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  • 1
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    Online Resource
    GABBR2 mutations determine phenotype in rett syndrome and epileptic encephalopathy
    Wiley ; 2017
    In:  Annals of Neurology Vol. 82, No. 3 ( 2017-09), p. 466-478
    Details
    In: Annals of Neurology, Wiley, Vol. 82, No. 3 ( 2017-09), p. 466-478
    Abstract: Rett syndrome (RTT) and epileptic encephalopathy (EE) are devastating neurodevelopmental disorders with distinct diagnostic criteria. However, highly heterogeneous and overlapping clinical features often allocate patients into the boundary of the two conditions, complicating accurate diagnosis and appropriate medical interventions. Therefore, we investigated the specific molecular mechanism that allows an understanding of the pathogenesis and relationship of these two conditions. Methods We screened novel genetic factors from 34 RTT‐like patients without MECP2 mutations, which account for ∼90% of RTT cases, by whole‐exome sequencing. The biological function of the discovered variants was assessed in cell culture and Xenopus tropicalis models. Results We identified a recurring de novo variant in GABAB receptor R2 ( GABBR2 ) that reduces the receptor function, whereas different GABBR2 variants in EE patients possess a more profound effect in reducing receptor activity and are more responsive to agonist rescue in an animal model. Interpretation GABBR2 is a genetic factor that determines RTT‐ or EE‐like phenotype expression depending on the variant positions. GABBR2 ‐mediated γ‐aminobutyric acid signaling is a crucial factor in determining the severity and nature of neurodevelopmental phenotypes. Ann Neurol 2017;82:466–478
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    URL: Article
    DOI: 10.1002/ana.v82.3
    DOI: 10.1002/ana.25032
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2037912-2
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  • 2
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    Impact of smoking on neurodegeneration and cerebrovascular disease markers in cognitively normal men
    Wiley ; 2016
    In:  European Journal of Neurology Vol. 23, No. 1 ( 2016-01), p. 110-119
    Details
    In: European Journal of Neurology, Wiley, Vol. 23, No. 1 ( 2016-01), p. 110-119
    Abstract: Smoking is a major risk factor for cognitive decline and dementia. However, the exact pathobiology of smoking remains unknown. The effects of smoking on cortical thickness as a biomarker of neurodegeneration or white matter hyperintensities and lacunes as biomarkers of cerebrovascular burden were concurrently evaluated. Methods Our study included 977 cognitively normal men who visited a health promotion centre and underwent medical check‐ups, including 3.0 T magnetic resonance imaging. Participants were categorized into never smoker, past smoker or current smoker groups and pack‐years and the years of smoking cessation were used as continuous variables. Results The current smoker group exhibited cortical thinning in frontal and temporo‐parietal regions compared with the never smoker group. These effects were particularly prominent in smokers with a high cumulative exposure to smoking in the current smoker group. However, there was no association between smoking and the severity of white matter hyperintensity or number of lacunes. Conclusion Our findings indicate that smoking might impact on neurodegeneration rather than cerebrovascular burdens in cognitively normal men, suggesting that smoking might be an important modifiable risk factor for the development of Alzheimer's disease.
    Type of Medium: Online Resource
    ISSN: 1351-5101 , 1468-1331
    URL: Issue
    URL: Article
    DOI: 10.1111/ene.2016.23.issue-1
    DOI: 10.1111/ene.12816
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2020241-6
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  • 3
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    Hepatitis C virus infections in oral lichen planus: a systematic review and meta‐analysis
    Wiley ; 2016
    In:  Australian Dental Journal Vol. 61, No. 3 ( 2016-09), p. 282-287
    Details
    In: Australian Dental Journal, Wiley, Vol. 61, No. 3 ( 2016-09), p. 282-287
    Abstract: A role for hepatitis C virus in oral lichen planus has been postulated. This systematic review and meta‐analysis of the existing epidemiological studies was conducted to determine if there is a correlation between oral lichen planus and hepatitis C virus infection. Methods We examined the association between hepatitis C virus and oral lichen planus by conducting a systematic review and meta‐analysis of case‐control studies that examined the prevalence of anti‐ HCV antibodies in the serum of cases and controls. We searched PubMed, Embase and The Cochrane Library databases from 2005 to January 2015. Associations were measured using random‐effect odds ratios ( OR s) combined with 95% confidence intervals. Results Nineteen eligible studies, encompassing 1807 cases of OLP and 2519 controls, were retrieved and included in this review. The summary estimate OR for all studies was 6.07 (95% CI : 2.73–13.48), showing a statistically significant difference in the proportion of HCV seropositivity among oral lichen planus patients, compared with controls and substantial heterogeneity between studies ( I 2 = 65%) as a result of a variety of geographical distributions. Conclusions The association of hepatitis C virus infection with oral lichen planus emphasizes the importance of hepatitis C virus screening in oral lichen planus patients.
    Type of Medium: Online Resource
    ISSN: 0045-0421 , 1834-7819
    URL: Issue
    URL: Article
    DOI: 10.1111/adj.2016.61.issue-3
    DOI: 10.1111/adj.12382
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2059014-3
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  • 4
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    A picture is worth a thousand words: maps of HIV indicators to inform research, programs, and policy from NA‐ACCORD and CCASAnet clinical cohorts
    Wiley ; 2016
    In:  Journal of the International AIDS Society Vol. 19, No. 1 ( 2016-01)
    Details
    In: Journal of the International AIDS Society, Wiley, Vol. 19, No. 1 ( 2016-01)
    Abstract: Maps are powerful tools for visualization of differences in health indicators by geographical region, but multi‐country maps of HIV indicators do not exist, perhaps due to lack of consistent data across countries. Our objective was to create maps of four HIV indicators in North, Central, and South American countries. Methods Using data from the North American AIDS Cohort Collaboration on Research and Design (NA‐ACCORD) and the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet), we mapped median CD4 at presentation for HIV clinical care, proportion retained in HIV primary care, proportion prescribed antiretroviral therapy (ART), and the proportion with suppressed plasma HIV viral load (VL) from 2010 to 2012 for North, Central, and South America. The 15 Canadian and US clinical cohorts and 7 clinical cohorts in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru represented approximately 2–7% of persons known to be living with HIV in these countries. Results Study populations were selected for each indicator: median CD4 at presentation for care was estimated among 14,811 adults; retention was estimated among 87,979 adults; ART use was estimated among 84,757 adults; and suppressed VL was estimated among 51,118 adults. Only three US states and the District of Columbia had a median CD4 at presentation 〉 350 cells/mm 3 . Haiti, Mexico, and several states had 〉 85% retention in care; lower (50–74%) retention in care was observed in the US West, South, and Mid‐Atlantic, and in Argentina, Brazil, and Peru. ART use was highest (90%) in Mexico. The percentages of patients with suppressed VL in the US South and Northeast were lower than in most of Central and South America. Conclusions These maps provide visualization of gaps in the quality of HIV care and allow for comparison between and within countries as well as monitoring policy and programme goals within geographical boundaries.
    Type of Medium: Online Resource
    ISSN: 1758-2652 , 1758-2652
    URL: Article
    DOI: 10.7448/IAS.19.1.20707
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2467110-1
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  • 5
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    Predictors of suicidal ideation in Korean American older adults: analysis of the Memory and Aging Study of Koreans (MASK)
    Wiley ; 2017
    In:  International Journal of Geriatric Psychiatry Vol. 32, No. 12 ( 2017-12), p. 1272-1279
    Details
    In: International Journal of Geriatric Psychiatry, Wiley, Vol. 32, No. 12 ( 2017-12), p. 1272-1279
    Abstract: Our aim is to investigate the prevalence and predictors of suicidal ideation among Korean American older adults and assess the self‐rated mental health of Korean American older adults with suicidal ideation with or without depressive syndrome. Methods The Memory and Aging Study of Koreans is a cross‐sectional, epidemiologic study of a community‐representative sample of Korean American older adults ( N  = 1116) residing in the Baltimore–Washington area. Participants were interviewed using the Korean version of the Patient Health Questionnaire (PHQ‐9K). In addition, demographic information, self‐rated mental health, and self‐rated physical health status were obtained. Results In this study, 14.7% of Korean American older adults reported suicidal ideation. Predictors of suicidal ideation included living alone, major or minor depressive syndrome (diagnosed by the PHQ‐9K), shorter duration of residency in the USA, and poorer self‐rated mental health status. Of those who reported suicidal ideation, 64% did not have minor or major depressive syndrome. However, their self‐rated mental health was as poor as that of those with major or minor depressive syndrome but without suicidal ideation. Conclusion Suicidal ideation without depressive syndromes was common among Korean American older adults. For this group of elders with poor self‐rated mental health, future studies should look to improving early detection of suicide risks and developing feasible suicide prevention interventions. Copyright © 2016 John Wiley & Sons, Ltd.
    Type of Medium: Online Resource
    ISSN: 0885-6230 , 1099-1166
    URL: Issue
    URL: Article
    DOI: 10.1002/gps.v32.12
    DOI: 10.1002/gps.4608
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 1500455-7
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  • 6
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    A comprehensive evaluation of CHEK2 germline mutations in men with prostate cancer
    Wiley ; 2018
    In:  The Prostate Vol. 78, No. 8 ( 2018-06), p. 607-615
    Details
    In: The Prostate, Wiley, Vol. 78, No. 8 ( 2018-06), p. 607-615
    Abstract: Germline mutations in CHEK2 have been associated with prostate cancer (PCa) risk. Our objective is to examine whether germline pathogenic CHEK2 mutations can differentiate risk of lethal from indolent PCa. Methods A case‐case study of 703 lethal PCa patients and 1455 patients with low‐risk localized PCa of European, African, and Chinese origin was performed. Germline DNA samples from these patients were sequenced for CHEK2 . Mutation carrier rates and their association with lethal PCa were analyzed using the Fisher exact test and Kaplan‐Meier survival analysis. Results In the entire study population, 40 (1.85%) patients were identified as carrying one of 15 different germline CHEK2 pathogenic or likely pathogenic mutations. CHEK2 mutations were detected in 16 (2.28%) of 703 lethal PCa patients compared with 24 (1.65%) of 1455 low‐risk PCa patients ( P  = 0.31). No association was found between CHEK2 mutation status and early‐diagnosis or PCa‐specific survival time. However, the most common mutation in CHEK2 , c.1100delC (p.T367 fs), had a significantly higher carrier rate (1.28%) in lethal PCa patients than low‐risk PCa patients of European American origin (0.16%), P  = 0.0038. The estimated Odds Ratio of this mutation for lethal PCa was 7.86. The carrier rate in lethal PCa was also significantly higher than that (0.46%) in 32 461 non‐Finnish European subjects from the Exome Aggregation Consortium (ExAC) ( P  = 0.01). Conclusions While overall CHEK2 mutations were not significantly more common in men with lethal compared to low‐risk PCa, the specific CHEK2 mutation, c.1100delC, appears to contribute to an increased risk of lethal PCa in European American men.
    Type of Medium: Online Resource
    ISSN: 0270-4137 , 1097-0045
    URL: Issue
    URL: Article
    DOI: 10.1002/pros.v78.8
    DOI: 10.1002/pros.23505
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 1494709-2
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  • 7
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    Effects of depth of neuromuscular block on surgical conditions during laparoscopic colorectal surgery: a randomised controlled trial
    Wiley ; 2018
    In:  Anaesthesia Vol. 73, No. 9 ( 2018-09), p. 1090-1096
    Details
    In: Anaesthesia, Wiley, Vol. 73, No. 9 ( 2018-09), p. 1090-1096
    Abstract: There have been few objective evaluations of the effects of deep neuromuscular blockade on intra‐operative conditions. In this prospective randomised controlled study, we evaluated the effects of deep neuromuscular block on surgical conditions during laparoscopic colorectal surgery. Patients were randomly allocated using a computer‐generated randomisation code to either moderate (train‐of‐four count 1–2 maintained and antagonised with neostigmine) or deep (post‐tetanic count 1–2 maintained and reversed with sugammadex) levels of neuromuscular blockade. The primary outcome measure was the number of abrupt increases in intra‐abdominal pressure intra‐operatively. Secondary outcome variables were intra‐operative restoration of spontaneous breathing, number of surgical requests for additional neuromuscular blockade, surgical rating of operating conditions and patient satisfaction. The surgeon who rated the surgical conditions score and investigator who checked the postoperative variables were blinded to patient allocation. In total, we recruited 70 patients of whom 64 (32 in each group) were analysed. Increases in intra‐abdominal pressure (14/32 vs. 6/32; p = 0.031), intra‐operative restoration of spontaneous breathing (16/32 vs. 2/32; p 〈 0.001) and request for additional neuromuscular blockade (21/32 vs. 8/32; p = 0.001) were more frequent in the moderate compared with the deep group. In patients undergoing elective laparoscopic colorectal surgery, deep neuromuscular blockade provided better surgical conditions than moderate neuromuscular blockade, as measured by a reduction in the incidence of intra‐abdominal pressure alarms.
    Type of Medium: Online Resource
    ISSN: 0003-2409 , 1365-2044
    URL: Issue
    URL: Article
    DOI: 10.1111/anae.2018.73.issue-9
    DOI: 10.1111/anae.14304
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2003379-5
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  • 8
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    Interleukin‐12 modulates the immunomodulatory properties of human periodontal ligament cells
    Wiley ; 2017
    In:  Journal of Periodontal Research Vol. 52, No. 3 ( 2017-06), p. 546-555
    Details
    In: Journal of Periodontal Research, Wiley, Vol. 52, No. 3 ( 2017-06), p. 546-555
    Abstract: The cytokine interleukin 12 ( IL ‐12) has been implicated as a potent stimulator of tissue degradation in the pathogenesis of several inflammatory diseases, including periodontitis. In patients with periodontitis, an increased level of IL ‐12 is found in serum and gingival crevicular fluid. As inflammatory cytokines have been demonstrated to induce activation of the immunomodulatory properties of mesenchymal stem cells ( MSC s), this study aimed to investigate the influence of IL ‐12 on these properties in human periodontal ligament ( hPDL ) cells. Material and Methods Human PDL cells were isolated from periodontal tissue and incubated with 0–10 ng/mL of IL‐12 for 24 h. The levels of expression of interferon gamma (IFN‐γ), indoleamine 2,3‐dioxygenase (IDO) and human leukocyte antigen G (HLA‐G), as well as of the stem cell markers, CD73, CD90 and CD105, were assessed by quantitative PCR. The level of IFN‐γ protein was measured by ELISA, and IDO activity was measured by activity assay. The participation of IFN‐γ in the expression of IDO and HLA‐G was analyzed using neutralizing antibody against IFN‐γ. Results IL‐12 upregulated the expression of IFN‐γ in a dose‐dependent manner. Moreover, IL‐12 induced the expression of the immunomodulatory proteins IDO and HLA‐G via an IFN‐γ‐dependent pathway, as indicated by experiments using an IFN‐γ neutralizing antibody. Addition of exogenous IFN‐γ upregulated the expression of HLA‐G and IDO. Expression of the stem cell markers CD73, CD90 and CD105, as well as the pluripotent markers Nanog homeobox, octamer‐binding transcription factor 4 and SRY‐box 2, were also upregulated in IL‐12‐treated hPDL cells. Finally, IL‐12 inhibited osteogenic differentiation of the hPDL cells and preserved the self‐clonal expansion property of these cells, as assessed by Alizarin Red S staining and the colony‐forming unit assay. Conclusion Expression of IL ‐12 during periodontitis may play an important role in the control of the inflammatory response via the induction of immunosuppressive molecules by hPDL cells. We hypothesize that this immunomodulatory property of IL ‐12 will serve as a protective mechanism to preserve a population of stem cells under inflammatory conditions.
    Type of Medium: Online Resource
    ISSN: 0022-3484 , 1600-0765
    URL: Issue
    URL: Article
    DOI: 10.1111/jre.2017.52.issue-3
    DOI: 10.1111/jre.12421
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2025633-4
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  • 9
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    Translating the ICAP Theory of Cognitive Engagement Into Practice
    Wiley ; 2018
    In:  Cognitive Science Vol. 42, No. 6 ( 2018-08), p. 1777-1832
    Details
    In: Cognitive Science, Wiley, Vol. 42, No. 6 ( 2018-08), p. 1777-1832
    Abstract: ICAP is a theory of active learning that differentiates students’ engagement based on their behaviors. ICAP postulates that I nteractive engagement, demonstrated by co‐generative collaborative behaviors, is superior for learning to C onstructive engagement, indicated by generative behaviors. Both kinds of engagement exceed the benefits of A ctive or P assive engagement, marked by manipulative and attentive behaviors, respectively. This paper discusses a 5‐year project that attempted to translate ICAP into a theory of instruction using five successive measures: (a) teachers’ understanding of ICAP after completing an online module, (b) their success at designing lesson plans using different ICAP modes, (c) fidelity of teachers’ classroom implementation, (d) modes of students’ enacted behaviors, and (e) students’ learning outcomes. Although teachers had minimal success in designing Constructive and Interactive activities, students nevertheless learned significantly more in the context of Constructive than Active activities. We discuss reasons for teachers’ overall difficulty in designing and eliciting Interactive engagement.
    Type of Medium: Online Resource
    ISSN: 0364-0213 , 1551-6709
    URL: Issue
    URL: Article
    DOI: 10.1111/cogs.2018.42.issue-6
    DOI: 10.1111/cogs.12626
    RVK:
    EQ 1000
    RVK:
    CL 1000
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 282371-8
    detail.hit.zdb_id: 2002940-8
    SSG: 25
    SSG: 5,2
    SSG: 7,11
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  • 10
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    Effect of the Cubic Phase Distribution on Ultrafine WC –10Co–0.5Cr– x Ta Cemented Carbide
    Wiley ; 2016
    In:  Journal of the American Ceramic Society Vol. 99, No. 3 ( 2016-03), p. 1047-1054
    Details
    In: Journal of the American Ceramic Society, Wiley, Vol. 99, No. 3 ( 2016-03), p. 1047-1054
    Abstract: The (Ta, W)C cubic phase distribution plays a key role in the microstructure and mechanical properties of ultrafine WC –Co–Cr 3 C 2 –TaC cemented carbides. By integration of thermodynamic calculations and key experiments, the influence of the cubic phase distribution in ultrafine WC –10Co–0.5Cr– x Ta cemented carbides was systematically investigated. A series of ultrafine grained cemented carbides were designed and fabricated through ball‐milling and vacuum sintering at 1410°C for 1 h. The microstructure was investigated using scanning electron microscopy ( SEM ). The electron backscattered diffraction ( EBSD ) was used to measure the orientation and size of cubic phase segregation. The results indicate that the cubic phase in the microstructure distributes more heterogeneously in the range of 0.2 to 0.7 wt% Ta addition, but finally the isolated cubic phase is homogeneously distributed with a Ta content from 0.7 to 1 wt%. Combining the thermodynamic calculation with the experiment, the mechanism for the microstructure evolution has been revealed. The mechanical properties of alloys substantially depend on the cubic phase distribution in the microstructure. A synergetic correlation between the transverse rupture strength (TRS) and Rockwell hardness was observed. The homogeneity of cubic phase can be designed and controlled effectively via the present approach.
    Type of Medium: Online Resource
    ISSN: 0002-7820 , 1551-2916
    URL: Issue
    URL: Article
    DOI: 10.1111/jace.2016.99.issue-3
    DOI: 10.1111/jace.14006
    RVK:
    VA 1120
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2008170-4
    detail.hit.zdb_id: 219232-9
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