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Article ; Online: Single dose thermoresponsive dexamethasone prodrug completely mitigates joint pain for 15 weeks in a murine model of osteoarthritis.

Chen, Ningrong / Wei, Xin / Zhao, Gang / Jia, Zhenshan / Fu, Xin / Jiang, Haochen / Xu, Xiaoke / Zhao, Zhifeng / Singh, Purva / Lessard, Samantha / Otero, Miguel / Goldring, Mary B / Goldring, Steven R / Wang, Dong

Nanomedicine : nanotechnology, biology, and medicine

2024 Volume 57, Page(s) 102735

Abstract: In this study, we aimed to assess the analgesic efficacy of a thermoresponsive polymeric dexamethasone (Dex) prodrug (ProGel-Dex) in a mouse model of osteoarthritis (OA). At 12 weeks post model establishment, the OA mice received a single intra-articular ...

Abstract	In this study, we aimed to assess the analgesic efficacy of a thermoresponsive polymeric dexamethasone (Dex) prodrug (ProGel-Dex) in a mouse model of osteoarthritis (OA). At 12 weeks post model establishment, the OA mice received a single intra-articular (IA) injection of ProGel-Dex, dose-equivalent Dex, or Saline. Comparing to Saline and Dex controls, ProGel-Dex provided complete and sustained pain relief for >15 weeks according to incapacitance tests. In vivo optical imaging confirmed the continuous presence of ProGel-Dex in joints for 15 weeks post-injection. According to micro-CT analysis, ProGel-Dex treated mice had significantly lower subchondral bone thickness and medial meniscus bone volume than Dex and Saline controls. Except for a transient delay of body weight increase and slightly lower endpoint liver and spleen weights, no other adverse effect was observed after ProGel-Dex treatment. These findings support ProGel-Dex's potential as a potent and safe analgesic candidate for management of OA pain.
MeSH term(s)	Mice ; Animals ; Dexamethasone/pharmacology ; Dexamethasone/therapeutic use ; Disease Models, Animal ; Prodrugs/pharmacology ; Prodrugs/therapeutic use ; Osteoarthritis/drug therapy ; Arthralgia/chemically induced ; Arthralgia/drug therapy ; Analgesics/pharmacology ; Analgesics/therapeutic use
Chemical Substances	Dexamethasone (7S5I7G3JQL) ; Prodrugs ; Analgesics
Language	English
Publishing date	2024-01-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2183417-9
ISSN	1549-9642 ; 1549-9634
ISSN (online)	1549-9642
ISSN	1549-9634
DOI	10.1016/j.nano.2024.102735
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Article ; Online: Preferences for physician weight status among women with overweight.

Goldring, M R / Persky, S

Obesity science & practice

2018 Volume 4, Issue 3, Page(s) 250–258

Abstract: Background: Women with overweight experience stigma in clinical interactions. Emerging evidence suggests that one near-term approach to offset the negative consequences of weight stigma could be to capitalize on benefits of patient-physician weight ... ...

Abstract	Background: Women with overweight experience stigma in clinical interactions. Emerging evidence suggests that one near-term approach to offset the negative consequences of weight stigma could be to capitalize on benefits of patient-physician weight concordance. However, it is likely that patient attitudes towards physicians with overweight are complicated and multifaceted and may include stigmatization of providers with overweight. Methods: Two-hundred ninety-eight women with overweight completed an online questionnaire and indicated preference for a physician who is 'overweight', 'not overweight', or indicated no preference. Participants provided reasons for their choice and answered questions about their weight-related beliefs and experiences. Results: The majority of women indicated no weight preference (63%), and a portion (36%) of the sample explicitly preferred physicians who are not overweight. Reasons provided for these preferences were primarily based on stereotyped notions of physician aptitude based on weight. Compared with having no preference, those who preferred physicians who are not overweight had fewer previous negative weight-related physician interactions and had increased beliefs about the controllability of weight. Conclusions: These findings elucidate patient attitudes towards physicians with overweight in a sample at increased risk for weight stigmatization. Findings underscore the need for stigma-reducing interventions so that clinical experiences for both women and physicians with overweight can be improved.
Language	English
Publishing date	2018-04-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2836381-4
ISSN	2055-2238 ; 2055-2238
ISSN (online)	2055-2238
ISSN	2055-2238
DOI	10.1002/osp4.162
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Article ; Online: Molecular biology of cholangiocarcinoma and its implications for targeted therapy in patient management.

Gilbert, T M / Randle, L / Quinn, M / McGreevy, O / O'leary, L / Young, R / Diaz-Neito, R / Jones, R P / Greenhalf, B / Goldring, C / Fenwick, S / Malik, H / Palmer, D H

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology

2024 , Page(s) 108352

Abstract: Cholangiocarcinoma (CCA) remains a devastating malignancy and a significant challenge to treat. The majority of CCA patients are diagnosed at an advanced stage, making the disease incurable in most cases. The advent of high-throughput genetic sequencing ... ...

Abstract	Cholangiocarcinoma (CCA) remains a devastating malignancy and a significant challenge to treat. The majority of CCA patients are diagnosed at an advanced stage, making the disease incurable in most cases. The advent of high-throughput genetic sequencing has significantly improved our understanding of the molecular biology underpinning cancer. The identification of 'druggable' genetic aberrations and the development of novel targeted therapies against them is opening up new treatment strategies. Currently, 3 targeted therapies are approved for use in CCA; Ivosidenib in patients with IDH1 mutations and Infigratinib/Pemigatinib in those with FGFR2 fusions. As our understanding of the biology underpinning CCA continues to improve it is highly likely that additional targeted therapies will become available in the near future. This is important, as it is thought up to 40 % of CCA patients harbour a potentially actionable mutation. In this review we provide an overview of the molecular pathogenesis of CCA and highlight currently available and potential future targeted treatments.
Language	English
Publishing date	2024-04-17
Publishing country	England
Document type	Journal Article
ZDB-ID	632519-1
ISSN	1532-2157 ; 0748-7983
ISSN (online)	1532-2157
ISSN	0748-7983
DOI	10.1016/j.ejso.2024.108352
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Article: Preferences for physician weight status among women with overweight

Goldring, M. R. / Persky, S.

Obesity science & practice. 2018 June, v. 4, no. 3

2018

Abstract: BACKGROUND: Women with overweight experience stigma in clinical interactions. Emerging evidence suggests that one near‐term approach to offset the negative consequences of weight stigma could be to capitalize on benefits of patient–physician weight ... ...

Abstract	BACKGROUND: Women with overweight experience stigma in clinical interactions. Emerging evidence suggests that one near‐term approach to offset the negative consequences of weight stigma could be to capitalize on benefits of patient–physician weight concordance. However, it is likely that patient attitudes towards physicians with overweight are complicated and multifaceted and may include stigmatization of providers with overweight. METHODS: Two‐hundred ninety‐eight women with overweight completed an online questionnaire and indicated preference for a physician who is ‘overweight’, ‘not overweight’, or indicated no preference. Participants provided reasons for their choice and answered questions about their weight‐related beliefs and experiences. RESULTS: The majority of women indicated no weight preference (63%), and a portion (36%) of the sample explicitly preferred physicians who are not overweight. Reasons provided for these preferences were primarily based on stereotyped notions of physician aptitude based on weight. Compared with having no preference, those who preferred physicians who are not overweight had fewer previous negative weight‐related physician interactions and had increased beliefs about the controllability of weight. CONCLUSIONS: These findings elucidate patient attitudes towards physicians with overweight in a sample at increased risk for weight stigmatization. Findings underscore the need for stigma‐reducing interventions so that clinical experiences for both women and physicians with overweight can be improved.
Keywords	obesity ; patients ; questionnaires ; risk ; stigma
Language	English
Dates of publication	2018-06
Size	p. 250-258.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	2836381-4
ISSN	2055-2238
ISSN	2055-2238
DOI	10.1002/osp4.162
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Article ; Online: Reversible deactivation of motor cortex reveals that areas in parietal cortex are differentially dependent on motor cortex for the generation of movement.

Bresee, Chris S / Cooke, Dylan F / Goldring, Adam B / Baldwin, Mary K L / Pineda, Carlos R / Krubitzer, Leah A

Journal of neurophysiology

2023 Volume 131, Issue 1, Page(s) 106–123

Abstract: Primates are characterized by specializations for manual manipulation, including expansion of posterior parietal cortex (PPC) and, in Catarrhines, evolution of a dexterous hand and opposable thumb. Previous studies examined functional interactions ... ...

Abstract	Primates are characterized by specializations for manual manipulation, including expansion of posterior parietal cortex (PPC) and, in Catarrhines, evolution of a dexterous hand and opposable thumb. Previous studies examined functional interactions between motor cortex and PPC in New World monkeys and galagos, by inactivating M1 and evoking movements from PPC. These studies found that portions of PPC depend on M1 to generate movements. We now add a species that more closely resembles humans in hand morphology and PPC: macaques. Inactivating portions of M1 resulted in all evoked movements being reduced (28%) or completely abolished (72%) at the PPC sites tested (in areas 5L, PF, and PFG). Anterior parietal area 2 was similarly affected (26% reduced and 74% abolished) and area 1 was the least affected (12% no effect, 54% reduced, and 34% abolished). Unlike previous studies in New World monkeys and galagos, interactions between both nonanalogous (heterotopic) and analogous (homotopic) M1 and parietal movement domains were commonly found in most areas. These experiments demonstrate that there may be two parallel networks involved in motor control: a posterior parietal network dependent on M1 and a network that includes area 1 that is relatively independent of M1. Furthermore, it appears that the relative size and number of cortical fields in parietal cortex in different species correlates with homotopic and heterotopic effect prevalence. These functional differences in macaques could contribute to more numerous and varied muscle synergies across major muscle groups, supporting the expansion of the primate manual behavioral repertoire observed in Old World monkeys.
MeSH term(s)	Humans ; Animals ; Motor Cortex/physiology ; Galago/physiology ; Parietal Lobe/physiology ; Movement/physiology ; Macaca ; Platyrrhini
Language	English
Publishing date	2023-12-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	80161-6
ISSN	1522-1598 ; 0022-3077
ISSN (online)	1522-1598
ISSN	0022-3077
DOI	10.1152/jn.00086.2023
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Article ; Online: Raised Intracranial Pressure in Three Children with Cystic Fibrosis Receiving Elexacaftor-Tezacaftor-Ivacaftor Modulator Therapy.

Southern, Kevin W / Barben, Jürg / Goldring, Stephen / Kneen, Rachel / Southward, Suzanne / Rajeev, Yashasvi / Davies, Jane C / Bush, Andrew

American journal of respiratory and critical care medicine

2023 Volume 208, Issue 1, Page(s) 103–105

MeSH term(s)	Humans ; Child ; Cystic Fibrosis/drug therapy ; Cystic Fibrosis/genetics ; Intracranial Pressure ; Cystic Fibrosis Transmembrane Conductance Regulator ; Aminophenols/therapeutic use ; Benzodioxoles/therapeutic use ; Mutation
Chemical Substances	elexacaftor (RRN67GMB0V) ; ivacaftor (1Y740ILL1Z) ; tezacaftor ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6) ; Aminophenols ; Benzodioxoles
Language	English
Publishing date	2023-05-25
Publishing country	United States
Document type	Letter
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202303-0380LE
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Article ; Online: Genomic profiling of idiopathic peri-hilar cholangiocarcinoma reveals new targets and mutational pathways.

Quinn, Leonard M / Haldenby, Sam / Antzcak, Philip / Fowler, Anna / Bullock, Katie / Kenny, John / Gilbert, Timothy / Andrews, Timothy / Diaz-Nieto, Rafael / Fenwick, Stephen / Jones, Robert / Costello-Goldring, Eithne / Poston, Graeme / Greenhalf, William / Palmer, Daniel / Malik, Hassan / Goldring, Chris

Scientific reports

2023 Volume 13, Issue 1, Page(s) 6681

Abstract: Peri-hilar cholangiocarcinoma (pCCA) is chemorefractory and limited genomic analyses have been undertaken in Western idiopathic disease. We undertook comprehensive genomic analyses of a U.K. idiopathic pCCA cohort to characterize its mutational profile ... ...

Abstract	Peri-hilar cholangiocarcinoma (pCCA) is chemorefractory and limited genomic analyses have been undertaken in Western idiopathic disease. We undertook comprehensive genomic analyses of a U.K. idiopathic pCCA cohort to characterize its mutational profile and identify new targets. Whole exome and targeted DNA sequencing was performed on forty-two resected pCCA tumors and normal bile ducts, with Gene Set Enrichment Analysis (GSEA) using one-tailed testing to generate false discovery rates (FDR). 60% of patients harbored one cancer-associated mutation, with two mutations in 20%. High frequency somatic mutations in genes not typically associated with cholangiocarcinoma included mTOR, ABL1 and NOTCH1. We identified non-synonymous mutation (p.Glu38del) in MAP3K9 in ten tumors, associated with increased peri-vascular invasion (Fisher's exact, p < 0.018). Mutation-enriched pathways were primarily immunological, including innate Dectin-2 (FDR 0.001) and adaptive T-cell receptor pathways including PD-1 (FDR 0.007), CD4 phosphorylation (FDR 0.009) and ZAP70 translocation (FDR 0.009), with overlapping HLA genes. We observed cancer-associated mutations in over half of our patients. Many of these mutations are not typically associated with cholangiocarcinoma yet may increase eligibility for contemporary targeted trials. We also identified a targetable MAP3K9 mutation, in addition to oncogenic and immunological pathways hitherto not described in any cholangiocarcinoma subtype.
MeSH term(s)	Humans ; Klatskin Tumor/pathology ; Bile Ducts, Intrahepatic/pathology ; Bile Duct Neoplasms/pathology ; Mutation ; Cholangiocarcinoma/pathology ; Genomics ; DNA Mutational Analysis ; MAP Kinase Kinase Kinases/genetics
Chemical Substances	MAP3K9 protein, human (EC 2.7.11.25) ; MAP Kinase Kinase Kinases (EC 2.7.11.25)
Language	English
Publishing date	2023-04-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-33096-0
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Article ; Online: Current Perspective: 3D Spheroid Models Utilizing Human-Based Cells for Investigating Metabolism-Dependent Drug-Induced Liver Injury.

Cox, Christopher R / Lynch, Stephen / Goldring, Christopher / Sharma, Parveen

Frontiers in medical technology

2020 Volume 2, Page(s) 611913

Abstract: Drug-induced liver injury (DILI) remains a leading cause for the withdrawal of approved drugs. This has significant financial implications for pharmaceutical companies, places increasing strain on global health services, and causes harm to patients. For ... ...

Abstract	Drug-induced liver injury (DILI) remains a leading cause for the withdrawal of approved drugs. This has significant financial implications for pharmaceutical companies, places increasing strain on global health services, and causes harm to patients. For these reasons, it is essential that
Language	English
Publishing date	2020-11-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	2673-3129
ISSN (online)	2673-3129
DOI	10.3389/fmedt.2020.611913
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Article ; Online: Genomics-informed weight management in primary care: anticipated public interest.

Persky, Susan / Goldring, Megan R / Cohen, Rachel W

Personalized medicine

2018 Volume 15, Issue 4, Page(s) 271–278

Abstract: Aim: An exploratory survey assessed the influence of current and potential future genomic applications for weight management on individuals' desires to address weight management within primary care. Materials & methods: A convenience sample of 714 US ... ...

Abstract	Aim: An exploratory survey assessed the influence of current and potential future genomic applications for weight management on individuals' desires to address weight management within primary care. Materials & methods: A convenience sample of 714 US adults aged 18-70 completed an online survey that presented three scenarios: no genomic information; current genomic capabilities; and potential future applications of genomics for weight management. Results: Participants had increased interest in weight management assistance through primary care when considering genomic applications in weight management, p (1,1.68) = 24.66, p < 0.001; this increase was more robust among individuals who felt their weight was important for their health, p (1,1.68) = 20.85, p < 0.001. Conclusion: Primary care systems may need to accommodate a rise in the volume of patients seeking weight management assistance as genomic approaches come to fruition.
MeSH term(s)	Adult ; Aged ; Female ; Genomics/methods ; Humans ; Male ; Middle Aged ; Precision Medicine/methods ; Primary Health Care ; Surveys and Questionnaires ; United States ; Weight Loss ; Weight Reduction Programs/methods ; Young Adult
Language	English
Publishing date	2018-06-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2299146-3
ISSN	1744-828X ; 1741-0541
ISSN (online)	1744-828X
ISSN	1741-0541
DOI	10.2217/pme-2018-0011
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Zs.A 6549: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Mothers' and fathers' cognitive and affective responses to epigenetics concepts.

Hollister, Brittany M / Yaremych, Haley E / Goldring, Megan R / Persky, Susan

Environmental epigenetics

2019 Volume 5, Issue 4, Page(s) dvz021

Abstract: Advances in our understanding of epigenetics present new opportunities to improve children's health through the counseling of parents about epigenetics concepts. However, it is important to first evaluate how parents respond to this type of information ... ...

Abstract	Advances in our understanding of epigenetics present new opportunities to improve children's health through the counseling of parents about epigenetics concepts. However, it is important to first evaluate how parents respond to this type of information and determine the consequences of educating parents about epigenetics. We have taken an initial step toward this goal by assessing parental responses to an epigenetics learning module. Parents (
Language	English
Publishing date	2019-11-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2831217-X
ISSN	2058-5888 ; 2058-5888
ISSN (online)	2058-5888
ISSN	2058-5888
DOI	10.1093/eep/dvz021
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