12 results
4 Resting State Functional Connectivity Impairments Implicate CNS Mechanisms Underlying Chronic Pain and Depression in Gulf War Veterans’ Illness
- Gabriell C Champion, Aliyah M Auerbach, Nayana Ambardekar, Thomas Novak, Anna Woodbury, Sheila A Rauch, Keith McGregor, Albert Y Leung, Kaundinya S Gopinath
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 518-519
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Objective:
Around 200,000 veterans (up to 32% of those deployed) of the 1991 Gulf War (GW) suffer from GW veterans’ illness (GWVI). GWVI is a poorly understood chronic medical condition, characterized by symptoms indicative of brain function deficits in multiple domains. Among the symptoms of brain impairment GWVI-related chronic headaches and body muscle and joint pain conditions (GWVI-HAP) are the most debilitating, affecting around 64% of the GWVI veterans. Further, depression carries a very high co-morbid rate (>50%) in patients with chronic pain, including GWVI-HAP. In this preliminary study, we examined the integrity of brain function networks in a group of GWI-HAP veterans, with resting state fMRI (rsfMRI).
Participants and Methods:Data from the first twenty-two GWVI-HAP veterans from two ongoing parallel clinical trials was examined. Of these 14 subjects (GWVI-HAP-DM) had mild depression (Hamilton Rating Scale for Depression (HSRD < 13); and 8 subjects (GWVI-HAP-DS) had moderate to severe depression (HSRD > 14). Written informed consent was obtained from all participants in the protocol approved by the local Institutional Review Board. RsfMRI data was acquired on a Siemens 3T Prisma-Fit MRI scanner using a 10-minute whole-brain high resolution simultaneous multi-slice (SMS) gradient echo echo-planar imaging (EPI) sequence: TR/TE/FA = 2.2 sec/ 27 msec/80°, and analyzed with well-established image processing pipelines. Functional connectivity (FC) to different regions implicated in depression and chronic pain was assessed with seed-based correlation analysis. Between group differences in FC were obtained with 2-sample t-tests.
Results:GWVI-HAP-DS group exhibited significantly (p < 0.05) reduced FC compared to GWVI-HAP-DM between frontal lobe (medial (mPFC), and dorsolateral (dlPFC) prefrontal cortex) and the striatum. This indicates that malfunction of fronto-striatal circuits could be a source of the increased chronic pain and depression seen in veterans with GWVI- HAP-DS. Dysregulation of fronto-striatal networks has been implicated in major depressive disorder as well as many chronic pain conditions. In addition, FC between mPFC, and salience network (SN; anterior insula and dorsal anterior cingulate) and limbic (subgenual and ventral anterior cingulate) regions were also reduced in GWVI-HAP-DS. Similarly, mPFC and SN also exhibited reduced FC to pain processing regions (posterior insula, centromedian thalamus and cerebellum). These FC impairments could reflect greater deficits in regulation of and salience attribution to emotions and nociception in the GWVI-HAP-DS group. Finally, GWVI-HAP-DS also exhibited reduced FC between nodes of the default mode network. DMN impairments also have been observed in many depressive and chronic pain conditions.
Conclusions:The results of this preliminary analysis implicate impairments in cognitive control of emotion and nociception as a mechanism underlying the enhanced chronic pain and depression observed in GWVI-HAP veterans, especially those with moderate to severe depression. A fuller picture of deficits in FC in brain function networks is expected to emerge as more GWI-HAP subjects of both groups along with age matched healthy controls are examined in this ongoing project. Better understanding of impairments in these networks in GWI-HAP will benefit the rehabilitation of veterans with GWI-HAP.
19 Exploring GABA Concentration Changes in Sensorimotor Cortex in Older Adults During Motor & Cognitive Performance
- Gabriell Champion, Lisa C Krishnamurthy, Joe R Nocera, Thomas S Novak, Kevin M Mammino, Keith M McGregor
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 332-333
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Objective:
Aging is associated with changes in cortical excitability which may affect motor learning and cognitive function via selective modulation of gamma aminobutyric acid (GABA). Previous studies using magnetic resonance spectroscopy (MRS) to measure GABA in older adults found that increased baseline GABA levels in the sensorimotor cortex (M1S1) were associated with better motor performance. GABA levels in M1S1 have tended to decrease during the execution of a repeated motor sequence. The dynamic change in GABA density in M1S1 in older adults is currently unknown and represents a critical gap in our understanding of how it could impact motor learning and cognitive performance. As such, the purpose of the current study is to quantify changes in cortical GABA during motor learning in the aging brain and examine those changes in relation to motor and cognitive performance. We hypothesize that older adults with greater dynamic range in M1S1 GABA levels will display more efficient motor learning and increased cognitive scores.
Participants and Methods:We report on a total of 18 healthy older adults aged 64 to 80 years (M = 70.44, SD = 4.99, 12 females). Using MRS at 3T, we measured changes in GABA concentration in M1S1 at rest, during an eight or 12 finger-movement motor entrainment task, and during a recall task. Gannett was used for GABA quantification relative to water. Change in GABA was calculated by subtracting Rest1 GABA from Recall1 GABA. In a separate session, participants completed a battery of cognitive assessments. We computed linear regressions to examine the relationship between dynamic GABA change, recall accuracy of the motor task and cognitive performance.
Results:In relation to motor performance, we found that both greater baseline (Rest1) GABA levels and greater dynamic change in GABA significantly predicted better recall accuracy on the motor task. For cognitive performance, we found that greater dynamic change in GABA significantly predicted better performance on Word Reading in the Stroop Color and Word Test and Delayed Recall in the Hopkins Verbal Learning Test (HVLT). No additional significant relationships were found for the remaining cognitive assessments.
Conclusions:Older adults who were able to accurately perform the task had a greater dynamic change in GABA and increased baseline GABA levels. These adults with greater dynamic change also had better cognitive performance on HVLT Delay and Stroop Word Reading. This modulation of GABA associated with better performance could be related to changes in neuroplasticity. Although these results are in the preliminary stages, they point to a greater understanding of aging related changes in motor and cognitive performance. We’ll continue to explore the relationship between sensory motor performance and changes in GABA concentration as a potential predictor for cognitive performance and future rehabilitation.
Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach – CORRIGENDUM
- Micah Cearns, Azmeraw T. Amare, Klaus Oliver Schubert, Anbupalam Thalamuthu, Joseph Frank, Fabian Streit, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, JeanMichel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, HsiChung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Mario Maj, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Vincent Millischer, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fasil TekolaAyele, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Stephanie H. Witt, Gloria Roberts, Peter P. Zandi, Martin Alda, Michael Bauer, Francis J. McMahon, Philip B. Mitchell, Thomas G. Schulze, Marcella Rietschel, Scott R. Clark, Bernhard T. Baune
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- Journal:
- The British Journal of Psychiatry / Volume 221 / Issue 2 / August 2022
- Published online by Cambridge University Press:
- 04 May 2022, p. 494
- Print publication:
- August 2022
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Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach
- Micah Cearns, Azmeraw T. Amare, Klaus Oliver Schubert, Anbupalam Thalamuthu, Joseph Frank, Fabian Streit, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, Jean-Michel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, Hsi-Chung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Mario Maj, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Vincent Millischer, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fasil Tekola-Ayele, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Stephanie H. Witt, Gloria Roberts, Peter P. Zandi, Martin Alda, Michael Bauer, Francis J. McMahon, Philip B. Mitchell, Thomas G. Schulze, Marcella Rietschel, Scott R. Clark, Bernhard T. Baune
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- Journal:
- The British Journal of Psychiatry / Volume 220 / Issue 4 / April 2022
- Published online by Cambridge University Press:
- 28 February 2022, pp. 219-228
- Print publication:
- April 2022
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Background
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
AimsTo use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
MethodThis study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
ResultsThe best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
ConclusionsUsing PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Characterisation of age and polarity at onset in bipolar disorder
- Janos L. Kalman, Loes M. Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A. Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B. Bigdeli, Frederike Stein, Tina Meller, Susanne Meinert, Helena Pelin, Fabian Streit, Sergi Papiol, Mark J. Adams, Rolf Adolfsson, Kristina Adorjan, Ingrid Agartz, Sofie R. Aminoff, Heike Anderson-Schmidt, Ole A. Andreassen, Raffaella Ardau, Jean-Michel Aubry, Ceylan Balaban, Nicholas Bass, Bernhard T. Baune, Frank Bellivier, Antoni Benabarre, Susanne Bengesser, Wade H Berrettini, Marco P. Boks, Evelyn J. Bromet, Katharina Brosch, Monika Budde, William Byerley, Pablo Cervantes, Catina Chillotti, Sven Cichon, Scott R. Clark, Ashley L. Comes, Aiden Corvin, William Coryell, Nick Craddock, David W. Craig, Paul E. Croarkin, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Srdjan Djurovic, Howard J. Edenberg, Mariam Al Eissa, Torbjørn Elvsåshagen, Bruno Etain, Ayman H. Fanous, Frederike Fellendorf, Alessia Fiorentino, Andreas J. Forstner, Mark A. Frye, Janice M. Fullerton, Katrin Gade, Julie Garnham, Elliot Gershon, Michael Gill, Fernando S. Goes, Katherine Gordon-Smith, Paul Grof, Jose Guzman-Parra, Tim Hahn, Roland Hasler, Maria Heilbronner, Urs Heilbronner, Stephane Jamain, Esther Jimenez, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, John R. Kelsoe, James L. Kennedy, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Farah Klöhn-Saghatolislam, James A. Knowles, Thorsten M. Kranz, Trine Vik Lagerberg, Mikael Landen, William B. Lawson, Marion Leboyer, Qingqin S. Li, Mario Maj, Dolores Malaspina, Mirko Manchia, Fermin Mayoral, Susan L. McElroy, Melvin G. McInnis, Andrew M. McIntosh, Helena Medeiros, Ingrid Melle, Vihra Milanova, Philip B. Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Markus M. Nöthen, Tomas Novak, John I. Nurnberger, Niamh O'Brien, Kevin S. O'Connell, Claire O'Donovan, Michael C. O'Donovan, Nils Opel, Abigail Ortiz, Michael J. Owen, Erik Pålsson, Carlos Pato, Michele T. Pato, Joanna Pawlak, Julia-Katharina Pfarr, Claudia Pisanu, James B. Potash, Mark H Rapaport, Daniela Reich-Erkelenz, Andreas Reif, Eva Reininghaus, Jonathan Repple, Hélène Richard-Lepouriel, Marcella Rietschel, Kai Ringwald, Gloria Roberts, Guy Rouleau, Sabrina Schaupp, William A Scheftner, Simon Schmitt, Peter R. Schofield, K. Oliver Schubert, Eva C. Schulte, Barbara Schweizer, Fanny Senner, Giovanni Severino, Sally Sharp, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Alessio Squassina, Pavla Stopkova, John Strauss, Alfonso Tortorella, Gustavo Turecki, Joanna Twarowska-Hauser, Marin Veldic, Eduard Vieta, John B. Vincent, Wei Xu, Clement C. Zai, Peter P. Zandi, Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics (ConLiGen), Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Arianna Di Florio, Jordan W. Smoller, Joanna M. Biernacka, Francis J. McMahon, Martin Alda, Bertram Müller-Myhsok, Nikolaos Koutsouleris, Peter Falkai, Nelson B. Freimer, Till F.M. Andlauer, Thomas G. Schulze, Roel A. Ophoff
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- Journal:
- The British Journal of Psychiatry / Volume 219 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 August 2021, pp. 659-669
- Print publication:
- December 2021
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Background
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Recommendations for Patients with Complex Nerve Injuries during the COVID-19 Pandemic
- Kristine M. Chapman, Michael J. Berger, Christopher Doherty, Dimitri J. Anastakis, Heather L. Baltzer, Kirsty Usher Boyd, Sean G. Bristol, Brett Byers, K. Ming Chan, Cameron J.B. Cunningham, Kristen M. Davidge, Jana Dengler, Kate Elzinga, Jennifer L. Giuffre, Lisa Hadley, A Robertson Harrop, Mahdis Hashemi, J. Michael Hendry, Kristin L. Jack, Emily M. Krauss, Timothy J. Lapp, Juliana Larocerie, Jenny C. Lin, Thomas A. Miller, Michael Morhart, Christine B. Novak, Russell O’Connor, Jaret L. Olsen, Benjamin R. Ritsma, Lawrence R. Robinson, Douglas C. Ross, Christiaan Schrag, Alexander Seal, David T. Tang, Jessica Trier, Gerald Wolff, Justin Yeung
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- Journal:
- Canadian Journal of Neurological Sciences / Volume 48 / Issue 1 / January 2021
- Published online by Cambridge University Press:
- 27 August 2020, pp. 50-55
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Beach sand and the potential for infectious disease transmission: observations and recommendations
- Helena M. Solo-Gabriele, Valerie J. Harwood, David Kay, Roger S. Fujioka, Michael J. Sadowsky, Richard L. Whitman, Andrew Wither, Manuela Caniça, Rita Carvalho da Fonseca, Aida Duarte, Thomas A. Edge, Maria J. Gargaté, Nina Gunde-Cimerman, Ferry Hagen, Sandra L. McLellan, Alexandra Nogueira da Silva, Monika Novak Babič, Susana Prada, Raquel Rodrigues, Daniela Romão, Raquel Sabino, Robert A. Samson, Esther Segal, Christopher Staley, Huw D. Taylor, Cristina Veríssimo, Carla Viegas, Helena Barroso, João C. Brandão
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- Journal:
- Journal of the Marine Biological Association of the United Kingdom / Volume 96 / Issue 1 / February 2016
- Published online by Cambridge University Press:
- 01 July 2015, pp. 101-120
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Recent studies suggest that sand can serve as a vehicle for exposure of humans to pathogens at beach sites, resulting in increased health risks. Sampling for microorganisms in sand should therefore be considered for inclusion in regulatory programmes aimed at protecting recreational beach users from infectious disease. Here, we review the literature on pathogen levels in beach sand, and their potential for affecting human health. In an effort to provide specific recommendations for sand sampling programmes, we outline published guidelines for beach monitoring programmes, which are currently focused exclusively on measuring microbial levels in water. We also provide background on spatial distribution and temporal characteristics of microbes in sand, as these factors influence sampling programmes. First steps toward establishing a sand sampling programme include identifying appropriate beach sites and use of initial sanitary assessments to refine site selection. A tiered approach is recommended for monitoring. This approach would include the analysis of samples from many sites for faecal indicator organisms and other conventional analytes, while testing for specific pathogens and unconventional indicators is reserved for high-risk sites. Given the diversity of microbes found in sand, studies are urgently needed to identify the most significant aetiological agent of disease and to relate microbial measurements in sand to human health risk.
Contributors
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- By Candice A. Alfano, J. Todd Arnedt, Alon Y. Avidan, Ruth M. Benca, Jed E. Black, Katy Borodkin, Kirk J. Brower, Ritchie E. Brown, Daniel J. Buysse, Dani Choufani, Deirdre A. Conroy, Samuele Cortese, Yaron Dagan, Joel E. Dimsdale, Karl Doghramji, Fabio Ferrarelli, Marcos G. Frank, Philip R. Gehrman, Chad C. Hagen, J. Allan Hobson, Magdolna Hornyak, Thomas D. Hurwitz, Anna Ivanenko, Andrew D. Krystal, Michel Lecendreux, In-Soo Lee, Robert W. McCarley, James T. McKenna, Valerie McLaughlin Crabtree, Thomas A. Mellman, Marta Novak, Michael Perlis, Aimee L. Pierce, David T. Plante, Donn Posner, Allen C. Richert, Dieter Riemann, Carlos H. Schenck, Michael Schredl, Gregory Stores, Andras Szentkiralyi, Michael E. Thase, Wendy M. Troxel, John W. Winkelman
- Edited by John W. Winkelman, David T. Plante, University of Wisconsin, Madison
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- Book:
- Foundations of Psychiatric Sleep Medicine
- Published online:
- 01 June 2011
- Print publication:
- 23 December 2010, pp vii-x
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Molecular pathogenesis and clinical implications of eczema herpeticum
- Caroline Bussmann, Wen-Ming Peng, Thomas Bieber, Natalija Novak
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- Journal:
- Expert Reviews in Molecular Medicine / Volume 10 / October 2008
- Published online by Cambridge University Press:
- 14 July 2008, e21
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A subgroup of patients with atopic dermatitis develops one or more episodes of a severe viral skin infection caused by herpes simplex virus superimposed on eczematous skin lesions. This condition is named atopic dermatitis complicated by eczema herpeticum. Characteristic features of patients developing eczema herpeticum include an early age of onset of atopic dermatitis with a persistent and severe course into adulthood, predilection for eczematous skin lesions in the head and neck area, elevated total serum IgE levels and increased allergen sensitisation. Deficiencies at the level of both the innate and the adaptive immune system, which have been identified in atopic dermatitis, are much more pronounced in this subgroup. Predisposing cellular factors include a reduced number of plasmacytoid dendritic cells in the epidermis and a modified capacity of these cells to produce type I interferons after allergen challenge. In addition, lower levels of antimicrobial peptides in the skin of atopic dermatitis patients, resulting in part from a Th2-prone micromilieu, contribute to the lack of an effective defence against viral attack. In this review, we summarise the current knowledge of the molecular pathogenesis of eczema herpeticum.
48 - Bladder exstrophy
- from Part V - Urology
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- By Thomas E. Novak, Brady Urological Institute, The Johns Hopkins Hospital, Baltimore, MD, USA, John P. Gearhart, Brady Urological Institute, The Johns Hopkins Hospital, Baltimore, MD, USA
- Edited by Mark D. Stringer, Keith T. Oldham, Pierre D. E. Mouriquand
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- Book:
- Pediatric Surgery and Urology
- Published online:
- 08 January 2010
- Print publication:
- 09 November 2006, pp 621-630
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Summary
Introduction
The epispadias/exstrophy complex encompasses a spectrum of rare midline defects in the pelvis and genitalia. Classic bladder exstrophy is a severe congenital malformation affecting approximately 1 in 40000 live births. Although the exact etiology remains unknown, current evidence seems to implicate poor mesenchymal ingrowth with subsequent deleterious effects on the timing and position of rupture of the cloacal membrane.
The birth of a child with bladder exstrophy marks the start of a lifelong journey. The severity of the defect promises an extensive surgical undertaking that starts most frequently during the first days of life and often extends through adolescence. Components of surgical correction include: closure of the bladder, posterior urethra, pelvis and abdominal wall at birth, genital reconstruction, and some form of continence procedure. The approach pioneered at the senior author's institution addresses these components in a modern, staged fashion. Alternatively, there are also proponents of complete primary closure, which attempts to address all components in a single operation. However, recent data from the American Academy of Pediatrics reveals inferior continence rates when this technique is used. Longer follow-up is needed to ascertain the applicability of this repair, as the associated complications are not insignificant.
With respect to outcomes, the goals of reconstruction in the exstrophy patient are urinary continence and satisfactory genital cosmesis and function. Although most children prefer to achieve continence with voiding per urethra, some will accomplish this same outcome with intermittent catheterization.
Bowing Parameter of AlxGa1-xN
- Feng Yun, Michael A. Reshchikov, Lei He, Thomas King, M. Zafar Iqbal, Hadis Morkoç, Steve W. Novak, Luncun Wei
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- Journal:
- MRS Online Proceedings Library Archive / Volume 722 / 2002
- Published online by Cambridge University Press:
- 01 February 2011, K3.2
- Print publication:
- 2002
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AlxGa1-xN samples covering the entire range of alloy compositions, 0≤x≤1, were grown by plasma-assisted MBE on c-plane sapphire substrates. The aluminum mole fraction was determined, by three different techniques, namely, x-ray diffraction, secondary ion mass spectroscopy, and Rutherford backscattering spectrometry. The energy bandgaps of the alloys were obtained from low temperature reflectance spectra. The data lead to a bowing parameter of b=1.0 eV in relating the bandgap of the AlxGa1-xN alloy to its chemical composition. A discussion of bowing parameter determination is presented along with possible causes for the large dispersion in previously reported bowing parameter values.
Looking Backward, Looking Forward: MLA Members Speak
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- Journal:
- PMLA / Publications of the Modern Language Association of America / Volume 115 / Issue 7 / December 2000
- Published online by Cambridge University Press:
- 23 October 2020, pp. 1986-2078
- Print publication:
- December 2000
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