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Article ; Online: Temperature and nutrition do not interact to shape the evolution of metabolic rate.

Alton, Lesley A / Kutz, Teresa / Bywater, Candice L / Lombardi, Emily / Cockerell, Fiona E / Layh, Sean / Winwood-Smith, Hugh / Arnold, Pieter A / Beaman, Julian E / Walter, Greg M / Monro, Keyne / Mirth, Christen K / Sgrò, Carla M / White, Craig R

Philosophical transactions of the Royal Society of London. Series B, Biological sciences

2024 Volume 379, Issue 1896, Page(s) 20220484

Abstract: Metabolic cold adaptation, or Krogh's rule, is the controversial hypothesis that predicts a monotonically negative relationship between metabolic rate and environmental temperature for ectotherms living along thermal clines measured at a common ... ...

Abstract	Metabolic cold adaptation, or Krogh's rule, is the controversial hypothesis that predicts a monotonically negative relationship between metabolic rate and environmental temperature for ectotherms living along thermal clines measured at a common temperature. Macrophysiological patterns consistent with Krogh's rule are not always evident in nature, and experimentally evolved responses to temperature have failed to replicate such patterns. Hence, temperature may not be the sole driver of observed variation in metabolic rate. We tested the hypothesis that temperature, as a driver of energy demand, interacts with nutrition, a driver of energy supply, to shape the evolution of metabolic rate to produce a pattern resembling Krogh's rule. To do this, we evolved replicate lines of
MeSH term(s)	Female ; Male ; Animals ; Temperature ; Drosophila melanogaster ; Nutritional Status
Language	English
Publishing date	2024-01-08
Publishing country	England
Document type	Journal Article
ZDB-ID	208382-6
ISSN	1471-2970 ; 0080-4622 ; 0264-3839 ; 0962-8436
ISSN (online)	1471-2970
ISSN	0080-4622 ; 0264-3839 ; 0962-8436
DOI	10.1098/rstb.2022.0484
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Article ; Online: Updated core competencies in pharmacoepidemiology to inform contemporary curricula and training for academia, government, and industry.

Osborne, Vicki / Goodin, Amie / Brown, Joshua / Winterstein, Almut G / Bate, Andrew / Cohet, Catherine / Pont, Lisa / Moeny, David / Klungel, Olaf / Pinheiro, Simone / Seeger, John / Chan, K Arnold / Edlavitch, Stanley / Tilson, Hugh / Layton, Deborah

Pharmacoepidemiology and drug safety

2024 Volume 33, Issue 4, Page(s) e5789

Abstract: Purpose: The first paper to specify the core content of pharmacoepidemiology as a profession was published by an ISPE (International Society for Pharmacoepidemiology) workgroup in 2012 (Jones JK et al. PDS 2012; 21[7]:677-689). Due to the broader and ... ...

Abstract	Purpose: The first paper to specify the core content of pharmacoepidemiology as a profession was published by an ISPE (International Society for Pharmacoepidemiology) workgroup in 2012 (Jones JK et al. PDS 2012; 21[7]:677-689). Due to the broader and evolving scope of pharmacoepidemiology, ISPE considers it important to proactively identify, update and expand the list of core competencies to inform curricula of education programs; thus, better positioning pharmacoepidemiologists across academic, government (including regulatory), and industry positions. The aim of this project was to update the list of core competencies in pharmacoepidemiology. Methods: To ensure applicability of findings to multiple areas, a working group was established consisting of ISPE members with positions in academia, industry, government, and other settings. All competencies outlined by Jones et al. were extracted from the initial manuscript and presented to the working group for review. Expert-based judgments were collated and used to identify consensus. It was noted that some competencies could contribute to multiple groups and could be directly or indirectly related to a group. Results: Five core domains were proposed: (1) Epidemiology, (2) Clinical Pharmacology, (3) Regulatory Science, (4) Statistics and data science, and (5) Communication and other professional skills. In total, 55 individual competencies were proposed, of which 25 were new competencies. No competencies from the original work were dropped but aggregation or amendments were made where considered necessary. Conclusions: While many core competencies in pharmacoepidemiology have remained the same over the past 10 years, there have also been several updates to reflect new and emerging concepts in the field.
MeSH term(s)	Humans ; Pharmacoepidemiology ; Academia ; Curriculum ; Clinical Competence ; Government
Language	English
Publishing date	2024-04-17
Publishing country	England
Document type	Journal Article
ZDB-ID	1099748-9
ISSN	1099-1557 ; 1053-8569
ISSN (online)	1099-1557
ISSN	1053-8569
DOI	10.1002/pds.5789
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Zs.A 3395: Show issues

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Article ; Online: An Observational Study of Dialogue about Uncertainty in Clinician-Family Counseling Conversations Following Prenatal Diagnosis of Complex Congenital Heart Disease.

Harris, Kelly W / Schweiberger, Kelsey / Kavanaugh-McHugh, Ann / Arnold, Robert M / Merlin, Jessica / Chang, Judy C / Kasparian, Nadine A

PEC innovation

2024 Volume 4, Page(s) 100265

Abstract: Objective: Families who receive a prenatal diagnosis of complex congenital heart disease (cCHD) often experience severe psychological distress and identify uncertainty as a key source of that distress. This study examined clinician-family conversations ... ...

Abstract	Objective: Families who receive a prenatal diagnosis of complex congenital heart disease (cCHD) often experience severe psychological distress and identify uncertainty as a key source of that distress. This study examined clinician-family conversations during initial fetal cardiology consultations to identify the topics of uncertainty discussed. Methods: In this observational, qualitative study, initial fetal cardiology consultations were audio-recorded, transcribed verbatim, and coded by two independent coders. A codebook was inductively and deductively developed and applied. This content analysis focused on uncertainty-related codes and associated themes. Results: During 19 consultations including five clinicians, 13 different cardiac diagnoses were discussed (seven with high mortality risk). Median consultation length was 37 min (IQR: 26-51), with only 11% of words spoken by families. On average, 51% of total words spoken focused on uncertainty in relation to cardiac diagnosis, etiology, comorbidities, prognosis, childbirth, therapeutics, and logistics. Family-initiated discussion on uncertainty largely focused on childbirth and pregnancy and postpartum logistics. Conclusions: Half of dialogue within initial fetal cardiology encounters discussed uncertainty surrounding prenatally diagnosed cCHD. Parent and clinician perspectives should be gathered on the essential content and optimal delivery of uncertainty-related topics. Innovation: This study is conceptually and methodologically innovative as one of the first to examine audio-recorded dialogue between fetal cardiology clinicians and families.
Language	English
Publishing date	2024-02-13
Publishing country	Netherlands
Document type	Journal Article
ISSN	2772-6282
ISSN (online)	2772-6282
DOI	10.1016/j.pecinn.2024.100265
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Article ; Online: Standard pleural interventions are not high-risk aerosol generating procedures.

Arnold, David T / Gregson, Florence K A / Sheikh, Sadiyah / Hamilton, Fergus W / Welch, Hugh / Dipper, Alexandra / Nava, George W / Dodd, James W / Clive, Amelia O / Bzdek, Bryan R / Reid, Jonathan P / Maskell, Nick A

The European respiratory journal

2021 Volume 58, Issue 4

MeSH term(s)	Aerosols ; Humans ; Infectious Disease Transmission, Patient-to-Professional ; Pandemics
Chemical Substances	Aerosols
Language	English
Publishing date	2021-10-14
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	639359-7
ISSN	1399-3003 ; 0903-1936
ISSN (online)	1399-3003
ISSN	0903-1936
DOI	10.1183/13993003.01064-2021
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Zs.A 2322: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: "I Just Want You to Hear That Term": Characterizing Language Used in Fetal Cardiology Consultations.

Schweiberger, Kelsey / Harris, Kelly W / Kavanaugh-McHugh, Ann / Soudi, Abdesalam / Arnold, Robert M / Merlin, Jessica S / Kasparian, Nadine A / Chang, Judy C

Journal of cardiovascular development and disease

2023 Volume 10, Issue 9

Abstract: The way clinicians communicate with parents during pregnancy about congenital heart disease (CHD) can significantly influence parental understanding of and psychological response to the diagnosis. A necessary first step to improving communication used in ...

Abstract	The way clinicians communicate with parents during pregnancy about congenital heart disease (CHD) can significantly influence parental understanding of and psychological response to the diagnosis. A necessary first step to improving communication used in fetal cardiology consultations is to understand and describe the language currently used, which this paper aims to do. Nineteen initial fetal cardiology consultations with parents were audio-recorded, transcribed verbatim, and coded by two independent coders. A codebook was inductively developed and applied to all transcripts. The finalized coding was used to characterize fetal cardiologists' language. We identified four discourse styles employed in fetal cardiology consultations: small talk, medical, plain, and person-centered. Plain language was used to define and emphasize the meaning of medical language. Person-centered language was used to emphasize the baby as a whole person. Each consultation included all four discourse styles, with plain and medical used most frequently. Person-centered was used less frequently and mostly occurred near the end of the encounters; whether this is the ideal balance of discourse styles is unknown. Clinicians also used person-centered language (as opposed to disease-centered language), which is recommended by medical societies. Future studies should investigate the ideal balance of discourse styles and the effects of clinician discourse styles on family outcomes, including parents' decision-making, psychological adjustment, and quality of life.
Language	English
Publishing date	2023-09-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2777082-5
ISSN	2308-3425 ; 2308-3425
ISSN (online)	2308-3425
ISSN	2308-3425
DOI	10.3390/jcdd10090394
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Article: A tumor suppressor role for PP2A-B56alpha through negative regulation of c-Myc and other key oncoproteins.

Arnold, Hugh K / Sears, Rosalie C

Cancer metastasis reviews

2008 Volume 27, Issue 2, Page(s) 147–158

Abstract: Loss or inhibition of the serine/threonine protein phosphatase 2A (PP2A) has revealed a critical tumor suppressor function for PP2A. However, PP2A has also been shown to have important roles in cell cycle progression and survival. Therefore, PP2A is not ... ...

Abstract	Loss or inhibition of the serine/threonine protein phosphatase 2A (PP2A) has revealed a critical tumor suppressor function for PP2A. However, PP2A has also been shown to have important roles in cell cycle progression and survival. Therefore, PP2A is not a typical tumor suppressor. This is most likely due to the fact that PP2A represents a large number of different holoenzymes. Further understanding of PP2A function(s), and especially its tumor suppressor activity, will depend largely on our ability to determine specific targets for these different PP2A holoenzymes and to gain an understanding of how these targets confer tumor suppressor activity or contribute to cell cycle progression and cell survival. Recent work has identified c-Myc as a target of the PP2A holoenzyme, PP2A-B56alpha. This holoenzyme also negatively regulates beta-catenin expression and modulates the anti-apoptotic activity of Bcl2, thus characterizing PP2A-B56alpha as a tumor suppressor PP2A holoenzyme. This review will focus on the role of PP2A-B56alpha in regulating c-Myc and will place this tumor suppressor activity of PP2A within the context of its other tumor suppressor functions. Finally, the mechanism(s) through which PP2A-B56alpha tumor suppressor activity may be lost in cancer will be discussed.
MeSH term(s)	Animals ; Humans ; Isoenzymes/physiology ; Oncogene Proteins/physiology ; Protein Phosphatase 2/physiology ; Proto-Oncogene Proteins c-myc/metabolism ; Signal Transduction/physiology
Chemical Substances	Isoenzymes ; Oncogene Proteins ; Proto-Oncogene Proteins c-myc ; Protein Phosphatase 2 (EC 3.1.3.16)
Language	English
Publishing date	2008-02-01
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	604857-2
ISSN	1573-7233 ; 0167-7659
ISSN (online)	1573-7233
ISSN	0167-7659
DOI	10.1007/s10555-008-9128-9
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Zs.A 1812: Show issues

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Article: Protein phosphatase 2A regulatory subunit B56alpha associates with c-myc and negatively regulates c-myc accumulation.

Arnold, Hugh K / Sears, Rosalie C

Molecular and cellular biology

2006 Volume 26, Issue 7, Page(s) 2832–2844

Abstract: Protein phosphatase 2A (PP2A) plays a prominent role in controlling accumulation of the proto-oncoprotein c-Myc. PP2A mediates its effects on c-Myc by dephosphorylating a conserved residue that normally stabilizes c-Myc, and in this way, PP2A enhances c- ... ...

Abstract	Protein phosphatase 2A (PP2A) plays a prominent role in controlling accumulation of the proto-oncoprotein c-Myc. PP2A mediates its effects on c-Myc by dephosphorylating a conserved residue that normally stabilizes c-Myc, and in this way, PP2A enhances c-Myc ubiquitin-mediated degradation. Stringent regulation of c-Myc levels is essential for normal cell function, as c-Myc overexpression can lead to cell transformation. Conversely, PP2A has tumor suppressor activity. Uncovering relevant PP2A holoenzymes for a particular target has been limited by the fact that cellular PP2A represents a large heterogeneous population of trimeric holoenzymes, composed of a conserved catalytic subunit and a structural subunit along with a variable regulatory subunit which directs the holoenzyme to a specific target. We now report the identification of a specific PP2A regulatory subunit, B56alpha, that selectively associates with the N terminus of c-Myc. B56alpha directs intact PP2A holoenzymes to c-Myc, resulting in a dramatic reduction in c-Myc levels. Inhibition of PP2A-B56alpha holoenzymes, using small hairpin RNA to knock down B56alpha, results in c-Myc overexpression, elevated levels of c-Myc serine 62 phosphorylation, and increased c-Myc function. These results uncover a new protein involved in regulating c-Myc expression and reveal a critical interconnection between a potent oncoprotein, c-Myc, and a well-documented tumor suppressor, PP2A.
MeSH term(s)	Catalytic Domain ; Down-Regulation/genetics ; Holoenzymes/biosynthesis ; Holoenzymes/metabolism ; Humans ; Phosphoprotein Phosphatases/chemistry ; Phosphoprotein Phosphatases/deficiency ; Phosphoprotein Phosphatases/genetics ; Phosphoprotein Phosphatases/metabolism ; Phosphorylation ; Protein Binding ; Protein Phosphatase 2 ; Protein Processing, Post-Translational ; Protein Subunits/genetics ; Protein Subunits/metabolism ; Proto-Oncogene Proteins c-myc/metabolism ; RNA Interference ; Serine/metabolism ; Transcriptional Activation/genetics ; Viral Proteins/metabolism
Chemical Substances	E4orf4 protein, adenovirus ; Holoenzymes ; Protein Subunits ; Proto-Oncogene Proteins c-myc ; Viral Proteins ; Serine (452VLY9402) ; Phosphoprotein Phosphatases (EC 3.1.3.16) ; Protein Phosphatase 2 (EC 3.1.3.16)
Language	English
Publishing date	2006-03-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1128/MCB.26.7.2832-2844.2006
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Zs.A 1666: Show issues

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Article ; Online: Sequence analysis of the rifampicin resistance determining region (RRDR) of rpoB gene in multidrug resistance confirmed and newly diagnosed tuberculosis patients of Punjab, Pakistan.

Hameed, Salma / Moganeradj, Kartyk / Mahmood, Nasir / McHugh, Timothy D / Chaudhry, Muhammad Nawaz / Arnold, Catherine

PloS one

2017 Volume 12, Issue 8, Page(s) e0183363

Abstract: Molecular screening of new patients suspected for TB could help in the effective control of TB in Pakistan as it is a high TB burden country. It will be informative to understand the prevalence of multi drug resistance for a better drug regimen ... ...

Abstract	Molecular screening of new patients suspected for TB could help in the effective control of TB in Pakistan as it is a high TB burden country. It will be informative to understand the prevalence of multi drug resistance for a better drug regimen management in this geographical area. The Rifampicin resistance determining region (RRDR) sequencing was used to identify mutations associated with drug resistance in DNA extracts from 130 known multidrug resistant (MDR) cultured strains and compared with mutations observed in DNA extracts directly from 86 sputum samples from consecutive newly diagnosed cases in Lahore, Pakistan. These newly diagnosed samples were positive for smear microscopy, chest X-ray and presumed sensitive to first line drugs. In the known MDR group the most frequent mutations conferring resistance were found in rpoB531 (n = 51, 39.2%). In the newly diagnosed tuberculosis group with no history of MDR, mutations in rpoB531 were seen in 10 of the samples (11.6%). Collectively, all mutations in the RRDR region studied were observed in 80 (61.5%) of known MDR cases and in 14 (16.3%) of the newly diagnosed cases. Using the RRDR as a surrogate marker for MDR, sequences for the newly diagnosed (presumed sensitive) group indicate much higher levels of MDR than the 3.9% WHO 2015 global estimate and suggests that molecular screening directly from sputum is urgently required to effectively address the detection and treatment gaps to combat MDR in this high burden country.
MeSH term(s)	Antitubercular Agents/therapeutic use ; Bacterial Proteins/genetics ; DNA-Directed RNA Polymerases/genetics ; Humans ; Microbial Sensitivity Tests ; Mutation ; Pakistan ; Rifampin/therapeutic use ; Tuberculosis, Multidrug-Resistant/drug therapy
Chemical Substances	Antitubercular Agents ; Bacterial Proteins ; rpoB protein, Mycobacterium tuberculosis ; DNA-Directed RNA Polymerases (EC 2.7.7.6) ; Rifampin (VJT6J7R4TR)
Language	English
Publishing date	2017-08-17
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0183363
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Article ; Online: Proceedings from the Albert Charitable Trust Inaugural Workshop on white matter and cognition in aging.

GeroScience

2019 Volume 42, Issue 1, Page(s) 81–96

Abstract: This third in a series of vascular cognitive impairment (VCI) workshops, supported by "The Leo and Anne Albert Charitable Trust," was held from February 8 to 12 at the Omni Resort in Carlsbad, CA. This workshop followed the information gathered from the ... ...

Abstract	This third in a series of vascular cognitive impairment (VCI) workshops, supported by "The Leo and Anne Albert Charitable Trust," was held from February 8 to 12 at the Omni Resort in Carlsbad, CA. This workshop followed the information gathered from the earlier two workshops suggesting that we focus more specifically on brain white matter in age-related cognitive impairment. The Scientific Program Committee (Frank Barone, Shawn Whitehead, Eric Smith, and Rod Corriveau) assembled translational, clinical, and basic scientists with unique expertise in acute and chronic white matter injury at the intersection of cerebrovascular and neurodegenerative etiologies. As in previous Albert Trust workshops, invited participants addressed key topics related to mechanisms of white matter injury, biomarkers of white matter injury, and interventions to prevent white matter injury and age-related cognitive decline. This report provides a synopsis of the presentations and discussions by the participants, including the existing knowledge gaps and the delineation of the next steps towards advancing our understanding of white matter injury and age-related cognitive decline. Workshop discussions and consensus resulted in action by The Albert Trust to (1) increase support from biannual to annual "White Matter and Cognition" workshops; (2) provide funding for two collaborative, novel research grants annually submitted by meeting participants; and (3) coordinate the formation of the "Albert Research Institute for White Matter and Cognition." This institute will fill a gap in white matter science, providing white matter and cognition communications, including annual updates from workshops and the literature and interconnecting with other Albert Trust scientific endeavors in cognition and dementia, and providing support for newly established collaborations between seasoned investigators and to the development of talented young investigators in the VCI-dementia (VCID) and white matter cognition arena.
MeSH term(s)	Aging ; Cognition ; Cognitive Dysfunction ; Dementia, Vascular ; Humans ; White Matter
Language	English
Publishing date	2019-12-06
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2886586-8
ISSN	2509-2723 ; 2509-2715
ISSN (online)	2509-2723
ISSN	2509-2715
DOI	10.1007/s11357-019-00141-8
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Zs.A 1502: Show issues

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Article ; Online: C-reactive protein modifies lipoprotein(a)-related risk for coronary heart disease: the BiomarCaRE project.

Arnold, Natalie / Blaum, Christopher / Goßling, Alina / Brunner, Fabian J / Bay, Benjamin / Ferrario, Marco M / Brambilla, Paolo / Cesana, Giancarlo / Leoni, Valerio / Palmieri, Luigi / Donfrancesco, Chiara / Padró, Teresa / Andersson, Jonas / Jousilahti, Pekka / Ojeda, Francisco / Zeller, Tanja / Linneberg, Allan / Söderberg, Stefan / Iacoviello, Licia /

Gianfagna, Francesco / Sans, Susana / Veronesi, Giovanni / Thorand, Barbara / Peters, Annette / Tunstall-Pedoe, Hugh / Kee, Frank / Salomaa, Veikko / Schnabel, Renate B / Kuulasmaa, Kari / Blankenberg, Stefan / Koenig, Wolfgang / Waldeyer, Christoph

European heart journal

2024 Volume 45, Issue 12, Page(s) 1043–1054

Abstract: Background and aims: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C- ... ...

Abstract	Background and aims: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population. Methods: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (<2 and ≥2 mg/L). Results: Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23-1.72) and 1.48 (1.23-1.78) for a hsCRP group of <2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥ 2 mg/L [1.34 (1.03-1.76)], whereas among participants with a hsCRP concentration <2 mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98-1.71)] (highest vs. lowest fifth, fully adjusted models; Pinteraction = 0.024). Conclusions: While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds.
MeSH term(s)	Humans ; C-Reactive Protein/metabolism ; Prospective Studies ; Risk Factors ; Lipoprotein(a) ; Coronary Disease/epidemiology ; Biomarkers/metabolism
Chemical Substances	C-Reactive Protein (9007-41-4) ; Lipoprotein(a) ; Biomarkers
Language	English
Publishing date	2024-01-04
Publishing country	England
Document type	Journal Article
ZDB-ID	603098-1
ISSN	1522-9645 ; 0195-668X
ISSN (online)	1522-9645
ISSN	0195-668X
DOI	10.1093/eurheartj/ehad867
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Zs.A 1563: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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