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Article: A Case of Multisystem Inflammatory Syndrome in Children Mimicking Acute Appendicitis in a COVID-19 Pandemic Area.

Jackson, Ramon J / Chavarria, Hector D / Hacking, Sean M

2020 Volume 12, Issue 9, Page(s) e10722

Abstract: The outbreak of the novel coronavirus (2019-nCoV) began in Wuhan, China and spread rapidly throughout the world. As of now, there have been numerous reports demonstrating clinical, radiological and pathological findings in adults. In children, the ... ...

Abstract	The outbreak of the novel coronavirus (2019-nCoV) began in Wuhan, China and spread rapidly throughout the world. As of now, there have been numerous reports demonstrating clinical, radiological and pathological findings in adults. In children, the disease has essentially been seen as mild and self-limiting. However, more recently, children have been presenting with findings reminiscent of Kawasaki's disease. And secondary to this, the benign nature of COVID-19 disease in children is beginning to be challenged. This phenomenon is now referred to as multisystem inflammatory syndrome in children (MIS-C). Further understanding the clinical course in MIS-C and its temporal association with coronavirus disease 2019 will be paramount for treatment and public health decision making. This correspondence describes a case of MIS-C with gastrointestinal manifestations mimicking acute appendicitis in a child presenting from a COVID-19 endemic area.
Keywords	covid19
Language	English
Publishing date	2020-09-29
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.10722
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Article: A Case of Multisystem Inflammatory Syndrome in Children Mimicking Acute Appendicitis in a COVID-19 Pandemic Area

Jackson, Ramon J. / Chavarria, Hector D. / Hacking, Sean M.

Cureus

Abstract: The outbreak of the novel coronavirus (2019-nCoV) began in Wuhan, China and spread rapidly throughout the world As of now, there have been numerous reports demonstrating clinical, radiological and pathological findings in adults In children, the disease ... ...

Abstract	The outbreak of the novel coronavirus (2019-nCoV) began in Wuhan, China and spread rapidly throughout the world As of now, there have been numerous reports demonstrating clinical, radiological and pathological findings in adults In children, the disease has essentially been seen as mild and self-limiting However, more recently, children have been presenting with findings reminiscent of Kawasaki's disease And secondary to this, the benign nature of COVID-19 disease in children is beginning to be challenged This phenomenon is now referred to as multisystem inflammatory syndrome in children (MIS-C) Further understanding the clinical course in MIS-C and its temporal association with coronavirus disease 2019 will be paramount for treatment and public health decision making This correspondence describes a case of MIS-C with gastrointestinal manifestations mimicking acute appendicitis in a child presenting from a COVID-19 endemic area
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #859069
Database	COVID19

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Article ; Online: Selective Janus kinase 1 inhibition resolves inflammation and restores hair growth offering a viable treatment option for alopecia areata.

Skin health and disease

2023 Volume 3, Issue 3, Page(s) e209

Abstract: Background: Janus Kinase (JAK) inhibition has recently demonstrated therapeutic efficacy in both restoring hair growth and resolving inflammation in Alopecia Areata (AA). These effects are dose dependent and mainly efficacious at ranges close to a ... ...

Abstract	Background: Janus Kinase (JAK) inhibition has recently demonstrated therapeutic efficacy in both restoring hair growth and resolving inflammation in Alopecia Areata (AA). These effects are dose dependent and mainly efficacious at ranges close to a questionable risk profile. Objectives: We explored the possibility to separate the beneficial and adverse effects of JAK inhibition by selectively inhibiting JAK1 and thereby avoiding side effects associated with JAK2 blockade. Methods: The C3H/HeJ mouse model of AA was used to demonstrate therapeutic efficacy in vivo with different regimens of a selection of JAK inhibitors in regards to systemic versus local drug exposure. Human peripheral blood lymphocytes were stimulated in vitro to demonstrate translation to the human situation. Results: We demonstrate that selective inhibition of JAK1 produces fast resolution of inflammation and complete restoration of hair growth in the C3H/HeJ mouse model of AA. Furthermore, we show that topical treatment does not restore hair growth and that treatment needs to be extended well beyond that of restored hair growth in order to reach treatment-free remission. For translatability to human disease, we show that cytokines involved in AA pathogenesis are similarly inhibited by selective JAK1 and pan-JAK inhibition in stimulated human peripheral lymphocytes and specifically in CD8 Conclusion: This study demonstrates that systemic exposure is required for efficacy in AA and we propose that a selective JAK1 inhibitor will offer a treatment option with a superior safety profile to pan-JAK inhibitors for these patients.
Language	English
Publishing date	2023-01-29
Publishing country	England
Document type	Journal Article
ISSN	2690-442X
ISSN (online)	2690-442X
DOI	10.1002/ski2.209
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Article ; Online: Delayed Systemic Treatment with Cannabinoid Receptor 2 Agonist Mitigates Spinal Cord Injury-Induced Osteoporosis More Than Acute Treatment Directly after Injury.

Tucci, Michelle A / Pride, Yilianys / Strickland, Suzanne / Marocho, Susanna M Salazar / Jackson, Ramon J / Jefferson, Joshua R / Chade, Alejandro R / Grill, Raymond J / Grayson, Bernadette E

Neurotrauma reports

2021 Volume 2, Issue 1, Page(s) 270–284

Abstract: Nearly all persons with spinal cord injury (SCI) will develop osteoporosis following injury, and further, up to 50% of all persons with SCI will sustain a fracture during their lives. The unique mechanisms driving osteoporosis following SCI remain ... ...

Abstract	Nearly all persons with spinal cord injury (SCI) will develop osteoporosis following injury, and further, up to 50% of all persons with SCI will sustain a fracture during their lives. The unique mechanisms driving osteoporosis following SCI remain unknown. The cannabinoid system modulation of bone metabolism through cannabinoid 1/2 (CB1/2) has been of increasing interest for the preservation of bone mass and density in models of osteoporosis. Using a thoracic vertebral level 8 (T8) complete transection in a mouse model, we performed daily treatment with a selective CB2 receptor agonist, HU308, compared with SCI-vehicle-treated and naïve control animals either immediately after injury for 40 days, or in a delayed paradigm, following 3 months after injury. The goal was to prevent or potentially reverse SCI-induced osteoporosis. In the acute phase, administration of the CB2 agonist was not able to preserve the rapid loss of cancellous bone. In the delayed-treatment paradigm, in cortical bone, HU308 increased cortical-area to total-area ratio and periosteal perimeter in the femur, and improved bone density in the distal femur and proximal tibia. Further, we report changes to the metaphyseal periosteum with increased presence of adipocyte and fat mass in the periosteum of SCI animals, which was not present in naïve animals. The layer of fat increased markedly in HU308-treated animals compared with SCI-vehicle-treated animals. Overall, these data show that CB2 agonism targets a number of cell types that can influence overall bone quality.
Language	English
Publishing date	2021-06-22
Publishing country	United States
Document type	Journal Article
ISSN	2689-288X
ISSN (online)	2689-288X
DOI	10.1089/neur.2020.0059
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Article: Impact of SARS-CoV-2 vaccines and recent chemotherapy on COVID-19 morbidity and mortality in patients with soft tissue sarcoma: an analysis from the OnCovid registry.

Vincenzi, Bruno / Cortellini, Alessio / Mazzocca, Alessandro / Orlando, Sarah / Romandini, Davide / Aguilar-Company, Juan / Ruiz-Camps, Isabel / Valverde Morales, Claudia / Eremiev-Eremiev, Simeon / Tondini, Carlo / Brunet, Joan / Bertulli, Rossella / Provenzano, Salvatore / Bower, Mark / Generali, Daniele / Salazar, Ramon / Sureda, Anna / Prat, Aleix / Vasiliki, Michalarea /

Therapeutic advances in medical oncology

2024 Volume 16, Page(s) 17588359231225028

Abstract: Background: To date, limited evidence exists on the impact of COVID-19 in patients with soft tissue sarcoma (STS), nor about the impact of SARS-CoV-2 vaccines and recent chemotherapy on COVID-19 morbidity and mortality in this specific population.: ... ...

Abstract	Background: To date, limited evidence exists on the impact of COVID-19 in patients with soft tissue sarcoma (STS), nor about the impact of SARS-CoV-2 vaccines and recent chemotherapy on COVID-19 morbidity and mortality in this specific population. Methods: We described COVID-19 morbidity and mortality among patients with STS across 'Omicron' (15 December 2021-31 January 2022), 'Pre-vaccination' (27 February 2020-30 November 2020), and 'Alpha-Delta' phase (01 December 2020-14 December 2021) using OnCovid registry participants (NCT04393974). Case fatality rate at 28 days (CFR Results: Out of 3820 patients, 97 patients with STS were included. The median age at COVID-19 diagnosis was 56 years (range: 18-92), with 65 patients (67%) aged < 65 years and most patients had a low comorbidity burden (65, 67.0%). The most frequent primary tumor sites were the abdomen (56.7%) and the gynecological tract (12.4%). In total, 36 (37.1%) patients were on cytotoxic chemotherapy within 4 weeks prior to COVID-19. The overall CFR Conclusion: In this study, we demonstrate an improvement in COVID-19 outcomes in patients with STS over time. Recent exposure to chemotherapy does not impact COVID-19 morbidity and mortality and SARS-CoV-2 vaccination confers protection against adverse outcomes from COVID-19 in this patient population.
Language	English
Publishing date	2024-01-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2503443-1
ISSN	1758-8359 ; 1758-8340
ISSN (online)	1758-8359
ISSN	1758-8340
DOI	10.1177/17588359231225028
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Article: Deep mixed ocean volume in the Labrador Sea in HighResMIP models

Koenigk, Torben / Fuentes-Franco, Ramon / Meccia, Virna L. / Gutjahr, Oliver / Jackson, Laura C. / New, Adrian L. / Ortega, Pablo / Roberts, Christopher D. / Roberts, Malcolm J. / Arsouze, Thomas / Iovino, Doroteaciro / Moine, Marie-Pierre / Sein, Dmitry V.

Climate dynamics. 2021 Oct., v. 57, no. 7-8

2021

Abstract: Simulations from seven global coupled climate models performed at high and standard resolution as part of the high resolution model intercomparison project (HighResMIP) are analyzed to study deep ocean mixing in the Labrador Sea and the impact of ... ...

Abstract	Simulations from seven global coupled climate models performed at high and standard resolution as part of the high resolution model intercomparison project (HighResMIP) are analyzed to study deep ocean mixing in the Labrador Sea and the impact of increased horizontal resolution. The representation of convection varies strongly among models. Compared to observations from ARGO-floats and the EN4 data set, most models substantially overestimate deep convection in the Labrador Sea. In four out of five models, all four using the NEMO-ocean model, increasing the ocean resolution from 1° to 1/4° leads to increased deep mixing in the Labrador Sea. Increasing the atmospheric resolution has a smaller effect than increasing the ocean resolution. Simulated convection in the Labrador Sea is mainly governed by the release of heat from the ocean to the atmosphere and by the vertical stratification of the water masses in the Labrador Sea in late autumn. Models with stronger sub-polar gyre circulation have generally higher surface salinity in the Labrador Sea and a deeper convection. While the high-resolution models show more realistic ocean stratification in the Labrador Sea than the standard resolution models, they generally overestimate the convection. The results indicate that the representation of sub-grid scale mixing processes might be imperfect in the models and contribute to the biases in deep convection. Since in more than half of the models, the Labrador Sea convection is important for the Atlantic Meridional Overturning Circulation (AMOC), this raises questions about the future behavior of the AMOC in the models.
Keywords	autumn ; climate ; convection ; data collection ; dynamics ; salinity
Language	English
Dates of publication	2021-10
Size	p. 1895-1918.
Publishing place	Springer Berlin Heidelberg
Document type	Article
ZDB-ID	1471747-5
ISSN	1432-0894 ; 0930-7575
ISSN (online)	1432-0894
ISSN	0930-7575
DOI	10.1007/s00382-021-05785-x
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Adopting human factors in early phase and experimental medicine research: A nested pilot study observing controlled human infection with SARS-CoV-2.

Higham, Helen E / Morgan, Lauren / Cooper, Cushla / Marshall, Julia / Mawer, Andrew / Jackson, Susan / Lopez-Ramon, Raquel / Hughes, Eileen / Richards, Duncan / McShane, Helen / Fullerton, James N

British journal of clinical pharmacology

2023

Abstract: Aims: The influence of human factors on safety in healthcare settings is well established, with targeted interventions reducing risk and enhancing team performance. In experimental and early phase clinical research participant safety is paramount and ... ...

Abstract	Aims: The influence of human factors on safety in healthcare settings is well established, with targeted interventions reducing risk and enhancing team performance. In experimental and early phase clinical research participant safety is paramount and safeguarded by guidelines, protocolized care and staff training; however, the real-world interaction and implementation of these risk-mitigating measures has never been subjected to formal system-based assessment. Methods: Independent structured observations, systematic review of study documents, and interviews and focus groups were used to collate data on three key tasks undertaken in a clinical research facility (CRF) during a SARS CoV-2 controlled human infection model (CHIM) study. The Systems Engineering Initiative for Patient Safety (SEIPS) was employed to analyse and categorize findings, and develop recommendations for safety interventions. Results: High levels of team functioning and a clear focus on participant safety were evident throughout the study. Despite this, latent risks in both study-specific and CRF work systems were identified in all four SEIPS domains (people, environment, tasks and tools). Fourteen actionable recommendations were generated collaboratively. These included inter-organization and inter-study standardization, optimized checklists for safety critical tasks, and use of simulation for team training and exploration of work systems. Conclusions: This pioneering application of human factors techniques to analyse work systems during the conduct of research in a CRF revealed risks unidentified by routine review and appraisal, and despite international guideline adherence. SEIPS may aid categorization of system problems and the formulation of recommendations that reduce risk and mitigate potential harm applicable across a trials portfolio.
Language	English
Publishing date	2023-10-30
Publishing country	England
Document type	Journal Article
ZDB-ID	188974-6
ISSN	1365-2125 ; 0306-5251 ; 0264-3774
ISSN (online)	1365-2125
ISSN	0306-5251 ; 0264-3774
DOI	10.1111/bcp.15949
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Article ; Online: Pandemic Phase-Adjusted Analysis of COVID-19 Outcomes Reveals Reduced Intrinsic Vulnerability and Substantial Vaccine Protection From Severe Acute Respiratory Syndrome Coronavirus 2 in Patients With Breast Cancer.

Tagliamento, Marco / Gennari, Alessandra / Lambertini, Matteo / Salazar, Ramon / Harbeck, Nadia / Del Mastro, Lucia / Aguilar-Company, Juan / Bower, Mark / Sharkey, Rachel / Dalla Pria, Alessia / Plaja, Andrea / Jackson, Amanda / Handford, Jasmine / Sita-Lumsden, Ailsa / Martinez-Vila, Clara / Matas, Marta / Miguel Rodriguez, Ana / Vincenzi, Bruno / Tonini, Giuseppe /

Bertuzzi, Alexia / Brunet, Joan / Pedrazzoli, Paolo / D'Avanzo, Francesca / Biello, Federica / Sinclair, Alasdair / Lee, Alvin J X / Rossi, Sabrina / Rizzo, Gianpiero / Mirallas, Oriol / Pimentel, Isabel / Iglesias, Maria / Sanchez de Torre, Ana / Guida, Annalisa / Berardi, Rossana / Zambelli, Alberto / Tondini, Carlo / Filetti, Marco / Mazzoni, Francesca / Mukherjee, Uma / Diamantis, Nikolaos / Parisi, Alessandro / Aujayeb, Avinash / Prat, Aleix / Libertini, Michela / Grisanti, Salvatore / Rossi, Maura / Zoratto, Federica / Generali, Daniele / Saura, Cristina / Lyman, Gary H / Kuderer, Nicole M / Pinato, David J / Cortellini, Alessio

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2023 Volume 41, Issue 15, Page(s) 2800–2814

Abstract: Purpose: Although representing the majority of newly diagnosed cancers, patients with breast cancer appear less vulnerable to COVID-19 mortality compared with other malignancies. In the absence of patients on active cancer therapy included in ... ...

Abstract	Purpose: Although representing the majority of newly diagnosed cancers, patients with breast cancer appear less vulnerable to COVID-19 mortality compared with other malignancies. In the absence of patients on active cancer therapy included in vaccination trials, a contemporary real-world evaluation of outcomes during the various pandemic phases, as well as of the impact of vaccination, is needed to better inform clinical practice. Methods: We compared COVID-19 morbidity and mortality among patients with breast cancer across prevaccination (February 27, 2020-November 30, 2020), Alpha-Delta (December 1, 2020-December 14, 2021), and Omicron (December 15, 2021-January 31, 2022) phases using OnCovid registry participants (ClinicalTrials.gov identifier: NCT04393974). Twenty-eight-day case fatality rate (CFR Results: By the data lock of February 4, 2022, the registry counted 613 eligible patients with breast cancer: 60.1% (n = 312) hormone receptor-positive, 25.2% (n = 131) human epidermal growth factor receptor 2-positive, and 14.6% (n = 76) triple-negative. The majority (61%; n = 374) had localized/locally advanced disease. Median age was 62 years (interquartile range, 51-74 years). A total of 193 patients (31.5%) presented ≥ 2 comorbidities and 69% (n = 330) were never smokers. In total, 392 (63.9%), 164 (26.8%), and 57 (9.3%) were diagnosed during the prevaccination, Alpha-Delta, and Omicron phases, respectively. Analysis of CFR Conclusion: Our findings highlight a consistent reduction of COVID-19 severity in patients with breast cancer during the Omicron outbreak in Europe. We also demonstrate that even in this population, a complete severe acute respiratory syndrome coronavirus 2 vaccination course is a strong determinant of improved morbidity and mortality from COVID-19.
MeSH term(s)	Humans ; Middle Aged ; Female ; SARS-CoV-2 ; COVID-19/epidemiology ; COVID-19/prevention & control ; Breast Neoplasms/epidemiology ; Breast Neoplasms/therapy ; COVID-19 Testing ; Pandemics ; Vaccines
Chemical Substances	Vaccines
Language	English
Publishing date	2023-01-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.22.01667
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Zs.A 1847: 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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Article ; Online: Fem1b promotes ubiquitylation and suppresses transcriptional activity of Gli1.

Gilder, Andrew S / Chen, Yong-Bin / Jackson, Ramon J / Jiang, Jin / Maher, Joseph F

Biochemical and biophysical research communications

2013 Volume 440, Issue 3, Page(s) 431–436

Abstract: The mammalian Fem1b gene encodes a homolog of FEM-1, a protein in the sex-determination pathway of the nematode Caenorhabditis elegans. Fem1b and FEM-1 proteins each contain a VHL-box motif that mediates their interaction with certain E3 ubiquitin ligase ...

Abstract	The mammalian Fem1b gene encodes a homolog of FEM-1, a protein in the sex-determination pathway of the nematode Caenorhabditis elegans. Fem1b and FEM-1 proteins each contain a VHL-box motif that mediates their interaction with certain E3 ubiquitin ligase complexes. In C. elegans, FEM-1 negatively regulates the transcription factor TRA-1, and functions as an E3 ubiquitin ligase substrate recognition subunit to target TRA-1 for ubiquitylation. TRA-1 is homologous to the mammalian Gli1 protein, a transcription factor that mediates Hedgehog signaling as well as having Hedgehog-independent functions. Whether the interaction between nematode FEM-1 and TRA-1 proteins is conserved, between corresponding mammalian homologs, has not been reported. Herein, we show that Fem1b interacts with Gli1 within cells, and directly binds Gli1. Fem1b also promotes ubiquitylation of Gli1, suppresses transcriptional activation by Gli1, and attenuates an oncogenic Gli1 autoregulatory loop in cancer cells, all dependent on the VHL-box of Fem1b. These findings have implications for understanding the cellular functions of Fem1b, and the regulation of Gli1 oncoprotein activity.
MeSH term(s)	Animals ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; DNA-Binding Proteins/metabolism ; HEK293 Cells ; Humans ; Immunoprecipitation ; Kruppel-Like Transcription Factors/genetics ; Kruppel-Like Transcription Factors/metabolism ; Mice ; NIH 3T3 Cells ; Neoplasms/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcription, Genetic ; Ubiquitin-Protein Ligase Complexes ; Ubiquitination ; Zinc Finger Protein GLI1
Chemical Substances	Caenorhabditis elegans Proteins ; Carrier Proteins ; Cell Cycle Proteins ; DNA-Binding Proteins ; FEM-1 protein, C elegans ; FEM1B protein, human ; GLI1 protein, human ; Gli1 protein, mouse ; Kruppel-Like Transcription Factors ; Transcription Factors ; Zinc Finger Protein GLI1 ; tra-1 protein, C elegans ; Fem1b protein, mouse (EC 2.3.2.23) ; Ubiquitin-Protein Ligase Complexes (EC 2.3.2.23)
Language	English
Publishing date	2013-09-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2013.09.090
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Zs.A 116: Show issues

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Article: Fem1b promotes ubiquitylation and suppresses transcriptional activity of Gli1

Gilder, Andrew S / Chen, Yong-Bin / Jackson, Ramon J / Jiang, Jin / Maher, Joseph F

Biochemical and biophysical research communications. 2013 Oct. 25, v. 440

2013

Abstract	The mammalian Fem1b gene encodes a homolog of FEM-1, a protein in the sex-determination pathway of the nematode Caenorhabditis elegans. Fem1b and FEM-1 proteins each contain a VHL-box motif that mediates their interaction with certain E3 ubiquitin ligase complexes. In C. elegans, FEM-1 negatively regulates the transcription factor TRA-1, and functions as an E3 ubiquitin ligase substrate recognition subunit to target TRA-1 for ubiquitylation. TRA-1 is homologous to the mammalian Gli1 protein, a transcription factor that mediates Hedgehog signaling as well as having Hedgehog-independent functions. Whether the interaction between nematode FEM-1 and TRA-1 proteins is conserved, between corresponding mammalian homologs, has not been reported. Herein, we show that Fem1b interacts with Gli1 within cells, and directly binds Gli1. Fem1b also promotes ubiquitylation of Gli1, suppresses transcriptional activation by Gli1, and attenuates an oncogenic Gli1 autoregulatory loop in cancer cells, all dependent on the VHL-box of Fem1b. These findings have implications for understanding the cellular functions of Fem1b, and the regulation of Gli1 oncoprotein activity.
Keywords	Caenorhabditis elegans ; genes ; mammals ; neoplasm cells ; oncogene proteins ; sex determination ; transcription (genetics) ; transcription factors ; transcriptional activation ; ubiquitin-protein ligase
Language	English
Dates of publication	2013-1025
Size	p. 431-436.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	205723-2
ISSN	0006-291X ; 0006-291X
ISSN (online)	0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2013.09.090
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