swaminathan, Bhairavi; Cuapio, Angélica; Alloza, Iraide; Matesanz, Fuencisla; Alcina, Antonio; García-Barcina, Maria; Fedetz, Maria; Fernández, Óscar; Lucas, Miguel; Órpez, Teresa; Pinto-Medel, Mª Jesus; Otaegui, David; Olascoaga, Javier; Urcelay, Elena; Ortiz, Miguel A.; Arroyo, Rafael; Oksenberg, Jorge R.; Antigüedad, Alfredo; Tolosa, Eva; Vandenbroeck, Koen

2013-01-01

CD6 has recently been identified and validated as risk gene for multiple sclerosis (MS), based on the association of a single nucleotide polymorphism (SNP), rs17824933, located in intron 1. CD6 is a cell surface scavenger receptor involved in T-cell activation and proliferation, as well as in thymocyte differentiation. In this study, we performed a haptag SNP screen of the CD6 gene locus using a total of thirteen tagging SNPs, of which three were non-synonymous SNPs, and replicated the recently reported GWAS SNP rs650258 in a Spanish-Basque collection of 814 controls and 823 cases. Validation of the six most strongly associated SNPs was performed in an independent collection of 2265 MS patients and 2600 healthy controls. We identified association of haplotypes composed of two non-synonymous SNPs [rs11230563 (R225W) and rs2074225 (A257V)] in the 2nd SRCR domain with susceptibility to MS (P max(T) permutation = 1×10−4). The effect of these haplotypes on CD6 surface expression and cytokine secretion was also tested. The analysis showed significantly different CD6 expression patterns in the distinct cell subsets, i.e. – CD4+ naïve cells, P = 0.0001; CD8+ naïve cells, P<0.0001; CD4+ and CD8+ central memory cells, P = 0.01 and 0.05, respectively; and natural killer T (NKT) cells, P = 0.02; with the protective haplotype (RA) showing higher expression of CD6. However, no significant changes were observed in natural killer (NK) cells, effector memory and terminally differentiated effector memory T cells. Our findings reveal that this new MS-associated CD6 risk haplotype significantly modifies expression of CD6 on CD4+ and CD8+ T cells. PMID:23638056

[Remediation Pb, Cd contaminated soil in lead-zinc mining areas by hydroxyapatite and potassium chloride composites].

PubMed

Wang, Li; Li, Yong-Hua; Ji, Yan-Fang; Yang, Lin-Sheng; Li, Hai-Rong; Zhang, Xiu-Wu; Yu, Jiang-Ping

2011-07-01

The composite agents containing potassium chloride (KCl) and Hydroxyapatite (HA) were used to remediate the lead and cadmium contaminated soil in Fenghuang lead-zinc mining-smelting areas, Hunan province. The objective of this study was to identify and evaluate the influence of Cl- to the fixing efficiency of Pb and Cd by HA. Two types of contaminated soil (HF-1, HF-2) were chosen and forty treatments were set by five different Hydroxyapatite (HA) dosages and four different Cl- dosages. The toxicity characteristic leaching procedure (TCLP) was used to evaluate the results. It showed that HA could efficiently fix the Pb and Cd from TCLP form. The maximum Pb-fixing efficiency and Cd-fixing efficiency of two types of soil were 83.3%, 97.27% and 35.96%, 57.82% when the HA: Pb: KCl molar ratio was 8: 1: 2. Compared to the fixing efficiency without KCl, KCl at the KCl: Pb molar ratio of 2 improved Pb-fixing efficiency and Cd-fixing efficiency by 6.26%, 0.33% and 7.74%, 0.83% respectively when the HA: Pb molar ratio was 8. Generally, Cl- can improve the Pb/Cd-fixing efficiency in heavy metal contaminated soil by Hydroxyapatite.

Functional Proteomics to Identify Moderators of CD8+ T-Cell Function in Melanoma

DTIC Science & Technology

2013-09-01

could then be used to develop imaging agents that are targeted to the TILs. We used an M13 phage vector, which displays a pentavalent peptide as...of the identified transcript. To directly indentify inhibitory molecules, we have proposed to use phage - display expression libraries to perform...of TCD8. 3. To determine the ligands for molecules that can modulate the TCD8 functional state. Body: A. Phage Screen Summary Phage display

Evaluation of rapid progressors in HIV infection as an extreme phenotype.

PubMed

Olson, Ashley D; Guiguet, Marguerite; Zangerle, Robert; Gill, John; Perez-Hoyos, Santiago; Lodi, Sara; Ghosn, Jade; Dorrucci, Maria; Johnson, Anne; Sannes, Mette; Moreno, Santiago; Porter, Kholoud

2014-09-01

Rapid CD4 cell loss represents an HIV phenotype used to identify causal variants of accelerated disease progression. The optimal rate and threshold for identifying this extreme phenotype in recently infected individuals is unclear. Using a cohort of patients with known dates of HIV-1 seroconversion (SC), CASCADE (Concerted Action on SeroConversion on AIDS and Death in Europe), we identified proportions experiencing nadir CD4 cell levels within 1 year of SC, and assessed their mean AIDS-free survival time at 10-year follow-up and hazard of AIDS/death, compared with those whose CD4 remained >500 cells per cubic millimeter. Follow-up was censored at December 31, 1996 to avoid bias due to combination antiretroviral therapy initiation. Of 4876 individuals, 2.8%, 7.3%, and 24.9% experienced ≥1 CD4 <100, 200, and 350 cells per cubic millimeter, respectively, within 1 year of SC. Minimum CD4 levels of 30, 166, 231, and 506 cells per cubic millimeter were experienced during this period by 1%, 5%, 10%, and 50% of individuals, respectively. Mean (95% confidence interval) AIDS-free survival at 10 years follow-up was 2.9 (2.3 to 3.6), 5.5 (5.0 to 6.1), 6.7 (6.5 to 7.0), 7.4 (7.2 to 7.6), and 8.1 (7.9 to 8.3), for those with minimum counts ≤100, 100-200, 200-350, 350-500, >500 cells per cubic millimeter, respectively. Using counts of >500 cells per cubic millimeter as reference, the hazard ratios (95% confidence interval) of AIDS/death were 15.0 (11.9 to 18.9), 3.6 (2.9 to 4.5), 2.1 (1.8 to 2.4), and 1.5 (1.3 to 1.7), respectively. The hazard ratio increased to 37.5 (26.5 to 53.1) when a minimum CD4 count <100 was confirmed within 1 year of SC. At least 1 CD4 ≤100 cells per cubic millimeter within the first year of SC identifies a rare group of individuals at high risk of disease progression and could form the basis for defining the rapid progressor phenotype.

Screening for Cd-Safe Cultivars of Chinese Cabbage and a Preliminary Study on the Mechanisms of Cd Accumulation.

PubMed

Wang, Jingjie; Yu, Nan; Mu, Guangmao; Shinwari, Kamran I; Shen, Zhenguo; Zheng, Luqing

2017-04-07

With the rapid progress of industrialization, the effects of environmental contamination on plant toxicity, and subsequently on human health, is a growing concern. For example, the heavy metal pollution of soil such as that caused by cadmium (Cd) is a serious threat. Therefore, screening for pollution-safe edible plants is an essential approach for growing plants under heavy metal-contaminated soils. In the current study, 35 Chinese cabbage ( Brassica pekinensis L.) cultivars were selected with the aim of screening for Cd-safe cultivars (CSCs), analyzing their safety, and exploring the mechanism of Cd accumulation. Our field-culture experiments revealed that the Cd content in the edible parts of the cultivars were varied and were determined to possibly be CSCs. Hydroponics experiments were used to simulate six different degrees of soil contamination (high and low Cd concentrations) on possible CSCs. The results indicated a significant difference ( p < 0.05) in Cd concentration in the cultivars, and verified the safety of these possible CSCs. The analyses of the transport coefficient and expression levels showed that the differences in Cd accumulation among the Chinese cabbage cultivars were related to the expression of genes involved in absorption and transport rather than a root-to-shoot translocation limitation.

Screening for Cd-Safe Cultivars of Chinese Cabbage and a Preliminary Study on the Mechanisms of Cd Accumulation

PubMed Central

Wang, Jingjie; Yu, Nan; Mu, Guangmao; Shinwari, Kamran I.; Shen, Zhenguo; Zheng, Luqing

2017-01-01

With the rapid progress of industrialization, the effects of environmental contamination on plant toxicity, and subsequently on human health, is a growing concern. For example, the heavy metal pollution of soil such as that caused by cadmium (Cd) is a serious threat. Therefore, screening for pollution-safe edible plants is an essential approach for growing plants under heavy metal-contaminated soils. In the current study, 35 Chinese cabbage (Brassica pekinensis L.) cultivars were selected with the aim of screening for Cd-safe cultivars (CSCs), analyzing their safety, and exploring the mechanism of Cd accumulation. Our field-culture experiments revealed that the Cd content in the edible parts of the cultivars were varied and were determined to possibly be CSCs. Hydroponics experiments were used to simulate six different degrees of soil contamination (high and low Cd concentrations) on possible CSCs. The results indicated a significant difference (p < 0.05) in Cd concentration in the cultivars, and verified the safety of these possible CSCs. The analyses of the transport coefficient and expression levels showed that the differences in Cd accumulation among the Chinese cabbage cultivars were related to the expression of genes involved in absorption and transport rather than a root-to-shoot translocation limitation. PMID:28387709

CD47 is an adverse prognostic factor and a therapeutic target in gastric cancer

PubMed Central

Yoshida, Kazumichi; Tsujimoto, Hironori; Matsumura, Kouji; Kinoshita, Manabu; Takahata, Risa; Matsumoto, Yusuke; Hiraki, Shuichi; Ono, Satoshi; Seki, Shuhji; Yamamoto, Junji; Hase, Kazuo

2015-01-01

CD47 is an antiphagocytic molecule that acts via ligation to signal regulatory protein alpha on phagocytes; its enhanced expression and therapeutic targeting have recently been reported for several malignancies. However, CD47 expression in gastric cancer is not well documented. Immunohistochemical expression of CD47 in surgical specimens was investigated. Expression of CD47 and CD44, a known gastric cancer stem cell marker, were investigated in gastric cancer cell lines by flow cytometry. MKN45 and MKN74 gastric cancer cells were sorted by fluorescence-activated cell sorting according to CD44 and CD47 expression levels, and their in vitro proliferation, spheroid-forming capacity, and in vivo tumorigenicity were studied. In vitro phagocytosis of cancer cells by human macrophages in the presence of a CD47 blocking monoclonal antibody (B6H12) and the survival of immunodeficient mice intraperitoneally engrafted with MKN45 cells and B6H12 were compared to experiments using control antibodies. Immunohistochemistry of the clinical specimens indicated that CD47 was positive in 57 out of 115 cases, and its positivity was an independent adverse prognostic factor. Approximately 90% of the MKN45 and MKN74 cells expressed CD47 and CD44. CD47hi gastric cancer cells showed significantly higher proliferation and spheroid colony formation than CD47lo, and CD44hiCD47hi cells showed the highest proliferation in vitro and tumorigenicity in vivo. B6H12 significantly enhanced in vitro phagocytosis of cancer cells by human macrophages and prolonged the survival of intraperitoneal cancer dissemination in mice compared to control antibodies. In conclusion, CD47 is an adverse prognostic factor and promising therapeutic target in gastric cancer. PMID:26077800

Identifying Adolescents at Highly Elevated Risk for Suicidal Behavior in the Emergency Department

PubMed Central

Berona, Johnny; Czyz, Ewa; Horwitz, Adam G.; Gipson, Polly Y.

2015-01-01

Abstract Objective: The feasibility and concurrent validity of adolescent suicide risk screening in medical emergency departments (EDs) has been documented. The objectives of this short-term prospective study of adolescents who screened positive for suicide risk in the ED were: 1) to examine adolescents' rate of suicidal behavior during the 2 months following their ED visits and compare it with reported rates for psychiatric samples; and 2) to identify possible predictors of acute risk for suicidal behavior in this at-risk sample. Method: Participants were 81 adolescents, ages 14–19 years, seeking services for psychiatric and nonpsychiatric chief complaints, who screened positive for suicide risk because of recent suicidal ideation, a suicide attempt, and/or depression plus alcohol or substance misuse. A comprehensive assessment of suicidal behavior, using the Columbia-Suicide Severity Rating Scale, was conducted at baseline and 2 month follow-up. Results: Six adolescents (7.4%) reported a suicide attempt and 15 (18.5%) engaged in some type of suicidal behavior (actual, aborted, or interrupted suicide attempt; preparatory behavior) during the 2 months following their ED visit. These rates suggest that this screen identified a high-risk sample. Furthermore, adolescents who screened positive for suicidal ideation and/or attempt plus depression and alcohol/substance misuse were most likely to engage in future suicidal behavior (38.9%). Conclusions: In this study, use of a higher screen threshold (multiple suicide risk factors) showed promise for identifying highly elevated acute risk for suicidal behavior. PMID:25746114

Performance of two commercial ELISAs for detecting IgA anti-human and anti-guinea pig tissue transglutaminase antibodies.

PubMed

Abrantes-Lemos, Clarice Pires; Nakhle, Maria Cristina; Damiao, Aderson Omar Mourao Cintra; Sipahi, Aytan Miranda; Carrilho, Flair José; Cancado, Eduardo Luiz R

2010-01-01

Sensitivity and specificity of anti-human tissue transglutaminase antibodies (anti-htTGA) seem to be superior to those of anti-tissue transglutaminase of guinea pig (anti-gptTGA) for screening patients with celiac disease (CD), but there are still controversies. The aim of this study was to evaluate the performance of two INOVA ELISA kits to detect IgA anti-htTGA and anti-gptTGA in patients with and without CD. The study groups were comprised of 49 anti-endomysial antibody (EMA)-positive untreated-CD, and 123 controls (EMA-negative treated CD, EMA-negative chronic diarrhea, autoimmune hepatitis, inflammatory bowel disease and healthy people). The agreement between the two ELISAs was statistically significant in all study groups and there was no significant difference between them (92.7% agreement; kappa = 0.70; kappa p = 0.001; McNemar p = 1). All patients with serum reactivity of more than 100 units had histologic diagnosis of CD. In seven of 10 patients with treated-CD who had control biopsies, villous atrophy was still present in four who tested positive by both kits. Two of three celiacs with histologic remission tested positive for both anti-tTGA. the anti-gptTGA and anti-htTGA determination were equally efficient in identifying patients with untreated-CD with high titers of EMA. Whatever the anti-tTGA ELISA used, the reactivity above 100 units was always related to active CD diagnosed by histologic alterations in intestinal biopsies. The anti-tTGA reactivity by both kits was not only similar in determining histologic activity in the follow-up of CD after a gluten free diet, but also in identifying positive sera from the control groups, regardless if CD has been confirmed by duodenal biopsies.

Hydrogel tissue construct-based high-content compound screening.

PubMed

Lam, Vy; Wakatsuki, Tetsuro

2011-01-01

Current pharmaceutical compound screening systems rely on cell-based assays to identify therapeutic candidates and potential toxicities. However, cells grown on 2D substrata or in suspension do not exhibit the mechanical or physiological properties of cells in vivo. To address this limitation, the authors developed an in vitro, high-throughput, 3D hydrogel tissue construct (HTC)-based assay system to quantify cell and tissue mechanical properties and multiple parameters of physiology. HTC mechanics was quantified using an automated device, and physiological status was assessed using spectroscopy-based indicators that were read on microplate readers. To demonstrate the application of this system, the authors screened 4 test compounds--rotenone (ROT), cytochalasin D (CD), 2,4-dinitrophenol (DNP), and Rho kinase inhibitor (H-1152)--for their ability to modulate HTC contractility without affecting actin integrity, mitochondrial membrane potential (MMP), or viability. All 4 compounds dose-dependently reduced HTC contractility. However, ROT was toxic, DNP dissipated MMP, and CD reduced both intracellular F-actin and viability. H-1152 was found to be the best candidate compound since it reduced HTC contractility with minimal side effects. The authors propose that their HTC-based assay system can be used to screen for compounds that modulate HTC contractility and assess the underlying physiological mechanism(s) of compound activity and toxicity.

Leishmania amazonensis Engages CD36 to Drive Parasitophorous Vacuole Maturation

PubMed Central

Okuda, Kendi; Tong, Mei; Dempsey, Brian; Moore, Kathryn J.; Gazzinelli, Ricardo T.; Silverman, Neal

2016-01-01

Leishmania amastigotes manipulate the activity of macrophages to favor their own success. However, very little is known about the role of innate recognition and signaling triggered by amastigotes in this host-parasite interaction. In this work we developed a new infection model in adult Drosophila to take advantage of its superior genetic resources to identify novel host factors limiting Leishmania amazonensis infection. The model is based on the capacity of macrophage-like cells, plasmatocytes, to phagocytose and control the proliferation of parasites injected into adult flies. Using this model, we screened a collection of RNAi-expressing flies for anti-Leishmania defense factors. Notably, we found three CD36-like scavenger receptors that were important for defending against Leishmania infection. Mechanistic studies in mouse macrophages showed that CD36 accumulates specifically at sites where the parasite contacts the parasitophorous vacuole membrane. Furthermore, CD36-deficient macrophages were defective in the formation of the large parasitophorous vacuole typical of L. amazonensis infection, a phenotype caused by inefficient fusion with late endosomes and/or lysosomes. These data identify an unprecedented role for CD36 in the biogenesis of the parasitophorous vacuole and further highlight the utility of Drosophila as a model system for dissecting innate immune responses to infection. PMID:27280707

Tumor immune evasion arises through loss of TNF sensitivity.

PubMed

Kearney, Conor J; Vervoort, Stephin J; Hogg, Simon J; Ramsbottom, Kelly M; Freeman, Andrew J; Lalaoui, Najoua; Pijpers, Lizzy; Michie, Jessica; Brown, Kristin K; Knight, Deborah A; Sutton, Vivien; Beavis, Paul A; Voskoboinik, Ilia; Darcy, Phil K; Silke, John; Trapani, Joseph A; Johnstone, Ricky W; Oliaro, Jane

2018-05-18

Immunotherapy has revolutionized outcomes for cancer patients, but the mechanisms of resistance remain poorly defined. We used a series of whole-genome clustered regularly interspaced short palindromic repeat (CRISPR)-based screens performed in vitro and in vivo to identify mechanisms of tumor immune evasion from cytotoxic lymphocytes [CD8 + T cells and natural killer (NK) cells]. Deletion of key genes within the tumor necrosis factor (TNF) signaling, interferon-γ (IFN-γ) signaling, and antigen presentation pathways provided protection of tumor cells from CD8 + T cell-mediated killing and blunted antitumor immune responses in vivo. Deletion of a number of genes in the TNF pathway also emerged as the key mechanism of immune evasion from primary NK cells. Our screens also identified that the metabolic protein 2-aminoethanethiol dioxygenase (Ado) modulates sensitivity to TNF-mediated killing by cytotoxic lymphocytes and is required for optimal control of tumors in vivo. Remarkably, we found that tumors delete the same genes when exposed to perforin-deficient CD8 + T cells, demonstrating that the dominant immune evasion strategy used by tumor cells is acquired resistance to T cell-derived cytokine-mediated antitumor effects. We demonstrate that TNF-mediated bystander killing is a potent T cell effector mechanism capable of killing antigen-negative tumor cells. In addition to highlighting the importance of TNF in CD8 + T cell- and NK cell-mediated killing of tumor cells, our study also provides a comprehensive picture of the roles of the TNF, IFN, and antigen presentation pathways in immune-mediated tumor surveillance. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Find and treat or find and lose? Tuberculosis treatment outcomes among screened newly arrived asylum seekers in Germany 2002 to 2014.

PubMed

Kuehne, Anna; Hauer, Barbara; Brodhun, Bonita; Haas, Walter; Fiebig, Lena

2018-03-01

BackgroundGermany has a low tuberculosis (TB) incidence. A relevant and increasing proportion of TB cases is diagnosed among asylum seekers upon screening. Aim: We aimed to assess whether cases identified by screening asylum seekers had equally successful and completely reported treatment outcomes as cases diagnosed by passive case finding and contact tracing in the general population. Methods: We analysed characteristics and treatment outcomes of pulmonary TB cases notified in Germany between 2002 and 2014, stratified by mode of case finding. We performed three multivariable analyses with different dependent variables: Model A: successful vs all other outcomes, Model B: successful vs documented non-successful clinical outcome and Model C: known outcome vs lost to follow-up. Results: TB treatment success was highest among cases identified by contact tracing (87%; 3,139/3,591), followed by passive case finding (74%; 28,804/39,019) and by screening asylum seekers (60%; 884/1,474). Cases identified by screening asylum seekers had 2.4 times higher odds of not having a successful treatment outcome as opposed to all other outcomes (A), 1.4 times higher odds of not having a successful treatment outcome as opposed to known non-successful outcomes (B) and 2.3 times higher odds of loss to follow-up (C) than cases identified by passive case finding. Conclusion: Screened asylum seekers had poorer treatment outcomes and were more often lost to follow-up. Linking patients to treatment facilities and investigating potential barriers to treatment completion are needed to secure screening benefits for asylum seekers and communities.

Comparative Evaluation of Preliminary Screening Methods for Colorectal Cancer in a Mass Program.

PubMed

Ye, Ding; Huang, Qiuchi; Li, Qilong; Jiang, Xiyi; Mamat, Mayila; Tang, Mengling; Wang, Jianbing; Chen, Kun

2017-09-01

The fecal immunochemical test (FIT) has been widely used in preliminary screening for colorectal cancer (CRC). The high-risk factor questionnaire (HRFQ) and quantitative risk-assessment method (QRAM) are recommended for estimating the risk of CRC qualitatively and quantitatively in China. We aimed to prospectively compare the diagnostic values of CRC preliminary screening methods to identify which method is preferable as a screening strategy. Individuals aged 40-74 years old were enrolled in a mass CRC screening program from January 1, 2007 to December 31, 2014, in Jiashan County, Zhejiang Province, China. FIT of two stool specimens at 1-week intervals was performed by laboratory personnel and face-to-face interviews were conducted by trained investigators. Screening data in the program were linked to a CRC surveillance and registry system, and CRC cases reported in the system were regarded as true patients. A total of 96,043 subjects were included. The sensitivity and specificity of FIT for detecting CRC cases were 75.49% (95% CI 69.84-80.39) and 90.36% (95% CI 90.17-90.54), respectively. QRAM was more sensitive (p < 0.001) and less specific (p < 0.001) than HRFQ. The sensitivity and specificity of FIT along with HRFQ were 86.56% (95% CI 81.81-90.22) and 81.37% (95% CI 81.12-81.62), and those of FIT along with QRAM were 88.93% (95% CI 84.47-92.23) and 73.95% (95% CI 73.67-74.23). Our findings suggest that CRC preliminary screening with FIT and QRAM in parallel has high sensitivity and satisfactory specificity, and is a useful strategy in mass screening programs.

Are we developing walkable suburbs through urban planning policy? Identifying the mix of design requirements to optimise walking outcomes from the 'Liveable Neighbourhoods' planning policy in Perth, Western Australia.

PubMed

Hooper, Paula; Knuiman, Matthew; Bull, Fiona; Jones, Evan; Giles-Corti, Billie

2015-05-16

Planning policy makers and practitioners are requesting clearer guidance on the 'essential' ingredients as assessed by public health researchers to ensure suburban neighbourhood environments are designed to promote active living behaviours such as walking. To identify the combination of design requirements from the 'Liveable Neighbourhoods' (LN) planning policy in Perth, Western Australia that were optimally supportive of walking. K-means cluster analysis identified groups of developments with homogeneous LN features from its community design (CD), movement network (MN), lot layout (LL) and public parkland (PP) elements. Walking behaviours measured using the Neighbourhood Physical Activity Questionnaire were compared between participants resident in the different clusters, adjusting for demographic characteristics, self-selection factors, stage of construction and scale of development. Compared with participants living in the referent cluster of 'poor CD and PP developments' those living in: 'MN and LL developments' had higher odds of doing any (OR = 1.74; 95 % CI = 1.22, 2.48) and ≥60 min walking for recreation (WR) (OR = 2.05; 1.46, 2.88); 'PP developments' had increased odds of doing any WR (OR = 3.53; 2.02, 6.17), ≥60 min WR (OR = 3.37; 1.98, 5.74) and any total walking (TW) (OR = 2.35; 1.36, 4.09); 'CD-MN developments' had increased odds of doing any walking for transport (WT) (OR = 2.64; 1.38, 5.06), ≥60 min WT (OR = 1.98; 1.09, 3.61), any TW (OR = 1.71; 1.44, 2.03), ≥60 min TW (OR = 1.77; 1.14, 2.76) and ≥150 min TW (OR = 1.47; 1.15, 1.86). This study is the first to have empirically identified a mix of specific and distinguishing planning policy neighbourhood design requirements to optimise walking outcomes. These findings will assist in the assessment of urban plans for greenfield suburban developments designed to promote walking and physical activity.

Practices to improve identification of Adult Antiretroviral Therapy failure at the Lighthouse Trust clinic in Lilongwe, Malawi

PubMed Central

Vorkas, Charles Kyriakos; Tweya, Hannock; Mzinganjira, Dalitso; Dickie, George; Weigel, Ralf; Phiri, Sam; Hosseinipour, Mina C.

2011-01-01

Summary Background Evaluating treatment failure is critical when deciding to modify antiretroviral therapy (ART). Virologic Assessment Forms (VAFs) were implemented in July 2008 as a prerequisite for ordering viral load. The form requires assessment of clinical and immunologic status. Methods Using the Electronic Medical Record (EMR), we retrospectively evaluated patients who met 2006 WHO guidelines for immunologic failure (≥15 years old; on ART ≥6 months; CD4 count 50% drop from peak OR CD4 persistently <100 cells) at the Lighthouse Trust clinic from 12/2007–12/2009. We compared virologic screening, VAF implementation and ART modification during the same period using Fisher’s exact tests and unpaired t-tests as appropriate. Results Of 7,000 enrolled ART patients ≥ 15 years old with at least two CD4 counts, 10% had immunologic failure with a median follow-up time on ART of 1.4 years (IQR: 0.8–2.3). Forty (6%) viral loads were ordered: 14 (35%) were detectable (>400 HIV RNA copies/mL) and 1 (7%) patient was switched to second-line therapy. Overall, 259 VAFs were completed: 67% for immunologic failure and 33% for WHO Stage 4 condition. Before VAF implementation, 1% of patients had viral loads drawn during routine care, whereas afterwards, 8% did (p<0.0001; 95% CI 0.03–0.08). Conclusions Clinicians did not identify a large proportion of immunologic failure patients for screening. Implementation of VAFs produced little improvement in virologic screening during routine care. Better training and monitoring systems are needed. PMID:22039960

A computational search for box C/D snoRNA genes in the Drosophila melanogaster genome.

PubMed

Accardo, M C; Giordano, E; Riccardo, S; Digilio, F A; Iazzetti, G; Calogero, R A; Furia, M

2004-12-12

In eukaryotes, the family of non-coding RNA genes includes a number of genes encoding small nucleolar RNAs (mainly C/D and H/ACA snoRNAs), which act as guides in the maturation or post-transcriptional modifications of target RNA molecules. Since in Drosophila melanogaster (Dm) only few examples of snoRNAs have been identified so far by cDNA libraries screening, integration of the molecular data with in silico identification of these types of genes could throw light on their organization in the Dm genome. We have performed a computational screening of the Dm genome for C/D snoRNA genes, followed by experimental validation of the putative candidates. Few of the 26 confirmed snoRNAs had been recognized by cDNA library analysis. Organization of the Dm genome was also found to be more variegated than previously suspected, with snoRNA genes nested in both the introns and exons of protein-coding genes. This finding suggests that the presence of additional mechanisms of snoRNA biogenesis based on the alternative production of overlapping mRNA/snoRNA molecules. Additional information is available at http://www.bioinformatica.unito.it/bioinformatics/snoRNAs.

Study of the structural organization of cyclodextrin-DNA complex loaded anionic and pH-sensitive liposomes

NASA Astrophysics Data System (ADS)

Silva, Sônia M. L.; Coelho, Letícia N.; Malachias, Ângelo; Perez, Carlos A.; Pesquero, Jorge L.; Magalhães-Paniago, Rogério; de Oliveira, Mônica C.

2011-04-01

The present study investigated the effect of the 6-monodeoxy-6-monoamine-β-cyclodextrin(Am-β-CD)/DNA (Am-β-CD/DNA) complex, as well as of culture medium components and proteins, at pH 7.4 and 5.0, on membranes of anionic and pH-sensitive liposomes comprised of DOPE-CHEMS, using energy dispersive X-ray diffraction (EDXD). At pH 7.4, the Am-β-CD/DNA complex induced the appearance of lamellar and hexagonal phases of DOPE. However, at pH 5.0, only non-lamellar phases could be observed. The presence of biological components led to a disruption of lipid order, but the pH-sensitivity of liposomes was maintained.

Tumour-associated circulating microparticles: A novel liquid biopsy tool for screening and therapy monitoring of colorectal carcinoma and other epithelial neoplasia.

PubMed

Willms, Arnulf; Müller, Clara; Julich, Henrike; Klein, Niklas; Schwab, Robert; Güsgen, Christoph; Richardsen, Ines; Schaaf, Sebastian; Krawczyk, Marcin; Krawczyk, Marek; Lammert, Frank; Schuppan, Detlef; Lukacs-Kornek, Veronika; Kornek, Miroslaw

2016-05-24

Up to date, novel tools for low-cost, minimal invasive cancer surveillance, cancer screening and treatment monitoring are in urgent need. Physicians consider the so-called liquid biopsy as a possible future tool successfully achieving these ultimate goals. Here, we aimed to identify circulating tumour-associated MPs (taMPs) that could aid in diagnosing minimal-invasively the presence and follow up treatment in non-small cell lung carcinoma (NSCLC), colorectal carcinoma (CRC) and pancreas carcinoma (PaCa). Tumour-associated MPs (taMPs) were quantified after isolation by centrifugation followed by flow cytometry analysis from the serum of cancer patients with CRC (n = 52), NSCLC (n = 40) and PaCa (n = 11). Healthy subjects (n = 55) or patients with struma nodosa (thyroid nodules) (n = 43) served as negative controls. In all three types of tumour entities, the presence of tumour was associated with an increase of circulating EpCAM+ and EpCAM+CD147+ taMPs. The presence of CD147+EpCAM+ taMPs were specific to tumour-bearing patients thus allowing the specific distinction of malignancies from patients with thyroid nodules. Increased level of EpCAM single positive MPs were, in turn, also detected in patients with thyroid nodules. Importantly, EpCAM+CD147+ taMPs correlated with the measured tumour-volume in CRC patients. EpCAM+ taMPs decreased at 7 days after curative R0 tumour resection suggesting a close dependence with tumour presence. AUROC values (up to 0.85 and 0.90), sensitivity/specificity scores, and positive/negative predictive values indicated a high diagnostic accuracy of EpCAM+CD147+ taMPs. Taken together, EpCAM+CD147+ double positive taMPs could potentially serve as novel promising clinical parameter for cancer screening, diagnosis, surveillance and therapy monitoring.

Automatic Classification of Users’ Health Information Need Context: Logistic Regression Analysis of Mouse-Click and Eye-Tracker Data

PubMed Central

Pian, Wenjing; Khoo, Christopher SG

2017-01-01

Background Users searching for health information on the Internet may be searching for their own health issue, searching for someone else’s health issue, or browsing with no particular health issue in mind. Previous research has found that these three categories of users focus on different types of health information. However, most health information websites provide static content for all users. If the three types of user health information need contexts can be identified by the Web application, the search results or information offered to the user can be customized to increase its relevance or usefulness to the user. Objective The aim of this study was to investigate the possibility of identifying the three user health information contexts (searching for self, searching for others, or browsing with no particular health issue in mind) using just hyperlink clicking behavior; using eye-tracking information; and using a combination of eye-tracking, demographic, and urgency information. Predictive models are developed using multinomial logistic regression. Methods A total of 74 participants (39 females and 35 males) who were mainly staff and students of a university were asked to browse a health discussion forum, Healthboards.com. An eye tracker recorded their examining (eye fixation) and skimming (quick eye movement) behaviors on 2 types of screens: summary result screen displaying a list of post headers, and detailed post screen. The following three types of predictive models were developed using logistic regression analysis: model 1 used only the time spent in scanning the summary result screen and reading the detailed post screen, which can be determined from the user’s mouse clicks; model 2 used the examining and skimming durations on each screen, recorded by an eye tracker; and model 3 added user demographic and urgency information to model 2. Results An analysis of variance (ANOVA) analysis found that users’ browsing durations were significantly different for the three health information contexts (P<.001). The logistic regression model 3 was able to predict the user’s type of health information context with a 10-fold cross validation mean accuracy of 84% (62/74), followed by model 2 at 73% (54/74) and model 1 at 71% (52/78). In addition, correlation analysis found that particular browsing durations were highly correlated with users’ age, education level, and the urgency of their information need. Conclusions A user’s type of health information need context (ie, searching for self, for others, or with no health issue in mind) can be identified with reasonable accuracy using just user mouse clicks that can easily be detected by Web applications. Higher accuracy can be obtained using Google glass or future computing devices with eye tracking function. PMID:29269342

Spectrum of MECP2 gene mutations in a cohort of Indian patients with Rett syndrome: report of two novel mutations.

PubMed

Das, Dhanjit Kumar; Raha, Sarbani; Sanghavi, Daksha; Maitra, Anurupa; Udani, Vrajesh

2013-02-15

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder, primarily affecting females and characterized by developmental regression, epilepsy, stereotypical hand movements, and motor abnormalities. Its prevalence is about 1 in 10,000 female births. Rett syndrome is caused by mutations within methyl CpG-binding protein 2 (MECP2) gene. Over 270 individual nucleotide changes which cause pathogenic mutations have been reported. However, eight most commonly occurring missense and nonsense mutations account for almost 70% of all patients. We screened 90 individuals with Rett syndrome phenotype. A total of 19 different MECP2 mutations and polymorphisms were identified in 27 patients. Of the 19 mutations, we identified 7 (37%) frameshift, 6 (31%) nonsense, 14 (74%) missense mutations and one duplication (5%). The most frequent pathogenic changes were: missense p.T158M (11%), p.R133C (7.4%), and p.R306C (7.4%) and nonsense p.R168X (11%), p.R255X (7.4%) mutations. We have identified two novel mutations namely p.385-388delPLPP present in atypical patients and p.Glu290AlafsX38 present in a classical patient of Rett syndrome. Sequence homology for p.385-388delPLPP mutation revealed that these 4 amino acids were conserved across mammalian species. This indicated the importance of these 4 amino acids in structure and function of the protein. A novel variant p.T479T has also been identified in a patient with atypical Rett syndrome. A total of 62 (69%) patients remained without molecular genetics diagnosis that necessitates further search for mutations in other genes like CDKL5 and FOXG1 that are known to cause Rett phenotype. The majority of mutations are detected in exon 4 and only one mutation was present in exon 3. Therefore, our study suggests the need for screening exon 4 of MECP2 as first line of diagnosis in these patients. Copyright © 2012 Elsevier B.V. All rights reserved.

Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non-alcoholic fatty liver disease

PubMed Central

Schwimmer, J B; Newton, K P; Awai, H I; Choi, L J; Garcia, M A; Ellis, L L; Vanderwall, K; Fontanesi, J

2013-01-01

Background Screening overweight and obese children for non-alcoholic fatty liver disease (NAFLD) is recommended by paediatric and endocrinology societies. However, gastroenterology societies have called for more data before making a formal recommendation. Aim To determine whether the detection of suspected NAFLD in overweight and obese children through screening in primary care and referral to paediatric gastroenterology resulted in a correct diagnosis of NAFLD. Methods Information generated in the clinical evaluation of 347 children identified with suspected NAFLD through screening in primary care and referral to paediatric gastroenterology was captured prospectively. Diagnostic outcomes were reported. The diagnostic performance of two times the upper limit of normal (ULN) for alanine aminotransferase (ALT) was assessed. Results Non-alcoholic fatty liver disease was diagnosed in 55% of children identified by screening and referral. Liver disease other than NAFLD was present in 18% of those referred. Autoimmune hepatitis was the most common alternative diagnosis. Children with NAFLD had significantly (P < 0.05) higher screening ALT (98 ± 95) than children with liver disease other than NAFLD (86 ± 74). Advanced fibrosis was present in 11% of children. For the diagnosis of NAFLD, screening ALT two times the clinical ULN had a sensitivity of 57% and a specificity of 71%. Conclusions Screening of overweight and obese children in primary care for NAFLD with referral to paediatric gastroenterology has the potential to identify clinically relevant liver pathology. Consensus is needed on how to value the risk and rewards of screening and referral, to identify children with liver disease in the most appropriate manner. PMID:24117728

Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non-alcoholic fatty liver disease.

PubMed

Schwimmer, J B; Newton, K P; Awai, H I; Choi, L J; Garcia, M A; Ellis, L L; Vanderwall, K; Fontanesi, J

2013-11-01

Screening overweight and obese children for non-alcoholic fatty liver disease (NAFLD) is recommended by paediatric and endocrinology societies. However, gastroenterology societies have called for more data before making a formal recommendation. To determine whether the detection of suspected NAFLD in overweight and obese children through screening in primary care and referral to paediatric gastroenterology resulted in a correct diagnosis of NAFLD. Information generated in the clinical evaluation of 347 children identified with suspected NAFLD through screening in primary care and referral to paediatric gastroenterology was captured prospectively. Diagnostic outcomes were reported. The diagnostic performance of two times the upper limit of normal (ULN) for alanine aminotransferase (ALT) was assessed. Non-alcoholic fatty liver disease was diagnosed in 55% of children identified by screening and referral. Liver disease other than NAFLD was present in 18% of those referred. Autoimmune hepatitis was the most common alternative diagnosis. Children with NAFLD had significantly (P < 0.05) higher screening ALT (98 ± 95) than children with liver disease other than NAFLD (86 ± 74). Advanced fibrosis was present in 11% of children. For the diagnosis of NAFLD, screening ALT two times the clinical ULN had a sensitivity of 57% and a specificity of 71%. Screening of overweight and obese children in primary care for NAFLD with referral to paediatric gastroenterology has the potential to identify clinically relevant liver pathology. Consensus is needed on how to value the risk and rewards of screening and referral, to identify children with liver disease in the most appropriate manner. © 2013 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

The role of sialomucin CD164 (MGC-24v or endolyn) in prostate cancer metastasis

PubMed Central

Havens, AM; Jung, Y; Sun, YX; Wang, J; Shah, RB; Bühring, HJ; Pienta, KJ; Taichman, RS

2006-01-01

Background The chemokine stromal derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 have been demonstrated to be crucial for the homing of stem cells and prostate cancers to the marrow. While screening prostate cancers for CXCL12-responsive adhesion molecules, we identified CD164 (MGC-24) as a potential regulator of homing. CD164 is known to function as a receptor that regulates stem cell localization to the bone marrow. Results Using prostate cancer cell lines, it was demonstrated that CXCL12 induced both the expression of CD164 mRNA and protein. Functional studies demonstrated that blocking CD164 on prostate cancer cell lines reduced the ability of these cells to adhere to human bone marrow endothelial cells, and invade into extracellular matrices. Human tissue microarrays stained for CD164 demonstrated a positive correlation with prostate-specific antigen levels, while its expression was negatively correlated with the expression of androgen receptor. Conclusion Our findings suggest that CD164 may participate in the localization of prostate cancer cells to the marrow and is further evidence that tumor metastasis and hematopoietic stem cell trafficking may involve similar processes. PMID:16859559

Bridging of a substrate between cyclodextrin and an enzyme’s active site pocket triggers a unique mode of inhibition

PubMed Central

Sule, Nitesh V; Ugrinov, Angel; Mallik, Sanku; Srivastava, D. K.

2014-01-01

Background Methionyl-7-amino-4-methylcoumarin (MetAMC) serves as a substrate for the E. coli Methionine aminopeptidase (MetAP) catalyzed reaction, and is routinely used for screening compounds to identify potential antibiotic agents. In pursuit of screening the enzyme’s inhibitors, we observed that 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), utilized to solubilize hydrophobic inhibitors, inhibited the catalytic activity of the enzyme, and such inhibition was not solely due to sequestration of the substrate by HP-β-CD. Methods The mechanistic path for the HP-β-CD mediated inhibition of MetAP was probed by performing a detailed account of steady-state kinetics, ligand binding, X-ray crystallographic, and molecular modeling studies. Results X-ray crystallographic data of the β-cyclodextrin—substrate (β-CD—MetAMC) complex reveal that while the AMC moiety of the substrate is confined within the CD cavity, the methionine moiety protrudes outward. The steady-state kinetic data for inhibition of MetAP by HP-β-CD—MetAMC conform to a model mechanism in which the substrate is “bridged” between HP-β-CD and the enzyme’s active-site pocket, forming HP-β-CD—MetAMC—MetAP as the catalytically inactive ternary complex. Molecular modeling shows that the scissile bond of HP-β-CD-bound MetAMC substrate does not reach within the proximity of the enzyme’s catalytic metal center, and thus the substrate fails to undergo cleavage. Conclusions The data presented herein suggests that the bridging of the substrate between the enzyme and HP-β-CD cavities is facilitated by interaction of their surfaces, and the resulting complex inhibits the enzyme activity. General Significance Due to its potential interaction with physiological proteins via sequestered substrates, caution must be exercised in HP-β-CD mediated delivery of drugs under pathophysiological conditions. PMID:25450177

Role of the C-terminal and chitin insertion domains on enzymatic activity of endochitinase ChiA74 of Bacillus thuringiensis.

PubMed

Juárez-Hernández, Estefania O; Casados-Vázquez, Luz E; Bideshi, Dennis K; Salcedo-Hernández, R; Barboza-Corona, José E

2017-09-01

ChiA74 has modular structure that includes a secretion signal peptide (sp) sequence, and catalytic (CD), chitin insertion (CID), fibronectin type-III (FnIII) and chitin binding (CBD) domains. We described for the first time the existence of a putative CID in ChiA74. Mature ChiA74 lacking its sp sequence (rChiA74Δsp, ∼70kDa) and two truncated versions, rChiA74Δsp-60, rChiA74Δsp-50 lacking, respectively, CBD and CDB-FnIII were produced. rChiA74Δsp and rChiA74Δsp-60 are unstable and were processed to generate stable proteins of ∼50kDa. With colloidal chitin, rChiA74Δsp and rChiA74Δsp-50 had higher activity than rChiA74Δsp-60. rChiA74Δsp showed similar ability to bind chitin than rChiA74Δsp-50. The catalytic efficiencies (kcat/Km) of rChiA74Δsp and rChiA74Δsp-50 were higher, ∼ 21-fold than rChiA74Δsp-60, using chitin as the substrate. Optimal activity was detected at pH 7 and 40°C. Data suggest that the CBD in ChiA74 is important for binding to chitin, but not necessary as the presence of a CID together with the CD in a stable truncated version (i.e. ChiA74Δsp-50) has similar affinity and hydrolytic activity as the mature enzyme. The CID of ChiA74 showed identities of ∼ 55% with CIDs of other chitinases such as those from B. circulans and B. licheniformis, respectively, and conserved residues important for interacting with chitin. Copyright © 2017 Elsevier B.V. All rights reserved.

Tissue distribution of mesenchymal stem cell marker Stro-1.

PubMed

Lin, Guiting; Liu, Gang; Banie, Lia; Wang, Guifang; Ning, Hongxiu; Lue, Tom F; Lin, Ching-Shwun

2011-10-01

Stro-1 is the best-known mesenchymal stem cell marker. However, despite its bone marrow origin, its localization in bone marrow has never been demonstrated. By immunofluorescence staining, we show here that ∼ 0.74% of nucleated bone marrow cells expressed Stro-1. We also found that ∼ 8.7% of CD34-expressing cells expressed Stro-1, and more than 20% of Stro-1-expressing cells did not express CD34. In adipose tissue Stro-1 expression was identified in the endothelium of arterioles and capillaries. Stro-1 was also localized in the endothelium of some but not all adipose tissue veins. Endothelial expression of Stro-1 was also identified in blood vessels in penis and in leg muscles, but not in other tested tissues. In these other tissues, Stro-1 was scantly expressed near but not in blood vessels. These variable and endothelial expression patterns of Stro-1 point to a need to re-examine published data that relied on Stro-1 as a mesenchymal stem cell marker.

Factors Associated with Breast Cancer Screening in a Country with National Health Insurance: Did We Succeed in Reducing Healthcare Disparities?

PubMed

Hayek, Samah; Enav, Teena; Shohat, Tamy; Keinan-Boker, Lital

2017-02-01

The effectiveness of breast cancer screening programs in reducing mortality is well established in the scientific literature. The National Breast Cancer Screening Program in Israel provides biennial mammograms for women of average risk aged 50-74 and annual mammograms for women aged 40-49 at higher risk. Compliance is high, but differential. This study explores different factors associated with breast cancer screening attendance among women aged 40-74 years. Two main outcomes were studied: ever been screened and been screened in the 2 years preceding the study, using the cross-sectional Knowledge, Attitudes and Practices (KAP) Survey conducted in 2010-2012 among 2575 Israeli women aged 21+ years. The independent variables were sociodemographic characteristics, perceived health status, lifestyle habits, and healthcare fund membership. Bivariate and multivariable logistic regressions were conducted. Of the 943 participants aged 50-74, 87% had ever been screened and 74.8% had attended screening for breast cancer in the last 2 years. In multivariable models, Jewish compared to Arab women (adjusted prevalence ratio [APR] = 2.09, 95% confidence interval [CI]: 1.02-4.32), and unmarried compared to married women (APR = 2.9, 95% CI: 1.2-7.2), were more likely to have ever been screened. The only factor associated with breast cancer screening in the 2 years preceding the study was healthcare fund membership. In women aged 40-49 years, ethnicity was the only contributing factor associated with breast cancer screening, with higher screening rates in the 2 years preceding the study in Jewish versus Arab women (APR = 3.7, 95% CI: 1.52-9.3). Breast cancer screening attendance in Israel is high. However, significant differences are observed by membership of healthcare fund and by ethnicity, calling for better targeted outreach programs at this level.

The Role of Socioeconomic Status and Health Care Access in Breast Cancer Screening Compliance Among Hispanics.

PubMed

Jadav, Smruti; Rajan, Suja S; Abughosh, Susan; Sansgiry, Sujit S

2015-01-01

Considerable disparities in breast cancer screening exist between Hispanic and non-Hispanic white (NHW) women. Identifying and quantifying the factors contributing to these racial-ethnic disparities can help shape interventions and policies aimed at reducing these disparities. This study, for the first time, identified and quantified individual-level sociodemographic and health-related factors that contribute to racial-ethnic disparities in breast cancer screening using the nonlinear Blinder-Oaxaca decomposition method. Analysis of the retrospective pooled cross-sectional Medical Expenditure Panel Survey data from 2000 to 2010 was conducted. Women aged 40 years and older were included in the study. Logistic regressions were used to estimate racial-ethnic disparities in breast cancer screening. Nonlinear Blinder-Oaxaca decomposition method was used to identify and quantify the contribution of each individual-level factor toward racial-ethnic disparities. Based on the unadjusted analyses, Hispanic women had lower odds of receiving mammogram screening (MS) (odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.69-0.80) and breast cancer screening (OR: 0.75; 95% CI: 0.70-0.81) as compared with NHW women. However, the relationship reversed in adjusted analyses, such that Hispanic women had higher odds of receiving MS (OR: 1.27; 95% CI: 1.16-1.40) and breast cancer screening (OR: 1.28; 95% CI: 1.17-1.40) as compared with NHW women. The Blinder-Oaxaca decomposition estimated that improving insurance status, access to care, education, and income will considerably increase screening rates among Hispanic women. The study projects that improving health care access and health education will considerably increase breast cancer screening compliance among Hispanic women. Policies like the Affordable Care Act, and patient navigation and health education interventions, might considerably reduce screening disparities in the Hispanic population.

Impact of extending screening mammography to older women: Information to support informed choices.

PubMed

Jacklyn, Gemma; Howard, Kirsten; Irwig, Les; Houssami, Nehmat; Hersch, Jolyn; Barratt, Alexandra

2017-10-15

From 2013 through 2017, the Australian national breast cancer screening programme is gradually inviting women aged 70-74 years to attend screening, following a policy decision to extend invitations to older women. We estimate the benefits and harms of the new package of biennial screening from age 50-74 compared with the previous programme of screening from age 50-69. Using a Markov model, we applied estimates of the relative risk reduction for breast cancer mortality and the risk of overdiagnosis from the Independent UK Panel on Breast Cancer Screening review to Australian breast cancer incidence and mortality data. We estimated screening specific outcomes (recalls for further imaging, biopsies, false positives, and interval cancer rates) from data published by BreastScreen Australia. When compared with stopping at age 69, screening 1,000 women to age 74 is likely to avert one more breast cancer death, with an additional 78 women receiving a false positive result and another 28 women diagnosed with breast cancer, of whom eight will be overdiagnosed and overtreated. The extra 5 years of screening results in approximately 7 more overdiagnosed cancers to avert one more breast cancer death. Thus extending screening mammography in Australia to older women results in a less favourable harm to benefit ratio than stopping at age 69. Supporting informed decision making for this age group should be a public health priority. © 2017 UICC.

Socioeconomic factors affecting colorectal, breast and cervical cancer screening in an Asian urban low-income setting at baseline and post-intervention.

PubMed

Wee, Liang En; Koh, Gerald Choon-Huat; Chin, Run Ting; Yeo, Wei Xin; Seow, Branden; Chua, Darren

2012-07-01

Inequalities in cancer screening are little studied in Asian societies. We determined whether area and individual measures of socio-economic status (SES) affected cancer screening participation in Singapore and prospectively evaluated an access-enhancing community-based intervention. The study population involved all residents aged >40 years in two housing estates comprising of owner-occupied (high-SES area) and rental (low-SES area) flats. From 2009 to 2011, non-adherents to regular screening for colorectal/breast/cervical cancer were offered free convenient screening over six months. Pre- and post-intervention screening rates were compared with McNemar's test. Multi-level logistic regression identified factors of regular screening at baseline; Cox regression analysis identified predictors of screening post-intervention. Participation was 78.2% (1081/1383). In the low-SES area, 7.7% (33/427), 20.4% (44/216), and 14.3% (46/321) had regular colorectal, cervical and breast cancer screening respectively. Post-intervention, screening rates in the low-SES area rose significantly to 19.0% (81/427), 25.4% (55/216), and 34.3% (74/216) respectively (p<0.001). Area SES was more consistently associated with screening than individual SES at baseline. Post-intervention, for colorectal cancer screening, those with higher education were more likely to attend (p=0.004); for female cancer screening, the higher-income were less likely to attend (p=0.032). Access-enhancing community-based interventions improve participation among disadvantaged strata of Asian societies. Copyright © 2012 Elsevier Inc. All rights reserved.

Chlamydia screening strategies and outcomes in educational settings: a systematic review.

PubMed

Jamil, Muhammad Shahid; Bauer, Heidi M; Hocking, Jane S; Ali, Hammad; Wand, Handan; Walker, Jennifer; Douglas, Laura; Donovan, Basil; Kaldor, John M; Guy, Rebecca J

2014-03-01

Chlamydia trachomatis (CT) screening programs have been established in educational settings in many countries during the past 2 decades. However, recent evidence suggests that high uptake of screening and management (treatment, partner notification, and retesting for reinfection) improves program effectiveness. We conducted a systematic review to understand the screening strategies, the extent of screening conducted, and uptake of management strategies in educational settings. Screening studies in educational settings were identified through a systematic search of published literature from 2005 to 2011. We identified 27 studies describing 30 screening programs in the United States/Canada (n = 10), Europe (n = 8), Australia/New Zealand (n = 5), and Asia (n = 4). Most studies targeted both male and female students (74%). Classroom-based strategies resulted in 21,117 testes overall (4 programs), followed by opportunistic screening during routine health examination (n = 13,470; 5 programs) and opportunistic screening at school-based health centers (n = 13,006; 5 programs). The overall median CT positivity was 4.7% (range, 1.3%-18.1%). Only 5 programs reported treatment rates (median, 100%; range, 86%-100%), 1 partner notification rate (71%), 1 retesting rate within a year of an initial CT diagnosis (47%), and 2 reported repeat positivity rates (21.1% and 26.3%). In conclusion, this systematic review shows that a variety of strategies have been used to screen large numbers of students in educational settings; however, only a few studies have reported CT management outcomes.

Only Follow-Up of Memory B Cells Helps Monitor Rituximab Administration to Patients with Neuromyelitis Optica Spectrum Disorders.

PubMed

Lebrun, Christine; Cohen, Mikael; Rosenthal-Allieri, Maria Alessandra; Bresch, Saskia; Benzaken, Sylvia; Marignier, Romain; Seitz-Polski, Barbara; Ticchioni, Michel

2018-06-07

Neuromyelitis optica spectrum disorders (NMOSD) are identified as a spectrum of inflammatory demyelinating disorders involving the brain, spinal cord and optic nerves. These disorders require early diagnosis and highly active immunosuppressive treatment. Rituximab (RTX) has demonstrated efficacy in limiting relapse in NMOSD when using several administration schedules. We questioned if the CD19+ CD27+ memory B cell count was a more reliable marker to monitor RTX administration than the RTX plasma level and CD19+ B cell count. We analyzed 125 blood samples from 17 NMOSD patients treated with RTX and also measured the level of anti-aquaporine-4 antibodies (anti-AQP-4 Abs), human anti-chimeric antibodies to the murine fragment of RTX (HACA-RTX Abs), and the RTX concentration. The mean follow-up time of the cohort was 7.4 (2-16) years. All patients improved with a mean EDSS going from 4 (1-8.5) to 2.7 (1-5.5). The mean interval between RTX infusions was 9.6 months with identification of prolonged responders. Total CD19+ B cell detection with the routine technique did not correlate to re-emergence of CD19+ CD27+ memory B cells. The RTX residual concentration did not correlate with the CD19+ CD27+ memory B cell count or with anti-RTX antibody production. In contrast to total CD19+ cell, detected with the routine technique, CD19+ CD27+ memory B cells are a reliable marker for biological relapse and allow a decrease in the frequency of infusions.

Fibroblast growth factor-2 (FGF2) and syndecan-1 (SDC1) are potential biomarkers for putative circulating CD15+/CD30+ cells in poor outcome Hodgkin lymphoma patients

PubMed Central

2013-01-01

Background High risk, unfavorable classical Hodgkin lymphoma (cHL) includes those patients with primary refractory or early relapse, and progressive disease. To improve the availability of biomarkers for this group of patients, we investigated both tumor biopsies and peripheral blood leukocytes (PBL) of untreated (chemo-naïve, CN) Nodular Sclerosis Classic Hodgkin Lymphoma (NS-cHL) patients for consistent biomarkers that can predict the outcome prior to frontline treatment. Methods and materials Bioinformatics data mining was used to generate 151 candidate biomarkers, which were screened against a library of 10 HL cell lines. Expression of FGF2 and SDC1 by CD30+ cells from HL patient samples representing good and poor outcomes were analyzed by qRT-PCR, immunohistochemical (IHC), and immunofluorescence analyses. Results To identify predictive HL-specific biomarkers, potential marker genes selected using bioinformatics approaches were screened against HL cell lines and HL patient samples. Fibroblast Growth Factor-2 (FGF2) and Syndecan-1 (SDC1) were overexpressed in all HL cell lines, and the overexpression was HL-specific when compared to 116 non-Hodgkin lymphoma tissues. In the analysis of stratified NS-cHL patient samples, expression of FGF2 and SDC1 were 245 fold and 91 fold higher, respectively, in the poor outcome (PO) group than in the good outcome (GO) group. The PO group exhibited higher expression of the HL marker CD30, the macrophage marker CD68, and metastatic markers TGFβ1 and MMP9 compared to the GO group. This expression signature was confirmed by qualitative immunohistochemical and immunofluorescent data. A Kaplan-Meier analysis indicated that samples in which the CD30+ cells carried an FGF2+/SDC1+ immunophenotype showed shortened survival. Analysis of chemo-naive HL blood samples suggested that in the PO group a subset of CD30+ HL cells had entered the circulation. These cells significantly overexpressed FGF2 and SDC1 compared to the GO group. The PO group showed significant down-regulation of markers for monocytes, T-cells, and B-cells. These expression signatures were eliminated in heavily pretreated patients. Conclusion The results suggest that small subsets of circulating CD30+/CD15+ cells expressing FGF2 and SDC1 represent biomarkers that identify NS-cHL patients who will experience a poor outcome (primary refractory and early relapsing). PMID:23988031

Characterization of novel biomarkers in selecting for subtype specific medulloblastoma phenotypes.

PubMed

Liang, Lisa; Aiken, Christopher; McClelland, Robyn; Morrison, Ludivine Coudière; Tatari, Nazanin; Remke, Marc; Ramaswamy, Vijay; Issaivanan, Magimairajan; Ryken, Timothy; Del Bigio, Marc R; Taylor, Michael D; Werbowetski-Ogilvie, Tamra E

2015-11-17

Major research efforts have focused on defining cell surface marker profiles for characterization and selection of brain tumor stem/progenitor cells. Medulloblastoma is the most common primary malignant pediatric brain cancer and consists of 4 molecular subgroups: WNT, SHH, Group 3 and Group 4. Given the heterogeneity within and between medulloblastoma variants, surface marker profiles may be subtype-specific. Here, we employed a high throughput flow cytometry screen to identify differentially expressed cell surface markers in self-renewing vs. non-self-renewing SHH medulloblastoma cells. The top 25 markers were reduced to 4, CD271/p75NTR/NGFR, CD106/VCAM1, EGFR and CD171/NCAM-L1, by evaluating transcript levels in SHH tumors relative to samples representing the other variants. However, only CD271/p75NTR/NGFR and CD171/NCAM-L1 maintain differential expression between variants at the protein level. Functional characterization of CD271, a low affinity neurotrophin receptor, in cell lines and primary cultures suggested that CD271 selects for lower self-renewing progenitors or stem cells. Moreover, CD271 levels were negatively correlated with expression of SHH pathway genes. Our study reveals a novel role for CD271 in SHH medulloblastoma and suggests that targeting CD271 pathways could lead to the design of more selective therapies that lessen the broad impact of current treatments on developing nervous systems.

Evaluation of Baseline CD4+ T Cell Counts and ART Requirement in Newly Diagnosed HIV Seropositive Individuals in a Tertiary Care Hospital of Northern India.

PubMed

Bhattar, Sonali; Mehra, Bhanu; Bhalla, Preena; Rawat, Deepti

2016-11-01

Antiretroviral Therapy (ART) has changed the outlook of Human Immune-deficiency Virus (HIV)/Acquired Immuno Deficiency Syndrome (AIDS) patients worldwide. To analyse the trends in baseline CD4+ T cell counts and ART requirements in newly diagnosed HIV seropositive individuals in a Tertiary care hospital of Northern India. Out of 1263 HIV seropositive clients identified from January 2012 to June 2014, the baseline CD4+ T cell counts of only those 470 clients were analysed, who registered at the linked ART centre. The mean baseline CD4+ count of the study group was 249.77±216.0cells/mm 3 and that of male and female were 300.31±240.47cells/mm 3 and 232.38±204.25cells/mm 3 respectively. A total of 259 of 334 (77.54%) HIV reactive males, 83 of 130 (63.85%) HIV reactive females and overall 348 of 470 (74.04%) required antiretroviral treatment on enrolment. In the present study, about three-fourth of newly diagnosed HIV positive Indian patients required initiation of ART at registration. The relatively low baseline CD4+ T cell counts in this population highlights the need for timely baseline CD4+ counts testing of HIV positive patients and the urgency of initiating treatment in HIV reactive individuals in Indian health care settings.

Potential of soluble CD26 as a serum marker for colorectal cancer detection

PubMed Central

Cordero, Oscar J; Imbernon, Monica; Chiara, Loretta De; Martinez-Zorzano, Vicenta S; Ayude, Daniel; de la Cadena, Maria Paez; Rodriguez-Berrocal, F Javier

2011-01-01

Colorectal cancer is characterized by a low survival rate even though the basis for colon cancer development, which involves the evolution of adenomas to carcinoma, is known. Moreover, the mortality rates continue to rise in economically transitioning countries although there is the opportunity to intervene in the natural history of the adenoma–cancer sequence through risk factors, screening, and treatment. Screening in particular accounted for most of the decline in colorectal cancer mortality achieved in the USA during the period 1975-2000. Patients show a better prognosis when the neoplasm is diagnosed early. Among the variety of screening strategies, the methods range from invasive and costly procedures such as colonoscopy to more low-cost and non-invasive tests such as the fecal occult blood test (guaiac and immunochemical). As a non-invasive biological serum marker would be of great benefit because of the performance of the test, several biomarkers, including cytologic assays, DNA and mRNA, and soluble proteins, have been studied. We found that the soluble CD26 (sCD26) concentration is diminished in serum of colorectal cancer patients compared to healthy donors, suggesting the potential utility of a sCD26 immunochemical detection test for early diagnosis. sCD26 originates from plasma membrane CD26 lacking its transmembrane and cytoplasmic domains. Some 90%–95% of sCD26 has been associated with serum dipeptidyl peptidase IV (DPP-IV) activity. DPP-IV, assigned to the CD26 cluster, is a pleiotropic enzyme expressed mainly on epithelial cells and lymphocytes. Our studies intended to validate this test for population screening to detect colorectal cancer and advanced adenomas are reviewed here. PMID:21773075

Predicting the risk for colorectal cancer with personal characteristics and fecal immunochemical test.

PubMed

Li, Wen; Zhao, Li-Zhong; Ma, Dong-Wang; Wang, De-Zheng; Shi, Lei; Wang, Hong-Lei; Dong, Mo; Zhang, Shu-Yi; Cao, Lei; Zhang, Wei-Hua; Zhang, Xi-Peng; Zhang, Qing-Huai; Yu, Lin; Qin, Hai; Wang, Xi-Mo; Chen, Sam Li-Sheng

2018-05-01

We aimed to predict colorectal cancer (CRC) based on the demographic features and clinical correlates of personal symptoms and signs from Tianjin community-based CRC screening data.A total of 891,199 residents who were aged 60 to 74 and were screened in 2012 were enrolled. The Lasso logistic regression model was used to identify the predictors for CRC. Predictive validity was assessed by the receiver operating characteristic (ROC) curve. Bootstrapping method was also performed to validate this prediction model.CRC was best predicted by a model that included age, sex, education level, occupations, diarrhea, constipation, colon mucosa and bleeding, gallbladder disease, a stressful life event, family history of CRC, and a positive fecal immunochemical test (FIT). The area under curve (AUC) for the questionnaire with a FIT was 84% (95% CI: 82%-86%), followed by 76% (95% CI: 74%-79%) for a FIT alone, and 73% (95% CI: 71%-76%) for the questionnaire alone. With 500 bootstrap replications, the estimated optimism (<0.005) shows good discrimination in validation of prediction model.A risk prediction model for CRC based on a series of symptoms and signs related to enteric diseases in combination with a FIT was developed from first round of screening. The results of the current study are useful for increasing the awareness of high-risk subjects and for individual-risk-guided invitations or strategies to achieve mass screening for CRC.

Clinical response to PD-1 blockade correlates with a sub-fraction of peripheral central memory CD4+ T cells in patients with malignant melanoma.

PubMed

Takeuchi, Yoshiko; Tanemura, Atsushi; Tada, Yasuko; Katayama, Ichiro; Kumanogoh, Atsushi; Nishikawa, Hiroyoshi

2018-02-03

Cancer immunotherapy that blocks immune checkpoint molecules, such as PD-1/PD-L1, unleashes dysfunctional antitumor T-cell responses and has durable clinical benefits in various types of cancers. Yet its clinical efficacy is limited to a small proportion of patients, highlighting the need for identifying biomarkers that can predict the clinical response by exploring antitumor responses crucial for tumor regression. Here, we explored comprehensive immune-cell responses associated with clinical benefits using PBMCs from patients with malignant melanoma treated with anti-PD-1 monoclonal antibody. Pre- and post-treatment samples were collected from two different cohorts (discovery set and validation set) and subjected to mass cytometry assays that measured the expression levels of 35 proteins. Screening by high dimensional clustering in the discovery set identified increases in three micro-clusters of CD4+ T cells, a subset of central memory CD4+ T cells harboring the CD27+FAS-CD45RA-CCR7+ phenotype, after treatment in long-term survivors, but not in non-responders. The same increase was also observed in clinical responders in the validation set. We propose that increases in this subset of central memory CD4+ T cells in peripheral blood can be potentially used as a predictor of clinical response to PD-1 blockade therapy in patients with malignant melanoma. © The Japanese Society for Immunology. 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

AFRL Projects to Replace Cadmium

DTIC Science & Technology

2005-03-01

Protocol does not – Identify/ select a material or process – Impose processing restrictions on candidates – Implement a material or process into production...within proper limits • Use XRF to measure composition and thickness – Strippability • Remove coating within 60 minutes • Replate coating and pass...product information available? Magnetron Sputtering to Replace Cd • Task 2: Coating Deposition and Screening – Selection of qualified vendors and

Evaluation of a mobile screening service for abdominal aortic aneurysm in Broken Hill, a remote regional centre in far western NSW.

PubMed

Lesjak, Margaret S; Flecknoe-Brown, Stephen C; Sidford, Jan R; Payne, Kerryn; Fletcher, John P; Lyle, David M

2010-04-01

To evaluate the feasibility of a mobile screening service model for abdominal aortic aneurysm (AAA) in a remote population centre in Australia. Screening test evaluation. A remote regional centre (population: 20 000) in far western NSW. Men aged 65-74 years, identified from the Australian Electoral roll. A mobile screening service using directed ultrasonography, a basic health check and post-screening consultation. Attendance at the screening program, occurrence of AAA in the target population and effectiveness of screening processes. A total of 516 men without a previous diagnosis of AAA were screened, an estimated response rate of 60%. Of these, 463 (89.7%) had a normal aortic diameter, 28 (5.4%) ectatic and 25 (4.9%) a small, moderate or significant aneurysm. Two men with AAA were recommended for surgery. Feedback from participants indicated that the use of a personalised letter of invitation helped with recruitment, that the screening process was acceptable and the service valued. It is feasible to organise and operate a mobile AAA screening service from moderate sized rural and remote population centres. This model could be scaled up to provide national coverage for rural and remote residents.

Combination Testing Using a Single MSH5 Variant alongside HLA Haplotypes Improves the Sensitivity of Predicting Coeliac Disease Risk in the Polish Population.

PubMed

Paziewska, Agnieszka; Cukrowska, Bozena; Dabrowska, Michalina; Goryca, Krzysztof; Piatkowska, Magdalena; Kluska, Anna; Mikula, Michal; Karczmarski, Jakub; Oralewska, Beata; Rybak, Anna; Socha, Jerzy; Balabas, Aneta; Zeber-Lubecka, Natalia; Ambrozkiewicz, Filip; Konopka, Ewa; Trojanowska, Ilona; Zagroba, Malgorzata; Szperl, Malgorzata; Ostrowski, Jerzy

2015-01-01

Assessment of non-HLA variants alongside standard HLA testing was previously shown to improve the identification of potential coeliac disease (CD) patients. We intended to identify new genetic variants associated with CD in the Polish population that would improve CD risk prediction when used alongside HLA haplotype analysis. DNA samples of 336 CD and 264 unrelated healthy controls were used to create DNA pools for a genome wide association study (GWAS). GWAS findings were validated with individual HLA tag single nucleotide polymorphism (SNP) typing of 473 patients and 714 healthy controls. Association analysis using four HLA-tagging SNPs showed that, as was found in other populations, positive predicting genotypes (HLA-DQ2.5/DQ2.5, HLA-DQ2.5/DQ2.2, and HLA-DQ2.5/DQ8) were found at higher frequencies in CD patients than in healthy control individuals in the Polish population. Both CD-associated SNPs discovered by GWAS were found in the CD susceptibility region, confirming the previously-determined association of the major histocompatibility (MHC) region with CD pathogenesis. The two most significant SNPs from the GWAS were rs9272346 (HLA-dependent; localized within 1 Kb of DQA1) and rs3130484 (HLA-independent; mapped to MSH5). Specificity of CD prediction using the four HLA-tagging SNPs achieved 92.9%, but sensitivity was only 45.5%. However, when a testing combination of the HLA-tagging SNPs and the MSH5 SNP was used, specificity decreased to 80%, and sensitivity increased to 74%. This study confirmed that improvement of CD risk prediction sensitivity could be achieved by including non-HLA SNPs alongside HLA SNPs in genetic testing.

Electro-active polymers containing pendent 2,7-diarylfluorene fragments as materials for OLEDs

NASA Astrophysics Data System (ADS)

Krucaite, G.; Tavgeniene, D.; Peciulyte, L.; Buika, G.; Liu, L.; Zhang, B.; Xie, Z.; Grigalevicius, S.

2016-05-01

Poly[2-phenyl-7-(4-vinylphenyl)-9,9-diethylfluorene)], poly[2-(1-naphtyl)-7-(4-vinylphenyl)-9,9-diethylfluorene)] and poly[2-(4-biphenyl)-7-(4-vinylphenyl)-9,9-diethylfluorene)] were synthesized and characterized by NMR spectroscopy, elemental analysis and gel permeation chromatography. The derivatives represent materials of high thermal stability with initial thermal destruction temperatures from 390°C to 400 °C. The glass transition temperatures of the amorphous materials were 182 °C, 151 °C and 159 °C respectively. Hole-transporting properties of the polymeric materials were tested in the structures of organic light emitting diodes with Alq3 as the green emitter and electron transporting material. The device containing hole-transporting layers of polymer with 2-(4-biphenyl)-7-(4-vinylphenyl)-9,9-diethylfluorene moieties exhibited the best overall performance with turn on voltage of 3.6 V, a maximum photometric efficiency of 3.1 cd/A and maximum brightness of about 5300 cd/m2.

Ecological risks and potential sources of heavy metals in agricultural soils from Huanghuai Plain, China.

PubMed

Zhou, Lingli; Yang, Bing; Xue, Nandong; Li, Fasheng; Seip, Hans Martin; Cong, Xin; Yan, Yunzhong; Liu, Bo; Han, Baolu; Li, Huiying

2014-01-01

A total of 224 agricultural soil samples from Huanghuai Plain in China were investigated for the concentrations of seven heavy metals (As, Cd, Cr, Hg, Ni, Pb, and Zn). The mean concentrations of the metals were 12, 0.17, 79, 0.04, 35, 25, and 74 mg/kg, respectively. These values are similar or slightly higher than background values in this region, except for Cd with a mean nearly twice the background value. The estimated ecological risks based on contamination factors and potential ecological risk indexes are also mostly low, but considerable for Cd and Hg. Multivariate analysis (including Pearson's correlation analysis, hierarchical cluster analysis, and principal component analysis) clearly revealed three distinct metal groups, i.e., Cr/Ni/Zn, As/Cd/Pb, and Hg, whose concentrations were closely associated with the distribution and pollution characteristics of industries in and around the plain. The main anthropogenic sources for the three metal groups were identified as atmospheric deposition, sewage irrigation/fertilizers usage, and atmospheric deposition/irrigation water, respectively. The present results are well suited for planning, risk assessment, and decision making by environmental managers of this region.

Recent temporal variations of trace metal content in an Italian white wine.

PubMed

Illuminati, Silvia; Annibaldi, Anna; Truzzi, Cristina; Scarponi, Giuseppe

2014-09-15

For the first time in Italy, the temporal variations of Cd, Pb and Cu content in an Italian white wine were studied over the period 1995-2010. A previously set up and optimized Square-Wave Anodic Stripping Voltammetric technique was used. Cd showed a first decrease (∼30%) due to the use of pesticides with progressively low Cd residues. Since 2000 Cd had constant and extremely low values (0.17±0.07 μg L(-1)). A significant decrease (∼74%) from 1995 to 2010 was observed for Pb (mean concentration, 18±10 μg L(-1)) probably due to the recent decrease in Pb emissions in the atmosphere following the phasing out of metal from gasoline (in Italy since 2002). The Cu reduction (mean value, 32±15 μg L(-1)) of ∼74% from 1995 to 2010 was related to the use of phytoiatric products with a progressively low Cu content. Copyright © 2014 Elsevier Ltd. All rights reserved.

Identification of novel tumor antigens with patient-derived immune-selected antibodies

PubMed Central

Rodriguez-Pinto, Daniel; Sparkowski, Jason; Keough, Martin P.; Phoenix, Kathryn N.; Vumbaca, Frank; Han, David K.; Gundelfinger, Eckart D.; Beesley, Philip

2010-01-01

The identification of tumor antigens capable of eliciting an immune response in vivo may be an effective method to identify therapeutic cancer targets. We have developed a method to identify such antigens using frozen tumor-draining lymph node samples from breast cancer patients. Immune responses in tumor-draining lymph nodes were identified by immunostaining lymph node sections for B-cell markers (CD20&CD23) and Ki67 which revealed cell proliferation in germinal center zones. Antigen-dependent somatic hypermutation (SH) and clonal expansion (CE) were present in heavy chain variable (VH) domain cDNA clones obtained from these germinal centers, but not from Ki67 negative germinal centers. Recombinant VH single-domain antibodies were used to screen tumor proteins and affinity select potential tumor antigens. Neuroplastin (NPTN) was identified as a candidate breast tumor antigen using proteomic identification of affinity selected tumor proteins with a recombinant VH single chain antibody. NPTN was found to be highly expressed in approximately 20% of invasive breast carcinomas and 50% of breast carcinomas with distal metastasis using a breast cancer tissue array. Additionally, NPTN over-expression in a breast cancer cell line resulted in a significant increase in tumor growth and angiogenesis in vivo which was related to increased VEGF production in the transfected cells. These results validate NPTN as a tumor-associated antigen which could promote breast tumor growth and metastasis if aberrantly expressed. These studies also demonstrate that humoral immune responses in tumor-draining lymph nodes can provide antibody reagents useful in identifying tumor antigens with applications for biomarker screening, diagnostics and therapeutic interventions. PMID:18568347

Prevalence of human papillomavirus infection & cervical abnormalities in HIV-positive women in eastern India.

PubMed

Chakravarty, Jaya; Chourasia, Ankita; Thakur, Minaxi; Singh, Abhishek Kumar; Sundar, Shyam; Agrawal, Nisha Rani

2016-01-01

India has the third highest burden of HIV and highest number of cervical cancer in the world. A cross-sectional study was performed to determine the prevalence and types of human papillomavirus (HPV) infection, and the factors associated with HPV infection and abnormal cervical cytology in HIV-positive women attending the Antiretroviral Therapy (ART) Centre in a tertiary care hospital in eastern India. We screened 216 HIV- positive women with Papanicolau smear cytology and HPV testing. HPV DNA was detected by using consensus primers followed by sequencing. Of the 216 HIV-positive women screened, 58 (26.85%) were HPV-positive; 56 (25.9%) were of high-risk (HR) HPV type. The most prevalent HPV type was HPV-16 (7.9%); non 16 and 18 HPV types were present in 17.6 per cent patients. Age ≤ 35 yr [(OR), 2.56 (1.26-5.19)], illiteracy [OR, 2.30 (1.19-4.46)], rural residence [OR, 3.99 (1.27-12.56)] and CD4 ≤ 350/µl [OR, 2.46 (1.26-4.83)] were associated with increased risk of acquisition of HPV. One hundred thirty nine (74.33%) patients had normal/ negative for intraepithelial lesions (NILM) cytology, three (1.60%) had atypical squamous cells of undetermined significance (ASCUS), 32 (17.11%) had low-grade squamous intraepithelial lesions (LSIL), 10 (5.35%) had high-grade squamous intraepithelial lesions (HSIL) and three (1.60%) had carcinoma cervix. WHO clinical Stage III and IV [OR, 2.83 (1.07-7.49)] and CD4 ≤ 350/µl [OR, 2.84 (1.30-6.20)] were risk factors for abnormal cytology. Our study showed 26.85 per cent HPV positivity in HIV infected women in this region, with HPV-16 as the commonest genotype. Abnormal cervical cytology was seen in about 25 per cent women. Regular Pap smear screening as recommended by the National AIDS Control Organization will help in early detection of cervical abnormalities in HIV- positive women.

The effectiveness of police custody assessments in identifying suspects with intellectual disabilities and attention deficit hyperactivity disorder

PubMed Central

2013-01-01

Background Intellectual Disabilities (ID) and Attention Deficit Hyperactivity Disorder (ADHD) are recognized psychological vulnerabilities in police interviews and court proceedings in England and Wales. The aims of this study were to investigate: (a) the prevalence of ID and/or ADHD among suspects detained at a large London metropolitan police station and their relationship with conduct disorder (CD), (b) the impact of their condition on police staff resources, (c) the effectiveness of current custody assessment tools in identifying psychological vulnerabilities, and (d) the use of ‘Appropriate Adults’ in interviews. Method A total of 200 individuals in a police custody suite were interviewed and screened for ID, ADHD (current symptoms) and CD. Results The screening rates for these three disorders were 6.7%, 23.5% and 76.3%, respectively. ADHD contributed significantly to increased requests being made of staff after controlling for CD and duration of time in custody. This is a novel finding. Reading and writing difficulties and mental health problems were often identified from the custody risk assessment tools, but they were not used effectively to inform on the need for the use of an Appropriate Adult. The frequency with which Appropriate Adults were provided to support detainees in police interviews (4.2%) remains almost identical to that found in a similar study conducted 20 years previously. Conclusions The current findings suggest that in spite of reforms recently made in custodial settings, procedures may not have had the anticipated impact of improving safeguards for vulnerable suspects. Detainees with ID and ADHD require an Appropriate Adult during police interviews and other formal custody procedures, which they commonly do not currently receive. The findings of the current study suggest this may be due, in large part, to the ineffective use of risk-assessment tools and healthcare professionals, which represent missed opportunities to identify such vulnerabilities. PMID:24261542

A search for H/ACA snoRNAs in yeast using MFE secondary structure prediction.

PubMed

Edvardsson, Sverker; Gardner, Paul P; Poole, Anthony M; Hendy, Michael D; Penny, David; Moulton, Vincent

2003-05-01

Noncoding RNA genes produce functional RNA molecules rather than coding for proteins. One such family is the H/ACA snoRNAs. Unlike the related C/D snoRNAs these have resisted automated detection to date. We develop an algorithm to screen the yeast genome for novel H/ACA snoRNAs. To achieve this, we introduce some new methods for facilitating the search for noncoding RNAs in genomic sequences which are based on properties of predicted minimum free-energy (MFE) secondary structures. The algorithm has been implemented and can be generalized to enable screening of other eukaryote genomes. We find that use of primary sequence alone is insufficient for identifying novel H/ACA snoRNAs. Only the use of secondary structure filters reduces the number of candidates to a manageable size. From genomic context, we identify three strong H/ACA snoRNA candidates. These together with a further 47 candidates obtained by our analysis are being experimentally screened.

Personal navigation increases colorectal cancer screening uptake.

PubMed

Ritvo, Paul G; Myers, Ronald E; Paszat, Lawrence F; Tinmouth, Jill M; McColeman, Joshua; Mitchell, Brian; Serenity, Mardie; Rabeneck, Linda

2015-03-01

Prior randomized, controlled trials (RCTs) indicate that patient navigation can boost colorectal cancer screening rates in primary care. The sparse literature on pragmatic trials of interventions designed to increase colorectal cancer screening adherence motivated this trial on the impact of a patient navigation intervention that included support for performance of the participants' preferred screening test (colonoscopy or stool blood testing). Primary care patients (n = 5,240), 50 to 74 years of age, with no prior diagnosis of bowel cancer and no record of a recent colorectal cancer screening test, were identified at the Group Health Centre in northern Ontario. These patients were randomly assigned to an intervention group (n = 2,629) or a usual care control group (n = 2,611). Intervention group participants were contacted by a trained nurse navigator by telephone to discuss colorectal cancer screening. Interested patients met with the navigator, who helped them identify and arrange for performance of the preferred screening test. Control group participants received usual care. Multivariate analyses were conducted using medical records data to assess intervention impact on screening adherence within 12 months after randomization. Mean patient age was 59 years, and 50% of participants were women. Colorectal cancer screening adherence was higher in the intervention group (35%) than in the control group (20%), a difference that was statistically significant (OR, 2.11; confidence interval, 1.87-2.39). Preference-based patient navigation increased screening uptake in a pragmatic RCT. Patient navigation increased colorectal cancer screening rates in a pragmatic RCT in proportions similar to those observed in explanatory RCTs. ©2014 American Association for Cancer Research.

The Missing Link in Epstein-Barr Virus Immune Evasion: the BDLF3 Gene Induces Ubiquitination and Downregulation of Major Histocompatibility Complex Class I (MHC-I) and MHC-II

PubMed Central

Quinn, Laura L.; Williams, Luke R.; White, Claire; Forrest, Calum; Rowe, Martin

2015-01-01

ABSTRACT The ability of Epstein-Barr virus (EBV) to spread and persist in human populations relies on a balance between host immune responses and EBV immune evasion. CD8+ cells specific for EBV late lytic cycle antigens show poor recognition of target cells compared to immediate early and early antigen-specific CD8+ cells. This phenomenon is due in part to the early EBV protein BILF1, whose immunosuppressive activity increases with lytic cycle progression. However, published data suggest the existence of a hitherto unidentified immune evasion protein further enhancing protection against late EBV antigen-specific CD8+ cells. We have now identified the late lytic BDLF3 gene as the missing link accounting for efficient evasion during the late lytic cycle. Interestingly, BDLF3 also contributes to evasion of CD4+ cell responses to EBV. We report that BDLF3 downregulates expression of surface major histocompatibility complex (MHC) class I and class II molecules in the absence of any effect upon other surface molecules screened, including CD54 (ICAM-1) and CD71 (transferrin receptor). BDLF3 both enhanced internalization of surface MHC molecules and reduced the rate of their appearance at the cell surface. The reduced expression of surface MHC molecules correlated with functional protection against CD8+ and CD4+ T cell recognition. The molecular mechanism was identified as BDLF3-induced ubiquitination of MHC molecules and their subsequent downregulation in a proteasome-dependent manner. IMPORTANCE Immune evasion is a necessary feature of viruses that establish lifelong persistent infections in the face of strong immune responses. EBV is an important human pathogen whose immune evasion mechanisms are only partly understood. Of the EBV immune evasion mechanisms identified to date, none could explain why CD8+ T cell responses to late lytic cycle genes are so infrequent and, when present, recognize lytically infected target cells so poorly relative to CD8+ T cells specific for early lytic cycle antigens. The present work identifies an additional immune evasion protein, BDLF3, that is expressed late in the lytic cycle and impairs CD8+ T cell recognition by targeting cell surface MHC class I molecules for ubiquitination and proteasome-dependent downregulation. Interestingly, BDLF3 also targets MHC class II molecules to impair CD4+ T cell recognition. BDLF3 is therefore a rare example of a viral protein that impairs both the MHC class I and class II antigen-presenting pathways. PMID:26468525

The Missing Link in Epstein-Barr Virus Immune Evasion: the BDLF3 Gene Induces Ubiquitination and Downregulation of Major Histocompatibility Complex Class I (MHC-I) and MHC-II.

PubMed

Quinn, Laura L; Williams, Luke R; White, Claire; Forrest, Calum; Zuo, Jianmin; Rowe, Martin

2016-01-01

The ability of Epstein-Barr virus (EBV) to spread and persist in human populations relies on a balance between host immune responses and EBV immune evasion. CD8(+) cells specific for EBV late lytic cycle antigens show poor recognition of target cells compared to immediate early and early antigen-specific CD8(+) cells. This phenomenon is due in part to the early EBV protein BILF1, whose immunosuppressive activity increases with lytic cycle progression. However, published data suggest the existence of a hitherto unidentified immune evasion protein further enhancing protection against late EBV antigen-specific CD8(+) cells. We have now identified the late lytic BDLF3 gene as the missing link accounting for efficient evasion during the late lytic cycle. Interestingly, BDLF3 also contributes to evasion of CD4(+) cell responses to EBV. We report that BDLF3 downregulates expression of surface major histocompatibility complex (MHC) class I and class II molecules in the absence of any effect upon other surface molecules screened, including CD54 (ICAM-1) and CD71 (transferrin receptor). BDLF3 both enhanced internalization of surface MHC molecules and reduced the rate of their appearance at the cell surface. The reduced expression of surface MHC molecules correlated with functional protection against CD8(+) and CD4(+) T cell recognition. The molecular mechanism was identified as BDLF3-induced ubiquitination of MHC molecules and their subsequent downregulation in a proteasome-dependent manner. Immune evasion is a necessary feature of viruses that establish lifelong persistent infections in the face of strong immune responses. EBV is an important human pathogen whose immune evasion mechanisms are only partly understood. Of the EBV immune evasion mechanisms identified to date, none could explain why CD8(+) T cell responses to late lytic cycle genes are so infrequent and, when present, recognize lytically infected target cells so poorly relative to CD8(+) T cells specific for early lytic cycle antigens. The present work identifies an additional immune evasion protein, BDLF3, that is expressed late in the lytic cycle and impairs CD8(+) T cell recognition by targeting cell surface MHC class I molecules for ubiquitination and proteasome-dependent downregulation. Interestingly, BDLF3 also targets MHC class II molecules to impair CD4(+) T cell recognition. BDLF3 is therefore a rare example of a viral protein that impairs both the MHC class I and class II antigen-presenting pathways. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Missed opportunity for alcohol problem prevention among army active duty service members postdeployment.

PubMed

Larson, Mary Jo; Mohr, Beth A; Adams, Rachel Sayko; Wooten, Nikki R; Williams, Thomas V

2014-08-01

We identified to what extent the Department of Defense postdeployment health surveillance program identifies at-risk drinking, alone or in conjunction with psychological comorbidities, and refers service members who screen positive for additional assessment or care. We completed a cross-sectional analysis of 333 803 US Army active duty members returning from Iraq or Afghanistan deployments in fiscal years 2008 to 2011 with a postdeployment health assessment. Alcohol measures included 2 based on self-report quantity-frequency items-at-risk drinking (positive Alcohol Use Disorders Identification Test alcohol consumption questions [AUDIT-C] screen) and severe alcohol problems (AUDIT-C score of 8 or higher)-and another based on the interviewing provider's assessment. Nearly 29% of US Army active duty members screened positive for at-risk drinking, and 5.6% had an AUDIT-C score of 8 or higher. Interviewing providers identified potential alcohol problems among only 61.8% of those screening positive for at-risk drinking and only 74.9% of those with AUDIT-C scores of 8 or higher. They referred for a follow-up visit to primary care or another setting only 29.2% of at-risk drinkers and only 35.9% of those with AUDIT-C scores of 8 or higher. This study identified missed opportunities for early intervention for at-risk drinking. Future research should evaluate the effect of early intervention on long-term outcomes.

Chromosomal aneuploidies and copy number variations in posterior fossa abnormalities diagnosed by prenatal ultrasonography.

PubMed

Lei, Ting; Feng, Jie-Ling; Xie, Ying-Jun; Xie, Hong-Ning; Zheng, Ju; Lin, Mei-Fang

2017-11-01

To explore the genetic aetiology of fetal posterior fossa abnormalities (PFAs). This study involved cases of PFAs that were identified by prenatal ultrasonographic screening and confirmed postnatally between January 2012 and January 2016. Conventional cytogenetic analyses and chromosomal microarray analysis were performed, and chromosomal aneuploidies and copy number variations (CNVs) were identified. Among 74 cases included in this study, 8 were of Blake's pouch cyst; 7, Dandy-Walker malformation; 11, vermian hypoplasia; 32, enlarged cisterna magna; and 16, cerebellar hypoplasia. The rates of nonbenign chromosomal aberrations (including chromosomal aneuploidies, pathogenic CNVs, and variants of unknown significance) were 2/8 (25.0%), 2/7 (28.5%), 8/11 (72.7%), 7/32 (21.9%), and 6/16 (37.5%), respectively. Cases were also classified as isolated PFAs (30/74), PFAs with other central nervous system (CNS) abnormalities (13/74), or PFAs with extra-CNS structural abnormalities (31/74). No fetuses with isolated PFAs or PFAs accompanied by other CNS abnormalities exhibited chromosomal aneuploidies or pathogenic CNVs. The rate of pathogenic chromosomal aberrations in the remaining fetuses was 17/31 (22.9%). The combined use of chromosomal microarray analysis and karyotype analysis might assist the prenatal diagnosis and management of PFAs, with extra-CNS structural abnormalities being detected by ultrasonography. © 2017 John Wiley & Sons, Ltd.

A Novel Inhibitor Of Topoisomerase I is Selectively Toxic For A Subset of Non-Small Cell Lung Cancer Cell Lines | Office of Cancer Genomics

Cancer.gov

SW044248, identified through a screen for chemicals that are selectively toxic for NSCLC cell lines, was found to rapidly inhibit macromolecular synthesis in sensitive, but not in insensitive cells. SW044248 killed approximately 15% of a panel of 74 NSCLC cell lines and was non-toxic to immortalized human bronchial cell lines.

Utility of quantitative sensory testing and screening tools in identifying HIV-associated peripheral neuropathy in Western Kenya: pilot testing.

PubMed

Cettomai, Deanna; Kwasa, Judith; Kendi, Caroline; Birbeck, Gretchen L; Price, Richard W; Bukusi, Elizabeth A; Cohen, Craig R; Meyer, Ana-Claire

2010-12-08

Neuropathy is the most common neurologic complication of HIV but is widely under-diagnosed in resource-constrained settings. We aimed to identify tools that accurately distinguish individuals with moderate/severe peripheral neuropathy and can be administered by non-physician healthcare workers (HCW) in resource-constrained settings. We enrolled a convenience sample of 30 HIV-infected outpatients from a Kenyan HIV-care clinic. A HCW administered the Neuropathy Severity Score (NSS), Single Question Neuropathy Screen (Single-QNS), Subjective Peripheral Neuropathy Screen (Subjective-PNS), and Brief Peripheral Neuropathy Screen (Brief-PNS). Monofilament, graduated tuning fork, and two-point discrimination examinations were performed. Tools were validated against a neurologist's clinical assessment of moderate/severe neuropathy. The sample was 57% male, mean age 38.6 years, and mean CD4 count 324 cells/µL. Neurologist's assessment identified 20% (6/30) with moderate/severe neuropathy. Diagnostic utilities for moderate/severe neuropathy were: Single-QNS--83% sensitivity, 71% specificity; Subjective-PNS-total--83% sensitivity, 83% specificity; Subjective-PNS-max and NSS--67% sensitivity, 92% specificity; Brief-PNS--0% sensitivity, 92% specificity; monofilament--100% sensitivity, 88% specificity; graduated tuning fork--83% sensitivity, 88% specificity; two-point discrimination--75% sensitivity, 58% specificity. Pilot testing suggests Single-QNS, Subjective-PNS, and monofilament examination accurately identify HIV-infected patients with moderate/severe neuropathy and may be useful diagnostic tools in resource-constrained settings.

Identification of cadmium-induced Agaricus blazei genes through suppression subtractive hybridization.

PubMed

Wang, Liling; Li, Haibo; Wei, Hailong; Wu, Xueqian; Ke, Leqin

2014-01-01

Cadmium (Cd) is one of the most serious environmental pollutants. Filamentous fungi are very promising organisms for controlling and reducing the amount of heavy metals released by human and industrial activities. However, the molecular mechanisms involved in Cd accumulation and tolerance of filamentous fungi are not fully understood. Agaricus blazei Murrill, an edible mushroom with medicinal properties, demonstrates high tolerance for heavy metals, especially Cd. To investigate the molecular mechanisms underlying the response of A. blazei after Cd exposure, we constructed a forward subtractive library that represents cadmium-induced genes in A. blazei under 4 ppm Cd stress for 14 days using suppression subtractive hybridization combined with mirror orientation selection. Differential screening allowed us to identify 39 upregulated genes, 26 of which are involved in metabolism, protein fate, cellular transport, transport facilitation and transport routes, cell rescue, defense and virulence, transcription, and the action of proteins with a binding function, and 13 are encoding hypothetical proteins with unknown functions. Induction of six A. blazei genes after Cd exposure was further confirmed by RT-qPCR. The cDNAs isolated in this study contribute to our understanding of genes involved in the biochemical pathways that participate in the response of filamentous fungi to Cd exposure. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Optimizing screening for tuberculosis and hepatitis B prior to starting tumor necrosis factor-α inhibitors in Crohn's disease.

PubMed

van der Have, Mike; Oldenburg, Bas; Fidder, Herma H; Belderbos, Tim D G; Siersema, Peter D; van Oijen, Martijn G H

2014-03-01

Treatment with tumor necrosis factor-α (TNF-α) inhibitors in patients with Crohn's disease (CD) is associated with potentially serious infections, including tuberculosis (TB) and hepatitis B virus (HBV). We assessed the cost-effectiveness of extensive TB screening and HBV screening prior to initiating TNF-α inhibitors in CD. We constructed two Markov models: (1) comparing tuberculin skin test (TST) combined with chest X-ray (conventional TB screening) versus TST and chest X-ray followed by the interferon-gamma release assay (extensive TB screening) in diagnosing TB; and (2) HBV screening versus no HBV screening. Our base-case included an adult CD patient starting with infliximab treatment. Input parameters were extracted from the literature. Direct medical costs were assessed and discounted following a third-party payer perspective. The main outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity and Monte Carlo analyses were performed over wide ranges of probability and cost estimates. At base-case, the ICERs of extensive screening and HBV screening were €64,340 and €75,760 respectively to gain one quality-adjusted life year. Sensitivity analyses concluded that extensive TB screening was a cost-effective strategy if the latent TB prevalence is more than 12 % or if the false positivity rate of TST is more than 20 %. HBV screening became cost-effective if HBV reactivation or HBV-related mortality is higher than 37 and 62 %, respectively. Extensive TB screening and HBV screening are not cost-effective compared with conventional TB screening and no HBV screening, respectively. However, when targeted at high-risk patient groups, these screening strategies are likely to become cost-effective.

Screening for Spiritual Struggle in an Adolescent Transgender Clinic: Feasibility and Acceptability.

PubMed

Grossoehme, Daniel H; Teeters, Alexis; Jelinek, Sue; Dimitriou, Sophia M; Conard, Lee Ann E

2016-01-01

Spiritual struggles are associated with poorer health outcomes, including depression, which has higher prevalence among transgender individuals than the general population. This study's objective was to improve the quality of care in an outpatient transgender clinic by screening patients and caregivers for spiritual struggle and future intervention. The quality improvement questions addressed were whether screening for spiritual struggle was feasible and acceptable; and whether the sensitivity and specificity of the Rush Protocol were acceptable. Revision of the screening was based on cognitive interviews with the 115 adolescents and caregivers who were screened. Prevalence of spiritual struggle was 38-47%. Compared to the Negative R-COPE, the Rush Protocol screener had sensitivities of 44-80% and specificities of 60-74%. The Rush Protocol was acceptable to adolescents seen in a transgender clinic, caregivers, and clinic staff; was feasible to deliver during outpatient clinic visits, and offers a straightforward means of identifying transgender persons and caregivers experiencing spiritual struggle.

Random plasma glucose in serendipitous screening for glucose intolerance: screening for impaired glucose tolerance study 2.

PubMed

Ziemer, David C; Kolm, Paul; Foster, Jovonne K; Weintraub, William S; Vaccarino, Viola; Rhee, Mary K; Varughese, Rincy M; Tsui, Circe W; Koch, David D; Twombly, Jennifer G; Narayan, K M Venkat; Phillips, Lawrence S

2008-05-01

With positive results from diabetes prevention studies, there is interest in convenient ways to incorporate screening for glucose intolerance into routine care and to limit the need for fasting diagnostic tests. The aim of this study is to determine whether random plasma glucose (RPG) could be used to screen for glucose intolerance. This is a cross-sectional study. The participants of this study include a voluntary sample of 990 adults not known to have diabetes. RPG was measured, and each subject had a 75-g oral glucose tolerance test several weeks later. Glucose intolerance targets included diabetes, impaired glucose tolerance (IGT), and impaired fasting glucose(110) (IFG(110); fasting glucose, 110-125 mg/dl, and 2 h glucose < 140 mg/dl). Screening performance was measured by area under receiver operating characteristic curves (AROC). Mean age was 48 years, and body mass index (BMI) was 30.4 kg/m(2); 66% were women, and 52% were black; 5.1% had previously unrecognized diabetes, and 24.0% had any "high-risk" glucose intolerance (diabetes or IGT or IFG(110)). The AROC was 0.80 (95% CI 0.74-0.86) for RPG to identify diabetes and 0.72 (0.68-0.75) to identify any glucose intolerance, both highly significant (p < 0.001). Screening performance was generally consistent at different times of the day, regardless of meal status, and across a range of risk factors such as age, BMI, high density lipoprotein cholesterol, triglycerides, and blood pressure. RPG values should be considered by health care providers to be an opportunistic initial screening test and used to prompt further evaluation of patients at risk of glucose intolerance. Such "serendipitous screening" could help to identify unrecognized diabetes and prediabetes.

Automatic Classification of Users' Health Information Need Context: Logistic Regression Analysis of Mouse-Click and Eye-Tracker Data.

PubMed

Pian, Wenjing; Khoo, Christopher Sg; Chi, Jianxing

2017-12-21

Users searching for health information on the Internet may be searching for their own health issue, searching for someone else's health issue, or browsing with no particular health issue in mind. Previous research has found that these three categories of users focus on different types of health information. However, most health information websites provide static content for all users. If the three types of user health information need contexts can be identified by the Web application, the search results or information offered to the user can be customized to increase its relevance or usefulness to the user. The aim of this study was to investigate the possibility of identifying the three user health information contexts (searching for self, searching for others, or browsing with no particular health issue in mind) using just hyperlink clicking behavior; using eye-tracking information; and using a combination of eye-tracking, demographic, and urgency information. Predictive models are developed using multinomial logistic regression. A total of 74 participants (39 females and 35 males) who were mainly staff and students of a university were asked to browse a health discussion forum, Healthboards.com. An eye tracker recorded their examining (eye fixation) and skimming (quick eye movement) behaviors on 2 types of screens: summary result screen displaying a list of post headers, and detailed post screen. The following three types of predictive models were developed using logistic regression analysis: model 1 used only the time spent in scanning the summary result screen and reading the detailed post screen, which can be determined from the user's mouse clicks; model 2 used the examining and skimming durations on each screen, recorded by an eye tracker; and model 3 added user demographic and urgency information to model 2. An analysis of variance (ANOVA) analysis found that users' browsing durations were significantly different for the three health information contexts (P<.001). The logistic regression model 3 was able to predict the user's type of health information context with a 10-fold cross validation mean accuracy of 84% (62/74), followed by model 2 at 73% (54/74) and model 1 at 71% (52/78). In addition, correlation analysis found that particular browsing durations were highly correlated with users' age, education level, and the urgency of their information need. A user's type of health information need context (ie, searching for self, for others, or with no health issue in mind) can be identified with reasonable accuracy using just user mouse clicks that can easily be detected by Web applications. Higher accuracy can be obtained using Google glass or future computing devices with eye tracking function. ©Wenjing Pian, Christopher SG Khoo, Jianxing Chi. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 21.12.2017.

Syphilis in Men Who Have Sex With Men: A Warning Sign for HIV Infection.

PubMed

Gállego-Lezáun, C; Arrizabalaga Asenjo, M; González-Moreno, J; Ferullo, I; Teslev, A; Fernández-Vaca, V; Payeras Cifre, A

2015-11-01

To describe the clinical and epidemiological characteristics of syphilis in men who have sex with men (MSM) in an area of Mallorca, Spain. We performed a retrospective analysis of syphilis cases in MSM seen at a hospital in Mallorca between January 2005 and June 2013. Fifty-five cases of syphilis were recorded in MSM during the study period (34.3% of all cases diagnosed), and 74.5% of these patients had human immunodeficiency virus (HIV) coinfection. The two diseases had been diagnosed simultaneously in 70.7% of this population. Patients with HIV coinfection had a median CD4 count of 456cells/μL (range, 29-979 cells/μL). Syphilis was diagnosed clinically in 49.1% of cases and by screening in the remaining 50.9%. The most common form of syphilis was late latent or indeterminate syphilis (41.9% of cases). In the group of men with syphilis, MSM had a higher risk of HIV infection. A majority of MSM with syphilis had HIV coinfection. HIV screening is therefore essential in this population and could even result in early diagnosis. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

Persistent decrease in alpha current density in fully remitted subjects with major depressive disorder treated with fluoxetine: A prospective electric tomography study.

PubMed

Almeida Montes, Luis Guillermo; Prado Alcántara, Hugo; Portillo Cedeño, Bertha Alicia; Hernández García, Ana Olivia; Fuentes Rojas, Patricia Elisa

2015-06-01

Major depressive disorder (MDD) is recurrent, and its pathophysiology is not fully understood. Studies using electric tomography (ET) have identified abnormalities in the current density (CD) of MDD subjects in regions associated with the neurobiology of MDD, such as the anterior cingulate cortex (ACC) and medial orbitofrontal cortex (mOFC). However, little is known regarding the long-term CD changes in MDD subjects who respond to antidepressants. The aim of this study was to compare CD between healthy and MDD subjects who received 1-year open-label treatment with fluoxetine. Thirty-two-channel electroencephalograms (EEGs) were collected from 70 healthy controls and 74 MDD subjects at baseline (pre-treatment), 1 and 2weeks and 1, 2, 6, 9 and 12months. Variable-resolution ET (VARETA) was used to assess the CD between subject groups at each time point. The MDD group exhibited decreased alpha CD (αCD) in the occipital and parietal cortices, ACC, mOFC, thalamus and caudate nucleus at each time point. The αCD abnormalities persisted in the MDD subjects despite their achieving full remission. The low sub-alpha band was different between the healthy and MDD subjects. Differences in the amount of αCD between sexes and treatment outcomes were observed. Lack of a placebo arm and the loss of depressed patients to follow-up were significant limitations. The persistence of the decrease in αCD might suggest that the underlying pathophysiologic mechanisms of MDD are not corrected despite the asymptomatic state of MDD subjects, which could be significant in understanding the highly recurrent nature of MDD. Copyright © 2015 Elsevier B.V. All rights reserved.

Pretransplantation soluble CD30 level as a predictor of acute rejection in kidney transplantation: a meta-analysis.

PubMed

Chen, Yile; Tai, Qiang; Hong, Shaodong; Kong, Yuan; Shang, Yushu; Liang, Wenhua; Guo, Zhiyong; He, Xiaoshun

2012-11-15

The question of whether high pretransplantation soluble CD30 (sCD30) level can be a predictor of kidney transplant acute rejection (AR) is under debate. Herein, we performed a meta-analysis on the predictive efficacy of sCD30 for AR in renal transplantation. PubMed (1966-2012), EMBASE (1988-2012), and Web of Science (1986-2012) databases were searched for studies concerning the predictive efficacy of sCD30 for AR after kidney transplantation. After a careful review of eligible studies, sensitivity, specificity, and other measures of the accuracy of sCD30 were pooled. A summary receiver operating characteristic curve was used to represent the overall test performance. Twelve studies enrolling 2507 patients met the inclusion criteria. The pooled estimates for pretransplantation sCD30 in prediction of allograft rejection risk were poor, with a sensitivity of 0.70 (95% confidence interval (CI), 0.66-0.74), a specificity of 0.48 (95% CI, 0.46-0.50), a positive likelihood ratio of 1.35 (95% CI, 1.20-1.53), a negative likelihood ratio of 0.68 (95% CI, 0.55-0.84), and a diagnostic odds ratio of 2.07 (95% CI, 1.54-2.80). The area under curve of the summary receiver operating characteristic curve was 0.60, indicating poor overall accuracy of the serum sCD30 level in the prediction of patients at risk for AR. The results of the meta-analysis show that the accuracy of pretransplantation sCD30 for predicting posttransplantation AR was poor. Prospective studies are needed to clarify the usefulness of this test for identifying risks of AR in transplant recipients.

Targeting CD6 for the treatment of experimental autoimmune uveitis.

PubMed

Zhang, Lingjun; Li, Yan; Qiu, Wen; Bell, Brent A; Dvorina, Nina; Baldwin, William M; Singer, Nora; Kern, Timothy; Caspi, Rachel R; Fox, David A; Lin, Feng

2018-06-01

CD6 is emerging as a new target for treating many pathological conditions in which T cells are integrally involved, but even the latest data from studies of CD6 gene engineered mice were still contradictory. To address this issue, we studied experimental autoimmune uveitis (EAU), a model of autoimmune uveitis, in wild-type (WT) and CD6 knockout (KO) mice. After EAU induction in WT and CD6 KO mice, we evaluated ocular inflammation and compared retinal antigen-specific T-cell responses using scanning laser ophthalmoscopy, spectral-domain optical coherence tomography, histopathology, and T cell recall assays. Uveitogenic T cells from WT and CD6 KO mice were adoptively transferred into WT naïve mice to confirm the impact of CD6 on T cells. In addition, we immunized CD6 KO mice with recombinant CD6 protein to develop mouse anti-mouse CD6 monoclonal antibodies (mAbs) in which functional antibodies exhibiting cross-reactivity with human CD6 were screened and identified for treatment studies. In CD6 KO mice with EAU, we found significantly decreased retinal inflammation and reduced autoreactive T-cell responses, and confirmed the impaired uveitogenic capacity of T cells from these mice in an adoptive transfer experiment. Notably, one of these cross-reactive mAbs significantly ameliorated retinal inflammation in EAU induced by the adoptive transfer of uveitogenic T cells. Together, these data strongly suggest that CD6 plays a previously unknown, but pivotal role in autoimmune uveitis, and may be a promising new treatment target for this blinding disease. In addition, the newly developed mouse anti-mouse/human CD6 mAbs could be valuable tools for testing CD6-targeted therapies in other mouse models of human diseases. Copyright © 2018 Elsevier Ltd. All rights reserved.

Determining the sensitivity of transrectal ultrasonography on a consecutive series of prostate cancers in a clinical and screening setting.

PubMed

Ciatto, Stefano; Bonardi, Rita; Lombardi, Claudio; Zappa, Marco; Gervasi, Ginetta

2002-01-01

To evaluate the sensitivity at transrectal ultrasonography (TRUS) for prostate cancer. A consecutive series of 170 prostate cancers identified by matching local cancer registry and TRUS archives at the Centro per lo Studio e la Prevenzione Oncologica of Florence. TRUS sensitivity was determined as the ratio of TRUS positive to total prostate cancers occurring at different intervals from TRUS date. Univariate and multivariate analyses of sensitivity determinants were performed. Sensitivity at 6 months, 1, 2 and 3 years after the test was 94.1% (95% CI, 90-98), 89.8% (95% CI, 85-95), 80.4% (95% CI, 74-87) and 74.1% (95% CI, 68-81%), respectively. A higher sensitivity (statistically significant) of TRUS was observed only if digital rectal examination was suspicious, whereas no association to sensitivity was observed for age, prostate-specific antigen or prostate-specific antigen density. The study provided a reliable estimate of TRUS sensitivity, particularly reliable being checked against a cancer registry: observed sensitivity was high, at least of the same magnitude of other cancer screening tests. TRUS, which is known to allow for considerable diagnostic anticipation and is more specific than prostate-specific antigen, might still be considered for its contribution to a screening approach.

Identification of amino acid residues involved in substrate specificity of plant acyl-ACP thioesterases using a bioinformatics-guided approach

PubMed Central

Mayer, Kimberly M; Shanklin, John

2007-01-01

Background The large amount of available sequence information for the plant acyl-ACP thioesterases (TEs) made it possible to use a bioinformatics-guided approach to identify amino acid residues involved in substrate specificity. The Conserved Property Difference Locator (CPDL) program allowed the identification of putative specificity-determining residues that differ between the FatA and FatB TE classes. Six of the FatA residue differences identified by CPDL were incorporated into the FatB-like parent via site-directed mutagenesis and the effect of each on TE activity was determined. Variants were expressed in E. coli strain K27 that allows determination of enzyme activity by GCMS analysis of fatty acids released into the medium. Results Substitutions at four of the positions (74, 86, 141, and 174) changed substrate specificity to varying degrees while changes at the remaining two positions, 110 and 221, essentially inactivated the thioesterase. The effects of substitutions at positions 74, 141, and 174 (3-MUT) or 74, 86, 141, 174 (4-MUT) were not additive with respect to specificity. Conclusion Four of six putative specificity determining positions in plant TEs, identified with the use of CPDL, were validated experimentally; a novel colorimetric screen that discriminates between active and inactive TEs is also presented. PMID:17201914

A novel immunotoxin reveals a new role for CD321 in endothelial cells

PubMed Central

Kim, Jia; Hokaiwado, Shintaro; Nawa, Makiko; Okamoto, Hayato; Kogiso, Tomohiko; Watabe, Tetsuro; Hattori, Nobutaka

2017-01-01

There are currently several antibody therapies that directly target tumors, and antibody-drug conjugates represent a novel moiety as next generation therapeutics. Here, we used a unique screening probe, DT3C, to identify functional antibodies that recognized surface molecules and functional epitopes, and which provided toxin delivery capability. Accordingly, we generated the 90G4 antibody, which induced DT3C-dependent cytotoxicity in endothelial cells. Molecular analysis revealed that 90G4 recognized CD321, a protein localized at tight junctions. Although CD321 plays a pivotal role in inflammation and lymphocyte trans-endothelial migration, little is known about its mechanism of action in endothelial cells. Targeting of CD321 by the 90G4 immunotoxin induced cell death. Moreover, 90G4 immunotoxin caused cytotoxicity primarily in migratory endothelial cells, but not in those forming sheets, suggesting a critical role for CD321 in tumor angiogenesis. We also found that hypoxia triggered redistribution of CD321 to a punctate localization on the basal side of cells, resulting in functional impairment of tight junctions and increased motility. Thus, our findings raise the intriguing possibility that endothelial CD321 presented cellular localization in tight junction as well as multifunctional dynamics in several conditions, leading to illuminate the importance of widely-expressed CD321 as a potential target for antitumor therapy. PMID:29028806

[Genome Rearrangements in Azospirillum brasilense Sp7 with the Involvement of the Plasmid pRhico and the Prophage phiAb-Cd].

PubMed

Katsy, E I; Petrova, L P

2015-12-01

Alphaproteobacteria of the species Azospirillum brasilense have a multicomponent genome that undergoes frequent spontaneous rearrangements, yielding changes in the plasmid profiles of strains. Specifically, variants (Cd, Sp7.K2, Sp7.1, Sp7.4, Sp7.8, etc.) of the type strainA. brasilense Sp7 that had lost a 115-MDa plasmid were previously selected. In many of them, the molecular weight of a 90-MDa plasmid (p90 or pRhico), which is a kind of "depot" for glycopolymer biosynthesis genes, increased. In this study, a collection of primers was designed to the plasmid pRhico and to the DNA of prophage phiAb-Cd integrated in it. The use ofthese primers in polymerase chain reactions allowed the detection of the probable excision of phiAb-Cd phage from the DNA of A. brasilense variants Sp7.4 and Sp7.8 and other alterations of the pRhico structure in A. brasilense strains Cd, Sp7.K2, and Sp7.8. The developed primers and PCR conditions may be recoin mended for primary analysis of spontaneous plasmid rearrangements in A. brasilense Sp7 and related strains.

Interaction Mode between Inclusion Complex of Vitamin K3 with γ- Cyclodextrin and Herring-Sperm DNA.

PubMed

Tang, Yan; Cai, Li; Xue, Kang; Wang, Chunling; Xiong, Xiaoli

2016-05-03

Methods including spectroscopy, electronic chemistry and thermodynamics were used to study the inclusion effect between γ-cyclodextrin (CD) and vitamin K3(K3), as well as the interaction mode between herring-sperm DNA (hsDNA) and γ-CD-K3 inclusion complex. The results from ultraviolet spectroscopic method indicated that VK3 and γ-CD formed 1:1 inclusion complex, with the inclusion constant Kf = 1.02 × 10(4) L/mol, which is based on Benesi-Hildebrand's viewpoint. The outcomes from the probe method and Scatchard methods suggested that the interaction mode between γ-CD-K3 and DNA was a mixture mode, which included intercalation and electrostatic binding effects. The binding constants were K (θ)25°C = 2.16 × 10(4) L/mol, and K(θ)37°C = 1.06 × 10(4) L/mol. The thermodynamic functions of the interaction between γ-CD-K3 and DNA were ΔrHm(θ) = -2.74 × 10(4) J/mol, ΔrSm(θ) = 174.74 J·mol(-1)K(-1), therefore, both ΔrHm(θ) (enthalpy) and ΔrSm(θ) (entropy) worked as driven forces in this action.

Maternal serum alpha-fetoprotein and human chorionic gonadotropin levels in women with human immunodeficiency virus.

PubMed

Gross, Susan; Castillo, Wilfrido; Crane, Marilyn; Espinosa, Bialines; Carter, Suzanne; DeVeaux, Richard; Salafia, Carolyn

2003-04-01

The purpose of this study was to establish whether there is a correlation between maternal serum genetic screen analyte results in pregnant women with human immunodeficiency virus and corresponding human immunodeficiency virus index values. Medical records of all pregnant women with human immunodeficiency virus who were delivered at Bronx Lebanon Hospital Center from January 2000 through December 2001 were reviewed for maternal serum screen results, viral load, CD4 counts and percent, antiretroviral therapy, opportunistic infections, substance abuse, and other demographic data. Statistical analysis was accomplished with the chi(2) test, Mann-Whitney U test, and Spearman rank correlation test, with a probability value of <.05 considered significant. Of the 98 women with human immunodeficiency virus who were delivered, 49 women (50%) had a maternal serum genetic screen available. Screened and unscreened women had similar severity of human immunodeficiency virus disease, CD4 count and percentage, and viral loads. Serum screen results showed elevations in maternal serum human chorionic gonadotropin (1.43 +/- 1.04 multiples of the median [MoM]; range, 0.2-5.2 MoM) and maternal serum alpha-fetoprotein (1.29 +/- 0.9 MoM; range, 0.5-3.3 MoM) compared with expected values in the general obstetric population. Maternal serum human chorionic gonadotropin was correlated inversely with CD4 count (P =.002) and CD4 percent (P <.0001). Maternal serum alpha-fetoprotein varied directly with viral load (P <.0001). Increasing maternal serum human chorionic gonadotropin and maternal serum alpha-fetoprotein levels in patients with human immunodeficiency virus are correlated with increasing viral load and decreasing CD4 counts.

A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways.

PubMed

Anderson, Robert P; Henry, Margaret J; Taylor, Roberta; Duncan, Emma L; Danoy, Patrick; Costa, Marylia J; Addison, Kathryn; Tye-Din, Jason A; Kotowicz, Mark A; Knight, Ross E; Pollock, Wendy; Nicholson, Geoffrey C; Toh, Ban-Hock; Brown, Matthew A; Pasco, Julie A

2013-08-28

Changing perspectives on the natural history of celiac disease (CD), new serology and genetic tests, and amended histological criteria for diagnosis cast doubt on past prevalence estimates for CD. We set out to establish a more accurate prevalence estimate for CD using a novel serogenetic approach. The human leukocyte antigen (HLA)-DQ genotype was determined in 356 patients with 'biopsy-confirmed' CD, and in two age-stratified, randomly selected community cohorts of 1,390 women and 1,158 men. Sera were screened for CD-specific serology. Only five 'biopsy-confirmed' patients with CD did not possess the susceptibility alleles HLA-DQ2.5, DQ8, or DQ2.2, and four of these were misdiagnoses. HLA-DQ2.5, DQ8, or DQ2.2 was present in 56% of all women and men in the community cohorts. Transglutaminase (TG)-2 IgA and composite TG2/deamidated gliadin peptide (DGP) IgA/IgG were abnormal in 4.6% and 5.6%, respectively, of the community women and 6.9% and 6.9%, respectively, of the community men, but in the screen-positive group, only 71% and 75%, respectively, of women and 65% and 63%, respectively, of men possessed HLA-DQ2.5, DQ8, or DQ2.2. Medical review was possible for 41% of seropositive women and 50% of seropositive men, and led to biopsy-confirmed CD in 10 women (0.7%) and 6 men (0.5%), but based on relative risk for HLA-DQ2.5, DQ8, or DQ2.2 in all TG2 IgA or TG2/DGP IgA/IgG screen-positive subjects, CD affected 1.3% or 1.9%, respectively, of females and 1.3% or 1.2%, respectively, of men. Serogenetic data from these community cohorts indicated that testing screen positives for HLA-DQ, or carrying out HLA-DQ and further serology, could have reduced unnecessary gastroscopies due to false-positive serology by at least 40% and by over 70%, respectively. Screening with TG2 IgA serology and requiring biopsy confirmation caused the community prevalence of CD to be substantially underestimated. Testing for HLA-DQ genes and confirmatory serology could reduce the numbers of unnecessary gastroscopies.

Cancer-associated CD43 glycoforms as target of immunotherapy

PubMed Central

Tuccillo, Franca Maria; Palmieri, Camillo; Fiume, Giuseppe; de Laurentiis, Annamaria; Schiavone, Marco; Falcone, Cristina; Iaccino, Enrico; Galandrini, Ricciarda; Capuano, Cristina; Santoni, Angela; D'Armiento, Francesco Paolo; Arra, Claudio; Barbieri, Antonio; Piaz, Fabrizio Dal; Venzon, David; Bonelli, Patrizia; Buonaguro, Franco Maria; Scala, Iris; Mallardo, Massimo; Quinto, Ileana; Scala, Giuseppe

2014-01-01

CD43 is a sialoglycosylated membrane protein that is involved in cell proliferation and differentiation. CD43 glycoforms that are recognized by the UN1 monoclonal antibody (mAb) were expressed in lymphoblastoid T-cell lines and solid tumors, such as breast, colon, gastric, and squamous cell lung carcinomas, while unexpressed in the normal counterparts. The cancer–association of UN1/CD43 epitope suggested the possibility to use the UN1 mAb for tumor diagnosis and therapy. In this study, we show that the UN1 mAb was endowed with anti-tumor activity in vivo since its passive transfer inhibited the growth of UN1-positive HPB-ALL lymphoblastoid T-cells in mice. Further, we demonstrate that tumor inhibition was due to UN1 mAb-dependent NK-mediated cytotoxicity. By screening a phage displayed random peptide library we identified the phagotope 2/165 as a mimotope of the UN1 antigen, as it harboured a peptide sequence that was specifically recognized by the UN1 mAb and inhibited the binding of the UN1 mAb to UN1-positive tumour cells. Based on sequence homology with the extracellular region of CD43 (amino acids 64 to 83), the 2/165 peptide sequence was likely mimicking the protein core of the UN1/CD43 epitope. When used as vaccine in mice, the 2/165 phagotope raised antibodies against the UN1/CD43 antigen, indicating that the 2/165 phagotope mimicked the UN1 antigen structure, and could represent a novel immunogen for cancer immunotherapy. These findings support the feasibility to use monoclonal antibodies to identify cancer-associated mimotopes for immunotherapy. PMID:24356816

Pericellular activation of proMMP-7 (promatrilysin-1) through interaction with CD151.

PubMed

Shiomi, Takayuki; Inoki, Isao; Kataoka, Fumio; Ohtsuka, Takashi; Hashimoto, Gakuji; Nemori, Ryoichi; Okada, Yasunori

2005-12-01

Matrix metalloproteinase-7 (MMP-7) (also known as matrilysin-1) is secreted as a proenzyme (proMMP-7) and plays a key role in the degradation of various extracellular matrix (ECM) and non-ECM molecules after activation. To identify the binding proteins related to proMMP-7 activation, a human lung cDNA library was screened by yeast two-hybrid system using proMMP-7 as bait. We identified a candidate molecule CD151, which is a member of the transmembrane 4 superfamily. Complex formation of proMMP-7 with CD151 was demonstrated by immunoprecipitation of the molecules from CaR-1 cells, a human rectal carcinoma cell line, expressing both proMMP-7 and CD151, and CD151 stable transfectants incubated with proMMP-7. Yeast two-hybrid assays using deletion mutants of proMMP-7 and CD151 suggested an interaction between the propeptide of proMMP-7 and the COOH-terminal extracellular loop of CD151. The binding activity of (125)I-labeled proMMP-7 to CD151 on the cell membranes was shown with CD151 stable transfectants. Laser-scanning confocal microscopy demonstrated that proMMP-7 colocalizes with CD151 on the cell membranes of CD151 stable transfectants and CaR-1 cells. In situ zymography using crosslinked carboxymethylated transferrin, a substrate of MMP-7, demonstrated proteinase activity on and around CD151 stable transfectants and CaR-1 cells, while the activity was abolished by their treatment with MMP inhibitors, anti-MMP-7 antibody or anti-CD151 antibody. In human lung adenocarcinoma tissues, colocalization of MMP-7 and CD151 was demonstrated on the carcinoma cells. Metalloproteinase activity was present in these tissues and could be inhibited by antibodies to MMP-7 or CD151. These data demonstrate for the first time that proMMP-7 is captured and activated on the cell membranes through interaction with CD151, and suggest the possibility that similar to the MT1-MMP/MMP-2 system, MMP-7 is involved in the pericellular activation mechanism mediated by CD151, a crucial step in proteolysis on the cell membranes under various pathophysiological conditions including cancer invasion and metastasis.

Feasibility and Acceptability of Cryptococcal Antigen Screening and Prevalence of Cryptocococcemia in Patients Attending a Resource-Limited HIV/AIDS Clinic in Malawi.

PubMed

Chipungu, Chifundo; Veltman, Jennifer A; Jansen, Perry; Chiliko, Peter; Lossa, Christina; Namarika, Dan; Benner, Blake; Hoffman, Risa M; Bristow, Claire C; Klausner, Jeffrey D

2015-01-01

The World Health Organization (WHO) recommends screening patients living with AIDS to detect and treat early cryptococcal infection. The authors evaluated a cryptococcal antigen (CrAg) screening and treatment program at an HIV/AIDS clinic in Malawi. Eligible patients were of age >18 years, had a CD4 count <100 cells/µL or WHO clinical HIV/AIDS stage III or IV. Of 552 patients who presented for care, 113 were eligible, and all (100%) agreed to CrAg screening. Of them, 2 (1.8%; 95% confidence interval [CI]: 0-4.2%) patients were CrAg positive. Among those with CD4 count <100 cells/µL or WHO stage IV, the CrAg prevalence was 3.5% (95% CI: 0-8.4%) and 5.0% (95% CI: 0-15%), respectively. A CrAg screening program was acceptable to new patients in a Malawian HIV/AIDS clinic. The CrAg prevalence for patients with CD4 count < 100 cells/µL and WHO stage IV was consistent with cost-effectiveness estimates. CrAg screening and treatment programs for patients living with AIDS should be expanded. © The Author(s) 2015.

Fluctuating Behavior of the French Population in Cancer Screening: 5th Edition of the EDIFICE Survey.

PubMed

Viguier, Jérôme; Morère, Jean-François; Pivot, Xavier; Touboul, Chantal; Lhomel, Christine; Couraud, Sébastien; de La Motte Rouge, Thibault; Eisinger, François

2018-03-05

The EDIFICE surveys have assessed cancer screening behavior in the French population since 2005. The 2016 edition was conducted among a representative sample of 1501 individuals (age, 50-75 years). The current analysis focuses on breast, colorectal, prostate, lung, and cervical cancer screening. The rate of women (50 to 74 years) declaring having had at least one breast cancer screening test in their lifetime remained stable and high between 2005 and 2016. Compliance with recommended screening intervals improved between 2005 and 2011 from 75 to 83%, respectively, then decreased significantly to 75% in 2016 (P = 0.02). Uptake of at least one lifetime colorectal cancer screening test procedure declared (individuals aged 50-74 years) increase from 25% in 2005 to 59% in 2011, stabilized at 60% in 2014, then reached 64% in 2016. Opportunistic prostate cancer screening (men aged 50-75 years) rose between 2005 and 2008 from 36 to 49%, plateaued until 2014 then dropped to 42% in 2016. The proportion of women aged 50-65 declaring having undergone one cervical cancer screening test dropped significantly between 2014 and 2016 from 99 to 94% (P < 0.01). Lastly, 11% of our survey population in 2014 and 2016 (55-74 years) declared having already undergone lung cancer screening. Cancer screening behavior fluctuates in France, regardless of the context, i.e., organized programs or opportunistic screening. This observation highlights the need for constant analysis of population attitudes to optimize public awareness campaigns.

Lung Cancer Screening Using Low Dose CT Scanning in Germany. Extrapolation of results from the National Lung Screening Trial.

PubMed

Stang, Andreas; Schuler, Martin; Kowall, Bernd; Darwiche, Kaid; Kühl, Hilmar; Jöckel, Karl-Heinz

2015-09-18

It is now debated whether the screening of heavy smokers for lung cancer with low dose computed tomography (low dose CT) might lower their mortality due to lung cancer. We use data from the National Lung Screening Trial (NLST) in the USA to predict the likely effects of such screening in Germany. The number of heavy smokers aged 55-74 in Germany was extrapolated from survey data obtained by the Robert Koch Institute. Published data from the NLST were then used to estimate the likely effects of low dose CT screening of heavy smokers in Germany. If low dose CT screening were performed on 50% of the heavy smokers in Germany aged 55-74, an estimated 1 329 506 persons would undergo such screening. If the screening were repeated annually, then, over three years, 916 918 screening CTs would reveal suspect lesions, and the diagnosis of lung cancer would be confirmed thereafter in 32 826 persons. At least one positive test result in three years would be obtained in 39.1% of the participants (519 837 persons). 4155 deaths from lung cancer would be prevented over 6.5 years, and the number of persons aged 55-74 who die of lung cancer in Germany would fall by 2.6%. 12 449 persons would have at least one complication, and 1074 persons would die in the 60 days following screening. The screening of heavy smokers for lung cancer can lower their risk of dying of lung cancer by 20% in relative terms, corresponding to an absolute risk reduction of 0.3 percentage points. These figures can provide the background for a critical discussion of the putative utility of this type of screening in Germany.

Identifying parents with risky alcohol consumption habits in a paediatric unit--are screening and brief intervention appropriate methods?

PubMed

Bjerregaard, Lene B L; Gerke, Oke; Rubak, Sune; Høst, Arne; Wagner, Lis

2011-06-01

There is no systematic identification of parents with excessive alcohol use who have a child admitted to hospital. Children in families with excessive alcohol issues form a high risk group as substantial alcohol consumption has a damaging influence on a child emotionally, cognitively, socially and physically. Alcohol consumption is a sensitive issue, and health staff needs knowledge, qualifications and adequate training in communicating with parents about this taboo. • To identify specific patterns in subgroups of parents by comparing results from screening and demographic variables • To identify systematic patterns in staff members by demographic variables to decide whether these factors influence the screening results. During 1 year, screening and brief intervention (SBI) was accomplished, including health staff conducting dialogues with parents of a hospitalized child using motivational interviewing (MI) and screening for risky alcohol behaviour by Cut down, Annoyance from others, feel Guilty, Early-morning Craving (CAGE)-C. Data were analysed by descriptive statistics, and relationships were tested with a statistical significance level of 0.05, using SPSS (version 16.0). Motivational dialogues with 779 parents were conducted by 43 staff members, and 11% of the parents were screened positive for risky alcohol behaviour. Drinking alcohol 4 days a week or more and drinking alcohol outside mealtimes were main risk factors. Parents' gender was the strongest predictor of screening positive and OR was 6.8 for men (CI 4.03-11.74) compared to women, p<0.0001. An OR of 1.2 for parents' age (CI 1.02-1.42) indicates the risk of screening positive increases with age, p=0.027. Brief intervention using CAGE-C and MI has proven successful in mapping parents' alcohol consumption patterns and in identifying parents with risky alcohol consumption habits. Health staff is able to manage health promotion and prevention when having the right competences and when being supervised. © 2010 The Authors. Scandinavian Journal of Caring Sciences © 2010 Nordic College of Caring Science.

Exploring the clinical utility of the DSM-5 conduct disorder specifier of 'with limited prosocial emotions' in an adolescent inpatient sample.

PubMed

Vanwoerden, Salome; Reuter, Tyson; Sharp, Carla

2016-08-01

With the recent addition of a callous-unemotional (CU) specifier to the diagnosis of conduct disorder (CD) in the DSM-5, studies are needed to evaluate the clinical utility of this specifier and the best ways to identify youth meeting criteria for this specifier in clinical samples. To this end, the current study examined cross-sectional correlates and treatment response across four groups of inpatient adolescents (N=382, ages 12-17): those with CD without the specifier, with CD and the CU specifier, CU alone, and a group of psychiatric controls. We used two different measures to identify adolescents with high levels of CU traits: the Antisocial Process Screening Device (APSD) [1] and the Inventory of Callous-Unemotional Traits (ICU) [2]. Questionnaires and structured interviews were used to evaluate a range of outcomes including presence of baseline levels and treatment outcomes of both externalizing and internalizing problems. Results indicated that the ICU, but not the APSD differentiated between conduct disordered youth with and without the specifier on externalizing behaviors in both cross-sectional relations and treatment response. The results of the current study caution the use of the most frequently used measure to identify the CU specifier, and make suggestions about alternatives. Copyright © 2016 Elsevier Inc. All rights reserved.

Wind Tunnel Analysis of the Airflow through Insect-Proof Screens and Comparison of Their Effect When Installed in a Mediterranean Greenhouse

PubMed Central

López, Alejandro; Molina-Aiz, Francisco D.; Valera, Diego L.; Peña, Araceli

2016-01-01

The present work studies the effect of three insect-proof screens with different geometrical and aerodynamic characteristics on the air velocity and temperature inside a Mediterranean multi-span greenhouse with three roof vents and without crops, divided into two independent sectors. First, the insect-proof screens were characterised geometrically by analysing digital images and testing in a low velocity wind tunnel. The wind tunnel tests gave screen discharge coefficient values of Cd,φ of 0.207 for screen 1 (10 × 20 threads·cm−2; porosity φ = 35.0%), 0.151 for screen 2 (13 × 30 threads·cm−2; φ = 26.3%) and 0.325 for screen 3 (10 × 20 threads·cm−2; porosity φ = 36.0%), at an air velocity of 0.25 m·s−1. Secondly, when screens were installed in the greenhouse, we observed a statistical proportionality between the discharge coefficient at the openings and the air velocity ui measured in the centre of the greenhouse, ui = 0.856 Cd + 0.062 (R2 = 0.68 and p-value = 0.012). The inside-outside temperature difference ΔTio diminishes when the inside velocity increases following the statistically significant relationship ΔTio = (−135.85 + 57.88/ui)0.5 (R2 = 0.85 and p-value = 0.0011). Different thread diameters and tension affects the screen thickness, and means that similar porosities may well be associated with very different aerodynamic characteristics. Screens must be characterised by a theoretical function Cd,φ = [(2eμ/Kpρ)·(1/us) + (2eY/Kp0.5)]−0.5 that relates the discharge coefficient of the screen Cd,φ with the air velocity us. This relationship depends on the three parameters that define the aerodynamic behaviour of porous medium: permeability Kp, inertial factor Y and screen thickness e (and on air temperature that determine its density ρ and viscosity μ). However, for a determined temperature of air, the pressure drop-velocity relationship can be characterised only with two parameters: ΔP = aus2 + bus. PMID:27187401

Wind Tunnel Analysis of the Airflow through Insect-Proof Screens and Comparison of Their Effect When Installed in a Mediterranean Greenhouse.

PubMed

López, Alejandro; Molina-Aiz, Francisco D; Valera, Diego L; Peña, Araceli

2016-05-12

The present work studies the effect of three insect-proof screens with different geometrical and aerodynamic characteristics on the air velocity and temperature inside a Mediterranean multi-span greenhouse with three roof vents and without crops, divided into two independent sectors. First, the insect-proof screens were characterised geometrically by analysing digital images and testing in a low velocity wind tunnel. The wind tunnel tests gave screen discharge coefficient values of Cd,φ of 0.207 for screen 1 (10 × 20 threads·cm(-2); porosity φ = 35.0%), 0.151 for screen 2 (13 × 30 threads·cm(-2); φ = 26.3%) and 0.325 for screen 3 (10 × 20 threads·cm(-2); porosity φ = 36.0%), at an air velocity of 0.25 m·s(-1). Secondly, when screens were installed in the greenhouse, we observed a statistical proportionality between the discharge coefficient at the openings and the air velocity ui measured in the centre of the greenhouse, ui = 0.856 Cd + 0.062 (R² = 0.68 and p-value = 0.012). The inside-outside temperature difference ΔTio diminishes when the inside velocity increases following the statistically significant relationship ΔTio = (-135.85 + 57.88/ui)(0.5) (R² = 0.85 and p-value = 0.0011). Different thread diameters and tension affects the screen thickness, and means that similar porosities may well be associated with very different aerodynamic characteristics. Screens must be characterised by a theoretical function Cd,φ = [(2eμ/Kpρ)·(1/us) + (2eY/Kp(0.5))](-0.5) that relates the discharge coefficient of the screen Cd,φ with the air velocity us. This relationship depends on the three parameters that define the aerodynamic behaviour of porous medium: permeability Kp, inertial factor Y and screen thickness e (and on air temperature that determine its density ρ and viscosity μ). However, for a determined temperature of air, the pressure drop-velocity relationship can be characterised only with two parameters: ΔP = aus² + bus.

Performance characteristics of a brief Family History Questionnaire to screen for Lynch syndrome in women with newly diagnosed endometrial cancer.

PubMed

Eiriksson, Lua; Aronson, Melyssa; Clarke, Blaise; Mojtahedi, Golnessa; Massey, Christine; Oza, Amit M; Gallinger, Steven; Pollett, Aaron; Mackay, Helen; Bernardini, Marcus Q; Ferguson, Sarah E

2015-02-01

The brief Family History Questionnaire (bFHQ) was developed to identify endometrial cancer patients whose family histories suggest Lynch syndrome (LS). We compared the bFHQ, extended Family History Questionnaire (eFHQ) and dictated medical records (DMRs) to determine which family history screening strategy is superior in identifying LS in unselected women with newly diagnosed endometrial cancer that have undergone universal germline testing. Prospective cohort study recruited women with newly diagnosed endometrial cancer to evaluate screening strategies to identify LS. Participants completed bFHQ and eFHQ, had tumor assessed with immunohistochemistry (IHC) for mismatch repair proteins (MMR) and micro-satellite instability testing and underwent universal germline testing for LS. The sensitivity, specificity, positive and negative predictive values (PPV, NPV) were compared between the family history screening strategies as well as IHC. 118 of 182 eligible patients (65%) consented; 87 patients (74%) were evaluable with both family history and germline mutation status. Median age was 61years (range 26-91). All 7 patients with confirmed LS were correctly identified by bFHQ, compared to 5 and 4 by eFHQ and DMR, respectively. The sensitivity, specificity, PPV and NPV values of bFHQ were 100%, 76.5%, 25.9% and 100%, respectively, performing similar to IHC testing. While eFHQ was more specific than bFHQ (86.7% vs. 76.5%, P=0.007), 2 cases of LS were missed. The patient-administered bFHQ effectively identified women with confirmed LS and is a good screening tool to triage women with endometrial cancer for further genetic assessment. Copyright © 2014 Elsevier Inc. All rights reserved.

Emphysema and soluble CD14 are associated with pulmonary nodules in HIV-infected patients: implications for lung cancer screening.

PubMed

Triplette, Matthew; Sigel, Keith M; Morris, Alison; Shahrir, Shahida; Wisnivesky, Juan P; Kong, Chung Y; Diaz, Phillip T; Petraglia, Alycia; Crothers, Kristina

2017-07-31

Lung cancer screening may benefit HIV-infected (HIV) smokers because of an elevated risk of lung cancer, but may have unique harms because of HIV-specific risk factors for false-positive screens. This study seeks to understand whether inflammatory biomarkers and markers of chronic lung disease are associated with noncalcified nodules at least 4 mm (NCN) in HIV compared with uninfected patients. This is a cohort study of Examinations of HIV-Associated Lung Emphysema (EXHALE), including 158 HIV and 133 HIV-uninfected participants. Participants underwent a laboratory assessment [including measurement of D-dimer, interleukin 6, and soluble CD14 (sCD14)], chest computed tomography (CT), and pulmonary function testing. We created multivariable logistic regression models to determine predictors of NCN in the participants stratified by HIV status, with attention to semiqualitative scoring of radiographic emphysema, markers of pulmonary function, and inflammatory biomarkers. Of the 291 participants, 69 had NCN on chest CT. As previously reported, there was no difference in prevalence of these nodules by HIV status. Emphysema and elevated sCD14 demonstrated an association with NCN in HIV participants independent of smoking status, CD4 cell count, HIV viral load, and pulmonary function. Emphysema and sCD14, a marker of immune activation, was associated with a higher prevalence of NCN on chest CT in HIV participants. Patients with chronic immune activation and emphysema may be at higher risk for both false-positive findings and incident lung cancer, thus screening in this group requires further study to understand the balance of benefits and harms.

Benefits and harms of lung cancer screening in HIV-infected individuals with CD4+ ≥ 500: a simulation study.

PubMed

Kong, Chung Yin; Sigel, Keith; Criss, Steven D; Sheehan, Deirdre F; Triplette, Matthew; Silverberg, Michael J; Henschke, Claudia I; Justice, Amy; Braithwaite, R Scott; Wisnivesky, Juan; Crothers, Kristina

2018-04-19

Lung cancer is the leading cause of non-AIDS-defining cancer deaths among HIV-infected individuals. Although lung cancer screening with low-dose computed tomography (LDCT) is endorsed by multiple national organizations, whether HIV-infected individuals would have similar benefit as uninfected individuals from lung cancer screening is unknown. Our objective was to determine the benefits and harms of lung cancer screening among HIV-infected individuals. We modified an existing simulation model, the Lung Cancer Policy Model, for HIV-infected patients. Veterans Aging Cohort Study, Kaiser Permanente Northern California HIV Cohort, and medical literature. Target population: HIV-infected current and former smokers. Lifetime. Population. Annual LDCT screening from ages 45, 50, or 55 until ages 72 or 77 years. Benefits assessed included lung cancer mortality reduction and life-years gained; harms assessed included numbers of LDCT examinations, false-positive results, and overdiagnosed cases. For HIV-infected patients with CD4 at least 500 and 100% antiretroviral therapy adherence, screening using the Centers for Medicare & Medicaid Services criteria (age 55-77, 30 pack-years of smoking, current smoker or quit within 15 years of screening) would reduce lung cancer mortality by 18.9%, similar to the mortality reduction of uninfected individuals. Alternative screening strategies utilizing lower screening age and/or pack-years criteria increase mortality reduction, but require more LDCT examinations. Strategies assumed 100% screening adherence. Lung cancer screening reduces mortality in HIV-infected patients with CD4 at least l500, with a number of efficient strategies for eligibility, including the current Centers for Medicare & Medicaid Services criteria.

Sulfasalazine attenuates evading anticancer response of CD133-positive hepatocellular carcinoma cells.

PubMed

Song, Yeonhwa; Jang, Jaewoo; Shin, Tae-Hoon; Bae, Sang Mun; Kim, Jin-Sun; Kim, Kang Mo; Myung, Seung-Jae; Choi, Eun Kyung; Seo, Haeng Ran

2017-03-03

CD133-positive cells in hepatocellular carcinoma (HCC) exhibit cancer stem cell (CSC)-like properties as well as resistance to chemotherapeutic agents and ionizing radiation; however, their function remains unknown. In this paper, we identified a hitherto unknown mechanism to overcome CD133-induced resistance to anticancer therapy. We applied an alternative approach to enrich the CD133-positive HCC population by manipulating 3D culture conditions. Defense mechanisms against reactive oxygen species (ROS) in CSC spheroids were evaluated by fluorescence image-based phenotypic screening system. Further, we studied the effect of sulfasalazine on ROS defense system and synergistic therapeutic efficacy of anticancer therapies both in culture and in vivo HCC xenograft mouse model. Here, we found that oxidative stress increase CD133 expression in HCC and increased CD133 expression enhanced the capacity of the defense system against ROS, and thereby play a central role in resistance to liver cancer therapy. Moreover, ablation of CD133 attenuated not only the capacity for defense against ROS, but also chemoresistance, in HCC through decreasing glutathione (GSH) levels in vitro. Sulfasalazine, a potent xCT inhibitor that plays an important role in maintaining GSH levels, impaired the ROS defense system and increased the therapeutic efficacy of anticancer therapies in CD133-positive HCC but not CD133-negative HCC in vivo and in vitro. These results strongly indicate functional roles for CD133 in ROS defense and in evading anticancer therapies in HCC, and suggest that sulfasalazine, administered in combination with conventional chemotherapy, might be an effective strategy against CD133-positive HCC cells.

BetaIg-h3 is involved in the HAb18G/CD147-mediated metastasis process in human hepatoma cells.

PubMed

Tang, Juan; Zhou, Hong-wei; Jiang, Jian-li; Yang, Xiang-min; Li, Yu; Zhang, Hong-xin; Chen, Zhi-nan; Guo, Wei-ping

2007-03-01

HAb18G/CD147, a new hepatoma-associated antigen cloned and screened from human hepatocellular carcinoma cDNA library, is closely correlated with metastasis process in human hepatoma cells. In the present study we aimed to identify the pivotal molecules of the HAb18G/CD147 signal transduction pathway. The investigation showed that betaig-h3, a secretory extracellular matrix (ECM) protein, was upregulated in HAb18G/CD147-expressing human hepatoma T7721 cells and was downregulated by depressing HAb18G/CD147 expression. The expression of betaig-h3, upregulated in human hepatoma cells, was positively relative to the expression of HAb18G/CD147 in different human hepatoma cell lines. By overexpressing betaig-h3 in human SMMC-7721 hepatoma cells, we discovered that betaig-h3 promoted cell adhesion, invasion, and matrix metalloproteinase (MMP) secretion potential. HAb18G/CD147-induced invasion and metastasis potential of human hepatoma cells can be attenuated by antibodies specific for betaig-h3, and no significant differences on inhibitory effects were observed among T7721 cells incubated with antibodies for betaig-h3 or HAb18G/CD147 or both types together. Taken together, our study suggests that betaig-h3, regulated by the expression of HAb18G/CD147, is involved in the HAb18G/CD147 signal transduction pathway and mediates the HAb18G/CD147-induced invasion and metastasis process of human hepatoma cells.

Impact of early screening for reflux in siblings on the detection of renal damage.

PubMed

Houle, Anne-Marie; Cheikhelard, Alaa; Barrieras, Diego; Rivest, Marie-Christine; Gaudreault, Valérie

2004-07-01

To assess the impact of screening siblings after detecting significant vesico-ureteric reflux (VUR) and renal scarring, as such screening might identify patients with VUR before urinary tract infections develop, but might also detect clinically insignificant VUR. We used a previously reported screening protocol to assess the clinical characteristics of patients, including the incidence of renal scarring, and their siblings, and compared the results. In all, 123 children were screened and 44 (36%) had VUR on voiding cystography. The median (range) age at screening was 9 (1-90) months. The grades of VUR detected were < III in 61% and > or = III in 39%; VUR was bilateral in 48%. In all, 37 siblings with VUR were assessed by ultrasonography; 70% were normal, including 12 (32%) children with VUR of grade > or = III. When used, renal scintigraphy was normal in 74% of siblings, vs 18% of index patients. However, when screened after 2 years old, siblings had twice the risk of already having renal damage on renal scintigraphy (P = 0.04). Early screening (< or = 2 years) appears to be more protective for avoiding renal damage than screening older patients. Thus we propose early screening in asymptomatic siblings to detect VUR before it becomes clinically significant.

Harms, benefits and costs of fecal immunochemical testing versus guaiac fecal occult blood testing for colorectal cancer screening.

PubMed

Goede, S Lucas; Rabeneck, Linda; van Ballegooijen, Marjolein; Zauber, Ann G; Paszat, Lawrence F; Hoch, Jeffrey S; Yong, Jean H E; Kroep, Sonja; Tinmouth, Jill; Lansdorp-Vogelaar, Iris

2017-01-01

The ColonCancerCheck screening program for colorectal cancer (CRC) in Ontario, Canada, is considering switching from biennial guaiac fecal occult blood test (gFOBT) screening between age 50-74 years to the more sensitive, but also less specific fecal immunochemical test (FIT). The aim of this study is to estimate whether the additional benefits of FIT screening compared to gFOBT outweigh the additional costs and harms. We used microsimulation modeling to estimate quality adjusted life years (QALYs) gained and costs of gFOBT and FIT, compared to no screening, in a cohort of screening participants. We compared strategies with various age ranges, screening intervals, and cut-off levels for FIT. Cost-efficient strategies were determined for various levels of available colonoscopy capacity. Compared to no screening, biennial gFOBT screening between age 50-74 years provided 20 QALYs at a cost of CAN$200,900 per 1,000 participants, and required 17 colonoscopies per 1,000 participants per year. FIT screening was more effective and less costly. For the same level of colonoscopy requirement, biennial FIT (with a high cut-off level of 200 ng Hb/ml) between age 50-74 years provided 11 extra QALYs gained while saving CAN$333,300 per 1000 participants, compared to gFOBT. Without restrictions in colonoscopy capacity, FIT (with a low cut-off level of 50 ng Hb/ml) every year between age 45-80 years was the most cost-effective strategy providing 27 extra QALYs gained per 1000 participants, while saving CAN$448,300. Compared to gFOBT screening, switching to FIT at a high cut-off level could increase the health benefits of a CRC screening program without considerably increasing colonoscopy demand.

Lactobacillus paracasei CBA L74 interferes with gliadin peptides entrance in Caco-2 cells.

PubMed

Sarno, Marco; Lania, Giuliana; Cuomo, Marialaura; Nigro, Federica; Passannanti, Francesca; Budelli, Andrea; Fasano, Francesca; Troncone, Riccardo; Auricchio, Salvatore; Barone, Maria Vittoria; Nigro, Roberto; Nanayakkara, Merlin

2014-12-01

Several recent reports describe a role of probiotics as a therapeutic approach for celiac disease (CD). Two undigested A-gliadin peptides, P31-43 and P57-68, are central to CD pathogenesis, inducing an innate and an adaptive immune response, respectively. They enter enterocytes and localize to vesicular compartment to induce their toxic/immunogenics effects. In this article, we tested the effect of probiotic Lactobacillus paracasei (LP) CBA L74 (International Depository Accession Number LMG P-24778), its supernatant and LP-fermented cereals on gliadin peptides, P31-43 and P57-68, entrance in Caco-2 cells. Both LP CBA L74 and its supernatant inhibit P31-43 (intensity of fluorescence; FI: 75%) and P57-68 (FI: 50%) entrance in Caco2 cells, indicating that this biological effect is due to some product included in LP CBA L74 supernatant. This effect was present also after fermentation of cereals. This study describes a novel effect of probiotics in the prevention of undigested gliadin peptides toxic effects.

Behavioral characterization of CD36 knockout mice with SHIRPA primary screen.

PubMed

Zhang, Shuxiao; Wang, Wei; Li, Juan; Cheng, Ke; Zhou, Jingjing; Zhu, Dan; Yang, Deyu; Liang, Zihong; Fang, Liang; Liao, Li; Xie, Peng

2016-02-15

CD36 is a member of the class B scavenger receptor family of cell surface proteins, which plays a major role in fatty acid, glucose and lipid metabolism. Besides, CD36 functions as a microglial surface receptor for amyloid beta peptide. Regarding this, we suggest CD36 might also contribute to neuropsychiatric disease. The aim of this study was to achieve a behavioral phenotype of CD36 knockout (CD36(-/-)) mice. We characterized the behavior of CD36(-/-) mice and C57BL/6J mice by subjecting them to a series of tests, which include SHIRPA primary behavioral screen test, 1% sucrose preference test, elevated plus-maze test, open-field test and forced swimming test. The results showed that CD36(-/-) mice traversed more squares, emitted more defecation, exhibited higher tail elevation and had more aggressive behaviors than C57BL/6J mice. The CD36(-/-) mice spent more time and traveled longer distance in periphery zone in the open-field test. Meanwhile, the numbers that CD36(-/-) mice entered in the open arms of elevated plus-maze were reduced. These findings suggest that CD36(-/-) mice present an anxious phenotype and might be involved in neuropsychiatric disorders. Copyright © 2015. Published by Elsevier B.V.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howe, Joshua D.; Morelock, Cody R.; Jiao, Yang

We present a joint computational and experimental study of Mg–Ni-MOF-74 and Mg–Cd-MOF-74 to gain insight into the mixing of metals and understand how metal mixing affects the structure of the undercoordinated open-metal sites. Our calculations predict that metal mixing is energetically preferred in these materials. Recent experimental work has demonstrated that Mg–Ni-MOF-74 shows a much greater surface area retention in the presence of water than Mg-MOF-74. To probe this effect, we study H 2O adsorption in Mg–Ni-MOF-74, finding that the adsorption energetics and electronic structure do not change significantly at the metal sites when compared to Mg-MOF-74 and Ni-MOF-74, respectively.more » Lastly, we conclude that the increased stability of Mg–Ni-MOF-74 is a result of a M–O bond length distortion in mixed-metal MOF-74, consistent with recent work on the stability of MOF-74 under water exposure.« less

A Functional, Genome-wide Evaluation of Liposensitive Yeast Identifies the “ARE2 Required for Viability” (ARV1) Gene Product as a Major Component of Eukaryotic Fatty Acid Resistance*

PubMed Central

Ruggles, Kelly V.; Garbarino, Jeanne; Liu, Ying; Moon, James; Schneider, Kerry; Henneberry, Annette; Billheimer, Jeff; Millar, John S.; Marchadier, Dawn; Valasek, Mark A.; Joblin-Mills, Aidan; Gulati, Sonia; Munkacsi, Andrew B.; Repa, Joyce J.; Rader, Dan; Sturley, Stephen L.

2014-01-01

The toxic subcellular accumulation of lipids predisposes several human metabolic syndromes, including obesity, type 2 diabetes, and some forms of neurodegeneration. To identify pathways that prevent lipid-induced cell death, we performed a genome-wide fatty acid sensitivity screen in Saccharomyces cerevisiae. We identified 167 yeast mutants as sensitive to 0.5 mm palmitoleate, 45% of which define pathways that were conserved in humans. 63 lesions also impacted the status of the lipid droplet; however, this was not correlated to the degree of fatty acid sensitivity. The most liposensitive yeast strain arose due to deletion of the “ARE2 required for viability” (ARV1) gene, encoding an evolutionarily conserved, potential lipid transporter that localizes to the endoplasmic reticulum membrane. Down-regulation of mammalian ARV1 in MIN6 pancreatic β-cells or HEK293 cells resulted in decreased neutral lipid synthesis, increased fatty acid sensitivity, and lipoapoptosis. Conversely, elevated expression of human ARV1 in HEK293 cells or mouse liver significantly increased triglyceride mass and lipid droplet number. The ARV1-induced hepatic triglyceride accumulation was accompanied by up-regulation of DGAT1, a triglyceride synthesis gene, and the fatty acid transporter, CD36. Furthermore, ARV1 was identified as a transcriptional of the protein peroxisome proliferator-activated receptor α (PPARα), a key regulator of lipid homeostasis whose transcriptional targets include DGAT1 and CD36. These results implicate ARV1 as a protective factor in lipotoxic diseases due to modulation of fatty acid metabolism. In conclusion, a lipotoxicity-based genetic screen in a model microorganism has identified 75 human genes that may play key roles in neutral lipid metabolism and disease. PMID:24273168

A new class of synthetic retinoid antibiotics effective against bacterial persisters.

PubMed

Kim, Wooseong; Zhu, Wenpeng; Hendricks, Gabriel Lambert; Van Tyne, Daria; Steele, Andrew D; Keohane, Colleen E; Fricke, Nico; Conery, Annie L; Shen, Steven; Pan, Wen; Lee, Kiho; Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Vlahovska, Petia M; Wuest, William M; Gilmore, Michael S; Gao, Huajian; Ausubel, Frederick M; Mylonakis, Eleftherios

2018-04-05

A challenge in the treatment of Staphylococcus aureus infections is the high prevalence of methicillin-resistant S. aureus (MRSA) strains and the formation of non-growing, dormant 'persister' subpopulations that exhibit high levels of tolerance to antibiotics and have a role in chronic or recurrent infections. As conventional antibiotics are not effective in the treatment of infections caused by such bacteria, novel antibacterial therapeutics are urgently required. Here we used a Caenorhabditis elegans-MRSA infection screen to identify two synthetic retinoids, CD437 and CD1530, which kill both growing and persister MRSA cells by disrupting lipid bilayers. CD437 and CD1530 exhibit high killing rates, synergism with gentamicin, and a low probability of resistance selection. All-atom molecular dynamics simulations demonstrated that the ability of retinoids to penetrate and embed in lipid bilayers correlates with their bactericidal ability. An analogue of CD437 was found to retain anti-persister activity and show an improved cytotoxicity profile. Both CD437 and this analogue, alone or in combination with gentamicin, exhibit considerable efficacy in a mouse model of chronic MRSA infection. With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure.

A new class of synthetic retinoid antibiotics effective against bacterial persisters

NASA Astrophysics Data System (ADS)

Kim, Wooseong; Zhu, Wenpeng; Hendricks, Gabriel Lambert; van Tyne, Daria; Steele, Andrew D.; Keohane, Colleen E.; Fricke, Nico; Conery, Annie L.; Shen, Steven; Pan, Wen; Lee, Kiho; Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Vlahovska, Petia M.; Wuest, William M.; Gilmore, Michael S.; Gao, Huajian; Ausubel, Frederick M.; Mylonakis, Eleftherios

2018-04-01

A challenge in the treatment of Staphylococcus aureus infections is the high prevalence of methicillin-resistant S. aureus (MRSA) strains and the formation of non-growing, dormant ‘persister’ subpopulations that exhibit high levels of tolerance to antibiotics and have a role in chronic or recurrent infections. As conventional antibiotics are not effective in the treatment of infections caused by such bacteria, novel antibacterial therapeutics are urgently required. Here we used a Caenorhabditis elegans–MRSA infection screen to identify two synthetic retinoids, CD437 and CD1530, which kill both growing and persister MRSA cells by disrupting lipid bilayers. CD437 and CD1530 exhibit high killing rates, synergism with gentamicin, and a low probability of resistance selection. All-atom molecular dynamics simulations demonstrated that the ability of retinoids to penetrate and embed in lipid bilayers correlates with their bactericidal ability. An analogue of CD437 was found to retain anti-persister activity and show an improved cytotoxicity profile. Both CD437 and this analogue, alone or in combination with gentamicin, exhibit considerable efficacy in a mouse model of chronic MRSA infection. With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure.

Catching TFSI: A Computational-Experimental Approach to β-Cyclodextrin-Based Host-Guest Systems as electrolytes for Li-Ion Batteries.

PubMed

Jeschke, Steffen; Jankowski, Piotr; Best, Adam S; Johansson, Patrik

2018-03-12

Cyclodextrins (CDs) are pyranoside-based macromolecules with a hydrophobic cavity to encapsulate small molecules. They are used as molecular vehicles, for instance in pharmaceutical drug delivery or as solubility enhancer of monomers for their polymerization in aqueous solution. In this context, it was discovered about 10 years ago that the bis(trifluoromethylsulonyl)imide (TFSI) anion forms host-guest complexes with βCD in aqueous media. This sparked interest in using the TFSI anion in lithium-based battery electrolytes open for its encapsulation by βCD as an attractive approach to increase the contribution of the cation to the total ion conductivity. By using semi-empirical quantum mechanical (SQM) methods and the conductor-like screening model for a real solvent (COSMO-RS), a randomly methylated βCD (RMβCD) is here identified as a suitable host for TFSI when using organic solvents often used in battery technology. By combining molecular dynamics (MD) simulations with different NMR and FTIR experiments, the formation of the corresponding RMβCD-TFSI complex was investigated. Finally, the effects of the addition RMβCD to a set of electrolytes on the ion conductivity are measured and explained using three distinct scenarios. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Missed Opportunity for Alcohol Problem Prevention Among Army Active Duty Service Members Postdeployment

PubMed Central

Mohr, Beth A.; Adams, Rachel Sayko; Wooten, Nikki R.; Williams, Thomas V.

2014-01-01

Objectives. We identified to what extent the Department of Defense postdeployment health surveillance program identifies at-risk drinking, alone or in conjunction with psychological comorbidities, and refers service members who screen positive for additional assessment or care. Methods. We completed a cross-sectional analysis of 333 803 US Army active duty members returning from Iraq or Afghanistan deployments in fiscal years 2008 to 2011 with a postdeployment health assessment. Alcohol measures included 2 based on self-report quantity-frequency items—at-risk drinking (positive Alcohol Use Disorders Identification Test alcohol consumption questions [AUDIT-C] screen) and severe alcohol problems (AUDIT-C score of 8 or higher)—and another based on the interviewing provider’s assessment. Results. Nearly 29% of US Army active duty members screened positive for at-risk drinking, and 5.6% had an AUDIT-C score of 8 or higher. Interviewing providers identified potential alcohol problems among only 61.8% of those screening positive for at-risk drinking and only 74.9% of those with AUDIT-C scores of 8 or higher. They referred for a follow-up visit to primary care or another setting only 29.2% of at-risk drinkers and only 35.9% of those with AUDIT-C scores of 8 or higher. Conclusions. This study identified missed opportunities for early intervention for at-risk drinking. Future research should evaluate the effect of early intervention on long-term outcomes. PMID:24922163

BRIEF REPORT: Screening Items to Identify Patients with Limited Health Literacy Skills

PubMed Central

Wallace, Lorraine S; Rogers, Edwin S; Roskos, Steven E; Holiday, David B; Weiss, Barry D

2006-01-01

BACKGROUND Patients with limited literacy skills are routinely encountered in clinical practice, but they are not always identified by clinicians. OBJECTIVE To evaluate 3 candidate questions to determine their accuracy in identifying patients with limited or marginal health literacy skills. METHODS We studied 305 English-speaking adults attending a university-based primary care clinic. Demographic items, health literacy screening questions, and the Rapid Estimate of Adult Literacy in Medicine (REALM) were administered to patients. To determine the accuracy of the candidate questions for identifying limited or marginal health literacy skills, we plotted area under the receiver operating characteristic (AUROC) curves for each item, using REALM scores as a reference standard. RESULTS The mean age of subjects was 49.5; 67.5% were female, 85.2% Caucasian, and 81.3% insured by TennCare and/or Medicare. Fifty-four (17.7%) had limited and 52 (17.0%) had marginal health literacy skills. One screening question, “How confident are you filling out medical forms by yourself?” was accurate in detecting limited (AUROC of 0.82; 95% confidence interval [CI]=0.77 to 0.86) and limited/marginal (AUROC of 0.79; 95% CI=0.74 to 0.83) health literacy skills. This question had significantly greater AUROC than either of the other questions (P<.01) and also a greater AUROC than questions based on demographic characteristics. CONCLUSIONS One screening question may be sufficient for detecting limited and marginal health literacy skills in clinic populations. PMID:16881950

Detecting specific cytotoxic T lymphocytes against SARS-coronavirus with DimerX HLA-A2:Ig fusion protein.

PubMed

Wang, Yue-Dan; Chen, Wei Feng

2004-11-01

To assess specific cytotoxic T lymphocytes (CTLs) against Severe acute respiratory syndrome (SARS)-coronavirus, a modified DimerX flow cytometry assay was performed with peripheral blood mononuclear cell (PBMC) from HLA-A2+ SARS-recovered donors at different time points post disease. CD8+DimerX-S1203+ CTLs were detected in the PBMC from these donors up to 3 months after recovery. The percentages of CD8+DimerX-S1203+ cells paralleled the numbers of interferon-gamma-positive spots in an ELISPOT assay using the same antigenic peptide. In conclusion, DimerX-based flow cytometry staining may prove to be a real-time method to screen for CTL directed at epitopes from a newly identified virus.

Pyrimethamine as a Potent and Selective Inhibitor of Acute Myeloid Leukemia Identified by High-throughput Drug Screening.

PubMed

Sharma, Amit; Jyotsana, Nidhi; Lai, Courteney K; Chaturvedi, Anuhar; Gabdoulline, Razif; Görlich, Kerstin; Murphy, Cecilia; Blanchard, Jan E; Ganser, Arnold; Brown, Eric; Hassell, John A; Humphries, R Keith; Morgan, Michael; Heuser, Michael

2016-01-01

Hematopoietic stem and progenitor cell differentiation are blocked in acute myeloid leukemia (AML) resulting in cytopenias and a high risk of death. Most patients with AML become resistant to treatment due to lack of effective cytotoxic and differentiation promoting compounds. High MN1 expression confers poor prognosis to AML patients and induces resistance to cytarabine and alltrans-retinoic acid (ATRA) induced differentiation. Using a high-throughput drug screening, we identified the dihydrofolate reductase (DHFR) antagonist pyrimethamine to be a potent inducer of apoptosis and differentiation in several murine and human leukemia cell lines. Oral pyrimethamine treatment was effective in two xenograft mouse models and specifically targeted leukemic cells in human AML cell lines and primary patient cells, while CD34+ cells from healthy donors were unaffected. The antileukemic effects of PMT could be partially rescued by excess folic acid, suggesting an oncogenic function of folate metabolism in AML. Thus, our study identifies pyrimethamine as a candidate drug that should be further evaluated in AML treatment.

Oppositional defiant- and conduct disorder-like problems: neurodevelopmental predictors and genetic background in boys and girls, in a nationwide twin study.

PubMed

Kerekes, Nóra; Lundström, Sebastian; Chang, Zheng; Tajnia, Armin; Jern, Patrick; Lichtenstein, Paul; Nilsson, Thomas; Anckarsäter, Henrik

2014-01-01

Background. Previous research has supported gender-specific aetiological factors in oppositional defiant disorder (ODD) and conduct disorder (CD). The aims of this study were to identify gender-specific associations between the behavioural problems-ODD/CD-like problems-and the neurodevelopmental disorders-attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD)-and to investigate underlying genetic effects. Methods. 17,220 twins aged 9 or 12 were screened using the Autism-Tics, AD/HD and other Comorbidities inventory. The main covariates of ODD- and CD-like problems were investigated, and the relative importance of unique versus shared hereditary and environmental effects was estimated using twin model fitting. Results. Social interaction problems (one of the ASD subdomains) was the strongest neurodevelopmental covariate of the behavioural problems in both genders, while ADHD-related hyperactivity/impulsiveness in boys and inattention in girls stood out as important covariates of CD-like problems. Genetic effects accounted for 50%-62% of the variance in behavioural problems, except in CD-like problems in girls (26%). Genetic and environmental effects linked to ADHD and ASD also influenced ODD-like problems in both genders and, to a lesser extent, CD-like problems in boys, but not in girls. Conclusions. The gender-specific patterns should be considered in the assessment and treatment, especially of CD.

CFTR mutation distribution among U.S. Hispanic and African American individuals: evaluation in cystic fibrosis patient and carrier screening populations.

PubMed

Sugarman, Elaine A; Rohlfs, Elizabeth M; Silverman, Lawrence M; Allitto, Bernice A

2004-01-01

We reviewed CFTR mutation distribution among Hispanic and African American individuals referred for CF carrier screening and compared mutation frequencies to those derived from CF patient samples. Results from CFTR mutation analyses received from January 2001 through September 2003, were analyzed for four populations: Hispanic individuals with a CF diagnosis (n = 159) or carrier screening indication (n = 15,333) and African American individuals with a CF diagnosis (n = 108) or carrier screening indication (n = 8,973). All samples were tested for the same 87 mutation panel. In the Hispanic population, 42 mutations were identified: 30 in the patient population (77.5% detection rate) and 33 among carrier screening referrals. Five mutations not included in the ACMG/ACOG carrier screening panel (3876delA, W1089X, R1066C, S549N, 1949del84) accounted for 7.55% detection in patients and 5.58% among carriers. Among African American referrals, 33 different mutations were identified: 21 in the patient population (74.4% detection) and 23 in the carrier screening population. Together, A559T and 711+5G>A were observed at a detection rate of 3.71% in CF patients and 6.38% in carriers. The mutation distribution seen in both the carrier screening populations reflected an increased frequency of mutations with variable expression such as D1152H, R117H, and L206W. A detailed analysis of CFTR mutation distribution in the Hispanic and African American patient and carrier screening populations demonstrates that a diverse group of mutations is most appropriate for diagnostic and carrier screening in these populations. To best serve the increasingly diverse U.S. population, ethnic-specific mutations should be included in mutation panels.

Chronic kidney diseases of uncertain etiology (CKDue) in Sri Lanka: geographic distribution and environmental implications.

PubMed

Chandrajith, Rohana; Nanayakkara, Shanika; Itai, Kozuyoshi; Aturaliya, T N C; Dissanayake, C B; Abeysekera, Thilak; Harada, Kouji; Watanabe, Takao; Koizumi, Akio

2011-06-01

The increase in the number of chronic kidney disease (CKD) patients from the north central region of Sri Lanka has become a environmental health issue of national concern. Unlike in other countries where long-standing diabetes and hypertension are the leading causes of renal diseases, the majority of CKD patients from this part of Sri Lanka do not show any identifiable cause. As the disease is restricted to a remarkably specific geographical terrain, particularly in the north central dry zone of the country, multidisciplinary in-depth research studies are required to identify possible etiologies and risk factors. During this study, population screening in the prevalent region and outside the region, analysis of geoenvironmental and biochemical samples were carried out. Population screening that was carried out using a multistage sampling technique indicated that the point prevalence of CKD with uncertain etiology is about 2-3% among those above 18 years of age. Drinking water collected from high-prevalent and non-endemic regions was analyzed for their trace and ultratrace element contents, including the nephrotoxic heavy metals Cd and U using ICP-MS. The results indicate that the affected regions contain moderate to high levels of fluoride. The Cd contents in drinking water, rice from affected regions and urine from symptomatic and non-symptomatic patients were much lower indicating that Cd is not a contributing factor for CKD with uncertain etiology in Sri Lanka. Although no single geochemical parameter could be clearly and directly related to the CKD etiology on the basis of the elements determined during this study, it is very likely that the unique hydrogeochemistry of the drinking water is closely associated with the incidence of the disease. © Springer Science+Business Media B.V. 2010

Intimate partner violence (IPV): The validity of an IPV screening instrument utilized among pregnant women in Tanzania and Vietnam

PubMed Central

Rasch, Vibeke; Van, Toan Ngo; Nguyen, Hanh Thi Thuy; Manongi, Rachel; Mushi, Declare; Meyrowitsch, Dan W.; Gammeltoft, Tine; Wu, Chun Sen

2018-01-01

Background Intimate partner violence (IPV) is a global problem that affects one-third of all women. The present study aims to develop and determine the validity of a screening instrument for the detection of IPV in pregnant women in Tanzania and Vietnam and to determine the minimum number of questions needed to identify IPV. Method An IPV screening instrument based on eight questions was tested on 1,116 Tanzanian and 1,309 Vietnamese women who attended antenatal care before 24 gestational weeks. The women were re-interviewed during their 30th-34th gestational week where the World Health Organization (WHO) IPV questionnaire was used as the gold standard. In all, 255 combinations of eight different questions were first tested on the Tanzanian study population where sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated. In the evaluation of the performance of the question combinations, different IPV types and the frequency of abusive acts were considered. The question combinations that performed best in Tanzania were subsequently evaluated in the Vietnamese study population. Results In Tanzania, a combination of three selected questions including one question on emotional IPV, one on physical IPV and one on sexual IPV was found to be most effective in identifying women who are exposed to at least one type of IPV during pregnancy (sensitivity = .80; specificity = .74). The performance of the identified combination was slightly less effective in Vietnam (sensitivity = .74; specificity = .68). Focusing on different IPV types, the best performance was found for exposure to physical IPV in both Tanzania (sensitivity = .93; specificity = .70) and Vietnam (sensitivity = .96; specificity = .55). In both countries, the sensitivity increased with the frequency of abuse whereas the specificity decreased. Conclusion By asking pregnant women three simple questions we were able to identify women who were exposed to IPV during pregnancy in two different countries. The question combination performed best in assessing physical IPV where it identified 93% and 96% of Vietnamese and Tanzanian women, respectively, who were exposed to physical IPV. PMID:29389954

Screening for Breast Cancer: Detection and Diagnosis

MedlinePlus

... page please turn JavaScript on. Feature: Screening For Breast Cancer Detection and Diagnosis Past Issues / Summer 2014 Table ... States Preventive Services Task Force updated recommendations on breast cancer screening, suggesting that women ages 50 to 74 ...

A new photoelectric ink based on nanocellulose/CdS quantum dots for screen-printing.

PubMed

Tang, Aimin; Liu, Yuan; Wang, Qinwen; Chen, Ruisong; Liu, Wangyu; Fang, Zhiqiang; Wang, Lishi

2016-09-05

CdS quantum dots with excellent photoelectrical properties embedded in nanocellulose could be exploited for use in photoelectrical ink. In this work, nanocellulose/CdS quantum dot composites were fabricated by controlling the carboxylate content of the nanocellulose and the molar ratio of Cd(2+)/-COOH. New photoelectric inks were prepared based on the composites, in which the CdS quantum dots acted as the pigment and the nanocellulose as the binder. The results of the photocurrent of the composites showed that the photocurrent could be tailored by the carboxylate content and the molar ratio of Cd(2+)/-COOH. And the photocurrent could be as high as 2μA. The surface tension of the photoelectric ink was 27.80±0.03mN/m and its viscosity was 30.3mPas. The photoelectric ink was stable with excellent fluidity and rheology, it could therefore be applied to screen-printing and three-dimensional (3D) printing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prevalence of celiac disease in patients with severe food allergy.

PubMed

Pillon, R; Ziberna, F; Badina, L; Ventura, A; Longo, G; Quaglia, S; De Leo, L; Vatta, S; Martelossi, S; Patano, G; Not, T; Berti, I

2015-10-01

The association between food allergy and celiac disease (CD) is still to be clarified. We screened for CD 319 patients with severe food allergy (IgE > 85 kU/l against food proteins and a history of severe allergic reactions) who underwent specific food oral immunotherapy (OIT), together with 128 children with mild allergy who recovered without OIT, and compared the prevalence data with our historical data regarding healthy schoolchildren. Sixteen patients (5%) with severe allergy and one (0.8%) with mild allergy tested positive for both genetic and serological CD markers, while the prevalence among the schoolchildren was 1%. Intestinal biopsies were obtained in 13/16 patients with severe allergy and in the one with mild allergy, confirming the diagnosis of CD. Sufferers from severe food allergy seem to be at a fivefold increased risk of CD. Our findings suggest that routine screening for CD should be recommended in patients with severe food allergy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Facile fabrication of CdSe/CdS quantum dots and their application on the screening of colorectal cancer

NASA Astrophysics Data System (ADS)

Cao, Hongfeng; Dong, Quanjin; Hu, Li; Tu, Shiliang; Chai, Rui; Dai, Qiaoqiong

2015-11-01

In this paper, a facile aqueous route to water-soluble CdSe/CdS quantum dots (QDs) under mild conditions has been developed. The samples were characterized by means of transmission electron microscopy, energy-dispersive X-ray spectroscopy, and photoluminescence (PL) spectroscopy. The PL property of the QDs can be controlled by adjusting the reaction time. The CdSe/CdS QDs after 48-h reaction with size of 5 nm have the strongest PL intensity located at 553 nm, and the highest quantum yield of 19.9 %. The obtained QDs were applied for the colorectal cancer screening. The QDs could be conjugated with antibody of aldo-keto reductase family 1, member B10 (AKR1B10) for the detection of AKR1B10. The AKR1B10 in PBS/5 % serum solution with concentration of 1 ng/mL could be well calibrated, and the limit of detection could be lower than 0.05 ng/mL.

Persistent conditioned place preference to aggression experience in adult male sexually-experienced CD-1 mice

PubMed Central

Golden, Sam A.; Aleyasin, Hossein; Heins, Robert; Flanigan, Meghan; Heshmati, Mitra; Takahashi, Aki; Russo, Scott J.; Shaham, Yavin

2016-01-01

We recently developed a conditioned place preference (CPP) procedure, commonly used to study rewarding drug effects, to demonstrate that dominant sexually-experienced CD-1 male mice form CPP to contexts previously associated with defeating subordinate male C57BL/6J mice. Here we further characterized conditioned and unconditioned aggression behavior in CD-1 mice. In Exp. 1 we used CD-1 mice that displayed a variable spectrum of unconditioned aggressive behavior toward younger subordinate C57BL/6J intruder mice. We then trained the CD-1 mice in the CPP procedure where one context was intruder-paired, while a different context was not. We then tested for aggression CPP 1 day after training. In Exp. 2, we tested CD-1 mice for aggression CPP 1 day and 18 days after training. In Exp. 3–4, we trained the CD-1 mice to lever-press for palatable food and tested them for footshock punishment-induced suppression of food-reinforced responding. In Exp. 5, we characterized unconditioned aggression in hybrid CD-1xC57BL/6J D1-Cre or D2-Cre F1 generation crosses. Persistent aggression CPP was observed in CD-1 mice that either immediately attacked C57BL/6J mice during all screening sessions or mice that gradually developed aggressive behavior during the screening phase. In contrast, CD-1 mice that did not attack the C57BL/6J mice during screening didn’t develop CPP to contexts previously paired with C57BL/6J mice. The aggressive phenotype did not predict resistance to punishment-induced suppression of food-reinforced responding. CD-1xD1-Cre or D2-Cre F1 transgenic mice showed strong unconditioned aggression. Our study demonstrates that aggression experience causes persistent CPP and introduces transgenic mice for circuit studies of aggression. PMID:27457669

Persistent conditioned place preference to aggression experience in adult male sexually-experienced CD-1 mice.

PubMed

Golden, S A; Aleyasin, H; Heins, R; Flanigan, M; Heshmati, M; Takahashi, A; Russo, S J; Shaham, Y

2017-01-01

We recently developed a conditioned place preference (CPP) procedure, commonly used to study rewarding drug effects, to demonstrate that dominant sexually-experienced CD-1 male mice form CPP to contexts previously associated with defeating subordinate male C57BL/6J mice. Here we further characterized conditioned and unconditioned aggression behavior in CD-1 mice. In Exp. 1 we used CD-1 mice that displayed a variable spectrum of unconditioned aggressive behavior toward younger subordinate C57BL/6J intruder mice. We then trained the CD-1 mice in the CPP procedure where one context was intruder-paired, while a different context was not. We then tested for aggression CPP 1 day after training. In Exp. 2, we tested CD-1 mice for aggression CPP 1 day and 18 days after training. In Exp. 3-4, we trained the CD-1 mice to lever-press for palatable food and tested them for footshock punishment-induced suppression of food-reinforced responding. In Exp. 5, we characterized unconditioned aggression in hybrid CD-1 × C57BL/6J D1-Cre or D2-Cre F1 generation crosses. Persistent aggression CPP was observed in CD-1 mice that either immediately attacked C57BL/6J mice during all screening sessions or mice that gradually developed aggressive behavior during the screening phase. In contrast, CD-1 mice that did not attack the C57BL/6J mice during screening did not develop CPP to contexts previously paired with C57BL/6J mice. The aggressive phenotype did not predict resistance to punishment-induced suppression of food-reinforced responding. CD-1 × D1-Cre or D2-Cre F1 transgenic mice showed strong unconditioned aggression. Our study demonstrates that aggression experience causes persistent CPP and introduces transgenic mice for circuit studies of aggression. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

A multi-phenotypic imaging screen to identify bacterial effectors by exogenous expression in a HeLa cell line.

PubMed

Collins, Adam; Huett, Alan

2018-05-15

We present a high-content screen (HCS) for the simultaneous analysis of multiple phenotypes in HeLa cells expressing an autophagy reporter (mcherry-LC3) and one of 224 GFP-fused proteins from the Crohn's Disease (CD)-associated bacterium, Adherent Invasive E. coli (AIEC) strain LF82. Using automated confocal microscopy and image analysis (CellProfiler), we localised GFP fusions within cells, and monitored their effects upon autophagy (an important innate cellular defence mechanism), cellular and nuclear morphology, and the actin cytoskeleton. This data will provide an atlas for the localisation of 224 AIEC proteins within human cells, as well as a dataset to analyse their effects upon many aspects of host cell morphology. We also describe an open-source, automated, image-analysis workflow to identify bacterial effectors and their roles via the perturbations induced in reporter cell lines when candidate effectors are exogenously expressed.

Immunogenicity and safety of 1 vs 2 doses of quadrivalent meningococcal conjugate vaccine in youth infected with human immunodeficiency virus.

PubMed

Lujan-Zilbermann, Jorge; Warshaw, Meredith G; Williams, Paige L; Spector, Stephen A; Decker, Michael D; Abzug, Mark J; Heckman, Barb; Manzella, Adam; Kabat, Bill; Jean-Philippe, Patrick; Nachman, Sharon; Siberry, George K

2012-10-01

To compare the immunogenicity of 1 vs 2 doses of meningococcal polysaccharide conjugate vaccine (MCV4) in youth infected with human immunodeficiency virus (HIV). P1065 was a phase I/II immunogenicity and safety trial of MCV4 in 324 youth infected with HIV performed at 27 sites of the International Maternal Pediatric Adolescent AIDS Clinical Trials Group network in the US. At entry subjects received 1 dose of MCV4. At 24 weeks, those with screening cluster of differentiation 4 (CD4)% ≥ 15 were randomized to receive a second dose or not, and all with screening CD4% <15 received a second dose. Immunogenicity was evaluated as the proportion of subjects with a ≥ 4-fold rise from entry in serum bactericidal antibody against each meningococcal serogroup (SG) at weeks 28 and 72. Logistic regression models adjusting for HIV disease severity were used to evaluate the effect of 1 vs 2 MCV4 doses among those with screening CD4% ≥ 15. Subjects randomized to receive 2 vs 1 MCV4 dose had significantly higher response rates to all SGs at week 28 and to all except Neisseria meningitidis SG Y at week 72, with adjusted ORs of 2.5-5.6. In 31 subjects with screening CD4% <15 who received 2 MCV4 doses, response rates ranged from 22%-55% at week 28 and 6%-28% at week 72. In youth infected with HIV with a CD4% ≥ 15, a second dose of MCV4 given 6 months after the initial dose significantly improves response rates at 28 and 72 weeks. Subjects with CD4% <15 at entry had lower response rates despite 2 doses of MCV4. Copyright © 2012 Mosby, Inc. All rights reserved.

Synergism of virtual screening and medicinal chemistry: identification and optimization of allosteric antagonists of metabotropic glutamate receptor 1.

PubMed

Noeske, Tobias; Trifanova, Dina; Kauss, Valerjans; Renner, Steffen; Parsons, Christopher G; Schneider, Gisbert; Weil, Tanja

2009-08-01

We report the identification of novel potent and selective metabotropic glutamate receptor 1 (mGluR1) antagonists by virtual screening and subsequent hit optimization. For ligand-based virtual screening, molecules were represented by a topological pharmacophore descriptor (CATS-2D) and clustered by a self-organizing map (SOM). The most promising compounds were tested in mGluR1 functional and binding assays. We identified a potent chemotype exhibiting selective antagonistic activity at mGluR1 (functional IC(50)=0.74+/-0.29 microM). Hit optimization yielded lead structure 16 with an affinity of K(i)=0.024+/-0.001 microM and greater than 1000-fold selectivity for mGluR1 versus mGluR5. Homology-based receptor modelling suggests a binding site compatible with previously reported mutation studies. Our study demonstrates the usefulness of ligand-based virtual screening for scaffold-hopping and rapid lead structure identification in early drug discovery projects.

A synthetic cannabinoid JWH-210 reduces lymphoid organ weights and T-cell activator levels in mice via CB2 receptors.

PubMed

Gu, Sun Mi; Lee, Hyun Jin; Lee, Tac-Hyung; Song, Yun Jeong; Kim, Young-Hoon; Han, Kyoung-Moon; Shin, Jisoon; Park, Hye-Kyung; Kim, Hyung Soo; Cha, Hye Jin; Yun, Jaesuk

2017-12-01

The problem of new psychoactive substances (NPS) is emerging globally. However, the immunotoxicity of synthetic cannabinoids is not evaluated extensively yet. The purpose of the present study was to investigate whether synthetic cannabinoids (JWH-210 and JWH-030) induce adverse effects on lymphoid organs, viability of splenocytes and thymocytes, and immune cell activator and cytokines in mice. JWH-210 (10 mg/kg, 3 days, i.p.) is more likely to have cytotoxicity and reduce lymphoid organ weight than JWH-030 of ICR mice in vivo. We also demonstrated that JWH-210 administration resulted in the decrease of expression levels of T-cell activator including Cd3e, Cd3g, Cd74p31, and Cd74p41, while JWH-030 increased Cd3g levels. In addition, JWH-210 reduced expression levels of cytokines, such as interleukin-3, interleukin-5, and interleukin-6. Furthermore, we demonstrated that a CB 2 receptor antagonist, AM630 inhibited JWH-210-induced cytotoxicity, whereas a CB 1 receptor antagonist, rimonabant did not in primary cultured splenocytes. These results suggest that JWH-210 has a cytotoxicity via CB 2 receptor action and results in decrement of lymphoid organ weights, T-cell activator, and cytokine mRNA expression levels.

The Simpson-Golabi-Behmel syndrome causative glypican-3, binds to and inhibits the dipeptidyl peptidase activity of CD26.

PubMed

Davoodi, Jamshid; Kelly, John; Gendron, Nathalie H; MacKenzie, Alex E

2007-06-01

Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked condition shown to be the result of deletions of the glypican-3 (GPC3) gene. GPC3 is a proteoglycan localized to the cell membrane via a glycosylphosphatidyl-inositol (GPI) anchor. To further elucidate the GPC3 function(s), we have screened various cell lines for proteins that interact with GPC3, resulting in the isolation of a 115 kDa protein, identified as CD26. The interaction occurred with both the glycosylated and unglycosylated forms of GPC3 and led to the inhibition of CD26 peptidase activity. Moreover, introduction of CD26 into Cos-1 cells was accompanied by the up-regulation of cell growth, while inclusion of recombinant GPC3 in the media reduced the growth of CD26 transfected Cos-1 cells, drastically. Furthermore, HepG2 C3A cells containing CD26 underwent apoptosis in the presence of recombinant GPC3 in both concentration and time-dependant manner. In light of the fact that inhibition of CD26 reduces the rate of cell proliferation, we propose that a number of physical findings observed in SGBS patients may be a consequence of a direct interaction of GPC3 with CD26. Furthermore, GPC3 without the GPI anchor is capable of inducing apoptosis indicating that neither the GPI anchor nor the membrane attachment is required for apoptosis induction.

High frequencies of circulating IFN-gamma-secreting CD8 cytotoxic T cells specific for a novel MHC class I-restricted Mycobacterium tuberculosis epitope in M. tuberculosis-infected subjects without disease.

PubMed

Pathan, A A; Wilkinson, K A; Wilkinson, R J; Latif, M; McShane, H; Pasvol, G; Hill, A V; Lalvani, A

2000-09-01

MHC class I-restricted CD8 cytotoxic T lymphocytes (CTL) are essential for protective immunity to Mycobacterium tuberculosis in animal models but their role in humans remains unclear. We therefore studied subjects who had successfully contained M. tuberculosis infection in vivo, i.e. exposed healthy household contacts and individuals with inactive self-healed pulmonary tuberculosis. Using the ELISPOT assay for IFN-gamma, we screened peptides from ESAT-6, a secreted antigen that is highly specific for M. tuberculosis. We identified a novel nonamer epitope: unstimulated peripheral blood-derived CD8 T cells displayed peptide-specific IFN-gamma release ex vivo while CD8 T cell lines and clones exhibited HLA-A68.02-restricted cytolytic activity and recognized endogenously processed antigen. The frequency of CD8 CTL specific for this single M. tuberculosis epitope, 1/2500 peripheral blood lymphocytes, was equivalent to the combined frequency of all IFN-gamma-secreting purified protein derivative-reactive T cells ex vivo. This highly focused CTL response was maintained in an asymptomatic contact over 2 years and is the most potent antigen-specific antimycobacterial CD8 CTL response hitherto described. Thus, human M. tuberculosis-specific CD8 CTL are not necessarily associated with active disease per se. Rather, our results are consistent with a protective role for these ESAT-6-specific CD8 T cells in the long-term control of M. tuberculosis in vivo in humans.

A plasmacytoid dendritic cell (CD123+/CD11c-) based assay system to predict contact allergenicity of chemicals

PubMed Central

Ayehunie, Seyoum; Snell, Maureen; Child, Matthew; Klausner, Mitchell

2009-01-01

A predictive allergenicity test system for assessing the contact allergenicity of chemicals is needed by the cosmetic and pharmaceutical industry to monitor product safety in the marketplace. Development of such non-animal alternative assay systems for skin sensitization and hazard identification has been pursued by policy makers and regulatory agencies. We investigated whether phenotypic and functional changes to a subset of dendritic cells (DC), plasmacytoid DC (pDC), could be used to identify contact allergens. To achieve this goal, normal human DC were generated from CD34+ progenitor cells and cryopreserved. Frozen DC were thawed and the pDC fraction (CD123+/CD11c-) was harvested using FACS sorting. The pDC were cultured, expanded, and exposed to chemical allergens (N=26) or non-allergens (N=22). Concentrations of each chemical that resulted in >50% viability was determined using FACS analysis of propidium iodide stained cells using pDC from 2-5 donors. Expression of the surface marker, CD86, which has been implicated in dendritic cell maturation, was used as a marker of allergenicity. CD86 expression increased (≥ 1.5 fold) for 25 of 26 allergens (sensitivity = 96%) but did not increase for 19 of 22 non-allergens (specificity = 86%). In a direct comparison to historical data for the regulatory approved, mouse local lymph node assay (LLNA) for 23 allergens and 22 non-allergens, the pDC method had sensitivity and specificity of 96% and 86%, respectively, while the sensitivity and specificity of the LLNA assay was 83% and 82%, respectively. In conclusion, CD86 expression in pDC appears to be a sensitive and specific indicator to identify contact allergenicity. Such an assay method utilizing normal human cells will be useful for high throughput screening of chemicals for allergenicity. PMID:19665512

Using resource modelling to inform decision making and service planning: the case of colorectal cancer screening in Ireland.

PubMed

Sharp, Linda; Tilson, Lesley; Whyte, Sophie; Ceilleachair, Alan O; Walsh, Cathal; Usher, Cara; Tappenden, Paul; Chilcott, James; Staines, Anthony; Barry, Michael; Comber, Harry

2013-03-19

Organised colorectal cancer screening is likely to be cost-effective, but cost-effectiveness results alone may not help policy makers to make decisions about programme feasibility or service providers to plan programme delivery. For these purposes, estimates of the impact on the health services of actually introducing screening in the target population would be helpful. However, these types of analyses are rarely reported. As an illustration of such an approach, we estimated annual health service resource requirements and health outcomes over the first decade of a population-based colorectal cancer screening programme in Ireland. A Markov state-transition model of colorectal neoplasia natural history was used. Three core screening scenarios were considered: (a) flexible sigmoidoscopy (FSIG) once at age 60, (b) biennial guaiac-based faecal occult blood tests (gFOBT) at 55-74 years, and (c) biennial faecal immunochemical tests (FIT) at 55-74 years. Three alternative FIT roll-out scenarios were also investigated relating to age-restricted screening (55-64 years) and staggered age-based roll-out across the 55-74 age group. Parameter estimates were derived from literature review, existing screening programmes, and expert opinion. Results were expressed in relation to the 2008 population (4.4 million people, of whom 700,800 were aged 55-74). FIT-based screening would deliver the greatest health benefits, averting 164 colorectal cancer cases and 272 deaths in year 10 of the programme. Capacity would be required for 11,095-14,820 diagnostic and surveillance colonoscopies annually, compared to 381-1,053 with FSIG-based, and 967-1,300 with gFOBT-based, screening. With FIT, in year 10, these colonoscopies would result in 62 hospital admissions for abdominal bleeding, 27 bowel perforations and one death. Resource requirements for pathology, diagnostic radiology, radiotherapy and colorectal resection were highest for FIT. Estimates depended on screening uptake. Alternative FIT roll-out scenarios had lower resource requirements. While FIT-based screening would quite quickly generate attractive health outcomes, it has heavy resource requirements. These could impact on the feasibility of a programme based on this screening modality. Staggered age-based roll-out would allow time to increase endoscopy capacity to meet programme requirements. Resource modelling of this type complements conventional cost-effectiveness analyses and can help inform policy making and service planning.

Choosing a CD-ROM Encyclopedia: How to Critically Evaluate the Product.

ERIC Educational Resources Information Center

Dickinson, Gail

1990-01-01

Offers criteria for the critical evaluation of CD-ROM encyclopedias. Differences between CD-ROM and print encyclopedias are discussed; search strategies are explained; evaluation criteria are suggested, including help messages, screen format, indexing method, and graphics and print options; future considerations are suggested, including…

Online self-test identifies women at high familial breast cancer risk in population-based breast cancer screening without inducing anxiety or distress.

PubMed

van Erkelens, A; Sie, A S; Manders, P; Visser, A; Duijm, L E; Mann, R M; Ten Voorde, M; Kroeze, H; Prins, J B; Hoogerbrugge, N

2017-06-01

Identifying high familial breast cancer (FBC) risk improves detection of yet unknown BRCA1/2-mutation carriers, for whom BC risk is both highly likely and potentially preventable. We assessed whether a new online self-test could identify women at high FBC risk in population-based BC screening without inducing anxiety or distress. After their visit for screening mammography, women were invited by email to take an online self-test for identifying highly increased FBC risk-based on Dutch guidelines. Exclusion criteria were previously diagnosed as increased FBC risk or a personal history of BC. Anxiety (State-Trait Anxiety Inventory Dutch Version), distress (Hospital Anxiety Depression Scale) and BC risk perception were assessed using questionnaires, which were completed immediately before and after taking the online self-test and 2 weeks later. Of the 562 women invited by email, 406 (72%) completed the online self-test while 304 also completed questionnaires (response rate 54%). After exclusion criteria, 287 (51%) were included for data analysis. Median age was 56 years (range 50-74). A high or moderate FBC risk was identified in 12 (4%) and three (1%) women, respectively. After completion of the online self-test, anxiety and BC risk perception were decreased while distress scores remained unchanged. Levels were below clinical relevance. Most women (85%) would recommend the self-test; few (3%) would not. The online self-test identified previously unknown women at high FBC risk (4%), who may carry a BRCA1/2-mutation, without inducing anxiety or distress. We therefore recommend offering this self-test to women who attend population-based screening mammography for the first time. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biosorption of cationic basic dye and cadmium by the novel biosorbent Bacillus catenulatus JB-022 strain.

PubMed

Kim, Su Young; Jin, Mi Ra; Chung, Chang Ho; Yun, Yeoung-Sang; Jahng, Kwang Yeop; Yu, Kang-Yeol

2015-04-01

Biosorption of heavy metals and dyes is a promising technology that involves the removal of toxic metals from industrial wastes. The present study aims to screen the bacterial strains isolated from soils and polluted pond for their potential biosorption of both cationic dye and cadmium. Bacillus catenulatus JB-022 strain removed 58% and 66% of cationic basic blue 3 (BB3) and cadmium (Cd(II)) at the respective concentrations of 2000 mg/L and 150 mg/L. The biosorption equilibrium data were well fitted by the Langmuir adsorption isotherm, and the kinetic studies indicated that the biosorption followed the pseudo-second-order model. The biosorption kinetics showed that the equilibrium was reached within 10 min and 5 min for BB3 and Cd(II), respectively. According to the Langmuir model, the maximum uptakes of BB3 and Cd(II) by the JB-022 biomass were estimated to be 139.74 and 64.28 mg/g, respectively. To confirm the surface morphology and functional groups, field emission scanning electron microscope, energy-dispersive X-ray spectrometer, X-ray diffraction, and Fourier transform infrared spectroscopy analyses were carried out, and the results revealed that the biomass of JB-022 has carboxyl and phosphonate groups as potential surface functional groups capable of binding to cationic pollutants. In conclusion, B. catenulatus JB-022 is proposed as an excellent biosorbent with potentially important applications in removal of cationic pollutants from wastewaters. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Meta-analysis of screening and case finding tools for depression in cancer: evidence based recommendations for clinical practice on behalf of the Depression in Cancer Care consensus group.

PubMed

Mitchell, Alex J; Meader, Nick; Davies, Evan; Clover, Kerrie; Carter, Gregory L; Loscalzo, Matthew J; Linden, Wolfgang; Grassi, Luigi; Johansen, Christoffer; Carlson, Linda E; Zabora, James

2012-10-01

To examine the validity of screening and case-finding tools used in the identification of depression as defined by an ICD10/DSM-IV criterion standard. We identified 63 studies involving 19 tools (in 33 publications) designed to help clinicians identify depression in cancer settings. We used a standardized rating system. We excluded 11 tools without at least two independent studies, leaving 8 tools for comparison. Across all cancer stages there were 56 diagnostic validity studies (n=10,009). For case-finding, one stem question, two stem questions and the BDI-II all had level 2 evidence (2a, 2b and 2c respectively) and given their better acceptability we gave the stem questions a grade B recommendation. For screening, two stem questions had level 1b evidence (with high acceptability) and the BDI-II had level 2c evidence. For every 100 people screened in advanced cancer, the two questions would accurately detect 18 cases, while missing only 1 and correctly reassure 74 with 7 falsely identified. For every 100 people screened in non-palliative settings the BDI-II would accurately detect 17 cases, missing 2 and correctly re-assure 70, with 11 falsely identified as cases. The main cautions are the reliance on DSM-IV definitions of major depression, the large number of small studies and the paucity of data for many tools in specific settings. Although no single tool could be offered unqualified support, several tools are likely to improve upon unassisted clinical recognition. In clinical practice, all tools should form part of an integrated approach involving further follow-up, clinical assessment and evidence based therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

Risk Assessment for CPAP Nonadherence in Adults with Newly-diagnosed Obstructive Sleep Apnea: Preliminary Testing of the Index for Nonadherence to PAP (I-NAP)

PubMed Central

Sawyer, Amy M.; King, Tonya S.; Hanlon, Alexandra; Richards, Kathy C.; Sweer, Leon; Rizzo, Albert; Weaver, Terri E.

2014-01-01

Purpose Identification of risk for CPAP nonadherence prior to home treatment is an opportunity to deliver targeted, adherence interventions. Study objectives included (1) test a risk screening questionnaire to prospectively identify CPAP nonadherence risk among adults with newly-diagnosed OSA; (2) reduce the questionnaire to a minimum item set that effectively identifies 1-month CPAP nonadherence; and (3) examine the diagnostic utility of the screening index. Methods A prospective, longitudinal study at two clinical sleep centers in the U.S. included adults with newly diagnosed OSA (n=97; AHI ≥ 5 events/hr) by polysomnogram (PSG) consecutively recruited to participate. After baseline participant and OSA characteristics were collected, a risk screening questionnaire was administered immediately following CPAP titration polysomnogram. One-month objective CPAP use was collected. Results Predominantly white (87%) males (55%) and females (45%) with obesity (BMI 38.3 kg/m2; SD 9.3) and severe OSA (AHI 36.8; SD 19.7) were included. One-month CPAP use was 4.25hrs/night (SD 2.35). Nineteen questionnaire items (I-NAP) reliably identified nonadherers defined at <4hr/night CPAP use (Wald X2[8] =34.67, p<0.0001) with ROC AUC 0.83 (95% CI 0.74-0.91). Optimal score cut-point for the INAP screening questionnaire were determined to maximize sensitivity (87%) while maintaining specificity >60% (63%). Conclusion A risk screening questionnaire employed immediately after titration PSG may reliably identify CPAP nonadherers and permit the delivery of targeted interventions to prevent or reduce nonadherence. This novel approach may enhance cost-effectiveness of care and permit appropriate allocation of resources for CPAP adherence. PMID:24595715

Understanding structure, metal distribution, and water adsorption in mixed-metal MOF-74

DOE PAGES

Howe, Joshua D.; Morelock, Cody R.; Jiao, Yang; ...

2016-11-30

We present a joint computational and experimental study of Mg–Ni-MOF-74 and Mg–Cd-MOF-74 to gain insight into the mixing of metals and understand how metal mixing affects the structure of the undercoordinated open-metal sites. Our calculations predict that metal mixing is energetically preferred in these materials. Recent experimental work has demonstrated that Mg–Ni-MOF-74 shows a much greater surface area retention in the presence of water than Mg-MOF-74. To probe this effect, we study H 2O adsorption in Mg–Ni-MOF-74, finding that the adsorption energetics and electronic structure do not change significantly at the metal sites when compared to Mg-MOF-74 and Ni-MOF-74, respectively.more » Lastly, we conclude that the increased stability of Mg–Ni-MOF-74 is a result of a M–O bond length distortion in mixed-metal MOF-74, consistent with recent work on the stability of MOF-74 under water exposure.« less

Optimal Cut-Off Points of Fasting Plasma Glucose for Two-Step Strategy in Estimating Prevalence and Screening Undiagnosed Diabetes and Pre-Diabetes in Harbin, China

PubMed Central

Sun, Bo; Lan, Li; Cui, Wenxiu; Xu, Guohua; Sui, Conglan; Wang, Yibaina; Zhao, Yashuang; Wang, Jian; Li, Hongyuan

2015-01-01

To identify optimal cut-off points of fasting plasma glucose (FPG) for two-step strategy in screening abnormal glucose metabolism and estimating prevalence in general Chinese population. A population-based cross-sectional study was conducted on 7913 people aged 20 to 74 years in Harbin. Diabetes and pre-diabetes were determined by fasting and 2 hour post-load glucose from the oral glucose tolerance test in all participants. Screening potential of FPG, cost per case identified by two-step strategy, and optimal FPG cut-off points were described. The prevalence of diabetes was 12.7%, of which 65.2% was undiagnosed. Twelve percent or 9.0% of participants were diagnosed with pre-diabetes using 2003 ADA criteria or 1999 WHO criteria, respectively. The optimal FPG cut-off points for two-step strategy were 5.6 mmol/l for previously undiagnosed diabetes (area under the receiver-operating characteristic curve of FPG 0.93; sensitivity 82.0%; cost per case identified by two-step strategy ¥261), 5.3 mmol/l for both diabetes and pre-diabetes or pre-diabetes alone using 2003 ADA criteria (0.89 or 0.85; 72.4% or 62.9%; ¥110 or ¥258), 5.0 mmol/l for pre-diabetes using 1999 WHO criteria (0.78; 66.8%; ¥399), and 4.9 mmol/l for IGT alone (0.74; 62.2%; ¥502). Using the two-step strategy, the underestimates of prevalence reduced to nearly 38% for pre-diabetes or 18.7% for undiagnosed diabetes, respectively. Approximately a quarter of the general population in Harbin was in hyperglycemic condition. Using optimal FPG cut-off points for two-step strategy in Chinese population may be more effective and less costly for reducing the missed diagnosis of hyperglycemic condition. PMID:25785585

Prostate and Colon Cancer Screening Messages in Popular Magazines

PubMed Central

Katz, Mira L; Sheridan, Stacey; Pignone, Michael; Lewis, Carmen; Battle, Jamila; Gollop, Claudia; O'Malley, Michael

2004-01-01

OBJECTIVES To 1) compare the number of articles published about prostate, colon, and breast cancer in popular magazines during the past 2 decades, and 2) evaluate the content of in-depth prostate and colon cancer screening articles identified from 1996 to 2001. DESIGN We used a searchable database to identify the number of prostate, colon, and breast cancer articles published in three magazines with the highest circulation from six categories. In addition, we performed a systematic review on the in-depth (≥2 pages) articles on prostate and colon cancer screening that appeared from 1996 through 2001. RESULTS Although the number of magazine articles on prostate and colon cancer published in the 1990s increased compared to the 1980s, the number of articles is approximately one third of breast cancer articles. There were 36 in-depth articles from 1996 to 2001 in which prostate or colon cancer screening were mentioned. Over 90% of the articles recommended screening. However, of those articles, only 76% (25/33; 95% confidence interval [CI], 58% to 89%) cited screening guidelines. The benefits of screening were mentioned in 89% (32/36; 95% CI, 74% to 97%) but the harms were only found in 58% (21/36; 95% CI, 41% to 75%). Only 28% (10/36; 95% CI, 14% to 45%) of the articles provided all the necessary information needed for the reader to make an informed decision. CONCLUSIONS In-depth articles about prostate and colon cancer in popular magazines do not appear as frequently as articles about breast cancer. The available articles on prostate and colon cancer screening often do not provide the information necessary for the reader to make an informed decision about screening. PMID:15242469

Induction of multipotential hematopoietic progenitors from human pluripotent stem cells via re-specification of lineage-restricted precursors

PubMed Central

Doulatov, Sergei; Vo, Linda T.; Chou, Stephanie S.; Kim, Peter G.; Arora, Natasha; Li, Hu; Hadland, Brandon K.; Bernstein, Irwin D.; Collins, James J.; Zon, Leonard I.; Daley, George Q.

2013-01-01

Summary Human pluripotent stem cells (hPSCs) represent a promising source of patient-specific cells for disease modeling, drug screens, and cellular therapies. However, the inability to derive engraftable human hematopoietic stem and progenitor (HSPCs) has limited their characterization to in vitro assays. We report a strategy to re-specify lineage-restricted CD34+CD45+ myeloid precursors derived from hPSCs into multilineage progenitors that can be expanded in vitro and engraft in vivo. HOXA9, ERG, and RORA conferred self-renewal and multilineage potential in vitro and maintained primitive CD34+CD38− cells. Screening cells via transplantation revealed that two additional factors, SOX4 and MYB, were required for engraftment. Progenitors specified with all five factors gave rise to reproducible short-term engraftment with myeloid and erythroid lineages. Erythroid precursors underwent hemoglobin switching in vivo, silencing embryonic and activating adult globin expression. Our combinatorial screening approach establishes a strategy for obtaining transcription factor-mediated engraftment of blood progenitors from human pluripotent cells. PMID:24094326

Patient Dashboard: the use of a colour-coded computerised clinical reminder in Whanganui regional general practices.

PubMed

McMenamin, John; Nicholson, Rick; Leech, Ken

2011-12-01

Clinical reminders have been shown to help general practice achieve an increase in some preventive care items, especially if they identify a patient's eligibility for the target item, prompt clinicians at the right time, provide a fast link to management tools and facilitate clinical recording. WRPHO has introduced the Patient Dashboard clinical reminder and monitored its impact on health targets. This paper reports the impact of a computerised colour-coded clinical reminder on achieving agreed health targets in Whanganui regional practices. Patient Dashboard was developed from previous versions in Auckland and Northland and provided to Whanganui regional practices with Primary Health Organisation (PHO) support. The Dashboard was linked with existing and new clinical management tools which automatically updated clinical records. Data from practices was pooled by Whanganui Regional Primary Health Organisation and target achievement rates reported over 15 months. Over the initial 15 months of Patient Dashboard use, recording of smoking status increased from 74% to 82% and of alcohol use from 15% to 47%. Screening for diabetes increased from 62% to 74%, cardiovascular risk assessment from 20% to 43%, cervical screening from 71% to 79%, and breast screening from 60% to 80%. Patient Dashboard was associated with increased performance indicators both for those targets which were part of a PHO programme and for targets without additional support.

When to screen children with Down syndrome for celiac disease?

PubMed

Pavlovic, Momcilo; Radlovic, Nedeljko; Lekovic, Zoran; Stojsic, Zorica; Puleva, Katja; Berenji, Karolina

2010-12-01

The coexistence of Down syndrome (DS) and celiac disease (CD) has been reported in many studies. In our study, we examined 82 children with DS aged 8 months to 8.6 years for the existence of CD using serological markers immunoglobulin A (IgA) and immunoglobulin G (IgG) transglutaminase antibodies, followed by follow-up determination of total IgA levels. In four children who were positive for one of the above-mentioned antibodies, enteric biopsy has been performed that showed absence of CD. Our findings raise doubt about the need for obligatory serological screening of children with DS aged <8 years.

CD-ROM and Libraries.

ERIC Educational Resources Information Center

Murphy, Brower

1985-01-01

The Compact Disc-Read Only Memory (CD-ROM) data format is explained and illustrated, noting current and potential applications. The "5-inch" compact laserdisc is described and photographs of an IBM PC/Hitachi CD-ROM system adopted by Library Corporation to support its MARC database--BiblioFile--are presented. Screen displays for…

CD-I and Full Motion Video.

ERIC Educational Resources Information Center

Chen, Ching-chih

1991-01-01

Describes compact disc interactive (CD-I) as a multimedia home entertainment system that combines audio, visual, text, graphic, and interactive capabilities. Full-screen video and full-motion video (FMV) are explained, hardware for FMV decoding is described, software is briefly discussed, and CD-I titles planned for future production are listed.…

[Clinical and genetic analysis for activated PI3K-δ syndrome by PIK3CD gene mutation].

PubMed

Liu, H; Tang, X L; Liu, J R; Li, H M; Zhao, S Y

2016-09-01

To analyze clinical and genetic features of activated PI3K-δ syndrome (APDS), a new form of immunodeficiency disease caused by PIK3CD gene mutation. Data of two patients diagnosed as APDS at Second Department of Respiratory Medicine of Beijing Children's Hospital Affiliated to Capital Medical University in 2015 were retrospectively reviewed. Pathogenetic genes were screened by whole exome sequencing, and identified by first generation sequencing. The identified pathogenetic genes were further verified in patients' parents. Then the gene sequencing results were analyzed. Both patients were females, aged 2 years and 4 months and 5 years respectively. The main clinical features of both cases were recurrent respiratory infections, enlargement of lymph node, hepatosplenomegaly, cytomegalovirus (CMV) or Epstein-Barr virus (EBV) viremia, decreased number of native CD4(+) T cell, inverted CD4(+) /CD8(+) T cell ratio and increased IgM. Patient 1 has decreased IgA and IgG. Patient 2 showed wide follicular hyperplasia of the airway mucosa. Both patients had de novo mutation in c. 3061G>A(E1021K)of PIK3CD gene, which was homozygous in patient 1 and heterozygous in patient 2. Both were treated with 500 mg/kg dose of gamma globulin intravenously at 4-weeks interval. Patient 1 started oral rapamycin therapy at the dose of 1 mg/(m(2)·d) and discontinued the treatment after 2 weeks. Patient 2 was given low dose of oral prednisone. The two patients were followed up for 2 months. The number of respiratory infection in both patients was decreased. Hepatosplenomegaly was subsided, while respiratory tract damage was not improved in patient 2. The clinical manifestations of APDS include recurrent respiratory tract infection, enlargement of lymph nodes, hepatosplenomegaly, and CMV or EBV infection. The immunophenotype is decreased native CD4(+) T cell, inverted CD4(+) /CD8(+) T cell ratio, increased IgM and decreased IgA/IgG for some patients. c. 3061G>A(E1021K)of PIK3CD gene is a common de novo mutation in APDS patients.

Subcellular distribution and chemical forms of cadmium in the edible seaweed, Porphyra yezoensis.

PubMed

Zhao, Yanfang; Wu, Jifa; Shang, Derong; Ning, Jinsong; Zhai, Yuxiu; Sheng, Xiaofeng; Ding, Haiyan

2015-02-01

The subcellular distribution and chemical forms of Cd were investigated in the edible seaweed, Porphyra yezoensis. The seaweed was exposed to different Cd concentrations (0.01, 0.05, 0.1, 0.5, 1.0 and 5.0mgl(-1)) for up to 96h. In both the controls (no Cd added) and treatment groups, 41.2-79.2% of Cd was localised in the cell wall, and the proportion of Cd in the cell wall increased with increasing concentrations of Cd and exposure time. In the control groups, 74.8% of Cd was extracted by 1M NaCl, followed by 2% acetic acid, HAC (18.9%). In the treatment groups, most Cd was extracted by 2% HAC. The proportion of Cd extracted by 2% HAC increased with exposure to increasing concentrations of Cd and over time. Cell wall deposition and forming of precipitates with phosphate may be a key strategy to reduce Cd toxicity in P. yezoensis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Radiation-Induced Breast Cancer Incidence and Mortality From Digital Mammography Screening: A Modeling Study.

PubMed

Miglioretti, Diana L; Lange, Jane; van den Broek, Jeroen J; Lee, Christoph I; van Ravesteyn, Nicolien T; Ritley, Dominique; Kerlikowske, Karla; Fenton, Joshua J; Melnikow, Joy; de Koning, Harry J; Hubbard, Rebecca A

2016-02-16

Estimates of risk for radiation-induced breast cancer from mammography screening have not considered variation in dose exposure or diagnostic work-up after abnormal screening results. To estimate distributions of radiation-induced breast cancer incidence and mortality from digital mammography screening while considering exposure from screening and diagnostic mammography and dose variation among women. 2 simulation-modeling approaches. U.S. population. Women aged 40 to 74 years. Annual or biennial digital mammography screening from age 40, 45, or 50 years until age 74 years. Lifetime breast cancer deaths averted (benefits) and radiation-induced breast cancer incidence and mortality (harms) per 100,000 women screened. Annual screening of 100,000 women aged 40 to 74 years was projected to induce 125 breast cancer cases (95% CI, 88 to 178) leading to 16 deaths (CI, 11 to 23), relative to 968 breast cancer deaths averted by early detection from screening. Women exposed at the 95th percentile were projected to develop 246 cases of radiation-induced breast cancer leading to 32 deaths per 100,000 women. Women with large breasts requiring extra views for complete examination (8% of population) were projected to have greater radiation-induced breast cancer risk (266 cancer cases and 35 deaths per 100,000 women) than other women (113 cancer cases and 15 deaths per 100,000 women). Biennial screening starting at age 50 years reduced risk for radiation-induced cancer 5-fold. Life-years lost from radiation-induced breast cancer could not be estimated. Radiation-induced breast cancer incidence and mortality from digital mammography screening are affected by dose variability from screening, resultant diagnostic work-up, initiation age, and screening frequency. Women with large breasts may have a greater risk for radiation-induced breast cancer. Agency for Healthcare Research and Quality, U.S. Preventive Services Task Force, National Cancer Institute.

Use of hand grip strength in nutrition risk screening of older patients admitted to general surgical wards.

PubMed

Byrnes, Angela; Mudge, Alison; Young, Adrienne; Banks, Merrilyn; Bauer, Judy

2018-04-16

Hand grip strength (HGS) has been proposed as an indicator of nutritional status that is objective, requires minimal assessor training and is quick to administer, making it attractive for use in the acute setting. This study aimed to determine the discriminatory ability of impaired HGS to screen for malnutrition in an older hospital population and assess the added value of combining this with existing screening tools. Measures were undertaken during acute admission in patients ≥65 years admitted to general surgical wards. Impaired HGS was defined as a mean value below the lower limit of the 95% CI of population norms and observed HGS standardised as a percentage of this value. Nutritional risk was assessed using the Malnutrition Screening Tool (MST) and malnutrition defined as Patient-Generated Subjective Global Assessment (PG-SGA) rating B or C. Discriminatory ability of impaired HGS to identify malnourished patients was tested using the area under the receiver operating characteristic curve (AUC). Seventy-five patients (mean age: 74.0 (SD 6.7) years, 60% male) were recruited. Impaired HGS did not accurately identify malnutrition (AUC (95% CI): 0.41 (0.25-0.58), P < 0.001), nor did it improve discriminatory ability of the MST (AUC (95% CI), MST: 0.83 (0.71-0.95), P = 0.32; MST/HGS combined: 0.68 (0.51-0.86), P = 0.035). HGS was not found to be suitable in screening older inpatients for malnutrition during admission to surgical wards. As such, screening for nutrition risk using an existing validated tool to identify patients for further in-depth nutritional assessment by an appropriately trained clinician remains the preferred method. © 2018 Dietitians Association of Australia.

Patients' awareness of symptoms of dysphagia.

PubMed

Boczko, Faerella

2006-11-01

To assess geriatric patients' assessment of their clinical symptoms of dysphagia by means of a customized dysphagia screening tool and the usefulness of this assessment to health care professionals. The screening tool was distributed to an appropriate cohort and the entries correlated with results of standard speech-language pathology clinical assessments. A large long-term care/subacute rehabilitation facility. There were 199 new admissions screened. The patients included 74 (37.2%) males and 125 (60.8%) females. Patients' ages ranged from 50 to 98 with the mean age of 79.9 years. The screening tool used requires yes/no patient responses to 9 clinical indicators of dysphagia: difficulty keeping liquids in the mouth; coughing after drinking; shortness of breath while drinking; voice change after drinking; coughing after eating; shortness of breath after eating; food getting stuck in the mouth/throat when eating; voice change after eating; difficulty with saliva. After completing the questionnaire, the speech-language pathologist then conducted a standard bedside swallowing examination using the same 9 indicators. The findings suggest that although patients are less discriminating than clinicians in recognizing swallowing problems, the screening tool as a generalized indicator of potential for dysphagia is consistent and reliable. Individual items should not be used as indicators of dysphagia, but as a whole, the screening tool completed by patients is a reliable indicator of potential for dysphagia. Patients' awareness of their own swallowing impairment represents an important aspect of functional recovery. The findings of the study indicate that when patients self-identify a swallowing problem, the speech-language pathologist also identifies the existence of a problem, although not the same problem identified by the patient, with the same intensity or with the same manifestation.

Efficiency evaluation for remediating paddy soil contaminated with cadmium and arsenic using water management, variety screening and foliage dressing technologies.

PubMed

Liao, Guojian; Wu, Qianhua; Feng, Renwei; Guo, Junkang; Wang, Ruigang; Xu, Yingming; Ding, Yongzhen; Fan, Zhilian; Mo, Liangyu

2016-04-01

Paddy soils in many regions of China have been seriously polluted by multiple heavy metals or metalloids, such as arsenic (As), cadmium (Cd) and lead (Pb). In order to ensure the safety of food and take full advantage of the limited farmland resources of China, exploring an effective technology to repair contaminated soils is urgent and necessary. In this study, three technologies were employed, including variety screening, water management and foliage dressing, to assess their abilities to reduce the accumulation of Cd and As in the grains of different rice varieties, and meanwhile monitor the related yields. The results of variety screening under insufficient field drying condition showed that the As and Cd contents in the grains of only four varieties [Fengliangyouxiang 1 (P6), Zhongzheyou 8 (P7), Guangliangyou 1128 (P10), Y-liangyou 696 (P11)] did not exceed their individual national standard. P6 gained a relatively high grain yield but accumulated less As and Cd in the grains despite of the relatively high As and Cd concentrations in the rhizosphere soil. However, long-playing field drying in water management trial significantly increased Cd but decreased As content in the grains of all tested three varieties including P6, suggesting an important role of water supply in controlling the accumulation of grain As and Cd. Selenium (Se) showed a stronger ability than silicon (Si) to reduce As and Cd accumulation in the grains of Fengliangyou 4 (P2) and Teyou 524 (P13), and keep the yields. The results of this study suggest that combined application of water management and foliage dressing may be an efficient way to control As and Cd accumulation in the grains of paddy rice exposing to As- and Cd-contaminated soils. Copyright © 2016 Elsevier Ltd. All rights reserved.

Coexistence of celiac disease & type 1 diabetes mellitus in children.

PubMed

Singh, Preeti; Seth, Anju; Kumar, Praveen; Sajjan, Sushma

2017-01-01

Type 1 diabetes mellitus (T1DM) and celiac disease (CD) tend to co-exist due to similar underlying genetic predisposition. Failure to recognize CD in patients with T1DM predisposes them to complications. The present study was aimed to assess children with T1DM for the presence of CD. This was a retrospective analysis of the records of children with T1DM attending paediatric endocrinology clinic at a tertiary care hospital in north India from January 2006 to May 2014. All children were screened for CD at the time of diagnosis of T1DM using IgA anti-tissue transglutaminase (anti-tTG) levels in serum. Seropositive children were subjected to upper gastrointestinal endoscopy and duodenal biopsy for histopathological confirmation. The children also underwent thyroid function testing (TFT); those with deranged TFT were evaluated for thyroid-specific antibodies. Positive serology for CD was present in 43 of 126 children with T1DM whose records were reviewed [34.1%; 95% confidence interval (CI): 25.9-43.1]. Confirmed CD was diagnosed in 17 (13.5%; CI: 8.1-20.7) of the children screened and 17 of 40 (42.5%; CI: 27.1-59.1) seropositive participants. Four out of 17 children with coexisting CD and T1DM also had autoimmune thyroiditis with overt hypothyroidism. The children with confirmed CD were more likely to have short stature [odds ratios (OR)-3.16; 95% CI: 1.09-9.20, P<0.05] and hypothyroidism (OR-6.4; 95% CI: 1.52-26.90, P<0.05). Our study showed a higher proportion of CD in children with T1DM as compared to that reported in general population. Regular screening of children with T1DM for CD is needed to improve metabolic control and prevent long-term complications.

Selection of indigenous Lactobacillus paracasei CD4 and Lactobacillus gastricus BTM 7 as probiotic: assessment of traits combined with principal component analysis.

PubMed

Sharma, K; Mahajan, R; Attri, S; Goel, G

2017-05-01

The population of the Himalayan region is known to consume a variety of fermented and nonfermented foods and as a result they have been benefited in terms of overall health, because of the associated beneficial microbes. Therefore, the focus of the present study was to identify new strains of lactic acid bacteria (LAB) from dairy products such as milk (cow, goat, buffalo) and fermented products (curd and buttermilk) with properties suitable for use as probiotic cultures. A total of 75 isolates tentatively identified as LAB from 100 samples were initially screened for production of β-haemolysin as indicators of virulence which resulted in 38 isolates with no haemolytic activity. Further subtractive screening based on resistance to gastrointestinal tract barriers (acid and bile salts) resulted in the selection of the eight most promising strains. All these eight strains were resistant to pH 2·0, 1% bile concentration and pancreatin (1 mg l -1 ). Among the eight isolates, three isolates were identified as Brevibacillus thermoruber and the others as Brevibacillus aydinogluensis, Lactobacillus gastricus, L. paracasei, Enterococcus sp. Weisella confusa based on 16S rDNA region. Among these isolates, L. paracasei CD4 and L. gastricus BTM7 indicated maximum tolerance to simulated gastric environment. Both the isolates possessed highest score for cell surface hydrophobicity, cell autoaggregation, adherence to Caco-2 cell lines and antimicrobial activity against clinical isolates of Escherichia coli and Shigella sp. comparable to standard strain of Lactobacillus rhamnosus GG. Further principal component analysis and clustering analysis based on Euclidean Similarity index of probiotic characters revealed that L. paracasei strain CD4 and L. gastricus strain BTM7 were placed closest to reference strain L. rhamnosus GG and were therefore identified as most promising probiotic candidate cultures. These characteristics suggest that these strains could be excellent candidates for probiotics. Milk-based products serve as reservoir for bacterial species with probiotic attributes. © 2017 The Society for Applied Microbiology.

Gastrointestinal symptoms in children with type 1 diabetes screened for celiac disease.

PubMed

Narula, Priya; Porter, Lesley; Langton, Josephine; Rao, Veena; Davies, Paul; Cummins, Carole; Kirk, Jeremy; Barrett, Timothy; Protheroe, Susan

2009-09-01

The association between celiac disease (CD) and type 1 diabetes mellitus (DM) is recognized. Most cases of CD in patients with DM are reported to be asymptomatic. The objectives of this study were to (1) compare and audit our practice with the published standards for screening for CD in children with DM, (2) characterize the children with DM and biopsy-confirmed CD, in terms of growth and gastrointestinal symptoms, and compare them with children with DM and negative celiac serology, and (3) document the effects of a gluten-free diet (GFD) after 1 year of gastrointestinal symptoms, growth, and insulin requirement. We performed a retrospective case-note review of 22 children with DM, positive celiac serology +/- biopsy-confirmed CD, and 50 children with DM and negative celiac serology. Twenty-two children (3.9% of the total diabetic population) had positive celiac serology on screening, with 17 (3%) having biopsy-confirmed CD. Ninety-four percent of the children had standardized celiac serology testing. At diagnosis of CD, 13 of the 17 biopsy-positive children (76.4%) had > or =1 gastrointestinal symptom. The frequency of gastrointestinal symptoms in negative celiac serology diabetic children was 6% (3 of 50) (P < .0005). Symptoms resolved in all children after introduction of a GFD. A significant improvement in weight SD score (P = .008) and BMI SD score (P = .02) was noted in those compliant with a GFD after 1 year. Children with DM and CD have a higher frequency of gastrointestinal symptoms than their diabetic peers with negative celiac serology and are not truly asymptomatic. Institution of a GFD has a positive effect on nutritional status and symptom resolution in the short-term.

Prevalence of celiac disease in nutritional anemia at a tertiary care center.

PubMed

Kavimandan, Amit; Sharma, Meenakshi; Verma, Anil K; Das, Prasenjit; Mishra, Prabhash; Sinha, Sanjeev; Mohan, Anant; Sreenivas, V; Datta Gupta, Siddhartha; Makharia, Govind K

2014-03-01

While anemia occurs in 80 % to 90 % of patients with celiac disease (CD), it may be the sole manifestation of CD. The prevalence of CD in Indian patients with nutritional anemia is not known. Adolescent and adult patients presenting with nutritional anemia were prospectively screened for CD using IgA anti-tissue transglutaminase antibody (anti-tTG Ab) followed, if positive, by upper gastrointestinal endoscopy and duodenal biopsy. Ninety-six patients [mean ± SD age 32.1 ± 13.1 years and median duration of anemia 11 months (range 1 to 144 months)] were screened. Of these patients, 80 had iron deficiency anemia, 11 had megaloblastic anemia, and 5 had dimorphic anemia. Seventy-three patients were on hematinics and 36.4 % had received blood transfusions. Nineteen had a history of chronic diarrhea and the mean ± SD duration of diarrhea in them was 9.7 ± 35.8 months. IgA anti-tTG Ab was positive in 13 patients, of whom 12 agreed to undergo duodenal biopsy. Ten patients had villous atrophy (Marsh grade 3a in three, 3b in one, and 3c in six) and two did not. Thus, 10 patients with nutritional anemia (iron deficiency 9, vitamin B12 deficiency 1) were diagnosed to have CD. On multivariate logistic regression, age, duration of symptoms, and presence of diarrhea were found to be the predictors of CD. All the patients with CD were put on gluten-free diet and with iron and vitamin supplementations and showed a significant improvement in hemoglobin concentration. CD screening should be included in the work up of otherwise unexplained nutritional anemia.

An efficient strategy for cell-based antibody library selection using an integrated vector system.

PubMed

Yoon, Hyerim; Song, Jin Myung; Ryu, Chun Jeih; Kim, Yeon-Gu; Lee, Eun Kyo; Kang, Sunghyun; Kim, Sang Jick

2012-09-18

Cell panning of phage-displayed antibody library is a powerful tool for the development of therapeutic and imaging agents since disease-related cell surface proteins in native complex conformation can be directly targeted. Here, we employed a strategy taking advantage of an integrated vector system which allows rapid conversion of scFv-displaying phage into scFv-Fc format for efficient cell-based scFv library selection on a tetraspanin protein, CD9. A mouse scFv library constructed by using a phagemid vector, pDR-D1 was subjected to cell panning against stable CD9 transfectant, and the scFv repertoire from the enriched phage pool was directly transferred to a mammalian cassette vector, pDR-OriP-Fc1. The resulting constructs enabled transient expression of enough amounts of scFv-Fcs in HEK293E cells, and flow cytometric screening of binders for CD9 transfectant could be performed simply by using the culture supernatants. All three clones selected from the screening showed correct CD9-specificity. They could immunoprecipitate CD9 molecules out of the transfectant cell lysate and correctly stain endogenous CD9 expression on cancer cell membrane. Furthermore, competition assay with a known anti-CD9 monoclonal antibody (mAb) suggested that the binding epitopes of some of them overlap with that of the mAb which resides within the large extracellular loop of CD9. This study demonstrates that scFv-Fc from mammalian transient expression can be chosen as a reliable format for rapid screening and validation in cell-based scFv library selection, and the strategy described here will be applicable to efficient discovery of antibodies to diverse cell-surface targets.

Trace elements in native and improved paddy rice from different climatic regions of Sri Lanka: implications for public health.

PubMed

Diyabalanage, Saranga; Navarathna, Thamara; Abeysundara, Hemalika T K; Rajapakse, Sanath; Chandrajith, Rohana

2016-01-01

Samples of 226 new improved and 21 indigenous rice ( Oryza sativa L.) varieties were collected from the rice fields in three climatic zones of Sri Lanka and concentrations of 18 trace elements (Li, B, Al, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Sr, Mo, Cd, Ba, Pb and Bi) were measured giving particular emphasis on Se, Cd and As using ICP-MS. The two way multivariate analysis of variance (MANOVA) method was employed to identify the differences in composition among rice from different climatic zones. The mean values obtained for both white and red rice were Se (36; 25 µg/kg), As (42; 45 µg/kg) and Cd (70; 123 µg/kg) on dry weight basis. However mean content of Se, As and Cd of native rice varieties were 69, 74 and 33 µg/kg, respectively. Statistical interpretations showed that in the majority of cases, there was a significant difference in Cd content among climatic zones whereas Se and Pb show differences between white and red rice varieties. Arsenic did not indicate any significant difference either between rice types or among climatic regions. Notably Se and As contents in indigenous rice were higher than that of improved rice types. To assess the safety of dietary of intake, daily intake of Se, Cd and As by rice were calculated. Non-gender specific Estimated Daily Intake (EDI) of Se, Cd and As consuming improved rice are 9.31, 24.1 and 12.2 µg day -1 , respectively. Since over 50 % of daily meals of people contain rice or rice based products, Se intake is expected to be deficient among the Sri Lankan population.

Population and High-Risk Group Screening for Glaucoma: The Los Angeles Latino Eye Study

PubMed Central

Francis, Brian A.; Vigen, Cheryl; Lai, Mei-Ying; Winarko, Jonathan; Nguyen, Betsy; Azen, Stanley

2011-01-01

Purpose. To evaluate the ability of various screening tests, both individually and in combination, to detect glaucoma in the general Latino population and high-risk subgroups. Methods. The Los Angeles Latino Eye Study is a population-based study of eye disease in Latinos 40 years of age and older. Participants (n = 6082) underwent Humphrey visual field testing (HVF), frequency doubling technology (FDT) perimetry, measurement of intraocular pressure (IOP) and central corneal thickness (CCT), and independent assessment of optic nerve vertical cup disc (C/D) ratio. Screening parameters were evaluated for three definitions of glaucoma based on optic disc, visual field, and a combination of both. Analyses were also conducted for high-risk subgroups (family history of glaucoma, diabetes mellitus, and age ≥65 years). Sensitivity, specificity, and receiver operating characteristic curves were calculated for those continuous parameters independently associated with glaucoma. Classification and regression tree (CART) analysis was used to develop a multivariate algorithm for glaucoma screening. Results. Preset cutoffs for screening parameters yielded a generally poor balance of sensitivity and specificity (sensitivity/specificity for IOP ≥21 mm Hg and C/D ≥0.8 was 0.24/0.97 and 0.60/0.98, respectively). Assessment of high-risk subgroups did not improve the sensitivity/specificity of individual screening parameters. A CART analysis using multiple screening parameters—C/D, HVF, and IOP—substantially improved the balance of sensitivity and specificity (sensitivity/specificity 0.92/0.92). Conclusions. No single screening parameter is useful for glaucoma screening. However, a combination of vertical C/D ratio, HVF, and IOP provides the best balance of sensitivity/specificity and is likely to provide the highest yield in glaucoma screening programs. PMID:21245400

A novel oral delivery system consisting in "drug-in cyclodextrin-in nanostructured lipid carriers" for poorly water-soluble drug: vinpocetine.

PubMed

Lin, Congcong; Chen, Fen; Ye, Tiantian; Zhang, Lina; Zhang, Wenji; Liu, Dandan; Xiong, Wei; Yang, Xinggang; Pan, Weisan

2014-04-25

The purpose of this study was to develop a new delivery system based on drug cyclodextrin (CD) complexation and loading into nanostructured lipid carriers (NLC) to improve the oral bioavailability of vinpocetine (VP). Three different CDs and three different methods to obtain solid vinpocetine-cyclodextrin-tartaric acid complexes (VP-CD-TA) were contrasted. The co-evaporation vinpocetine-β-cyclodextrin-tartaric acid loaded NLC (VP-β-CD-TA COE-loaded NLC) was obtained by emulsification ultrasonic dispersion method. VP-β-CD-TA COE-loaded NLC was suitably characterized for particle size, polydispersity index, zeta potential, entrapment efficiency and the morphology. The crystallization of drug in VP-CD-TA and NLC was investigated by differential scanning calorimetry (DSC). The in vitro release study was carried out at pH 1.2, pH 6.8 and pH 7.4 medium. New Zealand rabbits were applied to investigate the pharmacokinetic behavior in vivo. The VP-β-CD-TA COE-loaded NLC presented a superior physicochemical property and selected to further study. In the in vitro release study, VP-β-CD-TA COE-loaded NLC exhibited a higher dissolution rate in the pH 6.8 and pH 7.4 medium than VP suspension and VP-NLC. The relative bioavailability of VP-β-CD-TA COE-loaded NLC was 592% compared with VP suspension and 92% higher than VP-NLC. In conclusion, the new formulation significantly improved bioavailability of VP for oral delivery, demonstrated a perspective way for oral delivery of poorly water-soluble drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

Screening and analyzing genes associated with Amur tiger placental development.

PubMed

Li, Q; Lu, T F; Liu, D; Hu, P F; Sun, B; Ma, J Z; Wang, W J; Wang, K F; Zhang, W X; Chen, J; Guan, W J; Ma, Y H; Zhang, M H

2014-09-26

The Amur tiger is a unique endangered species in the world, and thus, protection of its genetic resources is extremely important. In this study, an Amur tiger placenta cDNA library was constructed using the SMART cDNA Library Construction kit. A total of 508 colonies were sequenced, in which 205 (76%) genes were annotated and mapped to 74 KEGG pathways, including 29 metabolism, 29 genetic information processing, 4 environmental information processing, 7 cell motility, and 5 organismal system pathways. Additionally, PLAC8, PEG10 and IGF-II were identified after screening genes from the expressed sequence tags, and they were associated with placental development. These findings could lay the foundation for future functional genomic studies of the Amur tiger.

BMI-1 targeting interferes with patient-derived tumor-initiating cell survival and tumor growth in prostate cancer

PubMed Central

Yusuff, Shamila; Davis, Stephani; Flaherty, Kathleen; Huselid, Eric; Patrizii, Michele; Jones, Daniel; Cao, Liangxian; Sydorenko, Nadiya; Moon, Young-Choon; Zhong, Hua; Medina, Daniel J.; Kerrigan, John; Stein, Mark N.; Kim, Isaac Y.; Davis, Thomas W.; DiPaola, Robert S.; Bertino, Joseph R.; Sabaawy, Hatem E.

2016-01-01

Purpose Current prostate cancer (PCa) management calls for identifying novel and more effective therapies. Self-renewing tumor-initiating cells (TICs) hold intrinsic therapy-resistance and account for tumor relapse and progression. As BMI-1 regulates stem cell self-renewal, impairing BMI-1 function for TICs-tailored therapies appears to be a promising approach. Experimental design We have previously developed a combined immunophenotypic and time-of-adherence assay to identify CD49bhiCD29hiCD44hi cells as human prostate TICs. We utilized this assay with patient derived prostate cancer cells and xenograft models to characterize the effects of pharmacological inhibitors of BMI-1. Results We demonstrate that in cell lines and patient-derived TICs, BMI-1 expression is upregulated and associated with stem cell-like traits. From a screened library, we identified a number of post-transcriptional small molecules that target BMI-1 in prostate TICs. Pharmacological inhibition of BMI-1 in patient-derived cells significantly decreased colony formation in vitro and attenuated tumor initiation in vivo, thereby functionally diminishing the frequency of TICs, particularly in cells resistant to proliferation- and androgen receptor (AR)-directed therapies, without toxic effects on normal tissues. Conclusions Our data offer a paradigm for targeting TICs and support the development of BMI-1-targeting therapy for a more effective PCa treatment. PMID:27307599

[Screening interview for early detection of high-functioning autism spectrum disorders].

PubMed

Hoffmann, Wiebke; Heinzel-Gutenbrunner, Monika; Becker, Katja; Kamp-Becker, Inge

2015-05-01

Various different questionnaires are available for the screening of autism spectrum disorders (ASD). These screening instruments show high sensitivity and are able to identify a large number of individuals with ASD, but they lack the specificity to differentiate individuals with ASD from those children and adolescents with other complex neurobehavioural disorders (such as attention-deficit/hyperactivity disorder, emotional disorders, and others), especially for those without intellectual disabilities. The present study evaluates the data of 309 individuals (153 with high-functioning ASD, 156 with other psychiatric disorders, IQ > 70) to find out whether selected items of the ADI-R can be used for an economic and sensitive screening of high-functioning ASD. The results show that 8 items of the ADI-R can be used to discriminate high-functioning ASD and other psychiatric disorders. A cutoff of 5 led to a sensitivity of 0.93 and a cutoff of 6 to a specificity of 0.74. The combination of early onset, serious abnormalities in social contact with stereotyped or compulsive-ritualized behaviour or interests can be detected with few interview questions for screening of ASD. Nevertheless, a more detailed and specific assessment in an expert setting should follow the screening process.

Interval cancers in a population-based screening program for colorectal cancer in catalonia, Spain.

PubMed

Garcia, M; Domènech, X; Vidal, C; Torné, E; Milà, N; Binefa, G; Benito, L; Moreno, V

2015-01-01

Objective. To analyze interval cancers among participants in a screening program for colorectal cancer (CRC) during four screening rounds. Methods. The study population consisted of participants of a fecal occult blood test-based screening program from February 2000 to September 2010, with a 30-month follow-up (n = 30,480). We used hospital administration data to identify CRC. An interval cancer was defined as an invasive cancer diagnosed within 30 months of a negative screening result and before the next recommended examination. Gender, age, stage, and site distribution of interval cancers were compared with those in the screen-detected group. Results. Within the study period, 97 tumors were screen-detected and 74 tumors were diagnosed after a negative screening. In addition, 17 CRC (18.3%) were found after an inconclusive result and 2 cases were diagnosed within the surveillance interval (2.1%). There was an increase of interval cancers over the four rounds (from 32.4% to 46.0%). When compared with screen-detected cancers, interval cancers were found predominantly in the rectum (OR: 3.66; 95% CI: 1.51-8.88) and at more advanced stages (P = 0.025). Conclusion. There are large numbers of cancer that are not detected through fecal occult blood test-based screening. The low sensitivity should be emphasized to ensure that individuals with symptoms are not falsely reassured.

In silico design and screening of hypothetical MOF-74 analogs and their experimental synthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Witman, Matthew; Ling, Sanliang; Anderson, Samantha

2016-01-01

We present thein silico designof MOFs exhibiting 1-dimensional rod topologies by enumerating MOF-74-type analogs based on the PubChem Compounds database. We simulate the adsorption behavior of CO 2in the generated analogs and experimentally validate a novel MOF-74 analog, Mg 2(olsalazine).

More training and awareness are needed to improve the recognition of undernutrition in hospitalised children.

PubMed

Huysentruyt, Koen; Goyens, Philippe; Alliet, Philippe; Bontems, Patrick; Van Hautem, Hilde; Philippet, Pierre; Vandenplas, Yvan; De Schepper, Jean

2015-08-01

Reports suggest that 10% of hospitalised children in Europe are undernourished. We investigated whether nutritional screening tools (NST) were used in Belgian secondary-level hospitals, examined strategies for detecting undernutrition and identified barriers preventing the systematic management of undernutrition. A nationwide questionnaire-based survey of paediatric departments in Belgian secondary-level hospitals was carried out from September 2013 to February 2014. Respondents were dived into French-speaking (Walloon + Brussels) and Dutch-speaking (Flemish) departments. We received replies from 71 of the 97 (73.2%) departments. Half of the departments - 39.5% Flemish speaking and 71.4% Walloon speaking - carried out nutritional screening. Undernutrition was identified by measuring weight and length or height (92.7% of cases), clinical appraisal (74.7%), mid-upper arm circumference and/or skin fold thickness (19.7%). There was no protocol for undernutrition in many Flemish (60.5%)- and Walloon (28.6%)-speaking departments. Reasons given for not screening were as follows: lack of training (46.9%), ignorance of NST (42.2%) and lack of time (29.7%). Half of the paediatric departments in Belgian secondary-level hospitals did not carry out nutritional screening, and differences in current practices and attitudes may be due to cultural and/or educational differences. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Breast MRI: patterns of utilization and impact on patient management in the community hospital setting.

PubMed

Lobrano, Mary Beth; Stolier, Alan; L'Hoste, Robert; Luttrell, Carol Anne

2012-01-01

The objective of our study was to investigate the indications for breast magnetic resonance imaging, or MRI, in our community hospital, determine how many probably benign MRI findings were malignant at follow-up, determine how many cancers were identified by MRI in screening patients, and evaluate the utility of MRI for surgical planning and problem-solving. Five hundred twenty-eight contrast-enhanced MRI's of the breast in 434 patients were retrospectively reviewed. MRI images/reports were compared to surgical pathology reports and the results of follow-up studies. Screening was the most common indication for breast MRI in our patient population. Five percent of findings termed "probably benign" on MRI proved to be malignant at follow-up. Eight malignancies were detected in six of 202 screened patients. Ten malignancies were diagnosed in 66 patients referred to MRI for problem-solving. In two of 74 patients with known breast cancer, an unsuspected ipsilateral cancer was identified on MRI. MRI proved useful in the community hospital setting for screening high-risk patients and problem-solving. The rate of malignancy in probably benign MRI findings was higher than the corresponding rate in mammography. The detection of additional ipsilateral and contralateral cancers in pre-operative patients with known breast cancer was not as high as expected, based on prior studies.

Validity of a novel computerized screening test system for mild cognitive impairment.

PubMed

Park, Jin-Hyuck; Jung, Minye; Kim, Jongbae; Park, Hae Yean; Kim, Jung-Ran; Park, Ji-Hyuk

2018-06-20

ABSTRACTBackground:The mobile screening test system for screening mild cognitive impairment (mSTS-MCI) was developed for clinical use. However, the clinical usefulness of mSTS-MCI to detect elderly with MCI from those who are cognitively healthy has yet to be validated. Moreover, the comparability between this system and traditional screening tests for MCI has not been evaluated. The purpose of this study was to examine the validity and reliability of the mSTS-MCI and confirm the cut-off scores to detect MCI. The data were collected from 107 healthy elderly people and 74 elderly people with MCI. Concurrent validity was examined using the Korean version of Montreal Cognitive Assessment (MoCA-K) as a gold standard test, and test-retest reliability was investigated using 30 of the study participants at four-week intervals. The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) were confirmed through Receiver Operating Characteristic (ROC) analysis, and the cut-off scores for elderly people with MCI were identified. Concurrent validity showed statistically significant correlations between the mSTS-MCI and MoCA-K and test-rests reliability indicated high correlation. As a result of screening predictability, the mSTS-MCI had a higher NPV than the MoCA-K. The mSTS-MCI was identified as a system with a high degree of validity and reliability. In addition, the mSTS-MCI showed high screening predictability, indicating it can be used in the clinical field as a screening test system for mild cognitive impairment.

A small molecule-based strategy for endothelial differentiation and three-dimensional morphogenesis from human embryonic stem cells.

PubMed

Geng, Yijie; Feng, Bradley

2016-07-01

The emerging models of human embryonic stem cell (hESC) self-organizing organoids provide a valuable in vitro platform for studying self-organizing processes that presumably mimic in vivo human developmental events. Here we report that through a chemical screen, we identified two novel and structurally similar small molecules BIR1 and BIR2 which robustly induced the self-organization of a balloon-shaped three-dimensional structure when applied to two-dimensional adherent hESC cultures in the absence of growth factors. Gene expression analyses and functional assays demonstrated an endothelial identity of this balloon-like structure, while cell surface marker analyses revealed a VE-cadherin(+)CD31(+)CD34(+)KDR(+)CD43(-) putative endothelial progenitor population. Furthermore, molecular marker labeling and morphological examinations characterized several other distinct DiI-Ac-LDL(+) multi-cellular modules and a VEGFR3(+) sprouting structure in the balloon cultures that likely represented intermediate structures of balloon-formation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howe, Joshua D.; Morelock, Cody R.; Jiao, Yang

We present a joint computational and experimental study of Mg–Ni-MOF-74 and Mg–Cd-MOF-74 to gain insight into the mixing of metals and understand how metal mixing affects the structure of the undercoordinated open-metal sites. Our calcula tions predict that metal mixing is energetically preferred in these materials. Recent experimental work has demonstrated that Mg–Ni-MOF-74 shows a much greater surface area retention in the presence of water than Mg-MOF-74. To probe this effect, we study H2O adsorption in Mg–Ni-MOF-74, finding that the adsorption en ergetics and electronic structure do not change significantly at the metal sites when compared to Mg-MOF-74 and Ni-MOF-74,more » respectively. We conclude that the in creased stability of Mg–Ni-MOF-74 is a result of a M–O bond length distortion in mixed-metal MOF-74, consistent with recent work on the stability of MOF-74 under water exposure.« less

Establishing a cost-per-result of laboratory-based, reflex Cryptococcal antigenaemia screening (CrAg) in HIV+ patients with CD4 counts less than 100 cells/μl using a Lateral Flow Assay (LFA) at a typical busy CD4 laboratory in South Africa.

PubMed

Cassim, Naseem; Schnippel, Kathryn; Coetzee, Lindi Marie; Glencross, Deborah Kim

2017-01-01

Cryptococcal meningitis is a major cause of mortality and morbidity in countries with high HIV prevalence, primarily affecting patients whose CD4 are < = 100 cells/μl. Routine Cryptococcal Antigen (CrAg) screening is thus recommended in the South African HIV treatment guidelines for all patients with CD4 counts < = 100 cells/μl, followed by pre-emptive anti-fungal therapy where CrAg results are positive. A laboratory-based reflexed CrAg screening approach, using a Lateral Flow Assay (LFA) on remnant EDTA CD4 blood samples, was piloted at three CD4 laboratories. This study aimed to assess the cost-per-result of laboratory-based reflexed CrAg screening at one pilot CD4 referral laboratory. CD4 test volumes from 2014 were extracted to estimate percentage of CD4 < = 100 cells/μl. Daily average volumes were derived, assuming 12 months per/year and 21.73 working days per/month. Costing analyses were undertaken using Microsoft Excel and Stata with a provider prospective. The cost-per-result was estimated using a bottom-up method, inclusive of test kits and consumables (reagents), laboratory equipment and technical effort costs. The ZAR/$ exchange of 14.696/$1 was used, where applicable. One-way sensitivity analyses on the cost-per-result were conducted for possible error rates (3%- 8%, reductions or increases in reagent costs as well as test volumes (ranging from -60% to +60%). The pilot CD4 laboratory performed 267000 CD4 tests in 2014; ~ 9.3% (27500) reported CD4< = 100 cells/μl, equivalent to 106 CrAg tests performed daily. A batch of 30-tests could be performed in 1.6 hours, including preparation and analysis time. A cost-per-result of $4.28 was reported, with reagents contributing $3.11 (72.8%), while technical effort and laboratory equipment overheads contributed $1.17 (27.2%) and $0.03 (<1%) respectively. One-way sensitivity analyses including increasing or decreasing test volumes by 60% revealed a cost-per-result range of $3.84 to $6.03. A cost-per-result of $4.28 was established in a typical CD4 service laboratory to enable local budgetary cost projections and programmatic cost-effectiveness modelling. Varying reagent costs linked to currency exchange and varying test volumes in different levels of service can lead to varying cost-per-test and technical effort to manage workload, with an inverse relationship of higher costs expected at lower volumes of tests.

Aryl Hydrocarbon Receptor Antagonists Promote the Expansion of Human Hematopoietic Stem Cells

PubMed Central

Boitano, Anthony E.; Wang, Jian; Romeo, Russell; Bouchez, Laure C.; Parker, Albert E.; Sutton, Sue E.; Walker, John R.; Flaveny, Colin A.; Perdew, Gary H.; Denison, Michael S.; Schultz, Peter G.; Cooke, Michael P.

2011-01-01

Although practiced clinically for over 40 years, the use of hematopoietic stem cell (HSC) transplants remains limited by the ability to expand these cells ex vivo. An unbiased screen with primary human HSC identified a purine derivative, StemRegenin 1 (SR1), that promotes the ex vivo expansion of CD34+ cells. Culture of HSC with SR1 led to a fifty-fold increase in cells expressing CD34, and a 17-fold increase in cells that retain the ability to engraft immunodeficient mice. Mechanistic studies show that SR1 acts by antagonizing the aryl hydrocarbon receptor (AhR). The identification of SR1 and AhR modulation as a means to induce ex vivo HSC expansion should facilitate the clinical use of HSC therapy. PMID:20688981

CD68 acts as a major gateway for malaria sporozoite liver infection

PubMed Central

Cha, Sung-Jae; Park, Kiwon; Srinivasan, Prakash; Schindler, Christian W.; van Rooijen, Nico; Stins, Monique

2015-01-01

After being delivered by the bite from an infected mosquito, Plasmodium sporozoites enter the blood circulation and infect the liver. Previous evidence suggests that Kupffer cells, a macrophage-like component of the liver blood vessel lining, are traversed by sporozoites to initiate liver invasion. However, the molecular determinants of sporozoite–Kupffer cell interactions are unknown. Understanding the molecular basis for this specific recognition may lead to novel therapeutic strategies to control malaria. Using a phage display library screen, we identified a peptide, P39, that strongly binds to the Kupffer cell surface and, importantly, inhibits sporozoite Kupffer cell entry. Furthermore, we determined that P39 binds to CD68, a putative receptor for sporozoite invasion of Kupffer cells that acts as a gateway for malaria infection of the liver. PMID:26216124

Structural and optical properties of CdSe nanosheets

NASA Astrophysics Data System (ADS)

Solanki, Rekha Garg; Rajaram, P.; Arora, Aman

2018-04-01

Nanosheets of CdSe have been synthesized using a solvothermal route using citric acid as an additive. It is found that the citric acid effectively controls the structural and optical properties of CdSe nanostructures. XRD studies confirm the formation of hexagonal wurtzite phase of CdSe. The FESEM micrographs show that the obtained CdSe nanocrystals are in the form of very thin sheets (nanosheets). Optical absorption studies as well as Photoluminescence spectra show that the optical gap is around 1.76 eV which is close to the reported bulk value of 1.74 eV. The prepared CdSe nanosheets because of large surface area may be useful for catalytic activities in medicine, biotechnology and environmental chemistry and in biomedical imaging for in vitro detection of a breast cancer cells.

Fingolimod treatment abrogates chikungunya virus-induced arthralgia.

PubMed

Teo, Teck-Hui; Chan, Yi-Hao; Lee, Wendy W L; Lum, Fok-Moon; Amrun, Siti Naqiah; Her, Zhisheng; Rajarethinam, Ravisankar; Merits, Andres; Rötzschke, Olaf; Rénia, Laurent; Ng, Lisa F P

2017-02-01

Chikungunya virus (CHIKV) is one of the many rheumatic arthropod-borne alphaviruses responsible for debilitating joint inflammation in humans. Despite the severity in many endemic regions, clinically approved intervention targeting the virus remains unavailable. CD4 + T cells have been shown to mediate CHIKV-induced joint inflammation in mice. We demonstrate here that transfer of splenic CD4 + T cells from virus-infected C57BL/6 mice into virus-infected T cell receptor-deficient (TCR -/- ) mice recapitulated severe joint pathology including inflammation, vascular leakages, subcutaneous edema, and skeletal muscle necrosis. Proteome-wide screening identified dominant CD4 + T cell epitopes in nsP1 and E2 viral antigens. Transfer of nsP1- or E2-specific primary CD4 + T cell lines into CHIKV-infected TCR -/- recipients led to severe joint inflammation and vascular leakage. This pathogenic role of virus-specific CD4 + T cells in CHIKV infections led to the assessment of clinically approved T cell-suppressive drugs for disease intervention. Although drugs targeting interleukin-2 pathway were ineffective, treatment with fingolimod, an agonist of sphingosine 1-phosphate receptor, successfully abrogated joint pathology in CHIKV-infected animals by blocking the migration of CD4 + T cells into the joints without any effect on viral replication. These results set the stage for further clinical evaluation of fingolimod in the treatment of CHIKV-induced joint pathologies. Copyright © 2017, American Association for the Advancement of Science.

Radiation-Induced Breast Cancer Incidence and Mortality from Digital Mammography Screening: A Modeling Study

PubMed Central

Miglioretti, Diana L.; Lange, Jane; van den Broek, Jeroen J.; Lee, Christoph I.; van Ravesteyn, Nicolien T.; Ritley, Dominique; Kerlikowske, Karla; Fenton, Joshua J.; Melnikow, Joy; de Koning, Harry J.; Hubbard, Rebecca A.

2016-01-01

Background Estimates of radiation-induced breast cancer risk from mammography screening have not previously considered dose exposure variation or diagnostic work-up after abnormal screening. Objective To estimate distributions of radiation-induced breast cancer incidence and mortality from digital mammography screening, considering exposure from screening and diagnostic mammography and dose variation across women. Design Two simulation-modeling approaches using common data on screening mammography from the Breast Cancer Surveillance Consortium and radiation dose from mammography from the Digital Mammographic Imaging Screening Trial. Setting U.S. population. Patients Women aged 40–74 years. Interventions Annual or biennial digital mammography screening from age 40, 45, or 50 until 74. Measurements Lifetime breast cancer deaths averted (benefits) and radiation-induced breast cancer incidence and mortality per 100,000 women screened (harms). Results On average, annual screening of 100,000 women aged 40 to 74 years was projected to induce 125 breast cancers (95% confidence interval [CI]=88–178) leading to 16 deaths (95% CI=11–23) relative to 968 breast cancer deaths averted by early detection from screening. Women exposed at the 95th percentile were projected to develop 246 radiation-induced breast cancers leading to 32 deaths per 100,000 women. Women with large breasts requiring extra views for complete breast examination (8% of population) were projected to have higher radiation-induced breast cancer incidence and mortality (266 cancers, 35 deaths per 100,000 women), compared to women with small or average breasts (113 cancers, 15 deaths per 100,000 women). Biennial screening starting at age 50 reduced risk of radiation-induced cancers 5-fold. Limitations We were unable to estimate years of life lost from radiation-induced breast cancer. Conclusions Radiation-induced breast cancer incidence and mortality from digital mammography screening are impacted by dose variability from screening and resultant diagnostic work-up, initiation age, and screening frequency. Women with large breasts may be at higher risk of radiation-induced breast cancer; however, the benefits of screening outweigh these risks. PMID:26756460

An integrated approach to assess heavy metal source apportionment in peri-urban agricultural soils.

PubMed

Huang, Ying; Li, Tingqiang; Wu, Chengxian; He, Zhenli; Japenga, Jan; Deng, Meihua; Yang, Xiaoe

2015-12-15

Three techniques (Isotope Ratio Analysis, GIS mapping, and Multivariate Statistical Analysis) were integrated to assess heavy metal pollution and source apportionment in peri-urban agricultural soils. The soils in the study area were moderately polluted with cadmium (Cd) and mercury (Hg), lightly polluted with lead (Pb), and chromium (Cr). GIS Mapping suggested Cd pollution originates from point sources, whereas Hg, Pb, Cr could be traced back to both point and non-point sources. Principal component analysis (PCA) indicated aluminum (Al), manganese (Mn), nickel (Ni) were mainly inherited from natural sources, while Hg, Pb, and Cd were associated with two different kinds of anthropogenic sources. Cluster analysis (CA) further identified fertilizers, waste water, industrial solid wastes, road dust, and atmospheric deposition as potential sources. Based on isotope ratio analysis (IRA) organic fertilizers and road dusts accounted for 74-100% and 0-24% of the total Hg input, while road dusts and solid wastes contributed for 0-80% and 19-100% of the Pb input. This study provides a reliable approach for heavy metal source apportionment in this particular peri-urban area, with a clear potential for future application in other regions. Copyright © 2015 Elsevier B.V. All rights reserved.

CD147 Promotes Entry of Pentamer-Expressing Human Cytomegalovirus into Epithelial and Endothelial Cells

PubMed Central

Pritchard, Sarah R.; Wisner, Todd W.; Liu, Jing; Jardetzky, Ted S.; Johnson, David C.

2018-01-01

ABSTRACT Human cytomegalovirus (HCMV) replicates in many diverse cell types in vivo, and entry into different cells involves distinct entry mechanisms and different envelope glycoproteins. HCMV glycoprotein gB is thought to act as the virus fusogen, apparently after being triggered by different gH/gL proteins that bind distinct cellular receptors or entry mediators. A trimer of gH/gL/gO is required for entry into all cell types, and entry into fibroblasts involves trimer binding to platelet-derived growth factor receptor alpha (PDGFRα). HCMV entry into biologically relevant epithelial and endothelial cells and monocyte-macrophages also requires a pentamer, gH/gL complexed with UL128, UL130, and UL131, and there is evidence that the pentamer binds unidentified receptors. We screened an epithelial cell cDNA library and identified the cell surface protein CD147, which increased entry of pentamer-expressing HCMV into HeLa cells but not entry of HCMV that lacked the pentamer. A panel of CD147-specific monoclonal antibodies inhibited HCMV entry into epithelial and endothelial cells, but not entry into fibroblasts. shRNA silencing of CD147 in endothelial cells inhibited HCMV entry but not entry into fibroblasts. CD147 colocalized with HCMV particles on cell surfaces and in endosomes. CD147 also promoted cell-cell fusion induced by expression of pentamer and gB in epithelial cells. However, soluble CD147 did not block HCMV entry and trimer and pentamer did not bind directly to CD147, supporting the hypothesis that CD147 acts indirectly through other proteins. CD147 represents the first HCMV entry mediator that specifically functions to promote entry of pentamer-expressing HCMV into epithelial and endothelial cells. PMID:29739904

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hiraishi, Nobuhiro; Ishida, Yo-ichi; Nagahama, Masami, E-mail: nagahama@my-pharm.ac.jp

Nuclear VCP-like 2 (NVL2) is a chaperone-like nucleolar ATPase of the AAA (ATPase associated with diverse cellular activities) family, which exhibits a high level of amino acid sequence similarity with the cytosolic AAA-ATPase VCP/p97. These proteins generally act on macromolecular complexes to stimulate energy-dependent release of their constituents. We previously showed that NVL2 interacts with RNA processing/degradation machinery containing an RNA helicase MTR4/DOB1 and an exonuclease complex, nuclear exosome, and involved in the biogenesis of 60S ribosomal subunits. These observations implicate NVL2 as a remodeling factor for the MTR4-exosome complex during the maturation of pre-ribosomal particles. Here, we used amore » proteomic screen and identified a WD repeat-containing protein 74 (WDR74) as a factor that specifically dissociates from this complex depending on the ATPase activity of NVL2. WDR74 shows weak amino acid sequence similarity with the yeast ribosome biogenesis protein Nsa1 and is co-localized with NVL2 in the nucleolus. Knockdown of WDR74 decreases 60S ribosome levels. Taken together, our results suggest that WDR74 is a novel regulatory protein of the MTR4-exsosome complex whose interaction is regulated by NVL2 and is involved in ribosome biogenesis. - Highlights: • WDR74 accumulates in MTR4-exosome complex upon expression of dominant-negative NVL2. • WDR74 is co-localized with NVL2 in the nucleolus. • WDR74, along with NVL2, is involved in the synthesis of 60S ribosomal subunits.« less

The Sun's Joules. [CD-ROM].

ERIC Educational Resources Information Center

Center for Renewable Energy and Sustainable Tech., Washington, DC.

An educational tool concerning renewable energy and the environment, this CD-ROM provides nearly 1,000 screens of text, graphics, videos, and interactive exercises. It also provides a detailed index, charts of U.S. energy consumption by state, an energy glossary, and a list of related Web sites. This CD-ROM, additionally, offers "The School…

Using Newspapers on CD-ROM as a Resource.

ERIC Educational Resources Information Center

Seedhouse, Paul

1996-01-01

Presents the advantages of using newspapers stored on CD-ROM as a resource for teaching current topics in civilization/culture and current affairs in the foreign- language class. Articles on CD-ROM can be used for vocabulary exercises and comprehension tests, and on-screen text can be altered as desired to create classroom activities. (four…

Genotyping of coeliac-specific human leucocyte antigen in children with type 1 diabetes: does this screening method make sense?

PubMed

Binder, Elisabeth; Loinger, Martina; Mühlbacher, Annelies; Edlinger, Michael; Steichen, Elisabeth; Meraner, Dagmar; Loacker, Lorin; Weigel, Guenter; Müller, Thomas; Fröhlich-Reiterer, Elke; Hofer, Sabine E

2017-07-01

Due to a high linkage disequilibrium of diabetes and coeliac-specific human leucocyte antigen (HLA) genotypes, the prevalence of coeliac disease (CD) in children and adolescents with diabetes mellitus type 1 (T1D) is much higher than in the general population. Recently, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) revised new screening guidelines in which genotyping for coeliac-specific HLA alleles is recommended for high-risk patients as patients with T1D. The aim of our study was to investigate the frequency and distribution of coeliac-specific HLA genotypes in paediatric patients with T1D. HLA genotyping was performed on paediatric patients with T1D, recruited at the Medical University Hospital of Innsbruck and Graz. The test was done by PCR. Statistical analysis was performed with IBM-SPSS V.20. In 121 paediatric patients with T1D (52% male), mean age 13.3 (SD 3.9) years, mean age at diabetes diagnosis 7.4 (SD 3.8) and mean diabetes duration of 5.9 (SD 3.3) years, HLA genotyping was conducted. Ninety-two per cent showed positive HLA DQ2 and/or HLA DQ8 genotypes. Thirty-four per cent carried HLA DQ2, 33% were HLA DQ2+DQ8 positive and 25% of the patients showed positive results for HLA DQ8 alone. Only 8% had no coeliac-specific HLA markers. Four (3%) patients were diagnosed with CD. The majority of paediatric patients with T1D has positive coeliac-specific HLA genotypes DQ2 and/or DQ8. Therefore, genotyping for coeliac-specific HLA alleles as a first-line test in patients with T1D as recommended in the ESPGHAN guidelines does not seem reasonable. Screening for coeliac-specific antibodies needs to be performed on a regular basis for patients with T1D. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Prevalence of human papillomavirus infection & cervical abnormalities in HIV-positive women in eastern India

PubMed Central

Chakravarty, Jaya; Chourasia, Ankita; Thakur, Minaxi; Singh, Abhishek Kumar; Sundar, Shyam; Agrawal, Nisha Rani

2016-01-01

Background & objectives: India has the third highest burden of HIV and highest number of cervical cancer in the world. A cross-sectional study was performed to determine the prevalence and types of human papillomavirus (HPV) infection, and the factors associated with HPV infection and abnormal cervical cytology in HIV-positive women attending the Antiretroviral Therapy (ART) Centre in a tertiary care hospital in eastern India. Methods: We screened 216 HIV- positive women with Papanicolau smear cytology and HPV testing. HPV DNA was detected by using consensus primers followed by sequencing. Results: Of the 216 HIV-positive women screened, 58 (26.85%) were HPV-positive; 56 (25.9%) were of high-risk (HR) HPV type. The most prevalent HPV type was HPV-16 (7.9%); non 16 and 18 HPV types were present in 17.6 per cent patients. Age ≤ 35 yr [(OR), 2.56 (1.26-5.19)], illiteracy [OR, 2.30 (1.19-4.46)], rural residence [OR, 3.99 (1.27-12.56)] and CD4 ≤350/μl [OR, 2.46 (1.26-4.83)] were associated with increased risk of acquisition of HPV. One hundred thirty nine (74.33%) patients had normal/ negative for intraepithelial lesions (NILM) cytology, three (1.60%) had atypical squamous cells of undetermined significance (ASCUS), 32 (17.11%) had low-grade squamous intraepithelial lesions (LSIL), 10 (5.35%) had high-grade squamous intraepithelial lesions (HSIL) and three (1.60%) had carcinoma cervix. WHO clinical Stage III and IV [OR, 2.83 (1.07-7.49)] and CD4 ≤350/μl [OR, 2.84 (1.30-6.20)] were risk factors for abnormal cytology. Interpretation &conclusions: Our study showed 26.85 per cent HPV positivity in HIV infected women in this region, with HPV-16 as the commonest genotype. Abnormal cervical cytology was seen in about 25 per cent women. Regular Pap smear screening as recommended by the National AIDS Control Organization will help in early detection of cervical abnormalities in HIV- positive women. PMID:26997018

Which Kindergarten Children are at Greatest Risk for Attention-deficit/Hyperactivity and Conduct Disorder Symptomatology as Adolescents?

PubMed Central

Morgan, Paul L.; Li, Hui; Cook, Michael; Farkas, George; Hillemeier, Marianne M.; Lin, Yu-chu

2015-01-01

Objective We sought to identify which kindergarten children are simultaneously at risk of moderate or severe symptomatology in both attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) as adolescents. These risk factor estimates have not been previously available. Method Multinomial logistic regression analyses of multi-informant ratings by the end of middle school of a population-based, longitudinal sample of children followed from kindergarten to eighth grade (N = 7,456). Results Kindergarten children from low SES households, those raised by mothers with depressive symptoms or experiencing emotional problems or substance abuse, or those who were punished by spanking were significantly more likely to later display severe levels of ADHD-CD symptomatology in eighth grade. Kindergarten children frequently engaging in ADHD-CD-type behaviors were more likely to later experience both moderate (covariate adjusted OR = 2.37) and severe (covariate adjusted OR = 3.63) ADHD-CD symptomatology. Low academic achievement uniquely increased the risk of both moderate and severe symptomatology (adjusted OR range = 1.7 to 2.24). Conclusions The results should guide early screening and school-based intervention efforts for ADHD-CD. Reducing children’s risk for adolescent ADHD-CD symptomatology may require remediating low behavioral and academic functioning by the end of kindergarten. When these two modifiable factors occur together they increase kindergarten children’s odds of experiencing severe ADHD-CD symptomatology in eighth grade by a multiplicative factor of 8.1. PMID:26192391

Longitudinal Rates of Colon Cancer Screening Use in Winnipeg, Canada: The Experience of a Universal Health-Care System with an Organized Colon Screening Program.

PubMed

Decker, Kathleen M; Demers, Alain A; Nugent, Zoann; Biswanger, Natalie; Singh, Harminder

2015-12-01

We examined trends in colorectal cancer (CRC) screening (fecal occult blood test (FOBT), colonoscopy, and flexible sigmoidoscopy (FS)) and differences in CRC screening by income in a population with an organized CRC screening program and universal health-care coverage. Individuals who had an FOBT, colonoscopy, or FS were identified from the provincial Physician Claims database and the population-based colon cancer screening registry. Trends in age-standardized rates were determined. Logistic regression was performed to explore the association between CRC screening and income quintiles by year. Up-to-date CRC screening (FOBT, colonoscopy, or FS) increased over time for men and women, all age groups, and all income quintiles. Up-to-date CRC screening was very high among 65- to 69- and 70- to 74-year-olds (70% and 73%, respectively). There was a shift toward the use of an FOBT for CRC screening for individuals in the lower income quintiles. The disparity in colonoscopy/FS coverage by income quintile was greater in 2012 than in 1995. Overall, there was no reduction in disparities by income in up-to-date CRC screening nor did the rate of increase in up-to-date CRC screening or FOBT use change after the introduction of the organized provincial CRC screening program. CRC screening is increasing over time for both men and women and all age groups. However, a disparity in up-to-date CRC screening by income persisted even with an organized CRC screening program in a universal health-care setting.

Multiparameter FLAER-based flow cytometry for screening of paroxysmal nocturnal hemoglobinuria enhances detection rates in patients with aplastic anemia.

PubMed

Sachdeva, Man Updesh Singh; Varma, Neelam; Chandra, Dinesh; Bose, Parveen; Malhotra, Pankaj; Varma, Subhash

2015-05-01

Flow cytometry is the gold standard methodology for screening of paroxysmal nocturnal hemoglobinuria. In the last few years, proaerolysin conjugated with fluorescein (FLAER) has become an important component of antibody panel used for the detection of paroxysmal nocturnal hemoglobinuria (PNH) clone. This study aimed to compare PNH clone detection by flow cytometry in the pre-FLAER era versus the FLAER era. This was a retrospective analysis of 4 years and included 1004 individuals screened for PNH clone, either presenting as hemolytic anemia or as aplastic anemia. In the pre-FLAER time period, the RBCs and neutrophils were screened with antibodies against CD55 and CD59. With the introduction of FLAER, neutrophils were screened with FLAER/CD24/CD15 and monocytes with FLAER/CD14/CD33 combination. A comparative analysis was done for detection of PNH clone in aplastic anemia patients versus non-aplastic anemia patients, as well as between pre-FLAER and FLAER era. Out of a total of 1004 individuals, 59 (5.8%) were detected to have PNH clone positivity. The frequency of PNH clone detected in aplastic anemia and non-aplastic anemia groups was 12.02 and 3.36%, respectively. The detection rate of PNH clone increased from 4.5% (32/711) in the pre-FLAER era to 9.2% (27/293) with the introduction of FLAER. However, this increase could be attributed to increased detection of PNH clone in the aplastic anemia group, which showed a significant increase from 8.3 to 18.2% after use of FLAER. In the non-aplastic group, PNH clone was detected with similar frequencies before and after use of FLAER (3.2 versus 3.8%, respectively). Mean PNH clone size was lower in the aplastic anemia group when compared with the non-aplastic group. RBCs always showed a lower clone size than neutrophils. PNH clone on neutrophils and monocytes was however similar. Inclusion of FLAER increases the sensitivity of the test which is especially useful in picking up small PNH clones in patients of aplastic anemia.

Type 2 diabetes mellitus: A risk factor for Helicobacter pylori infection: A hospital based case-control study

PubMed Central

Devrajani, Bikha Ram; Shah, Syed Zulfiquar Ali; Soomro, Aftab Ahmed; Devrajani, Tarachand

2010-01-01

Objective: To determine the frequency of Helicobacter pylori (H. pylori) infection in diabetic and non-diabetic patients and to compare the frequency of H. pylori infection in both groups. Study Design: Case control. Place and Duration: Department of Medicine, Liaquat University Hospital from October 2007 to March 2008. Materials and Methods: This hospital-based case-control study was conducted on 148 subjects and divided into two groups i.e. type 2 diabetics and non-diabetics; each group consisting of 74 patients. All diabetic patients of ≥ 35 years of age, both gender and the known cases with history of dyspepsia, epigastric pain or bloating for more than a month were screened for Helicobacter pylori infection. The collected data of both groups was evaluated and separated for analysis. Results: Majority of the patients were male with mean age ± SD, 52.86 ± 8.51. Among the diabetic group, HpSA was positive in 54/74 (73%), whereas in the non-diabetic group HpSA was positive in 38/74 (51.4%) cases. Fasting blood glucose was identified as low in 04 (5.40%) H. pylori infected - diabetic patients where as the blood glucose level of 07 (9.45%) known diabetic patients was raised despite the ongoing medication. Conclusion: Diabetic patients are more prone and at risk to acquire H. Pylori infection. Therefore proper monitoring of blood glucose level and screening for H. pylori infection are effective preventive measures for this life threatening infection. PMID:20431802

High prevalence of severe vitamin D deficiency in combined antiretroviral therapy-naive and successfully treated Swiss HIV patients.

PubMed

Mueller, Nicolas J; Fux, Christoph A; Ledergerber, Bruno; Elzi, Luigia; Schmid, Patrick; Dang, Thanh; Magenta, Lorenzo; Calmy, Alexandra; Vergopoulos, Athanasios; Bischoff-Ferrari, Heike A

2010-05-15

To evaluate the prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency in HIV-positive patients, a population at risk for osteoporosis. Retrospective assessment of vitamin D levels by season and initiation of combined antiretroviral therapy (cART). 25(OH)D was measured in 211 HIV-positive patients: samples were taken before initiation of cART from February to April or from August to October as well as 12 (same season) and 18 months (alternate season) after starting cART. 1,25-Dihydroxyvitamin D [1,25(OH)2D] was measured in a subset of 74 patients. Multivariable analyses included season, sex, age, ethnicity, BMI, intravenous drug use (IDU), renal function, time since HIV diagnosis, previous AIDS, CD4 cell count and cART, in particular nonnucleoside reverse transcriptase inhibitor (NNRTI) and tenofovir (TDF) use. At baseline, median 25(OH)D levels were 37 (interquartile range 20-49) nmol/l in spring and 57 (39-74) nmol/l in the fall; 25(OH)D deficiency less than 30 nmol/l was more prevalent in spring (42%) than in fall (14%), but remained unchanged regardless of cART exposure. In multivariable analysis, 25(OH)D levels were higher in white patients and those with a longer time since HIV diagnosis and lower in springtime measurements and in those with active IDU and NNRTI use. 1-Hydroxylation rates were significantly higher in patients with low 25(OH)D. Hepatitis C seropositivity, previous AIDS and higher CD4 cell counts correlated with lower 1,25(OH)2D levels, whereas BMI and TDF use were associated with higher levels. In TDF-treated patients, higher 1,25(OH)2D correlated with increases in serum alkaline phosphatase. Based on the high rate of vitamin D deficiency in HIV-positive patients, systematic screening with consideration of seasonality is warranted. The impact of NNRTIs on 25(OH)D and TDF on 1,25(OH)2D needs further attention.

Sources of heavy metal pollution in agricultural soils of a rapidly industrializing area in the Yangtze Delta of China.

PubMed

Xu, Xianghua; Zhao, Yongcun; Zhao, Xiaoyan; Wang, Yudong; Deng, Wenjing

2014-10-01

The rapid industrialization and urbanization in developing countries have increased pollution by heavy metals, which is a concern for human health and the environment. In this study, 230 surface soil samples (0-20cm) were collected from agricultural areas of Jiaxing, a rapidly industrializing area in the Yangtze Delta of China. Sequential Gaussian simulation (SGS) and multivariate factorial kriging analysis (FKA) were used to identify and explore the sources of heavy metal pollution for eight metals (Cu, Zn, Pb, Cr, Ni, Cd, Hg and As). Localized hot-spots of pollution were identified for Cu, Zn, Pb, Cr, Ni and Cd with area percentages of 0.48 percent, 0.58 percent, 2.84 percent, 2.41 percent, 0.74 percent, and 0.68 percent, respectively. The areas with Hg pollution covered approximately 38 percent whereas no potential pollution risk was found for As. The soil parent material and point sources of pollution had significant influences on Cr, Ni, Cu, Zn and Cd levels, except for the influence of agricultural management practices also accounted for micro-scale variations (nugget effect) for Cu and Zn pollution. Short-range (4km) diffusion processes had a significant influence on Cu levels, although they did not appear to be the dominant sources of Zn and Cd variation. The short-range diffusion pollution arising from current and historic industrial emissions and urbanization, and long-range (33km) variations in soil parent materials and/or diffusion jointly determined the current concentrations of soil Pb. The sources of Hg pollution risk may be attributed to the atmosphere deposition of industrial emission and historical use of Hg-containing pesticides. Copyright © 2014 Elsevier Inc. All rights reserved.

Experimental and theoretical XANES of CdSxSe1-x nanostructures

NASA Astrophysics Data System (ADS)

Yiu, Y. M.; Murphy, M. W.; Liu, L.; Hu, Y.; Sham, T. K.

2014-03-01

The morphology and electronic properties of the CdSxSe1-x nanostructures with varying alloy compositions have been acquired experimentally by X-ray Absorption Near-Edge Structures (XANES) at the Cd, Se and S K-edge and L3,2-edges. The theoretical XANES spectra have been calculated using the density functional approach. It is found that the optical band-gap emission of these CdSxSe1-x nano-ribbons can be tuned to the range between that of pure CdS (2.43 eV) and CdSe (1.74 eV) by changing the S and Se ratio. This gradual shift in (optical and structural) properties from CdS character to CdSe character is also seen in the electronic structures. The densities of states and band structures show that with the addition of Se replacing S in CdS, the band gap shrinks. The K and L3,2 edges of Cd, Se, and S of the XANES structures of both the CdS and CdSe in B4 (wurtzite) and B3 (cubic zinc-blende) structures have been calculated and compared.

Trace Metals in Noah's Ark Shells (Arca noae Linnaeus, 1758): Impact of Tourist Season and Human Health Risk.

PubMed

Ivanković, Dušica; Erk, Marijana; Župan, Ivan; Čulin, Jelena; Dragun, Zrinka; Bačić, Niko; Cindrić, Ana-Marija

2016-10-01

Commercially important bivalve Noah's Ark shell (Arca noae Linnaeus, 1758) represents a high-quality seafood product, but the data on levels of metal contaminants that could pose a human health risk and also on some essential elements that are important for health protection are lacking. This study examined the concentrations of Cd, Pb, Cr, Ni, Cu, Co, and Zn in the soft tissue of A. noae from harvesting area in the central Adriatic Sea, to survey whether heavy metals are within the acceptable limits for public health and whether tourism could have an impact on them. The concentrations of analysed metals varied for Cd: 0.15-0.74, Pb: 0.06-0.26, Cr: 0.11-0.34, Ni: 0.09-0.22, Cu: 0.65-1.95, Co: 0.04-0.09, and Zn: 18.3-74.7 mg/kg wet weight. These levels were lower than the permissible limits for safe consummation of seafood, and only for Cd, some precautions should be taken into account if older shellfish were consumed. Increase of Cd, Cr, and Cu in shell tissue was observed during the tourist season at the site closest to the marine traffic routes, indicating that metal levels in shellfish tissue should be monitored especially carefully during the peak tourist season to prevent eventual toxic effects due to increased intake of metals, specifically of Cd.

PARV4 prevalence, phylogeny, immunology and coinfection with HIV, HBV and HCV in a multicentre African cohort.

PubMed

Sharp, Colin P; Gregory, William F; Hattingh, Louise; Malik, Amna; Adland, Emily; Daniels, Samantha; van Zyl, Anriette; Carlson, Jonathan M; Wareing, Susan; Ogwu, Anthony; Shapiro, Roger; Riddell, Lynn; Chen, Fabian; Ndung'u, Thumbi; Goulder, Philip J R; Klenerman, Paul; Simmonds, Peter; Jooste, Pieter; Matthews, Philippa C

2017-04-07

Background: The seroprevalence of human parvovirus-4 (PARV4) varies considerably by region. In sub-Saharan Africa, seroprevalence is high in the general population, but little is known about the transmission routes or the prevalence of coinfection with blood-borne viruses, HBV, HCV and HIV.  Methods: To further explore the characteristics of PARV4 in this setting, with a particular focus on the prevalence and significance of coinfection, we screened a cohort of 695 individuals recruited from Durban and Kimberley (South Africa) and Gaborone (Botswana) for PARV4 IgG and DNA, as well as documenting HIV, HBV and HCV status.  Results: Within these cohorts, 69% of subjects were HIV-positive. We identified no cases of HCV by PCR, but 7.4% were positive for HBsAg. PARV4 IgG was positive in 42%; seroprevalence was higher in adults (69%) compared to children (21%) (p<0.0001) and in HIV-positive (52%) compared to HIV-negative individuals (24%) (p<0.0001), but there was no association with HBsAg status. We developed an on-line tool to allow visualization of coinfection data (https://purl.oclc.org/coinfection-viz). We identified five subjects who were PCR-positive for PARV4 genotype-3. Ex vivo CD8+ T cell responses spanned the entire PARV4 proteome and we propose a novel HLA-B*57:03-restricted epitope within the NS protein.  Conclusions: This characterisation of PARV4 infection provides enhanced insights into the epidemiology of infection and co-infection in African cohorts, and provides the foundations for planning further focused studies to elucidate transmission pathways, immune responses, and the clinical significance of this organism.

PARV4 prevalence, phylogeny, immunology and coinfection with HIV, HBV and HCV in a multicentre African cohort

PubMed Central

Sharp, Colin P.; Gregory, William F.; Hattingh, Louise; Malik, Amna; Adland, Emily; Daniels, Samantha; van Zyl, Anriette; Carlson, Jonathan M.; Wareing, Susan; Ogwu, Anthony; Shapiro, Roger; Riddell, Lynn; Chen, Fabian; Ndung'u, Thumbi; Goulder, Philip J.R.; Klenerman, Paul; Simmonds, Peter; Jooste, Pieter; Matthews, Philippa C.

2017-01-01

Background: The seroprevalence of human parvovirus-4 (PARV4) varies considerably by region. In sub-Saharan Africa, seroprevalence is high in the general population, but little is known about the transmission routes or the prevalence of coinfection with blood-borne viruses, HBV, HCV and HIV.  Methods: To further explore the characteristics of PARV4 in this setting, with a particular focus on the prevalence and significance of coinfection, we screened a cohort of 695 individuals recruited from Durban and Kimberley (South Africa) and Gaborone (Botswana) for PARV4 IgG and DNA, as well as documenting HIV, HBV and HCV status.  Results: Within these cohorts, 69% of subjects were HIV-positive. We identified no cases of HCV by PCR, but 7.4% were positive for HBsAg. PARV4 IgG was positive in 42%; seroprevalence was higher in adults (69%) compared to children (21%) (p<0.0001) and in HIV-positive (52%) compared to HIV-negative individuals (24%) (p<0.0001), but there was no association with HBsAg status. We developed an on-line tool to allow visualization of coinfection data ( https://purl.oclc.org/coinfection-viz). We identified five subjects who were PCR-positive for PARV4 genotype-3. Ex vivo CD8+ T cell responses spanned the entire PARV4 proteome and we propose a novel HLA-B*57:03-restricted epitope within the NS protein.  Conclusions: This characterisation of PARV4 infection provides enhanced insights into the epidemiology of infection and co-infection in African cohorts, and provides the foundations for planning further focused studies to elucidate transmission pathways, immune responses, and the clinical significance of this organism. PMID:28497124

Clinical efficacy of adalimumab in Crohn's disease: a real practice observational study in Japan.

PubMed

Takeshima, Fuminao; Yoshikawa, Daisuke; Higashi, Syuntaro; Morisaki, Tomohito; Oda, Hidetoshi; Ikeda, Maho; Machida, Haruhisa; Matsushima, Kayoko; Minami, Hitomi; Akazawa, Yuko; Yamaguchi, Naoyuki; Ohnita, Ken; Isomoto, Hajime; Ueno, Masato; Nakao, Kazuhiko

2016-07-29

There are few reports of the efficacy of adalimumab (ADA) for clinical remission and preventing postoperative recurrence in Crohn's disease (CD) in Asian real practice settings. We conducted a Japanese multicenter retrospective observational study. We evaluated patients with CD who were treated with ADA at 11 medical institutions in Japan to investigate the clinical efficacy of remission up to 52 weeks and the associated factors to achieve remission with a CD Activity Index (CDAI) < 150. The effects of preventing postoperative recurrence were also evaluated. In 62 patients, the remission rates were 33.9, 74.2, 75.8, 77.4, and 66.1 % at 0, 4, 12, 26, and 52 weeks, respectively. Although 10 patients discontinued treatment due to primary nonresponse, secondary nonresponse, or adverse events, the ongoing treatment rate at 52 weeks was 83.9 %. Comparison of remission and non-remission on univariate analysis identified colonic type and baseline CDAI value as significant associated factors (P < 0.05). In 16 patients who received ADA to prevent postoperative recurrence, the clinical remission maintenance rate was 93.8 % and the mucosal healing rate was 64.3 % during a mean postoperative follow-up period of 32.3 months. ADA effectively induced remission and prevented postoperative recurrence in patients with CD in a real practice setting.

Using resource modelling to inform decision making and service planning: the case of colorectal cancer screening in Ireland

PubMed Central

2013-01-01

Background Organised colorectal cancer screening is likely to be cost-effective, but cost-effectiveness results alone may not help policy makers to make decisions about programme feasibility or service providers to plan programme delivery. For these purposes, estimates of the impact on the health services of actually introducing screening in the target population would be helpful. However, these types of analyses are rarely reported. As an illustration of such an approach, we estimated annual health service resource requirements and health outcomes over the first decade of a population-based colorectal cancer screening programme in Ireland. Methods A Markov state-transition model of colorectal neoplasia natural history was used. Three core screening scenarios were considered: (a) flexible sigmoidoscopy (FSIG) once at age 60, (b) biennial guaiac-based faecal occult blood tests (gFOBT) at 55–74 years, and (c) biennial faecal immunochemical tests (FIT) at 55–74 years. Three alternative FIT roll-out scenarios were also investigated relating to age-restricted screening (55–64 years) and staggered age-based roll-out across the 55–74 age group. Parameter estimates were derived from literature review, existing screening programmes, and expert opinion. Results were expressed in relation to the 2008 population (4.4 million people, of whom 700,800 were aged 55–74). Results FIT-based screening would deliver the greatest health benefits, averting 164 colorectal cancer cases and 272 deaths in year 10 of the programme. Capacity would be required for 11,095-14,820 diagnostic and surveillance colonoscopies annually, compared to 381–1,053 with FSIG-based, and 967–1,300 with gFOBT-based, screening. With FIT, in year 10, these colonoscopies would result in 62 hospital admissions for abdominal bleeding, 27 bowel perforations and one death. Resource requirements for pathology, diagnostic radiology, radiotherapy and colorectal resection were highest for FIT. Estimates depended on screening uptake. Alternative FIT roll-out scenarios had lower resource requirements. Conclusions While FIT-based screening would quite quickly generate attractive health outcomes, it has heavy resource requirements. These could impact on the feasibility of a programme based on this screening modality. Staggered age-based roll-out would allow time to increase endoscopy capacity to meet programme requirements. Resource modelling of this type complements conventional cost-effectiveness analyses and can help inform policy making and service planning. PMID:23510135

A novel small-molecule compound targeting CD147 inhibits the motility and invasion of hepatocellular carcinoma cells

PubMed Central

Peng, Jian-long; Wang, Shi-jie; Geng, Jie-jie; Liu, Ji-de; Feng, Fei; Song, Fei; Li, Ling; Zhu, Ping; Jiang, Jian-li; Chen, Zhi-nan

2016-01-01

CD147, a type I transmembrane glycoprotein, is highly expressed in various cancer types and plays important roles in tumor progression, especially by promoting the motility and invasion of hepatocellular carcinoma (HCC) cells. These crucial roles make CD147 an attractive target for therapeutic intervention in HCC, but no small-molecule inhibitors of CD147 have been developed to date. To identify a candidate inhibitor, we used a pharmacophore model derived from the structure of CD147 to virtually screen over 300,000 compounds. The 100 highest-ranked compounds were subjected to biological assays, and the most potent one, dubbed AC-73 (ID number: AN-465/42834501), was studied further. We confirmed that AC-73 targeted CD147 and further demonstrated it can specifically disrupt CD147 dimerization. Moreover, molecular docking and mutagenesis experiments showed that the possible binding sites of AC-73 on CD147 included Glu64 and Glu73 in the N-terminal IgC2 domain, which two residues are located in the dimer interface of CD147. Functional assays revealed that AC-73 inhibited the motility and invasion of typical HCC cells, but not HCC cells that lacked the CD147 gene, demonstrating on-target action. Further, AC-73 reduced HCC metastasis by suppressing matrix metalloproteinase (MMP)-2 via down-regulation of the CD147/ERK1/2/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Finally, AC-73 attenuated progression in an orthotopic nude mouse model of liver metastasis, suggesting that AC-73 or its derivatives have potential for use in HCC intervention. We conclude that the novel small-molecule inhibitor AC-73 inhibits HCC mobility and invasion, probably by disrupting CD147 dimerization and thereby mainly suppressing the CD147/ERK1/2/STAT3/MMP-2 pathways, which are crucial for cancer progression. PMID:26882566

A chemically induced new pea (Pisum sativum) mutant SGECdt with increased tolerance to, and accumulation of, cadmium.

PubMed

Tsyganov, Viktor E; Belimov, Andrei A; Borisov, Alexey Y; Safronova, Vera I; Georgi, Manfred; Dietz, Karl-Josef; Tikhonovich, Igor A

2007-02-01

To date, there are no crop mutants described in the literature that display both Cd accumulation and tolerance. In the present study a unique pea (Pisum sativum) mutant SGECd(t) with increased Cd tolerance and accumulation was isolated and characterized. Ethylmethane sulfonate mutagenesis of the pea line SGE was used to obtain the mutant. Screening for Cd-tolerant seedlings in the M2 generation was performed using hydroponics in the presence of 6 microm CdCl2. Hybridological analysis was used to identify the inheritance of the mutant phenotype. Several physiological and biochemical characteristics of SGECd(t) were studied in hydroponic experiments in the presence of 3 microm CdCl2, and elemental analysis was conducted. The mutant SGECd(t) was characterized as having a monogenic inheritance and a recessive phenotype. It showed increased Cd concentrations in roots and shoots but no obvious morphological defects, demonstrating its capability to cope well with increased Cd levels in its tissues. The enhanced Cd accumulation in the mutant was accompanied by maintenance of homeostasis of shoot Ca, Mg, Zn and Mn contents, and root Ca and Mg contents. Through the application of La(+3) and the exclusion of Ca from the nutrient solution, maintenance of nutrient homeostasis in Cd-stressed SGECd(t) was shown to contribute to the increased Cd tolerance. Control plants of the mutant (i.e. no Cd treatment) had elevated concentrations of glutathione (GSH) in the roots. Through measurements of chitinase and guaiacol-dependent peroxidase activities, as well as proline and non-protein thiol (NPT) levels, it was shown that there were lower levels of Cd stress both in roots and shoots of SGECd(t). Accumulation of phytochelatins [(PCcalculated) = (NPT)-(GSH)] could be excluded as a cause of the increased Cd tolerance in the mutant. The SGECd(t) mutant represents a novel and unique model to study adaptation of plants to toxic heavy metal concentrations.

A Novel Epitope from CD22 Regulates Th1 and Th17 Cell Function in Systemic Lupus Erythematosus

PubMed Central

Chen, Xiao; Zhang, Li-Hua; Song, You; Cheng, Xiang; Zhou, Zi-Hua; Wang, Min; Guo, He-Ping; Du, Rong; Liao, Yu-Hua

2013-01-01

The published antibodies (Abs) against CD22 on B cells including Epratuzumab could inhibit B cell activation mainly through binding to C2-set Ig domain of CD22, but they are rarely reported to modulate the pathogenic CD4+ T cell function in systemic lupus erythematosus (SLE). Recently, it was proved that the extracellular amino-terminal V-set Ig domain of CD22 might mediate the interaction of B and T cells, but for now the exact effect of this domain on CD4+ T cell biology have not been identified. Thus, in this study, we screened out a peptide termed B2285 from this V-set Ig domain, developed the novel specific anti-B2285 Abs in rabbits, and investigated their effects in MRL/lpr mice with spontaneous SLE. The results showed that anti-B2285 Abs could ameliorate the disease severity obviously in spontaneous SLE mice with the decreased differentiations of Th1 and Th17 cells and no changes of Th2 and Treg cells. In co-cultured B cells and CD4+ T cells, this specific anti-CD22 Abs was observed to inhibit the anti-dsDNA Abs production, CD4+ T cells proliferation, the protein levels of T-bet and RORγt, and the mRNA levels of TNF-α, IFN-γ, IL-6 and IL-17 in CD4+ T cells. Moreover, the expression of CD45RO on CD4+ T cells could be also apparently diminished by this novel Abs. The data suggested that anti-B2285 Abs could slow SLE progression significantly by regulating Th1 and Th17 cells function via B-T cell interaction and the cytokine network regulation. The treatment against V-set Ig domain of CD22 would be a valuable therapeutic method for SLE and other autoimmune diseases. PMID:23704998

A novel epitope from CD22 regulates Th1 and Th17 cell function in systemic lupus erythematosus.

PubMed

Yuan, Jing; Yu, Miao; Cao, Ai-Lin; Chen, Xiao; Zhang, Li-Hua; Song, You; Cheng, Xiang; Zhou, Zi-Hua; Wang, Min; Guo, He-Ping; Du, Rong; Liao, Yu-Hua

2013-01-01

The published antibodies (Abs) against CD22 on B cells including Epratuzumab could inhibit B cell activation mainly through binding to C2-set Ig domain of CD22, but they are rarely reported to modulate the pathogenic CD4(+) T cell function in systemic lupus erythematosus (SLE). Recently, it was proved that the extracellular amino-terminal V-set Ig domain of CD22 might mediate the interaction of B and T cells, but for now the exact effect of this domain on CD4(+) T cell biology have not been identified. Thus, in this study, we screened out a peptide termed B2285 from this V-set Ig domain, developed the novel specific anti-B2285 Abs in rabbits, and investigated their effects in MRL/lpr mice with spontaneous SLE. The results showed that anti-B2285 Abs could ameliorate the disease severity obviously in spontaneous SLE mice with the decreased differentiations of Th1 and Th17 cells and no changes of Th2 and Treg cells. In co-cultured B cells and CD4(+) T cells, this specific anti-CD22 Abs was observed to inhibit the anti-dsDNA Abs production, CD4(+) T cells proliferation, the protein levels of T-bet and RORγt, and the mRNA levels of TNF-α, IFN-γ, IL-6 and IL-17 in CD4(+) T cells. Moreover, the expression of CD45RO on CD4(+) T cells could be also apparently diminished by this novel Abs. The data suggested that anti-B2285 Abs could slow SLE progression significantly by regulating Th1 and Th17 cells function via B-T cell interaction and the cytokine network regulation. The treatment against V-set Ig domain of CD22 would be a valuable therapeutic method for SLE and other autoimmune diseases.

A novel small-molecule compound targeting CD147 inhibits the motility and invasion of hepatocellular carcinoma cells.

PubMed

Fu, Zhi-guang; Wang, Li; Cui, Hong-yong; Peng, Jian-long; Wang, Shi-jie; Geng, Jie-jie; Liu, Ji-de; Feng, Fei; Song, Fei; Li, Ling; Zhu, Ping; Jiang, Jian-li; Chen, Zhi-nan

2016-02-23

CD147, a type I transmembrane glycoprotein, is highly expressed in various cancer types and plays important roles in tumor progression, especially by promoting the motility and invasion of hepatocellular carcinoma (HCC) cells. These crucial roles make CD147 an attractive target for therapeutic intervention in HCC, but no small-molecule inhibitors of CD147 have been developed to date. To identify a candidate inhibitor, we used a pharmacophore model derived from the structure of CD147 to virtually screen over 300,000 compounds. The 100 highest-ranked compounds were subjected to biological assays, and the most potent one, dubbed AC-73 (ID number: AN-465/42834501), was studied further. We confirmed that AC-73 targeted CD147 and further demonstrated it can specifically disrupt CD147 dimerization. Moreover, molecular docking and mutagenesis experiments showed that the possible binding sites of AC-73 on CD147 included Glu64 and Glu73 in the N-terminal IgC2 domain, which two residues are located in the dimer interface of CD147. Functional assays revealed that AC-73 inhibited the motility and invasion of typical HCC cells, but not HCC cells that lacked the CD147 gene, demonstrating on-target action. Further, AC-73 reduced HCC metastasis by suppressing matrix metalloproteinase (MMP)-2 via down-regulation of the CD147/ERK1/2/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Finally, AC-73 attenuated progression in an orthotopic nude mouse model of liver metastasis, suggesting that AC-73 or its derivatives have potential for use in HCC intervention. We conclude that the novel small-molecule inhibitor AC-73 inhibits HCC mobility and invasion, probably by disrupting CD147 dimerization and thereby mainly suppressing the CD147/ERK1/2/STAT3/MMP-2 pathways, which are crucial for cancer progression.

Adherence to multiple cancer screening tests among women living in Appalachia Ohio

PubMed Central

Katz, Mira L.; Reiter, Paul L.; Young, Gregory S.; Pennell, Michael L.; Tatum, Cathy M.; Paskett, Electra D.

2015-01-01

Background There is a lack of information about the correlates of completing all three cancer screening tests among women living in Appalachia. Methods Cross-sectional telephone interviews were conducted (April-September 2013) among women (n=637) ages 51-75 from 12 Appalachia Ohio counties. Outcomes of within screening guidelines were verified by medical record. Multivariable logistic regression models identified correlates of being within guidelines for all three cancer screening tests. Results Screening rates were: mammography (32.1%), Pap test (36.1%), and a colorectal cancer test (30.1%). Only 8.6% of women were within guidelines for all tests. Having had a check-up in the past two years and having received a screening recommendation were significantly related to being within guidelines for all three tests (p<0.01). Participants with higher annual household incomes ($60,000+; OR=3.53, 95% CI: 1.49, 8.33) and conditions requiring regular medical visits (OR=3.16, 95% CI: 1.29, 7.74) were more likely to be within guidelines for all three screening tests. Conclusion Less than 10% of women had completed screening within guidelines for all three screening tests. Regular contact with the healthcare system and higher incomes were significant predictors of being within guidelines. Impact Within guidelines rates for the three recommended cancer screening tests is low among women in Appalachia Ohio. This finding illustrates the need for innovative interventions to improve rates of multiple cancer screening tests. PMID:26282630

40 CFR 413.24 - Pretreatment standards for existing sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 1.9 1.0 Cu 4.5 2.7 Ni 4.1 2.6 Cr 7.0 4.0 Zn 4.2 2.6 Pb .6 .4 Cd 1.2 .7 Total metals 10.5 6.8 (d... exceed Ag 47 29 CN, T 74 39 Cu 176 105 Ni 160 100 Cr 273 156 Zn 164 102 Pb 23 16 Cd 47 29 Total metals...

40 CFR 413.24 - Pretreatment standards for existing sources.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 1.9 1.0 Cu 4.5 2.7 Ni 4.1 2.6 Cr 7.0 4.0 Zn 4.2 2.6 Pb .6 .4 Cd 1.2 .7 Total metals 10.5 6.8 (d... exceed Ag 47 29 CN, T 74 39 Cu 176 105 Ni 160 100 Cr 273 156 Zn 164 102 Pb 23 16 Cd 47 29 Total metals...

Dietary Supplement Use in Patients With Celiac Disease in the United States.

PubMed

Nazareth, Samantha; Lebwohl, Benjamin; Tennyson, Christina A; Simpson, Suzanne; Greenlee, Heather; Green, Peter H

2015-08-01

There has been increasing interest in the use of complementary and alternative medicine (CAM) in the general population. Little is known about CAM use in patients with celiac disease (CD). We aimed to determine the demographics and clinical characteristics of patients with biopsy-proven CD who use dietary supplements to treat their symptoms. CD patients completed a questionnaire on demographics, types of dietary supplement use, attitudes toward CAM, and 3 validated scales: CD-related Quality Of Life (CD-QOL), the CD Symptoms Index (CSI), and the CD Adherence Test (CDAT). Of 423 patients, 100 (23.6%) used dietary supplements to treat CD symptoms. The most frequently used supplement was probiotics (n=59). Supplement users had a higher CD-QOL score (75.06 vs. 71.43, P=0.04) but had more symptoms based on CSI (35.64 vs. 32.05, P=0.0032). On multivariable analysis, adjusting for age, sex, education, symptom improvement following a gluten-free diet, and where the survey was completed, patients presenting with classic symptoms (OR, 2.56; 95% CI, 1.01-6.44) or nonclassic symptoms (OR, 2.75; 95% CI, 1.04-7.24) were significantly more likely to use supplements than those with asymptomatic/screen-detected CD. Patients with biopsy-proven CD who have symptoms at diagnosis tend to use dietary supplements more than those that are screen detected. Those using supplements report persistent symptoms, but a higher quality of life. The contribution of the gluten-free diet and supplement use to quality of life in the symptomatic CD patient needs to be determined.

The Impact of Thyroid Autoimmunity on Thyroid Function in 12-year-old Children With Celiac Disease.

PubMed

Norström, Fredrik; van der Pals, Maria; Myléus, Anna; Hammarroth, Solveig; Högberg, Lotta; Isaksson, Anders; Ivarsson, Anneli; Carlsson, Annelie

2018-01-25

Celiac disease (CD) is associated with thyroid autoimmunity and other autoimmune diseases. However, data are lacking regarding the relationship between thyroid autoimmunity and thyroid function, especially in regard to CD. Our aim was to investigate the impact of thyroid autoimmunity on thyroid function in 12-year-old children with CD compared to their healthy peers. A case-referent study was conducted as part of a CD screening of 12-year-olds. Our study included 335 children with CD and 1,695 randomly selected referents. Thyroid autoimmunity was assessed with antibodies against thyroid peroxidase (TPOAb). Thyroid function was assessed with thyroid stimulating hormone and free thyroxine. TPOAb positivity significantly increased the risk of developing hypothyroidism in all children. The odds ratios (with 95% confidence intervals) were: 5.3 (2.7-11) in healthy 12-year-olds, 10 (3.2-32) in screening-detected CD cases, 19 (2.6-135) in previously diagnosed CD cases, and 12 (4.4-32) in all CD cases together. Among children with TPOAb positivity, hypothyroidism was significantly more common (odds ratio 3.1; 95% CI 1.03-9.6) in children with CD (10/19) than in children without CD (12/46). The risk of thyroid dysfunction due to thyroid autoimmunity is larger for those with CD than their healthy peers. Our study indicate that a gluten-free diet does not reduce the risk of thyroid dysfunction. Further studies are required for improved understanding of the role of the gluten-free diet for the risk of autoimmune diseases in children with CD.

MIF and D-DT are potential disease severity modifiers in male MS subjects

PubMed Central

Benedek, Gil; Meza-Romero, Roberto; Jordan, Kelley; Zhang, Ying; Nguyen, Ha; Kent, Gail; Li, Jia; Siu, Edwin; Frazer, Jenny; Piecychna, Marta; Du, Xin; Sreih, Antoine; Leng, Lin; Wiedrick, Jack; Caillier, Stacy J.; Offner, Halina; Oksenberg, Jorge R.; Yadav, Vijayshree; Bourdette, Dennis; Bucala, Richard; Vandenbark, Arthur A.

2017-01-01

Little is known about mechanisms that drive the development of progressive multiple sclerosis (MS), although inflammatory factors, such as macrophage migration inhibitory factor (MIF), its homolog D-dopachrome tautomerase (D-DT), and their common receptor CD74 may contribute to disease worsening. Our findings demonstrate elevated MIF and D-DT levels in males with progressive disease compared with relapsing-remitting males (RRMS) and female MS subjects, with increased levels of CD74 in females vs. males with high MS disease severity. Furthermore, increased MIF and D-DT levels in males with progressive disease were significantly correlated with the presence of two high-expression promoter polymorphisms located in the MIF gene, a −794CATT5–8 microsatellite repeat and a −173 G/C SNP. Conversely, mice lacking MIF or D-DT developed less-severe signs of experimental autoimmune encephalomyelitis, a murine model of MS, thus implicating both homologs as copathogenic contributors. These findings indicate that genetically controlled high MIF expression (and D-DT) promotes MS progression in males, suggesting that these two factors are sex-specific disease modifiers and raising the possibility that aggressive anti-MIF treatment of clinically isolated syndrome or RRMS males with a high-expresser genotype might slow or prevent the onset of progressive MS. Additionally, selective targeting of MIF:CD74 signaling might provide an effective, trackable therapeutic approach for MS subjects of both sexes. PMID:28923927

[Correlations between cellular immunity and invasiveness in differentiated thyroid cancer].

PubMed

Han, Ting; Liang, Jun; Meng, Chao; Yang, Ke; Li, Xiao-yi; Lin, Yan-song

2014-02-01

To investigate the relationship between the immunity and invasiveness in differentiated thyroid cancer (DTC). Totally 74 DTC who were treated in Peking Union Medical College Hospital from September 2012 to December 2012 were enrolled in this study. These 74 patients were divided into membrane invasion group (n=36) and without membrane invasion group (n=38); also, they were divided into distant metastasis group (n=18) and without distant metastasis group (n=56). Natural killer (NK) cells and T-cell subsets were chosen as indicators for cellular immunity to investigate the correlation between cellular immunity and invasiveness in DTC. Univariate analysis showed that the membrane invasion (Χ(2)=12.175, P=0.000) and distant metastasis (Χ(2)=8.139, P=0.006) correlated with cell immunity, whereas distant metastasis correlated with lymphocytic thyroiditis (Χ(2)=7.094, P=0.008). Further investigation shows that distant metastasis was associated with the percentage of CD8+T cell subgroup (Χ(2)=5.429, P=0.020), and membrane invasion was significantly associated with NK cells (Χ(2)=2.445, P=0.018) and CD4/CD8 disorder subgroup (Χ(2)=8.079, P=0.002). Multivariate analysis showed that cell immunity disorder was a risk factor for membrane invasion [OR=5.701,95%CI(2.075~15.666), P=0.001] and distant metastasis [OR=5.063,95%CI (1.571~16.320), P=0.008]. Further analysis showed that CD8+T cell was a risk factor for metastasis [OR=2.236,95%CI( 1.084~4.613), P=0.029], and CD4/CD8 disorders were the risk factors for membrane invasion [OR=2.802,95%CI(1.257~6.244), P=0.012]. Cell immunity in thyroid cancer has close relationship with membrane invasion and distant metastasis, especially when the percentage of CD8+T cells decreases and when the NK cells and CD4/CD8 are abnormal, which may lead to membrane invasion and distant metastasis.

Validity of the fine motor area of the 12-month ages and stages questionnaire in infants following major surgery.

PubMed

Smith, Cally; Wallen, Margaret; Walker, Karen; Bundy, Anita; Rolinson, Rachel; Badawi, Nadia

2012-08-01

The Ages and Stages Questionnaires (ASQ) are parent-report screening tools to identify infants at risk of developmental difficulties. The purpose of this study was to examine validity and internal reliability of the fine motor developmental area of the ASQ, 2nd edition (ASQ2-FM) for screening 12-month-old infants following major surgery. The ASQ2-FM was completed by caregivers of 74 infants who had cardiac surgery in the first 90 days of life, 104 infants who had noncardiac surgery in the first 90 days of life, and a control group of 154 infants. The Rasch item response analysis revealed that the ASQ2-FM had poor ability to discriminate among levels of fine motor ability. Sensitivity was poor (20%) and specificity was good (98%) when compared with the scores for the fine motor subscale of the Bayley Scales of Infant and Toddler Development. The ASQ2-FM under-identified infants at risk for fine motor delay; internal reliability and construct validity do not support use as a screening tool of fine motor development of infants aged 12 months who have undergone major surgery.

The importance of negative predictive value (NPV) of vulnerable elderly survey (VES 13) as a pre-screening test in older patients with cancer.

PubMed

Castagneto, B; Di Pietrantonj, C; Stevani, I; Anfossi, A; Arzese, M; Giorcelli, L; Giaretto, L

2013-12-01

The importance of prognostic value of the comprehensive geriatric assessment (CGA) is well known in geriatric oncology, but there is no consensus on the use of alternative abbreviated screening methods for the evaluation of older patient disabilities. The participants in this study underwent vulnerable elderly survey 13 (VES 13) at first entry in Oncology Department and were later assessed by a geriatrician according to CGA. A score >3 for VES 13 identified patients as vulnerable. Aim of this study was to evaluate the specificity, sensibility, positive predictive value (PPV), and negative predictive value (NPV) of VES 13 versus cumulative illness rating scale (CIRS), activities of daily living (ADL), instrumental activities of daily living (IADL), and short portable mental status questionnaire (SPMSQ). Hundred and seventeen patients (mean age 78.8 years) entered the study. The NPV of VES was 74.6% for CIRS, 90.1% for IADL, 93.0% for ADL, and 100% for SPMSQ. As for PPV, the VES 13 showed no accuracy. We can conclude that VES 13 demonstrated sufficient accuracy as a screening test in identifying elderly "fit" patients in order to spare the more time-consuming CGA.

Involvement of Sp1 and Microsatellite Repressor Sequences in the Transcriptional Control of the Human CD30 Gene

PubMed Central

Croager, Emma J.; Gout, Alexander M.; Abraham, Lawrence J.

2000-01-01

CD30, as a member of the tumor necrosis factor (TNF) receptor family, is expressed on the surface of activated lymphoid cells. CD30 overexpression is a characteristic of lymphoproliferative diseases such as Hodgkin’s/non-Hodgkin’s lymphomas, embryonal carcinoma, and a number of Th2-associated diseases. The CD30 gene has been mapped to a region of the murine genome that is involved in susceptibility to systemic lupus erythematosus. Functionally, CD30 may play a role in the deletion of autoreactive T cells. We were interested in determining the molecular nature of CD30 overexpression. Sequence comparison has revealed significant identity between the TATA-less human and murine CD30 promoters; they share a number of common consensus binding motifs. Transfection assays identified three regions of transcriptional importance; the region between position −1.2 kb and −336 bp, containing a CCAT microsatellite sequence, a conserved Sp1 site at positions −43 to −38, and a downstream promoter element (DPE) at positions +24 to +29. EMSA and DNase I footprinting showed specific DNA-protein interactions of the CD30 promoter with the Sp1 site and the CCAT repeat region. The DPE element was shown to be essential for start site selection. We conclude that the conserved Sp1 site at −43 to −38 is associated with maximum reporter gene activity, the DPE element is required for start site selection, and the CCAT tetranucleotide repeats act to repress transcription. We also have shown that the microsatellite is multiallelic, when we screened a random healthy population. Further studies are required to determine whether microsatellite instability in the repressor predisposes susceptible individuals to CD30 overexpression. PMID:10793083

Comparing diagnostic yield of a novel pan-enteric video capsule endoscope with ileocolonoscopy in patients with active Crohn's disease: a feasibility study.

PubMed

Leighton, Jonathan A; Helper, Debra J; Gralnek, Ian M; Dotan, Iris; Fernandez-Urien, Ignacio; Lahat, Adi; Malik, Pramod; Mullin, Gerard E; Rosa, Bruno

2017-01-01

Crohn's disease (CD) is typically diagnosed with ileocolonoscopy (IC); however, when inflammation is localized solely in the small bowel, visualization of the entire small-bowel mucosa can be challenging. The aim of this study was to compare the diagnostic yield of a pan-enteric video capsule endoscope (small-bowel colon [SBC] capsule) versus IC in patients with active CD. This was a prospective, multicenter study. Patients with known active CD and proven bowel luminal patency underwent a standardized colon cleansing protocol followed by ingestion of the capsule. After passage of the capsule, IC was performed and recorded. Lesions indicative of active CD were assessed. One hundred fourteen subjects were screened; 66 subjects completed both endoscopic procedures. The per-subject diagnostic yield rate for active CD lesions was 83.3% for SBC and 69.7% for IC (yield difference, 13.6%; 95% confidence interval [CI], 2.6%-24.7%); 65% of subjects had active CD lesions identified by both modalities. Of the 12 subjects who were positive for active CD by SBC only, 5 subjects were found to have active CD lesions in the terminal ileum. Three subjects were positive for active CD by IC only. Three hundred fifty-five classifying bowel segments were analyzed; the per-segment diagnostic yield rate was 40.6% for SBC and 32.7% for IC (yield difference 7.9%; 95% CI, 3.3%-12.4%). This preliminary study shows that the diagnostic yields for SBC might be higher than IC; however, the magnitude of difference between the two is difficult to estimate. Further study is needed to confirm these findings. Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Determinants in the β and δ subunit cytoplasmic loop regulate Golgi trafficking and surface expression of the muscle acetylcholine receptor.

PubMed

Rudell, Jolene Chang; Borges, Lucia S; Rudell, John B; Beck, Kenneth A; Ferns, Michael J

2014-01-03

The molecular determinants that govern nicotinic acetylcholine receptor (AChR) assembly and trafficking are poorly defined, and those identified operate largely during initial receptor biogenesis in the endoplasmic reticulum. To identify determinants that regulate later trafficking steps, we performed an unbiased screen using chimeric proteins consisting of CD4 fused to the muscle AChR subunit cytoplasmic loops. In C2 mouse muscle cells, we found that CD4-β and δ subunit loops were expressed at very low levels on the cell surface, whereas the other subunit loops were robustly expressed on the plasma membrane. The low surface expression of CD4-β and δ loops was due to their pronounced retention in the Golgi apparatus and also to their rapid internalization from the plasma membrane. Both retention and recovery were mediated by the proximal 25-28 amino acids in each loop and were dependent on an ordered sequence of charged and hydrophobic residues. Indeed, βK353L and δK351L mutations increased surface trafficking of the CD4-subunit loops by >6-fold and also decreased their internalization from the plasma membrane. Similarly, combined βK353L and δK351L mutations increased the surface levels of assembled AChR expressed in HEK cells to 138% of wild-type levels. This was due to increased trafficking to the plasma membrane and not decreased AChR turnover. These findings identify novel Golgi retention signals in the β and δ subunit loops that regulate surface trafficking of assembled AChR and may help prevent surface expression of unassembled subunits. Together, these results define molecular determinants that govern a Golgi-based regulatory step in nicotinic AChR trafficking.

Human Cytomegalovirus (HCMV)-Specific CD4+ T Cells Are Polyfunctional and Can Respond to HCMV-Infected Dendritic Cells In Vitro

PubMed Central

Sedikides, George X.; Mason, Gavin M.; Okecha, Georgina

2017-01-01

ABSTRACT Human cytomegalovirus (HCMV) infection and periodic reactivation are generally well controlled by the HCMV-specific T cell response in healthy people. While the CD8+ T cell response to HCMV has been extensively studied, the HCMV-specific CD4+ T cell effector response is not as well understood, especially in the context of direct interactions with HCMV-infected cells. We screened the gamma interferon (IFN-γ) and interleukin-10 (IL-10) responses to 6 HCMV peptide pools (pp65, pp71, IE1, IE2, gB, and US3, selected because they were the peptides most frequently responded to in our previous studies) in 84 donors aged 23 to 74 years. The HCMV-specific CD4+ T cell response to pp65, IE1, IE2, and gB was predominantly Th1 biased, with neither the loss nor the accumulation of these responses occurring with increasing age. A larger proportion of donors produced an IL-10 response to pp71 and US3, but the IFN-γ response was still dominant. CD4+ T cells specific to the HCMV proteins studied were predominantly effector memory cells and produced both cytotoxic (CD107a expression) and cytokine (macrophage inflammatory protein 1β secretion) effector responses. Importantly, when we measured the CD4+ T cell response to cytomegalovirus (CMV)-infected dendritic cells in vitro, we observed that the CD4+ T cells produced a range of cytotoxic and secretory effector functions, despite the presence of CMV-encoded immune evasion molecules. CD4+ T cell responses to HCMV-infected dendritic cells were sufficient to control the dissemination of virus in an in vitro assay. Together, the results show that HCMV-specific CD4+ T cell responses, even those from elderly individuals, are highly functional and are directly antiviral. IMPORTANCE Human cytomegalovirus (HCMV) infection is carried for a lifetime and in healthy people is kept under control by the immune system. HCMV has evolved many mechanisms to evade the immune response, possibly explaining why the virus is never eliminated during the host's lifetime. The dysfunction of immune cells associated with the long-term carriage of HCMV has been linked with poor responses to new pathogens and vaccines when people are older. In this study, we investigated the response of a subset of immune cells (CD4+ T cells) to HCMV proteins in healthy donors of all ages, and we demonstrate that the functionality of CD4+ T cells is maintained. We also show that CD4+ T cells produce effector functions in response to HCMV-infected cells and can prevent virus spread. Our work demonstrates that these HCMV-specific immune cells retain many important functions and help to prevent deleterious HCMV disease in healthy older people. PMID:28053099

Human Cytomegalovirus (HCMV)-Specific CD4+ T Cells Are Polyfunctional and Can Respond to HCMV-Infected Dendritic Cells In Vitro.

PubMed

Jackson, Sarah E; Sedikides, George X; Mason, Gavin M; Okecha, Georgina; Wills, Mark R

2017-03-15

Human cytomegalovirus (HCMV) infection and periodic reactivation are generally well controlled by the HCMV-specific T cell response in healthy people. While the CD8 + T cell response to HCMV has been extensively studied, the HCMV-specific CD4 + T cell effector response is not as well understood, especially in the context of direct interactions with HCMV-infected cells. We screened the gamma interferon (IFN-γ) and interleukin-10 (IL-10) responses to 6 HCMV peptide pools (pp65, pp71, IE1, IE2, gB, and US3, selected because they were the peptides most frequently responded to in our previous studies) in 84 donors aged 23 to 74 years. The HCMV-specific CD4 + T cell response to pp65, IE1, IE2, and gB was predominantly Th1 biased, with neither the loss nor the accumulation of these responses occurring with increasing age. A larger proportion of donors produced an IL-10 response to pp71 and US3, but the IFN-γ response was still dominant. CD4 + T cells specific to the HCMV proteins studied were predominantly effector memory cells and produced both cytotoxic (CD107a expression) and cytokine (macrophage inflammatory protein 1β secretion) effector responses. Importantly, when we measured the CD4 + T cell response to cytomegalovirus (CMV)-infected dendritic cells in vitro , we observed that the CD4 + T cells produced a range of cytotoxic and secretory effector functions, despite the presence of CMV-encoded immune evasion molecules. CD4 + T cell responses to HCMV-infected dendritic cells were sufficient to control the dissemination of virus in an in vitro assay. Together, the results show that HCMV-specific CD4 + T cell responses, even those from elderly individuals, are highly functional and are directly antiviral. IMPORTANCE Human cytomegalovirus (HCMV) infection is carried for a lifetime and in healthy people is kept under control by the immune system. HCMV has evolved many mechanisms to evade the immune response, possibly explaining why the virus is never eliminated during the host's lifetime. The dysfunction of immune cells associated with the long-term carriage of HCMV has been linked with poor responses to new pathogens and vaccines when people are older. In this study, we investigated the response of a subset of immune cells (CD4 + T cells) to HCMV proteins in healthy donors of all ages, and we demonstrate that the functionality of CD4 + T cells is maintained. We also show that CD4 + T cells produce effector functions in response to HCMV-infected cells and can prevent virus spread. Our work demonstrates that these HCMV-specific immune cells retain many important functions and help to prevent deleterious HCMV disease in healthy older people. Copyright © 2017 American Society for Microbiology.

Is systematic screening and treatment for latent tuberculosis infection in HIV patients useful in a low endemic setting?

PubMed

Maniewski, Ula; Payen, Marie-Christine; Delforge, Marc; De Wit, Stephane

2017-08-01

A decreasing incidence of tuberculosis (TB) among HIV patients has been documented in high-income settings and screening for tuberculosis is not systematically performed in many clinics (such as ours). Our objectives are to evaluate whether a same decline of incidence was seen in our Belgian tertiary center and to evaluate whether systematic screening and prophylaxis of tuberculosis should remain part of routine practice. Between 2005 and 2012, the annual incidence of tuberculosis among adult HIV patients was measured. The impact of demographic characteristics and CD 4 nadir on the incidence of active TB was evaluated. Among the 1167 patients who entered the cohort, 42 developed active TB with a significant decrease of annual incidence from 28/1000 patient-years in 2005 to 3/1000 patient-years in 2012. Among the 42 cases, 83% were of sub-Saharan origin. Median CD4 cell count upon HIV diagnosis was significantly lower in TB cases and 60% had a nadir CD4 below 200/μl. Thirty-six percent of incident TB occurred within 14 days after HIV diagnosis. A significant decline of TB incidence in HIV patients was observed. Incident TB occurred mainly in African patients, with low CD4 upon HIV diagnosis. A significant proportion of TB cases were discovered early in follow-up which probably reflects TB already present upon HIV diagnosis. In a low endemic setting, exclusion of active TB upon HIV diagnosis remains a priority and screening for LTBI should focus on HIV patients from high risk groups such as migrants from endemic regions, especially in patients with low CD4 nadir.

[Detection of ALK, ROS1 and RET fusion genes in non-small cell lung cancer patients and its clinicopathologic correlation].

PubMed

Zhong, Shan; Zhang, Haiping; Bai, Dongyu; Gao, Dehong; Zheng, Jie; Ding, Yi

2015-09-01

To study the prevalence of ALK, ROS1 and RET fusion genes in non-small cell lung cancer (NSCLC), and its correlation with clinicopathologic features. Formalin-fixed and paraffin-embedded tissue sections from samples of 302 patients with NSCLC were screened for ALK, ROS1, RET fusions by real-time polymerase chain reaction (PCR). All of the cases were validated by Sanger DNA sequencing. The relationship between ALK, ROS1, RET fusion genes and clinicopathologic features were analyzed. In the cohort of 302 NSCLC samples, 3.97% (12/302) were found to contain ALK fusion genes, including 3 cases with E13; A20 gene fusion, 3 cases with E6; A20 gene fusion and 3 cases with E20; A20 gene fusion. There was no statistically significant difference in patient's gender, age, smoking history and histologic type. Moreover, in the 302 NSCLC samples studied, 3.97% (12/302) were found to contain ROS1 fusion genes, with CD74-ROS1 fusion identified in 9 cases. There was no statistically significant difference in patients' gender, age, smoking history and histologic type. One non-smoking elderly female patient with pulmonary adenocarcinoma had RET gene fusion. None of the cases studied had concurrent ALK, ROS1 and RET mutations. The ALK, ROS1 and RET fusion gene mutation rates in NSCLC are low, they represent some specific molecular subtypes of NSCLC. Genetic testing has significant meaning to guide clinical targeted therapy.

Identification of effective screening strategies for cardiovascular disease prevention in a developing country: using cardiovascular risk-estimation and risk-reduction tools for policy recommendations.

PubMed

Selvarajah, Sharmini; Haniff, Jamaiyah; Kaur, Gurpreet; Guat Hiong, Tee; Bujang, Adam; Chee Cheong, Kee; Bots, Michiel L

2013-02-25

Recent increases in cardiovascular risk-factor prevalences have led to new national policy recommendations of universal screening for primary prevention of cardiovascular disease in Malaysia. This study assessed whether the current national policy recommendation of universal screening was optimal, by comparing the effectiveness and impact of various cardiovascular screening strategies. Data from a national population based survey of 24 270 participants aged 30 to 74 was used. Five screening strategies were modelled for the overall population and by gender; universal and targeted screening (four age cut-off points). Screening strategies were assessed based on the ability to detect high cardiovascular risk populations (effectiveness), incremental effectiveness, impact on cardiovascular event prevention and cost of screening. 26.7% (95% confidence limits 25.7, 27.7) were at high cardiovascular risk, men 34.7% (33.6, 35.8) and women 18.9% (17.8, 20). Universal screening identified all those at high-risk and resulted in one high-risk individual detected for every 3.7 people screened, with an estimated cost of USD60. However, universal screening resulted in screening an additional 7169 persons, with an incremental cost of USD115,033 for detection of one additional high-risk individual in comparison to targeted screening of those aged ≥35 years. The cost, incremental cost and impact of detection of high-risk individuals were more for women than men for all screening strategies. The impact of screening women aged ≥45 years was similar to universal screening in men. Targeted gender- and age-specific screening strategies would ensure more optimal utilisation of scarce resources compared to the current policy recommendations of universal screening.

Identification of effective screening strategies for cardiovascular disease prevention in a developing country: using cardiovascular risk-estimation and risk-reduction tools for policy recommendations

PubMed Central

2013-01-01

Background Recent increases in cardiovascular risk-factor prevalences have led to new national policy recommendations of universal screening for primary prevention of cardiovascular disease in Malaysia. This study assessed whether the current national policy recommendation of universal screening was optimal, by comparing the effectiveness and impact of various cardiovascular screening strategies. Methods Data from a national population based survey of 24 270 participants aged 30 to 74 was used. Five screening strategies were modelled for the overall population and by gender; universal and targeted screening (four age cut-off points). Screening strategies were assessed based on the ability to detect high cardiovascular risk populations (effectiveness), incremental effectiveness, impact on cardiovascular event prevention and cost of screening. Results 26.7% (95% confidence limits 25.7, 27.7) were at high cardiovascular risk, men 34.7% (33.6, 35.8) and women 18.9% (17.8, 20). Universal screening identified all those at high-risk and resulted in one high-risk individual detected for every 3.7 people screened, with an estimated cost of USD60. However, universal screening resulted in screening an additional 7169 persons, with an incremental cost of USD115,033 for detection of one additional high-risk individual in comparison to targeted screening of those aged ≥35 years. The cost, incremental cost and impact of detection of high-risk individuals were more for women than men for all screening strategies. The impact of screening women aged ≥45 years was similar to universal screening in men. Conclusions Targeted gender- and age-specific screening strategies would ensure more optimal utilisation of scarce resources compared to the current policy recommendations of universal screening. PMID:23442728

Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors

PubMed Central

Pizzamiglio, Sara; De Bortoli, Maida; Taverna, Elena; Signore, Michele; Veneroni, Silvia; Chi-shing Cho, William; Orlandi, Rosaria; Verderio, Paolo; Bongarzone, Italia

2017-01-01

We have previously reported hepcidin and ferritin increases in the plasma of breast cancer patients, but not in patients with benign breast disease. We hypothesized that these differences in systemic iron homeostasis may reflect alterations in different iron-related proteins also play a key biochemical and regulatory role in breast cancer. Thus, here we explored the expression of a bundle of molecules involved in both iron homeostasis and tumorigenesis in tissue samples. Enzyme-linked immunosorbent assay (ELISA) or reverse-phase protein array (RPPA), were used to measure the expression of 20 proteins linked to iron processes in 24 non-cancerous, and 56 cancerous, breast tumors. We found that cancerous tissues had higher level of hepcidin than benign lesions (p = 0.012). The univariate analysis of RPPA data highlighted the following seven proteins differentially expressed between non-cancerous and cancerous breast tissue: signal transducer and transcriptional activator 5 (STAT5), signal transducer and activator of transcription 3 (STAT3), bone morphogenetic protein 6 (BMP6), cluster of differentiation 74 (CD74), transferrin receptor (TFRC), inhibin alpha (INHA), and STAT5_pY694. These findings were confirmed for STAT5, STAT3, BMP6, CD74 and INHA when adjusting for age. The multivariate statistical analysis indicated an iron-related 10-protein panel effective in separating non-cancerous from cancerous lesions including STAT5, STAT5_pY694, myeloid differentiation factor 88 (MYD88), CD74, iron exporter ferroportin (FPN), high mobility group box 1 (HMGB1), STAT3_pS727, TFRC, ferritin heavy chain (FTH), and ferritin light chain (FTL). Our results showed an association between some iron-related proteins and the type of tumor tissue, which may provide insight in strategies for using iron chelators to treat breast cancer. PMID:28216608

Selective T cell-depleted haploidentical hematopoietic stem cell transplantation for relapsed/refractory neuroblastoma.

PubMed

Liu, Anthony P Y; Lee, Pamela P W; Kwok, Janette S Y; Leung, Rock Y Y; Chiang, Alan K S; Ha, Shau-Yin; Cheuk, Daniel K L; Chan, Godfrey C F

2018-06-19

Relapsed/refractory NB carries a bleak outcome, warranting novel treatment options. HaploHSCT induces a graft-versus-NB effect via natural killer cell alloreactivity. Review of patients with relapsed/refractory NB who underwent haploHSCT with ex vivo T-cell depletion in our unit from 2013 through 2018. Ten patients were identified (male=5; median age at haploHSCT=6.45 y, range: 3.49-11.02 y). Indications were relapsed in 7 and refractoriness in 3; disease status at haploHSCT was CR in 2, PR in 6, and PD in 2. All patients received peripheral blood stem cell grafts after ex vivo T-cell depletion (CD3/CD19-depletion=1; TCR-αβ/CD19-depletion=4; CD3/CD45RA-depletion=4; and TCR-αβ/CD45RA-depletion=1). Conditioning regimens were fludarabine-based. Neutrophils engrafted on median D + 10 (range: D + 9 to +13), and platelets engrafted (≥20 × 10 9 /L) on median D + 8 (range: D + 5 to D + 14). Early T- and NK-cell recovery were evident. Of the 10 patients, acute rejection developed in 1 (who died of PD despite rescue HSCT), and 1 died of sepsis before engraftment; 8 experienced full donor-chimerism post-HSCT. Among the 8, 6 experienced CR, 1 died of PD, and 1 died of pulmonary hypertensive crisis before evaluation. At publication, 4 were in remission (2.8, 7.4, 28.5, and 58.9 months). No significant GvHD occurred. HaploHSCT with selective ex vivo T-cell depletion may be a safe and useful salvage strategy for relapsed/refractory NB. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Presentation and progression of childhood-onset inflammatory bowel disease in Northern Stockholm County.

PubMed

Malmborg, Petter; Grahnquist, Lena; Ideström, Maja; Lindholm, Johan; Befrits, Ragnar; Björk, Jan; Montgomery, Scott; Hildebrand, Hans

2015-05-01

Some studies have suggested that childhood-onset inflammatory bowel disease (IBD) is characterized by extensive intestinal involvement and rapid progression to complications. Here, we report the presentation and progression of patients diagnosed with IBD during childhood in a population-based cohort from northern Stockholm County. Medical records for all 280 patients diagnosed in the period 1990-2007 with childhood-onset IBD in northern Stockholm County were followed until 2011 (median follow-up time, 8.8 yr). Disease phenotypes were classified according to the Paris pediatric IBD classification. Among the 74 patients with ulcerative colitis, 72% presented with pancolitis. Among the 200 patients with Crohn's disease (CD), 75% presented with colitis. Complicated disease behavior was observed in 18% of patients with CD by end of follow-up. Extension of the disease territory was observed in 22% of patients with ulcerative colitis and 15% of patients with CD. The cumulative risk of intra-abdominal surgery after 10 years was 8% (95% confidence interval, 4%-20%) for ulcerative colitis and 22% (95% confidence interval, 15%-28%) for patients with CD. Nonmucosal healing at 1 year was associated with a complicated disease course in patients with CD (hazard ratio = 14.56; 95% confidence interval, 1.79-118.68; P = 0.01). Patients with childhood-onset IBD were characterized by extensive colitis that was relatively stable over time and associated with a relatively low risk of complications and abdominal surgery. Our findings confirm the more extensive disease location in pediatric IBD but did not identify the proposed dynamic and aggressive nature of the childhood-onset phenotype. The association of nonmucosal healing with a complicated disease course suggests that endoscopy should guide treatment intensity in childhood-onset CD.

Structural, optical and dielectric investigation of CdFe2O4 nanoparticles

NASA Astrophysics Data System (ADS)

Sagadevan, Suresh; Pal, Kaushik; Zaman Chowdhury, Zaira; Enamul Hoque, Md

2017-07-01

A simple thermal decomposition technique has been executed for the synthesis of cadmium ferrite (CdFe2O4) nanoparticles. With the help of x-ray diffraction; scanning electron microscopy, energy-dispersive x-ray spectroscopy (EDS) and Fourier transform infrared spectroscopy the prepared nanoparticles were identified. The crystal size of the average particles aggregated and was found approximately to be 10-14 nm by means of XRD studies. However, the results of high-resolution transmission electron microscopy (HR-TEM) investigation ensured distinguished nanoparticles, and also the polycrystalline nature of those nanoparticles was confirmed by selected area diffraction (SAED) patterns. The scanning electron microscopy (SEM) images explored a random distribution of grains within the sample. Thin film surface topology of roughness and surface current measurement were studied by atomic force microscopy (TP-AFM, C-AFM). Hence, from the ultraviolet-visible (UV) spectroscopic absorption illustrated significant optical properties. Moreover, the optical energy band gap (E g) of CdFe2O4 nanoparticle was determined to be 1.74 eV. By studying the variation of dielectric constant and dielectric loss with respect to frequency, the CdFe2O4 nanoparticles electrical properties were analyzed. Analysis in the real and imaginary part of impedance explained their frequency and temperature dependence of the CdFe2O4 nanoparticles. The traditional solution-phase organometallic approach provides an effective way to synthesize high quality hydrophobic semiconductor-CdFe2O4 nanoparticles. Our simple, cost-effective approach is quite general, which is applicable to other nanomaterials, and it utilizes the currently mature in Nano-chemistry. The nanocomposite assemblies’ exhibit strong anisotropic optical and electrical properties are open up new possibilities in remarkable applications for optoelectronics in the near future.

RTS,S/AS01E Malaria Vaccine Induces Memory and Polyfunctional T Cell Responses in a Pediatric African Phase III Trial.

PubMed

Moncunill, Gemma; De Rosa, Stephen C; Ayestaran, Aintzane; Nhabomba, Augusto J; Mpina, Maximillian; Cohen, Kristen W; Jairoce, Chenjerai; Rutishauser, Tobias; Campo, Joseph J; Harezlak, Jaroslaw; Sanz, Héctor; Díez-Padrisa, Núria; Williams, Nana Aba; Morris, Daryl; Aponte, John J; Valim, Clarissa; Daubenberger, Claudia; Dobaño, Carlota; McElrath, M Juliana

2017-01-01

Comprehensive assessment of cellular responses to the RTS,S/AS01E vaccine is needed to understand potential correlates and ultimately mechanisms of protection against malaria disease. Cellular responses recognizing the RTS,S/AS01E-containing circumsporozoite protein (CSP) and Hepatitis B surface antigen (HBsAg) were assessed before and 1 month after primary vaccination by intracellular cytokine staining and 16-color flow cytometry in 105 RTS,S/AS01-vaccinated and 74 rabies-vaccinated participants (controls) in a pediatric phase III trial in Africa. RTS,S/AS01E-vaccinated children had significantly higher frequencies of CSP- and HBsAg-specific CD4 + T cells producing IL-2, TNF-α, and CD40L and HBsAg-specific CD4 + T producing IFN-γ and IL-17 than baseline and the control group. Vaccine-induced responses were identified in both central and effector memory (EM) compartments. EM CD4 + T cells expressing IL-4 and IL-21 were detected recognizing both vaccine antigens. Consistently higher response rates to both antigens in RTS,S/AS01E-vaccinated than comparator-vaccinated children were observed. RTS,S/AS01E induced polyfunctional CSP- and HBsAg-specific CD4 + T cells, with a greater degree of polyfunctionality in HBsAg responses. In conclusion, RTS,S/AS01E vaccine induces T cells of higher functional heterogeneity and polyfunctionality than previously characterized. Responses detected in memory CD4 + T cell compartments may provide correlates of RTS,S/AS01-induced immunity and duration of protection in future correlates of immunity studies.

Systematic review with meta-analysis: the efficacy of probiotics in inflammatory bowel disease.

PubMed

Derwa, Y; Gracie, D J; Hamlin, P J; Ford, A C

2017-08-01

Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD). Evidence implicates disturbances of the gastrointestinal microbiota in their pathogenesis. To perform a systematic review and meta-analysis to examine the efficacy of probiotics in IBD. MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (until November 2016). Eligible randomised controlled trials (RCTs) recruited adults with UC or CD, and compared probiotics with 5-aminosalicylates (5-ASAs) or placebo. Dichotomous symptom data were pooled to obtain a relative risk (RR) of failure to achieve remission in active IBD, or RR of relapse of disease activity in quiescent IBD, with 95% confidence intervals (CIs). The search identified 12 253 citations. Twenty-two RCTs were eligible. There was no benefit of probiotics over placebo in inducing remission in active UC (RR of failure to achieve remission=0.86; 95% CI=0.68-1.08). However, when only trials of VSL#3 were considered there appeared to be a benefit (RR=0.74; 95% CI=0.63-0.87). Probiotics appeared equivalent to 5-ASAs in preventing UC relapse (RR=1.02; 95% CI=0.85-1.23). There was no benefit of probiotics in inducing remission of active CD, in preventing relapse of quiescent CD, or in preventing relapse of CD after surgically induced remission. VSL#3 may be effective in inducing remission in active UC. Probiotics may be as effective as 5-ASAs in preventing relapse of quiescent UC. The efficacy of probiotics in CD remains uncertain, and more evidence from RCTs is required before their utility is known. © 2017 John Wiley & Sons Ltd.

Correlation between CD4 count and intensity of Candida colonization in the oropharynx of HIV-infected/ AIDS patient.

PubMed

Bandar, Ivo Novita Sah; Widodo, Djoko; Djauzi, Samsuridjal; Muthalib, Abdul; Soegondo, Sidartawan; Wahyuningsih, Retno

2006-01-01

To know the correlation between CD4 count and intensity of Candida colonizations in the oropharynx of HIV-infected/AIDS patients, to get the prevalence of oropharyngeal candidiasis (OPC), and to know what kind of Candida species that causes oropharynx candidiasis of HIV-infected/AIDS patients. A cross-sectional study was conducted in HIV-infected/AIDS patients who came as outpatients and inpatients in Cipto Mangunkusumo Hospital. The patients were interviewed, physically examined, their CD4 counts were checked, and their mouth rinse samples were taken to be cultured. Candida species was identified in CHROMagar media, and data were processed. From September 2004 until January 2005, 60 HIV-infected/AIDS patients were included in this study. There were 86.7% males and 13.3% females. Majority of the patients were from 20-30 years age group (85%). The most frequent transmission was among drug users (75%) followed by sexual contact (18.3%). The median of CD4 counts was 100 cells/il, ranged from 2 to 842 cells/il. Proportion of the OPC was 63.3% (CI 95% = 51.1 - 75.5). From 59 Candida isolates in this study, 74.58% were C. albicans. Candida non C. albicans species that were found in this trial were C. krusei, C. parapsilosis and C. tropicalis. There was significant correlation between low CD4 counts and high intensity of Candida colonization on the oropharynx of the subjects (r = -0.756). There was strong negative correlation (r = -0.756) between CD4 count and intensity of Candida colonization in the oropharynx of HIV-infected/AIDS patients. Proportion of OPC in this study was 63.3%. The most frequent species found in the oropharynx of the subjects was C. albicans.

Cadmium effects on sperm morphology and semenogelin with relates to increased ROS in infertile smokers: An in vitro and in silico approach.

PubMed

Ranganathan, Parameswari; Rao, Kamini A; Sudan, Jesu Jaya; Balasundaram, Sridharan

2018-06-01

Smoking releases cadmium (Cd), the metal toxicant which causes an imbalance in reactive oxygen species level in seminal plasma. This imbalance is envisaged to impair the sperm DNA morphology and thereby result in male infertility. In order to correlate this association, we performed in vitro and in silico studies and evaluated the influence of reactive oxygen species imbalance on sperm morphology impairments due to smoking. The study included 76 infertile smokers, 72 infertile non-smokers, 68 fertile smokers and 74 fertile non-smokers (control). Semen samples were collected at regular intervals from all the subjects. Semen parameters were examined by computer assisted semen analysis, quantification of metal toxicant by atomic absorption spectrophotometer, assessment of antioxidants through enzymatic and non-enzymatic methods, diagnosis of reactive oxygen species by nitro blue tetrazolium method and Cd influence on sperm protein by in vitro and in silico methods. Our analysis revealed that the levels of cigarette toxicants in semen were high, accompanied by low levels of antioxidants in seminal plasma of infertile smoker subjects. In addition the investigation of Cd treated sperm cells through scanning electronic microscope showed the mid piece damage of spermatozoa. The dispersive X-ray analysis to identify the elemental composition further confirmed the presence of Cd. Finally, the in-silico analysis on semenogelin sequences revealed the D-H-D motif which represents a favourable binding site for Cd coordination. Our findings clearly indicated the influence of Cd on reactive oxygen species leading to impaired sperm morphology leading to male infertility. Copyright © 2018 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.

Interval Colorectal Cancers following Guaiac Fecal Occult Blood Testing in the Ontario ColonCancerCheck Program.

PubMed

Paszat, Lawrence; Sutradhar, Rinku; Tinmouth, Jill; Baxter, Nancy; Rabeneck, Linda

2016-01-01

Background. This work examines the occurrence of interval colorectal cancers (CRCs) in the Ontario ColonCancerCheck (CCC) program. We define interval CRC as CRC diagnosed within 2 years following normal guaiac fecal occult blood testing (gFOBT). Methods. Persons aged 50-74 who completed a baseline CCC gFOBT kit in 2008 and 2009, without a prior history of CRC, or recent colonoscopy, flexible sigmoidoscopy, or gFOBT, were identified. Rates of CRC following positive and normal results at baseline and subsequent gFOBT screens were computed and overall survival was compared between those following positive and normal results. Results. Interval CRC was diagnosed within 24 months following the baseline screen among 0.16% of normals and following the subsequent screen among 0.18% of normals. Interval cancers comprised 38.70% of CRC following the baseline screen and 50.86% following the subsequent screen. Adjusting for age and sex, the hazard ratio (HR) for death following interval cancer compared to CRC following positive result was 1.65 (1.32, 2.05) following the first screen and 1.71 (1.00, 2.91) following the second screen. Conclusion. Interval CRCs following gFOBT screening comprise a significant proportion of CRC diagnosed within 2 years after gFOBT testing and are associated with a higher risk of death.

The role of CD147 expression in prostate cancer: a systematic review and meta-analysis.

PubMed

Ye, Yun; Li, Su-Liang; Wang, Yao; Yao, Yang; Wang, Juan; Ma, Yue-Yun; Hao, Xiao-Ke

2016-01-01

There are a number of studies which show that expression of CD147 is increased significantly in prostate cancer (PCa). However, conflicting conclusions have also been reported by other researchers lately. In order to arrive at a clear conclusion, a meta-analysis of eligible studies was conducted. We searched PubMed, MEDLINE, Cochrane Library, and the China National Knowledge Infrastructure databases to identify all the published case-control studies on the relationship between the expression of CD147 and PCa until February 2016. In the end, a total of 930 patients in eight studies were included in the meta-analysis. CD147 expression in the PCa patients increased significantly (odds ratio [OR], 4.65; 95% confidence interval [CI], 3.52-6.14; Z=10.79; P<0.05), but there was obvious heterogeneity between studies (I (2)=92.9%, P<0.05). Subgroup analysis showed that positive expression of CD147 was associated with PCa among the Asian population (OR, 21.01; 95% CI, 12.88-34.28; Z=12.19; P<0.05). Furthermore, it was significantly related to TNM stage (OR, 0.24; 95% CI, 0.17-0.35; Z=7.74; P<0.05), Gleason score (OR, 0.41; 95% CI, 0.31-0.56; Z=5.62; P<0.05), differentiation grade (OR, 0.27; 95% CI, 0.13-0.56; Z=3.47; P<0.05), and pretreatment serum prostate-specific antigen level (OR, 0.07; 95% CI, 0.03-0.16; Z=6.47; P<0.05). Positive expression of CD147 was related to PCa, significant heterogeneity was not found between Asian studies, and the result became more significant. The positive expression of CD147 was significantly related to the clinicopathological characteristics of PCa. This suggests that CD147 plays an essential role in poor prognosis and recurrence prediction.

The role of CD147 expression in prostate cancer: a systematic review and meta-analysis

PubMed Central

Ye, Yun; Li, Su-Liang; Wang, Yao; Yao, Yang; Wang, Juan; Ma, Yue-Yun; Hao, Xiao-Ke

2016-01-01

Background There are a number of studies which show that expression of CD147 is increased significantly in prostate cancer (PCa). However, conflicting conclusions have also been reported by other researchers lately. In order to arrive at a clear conclusion, a meta-analysis of eligible studies was conducted. Materials and methods We searched PubMed, MEDLINE, Cochrane Library, and the China National Knowledge Infrastructure databases to identify all the published case–control studies on the relationship between the expression of CD147 and PCa until February 2016. In the end, a total of 930 patients in eight studies were included in the meta-analysis. Results CD147 expression in the PCa patients increased significantly (odds ratio [OR], 4.65; 95% confidence interval [CI], 3.52–6.14; Z=10.79; P<0.05), but there was obvious heterogeneity between studies (I2=92.9%, P<0.05). Subgroup analysis showed that positive expression of CD147 was associated with PCa among the Asian population (OR, 21.01; 95% CI, 12.88–34.28; Z=12.19; P<0.05). Furthermore, it was significantly related to TNM stage (OR, 0.24; 95% CI, 0.17–0.35; Z=7.74; P<0.05), Gleason score (OR, 0.41; 95% CI, 0.31–0.56; Z=5.62; P<0.05), differentiation grade (OR, 0.27; 95% CI, 0.13–0.56; Z=3.47; P<0.05), and pretreatment serum prostate-specific antigen level (OR, 0.07; 95% CI, 0.03–0.16; Z=6.47; P<0.05). Conclusion Positive expression of CD147 was related to PCa, significant heterogeneity was not found between Asian studies, and the result became more significant. The positive expression of CD147 was significantly related to the clinicopathological characteristics of PCa. This suggests that CD147 plays an essential role in poor prognosis and recurrence prediction. PMID:27536064

Discovering new PI3Kα inhibitors with a strategy of combining ligand-based and structure-based virtual screening

NASA Astrophysics Data System (ADS)

Yu, Miao; Gu, Qiong; Xu, Jun

2018-02-01

PI3Kα is a promising drug target for cancer chemotherapy. In this paper, we report a strategy of combing ligand-based and structure-based virtual screening to identify new PI3Kα inhibitors. First, naïve Bayesian (NB) learning models and a 3D-QSAR pharmacophore model were built based upon known PI3Kα inhibitors. Then, the SPECS library was screened by the best NB model. This resulted in virtual hits, which were validated by matching the structures against the pharmacophore models. The pharmacophore matched hits were then docked into PI3Kα crystal structures to form ligand-receptor complexes, which are further validated by the Glide-XP program to result in structural validated hits. The structural validated hits were examined by PI3Kα inhibitory assay. With this screening protocol, ten PI3Kα inhibitors with new scaffolds were discovered with IC50 values ranging 0.44-31.25 μM. The binding affinities for the most active compounds 33 and 74 were estimated through molecular dynamics simulations and MM-PBSA analyses.

Differences in clinical condition and genotype at time of diagnosis of cystic fibrosis by newborn screening or by symptoms.

PubMed

Vernooij-van Langen, A M M; Gerzon, F L G R; Loeber, J G; Dompeling, E; Dankert-Roelse, J E

2014-01-01

Early diagnosis through newborn screening (NBS) and early treatment of cystic fibrosis (CF) do lead to better prognosis. In the Netherlands, the median age for a clinical diagnosis is six months, and after newborn screening this is 30 days. It is unknown if being diagnosed at the age of six months or before two months leads to a clinically relevant difference of the clinical condition at the time of diagnosis. The aim of this study is to assess the differences in clinical parameters at diagnosis between children with CF identified by newborn screening (NBS) or by clinical diagnosis (CD) in the Netherlands. From July 1st, 2007 to January 1st, 2012 all newly diagnosed CF patients were reported to the Dutch Paediatric Surveillance Unit (DPSU). All paediatricians received a questionnaire to collect data on mutations and clinical condition at diagnosis. Non-classical CF was excluded from the analysis on clinical condition. 204 new CF diagnoses were reported to the DPSU, 33 were reported twice and three had no CF after further testing. 127 questionnaires were returned (76%); 85 children were diagnosed because of clinical symptoms, 40 after NBS and two because of a positive family history. The median age at diagnosis was 34 weeks for a clinical diagnosis and 3 weeks after NBS. Non-classical CF was more prevalent in the NBS group (6 clinical, 14 NBS), mostly F508del/R117H7T (12). Compared to the NBS group, significantly more patients in the CD group showed failure to thrive, respiratory symptoms, and hospitalizations. 62% of the CD group showed abnormal signs at physical examination compared to 4% of the NBS group. At the time of diagnosis infants detected after NBS are in a significantly better condition than after a clinical diagnosis. Growth retardation is already seen when after NBS the diagnosis is confirmed, but NBS leads to a diagnosis before respiratory symptoms have developed. Copyright © 2014 Elsevier Inc. All rights reserved.

CD200/BTLA deletions in pediatric precursor B-cell acute lymphoblastic leukemia treated according to the EORTC-CLG 58951 protocol

PubMed Central

Ghazavi, Farzaneh; Clappier, Emmanuelle; Lammens, Tim; Suciu, Stefan; Caye, Aurélie; Zegrari, Samira; Bakkus, Marleen; Grardel, Nathalie; Benoit, Yves; Bertrand, Yves; Minckes, Odile; Costa, Vitor; Ferster, Alina; Mazingue, Françoise; Plat, Geneviève; Plouvier, Emmanuel; Poirée, Marilyne; Uyttebroeck, Anne; van der Werff-ten Bosch, Jutte; Yakouben, Karima; Helsmoortel, Hetty; Meul, Magali; Van Roy, Nadine; Philippé, Jan; Speleman, Frank; Cavé, Hélène; Van Vlierberghe, Pieter; De Moerloose, Barbara

2015-01-01

DNA copy number analysis has been instrumental for the identification of genetic alterations in B-cell precursor acute lymphoblastic leukemia. Notably, some of these genetic defects have been associated with poor treatment outcome and might be relevant for future risk stratification. In this study, we characterized recurrent deletions of CD200 and BTLA genes, mediated by recombination-activating genes, and used breakpoint-specific polymerase chain reaction assay to screen a cohort of 1154 cases of B-cell precursor acute lymphoblastic leukemia uniformly treated according to the EORTC-CLG 58951 protocol. CD200/BTLA deletions were identified in 56 of the patients (4.8%) and were associated with an inferior 8-year event free survival in this treatment protocol [70.2% ± 1.2% for patients with deletions versus 83.5% ± 6.4% for non-deleted cases (hazard ratio 2.02; 95% confidence interval 1.23–3.32; P=0.005)]. Genetically, CD200/BTLA deletions were strongly associated with ETV6-RUNX1-positive leukemias (P<0.0001), but were also identified in patients who did not have any genetic abnormality that is currently used for risk stratification. Within the latter population of patients, the presence of CD200/BTLA deletions was associated with inferior event-free survival and overall survival. Moreover, the multivariate Cox model indicated that these deletions had independent prognostic impact on event-free survival when adjusting for conventional risk criteria. All together, these findings further underscore the rationale for copy number profiling as an important tool for risk stratification in human B-cell precursor acute lymphoblastic leukemia. This trial was registered at www.ClinicalTrials.gov as #NCT00003728. PMID:26137961

CD200/BTLA deletions in pediatric precursor B-cell acute lymphoblastic leukemia treated according to the EORTC-CLG 58951 protocol.

PubMed

Ghazavi, Farzaneh; Clappier, Emmanuelle; Lammens, Tim; Suciu, Stefan; Caye, Aurélie; Zegrari, Samira; Bakkus, Marleen; Grardel, Nathalie; Benoit, Yves; Bertrand, Yves; Minckes, Odile; Costa, Vitor; Ferster, Alina; Mazingue, Françoise; Plat, Geneviève; Plouvier, Emmanuel; Poirée, Marilyne; Uyttebroeck, Anne; van der Werff-Ten Bosch, Jutte; Yakouben, Karima; Helsmoortel, Hetty; Meul, Magali; Van Roy, Nadine; Philippé, Jan; Speleman, Frank; Cavé, Hélène; Van Vlierberghe, Pieter; De Moerloose, Barbara

2015-10-01

DNA copy number analysis has been instrumental for the identification of genetic alterations in B-cell precursor acute lymphoblastic leukemia. Notably, some of these genetic defects have been associated with poor treatment outcome and might be relevant for future risk stratification. In this study, we characterized recurrent deletions of CD200 and BTLA genes, mediated by recombination-activating genes, and used breakpoint-specific polymerase chain reaction assay to screen a cohort of 1154 cases of B-cell precursor acute lymphoblastic leukemia uniformly treated according to the EORTC-CLG 58951 protocol. CD200/BTLA deletions were identified in 56 of the patients (4.8%) and were associated with an inferior 8-year event free survival in this treatment protocol [70.2% ± 1.2% for patients with deletions versus 83.5% ± 6.4% for non-deleted cases (hazard ratio 2.02; 95% confidence interval 1.23-3.32; P=0.005)]. Genetically, CD200/BTLA deletions were strongly associated with ETV6-RUNX1-positive leukemias (P<0.0001), but were also identified in patients who did not have any genetic abnormality that is currently used for risk stratification. Within the latter population of patients, the presence of CD200/BTLA deletions was associated with inferior event-free survival and overall survival. Moreover, the multivariate Cox model indicated that these deletions had independent prognostic impact on event-free survival when adjusting for conventional risk criteria. All together, these findings further underscore the rationale for copy number profiling as an important tool for risk stratification in human B-cell precursor acute lymphoblastic leukemia. This trial was registered at www.ClinicalTrials.gov as #NCT00003728. Copyright© Ferrata Storti Foundation.

Dose–Volume Modeling of Brachial Plexus-Associated Neuropathy After Radiation Therapy for Head-and-Neck Cancer: Findings From a Prospective Screening Protocol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Allen M., E-mail: amchen@mednet.ucla.edu; Wang, Pin-Chieh; Daly, Megan E.

2014-03-15

Purpose: Data from a prospective screening protocol administered for patients previously irradiated for head-and-neck cancer was analyzed to identify dosimetric predictors of brachial plexus-associated neuropathy. Methods and Materials: Three hundred fifty-two patients who had previously completed radiation therapy for squamous cell carcinoma of the head and neck were prospectively screened from August 2007 to April 2013 using a standardized self-administered instrument for symptoms of neuropathy thought to be related to brachial plexus injury. All patients were disease-free at the time of screening. The median time from radiation therapy was 40 months (range, 6-111 months). A total of 177 patients (50%)more » underwent neck dissection. Two hundred twenty-one patients (63%) received concurrent chemotherapy. Results: Fifty-one patients (14%) reported brachial plexus-related neuropathic symptoms with the most common being ipsilateral pain (50%), numbness/tingling (40%), and motor weakness and/or muscle atrophy (25%). The 3- and 5-year estimates of freedom from brachial plexus-associated neuropathy were 86% and 81%, respectively. Clinical/pathological N3 disease (P<.001) and maximum radiation dose to the ipsilateral brachial plexus (P=.01) were significantly associated with neuropathic symptoms. Cox regression analysis revealed significant dose–volume effects for brachial plexus-associated neuropathy. The volume of the ipsilateral brachial plexus receiving >70 Gy (V70) predicted for symptoms, with the incidence increasing with V70 >10% (P<.001). A correlation was also observed for the volume receiving >74 Gy (V74) among patients treated without neck dissection, with a cutoff of 4% predictive of symptoms (P=.038). Conclusions: Dose–volume guidelines were developed for radiation planning that may limit brachial plexus-related neuropathies.« less

Measuring Disability in Population Based Surveys: The Interrelationship between Clinical Impairments and Reported Functional Limitations in Cameroon and India

PubMed Central

2016-01-01

Purpose To investigate the relationship between two distinct measures of disability: self-reported functional limitations and objectively-screened clinical impairments. Methods We undertook an all age population-based survey of disability in two areas: North-West Cameroon (August/October 2013) and Telangana State, India (Feb/April 2014). Participants were selected for inclusion via two-stage cluster randomised sampling (probability proportionate to size cluster selection and compact segment sampling within clusters). Disability was defined as the presence of self-reported functional limitations across eight domains, or presence of moderate or greater clinical impairments. Clinical impairment screening comprised of visual acuity testing for vision impairment, pure tone audiometry for hearing impairment, musculoskeletal functioning assessment for musculoskeletal impairment, reported seizure history for epilepsy and reported symptoms of clinical depression (depression adults only). Information was collected using structured questionnaires, observations and examinations. Results Self-reported disability prevalence was 5.9% (95% CI 4.7–7.4) and 7.5% (5.9–9.4) in Cameroon and India respectively. The prevalence of moderate or greater clinical impairments in the same populations were 8.4% (7.5–9.4) in Cameroon and 10.5% (9.4–11.7) in India. Overall disability prevalence (self-report and/or screened positive to a moderate or greater clinical impairment) was 10.5% in Cameroon and 12.2% in India, with limited overlap between the sub-populations identified using the two types of tools. 33% of participants in Cameroon identified to have a disability, and 45% in India, both reported functional limitations and screened positive to objectively-screened impairments, whilst the remainder were identified via one or other tool only. A large proportion of people with moderate or severe clinical impairments did not self-report functional difficulties despite reporting participation restrictions. Conclusion Tools to assess reported functional limitation alone are insufficient to identify all persons with participation restrictions and moderate or severe clinical impairments. A self-reported functional limitation tool followed by clinical screening of all those who report any level of difficulty would identify 94% of people with disabilities in Cameroon and 95% in India, meeting the study criteria. PMID:27741320

Archive of mass spectral data files on recordable CD-ROMs and creation and maintenance of a searchable computerized database.

PubMed

Amick, G D

1999-01-01

A database containing names of mass spectral data files generated in a forensic toxicology laboratory and two Microsoft Visual Basic programs to maintain and search this database is described. The data files (approximately 0.5 KB/each) were collected from six mass spectrometers during routine casework. Data files were archived on 650 MB (74 min) recordable CD-ROMs. Each recordable CD-ROM was given a unique name, and its list of data file names was placed into the database. The present manuscript describes the use of search and maintenance programs for searching and routine upkeep of the database and creation of CD-ROMs for archiving of data files.

CD68 acts as a major gateway for malaria sporozoite liver infection.

PubMed

Cha, Sung-Jae; Park, Kiwon; Srinivasan, Prakash; Schindler, Christian W; van Rooijen, Nico; Stins, Monique; Jacobs-Lorena, Marcelo

2015-08-24

After being delivered by the bite from an infected mosquito, Plasmodium sporozoites enter the blood circulation and infect the liver. Previous evidence suggests that Kupffer cells, a macrophage-like component of the liver blood vessel lining, are traversed by sporozoites to initiate liver invasion. However, the molecular determinants of sporozoite-Kupffer cell interactions are unknown. Understanding the molecular basis for this specific recognition may lead to novel therapeutic strategies to control malaria. Using a phage display library screen, we identified a peptide, P39, that strongly binds to the Kupffer cell surface and, importantly, inhibits sporozoite Kupffer cell entry. Furthermore, we determined that P39 binds to CD68, a putative receptor for sporozoite invasion of Kupffer cells that acts as a gateway for malaria infection of the liver. © 2015 Cha et al.

SIRPA is a specific cell-surface marker for isolating cardiomyocytes derived from human pluripotent stem cells.

PubMed

Dubois, Nicole C; Craft, April M; Sharma, Parveen; Elliott, David A; Stanley, Edouard G; Elefanty, Andrew G; Gramolini, Anthony; Keller, Gordon

2011-10-23

To identify cell-surface markers specific to human cardiomyocytes, we screened cardiovascular cell populations derived from human embryonic stem cells (hESCs) against a panel of 370 known CD antibodies. This screen identified the signal-regulatory protein alpha (SIRPA) as a marker expressed specifically on cardiomyocytes derived from hESCs and human induced pluripotent stem cells (hiPSCs), and PECAM, THY1, PDGFRB and ITGA1 as markers of the nonmyocyte population. Cell sorting with an antibody against SIRPA allowed for the enrichment of cardiac precursors and cardiomyocytes from hESC/hiPSC differentiation cultures, yielding populations of up to 98% cardiac troponin T-positive cells. When plated in culture, SIRPA-positive cells were contracting and could be maintained over extended periods of time. These findings provide a simple method for isolating populations of cardiomyocytes from human pluripotent stem cell cultures, and thereby establish a readily adaptable technology for generating large numbers of enriched cardiomyocytes for therapeutic applications.

Glandular Lesions of the Cervix in Clinical Practice: A Cytology, Histology, and Human Papillomavirus Correlation Study From 2 Institutions.

PubMed

Miller, Ross A; Mody, Dina R; Tams, Kimberlee C; Thrall, Michael J

2015-11-01

The Papanicolaou (Pap) test has indisputably decreased cervical cancer mortality, as rates have declined by up to 80% in the United States since its implementation. However, the Pap test is considered less sensitive for detecting glandular lesions than for detecting those of squamous origin. Some studies have even suggested an increasing incidence of cervical adenocarcinoma, which may be a consequence of a relatively reduced ability to detect glandular lesions with cervical cancer screening techniques. To evaluate the detection rate of glandular lesions with screening techniques currently used for cervical cancer screening and to provide insight as to which techniques are most efficacious in our study population. We retrospectively reviewed any available cytology, human papillomavirus (HPV), and histologic malignancy data in patients diagnosed with adenocarcinoma in situ and adenocarcinoma from 2 geographically and socioeconomically disparate hospital systems. Identified patients having had a negative/unsatisfactory Pap test within 5 years of adenocarcinoma in situ or adenocarcinoma tissue diagnosis were considered Pap test screening failures. Patients with negative HPV tests on cytology samples were considered HPV screening failures. One hundred thirty cases were identified (age range, 22-93 years); 39 (30%) had no Pap history in our files. Eight of 91 remaining cases (8.8%) were screening failures. The detected sensitivity for identifying adenocarcinoma in situ/adenocarcinoma in this study was 91.2% by cytology alone and 92.3% when incorporating HPV testing. The most common cytologic diagnosis was atypical glandular cells (25 cases), and those diagnosed with adenocarcinoma were 7.4 years older than those diagnosed with adenocarcinoma in situ (50.3 versus 42.9 years). Nine of 24 HPV-tested cases (37.5%) were called atypical squamous cell of undetermined significance on cytology. Our results highlight the importance of combined Pap and HPV cotesting. Although the number of cases identified is relatively small, our data suggest screening for squamous lesions facilitates the recognition of glandular lesions in the cervix. Additionally, increased use of combined Pap and HPV cotesting may decrease detection failure rates with regard to glandular lesions.

A catalytic chemodosimetric approach for detection of nanomolar cyanide ions in water, blood serum and live cell imaging.

PubMed

Kumar, Rahul; Sandhu, Sana; Hundal, Geeta; Singh, Prabhpreet; Walia, Amandeep; Vanita, Vanita; Kumar, Subodh

2015-12-07

Naphthimidazolium based monocationic chemodosimeters CD-1 and CD-2 undergo cyanide mediated catalytic transformation in the presence of cyanide ions (0.01% to 1% of CD-1/CD-2 concentrations) with a turnover number from 70 to 360. These chemodosimeters can detect as low as 0.5 nM and 1 nM cyanide ions under nearly physiological conditions (HEPES buffer-DMSO (5%), pH 7.4). The structures of CD-1 and its cyanide induced hydrolyzed product 4 have been confirmed by single crystal X-ray crystallography. CD-1 can also be used for the determination of 2 nM cyanide in the presence of blood serum. CD-1 and CD-2 also find applications in live cell imaging of 10 nM cyanide ions in rat brain C6 glioma cells. To the best of our knowledge, this is the first report where high sensitivity towards cyanide ions has been achieved through catalytic hydrolysis of the fluorescent chemodosimeter.

Cervical Cancer Screening in Cameroon: Interobserver Agreement on the Interpretation of Digital Cervicography Results.

PubMed

Manga, Simon; Parham, Groesbeck; Benjamin, Nkoum; Nulah, Kathleen; Sheldon, Lisa Kennedy; Welty, Edith; Ogembo, Javier Gordon; Bradford, Leslie; Sando, Zacharie; Shields, Ray; Welty, Thomas

2015-10-01

The World Health Organization recommends visual inspection with acetic acid (VIA) for cervical cancer screening in resource-limited settings. In Cameroon, we use digital cervicography (DC) to capture images of the cervix after VIA. This study evaluated interobserver agreement of DC results, compared DC with histopathologic results, and examined interobserver agreement among screening methods. Three observers, blinded to each other's interpretations, evaluated 540 DC photographs as follows: (1) negative/positive for acetowhite lesions or cancer and (2) assigned a presumptive diagnosis of histopathologic lesion grade in the 91 cases that had a histopathologic diagnosis. Observer A was the actual screening nurse; B, a reproductive health nurse; C, a gynecologic oncologist; and D, the histopathologic diagnosis. We compared inter-rater agreement of DC impressions among observers A, B, and C, and with D, with Cohen kappas. For interpretations of DC, (negative/positive) strengths of agreement of paired observers were the following: A/B, moderate [K, 0.54; 95% confidence interval (CI), 0.47-0.61], A/C, fair (K, 0.37; 95% CI, 0.29-0.44), and B/C, moderate (K, 0.45; 95% CI, 0.37-0.53). For presumptive pathologic grading, strengths of agreement for weighted Ks were as follows: A/B, moderate (K, 0.42; 95% CI, 0.28-0.56); A/C, fair (K, 0.33; 95% CI, 0.20-0.46); B/C, fair (K, 0.54; 95% CI, 0.40-0.67); A/D, moderate (K, 0.59; 95% CI, 0.45-0.74); B/D, moderate (K, 0.58; 95% CI, 0.46-0.70); and C/D, moderate (K, 0.50; 95% CI, 0.37-0.63). Interobserver agreement of DC interpretations was mostly moderate among the 3 observers, between them and histopathology, and comparable to that of other visual-based screening methods, i.e., VIA, cytology, or colposcopy.

The influence of CdS intermediate layer on CdSe/CdS co-sensitized free-standing TiO2 nanotube solar cells

NASA Astrophysics Data System (ADS)

Ren, Xuefeng; Yu, Libo; Li, Zhen; Song, Hai; Wang, Qingyun

2018-01-01

We build CdSe quantum dots (QDs) sensitized TiO2 NT solar cells (CdSe/TiO2 solar cells) by successive ionic layer adsorption reaction (SILAR) method on free-standing translucent TiO2 nanotube (NT) film. The best power conversion efficiency (PCE) 0.74% is obtained with CdSe/TiO2 NT solar cells, however, it is very low. Hence, we introduced the CdS QDs layer located between CdSe QDs and TiO2 NT to achieve an enhanced photovoltaic performance. The J-V test results indicated that the insert of CdS intermediate layer yield a significant improvement of PCE to 2.52%. Combining experimental and theoretical analysis, we find that the effects caused by a translucent TiO2 nanotube film, a better lattices match between CdS and TiO2, and a new formed stepwise band edges structure not only improve the light harvesting efficiency but also increase the driving force of electrons, leading to the improvement of photovoltaic performance.

40 CFR 413.14 - Pretreatment standards for existing sources.

Code of Federal Regulations, 2011 CFR

2011-07-01

... exceed CN, T 1.9 1.0 Cu 4.5 2.7 Ni 4.1 2.6 Cr 7.0 4.0 Zn 4.2 2.6 Pb .6 .4 Cd 1.2 .7 Total metals 10.5 6.8... monitoring days shall not exceed CN, T 74 39 Cu 176 105 Ni 160 100 Cr 273 156 Zn 164 102 Pb 23 16 Cd 47 29...

40 CFR 413.14 - Pretreatment standards for existing sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... exceed CN, T 1.9 1.0 Cu 4.5 2.7 Ni 4.1 2.6 Cr 7.0 4.0 Zn 4.2 2.6 Pb .6 .4 Cd 1.2 .7 Total metals 10.5 6.8... monitoring days shall not exceed CN, T 74 39 Cu 176 105 Ni 160 100 Cr 273 156 Zn 164 102 Pb 23 16 Cd 47 29...

Antibiotics associated with increased risk of new-onset Crohn's disease but not ulcerative colitis: a meta-analysis.

PubMed

Ungaro, Ryan; Bernstein, Charles N; Gearry, Richard; Hviid, Anders; Kolho, Kaija-Leena; Kronman, Matthew P; Shaw, Souradet; Van Kruiningen, Herbert; Colombel, Jean-Frédéric; Atreja, Ashish

2014-11-01

The objective of this study was to perform a meta-analysis investigating antibiotic exposure as a risk factor for developing inflammatory bowel disease (IBD). A literature search using Medline, Embase, and Cochrane databases was performed to identify studies providing data on the association between antibiotic use and newly diagnosed IBD. Included studies reported Crohn's disease (CD), ulcerative colitis (UC), or a composite of both (IBD) as the primary outcome and evaluated antibiotic exposure before being diagnosed with IBD. A random-effects meta-analysis was conducted to determine overall pooled estimates and 95% confidence intervals (CIs). A total of 11 observational studies (8 case-control and 3 cohort) including 7,208 patients diagnosed with IBD were analyzed. The pooled odds ratio (OR) for IBD among patients exposed to any antibiotic was 1.57 (95% CI 1.27-1.94). Antibiotic exposure was significantly associated with CD (OR 1.74, 95% CI 1.35-2.23) but was not significant for UC (OR 1.08, 95% CI 0.91-1.27). Exposure to antibiotics most markedly increased the risk of CD in children (OR 2.75, 95% CI 1.72-4.38). All antibiotics were associated with IBD, with the exception of penicillin. Exposure to metronidazole (OR 5.01, 95% CI 1.65-15.25) or fluoroquinolones (OR 1.79, 95% CI 1.03-3.12) was most strongly associated with new-onset IBD. Exposure to antibiotics appears to increase the odds of being newly diagnosed with CD but not UC. This risk is most marked in children diagnosed with CD.

Recognition of Naegleriae ameba surface protein epitopes by anti-human CD45 antibodies.

PubMed

Ravine, Terrence J; Polski, Jacek M; Jenkins, James

2010-04-01

Phagocytosis is a highly conserved mechanism exhibited by both free-living amebas and mammalian blood cells. Similarities demonstrated by either cell type during engulfment of the same bacterial species may imply analogous surface proteins involved in receptor-mediated endocytosis. The increased availability of anti-human leukocyte antibodies or clusters of differentiation (CD) markers used in conjunction with flow cytometric (FCM) and/or immunohistochemical (IHC) analysis provides investigators with a relatively easy method to screen different cell populations for comparable plasma membrane proteins. In this study, we incubated Naegleria and Acanthamoeba amebas with several directly conjugated anti-human leukocyte monoclonal antibodies (mAb) for similarly recognized amebic epitopes. CD marker selection was based upon a recognized role of each mAb in phagocyte activation and/or uptake of bacteria. These included CD14, CD45, and CD206. In FCM, only one CD45 antibody demonstrated strong reactivity with both Naegleria fowleri and Naegleria gruberi that was not expressed in similarly tested Acanthamoeba species. Additional testing of N. gruberi by IHC demonstrated reactivity to a different CD45 antibody. Our results suggest a possible utility of using anti-human leukocyte antibodies to screen amebic cells for similarly expressed protein epitopes. In doing so, several important items must be considered when selecting potential mAbs for testing to increase the probability of a positive result.

Cryptococcal antigen screening by lay cadres using a rapid test at the point of care: A feasibility study in rural Lesotho.

PubMed

Rick, Fernanda; Niyibizi, Aline Aurore; Shroufi, Amir; Onami, Kazumi; Steele, Sarah-Jane; Kuleile, Malehlohonolo; Muleya, Innocent; Chiller, Tom; Walker, Tiffany; Van Cutsem, Gilles

2017-01-01

Cryptococcal meningitis is one of the leading causes of death among people with HIV in Africa, primarily due to delayed presentation, poor availability and high cost of treatment. Routine cryptococcal antigen (CrAg) screening of patients with a CD4 count less than 100 cells/mm3, followed by pre-emptive therapy if positive, might reduce mortality in high prevalence settings. Using the cryptococcal antigen (CrAg) lateral flow assay (LFA), screening is possible at the point of care (POC). However, critical shortages of health staff may limit adoption. This study investigates the feasibility of lay counsellors conducting CrAg LFA screening in rural primary care clinics in Lesotho. From May 2014 to June 2015, individuals who tested positive for HIV were tested for CD4 count and those with CD4 <100 cells/mm3 were screened with CrAg LFA. All tests were performed by lay counsellors. CrAg-positive asymptomatic patients received fluconazole, while symptomatic patients were referred to hospital. Lay counsellors were trained and supervised by a laboratory technician and counsellor activity supervisor. Additionally, nurses and doctors were trained on CrAg screening and appropriate treatment. During the study period, 1,388 people were newly diagnosed with HIV, of whom 129 (9%) presented with a CD4 count <100 cells/mm3. Of these, 128 (99%) were screened with CrAg LFA and 14/128 (11%) tested positive. Twelve of the 14 (86%) were asymptomatic, and received outpatient fluconazole. All commenced ART with a median time to initiation of 15.5 days [IQR: 14-22]. Of the asymptomatic patients, nine (75%) remained asymptomatic after a median time of 5 months [IQR; 3-6] of follow up. One (8%) became co-infected with tuberculosis and died and two were transferred out. The two patients with symptomatic cryptococcal meningitis (CM) were referred to hospital, where they later died. CrAg LFA screening by lay counsellors followed by pre-emptive fluconazole treatment for asymptomatic cases, or referral to hospital for symptomatic cases, proved feasible. However, regular follow-up to ensure proper management of cryptococcal disease was needed. These early results support the wider use of CrAg LFA screening in remote primary care settings where upper cadres of healthcare staff may be in short supply.

Cryptococcal antigen screening by lay cadres using a rapid test at the point of care: A feasibility study in rural Lesotho

PubMed Central

Rick, Fernanda; Niyibizi, Aline Aurore; Shroufi, Amir; Onami, Kazumi; Steele, Sarah-Jane; Kuleile, Malehlohonolo; Muleya, Innocent; Chiller, Tom; Walker, Tiffany; Van Cutsem, Gilles

2017-01-01

Introduction Cryptococcal meningitis is one of the leading causes of death among people with HIV in Africa, primarily due to delayed presentation, poor availability and high cost of treatment. Routine cryptococcal antigen (CrAg) screening of patients with a CD4 count less than 100 cells/mm3, followed by pre-emptive therapy if positive, might reduce mortality in high prevalence settings. Using the cryptococcal antigen (CrAg) lateral flow assay (LFA), screening is possible at the point of care (POC). However, critical shortages of health staff may limit adoption. This study investigates the feasibility of lay counsellors conducting CrAg LFA screening in rural primary care clinics in Lesotho. Methods From May 2014 to June 2015, individuals who tested positive for HIV were tested for CD4 count and those with CD4 <100 cells/mm3 were screened with CrAg LFA. All tests were performed by lay counsellors. CrAg-positive asymptomatic patients received fluconazole, while symptomatic patients were referred to hospital. Lay counsellors were trained and supervised by a laboratory technician and counsellor activity supervisor. Additionally, nurses and doctors were trained on CrAg screening and appropriate treatment. Results During the study period, 1,388 people were newly diagnosed with HIV, of whom 129 (9%) presented with a CD4 count <100 cells/mm3. Of these, 128 (99%) were screened with CrAg LFA and 14/128 (11%) tested positive. Twelve of the 14 (86%) were asymptomatic, and received outpatient fluconazole. All commenced ART with a median time to initiation of 15.5 days [IQR: 14–22]. Of the asymptomatic patients, nine (75%) remained asymptomatic after a median time of 5 months [IQR; 3–6] of follow up. One (8%) became co-infected with tuberculosis and died and two were transferred out. The two patients with symptomatic cryptococcal meningitis (CM) were referred to hospital, where they later died. Conclusions CrAg LFA screening by lay counsellors followed by pre-emptive fluconazole treatment for asymptomatic cases, or referral to hospital for symptomatic cases, proved feasible. However, regular follow-up to ensure proper management of cryptococcal disease was needed. These early results support the wider use of CrAg LFA screening in remote primary care settings where upper cadres of healthcare staff may be in short supply. PMID:28877182

Trends in Cancer Screening Rates among Korean Men and Women: Results of the Korean National Cancer Screening Survey, 2004-2013.

PubMed

Suh, Mina; Choi, Kui Son; Park, Boyoung; Lee, Yoon Young; Jun, Jae Kwan; Lee, Duk-Hyoung; Kim, Yeol

2016-01-01

The Korean National Cancer Screening Survey (KNCSS), a nationwide cross-sectional survey, has been conducted annually since 2004. The current study was conducted to report on the trends in screening rates among Korean men and women, and to evaluate policies regarding cancer screening programs implemented to reduce the burden of cancer. The current study used KNCSS data. The eligible study population included men aged 40-74 years and women aged 30-74 years with no cancer history. The lifetime screening rate, screening rate with recommendation, and changes in annual rates were calculated for five major cancers (i.e., stomach, liver, colorectal, breast, and cervix uteri). The screening rates with recommendation increased by 4.2% (95% confidence interval [CI], 3.7% to 4.8%) annually for stomach cancer, 1.2% (95% CI, 0.1% to 2.4%) for liver cancer, 3.0% (95% CI, 1.8% to 4.1%) for colorectal cancer, 3.7% (95% CI, 2.7% to 4.8%) for breast cancer, and 1.3% (95% CI, 0.8% to 1.8%) for cervical cancer. In 2013, the screening rates with recommendation for stomach, liver, colorectal, breast, and cervical cancers were 73.6%, 33.6%, 55.6%, 59.7%, and 67.0%, respectively. Both the lifetime screening rates and screening rates with recommendation for the five above-mentioned cancers increased annually from 2004 to 2013.

Synthetic Lethality Reveals Mechanisms of Mycobacterium tuberculosis Resistance to β-Lactams

PubMed Central

Lun, Shichun; Miranda, David; Kubler, Andre; Guo, Haidan; Maiga, Mariama C.; Winglee, Kathryn; Pelly, Shaaretha

2014-01-01

ABSTRACT Most β-lactam antibiotics are ineffective against Mycobacterium tuberculosis due to the microbe’s innate resistance. The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains has prompted interest to repurpose this class of drugs. To identify the genetic determinants of innate β-lactam resistance, we carried out a synthetic lethality screen on a transposon mutant library for susceptibility to imipenem, a carbapenem β-lactam antibiotic. Mutations in 74 unique genes demonstrated synthetic lethality. The majority of mutations were in genes associated with cell wall biosynthesis. A second quantitative real-time PCR (qPCR)-based synthetic lethality screen of randomly selected mutants confirmed the role of cell wall biosynthesis in β-lactam resistance. The global transcriptional response of the bacterium to β-lactams was investigated, and changes in levels of expression of cell wall biosynthetic genes were identified. Finally, we validated these screens in vivo using the MT1616 transposon mutant, which lacks a functional acyl-transferase gene. Mice infected with the mutant responded to β-lactam treatment with a 100-fold decrease in bacillary lung burden over 4 weeks, while the numbers of organisms in the lungs of mice infected with wild-type bacilli proliferated. These findings reveal a road map of genes required for β-lactam resistance and validate synthetic lethality screening as a promising tool for repurposing existing classes of licensed, safe, well-characterized antimicrobials against tuberculosis. PMID:25227469

Explicating perceived barriers to mammography for the USCREEN project: concerns about breast implants, faith violations, and perceived recommendations.

PubMed

Jensen, Jakob D; Ratcliff, Chelsea; Weaver, Jeremy; Krakow, Melinda M; Payton, William; Loewen, Sherrie

2015-11-01

In line with the health belief model, perceived barriers have proven to be a key determinant of intentions to screen for breast cancer. The standard measure of perceived barriers to breast cancer screening is an 11 item scale developed by Victoria Champion. However, perceived barriers emerge and change over time, and Champion's perceived barriers scale was last revised in 1999. Moreover, the original scale did not address barriers which may be more pronounced in particular populations, such as congruity of action with faith. As part of the Utah Screening Project, a sample of women 40-74 (N = 341, Mage = 51.19, SD = 8.11) were recruited from four Utah counties in 2014 to complete a survey. The results revealed that the four new perceived barrier items explained 6.4 % of intentions to screen, above and beyond other predictors. In addition to barriers identified in past research, the current study identified several novel barriers including (a) concerns about negative effects to breast implants, (b) perceived conflict with faith, and the (c) perception that mammography is no longer recommended. The new perceived barriers items are useful to researchers interested in exploring barriers not addressed by the original instrument. The barriers also suggest potential belief-based targets and channels (e.g., plastic surgery clinics, faith-based interventions) for delivering mammography interventions.

Early Reticulocytosis and Anemia Are Associated with Abnormal and Conditional Transcranial Doppler Velocities in Children with Sickle Cell Anemia.

PubMed

Meier, Emily Riehm; Fasano, Ross M; Estrada, Monica; He, Jianping; Luban, Naomi L C; McCarter, Robert

2016-02-01

To improve prediction of sickle cell anemia severity at an early age, we evaluated whether absolute reticulocyte count (ARC) or hemoglobin (Hb) levels during early infancy (2-6 months of age) in patients with sickle cell anemia predict the risk of later developing an abnormal (abTCD) or conditional (cdTCD) Transcranial Doppler (TCD). We used chart review to identify 121 consecutive patients who underwent TCD screening and had steady state ARC and Hb levels recorded between 2 and 6 months of age. Cox regression analysis was used to determine the relationship between ARC, Hb levels, and risk of developing cdTCD/abTCD over time. Mean ARC in early infancy was highest and mean Hb lowest in those children with abTCDs and cdTCDs. Cox regression analysis revealed that those subjects with an ARC ≥200 K/μL in early infancy had nearly 3 times the risk of having an abTCD/cdTCD than the group with an ARC <200 K/μL, and patients with a Hb <8.5 g/dL had 2.7 times the risk of having an abTCD/cdTCD. These data suggest that both elevated ARC and low baseline Hb during early infancy are associated with an increased risk of developing a cdTCD or abTCD later in childhood. Copyright © 2016 Elsevier Inc. All rights reserved.

Community-Based Validation of the Social Phobia Screener (SOPHS).

PubMed

Batterham, Philip J; Mackinnon, Andrew J; Christensen, Helen

2017-10-01

There is a need for brief, accurate screening scales for social anxiety disorder to enable better identification of the disorder in research and clinical settings. A five-item social anxiety screener, the Social Phobia Screener (SOPHS), was developed to address this need. The screener was validated in two samples: (a) 12,292 Australian young adults screened for a clinical trial, including 1,687 participants who completed a phone-based clinical interview and (b) 4,214 population-based Australian adults recruited online. The SOPHS (78% sensitivity, 72% specificity) was found to have comparable screening performance to the Social Phobia Inventory (77% sensitivity, 71% specificity) and Mini-Social Phobia Inventory (74% sensitivity, 73% specificity) relative to clinical criteria in the trial sample. In the population-based sample, the SOPHS was also accurate (95% sensitivity, 73% specificity) in identifying Diagnostic and Statistical Manual of Mental Disorders-Fifth edition social anxiety disorder. The SOPHS is a valid and reliable screener for social anxiety that is freely available for use in research and clinical settings.

Preferences for Mental Health Screening Among Pregnant Women: A Cross-Sectional Study.

PubMed

Kingston, Dawn E; Biringer, Anne; McDonald, Sheila W; Heaman, Maureen I; Lasiuk, Gerri C; Hegadoren, Kathy M; McDonald, Sarah D; Veldhuyzen van Zanten, Sander; Sword, Wendy; Kingston, Joshua J; Jarema, Karly M; Vermeyden, Lydia; Austin, Marie-Paule

2015-10-01

The process of mental health screening can influence disclosure, uptake of referral, and treatment; however, no studies have explored pregnant women's views of methods of mental health screening. The objectives of this study are to determine pregnant women's comfort and preferences regarding mental health screening. Pregnant women were recruited (May-December 2013) for this cross-sectional descriptive survey from prenatal classes and maternity clinics in Alberta, Canada, if they were aged >16 years and spoke/read English. Descriptive statistics summarized acceptability of screening, and multivariable logistic regression identified factors associated with women's comfort with screening methods. Analysis was conducted in January-December 2014. The participation rate was 92% (N=460/500). Overall, 97.6% of women reported that they were very (74.8%) or somewhat (22.8%) comfortable with mental health screening in pregnancy. Women were most comfortable with completing paper- (>90%) and computer-based (>82%) screening in a clinic or at home, with fewest reporting comfort with telephone-based screening (62%). The majority of women were very/somewhat comfortable with provider-initiated (97.4%) versus self-initiated (68.7%) approaches. Women's ability to be honest with their provider about emotional health was most strongly associated with comfort with each method of screening. The majority of pregnant women viewed prenatal mental health screening favorably and were comfortable with a variety of screening methods. These findings provide evidence of high acceptability of screening--a key criterion for implementation of universal screening--and suggest that providers can select from a variety of screening methods best suited for their clinical setting. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Statistical analyses in Swedish randomised trials on mammography screening and in other randomised trials on cancer screening: a systematic review

PubMed Central

Boniol, Mathieu; Smans, Michel; Sullivan, Richard; Boyle, Peter

2015-01-01

Objectives We compared calculations of relative risks of cancer death in Swedish mammography trials and in other cancer screening trials. Participants Men and women from 30 to 74 years of age. Setting Randomised trials on cancer screening. Design For each trial, we identified the intervention period, when screening was offered to screening groups and not to control groups, and the post-intervention period, when screening (or absence of screening) was the same in screening and control groups. We then examined which cancer deaths had been used for the computation of relative risk of cancer death. Main outcome measures Relative risk of cancer death. Results In 17 non-breast screening trials, deaths due to cancers diagnosed during the intervention and post-intervention periods were used for relative risk calculations. In the five Swedish trials, relative risk calculations used deaths due to breast cancers found during intervention periods, but deaths due to breast cancer found at first screening of control groups were added to these groups. After reallocation of the added breast cancer deaths to post-intervention periods of control groups, relative risks of 0.86 (0.76; 0.97) were obtained for cancers found during intervention periods and 0.83 (0.71; 0.97) for cancers found during post-intervention periods, indicating constant reduction in the risk of breast cancer death during follow-up, irrespective of screening. Conclusions The use of unconventional statistical methods in Swedish trials has led to overestimation of risk reduction in breast cancer death attributable to mammography screening. The constant risk reduction observed in screening groups was probably due to the trial design that optimised awareness and medical management of women allocated to screening groups. PMID:26152677

Selective detection of pyrophosphate anion by a simple Cd(II) based terpyridine complex

NASA Astrophysics Data System (ADS)

Purohit, Aditya Kumar; Ghosh, Biswa Nath; Kar, Pravin Kumar

2018-01-01

A simple ratiometric terpyridine-Cd(ll) complex was synthesized by the treatment of CdCl2 with terpyridine ligand 4‧-(4-N,N‧-dimethylaminophenyl)-2,2‧:6‧,2″-terpyridine. The synthesized complex was found to act as a selective fluorescent chemosensor for pyrophosphate P2O74 - (PPi) over other anions like F-, Cl-, Br-, CO32 -, SO32 -, AcO-, NO2-, and H2PO4-. Furthermore, the receptor probe was also successfully employed in HeLa cell for PPi detection, which indicates this can be used as a chemosensor for cells.

Downwards Vertical Attention Bias in Conversion Disorder vs Controls: A Pilot Study.

PubMed

Gazit, Sivan; Elkana, Odelia; Dawidowicz, Liraz; Yeshayahu, Liel; Biran, Iftah

Conversion disorder (CD) is a largely enigmatic disorder, one that requires a thorough ruling-out process. Prior research suggests that metaphors and conceptualization are rooted in physical experience, and that we interpret our affective world through metaphors. Spatial metaphors (interaction of affect and vertical space) are a prominent example of the grounding of metaphors. This is a relatively unpaved direction of research of CD. The present pilot study sought to explore this view by investigating the "healthy is up, sick is down" spatial metaphors (e.g., "fell ill" and "top shape") in patients with CD, examining the correlation between the processing of bodily-related words, CD, and vertical space. We hypothesized that patients with CD, who experience their bodies as ill, will demonstrate a downwards bias when processing bodily-related words; corresponding to the "healthy is up, sick is down" spatial metaphor. A total of 8 female patients (ages M-38.13 SD-10.44) and 42 female controls (ages M-36.4 SD-14.57) performed a visual attention task. Participants were asked to identify a spatial probe at the top or the bottom of a screen, following either a bodily related (e.g., arm) or non-bodily related (e.g., clock) prime word. As predicted, when processing bodily-related words, patients with CD demonstrated a downwards attention bias. Moreover, the higher the patient's level of somatization, the faster the patient detected lower (vs upper) spatial targets. This study suggests that the changed health paradigm of patients with CD is grounded in sensorimotor perception. Further research could propose new diagnostic and treatment options for CD. Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Multistate transitional models for measuring adherence to breast cancer screening: A population-based longitudinal cohort study with over two million women.

PubMed

Sutradhar, R; Gu, S; Paszat, L F

2017-06-01

Objective Prior work on the disparities among women in breast cancer screening adherence has been methodologically limited. This longitudinal study determines and examines the factors associated with becoming adherent. Methods In a cohort of Canadian women aged 50-74, a three-state transitional model was used to examine adherence to screening for breast cancer. The proportion of time spent being non-adherent with screening was calculated for each woman during her observation window. Using age as the time scale, a relative rate multivariable regression was implemented under the three-state transitional model, to examine the association between covariates (all time-varying) and the rate of becoming adherent. Results The cohort consisted of 2,537,960 women with a median follow-up of 8.46 years. Nearly 31% of women were continually up-to-date with breast screening. Once a woman was non-adherent, the rate of becoming adherent was higher among longer term residents (relative rate = 1.289, 95% confidence interval 1.275-1.302), those from wealthier neighbourhoods, and those who had an identifiable primary care provider who was female or had graduated in Canada. Conclusion Individual and physician-level characteristics play an important role in a woman's adherence to screening. This work improves the quality of evidence regarding disparities among women in adherence to breast cancer screening and provides a novel methodological foundation to investigate adherence for other types of screening, including cervix and colorectal cancer screening.

Registry-based Study of Trends in Breast Cancer Screening Mammography before and after the 2009 U.S. Preventive Services Task Force Recommendations

PubMed Central

Bolton, Kenyon C.; Mace, John L.; Herschorn, Sally D.; James, Ted A.; Vacek, Pamela M.; Weaver, Donald L.; Geller, Berta M.

2014-01-01

Purpose To determine whether the 2009 U.S. Preventive Services Task Force (USPSTF) guidelines for breast cancer mammography screening were followed by changes in screening utilization in the state of Vermont. Materials and Methods This retrospective study was HIPAA compliant and approved by the institutional review board, with waiver of informed consent. Trends in screening mammography utilization during 1997–2011 were examined among approximately 150 000 women aged 40 years and older in the state of Vermont using statewide mammography registry data. Results The percentage of Vermont women aged 40 years and older screened in the past year declined from 45.3% in 2009% to 41.6% in 2011 (an absolute decrease of −3.7 percentage points; 95% confidence interval [CI]: −3.3, −4.1). The largest decline in utilization was among women aged 40–49 years (−4.8 percentage points; 95% CI: −4.1, −5.4), although substantial declines were also observed among women aged 50–74 years (−3.0 percentage points; 95% CI: −2.6, −3.5) and women aged 75 years and older (−3.1 percentage points; 95% CI: −2.3, −4.0). The percentage of women aged 50–74 years screened within the past 2 years declined by −3.4 percentage points (95% CI: −3.0, −3.9) from 65.4% in 2009 to 61.9% in 2011. Conclusion After years of increasing screening mammography utilization in Vermont, there was a decline in screening, which coincided with the release of the 2009 USPSTF recommendations. The age-specific patterns in utilization were generally consistent with the USPSTF recommendations, although there was also evidence that the percentage of women aged 50–74 years screened in the past 2 years declined since 2009. © RSNA, 2013 PMID:24072778

Evaluation of a Public-sector, Provider-initiated Cryptococcal Antigen Screening and Treatment Program, Western Cape, South Africa

PubMed Central

Smith, Mariette; Smith, Rachel; Osler, Meg; Kelly, Nicola; Cross, Anna; Boulle, Andrew; Meintjes, Graeme; Govender, Nelesh P.

2016-01-01

Background Screening for serum cryptococcal antigen (CrAg) may identify those at risk for disseminated cryptococcal disease (DCD), and pre-emptive fluconazole treatment may prevent progression to DCD. In August 2012, the Western Cape Province (WC), South Africa, adopted provider-initiated CrAg screening. We evaluated the implementation and effectiveness of this large-scale public-sector program during its first year, September 1, 2012—August 31, 2013. Methods We used data from the South African National Health Laboratory Service, WC provincial HIV program, and nationwide surveillance data for DCD. We assessed the proportion of eligible patients screened for CrAg (CrAg test done within 30 days of CD4 date) and the prevalence of CrAg positivity. Incidence of DCD among those screened was compared with those not screened. Results Of 4,395 eligible patients, 26.6% (n=1170) were screened. The proportion of patients screened increased from 15.9% in September 2012 to 36.6% in August 2013. The prevalence of positive serum CrAg was 2.1%. Treatment data were available for 13 of 24 CrAg-positive patients; nine of 13 were treated with fluconazole. Nine (0.8%) incident cases of DCD occurred among the 1170 patients who were screened for CrAg vs. 49 (1.5%) incident cases among the 3225 patients not screened (p=0.07). Conclusions Relatively few eligible patients were screened under the WC provider-initiated CrAg screening program. Unscreened patients were nearly twice as likely to develop DCD. CrAg screening can reduce the burden of DCD, but needs to be implemented well. To improve screening rates, countries should consider laboratory-based reflexive screening when possible. PMID:26926942

Adherence to colorectal cancer screening: four rounds of faecal immunochemical test-based screening.

PubMed

van der Vlugt, Manon; Grobbee, Esmée J; Bossuyt, Patrick Mm; Bongers, Evelien; Spijker, Wolfert; Kuipers, Ernst J; Lansdorp-Vogelaar, Iris; Essink-Bot, Marie-Louise; Spaander, Manon C W; Dekker, Evelien

2017-01-03

The effectiveness of faecal immunochemical test (FIT)-based screening programs is highly dependent on consistent participation over multiple rounds. We evaluated adherence to FIT screening over four rounds and aimed to identify determinants of participation behaviour. A total of 23 339 randomly selected asymptomatic persons aged 50-74 years were invited for biennial FIT-based colorectal cancer screening between 2006 and 2014. All were invited for every consecutive round, except for those who had moved out of the area, passed the upper age limit, or had tested positive in a previous screening round. A reminder letter was sent to non-responders. We calculated participation rates per round, response rates to a reminder letter, and differences in participation between subgroups defined by age, sex, and socioeconomic status (SES). Over the four rounds, participation rates increased significantly, from 60% (95% CI 60-61), 60% (95% CI 59-60), 62% (95% CI 61-63) to 63% (95% CI 62-64; P for trend<0.001) with significantly higher participation rates in women in all rounds (P<0.001). Of the 17 312 invitees eligible for at least two rounds of FIT screening, 12 455 (72%) participated at least once, whereas 4857 (28%) never participated; 8271 (48%) attended all rounds when eligible. Consistent participation was associated with older age, female sex, and higher SES. Offering a reminder letter after the initial invite in the first round increased uptake with 12%; in subsequent screening rounds this resulted in an additional uptake of up to 10%. In four rounds of a pilot biennial FIT-screening program, we observed a consistently high and increasing participation rate, whereas sending reminders remain effective. The substantial proportion of inconsistent participants suggests the existence of incidental barriers to participation, which, if possible, should be identified and removed.

Elevation of autoantibody level against PDCD11 in patients with transient ischemic attack

PubMed Central

Yoshida, Yoichi; Wang, Hao; Hiwasa, Takaki; Machida, Toshio; Kobayashi, Eiichi; Mine, Seiichiro; Tomiyoshi, Go; Nakamura, Rika; Shinmen, Natsuko; Kuroda, Hideyuki; Takizawa, Hirotaka; Kashiwado, Koichi; Kamitsukasa, Ikuo; Shin, Hideo; Wada, Takeshi; Aotsuka, Akiyo; Nishi, Eiichiro; Ohno, Mikiko; Takemoto, Minoru; Yokote, Koutaro; Takahashi, Sho; Matsushima, Jun; Zhang, Xiao-Meng; Takiguchi, Masaki; Iwadate, Yasuo

2018-01-01

Background Disease specific autoantibodies have been detected in the sera of patients with atherosclerosis-related diseases, such as cerebral infarction, cardiovascular disease. In the present study, we aimed to identify novel autoantibodies responsible for transient ischemic attack (TIA), a prodromal condition for cerebral infarction. Methods To identify candidate antigens, we screened a human aortic endothelial cell cDNA library using sera from 20 patients with TIA. Serum antibody levels were measured using amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in 2 independent patient/healthy donor (HD) cohorts (n = 192 and n = 906 in the second screening and validation cohort, respectively). Results First screening identified 3 candidate antigens. Of these, programmed cell death 11 (PDCD11) was determined to be associated with stroke (p < 0.0001), as evidenced from the second screening using AlphaLISA. The validation cohort revealed significantly higher antibody levels against PDCD11 (PDCD11-Ab levels) in patients with TIA than in HDs. Multivariate logistic regression analysis indicated that the predictive value of PDCD11-Ab levels for TIA [Odds ratio (OR): 2.44, 95% confidence interval (CI): 1.33-4.57, p = 0.0039] was not inferior to other known risk factors for ischemic stroke, including age (OR: 4.97, 95% CI: 2.67–9.48, p < 0.0001); hypertension (OR: 3.21, 95% CI: 1.76–5.86, p = 0.0001); and diabetes (OR: 4.31, 95% CI: 1.74–11.2, p = 0.0015). Conclusion Serum PDCD11-Ab level may serve as a potential biomarker for TIA. PMID:29507658

Intestinal Parasitosis in Relation to Anti-Retroviral Therapy, CD4(+) T-cell Count and Diarrhea in HIV Patients.

PubMed

Khalil, Shehla; Mirdha, Bijay Ranjan; Sinha, Sanjeev; Panda, Ashutosh; Singh, Yogita; Joseph, Anju; Deb, Manorama

2015-12-01

Intestinal parasitic infections are one of the major causes of diarrhea in human immunodeficiency virus (HIV) seropositive individuals. Antiretroviral therapy has markedly reduced the incidence of many opportunistic infections, but parasite-related diarrhea still remains frequent and often underestimated especially in developing countries. The present hospital-based study was conducted to determine the spectrum of intestinal parasitosis in adult HIV/AIDS (acquired immunodeficiency syndrome) patients with or without diarrhea with the levels of CD4(+) T-cell counts. A total of 400 individuals were enrolled and were screened for intestinal parasitosis. Of these study population, 200 were HIV seropositives, and the remaining 200 were HIV uninfected individuals with or without diarrhea. Intestinal parasites were identified by using microscopy as well as PCR assay. A total of 130 (32.5%) out of 400 patients were positive for any kinds of intestinal parasites. The cumulative number of parasite positive patients was 152 due to multiple infections. A significant association of Cryptosporidium (P<0.001) was detected among individuals with CD4(+) T-cell counts less than 200 cells/μl.

A new technique for promoting cyclic utilization of cyclodextrins in biotransformation.

PubMed

Shen, Yanbing; Yu, Ziqi; Yang, Xu; Wang, Fang; Luo, Jianmei; Wang, Min

2017-01-01

Cyclodextrins (CDs) can improve the productivity of steroid biotransformation by enhancing substrate solubility. CDs can be recycled by grafting them with appropriate carriers. Loofah fiber is an excellent grafting material for CDs, and can be applied to the biotransformation and recycling of β-cyclodextrin (β-CD). In this work, a technique for recycling β-CD in cortisone acetate (CA) biotransformation by Arthrobacter simplex CPCC 140451 was studied. Loofah fiber-grafted β-CD (LF-β-CD) was prepared using epichlorohydrin, which is a cross-linking agent. The grafting yield of β-CD was 74.8 mg g -1 dried fibers. LF-β-CD could increase the solubility of CA and enhance biotransformation. The initial conversion rate of CA was 1.5-fold higher than that of the blank group. LF-β-CD was also used in biocatalytic reactions for eight cycles, and it maintained the conversion ratio of CA at approximately 90%. Given the above positive results, LF-β-CD can be utilized in biotechnological recycling applications. This method can also be applied to CD derivatives and hydrophobic compounds.

Photosensitive space charge limited current in screen printed CdTe thin films

NASA Astrophysics Data System (ADS)

Vyas, C. U.; Pataniya, Pratik; Zankat, Chetan K.; Patel, Alkesh B.; Pathak, V. M.; Patel, K. D.; Solanki, G. K.

2018-05-01

Group II-VI Compounds have emerged out as most suitable in the class of photo sensitive material. They represent a strong position in terms of their applications in the field of detectors as well as photo voltaic devices. Cadmium telluride is the prime member of this Group, because of high acceptance of this material as active component in opto-electronic devices. In this paper we report preparation and characterization of CdTe thin films by using a most economical screen printing technique in association with sintering at 510°C temperature. Surface morphology and smoothness are prime parameters of any deposited to be used as an active region of devices. Thus, we studied of the screen printed thin film by means of atomic force microscopy (AFM) and scanning electron microscopy (SEM) for this purpose. However, growth processes induced intrinsic defects in fabricated films work as charge traps and affect the conduction process significantly. So the conduction mechanism of deposited CdTe thin film is studied under dark as well as illuminated conditions. It is found that the deposited films showed the space charge limited conduction (SCLC) mechanism and hence various parameters of space charge limited conduction (SCLC) of CdTe film were evaluated and discussed and the photo responsive resistance is also presented in this paper.

Blinded Validation of Breath Biomarkers of Lung Cancer, a Potential Ancillary to Chest CT Screening

PubMed Central

Phillips, Michael; Bauer, Thomas L.; Cataneo, Renee N.; Lebauer, Cassie; Mundada, Mayur; Pass, Harvey I.; Ramakrishna, Naren; Rom, William N.; Vallières, Eric

2015-01-01

Background Breath volatile organic compounds (VOCs) have been reported as biomarkers of lung cancer, but it is not known if biomarkers identified in one group can identify disease in a separate independent cohort. Also, it is not known if combining breath biomarkers with chest CT has the potential to improve the sensitivity and specificity of lung cancer screening. Methods Model-building phase (unblinded): Breath VOCs were analyzed with gas chromatography mass spectrometry in 82 asymptomatic smokers having screening chest CT, 84 symptomatic high-risk subjects with a tissue diagnosis, 100 without a tissue diagnosis, and 35 healthy subjects. Multiple Monte Carlo simulations identified breath VOC mass ions with greater than random diagnostic accuracy for lung cancer, and these were combined in a multivariate predictive algorithm. Model-testing phase (blinded validation): We analyzed breath VOCs in an independent cohort of similar subjects (n = 70, 51, 75 and 19 respectively). The algorithm predicted discriminant function (DF) values in blinded replicate breath VOC samples analyzed independently at two laboratories (A and B). Outcome modeling: We modeled the expected effects of combining breath biomarkers with chest CT on the sensitivity and specificity of lung cancer screening. Results Unblinded model-building phase. The algorithm identified lung cancer with sensitivity 74.0%, specificity 70.7% and C-statistic 0.78. Blinded model-testing phase: The algorithm identified lung cancer at Laboratory A with sensitivity 68.0%, specificity 68.4%, C-statistic 0.71; and at Laboratory B with sensitivity 70.1%, specificity 68.0%, C-statistic 0.70, with linear correlation between replicates (r = 0.88). In a projected outcome model, breath biomarkers increased the sensitivity, specificity, and positive and negative predictive values of chest CT for lung cancer when the tests were combined in series or parallel. Conclusions Breath VOC mass ion biomarkers identified lung cancer in a separate independent cohort, in a blinded replicated study. Combining breath biomarkers with chest CT could potentially improve the sensitivity and specificity of lung cancer screening. Trial Registration ClinicalTrials.gov NCT00639067 PMID:26698306

Cadmium sorption and extractability in tropical soils with variable charge.

PubMed

Colzato, Marina; Alleoni, Luís Reynaldo Ferracciú; Kamogawa, Marcos Yassuo

2018-05-14

The availability of cadmium (Cd) for plants and its impact in the environment depends on Cd sorption in soil colloids. The study of Cd sorption in soil and its fractionation is an interesting tool for the evaluation of Cd affinity with soil pools. The objective with this study was to evaluate Cd sorption and desorption in tropical soils with variable charge (three Oxisols), in a Mollisol and in two Entisols with diverse physical, chemical, and mineralogical attributes. We used a thermodynamic approach to evaluate Cd sorption and performed a chemical fractionation of Cd in the six soils. Data from Cd sorption fit the Langmuir model (r > 0.94), and the sorption capacity ranged from 0.33 to 11.5 mmol kg -1 . The Gibbs standard free energy was positively correlated to Cd sorption capacity (r = 0.74, except for the Quartzipsamments), and it was more favorable in soils with great sorption capacity. Distribution of Cd among fractions was not affected (t test, α = 0.05) by initial concentration, and there was a predominance of Cd extractable in 0.1 mol L -1 CaCl 2 .

The chemokine receptor CCR1 is identified in mast cell-derived exosomes.

PubMed

Liang, Yuting; Qiao, Longwei; Peng, Xia; Cui, Zelin; Yin, Yue; Liao, Huanjin; Jiang, Min; Li, Li

2018-01-01

Mast cells are important effector cells of the immune system, and mast cell-derived exosomes carrying RNAs play a role in immune regulation. However, the molecular function of mast cell-derived exosomes is currently unknown, and here, we identify differentially expressed genes (DEGs) in mast cells and exosomes. We isolated mast cells derived exosomes through differential centrifugation and screened the DEGs from mast cell-derived exosomes, using the GSE25330 array dataset downloaded from the Gene Expression Omnibus database. Biochemical pathways were analyzed by Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway on the online tool DAVID. DEGs-associated protein-protein interaction networks (PPIs) were constructed using the STRING database and Cytoscape software. The genes identified from these bioinformatics analyses were verified by qRT-PCR and Western blot in mast cells and exosomes. We identified 2121 DEGs (843 up and 1278 down-regulated genes) in HMC-1 cell-derived exosomes and HMC-1 cells. The up-regulated DEGs were classified into two significant modules. The chemokine receptor CCR1 was screened as a hub gene and enriched in cytokine-mediated signaling pathway in module one. Seven genes, including CCR1, CD9, KIT, TGFBR1, TLR9, TPSAB1 and TPSB2 were screened and validated through qRT-PCR analysis. We have achieved a comprehensive view of the pivotal genes and pathways in mast cells and exosomes and identified CCR1 as a hub gene in mast cell-derived exosomes. Our results provide novel clues with respect to the biological processes through which mast cell-derived exosomes modulate immune responses.

Screening athletes with Down syndrome for ocular disease.

PubMed

Gutstein, Walter; Sinclair, Stephen H; North, Rachel V; Bekiroglu, N

2010-02-01

Persons with Down syndrome are well known to have a high prevalence of vision and eye health problems, many of which are undetected or untreated primarily because of infrequent ocular examinations. Public screening programs, directed toward the pediatric population, have become more popular and commonly use letter or symbol charts. This study compares 2 vision screening methods, the Lea Symbol chart and a newly developed interactive computer program, the Vimetrics Central Vision Analyzer (CVA), in their ability to identify ocular disease in the Down syndrome population. Athletes with Down syndrome participating in the European Special Olympics underwent an ocular screening including history, auto-refraction, colour vision assessment, stereopsis assessment, motility assessment, pupil reactivity, and tonometry testing, as well as anterior segment and fundus examinations to evaluate for ocular disease. Visual acuity was tested with the Lea chart and CVA to evaluate these as screening tests for detecting ocular disease as well as significant, uncorrected refractive errors. Among the 91 athletes that presented to the screening, 79 (158 eyes) were sufficiently cooperative for the examination to be completed. Mean age was 26 years +/-10.8 SD. Significant, uncorrected refractive errors (>/=1.00 spherical equivalent) were detected in 28 (18%) eyes and ocular pathology in 51 (32%) eyes. The Lea chart sensitivity and specificity were 43% and 74%, respectively, for detecting ocular pathology and 58% and 100% for detecting uncorrected refractive errors. The CVA sensitivity and specificity were 70% and 86% for detecting pathology and 71% and 100% for detecting uncorrected refractive errors. This study confirmed the findings of prior studies in identifying a significant presence of uncorrected refractive errors and ocular pathology in the Down syndrome population. Screening with the Lea symbol chart found borderline sufficient sensitivity and specificity for the test to be used for screening in this population. The better sensitivity and specificity of the CVA, if adjusted normative values are utilized, appear to make this test sufficient for testing Down syndrome children for identifying both refractive errors and ocular pathology. Copyright 2010 American Optometric Association. Published by Elsevier Inc. All rights reserved.

Screening and Rapid Molecular Diagnosis of Tuberculosis in Prisons in Russia and Eastern Europe: A Cost-Effectiveness Analysis

PubMed Central

Winetsky, Daniel E.; Negoescu, Diana M.; DeMarchis, Emilia H.; Almukhamedova, Olga; Dooronbekova, Aizhan; Pulatov, Dilshod; Vezhnina, Natalia; Owens, Douglas K.; Goldhaber-Fiebert, Jeremy D.

2012-01-01

Background Prisons of the former Soviet Union (FSU) have high rates of multidrug-resistant tuberculosis (MDR-TB) and are thought to drive general population tuberculosis (TB) epidemics. Effective prison case detection, though employing more expensive technologies, may reduce long-term treatment costs and slow MDR-TB transmission. Methods and Findings We developed a dynamic transmission model of TB and drug resistance matched to the epidemiology and costs in FSU prisons. We evaluated eight strategies for TB screening and diagnosis involving, alone or in combination, self-referral, symptom screening, mass miniature radiography (MMR), and sputum PCR with probes for rifampin resistance (Xpert MTB/RIF). Over a 10-y horizon, we projected costs, quality-adjusted life years (QALYs), and TB and MDR-TB prevalence. Using sputum PCR as an annual primary screening tool among the general prison population most effectively reduced overall TB prevalence (from 2.78% to 2.31%) and MDR-TB prevalence (from 0.74% to 0.63%), and cost US$543/QALY for additional QALYs gained compared to MMR screening with sputum PCR reserved for rapid detection of MDR-TB. Adding sputum PCR to the currently used strategy of annual MMR screening was cost-saving over 10 y compared to MMR screening alone, but produced only a modest reduction in MDR-TB prevalence (from 0.74% to 0.69%) and had minimal effect on overall TB prevalence (from 2.78% to 2.74%). Strategies based on symptom screening alone were less effective and more expensive than MMR-based strategies. Study limitations included scarce primary TB time-series data in FSU prisons and uncertainties regarding screening test characteristics. Conclusions In prisons of the FSU, annual screening of the general inmate population with sputum PCR most effectively reduces TB and MDR-TB prevalence, doing so cost-effectively. If this approach is not feasible, the current strategy of annual MMR is both more effective and less expensive than strategies using self-referral or symptom screening alone, and the addition of sputum PCR for rapid MDR-TB detection may be cost-saving over time. Please see later in the article for the Editors' Summary PMID:23209384

Factors Associated with Informed Decisions and Participation in Bowel Cancer Screening among Adults with Lower Education and Literacy.

PubMed

Smith, Sian K; Simpson, Judy M; Trevena, Lyndal J; McCaffery, Kirsten J

2014-08-01

Making informed decisions about cancer screening involves understanding the benefits and harms in conjunction with personal values. There is little research examining factors associated with informed decision making or participation in screening in the context of a decision aid trial. To identify factors associated with informed choice and participation in fecal occult blood testing (FOBT) among lower education populations. Randomized controlled trial of an FOBT decision aid conducted between July and November 2008. Socioeconomically disadvantaged areas in New South Wales, Australia. Included 572 adults aged 55 to 64 years with lower education. Sociodemographic variables, perceived health literacy, and involvement preferences in decision making were examined to identify predictors of informed choice (knowledge, attitudes, and behavior). Multivariate analysis identified independent predictors of making an informed choice as having higher education (relative risk [RR], 1.49; 95% confidence interval [CI], 1.13-1.95; P = 0.001), receiving the decision aid (RR, 2.88; 95% CI, 1.87-4.44; P < 0.001), and being male (RR, 1.48; 95% CI, 1.11-1.97; P = 0.009). Participants with no confidence in completing forms and poorer self-reported health were less likely to make an informed choice (RR, 0.74; 95% CI, 0.53-1.03; P = 0.05 and RR, 0.57; 95% CI, 0.36-0.89; P = 0.007, respectively). Independent predictors of completing the FOBT were positive screening attitudes, receiving the standard information, preference for making the decision alone, and knowing that screening may lead to false-positive/negative results. We did not objectively measure health literacy. Participants with the lowest levels of education had greater difficulties making an informed choice about participation in bowel screening. Alternative methods are needed to support informed decision making among lower education populations. © The Author(s) 2014.

Clinical features of celiac disease: a prospective birth cohort.

PubMed

Agardh, Daniel; Lee, Hye-Seung; Kurppa, Kalle; Simell, Ville; Aronsson, Carin Andrén; Jörneus, Ola; Hummel, Michael; Liu, Edwin; Koletzko, Sibylle

2015-04-01

To investigate clinical features of celiac disease (CD) and their association with risk factors for CD in a genetic risk birth cohort. Children from 6 clinical centers in 4 countries positive for HLA-DR3-DQ2 or DR4-DQ8 were annually screened for tissue transglutaminase antibodies (tTGA) and assessed for symptoms by questionnaires. Associations of symptoms with anthropometrics, known risk factors for CD, tTGA levels, and mucosal lesions in those biopsied were examined. Of 6706 screened children, 914 developed persistent positive tTGA, 406 underwent biopsies, and 340 had CD. Compared with age-matched tTGA-negative children, those with persistent tTGA were more likely to have symptoms at 2 (34% vs 19%, P < .001) and 3 years of age (28% vs 19%, P = .009) but not at 4 years (27% vs 21%, NS). Z-scores for height, weight, and BMI did not differ between groups. In children with persistent tTGA, having ≥ 1 symptom was associated with family history of CD (odds ratio = 2.59, 95% confidence interval, 1.21-5.57) but not with age, gender, or HLA-DR3-DQ2 homozygosity. At seroconversion, tTGA levels were higher in symptomatic than asymptomatic children (P < .001), in those from CD families (P < .001), and in US participants (P < .001) but not associated with age, gender, or HLA genotype. tTGA levels correlated with severity of mucosal lesions both in symptomatic (r = 0.53, P < .001) and asymptomatic children (r = 0.22, P = .01). A majority of children detected with persistent tTGA in screenings are asymptomatic and have normal growth by age 4 years. tTGA levels correlate more strongly with severity of mucosal lesions in symptomatic as compared with asymptomatic children. Copyright © 2015 by the American Academy of Pediatrics.

Optimization of Lipase production from a novel strain Thalassospira permensis M35-15 using Response Surface Methodology

PubMed Central

Kai, Wang; Peisheng, Yan

2016-01-01

ABSTRACT Lipases can catalyze the hydrolysis of glycerol, esters and long chain fatty acids. A lipase producing isolate M35-15 was screened and identified as Thalassospira permensis using 16S rRNA gene sequence analysis. To our knowledge this is the first report on Thalassospira permensis producing lipases. In this paper the optimization of medium composition for the increase in bacterial lipase was achieved using statistical methods. Firstly the key ingredients were selected by Plackett-Burman experimental design, then the levels of the ingredients were optimized using central composite design of Response Surface Methodology. The predicted optimal lipase activity was 11.49 U under the conditions that medium composition were 5.15 g/l glucose, 11.74 g/l peptone, 6.74 g/l yeast powder and 22.90 g/l olive oil emulsifier. PMID:27285376

Optimization of Lipase production from a novel strain Thalassospira permensis M35-15 using Response Surface Methodology.

PubMed

Kai, Wang; Peisheng, Yan

2016-09-02

Lipases can catalyze the hydrolysis of glycerol, esters and long chain fatty acids. A lipase producing isolate M35-15 was screened and identified as Thalassospira permensis using 16S rRNA gene sequence analysis. To our knowledge this is the first report on Thalassospira permensis producing lipases. In this paper the optimization of medium composition for the increase in bacterial lipase was achieved using statistical methods. Firstly the key ingredients were selected by Plackett-Burman experimental design, then the levels of the ingredients were optimized using central composite design of Response Surface Methodology. The predicted optimal lipase activity was 11.49 U under the conditions that medium composition were 5.15 g/l glucose, 11.74 g/l peptone, 6.74 g/l yeast powder and 22.90 g/l olive oil emulsifier.

Comparative transcriptomics reveals genes involved in metabolic and immune pathways in the digestive gland of scallop Chlamys farreri following cadmium exposure

NASA Astrophysics Data System (ADS)

Zhang, Hui; Zhai, Yuxiu; Yao, Lin; Jiang, Yanhua; Li, Fengling

2017-05-01

Chlamys farreri is an economically important mollusk that can accumulate excessive amounts of cadmium (Cd). Studying the molecular mechanism of Cd accumulation in bivalves is difficult because of the lack of genome background. Transcriptomic analysis based on high-throughput RNA sequencing has been shown to be an efficient and powerful method for the discovery of relevant genes in non-model and genome reference-free organisms. Here, we constructed two cDNA libraries (control and Cd exposure groups) from the digestive gland of C. farreri and compared the transcriptomic data between them. A total of 227 673 transcripts were assembled into 105 071 unigenes, most of which shared high similarity with sequences in the NCBI non-redundant protein database. For functional classification, 24 493 unigenes were assigned to Gene Ontology terms. Additionally, EuKaryotic Ortholog Groups and Kyoto Encyclopedia of Genes and Genomes analyses assigned 12 028 unigenes to 26 categories and 7 849 unigenes to five pathways, respectively. Comparative transcriptomics analysis identified 3 800 unigenes that were differentially expressed in the Cd-treated group compared with the control group. Among them, genes associated with heavy metal accumulation were screened, including metallothionein, divalent metal transporter, and metal tolerance protein. The functional genes and predicted pathways identified in our study will contribute to a better understanding of the metabolic and immune system in the digestive gland of C. farreri. In addition, the transcriptomic data will provide a comprehensive resource that may contribute to the understanding of molecular mechanisms that respond to marine pollutants in bivalves.

Leonardo da Vinci meets celiac disease.

PubMed

Zanchi, Chiara; Ventura, Giovanna; Di Leo, Grazia; Orzes, Nicoletta; Ronfani, Luca; Not, Tarcisio; Ventura, Alessandro

2013-02-01

Leonardo da Vinci's face symmetry derives from 3 equal craniofacial segments: trichion-nasion (tn), which represents the superior third of the face, nasion-subnasal (ns) that is the medium third of the face, and subnasal-gnathion (sg) that is the length of the lower third of the face. It has been reported that adult subjects with celiac disease (CD) can be identified on the basis of a greater extension of the forehead in comparison to the medium third of the face, with a high tn/ns ratio. The aim of the present study was to investigate the correlation between facial asymmetry and CD in childhood and adulthood. We studied 126 biopsy-proven patients with CD (76 children and 50 adults) and 102 healthy controls (43 children and 59 adults). Their faces were photographed; the pictures were edited using a software program to calculate the facial segments. The tn length was significantly different between adult celiac and adult controls (7.43 ± 1.46 cm vs 6.38 ± 1.73 cm, P = 0.001). The cutoff of 6.5 cm tn, derived from receiver operating characteristic curve analysis, identified 43 of 50 patients (sensitivity 86%), but 34 of 59 controls were positive (specificity 54.2%). The positive predictive value was 56%; however, the tn/ns ratio was not significantly different between celiacs and controls. Neither the tn length nor the tn/ns ratio in celiacs correlated to the time of gluten exposure. Adults, but not children, with celiac disease show a forehead extension significantly greater than controls, but this test's specificity appears too low to be used in the screening of CD.

Differences in Patient Outcomes of Prevalence, Interval, and Screen-Detected Lung Cancers in the CT Arm of the National Lung Screening Trial

PubMed Central

Massion, Pierre P.; Thompson, Zachary J.; Eschrich, Steven A.; Balagurunathan, Yoganand; Goldof, Dmitry; Aberle, Denise R.; Gillies, Robert J.

2016-01-01

Lung cancer screening identifies cancers with heterogeneous behaviors. Some lung cancers will be identified among patients who had prior negative CT screens and upon follow-up scans develop a de novo nodule that was determined to be cancerous. Other lung cancers will be identified among patients who had one or more prior stable positive scans that were not determined to be lung cancer (indeterminate pulmonary nodules), but in follow-up scans was diagnosed with an incidence lung cancer. Using data from the CT arm of the National Lung Screening Trial, this analysis investigated differences in patient characteristics and survival endpoints between prevalence-, interval-, and screen-detected lung cancers, characterized based on sequence of screening results. Lung cancers immediately following a positive baseline (T0), and prior to the T1 screen, formed the prevalence cohort. Interval cancers were diagnosed following a negative screen at any time point prior to the next screening round. Two cohorts of screen-detected lung cancers (SDLC) were identified that had a baseline positive screen that was that was not determined to be lung cancer (i.e., an indeterminate pulmonary nodule), but in follow-up scans was diagnosed with an incidence lung cancer 12 (SDLC1) or 24 (SDLC2) months later. Two other incidence cohorts had screen-detected lung cancers that had baseline negative screen and upon follow-up scans developed a de novo nodule determined to be cancerous at 12 (SDLC3) or 24 (SDLC4) months later. Differences in patient characteristics, progression-free survival (PFS), and overall survival (OS) were assessed. The lung cancer-specific death rate was higher for SDLC3/SDLC4 compared to SDLC1/SDLC2 lung cancers (136.6/1,000 person-years vs. 71.3/1,000 person-years, P < 0.001). Moreover, PFS and OS were significantly lower for SDLC3/SDLC4 compared to SDLC1/SDLC2 (P < 0.004; P < 0.002, respectively). The findings were consistent when stratified by stage and histology. Multivariable Cox proportional models revealed that the SDLC3/SDLC4 case groups were associated with significantly poorer PFS (HR = 1.89; 95% CI 1.31–2.74) and OS (HR = 1.80; 95% CI 1.21–2.67) compared to SDLC1/SDLC2 lung cancers (HR = 1.00). Lung cancer patients who develop a de novo nodule that determined to be cancerous (i.e., at least one negative CT screen prior to cancer diagnosis) had poorer survival outcomes compared to patients who had at least one positive screen prior to cancer diagnosis. As such, the observation that de novo screen-detected are associated with poorer survival could be attributed to faster growing, more aggressive cancers that arose from a lung environment previously lacking focal abnormalities. PMID:27509046

The mental health needs of incarcerated youth in British Columbia, Canada.

PubMed

Gretton, Heather M; Clift, Robert J W

2011-01-01

The purpose of the study was to identify the current prevalence of mental disorders and mental health needs among incarcerated male and female youths in Canada, and to present these data in the context of rates found in other jurisdictions. One hundred forty male and 65 female incarcerated young offenders in British Columbia were screened with the Massachusetts Youth Screening Instrument Version 2 (MAYSI-2); provisional psychiatric diagnoses were assessed with the Diagnostic Interview Schedule for Children Version IV (DISC-IV); abuse history and aggressive symptoms of Conduct Disorder (CD) were coded from file information. Nearly all youths (91.9% of males and 100% of females) met the criteria for at least one mental disorder. Substance abuse and dependence disorders were highly prevalent (85.5% of males and 100% of females). Aggressive forms of CD were common (72.9% of males and 84.3% of females), as were exposure to physical abuse (60.8% of males and 54.3% of females) and sexual abuse (21.2% of males and 42.4% of females). Female youths had significantly higher odds of presenting with: (1) substance abuse/dependence disorders; (2) current suicide ideation; (3) sexual abuse; (4) PTSD; (5) symptoms of depression and anxiety; (6) Oppositional Defiant Disorder; and (7) multiple mental disorder diagnoses. Male youths had significantly higher odds of presenting with aggressive symptoms of CD. Overall, rates of mental disorder among this sample of serious and violent young offenders were higher than rates previously reported for incarcerated youths - both in Canada and in other jurisdictions. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

[Calculation of environmental dredging depth of heavy sediments in Zhushan Bay of Taihu Lake metal polluted].

PubMed

Jiang, Xia; Wang, Wen-Wen; Wang, Shu-Hang; Jin, Xiang-Can

2012-04-01

Horizontal distribution of heavy metals in surface sediments of Zhushan Bay was investigated, and core sediment samples were collected in the representative area. Core sediments were divided into oxide layer (A), polluted layer (B), upper polluted transition layer(C1), lower polluted transition layer(C2) and normal mud layer(D) from top to bottom. The change of total contents of Cr, Ni, Cu, Zn, As, Cd, Hg, Pb and contents of biological available Cr, Ni, Cu, Zn, As, Cd, Pb with depths were analyzed. Ecological risk assessment of heavy metals in sediments was done by potential ecological risk index method. At last, environmental dredging depth was calculated. The results shows that the contents of Cr, Ni, Cu, Zn, As, Cd, Hg, Pb are 30.56-216.58, 24.07-59.95, 16.71-140.30, 84.31-193.43, 3.39-22.30, 0.37-1.59, 0.00-0.80 and 9.67-99.35 mg x kg(-1), respectively. The average concentrations of Cr, Ni, Cu, Zn, As, Cd, Hg, Pb are 79.74, 37.74, 44.83, 122.39, 10.39, 0.77, 0.14 and 40.08 mg x kg(-1), respectively. Heavy metals in the surface sediments of Zhushan Bay mainly distribute in the west bank and the estuaries of Taige canal, Yincun Port, and Huanshan River,and Cd pollution is relatively serious. There is an accumulative effect of heavy metals in Zhushan Bay, and the contents of biological available metals decrease with depths. Ecological risk grades of Cd in layer A and B are high, and the comprehensive potential ecological risk grades of each layer are in middle or low. The environmental dredging layers are A and B, and the average dredging depth is 0.39 m.

Temporal lobe volumes in patients with hippocampal sclerosis with or without cortical dysplasia.

PubMed

Diehl, B; Najm, I; LaPresto, E; Prayson, R; Ruggieri, P; Mohamed, A; Ying, Z; Lieber, M; Babb, T; Bingaman, W; Lüders, H O

2004-05-25

Recent MRI-based volume reconstruction studies in intractable temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) suggested atrophy that extends to the adjacent neocortical areas. To study the extent of temporal lobe volume (TLV) abnormalities in patients with pathologically confirmed HS (with or without cortical dysplasia [CD]) who underwent anterior temporal lobectomy for the treatment of drug-resistant TLE. Fifty patients (right TLE: n = 24; left TLE: n = 26) were found to have HS (hippocampal cell loss of >30%). Associated neocortical CD was seen in 20 patients (43%). MRI-based TLVs and hippocampal and hemispheric volume reconstructions in all patients were compared between pathologic groups and with volumes acquired from 10 age-matched control subjects. TLVs ipsilateral to the epileptogenic zone in patients with TLE were smaller than TLVs in control subjects (p < 0.01). In patients with left TLE, TLVs ipsilateral to the epileptogenic zone were smaller than contralateral TLVs (left: 66.6 +/- 8.3 cm3, right: 74.9 +/- 10.0 cm3; p < 0.001). In patients with right TLE, there were no significant asymmetries. The contralateral TLVs (regardless of the side of surgery) were smaller in the HS + CD group than the HS group (HS + CD group: 74.9 +/- 8.6 cm3, HS group: 79.7 +/- 6.6 cm3; p < 0.05). Patients with HS + CD had a tendency to have less hippocampal atrophy and slightly smaller TLVs ipsilateral to the epileptogenic zone, accounting for significantly smaller TLV/hippocampal volume ratios compared with patients with HS alone. Drug-resistant TLE due to HS is associated with extrahippocampal temporal lobe atrophy. The presence of bilateral temporal lobe atrophy is suggestive of a more widespread (bilateral) temporal lobe involvement in patients with HS and CD.

Screening for DSM-IV-TR Cognitive Disorder NOS in Parkinson’s disease using the Mattis Dementia Rating Scale

PubMed Central

Pontone, Gregory M.; Palanci, Justin; Williams, James R.; Bassett, Susan Spear

2012-01-01

Objective This study explores the utility of the Mattis Dementia Rating Scale (MDRS) as a screening tool for the Diagnostic and Statistical Manual for Mental Disorders 4th edition (DSM-IV-TR) diagnosis Cognitive Disorder Not Otherwise Specified in Parkinson’s disease(PD). Methods 125 individuals with PD were diagnosed using DSM-IV-TR criteria for Cognitive Disorder NOS and dementia. Receiver operating characteristics tested the discriminant validity of the MDRS, with the clinician’s diagnosis serving as the gold standard. Results The MDRS ROC curve to discriminate subjects with Cognitive Disorder NOS from non-demented subjects had an AUC of 0.59 (std. err.= 0.08, 95% CI: 0.43–0.74). Conclusions The MDRS is not effective for identifying PD patients with Cognitive Disorder NOS without dementia. PMID:22628158

Defect printability of ArF alternative phase-shift mask: a critical comparison of simulation and experiment

NASA Astrophysics Data System (ADS)

Ozawa, Ken; Komizo, Tooru; Ohnuma, Hidetoshi

2002-07-01

An alternative phase shift mask (alt-PSM) is a promising device for extending optical lithography to finer design rules. There have been few reports, however, on the mask's ability to identify phase defects. We report here an alt-PSM of a single-trench type with undercut for ArF exposure, with programmed phase defects used to evaluate defect printability by measuring aerial images with a Zeiss MSM193 measuring system. The experimental results are simulated using the TEMPEST program. First, a critical comparison of the simulation and the experiment is conducted. The actual measured topographies of quartz defects are used in the simulation. Moreover, a general simulation study on defect printability using an alt-PSM for ArF exposure is conducted. The defect dimensions, which produce critical CD errors, are determined by simulation that takes into account the full 3-dimensional structure of phase defects as well as a simplified structure. The critical dimensions of an isolated bump defect identified by the alt-PSM of a single-trench type with undercut for ArF exposure are 300 nm in bottom dimension and 74 degrees in height (phase) for the real shape, where the depth of wet-etching is 100 nm and the CD error limit is +/- 5 percent.

Comparison of analytical methods for the determination of histamine in reference canned fish samples

NASA Astrophysics Data System (ADS)

Jakšić, S.; Baloš, M. Ž.; Mihaljev, Ž.; Prodanov Radulović, J.; Nešić, K.

2017-09-01

Two screening methods for histamine in canned fish, an enzymatic test and a competitive direct enzyme-linked immunosorbent assay (CD-ELISA), were compared with the reversed-phase liquid chromatography (RP-HPLC) standard method. For enzymatic and CD-ELISA methods, determination was conducted according to producers’ manuals. For RP-HPLC, histamine was derivatized with dansyl-chloride, followed by RP-HPLC and diode array detection. Results of analysis of canned fish, supplied as reference samples for proficiency testing, showed good agreement when histamine was present at higher concentrations (above 100 mg kg-1). At a lower level (16.95 mg kg-1), the enzymatic test produced some higher results. Generally, analysis of four reference samples according to CD-ELISA and RP-HPLC showed good agreement for histamine determination (r=0.977 in concentration range 16.95-216 mg kg-1) The results show that the applied enzymatic test and CD-ELISA appeared to be suitable screening methods for the determination of histamine in canned fish.

Content analysis of age verification, purchase and delivery methods of internet e-cigarette vendors, 2013 and 2014.

PubMed

Williams, Rebecca S; Derrick, Jason; Liebman, Aliza Kate; LaFleur, Kevin; Ribisl, Kurt M

2018-05-01

Identify the population of internet e-cigarette vendors (IEVs) and conduct content analyses of their age verification, purchase and delivery methods in 2013 and 2014. We used multiple sources to identify IEV websites, primarily complex search algorithms scanning more than 180 million websites. In 2013, we manually screened 32 446 websites, identifying 980 IEVs, selecting the 281 most popular for content analysis. This methodology yielded 31 239 websites for screening in 2014, identifying 3096 IEVs, with 283 selected for content analysis. The proportion of vendors that sold online-only, with no retail store, dropped significantly from 2013 (74.7%) to 2014 (64.3%) (p<0.01), with a corresponding significant decrease in US-based vendors (71.9% in 2013 and 65% in 2014). Most vendors did little to prevent youth access in either year, with 67.6% in 2013 and 63.2% in 2014 employing no age verification or relying exclusively on strategies that cannot effectively verify age. Effective age verification strategies such as online age verification services (7.1% in 2013 and 8.5% in 2014), driving licences (1.8% in 2013 and 7.4% in 2014, p<0.01) or age verification at delivery (6.4% in 2013 and 8.1% in 2104) were rarely advertised on IEV websites. Nearly all vendors advertised accepting credit cards, and about ¾ shipping via United States Postal Service, similar to the internet cigarette industry prior to federal bans. The number of IEVs grew sharply from 2013 to 2014, with poor age verification practices. New and expanded regulations for online e-cigarette sales are needed, including strict age and identity verification requirements. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Exclusion-Based Capture and Enumeration of CD4+ T Cells from Whole Blood for Low-Resource Settings.

PubMed

Howard, Alexander L; Pezzi, Hannah M; Beebe, David J; Berry, Scott M

2014-06-01

In developing countries, demand exists for a cost-effective method to evaluate human immunodeficiency virus patients' CD4(+) T-helper cell count. The TH (CD4) cell count is the current marker used to identify when an HIV patient has progressed to acquired immunodeficiency syndrome, which results when the immune system can no longer prevent certain opportunistic infections. A system to perform TH count that obviates the use of costly flow cytometry will enable physicians to more closely follow patients' disease progression and response to therapy in areas where such advanced equipment is unavailable. Our system of two serially-operated immiscible phase exclusion-based cell isolations coupled with a rapid fluorescent readout enables exclusion-based isolation and accurate counting of T-helper cells at lower cost and from a smaller volume of blood than previous methods. TH cell isolation via immiscible filtration assisted by surface tension (IFAST) compares well against the established Dynal T4 Quant Kit and is sensitive at CD4 counts representative of immunocompromised patients (less than 200 TH cells per microliter of blood). Our technique retains use of open, simple-to-operate devices that enable IFAST as a high-throughput, automatable sample preparation method, improving throughput over previous low-resource methods. © 2013 Society for Laboratory Automation and Screening.

Identification of GAPDH on the surface of Plasmodium sporozoites as a new candidate for targeting malaria liver invasion

PubMed Central

Kim, Min-Sik

2016-01-01

Malaria transmission begins when an infected mosquito delivers Plasmodium sporozoites into the skin. The sporozoite subsequently enters the circulation and infects the liver by preferentially traversing Kupffer cells, a macrophage-like component of the liver sinusoidal lining. By screening a phage display library, we previously identified a peptide designated P39 that binds to CD68 on the surface of Kupffer cells and blocks sporozoite traversal. In this study, we show that the P39 peptide is a structural mimic of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) on the sporozoite surface and that GAPDH directly interacts with CD68 on the Kupffer cell surface. Importantly, an anti-P39 antibody significantly inhibits sporozoite liver invasion without cross-reacting with mammalian GAPDH. Therefore, Plasmodium-specific GAPDH epitopes may provide novel antigens for the development of a prehepatic vaccine. PMID:27551151

Identification of GAPDH on the surface of Plasmodium sporozoites as a new candidate for targeting malaria liver invasion.

PubMed

Cha, Sung-Jae; Kim, Min-Sik; Pandey, Akhilesh; Jacobs-Lorena, Marcelo

2016-09-19

Malaria transmission begins when an infected mosquito delivers Plasmodium sporozoites into the skin. The sporozoite subsequently enters the circulation and infects the liver by preferentially traversing Kupffer cells, a macrophage-like component of the liver sinusoidal lining. By screening a phage display library, we previously identified a peptide designated P39 that binds to CD68 on the surface of Kupffer cells and blocks sporozoite traversal. In this study, we show that the P39 peptide is a structural mimic of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) on the sporozoite surface and that GAPDH directly interacts with CD68 on the Kupffer cell surface. Importantly, an anti-P39 antibody significantly inhibits sporozoite liver invasion without cross-reacting with mammalian GAPDH. Therefore, Plasmodium-specific GAPDH epitopes may provide novel antigens for the development of a prehepatic vaccine. © 2016 Cha et al.

Who attends a UK diabetes screening programme? Findings from the ADDITION-Cambridge study.

PubMed

Sargeant, L A; Simmons, R K; Barling, R S; Butler, R; Williams, K M; Prevost, A T; Kinmonth, A L; Wareham, N J; Griffin, S J

2010-09-01

One of the factors influencing the cost-effectiveness of population screening for Type 2 diabetes may be uptake. We examined attendance and practice- and individual-level factors influencing uptake at each stage of a diabetes screening programme in general practice. A stepwise screening programme was undertaken among 135, 825 people aged 40-69 years without known diabetes in 49 general practices in East England. The programme included a score based on routinely available data (age, sex, body mass index and prescribed medication) to identify those at high risk, who were offered random capillary blood glucose (RBG) and glycosylated haemoglobin tests. Those screening positive were offered fasting capillary blood glucose (FBG) and confirmatory oral glucose tolerance tests (OGTT). There were 33 539 high-risk individuals invited for a RBG screening test; 24 654 (74%) attended. Ninety-four per cent attended the follow-up FBG test and 82% the diagnostic OGTT. Seventy per cent of individuals completed the screening programme. Practices with higher general practitioner staff complements and those located in more deprived areas had lower uptake for RBG and FBG tests. Male sex and a higher body mass index were associated with lower attendance for RBG testing. Older age, prescription of antihypertensive medication and a higher risk score were associated with higher attendance for FBG and RBG tests. High attendance rates can be achieved by targeted stepwise screening of individuals assessed as high risk by data routinely available in general practice. Different strategies may be required to increase initial attendance, ensure completion of the screening programme, and reduce the risk that screening increases health inequalities.

Induced miR-99a expression represses Mtor cooperatively with miR-150 to promote regulatory T-cell differentiation

PubMed Central

Warth, Sebastian C; Hoefig, Kai P; Hiekel, Anian; Schallenberg, Sonja; Jovanovic, Ksenija; Klein, Ludger; Kretschmer, Karsten; Ansel, K Mark; Heissmeyer, Vigo

2015-01-01

Peripheral induction of regulatory T (Treg) cells provides essential protection from inappropriate immune responses. CD4+ T cells that lack endogenous miRNAs are impaired to differentiate into Treg cells, but the relevant miRNAs are unknown. We performed an overexpression screen with T-cell-expressed miRNAs in naive mouse CD4+ T cells undergoing Treg differentiation. Among 130 candidates, the screen identified 29 miRNAs with a negative and 10 miRNAs with a positive effect. Testing reciprocal Th17 differentiation revealed specific functions for miR-100, miR-99a and miR-10b, since all of these promoted the Treg and inhibited the Th17 program without impacting on viability, proliferation and activation. miR-99a cooperated with miR-150 to repress the expression of the Th17-promoting factor mTOR. The comparably low expression of miR-99a was strongly increased by the Treg cell inducer “retinoic acid”, and the abundantly expressed miR-150 could only repress Mtor in the presence of miR-99a. Our data suggest that induction of Treg cell differentiation is regulated by a miRNA network, which involves cooperation of constitutively expressed as well as inducible miRNAs. PMID:25712478

Knowledge of binge eating disorder: a cross-sectional survey of physicians in the United States.

PubMed

Supina, Dylan; Herman, Barry K; Frye, Carla B; Shillington, Alicia C

2016-01-01

Binge eating disorder (BED)--now a designated disorder in the DSM-5--is the most prevalent eating disorder (ED), affecting 2-3% of the US population. This survey of US physicians assesses how BED is diagnosed, treated and referred. Internists, family practitioners, obstetrics/gynecologist (OB/GYNs) and psychiatrists were randomly selected from a nationally-representative panel. Participants completed an online survey and reviewed case vignettes consistent with DSM-5-defined BED, then answered questions to elicit whether they would assess for psychiatric conditions including EDs. Those reporting they would screen and who correctly identified BED in vignettes received additional questions about BED diagnosis, treatment, and referral patterns. Of 278 physicians surveyed, 96% were board-certified and 87% had practiced >10 years. 23% were psychiatrists, 27% family practitioners, 31% internists and 19% OB/GYNs. 92% were 'somewhat likely' to screen for ED after reviewing DSM-5-consistent vignettes. 206 (74%) correctly identified BED. Of these, 33% and 68% reported they proactively screen eating habits for all patients and obese patients, respectively. 10% reported not screening eating habits even in the presence of ED symptoms. Fewer than half reported using DSM criteria in Diagnosing BED, and 56 (27%) did not recognize BED to be a discreet ED. Although ED awareness is improving, understanding BED as a distinct ED is lacking, which may result in low rates of screening and diagnosis. This study illustrates how taking a complete patient history (including probing BED characteristics) may be an effective first-line strategy for clinicians to facilitate optimal care for these patients.

Optimised cord blood sample selection for small‑scale CD34+ cell immunomagnetic isolation.

PubMed

Perdomo-Arciniegas, Ana-María; Vernot, Jean-Paul

2012-03-01

Haematopoietic stem cells (HSCs) are defined as multipotential cells, capable of self-renewal and reconstituting in vivo the haematopoietic compartment. The CD34 antigen is considered an important HSCs marker in humans. Immunomagnetic isolation, by targeting CD34 antigen, is widely used for human HSC separation. This method allows the enrichment of human HSCs that are present at low frequencies in umbilical cord blood (CB). Immunomagnetic CD34+-cell isolation reproducibility, regarding cell yield and purity, is affected by the CD34+ cell frequency and total cell numbers present in a given sample; CB HSC purification may thus yield variable results, which also depend on the volume and density fractionation-derived cell loss of a CB sample. The uncertainty of such an outcome and associated technical costs call for a cost-effective sample screening strategy. A correlation analysis using clinical and laboratory data from 59 CB samples was performed to establish predictive variables for CD34+-immunomagnetic HSCs isolation. This study described the positive association of CD34+-cell isolation with white and red cell numbers present after cell fractionation. Furthermore, purity has been correlated with lymphocyte percentages. Predictive variable cut-off values, which are particularly useful in situations involving low CB volumes being collected (such as prevalent late umbilical cord clamping clinical practice), were proposed for HSC isolation sampling. Using the simple and cost-effective CB sample screening criteria described here would lead to avoiding costly inefficient sample purification, thereby ensuring that pure CD34+ cells are obtained in the desired numbers following CD34 immunomagnetic isolation.

Pinning down high-performance Cu-chalcogenides as thin-film solar cell absorbers: A successive screening approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yubo; Zhang, Wenqing, E-mail: wqzhang@mail.sic.ac.cn, E-mail: pzhang3@buffalo.edu; State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050

2016-05-21

Photovoltaic performances of Cu-chalcogenides solar cells are strongly correlated with the absorber fundamental properties such as optimal bandgap, desired band alignment with window material, and high photon absorption ability. According to these criteria, we carry out a successive screening for 90 Cu-chalcogenides using efficient theoretical approaches. Besides the well-recognized CuInSe{sub 2} and Cu{sub 2}ZnSnSe{sub 4} materials, several novel candidates are identified to have optimal bandgaps of around 1.0–1.5 eV, spike-like band alignments with CdS window layer, sharp photon absorption edges, and high absorption coefficients. These new systems have great potential to be superior absorbers for photovolatic applications if their carrriermore » transport and defect properties are properly optimized.« less

Expansion of CD14+CD16+ monocytes producing TNF-α in complication-free diabetes type 1 juvenile onset patients.

PubMed

Myśliwska, Jolanta; Smardzewski, Marcin; Marek-Trzonkowska, Natalia; Myśliwiec, Małgorzata; Raczyńska, Krystyna

2012-10-01

We concentrated on the complication-free phase of juvenile onset type 1 diabetes mellitus (T1DM) searching for associations between concentration of inflammatory factors TNF-α, CRP and VEGF and two monocyte subsets the CD14(++)CD16(-) and CD14(+)CD16(+). We analysed a randomly selected group of 150 patients without complications (disease duration 2.74 ± 2.51 years) at the start of the project and 5 years later. They were compared with 24 patients with retinopathy (6.53 ± 3.39 years of disease) and 30 healthy volunteers. Our results indicate that in the complication-free period the concentration of TNF-α significantly increased and continued to increase after retinopathy was established. After 5 years the percentage and absolute number of CD14(+)CD16(+) monocytes doubled in complication-free patients. Our study indicates that the size of CD14(+)CD16(+) monocyte subset may be used alternatively to CRP values as an indicator of inflammation grade. Our results imply the necessity of trials using anti-TNF-α therapy in the complication-free phase of the disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

Assay for identification of heterozygous single-nucleotide polymorphism (Ala67Thr) in human poliovirus receptor gene.

PubMed

Nandi, Shyam Sundar; Sharma, Deepa Kailash; Deshpande, Jagadish M

2016-07-01

It is important to understand the role of cell surface receptors in susceptibility to infectious diseases. CD155 a member of the immunoglobulin super family, serves as the poliovirus receptor (PVR). Heterozygous (Ala67Thr) polymorphism in CD155 has been suggested as a risk factor for paralytic outcome of poliovirus infection. The present study pertains to the development of a screening test to detect the single nucleotide (SNP) polymorphism in the CD155 gene. New primers were designed for PCR, sequencing and SNP analysis of Exon2 of CD155 gene. DNAs extracted from either whole blood (n=75) or cells from oral cavity (n=75) were used for standardization and validation of the SNP assay. DNA sequencing was used as the gold standard method. A new SNP assay for detection of heterozygous Ala67Thr genotype was developed and validated by testing 150 DNA samples. Heterozygous CD155 was detected in 27.33 per cent (41/150) of DNA samples tested by both SNP detection assay and sequencing. The SNP detection assay was successfully developed for identification of Ala67Thr polymorphism in human PVR/CD155 gene. The SNP assay will be useful for large scale screening of DNA samples.

Association of variants in innate immune genes with asthma and eczema

PubMed Central

Sharma, Sunita; Poon, Audrey; Himes, Blanca E.; Lasky-Su, Jessica; Sordillo, Joanne E.; Belanger, Kathleen; Milton, Donald K.; Bracken, Michael B.; Triche, Elizabeth W.; Leaderer, Brian P.; Gold, Diane R.; Litonjua, Augusto A.

2012-01-01

Background The innate immune pathway is important in the pathogenesis of asthma and eczema. However, only a few variants in these genes have been associated with either disease. We investigate the association between polymorphisms of genes in the innate immune pathway with childhood asthma and eczema. In addition, we compare individual associations with those discovered using a multivariate approach. Methods Using a novel method, case control based association testing (C2BAT), 569 single nucleotide polymorphisms (SNPs) in 44 innate immune genes were tested for association with asthma and eczema in children from the Boston Home Allergens and Asthma Study and the Connecticut Childhood Asthma Study. The screening algorithm was used to identify the top SNPs associated with asthma and eczema. We next investigated the interaction of innate immune variants with asthma and eczema risk using Bayesian networks. Results After correction for multiple comparisons, 7 SNPs in 6 genes (CARD25, TGFB1, LY96, ACAA1, DEFB1, and IFNG) were associated with asthma (adjusted p-value<0.02), while 5 SNPs in 3 different genes (CD80, STAT4, and IRAKI) were significantly associated with eczema (adjusted p-value < 0.02). None of these SNPs were associated with both asthma and eczema. Bayesian network analysis identified 4 SNPs that were predictive of asthma and 10 SNPs that predicted eczema. Of the genes identified using Bayesian networks, only CD80 was associated with eczema in the single-SNP study. Using novel methodology that allows for screening and replication in the same population, we have identified associations of innate immune genes with asthma and eczema. Bayesian network analysis suggests that additional SNPs influence disease susceptibility via SNP interactions. Conclusion Our findings suggest that innate immune genes contribute to the pathogenesis of asthma and eczema, and that these diseases likely have different genetic determinants. PMID:22192168

CD-ROM End-User Instruction: A Planning Model.

ERIC Educational Resources Information Center

Johnson, Mary E.; Rosen, Barbara S.

1990-01-01

Discusses methods and content of library instruction for CD-ROM searching in terms of the needs of end-users. Instructional methods explored include staff instruction, structured instruction, database documentation, tutorials and help screens, and floaters. Suggestions for effective instruction in transfer of skills, database content, database…

Yield of coeliac screening in abdominal pain-associated functional gastrointestinal system disorders.

PubMed

Kansu, Aydan; Kuloğlu, Zarife; Demir, Arzu; Yaman, Aytaç

2015-11-01

Chronic abdominal pain (CAP) in childhood is common and in the majority functional. While CAP is one of the complaints of coeliac disease (CD), whether CAP as a sole complaint is indicative of CD is unclear. Our aim was to evaluate the relationship between CAP and CD. The study was conducted on 1047 children (61.1% female, mean age 9.6 ± 4.1 years) with CAP. Patients were evaluated according to the Rome III criteria. Patients with alarm symptoms and conditions known to be associated with CD were excluded. Patients were screened for CD using a rapid tissue transglutaminase (tTG) test; positive cases were tested by tTG ELISA, and duodenal biopsies were obtained if tTG was above the normal limit. Functional dyspepsia (FD), irritable bowel syndrome (IBS) and functional abdominal pain (FAP) were diagnosed in 384 (36.7%), 274 (26.2%) and 389 (37.2%) patients, respectively. In 13 patients, the tTG rapid test was positive; 10 were also positive for tTG by ELISA and histopathological evaluations diagnosed CD in all 10 patients. The overall prevalence of CD was 0.95% (2.2%, 0.5% and 0.5% in patients with IBS, FD and FAP, respectively). The prevalence of CD in patients with IBS was higher than expected but with borderline statistical significance (P = 0.053). CD is found as common in children with FD and FAP as in the general population. CD was more commonly diagnosed in IBS patients with borderline statistical significance. We suggest that particular attention be paid to children with IBS. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Drug Screening Identifies Niclosamide as an Inhibitor of Breast Cancer Stem-Like Cells

PubMed Central

Wang, Yu-Chi; Chao, Tai-Kuang; Chang, Cheng-Chang; Yo, Yi-Te; Yu, Mu-Hsien; Lai, Hung-Cheng

2013-01-01

The primary cause of death from breast cancer is the progressive growth of tumors and resistance to conventional therapies. It is currently believed that recurrent cancer is repopulated according to a recently proposed cancer stem cell hypothesis. New therapeutic strategies that specifically target cancer stem-like cells may represent a new avenue of cancer therapy. We aimed to discover novel compounds that target breast cancer stem-like cells. We used a dye-exclusion method to isolate side population (SP) cancer cells and, subsequently, subjected these SP cells to a sphere formation assay to generate SP spheres (SPS) from breast cancer cell lines. Surface markers, stemness genes, and tumorigenicity were used to test stem properties. We performed a high-throughput drug screening using these SPS. The effects of candidate compounds were assessed in vitro and in vivo. We successfully generated breast cancer SPS with stem-like properties. These SPS were enriched for CD44high (2.8-fold) and CD24low (4-fold) cells. OCT4 and ABCG2 were overexpressed in SPS. Moreover, SPS grew tumors at a density of 103, whereas an equivalent number of parental cells did not initiate tumor formation. A clinically approved drug, niclosamide, was identified from the LOPAC chemical library of 1,258 compounds. Niclosamide downregulated stem pathways, inhibited the formation of spheroids, and induced apoptosis in breast cancer SPS. Animal studies also confirmed this therapeutic effect. The results of this proof-of-principle study may facilitate the development of new breast cancer therapies in the near future. The extension of niclosamide clinical trials is warranted. PMID:24058587

SWATH™- and iTRAQ-based quantitative proteomic analyses reveal an overexpression and biological relevance of CD109 in advanced NSCLC.

PubMed

Zhang, Fanglin; Lin, Hechun; Gu, Aiqin; Li, Jing; Liu, Lei; Yu, Tao; Cui, Yongqi; Deng, Wei; Yan, Mingxia; Li, Jinjun; Yao, Ming

2014-05-06

To identify cancer-related proteins, we used isobaric tags in a relative and absolute quantitation (iTRAQ) proteomic approach and SWATH™ quantification approach to analyze the secretome of an isogenic pair of highly metastatic and low metastatic non-small-cell lung cancer (NSCLC) cell lines. In addition, we compared two groups of pooled serum samples (12 early-stage and 12 late-stage patients) to mine data for candidates screened by iTRAQ-labeled proteomic analysis. A total of 110 proteins and 71 proteins were observed to be significantly differentially expressed in the cell line secretome and NSCLC sera, respectively. Among these proteins, CD109 was found to be highly expressed in both the highly metastatic cell line secretome and the group of late-stage patients. A sandwich ELISA assay also demonstrated an elevation of serum CD109 levels in individual NSCLC patients (n=30) compared with healthy subjects (n=19). Furthermore, CD109 displayed higher expression in lung cancer tissues compared with their matched noncancerous lung tissues (n=72). In addition, the knockdown of CD109 influenced several NSCLC cell bio-functions, for instance, depressing cell growth, affecting cell cycle phases. These phenomena suggest that CD109 plays a critical role in NSCLC progression. We simultaneously applied two quantitative proteomic approaches-iTRAQ-labeling and SWATH™-to analyze the secretome of metastatic cell lines, in order to explore the cancer-associated proteins in conditioned media. In this study, our results indicate that CD109 plays a critical role in non-small-cell lung cancer (NSCLC) progression, and is overexpressed in advanced NSCLC. Copyright © 2014 Elsevier B.V. All rights reserved.

Expression of Master Regulators of T-cell, Helper T-cell and Follicular Helper T-cell Differentiation in Angioimmunoblastic T-cell Lymphoma.

PubMed

Matsumoto, Yosuke; Nagoshi, Hisao; Yoshida, Mihoko; Kato, Seiichi; Kuroda, Junya; Shimura, Kazuho; Kaneko, Hiroto; Horiike, Shigeo; Nakamura, Shigeo; Taniwaki, Masafumi

2017-11-01

Objective It has been postulated that the normal counterpart of angioimmunoblastic T-cell lymphoma (AITL) is the follicular helper T-cell (TFH). Recent immunological studies have identified several transcription factors responsible for T-cell differentiation. The master regulators associated with T-cell, helper T-cell (Th), and TFH differentiation are reportedly BCL11B, Th-POK, and BCL6, respectively. We explored the postulated normal counterpart of AITL with respect to the expression of the master regulators of T-cell differentiation. Methods We performed an immunohistochemical analysis in 15 AITL patients to determine the expression of the master regulators and several surface markers associated with T-cell differentiation. Results BCL11B was detected in 10 patients (67%), and the surface marker of T-cells (CD3) was detected in all patients. Only 2 patients (13%) expressed the marker of naïve T-cells (CD45RA), but all patients expressed the marker of effector T-cells (CD45RO). Nine patients expressed Th-POK (60%), and 7 (47%) expressed a set of surface antigens of Th (CD4-positive and CD8-negative). In addition, BCL6 and the surface markers of TFH (CXCL13, PD-1, and SAP) were detected in 11 (73%), 8 (53%), 14 (93%), and all patients, respectively. Th-POK-positive/BCL6-negative patients showed a significantly shorter overall survival (OS) than the other patients (median OS: 33.0 months vs. 74.0 months, p=0.020; log-rank test). Conclusion Many of the AITL patients analyzed in this study expressed the master regulators of T-cell differentiation. The clarification of the diagnostic significance and pathophysiology based on the expression of these master regulators in AITL is expected in the future.

Particle size distribution and characteristics of heavy metals in road-deposited sediments from Beijing Olympic Park.

PubMed

Li, Haiyan; Shi, Anbang; Zhang, Xiaoran

2015-06-01

Due to rapid urbanization and industrialization, heavy metals in road-deposited sediments (RDSs) of parks are emitted into the terrestrial, atmospheric, and water environment, and have a severe impact on residents' and tourists' health. To identify the distribution and characteristic of heavy metals in RDS and to assess the road environmental quality in Chinese parks, samples were collected from Beijing Olympic Park in the present study. The results indicated that particles with small grain size (<150 μm) were the dominant fraction. The length of dry period was one of the main factors affecting the particle size distribution, as indicated by the variation of size fraction with the increase of dry days. The amount of heavy metal (i.e., Cu, Zn, Pb and Cd) content was the largest in particles with small size (<150 μm) among all samples. Specifically, the percentage of Cu, Zn, Pb and Cd in these particles was 74.7%, 55.5%, 56.6% and 71.3%, respectively. Heavy metals adsorbed in sediments may mainly be contributed by road traffic emissions. The contamination levels of Pb and Cd were higher than Cu and Zn on the basis of the mean heavy metal contents. Specifically, the geoaccumulation index (Igeo) decreased in the order: Cd>Pb>Cu>Zn. This study analyzed the mobility of heavy metals in sediments using partial sequential extraction with the Tessier procedure. The results revealed that the apparent mobility and potential metal bioavailability of heavy metals in the sediments, based on the exchangeable and carbonate fractions, decreased in the order: Cd>Zn≈Pb>Cu. Copyright © 2015. Published by Elsevier B.V.

Mucosal Healing and the Risk of Ischemic Heart Disease or Atrial Fibrillation in Patients with Celiac Disease; A Population-Based Study

PubMed Central

Lebwohl, Benjamin; Emilsson, Louise; Fröbert, Ole; Einstein, Andrew J.; Green, Peter H. R.; Ludvigsson, Jonas F.

2015-01-01

Background Patients with celiac disease (CD), characterized histologically by villous atrophy (VA) of the small intestine, have an increased risk of ischemic heart disease (IHD) and atrial fibrillation (AF), risks that persist for years after commencing the gluten-free diet. It is unknown whether persistent VA on follow-up biopsy, rather than mucosal healing, affects the risk of IHD or AF. Methods We identified patients with histologic evidence of CD diagnosed at all 28 pathology departments in Sweden. Among patients who underwent a follow-up small intestinal biopsy, we compared patients with persistent VA to those who showed histologic improvement, with regard to the development of IHD (angina pectoris or myocardial infarction) or AF. Results Among patients with CD and a follow-up biopsy (n = 7,440), the median age at follow-up biopsy was 25 years, with 1,063 (14%) patients who were ≥60 years at the time of follow-up biopsy. Some 196 patients developed IHD and 205 patients developed AF. After adjusting for age, gender, duration of CD, calendar period, and educational attainment, there was no significant effect of persistent VA on IHD (adjusted HR 0.97; 95%CI 0.73–1.30). Adjusting for diabetes had a negligible effect (adjusted HR 0.98; 95%CI 0.73–1.31). There was no significant association between persistent VA and the risk of AF (adjusted HR 0.98; 95%CI 0.74–1.30). Conclusions In this population-based study of patients with CD, persistent VA on follow-up biopsy was not associated with an increased risk of IHD or AF. Failed mucosal healing does not influence the risk of these cardiac events. PMID:25635403

Consumption of vegetables and fruit and the risk of inflammatory bowel disease: a meta-analysis.

PubMed

Li, Fang; Liu, Xiaoqin; Wang, Weijing; Zhang, Dongfeng

2015-06-01

To date, associations between consumption of vegetables and fruit and the risk of inflammatory bowel disease have been a controversial subject. Therefore, we carried out a meta-analysis to evaluate the associations. A comprehensive search was performed in PubMed, Embase, Web of Science, and the China National Knowledge Infrastructure to identify all relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) from random-effects or fixed-effects models were calculated. Publication bias was estimated using Egger's test and the funnel plot. A total of 14 case-control studies were included in this meta-analysis. On the basis of the highest versus the lowest analysis, consumption of vegetables was associated inversely with the risk of ulcerative colitis (UC) (OR=0.71, 95% CI 0.58-0.88, n=9 studies), but not with Crohn's disease (CD) (OR=0.66, 95% CI 0.40-1.09, n=8 studies). Higher consumption of fruit was associated inversely with the risk of UC (OR=0.69, 95% CI 0.49-0.96, n=8 studies) and CD (OR=0.57, 95% CI 0.44-0.74, n=10 studies). For intake of vegetables and the risk of CD, subgroup analysis showed a significant association for studies carried out in Europe (OR=0.36, 95% CI 0.23-0.57), but not in Asia (OR=1.00, 95% CI 0.50-2.03). No significant publication bias was found for the analysis of intake of vegetables and the risk of UC, intake of fruit and the risk of UC, and intake of vegetables and the risk of CD. This meta-analysis indicates that consumption of vegetables and fruit might be associated inversely with the risk of UC and CD, and the results need to be further confirmed.

Performance comparison of small-pixel CdZnTe radiation detectors with gold contacts formed by sputter and electroless deposition

NASA Astrophysics Data System (ADS)

Bell, S. J.; Baker, M. A.; Duarte, D. D.; Schneider, A.; Seller, P.; Sellin, P. J.; Veale, M. C.; Wilson, M. D.

2017-06-01

Recent improvements in the growth of wide-bandgap semiconductors, such as cadmium zinc telluride (CdZnTe or CZT), has enabled spectroscopic X/γ-ray imaging detectors to be developed. These detectors have applications covering homeland security, industrial analysis, space science and medical imaging. At the Rutherford Appleton Laboratory (RAL) a promising range of spectroscopic, position sensitive, small-pixel Cd(Zn)Te detectors have been developed. The challenge now is to improve the quality of metal contacts on CdZnTe in order to meet the demanding energy and spatial resolution requirements of these applications. The choice of metal deposition method and fabrication process are of fundamental importance. Presented is a comparison of two CdZnTe detectors with contacts formed by sputter and electroless deposition. The detectors were fabricated with a 74 × 74 array of 200 μm pixels on a 250 μm pitch and bump-bonded to the HEXITEC ASIC. The X/γ-ray emissions from an 241Am source were measured to form energy spectra for comparison. It was found that the detector with contacts formed by electroless deposition produced the best uniformity and energy resolution; the best pixel produced a FWHM of 560 eV at 59.54 keV and 50% of pixels produced a FWHM better than 1.7 keV . This compared with a FWHM of 1.5 keV for the best pixel and 50% of pixels better than 4.4 keV for the detector with sputtered contacts.

Lab on a CD.

PubMed

Madou, Marc; Zoval, Jim; Jia, Guangyao; Kido, Horacio; Kim, Jitae; Kim, Nahui

2006-01-01

In this paper, centrifuge-based microfluidic platforms are reviewed and compared with other popular microfluidic propulsion methods. The underlying physical principles of centrifugal pumping in microfluidic systems are presented and the various centrifuge fluidic functions, such as valving, decanting, calibration, mixing, metering, heating, sample splitting, and separation, are introduced. Those fluidic functions have been combined with analytical measurement techniques, such as optical imaging, absorbance, and fluorescence spectroscopy and mass spectrometry, to make the centrifugal platform a powerful solution for medical and clinical diagnostics and high throughput screening (HTS) in drug discovery. Applications of a compact disc (CD)-based centrifuge platform analyzed in this review include two-point calibration of an optode-based ion sensor, an automated immunoassay platform, multiple parallel screening assays, and cellular-based assays. The use of modified commercial CD drives for high-resolution optical imaging is discussed as well. From a broader perspective, we compare technical barriers involved in applying microfluidics for sensing and diagnostic use and applying such techniques to HTS. The latter poses less challenges and explains why HTS products based on a CD fluidic platform are already commercially available, whereas we might have to wait longer to see commercial CD-based diagnostics.

Brief assessment of food insecurity accurately identifies high-risk US adults.

PubMed

Gundersen, Craig; Engelhard, Emily E; Crumbaugh, Amy S; Seligman, Hilary K

2017-06-01

To facilitate the introduction of food insecurity screening into clinical settings, we examined the test performance of two-item screening questions for food insecurity against the US Department of Agriculture's Core Food Security Module. We examined sensitivity, specificity and accuracy of various two-item combinations of questions assessing food insecurity in the general population and high-risk population subgroups. 2013 Current Population Survey December Supplement, a population-based US survey. All survey participants from the general population and high-risk subgroups. The test characteristics of multiple two-item combinations of questions assessing food insecurity had adequate sensitivity (>97 %) and specificity (>70 %) for widespread adoption as clinical screening measures. We recommend two specific items for clinical screening programmes based on their widespread current use and high sensitivity for detecting food insecurity. These items query how often the household 'worried whether food would run out before we got money to buy more' and how often 'the food that we bought just didn't last and we didn't have money to get more'. The recommended items have sensitivity across high-risk population subgroups of ≥97 % and a specificity of ≥74 % for food insecurity.

Adversity and Resilience Are Associated with Outcome after Mild Traumatic Brain Injury in Military Service Members.

PubMed

Reid, Matthew W; Cooper, Douglas B; Lu, Lisa H; Iverson, Grant L; Kennedy, Jan E

2018-05-15

The objective of this study was to assess the associations between resilience, adversity, post-concussion symptoms, and post-traumatic stress symptom reporting after mild traumatic brain injury (mTBI). We hypothesized that resilience would be associated with less symptom reporting, and adversity would be associated with greater symptom reporting. This was a cross-sectional study of retrospective data collected for an ongoing TBI repository. United States military service members who screened positive for mTBI during a primary care visit completed the Trauma History Screen (THS), Connor-Davidson Resilience Scale (CD-RISC), Neurobehavioral Symptom Inventory (NSI), and post-traumatic stress disorder (PTSD) Checklist-Civilian Version (PCL-C). Data collected from February 2015 to August 2016 were used for the present study. Only participants with complete data for the above measures were included, yielding a sample size of 165 participants. Adversity (THS) and resilience (CD-RISC) scores were each correlated significantly with post-concussion (NSI) and traumatic stress (PCL-C) total and subscale scores in the hypothesized direction. Interactions between adversity and resilience were absent for all measures except the NSI sensory subscale. Four traumatic event types were significantly associated positively with most NSI and PCL-C total and subscale scores, but the age at which traumatic events were first experienced showed few and mixed significant associations. In conclusion, resilience and adversity were significantly associated with symptom endorsement after mTBI. Screening for cumulative adversity may identify individuals at greater risk of developing persistent post-concussion symptoms and/or PTSD, and interventions that increase resilience may reduce symptom severity.

Colon Cancer Screening Programs: Impact of an Organized Screening Strategy Assessed by the EDIFICE Surveys.

PubMed

Viguier, Jérôme; Morère, Jean-François; Brignoli-Guibaudet, Lysel; Lhomel, Christine; Couraud, Sébastien; Eisinger, François

2018-03-05

The aim of EDIFICE surveys is to improve insight into the behavior of the French population with regard to cancer prevention and participation in screening programs. Via the colorectal cancer screening program, all average-risk individuals in the 50-74-year age group are invited every 2 years to do a guaiac-based or, since April 2015, an immunochemical fecal occult blood test. The fifth edition of the nationwide observational survey was conducted by phone interviews using the quota method. A representative sample of 1299 individuals with no history of cancer (age, 50-74 years) was interviewed between 22 November and 7 December 2016. The present analysis focuses on minimum lifetime uptake of screening tests, compliance to recommended repeat-screening intervals, and reasons for non-participation. In 2016, 64% survey participants had been screened at least once and 38% had been screened in the previous 2 years, suggesting a trend towards increasing participation rates, particularly in the younger age categories and among men. The 2016 data also suggest that the newly implemented FIT-based screening program has been well perceived by the population. Up to one in four individuals cited "no risk factors" as the reason for not undergoing screening. This reveals ignorance of the fact that the colorectal cancer screening program actually targets all average-risk individuals in a given age group, without individual risk factors. We suggest the next step should be dedicated to educational approaches to explain exactly what screening involves and to persuasive messages targeting those who to date have remained unreceptive to information campaigns.

Bioaccessibility and Human Exposure Assessment of Cadmium and Arsenic in Pakchoi Genotypes Grown in Co-Contaminated Soils

PubMed Central

Wei, Yanyan; Zheng, Xiaoman; Shohag, Md. Jahidul Islam; Gu, Minghua

2017-01-01

In many countries cadmium (Cd) and arsenic (As) commonly coexist in soils contaminated by mining activities, and can easily enter the human body via consumption of leafy vegetables, like the popularly consumed pakchoi (Brassica chinensis L.), causing major health concerns. In the present study, bioaccessibility and human exposure of Cd and As were assessed in twenty genotypes of pakchoi cultured at two different levels of co-contamination to identify low health risk genotypes. The bioaccessibilities of Cd and As represent a fraction of the total metals content could be bioaccessible for human, in the present study, significant differences in pakchoi Cd and As bioaccessibility were observed among all tested genotypes and co-contaminated levels. Cd and As bioaccessibility of pakchoi were in the ranges of 24.0–87.6% and 20.1–82.5%, respectively, for in the high level co-contaminated soils, which was significantly higher than for low level co-contaminated soils with 7.9–71.8% for Cd bioaccessibility and 16.1–59.0% for As bioaccessibility. The values of bioaccessible established daily intakes (BEDI) and the total bioaccessible target hazard quotients (TBTHQ) of Cd and As were also considerably higher in high level co-contaminated soils than in low level co-contaminated soils. Two genotypes (Meiguanqinggengcai and Zhenqing60F1) contained relatively low concentrations and bioaccessible Cd and As and, their BEDI and TBTHQ for Cd and As ranged below the tolerable limits set by the FAO/WHO (BEDI of Cd < 0.83 μg kg−1 bw day−1, BEDI of As < 3 μg kg−1 bw day−1) and United States Environmental Protection Agency (TBTHQ for Cd and As < 1), this applied for both levels of co-contaminated soils for adults and children. Consequently, these findings suggest identification of safe genotypes in leafy vegetable with low health risk via genotypic screening and breeding methods could be a useful strategy to ensure the safety of food crops grown in those Cd and As co-contaminated fields due to mining activities. PMID:28850097

Bioaccessibility and Human Exposure Assessment of Cadmium and Arsenic in Pakchoi Genotypes Grown in Co-Contaminated Soils.

PubMed

Wei, Yanyan; Zheng, Xiaoman; Shohag, Md Jahidul Islam; Gu, Minghua

2017-08-29

In many countries cadmium (Cd) and arsenic (As) commonly coexist in soils contaminated by mining activities, and can easily enter the human body via consumption of leafy vegetables, like the popularly consumed pakchoi ( Brassica chinensis L.), causing major health concerns. In the present study, bioaccessibility and human exposure of Cd and As were assessed in twenty genotypes of pakchoi cultured at two different levels of co-contamination to identify low health risk genotypes. The bioaccessibilities of Cd and As represent a fraction of the total metals content could be bioaccessible for human, in the present study, significant differences in pakchoi Cd and As bioaccessibility were observed among all tested genotypes and co-contaminated levels. Cd and As bioaccessibility of pakchoi were in the ranges of 24.0-87.6% and 20.1-82.5%, respectively, for in the high level co-contaminated soils, which was significantly higher than for low level co-contaminated soils with 7.9-71.8% for Cd bioaccessibility and 16.1-59.0% for As bioaccessibility. The values of bioaccessible established daily intakes (BEDI) and the total bioaccessible target hazard quotients (TBTHQ) of Cd and As were also considerably higher in high level co-contaminated soils than in low level co-contaminated soils. Two genotypes (Meiguanqinggengcai and Zhenqing60F1) contained relatively low concentrations and bioaccessible Cd and As and, their BEDI and TBTHQ for Cd and As ranged below the tolerable limits set by the FAO/WHO (BEDI of Cd < 0.83 μg kg -1 bw day -1 , BEDI of As < 3 μg kg -1 bw day -1 ) and United States Environmental Protection Agency (TBTHQ for Cd and As < 1), this applied for both levels of co-contaminated soils for adults and children. Consequently, these findings suggest identification of safe genotypes in leafy vegetable with low health risk via genotypic screening and breeding methods could be a useful strategy to ensure the safety of food crops grown in those Cd and As co-contaminated fields due to mining activities.

Longitudinal predictors of colorectal cancer screening among participants in a randomized controlled trial.

PubMed

Murphy, Caitlin C; Vernon, Sally W; Haddock, Nicole M; Anderson, Melissa L; Chubak, Jessica; Green, Beverly B

2014-09-01

Few studies use longitudinal data to identify predictors of colorectal cancer screening (CRCS). We examined predictors of (1) initial CRCS during the first year of a randomized trial, and (2) repeat CRCS during the second year of the trial among those that completed FOBT in Year 1. The sample comprised 1247 participants of the Systems of Support to Increase Colorectal Cancer Screening (SOS) Trial (Group Health Cooperative, August 2008 to November 2011). Potential predictors of CRCS were identified with logistic regression and included sociodemographics, health history, and validated scales of psychosocial constructs. Prior CRCS (OR 2.64, 95% CI 1.99-3.52) and intervention group (Automated: OR 2.06 95% CI 1.43-2.95; Assisted: OR 4.03, 95% CI 2.69-6.03; Navigated: OR 5.64, 95% CI 3.74-8.49) were predictors of CRCS completion at Year 1. For repeat CRCS at Year 2, prior CRCS at baseline (OR 1.97, 95% CI 1.25-3.11), intervention group (Automated: OR 9.27, 95% CI 4.56-18.82; Assisted: OR 11.17, 95% CI 5.44-22.94; Navigated: OR 13.10, 95% CI 6.33-27.08), and self-efficacy (OR 1.32, 95% CI 1.00-1.73) were significant predictors. Self-efficacy and prior CRCS are important predictors of future screening behavior. CRCS completion increased when access barriers were removed through interventions. Copyright © 2014 Elsevier Inc. All rights reserved.

Blood-based markers of efficacy and resistance to cetuximab treatment in metastatic colorectal cancer: results from CALGB 80203 (Alliance).

PubMed

Hatch, Ace J; Sibley, Alexander B; Starr, Mark D; Brady, J Chris; Jiang, Chen; Jia, Jingquan; Bowers, Daniel L; Pang, Herbert; Owzar, Kouros; Niedzwiecki, Donna; Innocenti, Federico; Venook, Alan P; Hurwitz, Herbert I; Nixon, Andrew B

2016-09-01

Circulating protein markers were assessed in patients with colorectal cancer (CRC) treated with cetuximab in CALGB 80203 to identify prognostic and predictive biomarkers. Patients with locally advanced or metastatic CRC received FOLFOX or FOLFIRI chemotherapy (chemo) or chemo in combination with cetuximab. Baseline plasma samples from 152 patients were analyzed for six candidate markers [epidermal growth factor (EGF), heparin-binding EGF (HBEGF), epidermal growth factor receptor (EGFR), HER2, HER3, and CD73]. Analyte levels were associated with survival endpoints using univariate Cox proportional hazards models. Predictive markers were identified using a treatment-by-marker interaction term in the Cox model. Plasma levels of EGF, HBEGF, HER3, and CD73 were prognostic for overall survival (OS) across all patients (KRAS mutant and wild-type). High levels of EGF predicted for lack of OS benefit from cetuximab in KRAS wild-type (WT) patients (chemo HR = 0.98, 95% CI = 0.74-1.29; chemo+cetuximab HR = 1.54, 95% CI = 1.05-2.25; interaction P = 0.045) and benefit from cetuximab in KRAS mutant patients (chemo HR = 1.72, 95% CI = 1.02-2.92; chemo+cetuximab HR = 0.90, 95% CI = 0.67-1.21; interaction P = 0.026). Across all patients, higher HER3 levels were associated with significant OS benefit from cetuximab treatment (chemo HR = 4.82, 95% CI = 1.68-13.84; chemo+cetuximab HR = 0.95, 95% CI = 0.31-2.95; interaction P = 0.046). CD73 was also identified as predictive of OS benefit in KRAS WT patients (chemo HR = 1.28, 95% CI = 0.88-1.84; chemo+cetuximab HR = 0.60, 95% CI = 0.32-1.13; interaction P = 0.049). Although these results are preliminary, and confirmatory studies are necessary before clinical application, the data suggest that HER3 and CD73 may play important roles in the biological response to cetuximab. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Differential Recognition Preferences of the Three Src Homology 3 (SH3) Domains from the Adaptor CD2-associated Protein (CD2AP) and Direct Association with Ras and Rab Interactor 3 (RIN3)*

PubMed Central

Rouka, Evgenia; Simister, Philip C.; Janning, Melanie; Kumbrink, Joerg; Konstantinou, Tassos; Muniz, João R. C.; Joshi, Dhira; O'Reilly, Nicola; Volkmer, Rudolf; Ritter, Brigitte; Knapp, Stefan; von Delft, Frank; Kirsch, Kathrin H.; Feller, Stephan M.

2015-01-01

CD2AP is an adaptor protein involved in membrane trafficking, with essential roles in maintaining podocyte function within the kidney glomerulus. CD2AP contains three Src homology 3 (SH3) domains that mediate multiple protein-protein interactions. However, a detailed comparison of the molecular binding preferences of each SH3 remained unexplored, as well as the discovery of novel interactors. Thus, we studied the binding properties of each SH3 domain to the known interactor Casitas B-lineage lymphoma protein (c-CBL), conducted a peptide array screen based on the recognition motif PxPxPR and identified 40 known or novel candidate binding proteins, such as RIN3, a RAB5-activating guanine nucleotide exchange factor. CD2AP SH3 domains 1 and 2 generally bound with similar characteristics and specificities, whereas the SH3-3 domain bound more weakly to most peptide ligands tested yet recognized an unusually extended sequence in ALG-2-interacting protein X (ALIX). RIN3 peptide scanning arrays revealed two CD2AP binding sites, recognized by all three SH3 domains, but SH3-3 appeared non-functional in precipitation experiments. RIN3 recruited CD2AP to RAB5a-positive early endosomes via these interaction sites. Permutation arrays and isothermal titration calorimetry data showed that the preferred binding motif is Px(P/A)xPR. Two high-resolution crystal structures (1.65 and 1.11 Å) of CD2AP SH3-1 and SH3-2 solved in complex with RIN3 epitopes 1 and 2, respectively, indicated that another extended motif is relevant in epitope 2. In conclusion, we have discovered novel interaction candidates for CD2AP and characterized subtle yet significant differences in the recognition preferences of its three SH3 domains for c-CBL, ALIX, and RIN3. PMID:26296892

Mechanical Component Diagnostic System

DTIC Science & Technology

1991-01-01

Control and Display Unit ( CADU ) executes the system software and controls data acquisition that is carried out by 6 the Data Acquisition Unit (DAU... CADU screen. Displays intended for the CD are also echoed on the CADU in the FDR backup mode. If initialization is successful, clocks are synchronized...and normal MCDS monitoring mode is entered. If there is no display on the CD, the user may manually switch to the backup CD display on the CADU . Hence

Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology

PubMed Central

Ludvigsson, Jonas F; Bai, Julio C; Biagi, Federico; Card, Timothy R; Ciacci, Carolina; Ciclitira, Paul J; Green, Peter H R; Hadjivassiliou, Marios; Holdoway, Anne; van Heel, David A; Kaukinen, Katri; Leffler, Daniel A; Leonard, Jonathan N; Lundin, Knut E A; McGough, Norma; Davidson, Mike; Murray, Joseph A; Swift, Gillian L; Walker, Marjorie M; Zingone, Fabiana; Sanders, David S

2014-01-01

A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD. PMID:24917550

Perceived discrimination and cancer screening behaviors in US Hispanics: the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study.

PubMed

Valdovinos, Cristina; Penedo, Frank J; Isasi, Carmen R; Jung, Molly; Kaplan, Robert C; Giacinto, Rebeca Espinoza; Gonzalez, Patricia; Malcarne, Vanessa L; Perreira, Krista; Salgado, Hugo; Simon, Melissa A; Wruck, Lisa M; Greenlee, Heather A

2016-01-01

Perceived discrimination has been associated with lower adherence to cancer screening guidelines. We examined whether perceived discrimination was associated with adherence to breast, cervical, colorectal, and prostate cancer screening guidelines in US Hispanic/Latino adults. Data were obtained from the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study, including 5,313 Hispanic adults aged 18–74 from Bronx, NY, Chicago, IL, Miami, FL, and San Diego, CA, and those who were within appropriate age ranges for specific screening tests were included in the analysis. Cancer screening behaviors were assessed via self-report. Perceived discrimination was measured using the Perceived Ethnic Discrimination Questionnaire. Confounder-adjusted multivariable polytomous logistic regression models assessed the association between perceived discrimination and adherence to cancer screening guidelines. Among women eligible for screening, 72.1 % were adherent to cervical cancer screening guidelines and 71.3 %were adherent to breast cancer screening guidelines. In participants aged 50–74, 24.6 % of women and 27.0 % of men were adherent to fecal occult blood test guidelines; 43.5 % of women and 34.8 % of men were adherent to colonoscopy/sigmoidoscopy guidelines; 41.0 % of men were adherent to prostate-specific antigen screening guidelines. Health insurance coverage, rather than perceived ethnic discrimination,was the variable most associated with receiving breast, cervical,colorectal, or prostate cancer screening. The influence of discrimination as a barrier to cancer screening may be modest among Hispanics/Latinos in urban US regions. Having health insurance facilitates cancer screening in this population. Efforts to increase cancer screening in Hispanics/Latinos should focus on increasing access to these services, especially among the uninsured.

Lifestyle predictors for non-participation and outcome in the second round of faecal immunochemical test in colorectal cancer screening.

PubMed

Knudsen, Markus Dines; Berstad, Paula; Hjartåker, Anette; Gulichsen, Elisabeth Haagensen; Hoff, Geir; de Lange, Thomas; Bernklev, Tomm; Botteri, Edoardo

2017-08-08

To reduce colorectal cancer (CRC) mortality through population-based screening programmes using faecal tests, it is important that individuals continue to participate in the repeated rounds of screening. We aimed to identify lifestyle predictors for discontinuation of faecal immunochemical test (FIT) screening after the first round, as well as lifestyle predictors for colorectal neoplasia detected in the second-round FIT screening. In this longitudinal study, we invited 6959 individuals aged 50-74 years from south-east Norway for a first round of FIT screening and to complete a self-reported lifestyle questionnaire on demographic factors, body mass index (BMI, kg m -2 ), smoking habits, physical activity, consumption of alcohol and dietary items. Two years later, we estimated the associations between these factors, non-participation and screening results in the second round of FIT screening using adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Of the 3114 responders to the questionnaire who completed the first-round FIT and who were invited to participate in second-round FIT screening, 540 (17%) did not participate. The OR and (95% CI) for discontinuation of FIT screening after the first round was 1.61 (1.24-2.10) for current smoking compared with non-smoking; 2.01 (1.25-3.24) for BMI⩾35 kg m -2 compared with BMI 16.9-24.9 kg m -2 and 0.70 (0.52-0.94) for physical activity in the third quartile vs the first. Among participants, smoking, high BMI and high alcohol consumption were associated with an increased odds of detecting colorectal neoplasia (n=107). These results may indicate that Norwegian FIT screening participants who discontinue after the first round have lifestyle behaviours associated with increased risk of CRC.

Ocean acidification increases cadmium accumulation in marine bivalves: a potential threat to seafood safety.

PubMed

Shi, Wei; Zhao, Xinguo; Han, Yu; Che, Zhumei; Chai, Xueliang; Liu, Guangxu

2016-01-21

To date, the effects of ocean acidification on toxic metals accumulation and the underlying molecular mechanism remains unknown in marine bivalve species. In the present study, the effects of the realistic future ocean pCO2 levels on the cadmium (Cd) accumulation in the gills, mantle and adductor muscles of three bivalve species, Mytilus edulis, Tegillarca granosa, and Meretrix meretrix, were investigated. The results obtained suggested that all species tested accumulated significantly higher Cd (p < 0.05) in the CO2 acidified seawater during the 30 days experiment and the health risk of Cd (based on the estimated target hazard quotients, THQ) via consumption of M. meretrix at pH 7.8 and 7.4 significantly increased 1.21 and 1.32 times respectively, suggesting a potential threat to seafood safety. The ocean acidification-induced increase in Cd accumulation may have occurred due to (i) the ocean acidification increased the concentration of Cd and the Cd(2+)/Ca(2+) in the seawater, which in turn increased the Cd influx through Ca channel; (ii) the acidified seawater may have brought about epithelia damage, resulting in easier Cd penetration; and (iii) ocean acidification hampered Cd exclusion.

Ocean acidification increases cadmium accumulation in marine bivalves: a potential threat to seafood safety

PubMed Central

Shi, Wei; Zhao, Xinguo; Han, Yu; Che, Zhumei; Chai, Xueliang; Liu, Guangxu

2016-01-01

To date, the effects of ocean acidification on toxic metals accumulation and the underlying molecular mechanism remains unknown in marine bivalve species. In the present study, the effects of the realistic future ocean pCO2 levels on the cadmium (Cd) accumulation in the gills, mantle and adductor muscles of three bivalve species, Mytilus edulis, Tegillarca granosa, and Meretrix meretrix, were investigated. The results obtained suggested that all species tested accumulated significantly higher Cd (p < 0.05) in the CO2 acidified seawater during the 30 days experiment and the health risk of Cd (based on the estimated target hazard quotients, THQ) via consumption of M. meretrix at pH 7.8 and 7.4 significantly increased 1.21 and 1.32 times respectively, suggesting a potential threat to seafood safety. The ocean acidification-induced increase in Cd accumulation may have occurred due to (i) the ocean acidification increased the concentration of Cd and the Cd2+/Ca2+ in the seawater, which in turn increased the Cd influx through Ca channel; (ii) the acidified seawater may have brought about epithelia damage, resulting in easier Cd penetration; and (iii) ocean acidification hampered Cd exclusion. PMID:26795597

Thermodynamic study on the effects of β-cyclodextrin inclusion with berberine

NASA Astrophysics Data System (ADS)

Yu, Jun-Sheng; Wei, Fang-Di; Gao, Wei; Zhao, Chang-Chun

2002-01-01

The fluorescence enhancement of berberine (Berb) as a result of complex with β-cyclodextrin (β-CD) is investigated. The association constants of α-CD and β-CD with Berb are 60 and 137 M -1 at 20 °C in pH 7.20 aqueous solution. Effects of temperature on the forming inclusion complexes of β-CD with Berb have been examined through using fluorescence titration. Enthalpy and entropy values calculated from fluorescence data are -33.7·kJ mol -1 and 74.3 J·mol -1·K -1, respectively. It was found that the dielectric constant of β-CD cavity is about 24 in a rough analogy with absolute alcohol. These results suggest that the extrusion of 'high energy water' molecules from the cavity of β-CD and hydrophobic interaction upon the inclusion complex formation are the main forces of the inclusion reaction. Effect of pH on the association of β-CD with Berb was also studied. Mechanism of the inclusion of β-CD with Berb is further studied by absorption and NMR measurements. Results show that β-CD forms a 1:1 inclusion complex with Berb.

Detection of paroxysmal nocturnal hemoglobinuria clones in patients with myelodysplastic syndromes and related bone marrow diseases, with emphasis on diagnostic pitfalls and caveats

PubMed Central

Wang, Sa A.; Pozdnyakova, Olga; Jorgensen, Jeffrey L.; Medeiros, L. Jeffrey; Stachurski, Dariusz; Anderson, Mary; Raza, Azra; Woda, Bruce A.

2009-01-01

Background The presence of paroxysmal nocturnal hemoglobinuria clones in the setting of aplastic anemia or myelodysplastic syndrome has been shown to have prognostic and therapeutic implications. However, the status of paroxysmal nocturnal hemoglobinuria clones in various categories of myelodysplastic syndrome and in other bone marrow disorders is not well-studied. Design and Methods By using multiparameter flow cytometry immunophenotypic analysis with antibodies specific for four glycosylphosphatidylinositol-anchored proteins (CD55, CD59, CD16, CD66b) and performing an aerolysin lysis confirmatory test in representative cases, we assessed the paroxysmal nocturnal hemoglobinuria-phenotype granulocytes in 110 patients with myelodysplastic syndrome, 15 with myelodysplastic/myeloproliferative disease, 5 with idiopathic myelofibrosis and 6 with acute myeloid leukemia. Results Paroxysmal nocturnal hemoglobinuria-phenotype granulocytes were detected in nine patients with low grade myelodysplastic syndrome who showed clinicopathological features of bone marrow failure, similar to aplastic anemia. All paroxysmal nocturnal hemoglobinuria-positive cases demonstrated loss of the four glycosylphosphatidylinositol-anchored proteins, with CD16−CD66b− clones being larger than those of CD55−CD59− (p<0.05). Altered glycosylphosphatidylinositol-anchored protein expression secondary to granulocytic hypogranulation, immaturity, and/or immunophenotypic abnormalities was present in a substantial number of cases and diagnostically challenging. Conclusions These results show that routine screening for paroxysmal nocturnal hemoglobinuria clones in patients with an intrinsic bone marrow disease who show no clinical evidence of hemolysis has an appreciable yield in patients with low grade myelodysplastic syndromes. The recognition of diagnostic caveats and pitfalls associated with the underlying intrinsic bone marrow disease is essential in interpreting paroxysmal nocturnal hemoglobinuria testing correctly. In our experience, the CD16/CD66b antibody combination is superior to CD55/CD59 in screening for subclinical paroxysmal nocturnal hemoglobinuria because it detects a large clone size and is less subject to analytical interference. PMID:19001281

Detection of paroxysmal nocturnal hemoglobinuria clones in patients with myelodysplastic syndromes and related bone marrow diseases, with emphasis on diagnostic pitfalls and caveats.

PubMed

Wang, Sa A; Pozdnyakova, Olga; Jorgensen, Jeffrey L; Medeiros, L Jeffrey; Stachurski, Dariusz; Anderson, Mary; Raza, Azra; Woda, Bruce A

2009-01-01

The presence of paroxysmal nocturnal hemoglobinuria clones in the setting of aplastic anemia or myelodysplastic syndrome has been shown to have prognostic and therapeutic implications. However, the status of paroxysmal nocturnal hemoglobinuria clones in various categories of myelodysplastic syndrome and in other bone marrow disorders is not well-studied. By using multiparameter flow cytometry immunophenotypic analysis with antibodies specific for four glycosylphosphatidylinositol-anchored proteins (CD55, CD59, CD16, CD66b) and performing an aerolysin lysis confirmatory test in representative cases, we assessed the paroxysmal nocturnal hemoglobinuria-phenotype granulocytes in 110 patients with myelodysplastic syndrome, 15 with myelodysplastic/myeloproliferative disease, 5 with idiopathic myelofibrosis and 6 with acute myeloid leukemia. Paroxysmal nocturnal hemoglobinuria-phenotype granulocytes were detected in nine patients with low grade myelodysplastic syndrome who showed clinicopathological features of bone marrow failure, similar to aplastic anemia. All paroxysmal nocturnal hemoglobinuria-positive cases demonstrated loss of the four glycosylphosphatidylinositol-anchored proteins, with CD16(-)CD66b(-) clones being larger than those of CD55(-)CD59(-) (p<0.05). Altered glycosylphosphatidylinositol-anchored protein expression secondary to granulocytic hypogranulation, immaturity, and/or immunophenotypic abnormalities was present in a substantial number of cases and diagnostically challenging. These results show that routine screening for paroxysmal nocturnal hemoglobinuria clones in patients with an intrinsic bone marrow disease who show no clinical evidence of hemolysis has an appreciable yield in patients with low grade myelodysplastic syndromes. The recognition of diagnostic caveats and pitfalls associated with the underlying intrinsic bone marrow disease is essential in interpreting paroxysmal nocturnal hemoglobinuria testing correctly. In our experience, the CD16/CD66b antibody combination is superior to CD55/CD59 in screening for subclinical paroxysmal nocturnal hemoglobinuria because it detects a large clone size and is less subject to analytical interference.

The study and characteristics of ZnO/CdS nanocomposite and its application on nanoantibacterial activities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ali, Tinku; Tripathi, P.; Ahammed, Nashiruddin

We have studied the structural and optical properties of ZnO/CdS nanocomposite and its application on nanoantibacterial activities. In this paper, we have used X-ray diffraction, Transmission electron microscope (TEM) and Energy dispersive X-ray spectroscopy (EDX) techniques in order to know about the structural and optical properties of synthesized ZnO/CdS nanocomposite. After TEM and EDX analysis it has been confirmed that the shape of this nanocomposite is hexagonal and it has no impurity. The optical absorption spectra of pure ZnO and ZnO/CdS nanocomposite have been presented by UV-Visible Spectrometer and the estimated band gap from absorption peak has been found tomore » be 3.36 and 3.74 eV respectively. Antibacterial activity of ZnO/CdS nanocomposite was evaluated by using standard zone of inhibition (ZOI) microbiology assay. The synthesized ZnO/CdS showed promising antibacterial activity against Staphylococcus aureus in dose dependent manner.« less

Disease-Causing 7.4 kb Cis-Regulatory Deletion Disrupting Conserved Non-Coding Sequences and Their Interaction with the FOXL2 Promotor: Implications for Mutation Screening

PubMed Central

Dostie, Josée; Lemire, Edmond; Bouchard, Philippe; Field, Michael; Jones, Kristie; Lorenz, Birgit; Menten, Björn; Buysse, Karen; Pattyn, Filip; Friedli, Marc; Ucla, Catherine; Rossier, Colette; Wyss, Carine; Speleman, Frank; De Paepe, Anne; Dekker, Job; Antonarakis, Stylianos E.; De Baere, Elfride

2009-01-01

To date, the contribution of disrupted potentially cis-regulatory conserved non-coding sequences (CNCs) to human disease is most likely underestimated, as no systematic screens for putative deleterious variations in CNCs have been conducted. As a model for monogenic disease we studied the involvement of genetic changes of CNCs in the cis-regulatory domain of FOXL2 in blepharophimosis syndrome (BPES). Fifty-seven molecularly unsolved BPES patients underwent high-resolution copy number screening and targeted sequencing of CNCs. Apart from three larger distant deletions, a de novo deletion as small as 7.4 kb was found at 283 kb 5′ to FOXL2. The deletion appeared to be triggered by an H-DNA-induced double-stranded break (DSB). In addition, it disrupts a novel long non-coding RNA (ncRNA) PISRT1 and 8 CNCs. The regulatory potential of the deleted CNCs was substantiated by in vitro luciferase assays. Interestingly, Chromosome Conformation Capture (3C) of a 625 kb region surrounding FOXL2 in expressing cellular systems revealed physical interactions of three upstream fragments and the FOXL2 core promoter. Importantly, one of these contains the 7.4 kb deleted fragment. Overall, this study revealed the smallest distant deletion causing monogenic disease and impacts upon the concept of mutation screening in human disease and developmental disorders in particular. PMID:19543368

Gedunin and Azadiradione: Human Pancreatic Alpha-Amylase Inhibiting Limonoids from Neem (Azadirachta indica) as Anti-Diabetic Agents.

PubMed

Ponnusamy, Sudha; Haldar, Saikat; Mulani, Fayaj; Zinjarde, Smita; Thulasiram, Hirekodathakallu; RaviKumar, Ameeta

2015-01-01

Human pancreatic α-amylase (HPA) inhibitors offer an effective strategy to lower postprandial hyperglycemia via control of starch breakdown. Limonoids from Azadirachta indica known for their therapeutic potential were screened for pancreatic α-amylase inhibition, a known anti-diabetic target. Studies were carried out to reveal their mode of action so as to justify their hypoglycemic potential. Of the nine limonoids isolated/semi-synthesized from A.indica and screened for α-amylase inhibition, azadiradione and exhibited potential inhibition with an IC50 value of 74.17 and 68.38 μM, respectively against HPA under in vitro conditions. Further screening on AR42J α-amylase secretory cell line for cytotoxicity and bioactivity revealed that azadiradione and gedunin exhibited cytotoxicity with IC50 of 11.1 and 13.4μM. Maximal secreted α-amylase inhibition of 41.8% and 53.4% was seen at 3.5 and 3.3μM, respectively. Michaelis-Menten kinetics suggested a mixed mode of inhibition with maltopentaose (Ki 42.2, 18.6 μM) and starch (Ki' 75.8, 37.4 μM) as substrate with a stiochiometry of 1:1 for both azadiradione and gedunin, respectively. The molecular docking simulation indicated plausible π-alkyl and alkyl-alkyl interactions between the aromatic amino acids and inhibitors. Fluorescence and CD confirmed the involvement of tryptophan and tyrosine in ligand binding to HPA. Thermodynamic parameters suggested that binding is enthalpically and entropically driven with ΔG° of -21.25 kJ mol-1 and -21.16 kJ mol-1 for azadiradione and gedunin, respectively. Thus, the limonoids azadiradione and gedunin could bind and inactivate HPA (anti-diabetic target) and may prove to be lead drug candidates to reduce/control post-prandial hyperglycemia.

Systematic Review with Meta-analysis: Recurrence of Crohn's disease after Total Colectomy with Permanent Ileostomy

PubMed Central

Fumery, Mathurin; Dulai, Parambir S.; Meirick, Paul; Farrell, Ann M.; Ramamoorthy, Sonia; Sandborn, William J.; Singh, Siddharth

2016-01-01

Background Subtotal or total colectomy or proctocolectomy with permanent ileostomy (TC-PI) may be a treatment option for medically refractory colonic Crohn's disease (CD). Aim To perform a systematic review and meta-analysis to evaluate the rate, risk factors and outcomes of CD recurrence after TC-PI. Methods In a systematic review ending March 31, 2016, we identified 18 cohort studies (1438 adults) who underwent TC-PI for colonic CD (median follow-up, 7.4 years; interquartile range, 5.3-9.0). We estimated pooled rates (with 95% confidence interval [CI]) of clinical and surgical recurrence, and risk factors for disease recurrence. Results On meta-analysis, the risk of clinical recurrence after TC-PI was 28.0% (95% CI, 21.7-35.3; 14 studies, 260/1004 patients), with a 5- and 10-year median cumulative rate of 23.5% (range, 7-35) and 40% (range, 11-60), respectively. The risk of surgical recurrence was 16.0% (95% CI, 11.1-22.7; 10 studies; 183/1092 patients), with a 5- and 10-year median cumulative rate of 10% (range, 3-29) and 18.5% (range, 14-34), respectively. The risk of clinical and surgical recurrence in patients without ileal disease at baseline was 11.5% (95% CI, 7.7-16.8) and 10.4% (95% CI, 4.5-22.5), respectively. History of ileal disease was associated with 3.2 times higher risk of disease recurrence (RR, 3.2; 95% CI, 1.8-5.6). Other inconsistent risk factors for disease recurrence were penetrating disease and young age at disease onset. Conclusions Small bowel clinical recurrence occurs in about 28% of patients after TC-PI for colonic CD. Disease recurrence risk is 3.2 times higher in patients with history of ileal disease, and continued medical therapy may be advisable in this population. In patients without ileal inflammation at surgery, continued endoscopic surveillance may identify asymptomatic disease recurrence to guide therapy. PMID:27928830

Genetic heterogeneity of Beta thalassemia in Lebanon reflects historic and recent population migration.

PubMed

Makhoul, N J; Wells, R S; Kaspar, H; Shbaklo, H; Taher, A; Chakar, N; Zalloua, P A

2005-01-01

Beta thalassemia is an autosomal recessive disorder characterized by reduced (beta(+)) or absent (beta(0)) beta-globin chain synthesis. In Lebanon it is the most predominant genetic defect. In this study we investigated the religious and geographic distribution of the beta-thalassemia mutations identified in Lebanon, and traced their precise origins. A total of 520 beta-globin chromosomes from patients of different religious and regional backgrounds was studied. Beta thalassemia mutations were identified using Amplification Refractory Mutation System (ARMS) PCR or direct gene sequencing. Six (IVS-I-110, IVS-I-1, IVS-I-6, IVS-II-1, cd 5 and the C > T substitution at cd 29) out of 20 beta-globin defects identified accounted for more than 86% of the total beta-thalassemia chromosomes. Sunni Muslims had the highest beta-thalassemia carrier rate and presented the greatest heterogeneity, with 16 different mutations. Shiite Muslims followed closely with 13 mutations, whereas Maronites represented 11.9% of all beta-thalassemic subjects and carried 7 different mutations. RFLP haplotype analysis showed that the observed genetic diversity originated from both new mutational events and gene flow from population migration. This study provides information about the types and distribution of beta-thalassemia mutations within each religious group and geographic region, which is essential for the implementation of screening and prevention programs.

The Danish Cardiovascular Screening Trial (DANCAVAS): study protocol for a randomized controlled trial.

PubMed

Diederichsen, Axel Cosmus Pyndt; Rasmussen, Lars Melholt; Søgaard, Rikke; Lambrechtsen, Jess; Steffensen, Flemming Hald; Frost, Lars; Egstrup, Kenneth; Urbonaviciene, Grazina; Busk, Martin; Olsen, Michael Hecht; Mickley, Hans; Hallas, Jesper; Lindholt, Jes Sanddal

2015-12-05

The significant increase in the average life expectancy has increased the societal challenge of managing serious age-related diseases, especially cancer and cardiovascular diseases. A routine check by a general practitioner is not sufficient to detect incipient cardiovascular disease. Population-based randomized clinically controlled screening trial. 45,000 Danish men aged 65-74 years living on the Island of Funen, or in the surrounding communities of Vejle and Silkeborg. No exclusion criteria are used. One-third will be invited to cardiovascular seven-faceted screening examinations at one of four locations. The screening will include: (1) low-dose non-contrast CT scan to detect coronary artery calcification and aortic/iliac aneurysms, (2) brachial and ankle blood pressure index to detect peripheral arterial disease and hypertension, (3) a telemetric assessment of the heart rhythm, and (4) a measurement of the cholesterol and plasma glucose levels. Up-to-date cardiovascular preventive treatment is recommended in case of positive findings. To investigate whether advanced cardiovascular screening will prevent death and cardiovascular events, and whether the possible health benefits are cost effective. Registry-based follow-up on all cause death (primary outcome), and costs after 3, 5 and 10 years (secondary outcome). Each of the 45,000 individuals is, by EPIDATA, given a random number from 1-100. Those numbered 67+ will be offered screening; the others will act as a control group. Only those randomized to the screening will be invited to the examination;the remaining participants will not. Numbers randomized: A total of 45,000 men will be randomized 1:2. Recruitment: Enrollment started October 2014. A 5% reduction in overall mortality (HR=0.95), with the risk for a type 1 error=5% and the risk for a type II error=80%, is expected. We expect a 2-year enrollment, a 10-year follow-up, and a median survival of 15 years among the controls. The attendance to screening is assumed to be 70%. The primary aim of this so far stand-alone population-based, randomized trial will be to evaluate the health benefits and costeffectiveness of using non-contrast full truncus computer tomography (CT) scans (to measure coronary artery calcification (CAC) and identify aortic/iliac aneurysms) and measurements of the ankle brachial blood pressure index (ABI) as part of a multifocal screening and intervention program for CVD in men aged 65-74. Attendance rate and compliance to initiated preventive actions must be expected to become of major importance. Current Controlled Trials: ISRCTN12157806 (21 March 2015).

T-screen and yeast assay for the detection of the thyroid-disrupting activities of cadmium, mercury, and zinc.

PubMed

Li, Jian; Liu, Yun; Kong, Dongdong; Ren, Shujuan; Li, Na

2016-05-01

In the present study, a two-hybrid yeast bioassay and a T-screen were used to screen for the thyroid receptor (TR)-disrupting activity of select metallic compounds (CdCl2, ZnCl2, HgCl2, CuSO4, MnSO4, and MgSO4). The results reveal that none of the tested metallic compounds showed TR-agonistic activity, whereas ZnCl2, HgCl2, and CdCl2 demonstrated TR antagonism. For the yeast assay, the dose-response relationship of these metallic compounds was established, and the concentrations producing 20 % of the maximum effect of ZnCl2, HgCl2, and CdCl2 were 9.1 × 10(-5), 3.2 × 10(-6), and 1.2 × 10(-6) mol/L, respectively. The T-screen also supported the finding that ZnCl2, HgCl2, and CdCl2 decreased the cell proliferation at concentrations ranging from 10(-6) to 10(-4) mol/L. Furthermore, the thyroid-disrupting activity of metallic compounds in environmental water samples collected from the Guanting Reservoir, Beijing, China was evaluated. Solid-phase extraction was used to separate the organic extracts, and a modified two-hybrid yeast bioassay revealed that the metallic compounds in the water samples could affect thyroid hormone-induced signaling by decreasing the binding of the thyroid hormone. The addition of ethylenediaminetetraacetic acid (30 mg/L) could eliminate the effects. Thus, the cause(s) of the thyroid toxicity in the water samples appeared to be partly related to the metallic compounds.

Screening of celiac disease in patients with autoimmune thyroid disease from Southern Brazil.

PubMed

Teixeira, Laila M; Nisihara, Renato; Utiyama, Shirley Ramos da Rosa; Bem, Ricardo S de; Marcatto, Cristina; Bertolazo, Michelli; Carvalho, Gisah A de

2014-08-01

The objective of this study was to determine the prevalence of celiac disease (CD) in adults with autoimmune thyroid disease (ATD) from the endocrinology outpatient setting in a university hospital in Southern Brazil. From the years 2007 to 2011, 254 patients with ATD were enrolled consecutively, Grave's disease was diagnosed in 143 (56.3%) and Hashimoto's thyroiditis in 111 (43.7%) of them. All patients answered a questionnaire related to symptoms that could be associated with CD and serum samples to screen for IgA anti-endomysial (EmA-IgA) were collected. EmA-IgA-positive patients were offered upper gastrointestinal endoscopy and biopsy of duodenum. A total of 254 patients were included; 222 (87.4%) female, mean age 45.4 ± 13.43 years (18 to 79 years). EmA-IgA was positive in seven patients (2.7%) and five done endoscopy with biopsy. Of these, three diagnosis of CD was confirmed (1.2%). All the three patients with CD had higher EmA-IgA titration, were female and had Hashimoto's thyroiditis. Like other patients with ATD, CD patients had nonspecific gastrointestinal symptoms, such as heartburn and gastric distention. In our study, one in each 85 patients confirmed the diagnosis of CD. We found a prevalence of 1.2% (1:85) of confirmed CD among Brazilian patients with ATD. Although some IgA-EmA positive patients had Graves' disease and one was male, all three patients with confirmed CD were female and had Hashimoto's thyroiditis.

Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) | Division of Cancer Prevention

Cancer.gov

The PLCO Cancer Screening Trial was a population-based randomized trial to determine the effects of screening on cancer-related mortality and secondary endpoints in more than 150,000 men and women aged 55 to 74. The PLCO Biorepository, accessible by the Cancer Data Access System (CDAS) web portal, contains about 2.7 million biologic specimens from intervention participants

Mammography Use Among Medicare Beneficiaries After Elimination of Cost Sharing.

PubMed

Sabatino, Susan A; Thompson, Trevor D; Guy, Gery P; de Moor, Janet S; Tangka, Florence K

2016-04-01

We examined mammography use before and after Medicare eliminated cost sharing for screening mammography in January 2011. Using National Health Interview Survey data, we examined changes in mammography use between 2010 and 2013 among Medicare beneficiaries aged 65-74 years. Logistic regression and predictive margins were used to examine changes in use after adjusting for covariates. In 2013, 74.7% of women reported a mammogram within 2 years, a 3.5 percentage point increase (95% confidence interval, -0.3, 7.2) compared with 2010. Increases occurred among women aged 65-69 years, unmarried women, and women with usual sources of care and 2-5 physician visits in the prior year. After adjustment, mammography use increased in 2013 versus 2010 (74.8% vs. 71.3%, P=0.039). Interactions between year and income, insurance, race, or ethnicity were not significant. There was a modest increase in mammography use from 2010 to 2013 among Medicare beneficiaries aged 65-74 years, possibly consistent with an effect of eliminating Medicare cost sharing during this time. Findings suggest that eliminating cost sharing might increase use of recommended screening services.

75 FR 58404 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-24

... sclerosis, CD74 deficiency, Ehlers Danlos syndrome (EDS), Marfan/Loewe Dietz syndrome, fibromuscular dysplasia, Kawasaki syndrome, pseudoxanthoma elasticum, and premature placental calcification. Applications... component of the addictive syndrome, with approximately two-thirds of patients relapsing within three months...

Cadmium accumulation in different rice cultivars and screening for pollution-safe cultivars of rice.

PubMed

Yu, Hui; Wang, Junli; Fang, Wei; Yuan, Jiangang; Yang, Zhongyi

2006-11-01

Large areas of contaminated land are being used for agricultural production in some countries due to the high demand for food. To minimize the influx of pollutants to the human food chain through consumption of agricultural products, we propose the concept of pollution-safe cultivars (PSCs), i.e. cultivars whose edible parts accumulate a specific pollutant at a level low enough for safe consumption, even when grown in contaminated soil. We tested the feasibility of the PSC concept by growing 43 cultivars of paddy rice (Oryza sativa L., including 20 normal and 23 hybrid cultivars) under a high (75.69-77.55 mg kg(-1)) and a low (1.75-1.85 mg kg(-1)) cadmium (Cd) exposure. These pot experiments took place in the spring and summer of 2004. At the low level of Cd exposure, 30 out of the 43 tested cultivars were found to be Cd-PSCs. Grain Cd concentrations were highly correlated (p<0.01) between the two experiments, suggesting that Cd accumulation in rice grain is genotype-dependent and that the selection of PSCs is possible, at least at a certain level of soil contamination. No Cd-PSCs were found under the high level of Cd exposure. Yield was enhanced in some cultivars and depressed in others in response to elevated soil Cd, indicating that farmers cannot rely on yield depression as an indicator of toxicity of the grains. It is therefore important and feasible to screen for PSCs and to establish PSC breeding programs to effectively and efficiently reduce the risk of human exposure to soil pollutants, such as Cd, through crop consumption.

The chemokine receptor CCR1 is identified in mast cell-derived exosomes

PubMed Central

Liang, Yuting; Qiao, Longwei; Peng, Xia; Cui, Zelin; Yin, Yue; Liao, Huanjin; Jiang, Min; Li, Li

2018-01-01

Mast cells are important effector cells of the immune system, and mast cell-derived exosomes carrying RNAs play a role in immune regulation. However, the molecular function of mast cell-derived exosomes is currently unknown, and here, we identify differentially expressed genes (DEGs) in mast cells and exosomes. We isolated mast cells derived exosomes through differential centrifugation and screened the DEGs from mast cell-derived exosomes, using the GSE25330 array dataset downloaded from the Gene Expression Omnibus database. Biochemical pathways were analyzed by Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway on the online tool DAVID. DEGs-associated protein-protein interaction networks (PPIs) were constructed using the STRING database and Cytoscape software. The genes identified from these bioinformatics analyses were verified by qRT-PCR and Western blot in mast cells and exosomes. We identified 2121 DEGs (843 up and 1278 down-regulated genes) in HMC-1 cell-derived exosomes and HMC-1 cells. The up-regulated DEGs were classified into two significant modules. The chemokine receptor CCR1 was screened as a hub gene and enriched in cytokine-mediated signaling pathway in module one. Seven genes, including CCR1, CD9, KIT, TGFBR1, TLR9, TPSAB1 and TPSB2 were screened and validated through qRT-PCR analysis. We have achieved a comprehensive view of the pivotal genes and pathways in mast cells and exosomes and identified CCR1 as a hub gene in mast cell-derived exosomes. Our results provide novel clues with respect to the biological processes through which mast cell-derived exosomes modulate immune responses. PMID:29511430

Development and Evaluation of an Optimal Human Single-Chain Variable Fragment-Derived BCMA-Targeted CAR T Cell Vector.

PubMed

Smith, Eric L; Staehr, Mette; Masakayan, Reed; Tatake, Ishan J; Purdon, Terence J; Wang, Xiuyan; Wang, Pei; Liu, Hong; Xu, Yiyang; Garrett-Thomson, Sarah C; Almo, Steven C; Riviere, Isabelle; Liu, Cheng; Brentjens, Renier J

2018-06-06

B cell maturation antigen (BCMA) has recently been identified as an important multiple myeloma (MM)-specific target for chimeric antigen receptor (CAR) T cell therapy. In CAR T cell therapy targeting CD19 for lymphoma, host immune anti-murine CAR responses limited the efficacy of repeat dosing and possibly long-term persistence. This clinically relevant concern can be addressed by generating a CAR incorporating a human single-chain variable fragment (scFv). We screened a human B cell-derived scFv phage display library and identified a panel of BCMA-specific clones from which human CARs were engineered. Despite a narrow range of affinity for BCMA, dramatic differences in CAR T cell expansion were observed between unique scFvs in a repeat antigen stimulation assay. These results were confirmed by screening in a MM xenograft model, where only the top preforming CARs from the repeat antigen stimulation assay eradicated disease and prolonged survival. The results of this screening identified a highly effective CAR T cell therapy with properties, including rapid in vivo expansion (>10,000-fold, day 6), eradication of large tumor burden, and durable protection to tumor re-challenge. We generated a bicistronic construct including a second-generation CAR and a truncated-epithelial growth factor receptor marker. CAR T cell vectors stemming from this work are under clinical investigation. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Hearing Loss in HIV-Infected Children in Lilongwe, Malawi

PubMed Central

Hrapcak, Susan; Kuper, Hannah; Bartlett, Peter; Devendra, Akash; Makawa, Atupele; Kim, Maria; Kazembe, Peter; Ahmed, Saeed

2016-01-01

Introduction With improved access to antiretroviral therapy (ART), HIV infection is becoming a chronic illness. Preliminary data suggest that HIV-infected children have a higher risk of disabilities, including hearing impairment, although data are sparse. This study aimed to estimate the prevalence and types of hearing loss in HIV-infected children in Lilongwe, Malawi. Methods This was a cross-sectional survey of 380 HIV-infected children aged 4–14 years attending ART clinic in Lilongwe between December 2013-March 2014. Data was collected through pediatric quality of life and sociodemographic questionnaires, electronic medical record review, and detailed audiologic testing. Hearing loss was defined as >20 decibels hearing level (dBHL) in either ear. Predictors of hearing loss were explored by regression analysis generating age- and sex-adjusted odds ratios. Children with significant hearing loss were fitted with hearing aids. Results Of 380 patients, 24% had hearing loss: 82% conductive, 14% sensorineural, and 4% mixed. Twenty-one patients (23% of those with hearing loss) were referred for hearing aid fitting. There was a higher prevalence of hearing loss in children with history of frequent ear infections (OR 7.4, 4.2–13.0) and ear drainage (OR 6.4, 3.6–11.6). Hearing loss was linked to history of WHO Stage 3 (OR 2.4, 1.2–4.5) or Stage 4 (OR 6.4, 2.7–15.2) and history of malnutrition (OR 2.1, 1.3–3.5), but not to duration of ART or CD4. Only 40% of caregivers accurately perceived their child’s hearing loss. Children with hearing impairment were less likely to attend school and had poorer emotional (p = 0.02) and school functioning (p = 0.04). Conclusions There is an urgent need for improved screening tools, identification and treatment of hearing problems in HIV-infected children, as hearing loss was common in this group and affected school functioning and quality of life. Clear strategies were identified for prevention and treatment, since most hearing loss was conductive in nature, likely due to frequent ear infections, and many children with hearing loss qualified for hearing aids. Screening strategies need to be developed and tested since caregivers were not reliable at identifying hearing loss, and often mis-identified children with normal hearing as having hearing loss. Children with frequent ear infections, ear drainage, TB, severe HIV disease, or low BMI should receive more frequent ear assessments and hearing evaluations. PMID:27551970

Convergent and Discriminant Validity of the Microcomputer Evaluation Screening and Assessment (MESA) Interest Survey.

ERIC Educational Resources Information Center

Janikowski, Timothy P.; And Others

1990-01-01

Examined construct validity of Microcomputer Evaluation Screening and Assessment (MESA) Interest Survey. Administered MESA and United States Employment Service (USES) Interest Inventory to 74 volunteer rehabilitation clients. Evidence supported convergent and discriminant validity of MESA. Found fewer significant intercorrelations among MESA…

Characterization of antibodies against ferret immunoglobulins, cytokines and CD markers.

PubMed

Martel, Cyril Jean-Marie; Aasted, Bent

2009-12-15

Ferret IgG and IgM were purified from normal serum, while ferret IgA was purified from bile. The estimated molecular weights of the immunoglobulin gamma, alpha and mu heavy chains were found to be 54kDa, 69kDa and 83kDa, respectively. For immunological (ELISA) quantification of ferret immunoglobulins, we identified and characterized polyclonal antibodies towards ferret IgG, IgM and IgA. We also identified 22 monoclonal antibodies (mAbs) raised mostly against human CD markers which cross-reacted with ferret leukocytes. These antibodies were originally specific against human CD8, CD9, CD14, CD18, CD25, CD29, CD32, CD44, CD61, CD71, CD79b, CD88, CD104, CD172a and mink CD3. Finally, we identified 4 cross-reacting mAbs with specificities against ferret interferon-gamma, TNF-alpha, interleukin-4 and interleukin-8.

Molecular characterization of α- and β-thalassemia in the Yulin region of Southern China.

PubMed

He, Sheng; Li, Jihui; Li, Dong Ming; Yi, Shang; Lu, Xiongcai; Luo, Yudi; Liang, Yi; Feng, Chunfeng; Chen, Biyan; Zheng, Chenguang; Qiu, Xiaoxia

2018-05-20

Thalassemia is one of the most common hereditary blood disorders. Epidemiological data regarding the prevalence and distribution of mutations is important for planning a thalassemia control program. To reveal the prevalence of thalassemia and mutation spectrum in the Yulin region of southern China, we screened 130,318 individuals from Yulin region by hematological and genetic analysis. Totally, 24,886 (19.10%) subjects were diagnosed with thalassemia, including 16,308 (12.51%) subjects with α-thalassemia alone, 6658 (5.11%) subjects with β-thalassemia alone and 1920 (1.47%) subjects with both α- and β-thalassemia. Ten α-thalassemia mutations were identified in the α-thalassemia subjects, with the common α-thalassemia mutations being -- SEA mutation (51.91%), -α 3.7 (19.90%), α CS α (10.58%), -α 4.2 (8.13%), α WS α (7.67%). Thirteen β-thalassemia mutations and 31 genotypes were characterized in the β-thalassemia subjects. The seven common mutations [CD41-42 (-CTTT) (43.31%), CD17 (A > T) (34.58%), CD26 (G > A) (6.86%), CD71-72 (+A) (4.25%), -28 (A > G) (3.90%), IVS-II-654 (C > T) (3.53%) and IVS-I-1 (G > T) (2.22%)] accounted for 98.65% of all β-thalassemia defects. Furthermore, 6 cases of α-triplication and 3 cases of mutation -α 2.4 were first identified in this region. Our data illustrated that there was great heterogeneity and extensive spectrum of thalassemias in the Yulin populations. The findings will contribute an available reference for prevention of thalassemia in this region. Copyright © 2018 Elsevier B.V. All rights reserved.

Characteristics of Japanese inflammatory bowel disease susceptibility loci.

PubMed

Arimura, Yoshiaki; Isshiki, Hiroyuki; Onodera, Kei; Nagaishi, Kanna; Yamashita, Kentaro; Sonoda, Tomoko; Matsumoto, Takayuki; Takahashi, Atsushi; Takazoe, Masakazu; Yamazaki, Keiko; Kubo, Michiaki; Fujimiya, Mineko; Imai, Kohzoh; Shinomura, Yasuhisa

2014-08-01

There are substantial differences in inflammatory bowel disease (IBD) genetics depending on the populations examined. We aimed to identify Japanese population-specific or true culprit susceptibility genes through a meta-analysis of past genetic studies of Japanese IBD. For this study, we reviewed 2,703 articles. The review process consisted of three screening stages: we initially searched for relevant studies and then relevant single nucleotide polymorphisms (SNPs). Finally, we adjusted them for the meta-analysis. To maximize our chances of analysis, we introduced proxy SNPs during the first stage. To minimize publication bias, no significant SNPs and solitary SNPs without pairs were combined to be reconsidered during the third stage. Additionally, two SNPs were newly genotyped. Finally, we conducted a meta-analysis of 37 published studies in 50 SNPs located at 22 loci corresponding to the total number of 4,853 Crohn's disease (CD), 5,612 ulcerative colitis (UC) patients, and 14,239 healthy controls. We confirmed that the NKX2-3 polymorphism is associated with common susceptibility to IBD and that HLA-DRB1*0450 alleles increase susceptibility to CD but reduce risk for UC while HLA-DRB1*1502 alleles increase susceptibility to UC but reduce CD risk. Moreover, we found individual disease risk loci: TNFSF15 and TNFα to CD and HLA-B*5201, and NFKBIL1 to UC. The genetic risk of HLA was substantially high (odds ratios ranged from 1.54 to 2.69) while that of common susceptibility loci to IBD was modest (odds ratio ranged from 1.13 to 1.24). Results indicate that Japanese IBD susceptibility loci identified by the meta-analysis are closely associated with the HLA regions.

Clinical and genetic features of cervical dystonia in a large multicenter cohort

PubMed Central

Vemula, Satya R.; Xiao, Jianfeng; Thompson, Misty M.; Perlmutter, Joel S.; Wright, Laura J.; Jinnah, H.A.; Rosen, Ami R.; Hedera, Peter; Comella, Cynthia L.; Weissbach, Anne; Junker, Johanna; Jankovic, Joseph; Barbano, Richard L.; Reich, Stephen G.; Rodriguez, Ramon L.; Berman, Brian D.; Chouinard, Sylvain; Severt, Lawrence; Agarwal, Pinky; Stover, Natividad P.

2016-01-01

Objective: To characterize the clinical and genetic features of cervical dystonia (CD). Methods: Participants enrolled in the Dystonia Coalition biorepository (NCT01373424) with initial manifestation as CD were included in this study (n = 1,000). Data intake included demographics, family history, and the Global Dystonia Rating Scale. Participants were screened for sequence variants (SVs) in GNAL, THAP1, and Exon 5 of TOR1A. Results: The majority of participants were Caucasian (95%) and female (75%). The mean age at onset and disease duration were 45.5 ± 13.6 and 14.6 ± 11.8 years, respectively. At the time of assessment, 68.5% had involvement limited to the neck, shoulder(s), and proximal arm(s), whereas 47.4% had dystonia limited to the neck. The remaining 31.5% of the individuals exhibited more extensive anatomical spread. A head tremor was noted in 62% of the patients. Head tremor and laryngeal dystonia were more common in females. Psychiatric comorbidities, mainly depression and anxiety, were reported by 32% of the participants and were more common in females. Family histories of dystonia, parkinsonian disorder, and tremor were present in 14%, 11%, and 29% of the patients, respectively. Pathogenic or likely pathogenic SVs in THAP1, TOR1A, and GNAL were identified in 8 participants (0.8%). Two individuals harbored novel missense SVs in Exon 5 of TOR1A. Synonymous and noncoding SVs in THAP1 and GNAL were identified in 4% of the cohort. Conclusions: Head tremor, laryngeal dystonia, and psychiatric comorbidities are more common in female participants with CD. Coding and noncoding variants in GNAL, THAP1, and TOR1A make small contributions to the pathogenesis of CD. PMID:27123488

Evaluation of the NZ guidelines for screening for persistent postpartum hyperglycaemia following gestational diabetes.

PubMed

Hughes, Ruth C E; Florkowski, Chris; Gullam, Joanna E

2017-11-17

Recent New Zealand guidelines recommend annual glycated haemoglobin (HbA1c) measurements from three months postpartum, replacing the glucose tolerance test (GTT) at six weeks, to screen for persistent hyperglycaemia following gestational diabetes. Data suggest that this screening approach may miss cases of type 2 diabetes, but are they detected at subsequent screening and will screening rates improve? Our aim was to evaluate the effectiveness of HbA1c monitoring in improving screening rates following gestational diabetes and in detecting postpartum hyperglycaemia. During 2015 in Christchurch, all women with gestational diabetes were offered HbA1c and GTT measurements at three months postpartum and subsequent annual HbA1c measurements were recommended. Data from electronic hospital records were collected for a minimum 18 months postpartum. Of the cohort of 333 women, 218 (65%) completed both HbA1c and GTT at three months postpartum, 74 (22%) HbA1c only, 16 (5%) GTT only, 25 (8%) no screening; 184 (55%) had subsequent HbA1c tests. Diabetes was detected by GTT in five (2%) women and by HbA1c in only one out of five (20%); the disagreement between tests resolved in three out of four (75%) women with subsequent testing. Prediabetes was detected by GTT in 30 (14%) women; however, HbA1c only detected five out of 30 (17%) and subsequent HbA1c testing identified a further two out of 30 with prediabetes. HbA1c measurement at three months postpartum had a good uptake. However, most cases of diabetes were identified by subsequent HbA1c testing, the uptake of which was suboptimal. The importance of annual HbA1c monitoring following gestational diabetes needs greater emphasis. © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Modulation of the immune response by infection with Cryptosporidium spp. in children with allergic diseases.

PubMed

Guangorena-Gómez, J O; Maravilla-Domínguez, A; García-Arenas, G; Cervantes-Flores, M; Meza-Velázquez, R; Rivera-Guillén, M; Acosta-Saavedra, L C; Goytia-Acevedo, R C

2016-08-01

It has been demonstrated that the allergic response can be ameliorated by the administration of pathogen derivatives that activate Toll-like receptors and induce a Th1-type immune response (IR). Cryptosporidium is a parasite that promotes an IR via Toll-like receptors and elicits the production of Th1-type cytokines, which limit cryptosporidiosis. The aim of this study was to investigate allergy-related immune markers in children naturally infected with Cryptosporidium. In a cross-sectional study, 49 children with or without clinical diagnosis of allergies, oocysts of Cryptosporidium spp. in the faeces were screened microscopically. We microscopically screened for leucocytes, examined T and B cells for allergy-related activation markers using flow cytometry and evaluated serum for total IgE using chemiluminescence. Children with allergies and Cryptosporidium in the faeces had significantly lower levels of total IgE, B cells, CD19(+) CD23(+) and CD19(+) CD124(+) cells as well as a greater percentage of interferon-gamma (IFN-γ(+) ) and IL-4(+) CD4(+) cells than children with allergies without Cryptosporidium. This is the first description of the modulation of the IR in children with allergic diseases in the setting of natural Cryptosporidium infection. Our findings suggest the involvement of CD4(+) cells producing IL-4 and IFN-γ in the IR to Cryptosporidium in naturally infected children. © 2016 John Wiley & Sons Ltd.

Screening Physical Activity in Family Practice: Validity of the Spanish Version of a Brief Physical Activity Questionnaire

PubMed Central

Puig-Ribera, Anna; Martín-Cantera, Carlos; Puigdomenech, Elisa; Real, Jordi; Romaguera, Montserrat; Magdalena-Belio, José Félix; Recio-Rodríguez, Jose Ignacio; Rodriguez-Martin, Beatriz; Arietaleanizbeaskoa, Maria Soledad; Repiso–Gento, Irene; Garcia-Ortiz, Luis

2015-01-01

Objectives The use of brief screening tools to identify inactive patients is essential to improve the efficiency of primary care-based physical activity (PA) programs. However, the current employment of short PA questionnaires within the Spanish primary care pathway is unclear. This study evaluated the validity of the Spanish version of a Brief Physical Activity Assessment Tool (SBPAAT). Methods A validation study was carried out within the EVIDENT project. A convenience sample of patients (n = 1,184; age 58.9±13.7 years; 60.5% female) completed the SBPAAT and the 7-day Physical Activity Recall (7DPAR) and, in addition, wore an accelerometer (ActiGraph GT3X) for seven consecutive days. Validity was evaluated by measuring agreement, Kappa correlation coefficients, sensitivity and specificity in achieving current PA recommendations with the 7DPAR. Pearson correlation coefficients with the number of daily minutes engaged in moderate and vigorous intensity PA according to the accelerometer were also assessed. Comparison with accelerometer counts, daily minutes engaged in sedentary, light, moderate, and vigorous intensity PA, total daily kilocalories, and total PA and leisure time expenditure (METs-hour-week) between the sufficiently and insufficiently active groups identified by SBPAAT were reported. Results The SBPAAT identified 41.3% sufficiently active (n = 489) and 58.7% insufficiently active (n = 695) patients; it showed moderate validity (k = 0.454, 95% CI: 0.402–0.505) and a specificity and sensitivity of 74.3% and 74.6%, respectively. Validity was fair for identifying daily minutes engaged in moderate (r = 0.215, 95% CI:0.156 to 0.272) and vigorous PA (r = 0.282, 95% CI:0.165 to 0.391). Insufficiently active patients according to the SBPAAT significantly reported fewer counts/minute (-22%), fewer minutes/day of moderate (-11.38) and vigorous PA (-2.69), spent fewer total kilocalories/day (-753), and reported a lower energy cost (METs-hour-week) of physical activities globally (-26.82) and during leisure time (-19.62). Conclusions The SBPAAT is a valid tool to identify Spanish-speaking patients who are insufficiently active to achieve health benefits. PMID:26379036

Screening Physical Activity in Family Practice: Validity of the Spanish Version of a Brief Physical Activity Questionnaire.

PubMed

Puig-Ribera, Anna; Martín-Cantera, Carlos; Puigdomenech, Elisa; Real, Jordi; Romaguera, Montserrat; Magdalena-Belio, José Félix; Recio-Rodríguez, Jose Ignacio; Rodriguez-Martin, Beatriz; Arietaleanizbeaskoa, Maria Soledad; Repiso-Gento, Irene; Garcia-Ortiz, Luis

2015-01-01

The use of brief screening tools to identify inactive patients is essential to improve the efficiency of primary care-based physical activity (PA) programs. However, the current employment of short PA questionnaires within the Spanish primary care pathway is unclear. This study evaluated the validity of the Spanish version of a Brief Physical Activity Assessment Tool (SBPAAT). A validation study was carried out within the EVIDENT project. A convenience sample of patients (n = 1,184; age 58.9±13.7 years; 60.5% female) completed the SBPAAT and the 7-day Physical Activity Recall (7DPAR) and, in addition, wore an accelerometer (ActiGraph GT3X) for seven consecutive days. Validity was evaluated by measuring agreement, Kappa correlation coefficients, sensitivity and specificity in achieving current PA recommendations with the 7DPAR. Pearson correlation coefficients with the number of daily minutes engaged in moderate and vigorous intensity PA according to the accelerometer were also assessed. Comparison with accelerometer counts, daily minutes engaged in sedentary, light, moderate, and vigorous intensity PA, total daily kilocalories, and total PA and leisure time expenditure (METs-hour-week) between the sufficiently and insufficiently active groups identified by SBPAAT were reported. The SBPAAT identified 41.3% sufficiently active (n = 489) and 58.7% insufficiently active (n = 695) patients; it showed moderate validity (k = 0.454, 95% CI: 0.402-0.505) and a specificity and sensitivity of 74.3% and 74.6%, respectively. Validity was fair for identifying daily minutes engaged in moderate (r = 0.215, 95% CI:0.156 to 0.272) and vigorous PA (r = 0.282, 95% CI:0.165 to 0.391). Insufficiently active patients according to the SBPAAT significantly reported fewer counts/minute (-22%), fewer minutes/day of moderate (-11.38) and vigorous PA (-2.69), spent fewer total kilocalories/day (-753), and reported a lower energy cost (METs-hour-week) of physical activities globally (-26.82) and during leisure time (-19.62). The SBPAAT is a valid tool to identify Spanish-speaking patients who are insufficiently active to achieve health benefits.

Disparities in cancer screening in individuals with a family history of breast or colorectal cancer.

PubMed

Ponce, Ninez A; Tsui, Jennifer; Knight, Sara J; Afable-Munsuz, Aimee; Ladabaum, Uri; Hiatt, Robert A; Haas, Jennifer S

2012-03-15

Understanding racial/ethnic disparities in cancer screening by family history risk could identify critical opportunities for patient and provider interventions tailored to specific racial/ethnic groups. The authors evaluated whether breast cancer (BC) and colorectal cancer (CRC) disparities varied by family history risk using a large, multiethnic population-based survey. By using the 2005 California Health Interview Survey, BC and CRC screening were evaluated separately with weighted multivariate regression analyses, and stratified by family history risk. Screening was defined for BC as mammogram within the past 2 years for women aged 40 to 64 years; for CRC, screening was defined as annual fecal occult blood test, sigmoidoscopy within the past 5 years, or colonoscopy within the past 10 years for adults aged 50 to 64 years. The authors found no significant BC screening disparities by race/ethnicity or income in the family history risk groups. Racial/ethnic disparities were more evident in CRC screening, and the Latino-white gap widened among individuals with family history risk. Among adults with a family history for CRC, the magnitude of the Latino-white difference in CRC screening (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.11-0.60) was more substantial than that for individuals with no family history (OR, 0.74; 95% CI, 0.59-0.92). Knowledge of their family history widened the Latino-white gap in CRC screening among adults. More aggressive interventions that enhance the communication between Latinos and their physicians about family history and cancer risk could reduce the substantial Latino-white screening disparity in Latinos most susceptible to CRC. Copyright © 2011 American Cancer Society.

The Association Between Post-traumatic Stress Disorder and Markers of Inflammation and Immune Activation in HIV-Infected Individuals With Controlled Viremia.

PubMed

Siyahhan Julnes, Peter; Auh, Sungyoung; Krakora, Rebecca; Withers, Keenan; Nora, Diana; Matthews, Lindsay; Steinbach, Sally; Snow, Joseph; Smith, Bryan; Nath, Avindra; Morse, Caryn; Kapetanovic, Suad

2016-01-01

Post-traumatic stress disorder (PTSD) may be associated with chronic immune dysregulation and a proinflammatory state. Among HIV-infected individuals, PTSD is associated with greater morbidity and mortality, but the association with immune dysfunction has not been evaluated. This study explores the association between PTSD and selected markers of inflammation and immune activation in a cohort of HIV-infected, virally-suppressed individuals. HIV-infected adults who were virologically controlled on antiretroviral medications were recruited through a screening protocol for studies of HIV-related neurocognitive disorders. Each participant underwent blood draws, urine toxicology screen, and completed the Client Diagnostic Questionnaire, a semistructured psychiatric interview. Of 114 eligible volunteers, 72 (63%) were male, 77 (68%) African American, and 34 (30%) participants met criteria for PTSD. Participants with PTSD were more likely to be current smokers (79%) than those without (60%) (p = 0.05). The PTSD cohort had significantly higher total white blood cell counts (5318 and 6404 cells/uL, p = 0.03), absolute neutrophil count (2767 and 3577 cells/uL, p = 0.02), CD8% (43 and 48, p = 0.05), and memory CD8% (70 and 78%, p = 0.04); lower naïve CD8% (30 and 22%, p = 0.04) and higher rate of high-sensitivity C-reactive protein >3mg/L (29 and 20, p = 0.03). A high prevalence of PTSD was identified in this cohort of HIV-infected adults who were virally suppressed. These results suggest that PTSD may be associated with immune dysregulation even among antiretroviral therapy-adherent HIV-infected individuals. Published by Elsevier Inc.

The Association between Post-Traumatic Stress Disorder and Markers of Inflammation and Immune Activation in HIV-Infected individuals with Controlled Viremia

PubMed Central

Siyahhan Julnes, Peter; Auh, Sungyoung; Krakora, Rebecca; Withers, Keenan; Nora, Diana; Matthews, Lindsay; Steinbach, Sally; Snow, Joseph; Smith, Bryan; Nath, Avindra; Morse, Caryn; Kapetanovic, Suad

2016-01-01

Introduction Post-traumatic stress disorder (PTSD) may be associated with chronic immune dysregulation and a pro-inflammatory state. Among HIV-infected individuals, PTSD is associated with greater morbidity and mortality, but the association with immune dysfunction has not been evaluated. This study explores the association between PTSD and selected markers of inflammation and immune activation in a cohort of HIV-infected, virally-suppressed individuals. Methods HIV-infected adults who were virologically controlled on anti-retroviral medications were recruited through a screening protocol for studies of HIV-related neurocognitive disorders. Each participant underwent blood draws, urine toxicology screen, and completed the Client Diagnostic Questionnaire (CDQ), a semi-structured psychiatric interview. Results Of 114 eligible volunteers; 72 (63%) were male, 77 (68%) African American, and 34 (30%) participants met criteria for PTSD. Participants with PTSD were more likely to be current smokers (79%) than those without (60%) (p=0.05). The PTSD cohort had significantly higher total white blood cell counts (5318 and 6404 cells/uL, p=0.03), absolute neutrophil count (2767 and 3577 cells/uL, p=0.02), CD8% (43 and 48, p=0.05) and memory CD8% (70 and 78%, p=0.04); lower naïve CD8% (30 and 22%, p=0.04), and higher rate of high-sensitivity C-reactive protein >3 mg/L (29 and 20, p=0.03). Discussion A high prevalence of PTSD was identified in this cohort of HIV-infected adults who were virally-suppressed. These results suggest that PTSD may be associated with immune dysregulation even among ART-adherent HIV-infected individuals. PMID:27095586

Controllable fabrication and characterization of biocompatible core-shell particles and hollow capsules as drug carrier

NASA Astrophysics Data System (ADS)

Hao, Lingyun; Gong, Xinglong; Xuan, Shouhu; Zhang, Hong; Gong, Xiuqing; Jiang, Wanquan; Chen, Zuyao

2006-10-01

SiO 2@CdSe core-shell particles were fabricated by controllable deposition CdSe nanoparticles on silica colloidal spheres. Step-wise coating process was tracked by the TEM and XRD measurements. In addition, SiO 2@CdSe/polypyrrole(PPy) multi-composite particles were synthesized based on the as-prepared SiO 2@CdSe particles by cationic polymerization. The direct electrochemistry of myoglobin (Mb) could be performed by immobilizing Mb on the surface of SiO 2@CdSe particles. Immobilized with Mb, SiO 2@CdSe/PPy-Mb also displayed good bioelectrochemical activity. It confirmed the good biocompatible property of the materials with protein. CdSe hollow capsules were further obtained as the removal of the cores of SiO 2@CdSe spheres. Hollow and porous character of CdSe sub-meter size capsules made them becoming hopeful candidates as drug carriers. Doxorubicin, a typical an antineoplastic drug, was introduced into the capsules. A good sustained drug release behavior of the loading capsules was discovered via performing a release test in the PBS buffer (pH 7.4) solution at 310 k. Furthermore, SiO 2@CdSe/PPy could be converted to various smart hollow capsules via selectively removal of their relevant components.

The prevalence of abnormal celiac antibodies and celiac disease in patients with suspected irritable bowel syndrome: a prospective multi-center US study

PubMed Central

Cash, Brooks D.; Rubenstein, Joel H.; Young, Patrick E.; Gentry, Andrew; Nojkov, Borko; Lee, Dong; Andrews, A. Hirsohi; Dobhan, Richard; Chey, William D.

2011-01-01

Background & Aims Guidelines recommend that patients with symptoms of non-constipated inflammatory bowel syndrome (NC-IBS) undergo testing for celiac disease (CD). We evaluated the prevalence of CD antibodies and biopsy confirmed CD among patients with NC-IBS in a large US population. Methods In a study conducted at 4 sites, from 2003 to 2008, we compared data from 492 patients with symptoms of NC-IBS to 458 asymptomatic individuals who underwent colonoscopy examinations for cancer screening or polyp surveillance (controls). All participants provided blood samples for specific and non-specific CD-associated antibodies. Additionally, patients with IBS were analyzed for complete blood cell counts, metabolic factors, erythrocyte sedimentation rates, and levels of C-reactive protein and thyroid-stimulating hormone. Any subjects found to have CD-associated antibodies were offered esophagogastroduodenoscopy and duodenal biopsy analysis. Results Of patients with NC-IBS, 7.3% had abnormal results in tests for CD-associated antibodies, compared to 4.8% of controls (adjusted odds ratio=1.49; 95% confidence interval, 0.76–2.90. P=.25). Within the NC-IBS group, 6.51% had antibodies against gliadin, 1.22% against tissue transglutaminase, and 0.61% against endomysium (P>.05 vs controls for all antibodies tested). CD was confirmed in 0.41% of patients in the NC-IBS group and 0.44% of controls (P>0.99). Conclusions Although CD-associated antibodies are relatively common, the prevalence of CD among patients with NC-IBS is similar to that among controls in a large US population. These findings challenge recommendations to routinely screen patients with NC-IBS for CD. More than 7% of patients with NC-IBS had CD-associated antibodies, indicating that gluten sensitivity might mediate IBS symptoms; further studies are needed. PMID:21762658

HEAVY METALS IN RECOVERED FINES FOR CONSTRUCTION AND DEMOLITION DEBRIS RECYCLING FACILITIES IN FLORIDA

EPA Science Inventory

A major product recovered from the processing and recycling of construction and demolition (C&D) debris is screened soil, also referred to as fines. A proposed reuse option for C&D debris fines is fill material, typically in construction projects as a substitute for natural soil....

Big Hand Produces CD-I World Disc--First Title Authored Entirely with MediaMogul.

ERIC Educational Resources Information Center

Buckman, Brad; Grant, Valerie

1993-01-01

Discusses Big Hand Productions' development of CD-I-WORLD, an interactive multimedia magazine on compact disk, designed for mass appeal and complete with advertising. Features of MediaMogul, the prepackaged authoring software that made production of this innovation possible, are described. Sample screen displays are included. (EA)

CDKL2 promotes epithelial-mesenchymal transition and breast cancer progression

PubMed Central

Li, Linna; Liu, Chunping; Amato, Robert J.; Chang, Jeffrey T.; Du, Guangwei; Li, Wenliang

2014-01-01

The epithelial–mesenchymal transition (EMT) confers mesenchymal properties on epithelial cells and has been closely associated with the acquisition of aggressive traits by epithelial cancer cells. To identify novel regulators of EMT, we carried out cDNA screens that covered 500 human kinases. Subsequent characterization of candidate kinases led us to uncover cyclin-dependent kinase-like 2 (CDKL2) as a novel potent promoter for EMT and breast cancer progression. CDKL2-expressing human mammary gland epithelial cells displayed enhanced mesenchymal traits and stem cell-like phenotypes, which was acquired through activating a ZEB1/E-cadherin/β-catenin positive feedback loop and regulating CD44 mRNA alternative splicing to promote conversion of CD24high cells to CD44high cells. Furthermore, CDKL2 enhanced primary tumor formation and metastasis in a breast cancer xenograft model. Notably, CDKL2 is expressed significantly higher in mesenchymal human breast cancer cell lines than in epithelial lines, and its over-expression/amplification in human breast cancers is associated with shorter disease-free survival. Taken together, our study uncovered a major role for CDKL2 in promoting EMT and breast cancer progression. PMID:25333262

CD8+ T Lymphocyte Expansion, Proliferation and Activation in Dengue Fever

PubMed Central

de Matos, Andréia Manso; Carvalho, Karina Inacio; Rosa, Daniela Santoro; Villas-Boas, Lucy Santos; da Silva, Wanessa Cardoso; Rodrigues, Célia Luiza de Lima; Oliveira, Olímpia Massae Nakasone Peel Furtado; Levi, José Eduardo; Araújo, Evaldo Stanislau Affonso; Pannuti, Claudio Sergio; Luna, Expedito José Albuquerque; Kallas, Esper George

2015-01-01

Dengue fever induces a robust immune response, including massive T cell activation. The level of T cell activation may, however, be associated with more severe disease. In this study, we explored the level of CD8+ T lymphocyte activation in the first six days after onset of symptoms during a DENV2 outbreak in early 2010 on the coast of São Paulo State, Brazil. Using flow cytometry we detected a progressive increase in the percentage of CD8+ T cells in 74 dengue fever cases. Peripheral blood mononuclear cells from 30 cases were thawed and evaluated using expanded phenotyping. The expansion of the CD8+ T cells was coupled with increased Ki67 expression. Cell activation was observed later in the course of disease, as determined by the expression of the activation markers CD38 and HLA-DR. This increased CD8+ T lymphocyte activation was observed in all memory subsets, but was more pronounced in the effector memory subset, as defined by higher CD38 expression. Our results show that most CD8+ T cell subsets are expanded during DENV2 infection and that the effector memory subset is the predominantly affected sub population. PMID:25675375

Oral aspects in celiac disease children: clinical and dental enamel chemical evaluation.

PubMed

de Carvalho, Fabrício Kitazono; de Queiroz, Alexandra Mussolino; Bezerra da Silva, Raquel Assed; Sawamura, Regina; Bachmann, Luciano; Bezerra da Silva, Léa Assed; Nelson-Filho, Paulo

2015-06-01

The aim of this study was to evaluate the oral manifestations of celiac disease (CD), the chemical composition of dental enamel, and the occurrence of CD in children with dental enamel defects (DEDs). In the study, 52 children with CD and 52 controls were examined for DEDs, recurrent aphthous stomatitis (RAS), dental caries experience, and salivary parameters. In addition, 10 exfoliated primary enamel molars from each group were analyzed by energy dispersive x-ray spectroscopy and Fourier transform infrared spectroscopy. Fifty children with DEDs were submitted to CD diagnosis. Among the children with CD, a higher prevalence of DEDs (P = .00001) and RAS (P = .0052), lower caries experience (P = .0024), and reduction of salivary flow (P = .0060) were observed. Dental enamel from the children with CD demonstrated a lower calcium-to-phosphorus ratio (P = .0136), but no difference in the carbonate-to-phosphate ratio (P = .5862) was observed. In the multivariate analysis, CD was a protective factor for caries (OR = 0.74) and a risk factor for RAS (OR3.23). The children with CD presented with more RAS, DEDs, reduction of salivary flow, and chemical alterations in the enamel. Copyright © 2015 Elsevier Inc. All rights reserved.

Prevalence of Chagas Disease in a U.S. Population of Latin American Immigrants with Conduction Abnormalities on Electrocardiogram

PubMed Central

Hernandez, Salvador; Sanchez, Daniel R.; Dufani, Jalal; Salih, Mohsin; Abuhamidah, Adieb M.; Olmedo, Wilman; Bradfield, Jason S.; Forsyth, Colin J.; Meymandi, Sheba K.

2017-01-01

Chagas disease (CD) affects over six million people and is a leading cause of cardiomyopathy in Latin America. Given recent migration trends, there is a large population at risk in the United States (US). Early stage cardiac involvement from CD usually presents with conduction abnormalities on electrocardiogram (ECG) including right bundle branch block (RBBB), left anterior or posterior fascicular block (LAFB or LPFB, respectively), and rarely, left bundle branch block (LBBB). Identification of disease at this stage may lead to early treatment and potentially delay the progression to impaired systolic function. All ECGs performed in a Los Angeles County hospital and clinic system were screened for the presence of RBBB, LAFB, LPFB, or LBBB. Patients were contacted and enrolled in the study if they had previously resided in Latin America for at least 12 months and had no history of cardiac disease. Enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA) tests were utilized to screen for Trypanosoma cruzi seropositivity. A total of 327 consecutive patients were screened for CD from January 2007 to December 2010. The mean age was 46.3 years and the mean length of stay in the US was 21.2 years. Conduction abnormalities were as follows: RBBB 40.4%, LAFB 40.1%, LPFB 2.8%, LBBB 5.5%, RBBB and LAFB 8.6%, and RBBB and LPFB 2.8%. Seventeen patients were positive by both ELISA and IFA (5.2%). The highest prevalence rate was among those with RBBB and LAFB (17.9%). There is a significant prevalence of CD in Latin American immigrants residing in Los Angeles with conduction abnormalities on ECG. Clinicians should consider evaluating all Latin American immigrant patients with unexplained conduction disease for CD. PMID:28056014

Drug Susceptibility and Resistance Mutations After First-Line Failure in Resource Limited Settings

PubMed Central

Wallis, Carole L.; Aga, Evgenia; Ribaudo, Heather; Saravanan, Shanmugam; Norton, Michael; Stevens, Wendy; Kumarasamy, Nagalingeswaran; Bartlett, John; Katzenstein, David

2014-01-01

Background. The development of drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) has been associated with baseline human immunodeficiency virus (HIV)-1 RNA level (VL), CD4 cell counts (CD4), subtype, and treatment failure duration. This study describes drug resistance and levels of susceptibility after first-line virologic failure in individuals from Thailand, South Africa, India, Malawi, Tanzania. Methods. CD4 and VL were captured at AIDs Clinical Trial Group (ACTG) A5230 study entry, a study of lopinavir/ritonavir (LPV/r) monotherapy after first-line virologic failure on an NNRTI regimen. HIV drug-resistance mutation associations with subtype, site, study entry VL, and CD4 were evaluated using Fisher exact and Kruskall–Wallis tests. Results. Of the 207 individuals who were screened for A5230, sequence data were available for 148 individuals. Subtypes observed: subtype C (n = 97, 66%) AE (n = 27, 18%), A1 (n = 12, 8%), and D (n = 10, 7%). Of the 148 individuals, 93% (n = 138) and 96% (n = 142) had at least 1 reverse transcriptase (RT) mutation associated with NRTI and NNRTI resistance, respectively. The number of NRTI mutations was significantly associated with a higher study screening VL and lower study screening CD4 (P < .001). Differences in drug-resistance patterns in both NRTI and NNRTI were observed by site. Conclusions. The degree of NNRTI and NRTI resistance after first-line virologic failure was associated with higher VL at study entry. Thirty-two percent of individuals remained fully susceptible to etravirine and rilpivirine, protease inhibitor resistance was rare. Some level of susceptibility to NRTI remained; however, VL monitoring and earlier virologic failure detection may result in lower NRTI resistance. PMID:24795328

CO 2 Dynamics in Pure and Mixed-Metal MOFs with Open Metal Sites

DOE PAGES

Marti, Robert M.; Howe, Joshua D.; Morelock, Cody R.; ...

2017-09-22

Metal–organic frameworks (MOFs), such as MOF-74, can have open metal sites to which adsorbates such as CO 2 preferentially bind. 13C NMR of 13CO 2 is highly informative about the binding sites present in Mg-MOF-74. We used this technique to investigate loadings between ~0.88 and 1.15 molecules of CO 2 per metal in Mg-MOF-74 at 295 K. 13C lineshapes recorded as a function of loading can be understood in terms of the dependence of the CO 2 NMR frequency on the angle (θ) with respect to the CO 2 axis and the channel of the MOF, reflected in the Legendremore » polynomial, P 2. In the fast motion limit, the NMR spectra reveal the time-averaged value of P 2, where θ is the angle between the instantaneous CO 2 axis and the channel axis. DFT calculations were used to determine a weighted average of P 2 in this regime and are in good agreement with experimental data. Static variable temperature 13C NMR from cryogenic temperatures to room temperature was used to investigate 13CO 2 binding in Mg-MOF-74 loaded at two levels (~0.88 and 1.08 molecules of CO 2 per metal), revealing temperature-dependent lineshapes. We have investigated the effect of partial substitution of Cd for Mg in Mg-MOF-74 on the 13CO 2 variable temperature NMR spectra. The chemical shift anisotropy (CSA) that leads to characteristic lineshapes of 13C indicates that incorporation of Cd leads to weaker binding energies for adsorbed CO 2.« less

CO 2 Dynamics in Pure and Mixed-Metal MOFs with Open Metal Sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marti, Robert M.; Howe, Joshua D.; Morelock, Cody R.

Metal–organic frameworks (MOFs), such as MOF-74, can have open metal sites to which adsorbates such as CO 2 preferentially bind. 13C NMR of 13CO 2 is highly informative about the binding sites present in Mg-MOF-74. We used this technique to investigate loadings between ~0.88 and 1.15 molecules of CO 2 per metal in Mg-MOF-74 at 295 K. 13C lineshapes recorded as a function of loading can be understood in terms of the dependence of the CO 2 NMR frequency on the angle (θ) with respect to the CO 2 axis and the channel of the MOF, reflected in the Legendremore » polynomial, P 2. In the fast motion limit, the NMR spectra reveal the time-averaged value of P 2, where θ is the angle between the instantaneous CO 2 axis and the channel axis. DFT calculations were used to determine a weighted average of P 2 in this regime and are in good agreement with experimental data. Static variable temperature 13C NMR from cryogenic temperatures to room temperature was used to investigate 13CO 2 binding in Mg-MOF-74 loaded at two levels (~0.88 and 1.08 molecules of CO 2 per metal), revealing temperature-dependent lineshapes. We have investigated the effect of partial substitution of Cd for Mg in Mg-MOF-74 on the 13CO 2 variable temperature NMR spectra. The chemical shift anisotropy (CSA) that leads to characteristic lineshapes of 13C indicates that incorporation of Cd leads to weaker binding energies for adsorbed CO 2.« less

40 CFR 74.41 - Identifying allowances.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 16 2011-07-01 2011-07-01 false Identifying allowances. 74.41 Section 74.41 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) SULFUR DIOXIDE OPT-INS Allowance Tracking and Transfer and End of Year Compliance § 74.41 Identifying...