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Article: Metabolic abnormalities in the bone marrow cells of young offspring born to obese mothers.

Alina, Maloyan / Phillips, Elysse / Alharithi, Yem / Kadam, Leena / Coussens, Lisa / Kumar, Sushil

Research square

2024

Abstract: Intrauterine metabolic reprogramming occurs in obese mothers during gestation, putting the offspring at high risk of developing obesity and associated metabolic disorders even before birth. We have generated a mouse model of maternal high-fat diet- ... ...

Abstract	Intrauterine metabolic reprogramming occurs in obese mothers during gestation, putting the offspring at high risk of developing obesity and associated metabolic disorders even before birth. We have generated a mouse model of maternal high-fat diet-induced obesity that recapitulates the metabolic changes seen in humans born to obese women. Here, we profiled and compared the metabolic characteristics of bone marrow cells of newly weaned 3-week-old offspring of dams fed either a high-fat (Off-HFD) or a regular diet (Off-RD). We utilized a state-of-the-art targeted metabolomics approach coupled with a Seahorse metabolic analyzer. We revealed significant metabolic perturbation in the offspring of HFD-fed vs. RD-fed dams, including utilization of glucose primarily via oxidative phosphorylation. We also found a reduction in levels of amino acids, a phenomenon previously linked to bone marrow aging. Using flow cytometry, we identified a unique B cell population expressing CD19 and CD11b in the bone marrow of three-week-old offspring of high-fat diet-fed mothers, and found increased expression of Cyclooxygenase-2 (COX-2) on myeloid CD11b, and on CD11b
Language	English
Publishing date	2024-01-16
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3830161/v1
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Article ; Online: Jeff Pollard (1950-2023).

Coussens, Lisa M / De Palma, Michele / Mariani, Samanta A / Cassetta, Luca

Nature reviews. Cancer

2023 Volume 23, Issue 8, Page(s) 507

Language	English
Publishing date	2023-05-28
Publishing country	England
Document type	Editorial
ZDB-ID	2062767-1
ISSN	1474-1768 ; 1474-175X
ISSN (online)	1474-1768
ISSN	1474-175X
DOI	10.1038/s41568-023-00600-7
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Zs.A 5563: 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: Tuberculosis prevalence: beyond the tip of the iceberg.

Houben, Rein M G J / Esmail, Hanif / Cobelens, Frank / Williams, Caroline M L / Coussens, Anna K

The Lancet. Respiratory medicine

2022 Volume 10, Issue 6, Page(s) 537–539

MeSH term(s)	Humans ; Tuberculosis/epidemiology
Language	English
Publishing date	2022-05-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2686754-0
ISSN	2213-2619 ; 2213-2600
ISSN (online)	2213-2619
ISSN	2213-2600
DOI	10.1016/S2213-2600(22)00184-9
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Article ; Online: Physician Antipsychotic Overprescribing Letters and Cognitive, Behavioral, and Physical Health Outcomes Among People With Dementia: A Secondary Analysis of a Randomized Clinical Trial.

Harnisch, Michelle / Barnett, Michael L / Coussens, Stephen / Thomas, Kali S / Olfson, Mark / Berhane, Kiros / Sacarny, Adam

JAMA network open

2024 Volume 7, Issue 4, Page(s) e247604

Abstract: Importance: Antipsychotics, such as quetiapine, are frequently prescribed to people with dementia to address behavioral symptoms but can also cause harm in this population.: Objective: To determine whether warning letters to high prescribers of ... ...

Abstract	Importance: Antipsychotics, such as quetiapine, are frequently prescribed to people with dementia to address behavioral symptoms but can also cause harm in this population. Objective: To determine whether warning letters to high prescribers of quetiapine can successfully reduce its use among patients with dementia and to investigate the impacts on patients' health outcomes. Design, setting, and participants: This is a secondary analysis of a randomized clinical trial of overprescribing letters that began in April 2015 and included the highest-volume primary care physician (PCP) prescribers of quetiapine in original Medicare. Outcomes of patients with dementia were analyzed in repeated 90-day cross-sections through December 2018. Analyses were conducted from September 2021 to February 2024. Interventions: PCPs were randomized to a placebo letter or 3 overprescribing warning letters stating that their prescribing of quetiapine was high and under review by Medicare. Main outcomes and measures: The primary outcome of this analysis was patients' total quetiapine use in days per 90-day period (the original trial primary outcome was total quetiapine prescribing by study PCPs). Prespecified secondary outcomes included measures of cognitive function and behavioral symptoms from nursing home assessments, indicators of depression from screening questionnaires in assessments and diagnoses in claims, metabolic diagnoses derived from assessments and claims, indicators of use of the hospital and other health care services, and death. Outcomes were analyzed separately for patients living in nursing homes and in the community. Results: Of the 5055 study PCPs, 2528 were randomized to the placebo letter, and 2527 were randomized to the 3 warning letters. A total of 84 881 patients with dementia living in nursing homes and 261 288 community-dwelling patients with dementia were attributed to these PCPs. There were 92 874 baseline patients (mean [SD] age, 81.5 [10.5] years; 64 242 female [69.2%]). The intervention reduced quetiapine use among both nursing home patients (adjusted difference, -0.7 days; 95% CI, -1.3 to -0.1 days; P = .02) and community-dwelling patients (adjusted difference, -1.5 days; 95% CI, -1.8 to -1.1 days; P < .001). There were no detected adverse effects on cognitive function (cognitive function scale adjusted difference, 0.01; 95% CI, -0.01 to 0.03; P = .19), behavioral symptoms (agitated or reactive behavior adjusted difference, -0.2%; 95% CI -1.2% to 0.8% percentage points; P = .72), depression, metabolic diagnoses, or more severe outcomes, including hospitalization and death. Conclusions and relevance: This study found that overprescribing warning letters to PCPs safely reduced quetiapine prescribing to their patients with dementia. This intervention and others like it may be useful for future efforts to promote guideline-concordant care. Trial registration: ClinicalTrials.gov Identifier: NCT05172687.
MeSH term(s)	Humans ; Dementia/drug therapy ; Dementia/psychology ; Antipsychotic Agents/therapeutic use ; Female ; Male ; Aged ; Quetiapine Fumarate/therapeutic use ; Inappropriate Prescribing/statistics & numerical data ; Aged, 80 and over ; Practice Patterns, Physicians'/statistics & numerical data ; United States ; Medicare ; Cognition/drug effects
Chemical Substances	Antipsychotic Agents ; Quetiapine Fumarate (2S3PL1B6UJ)
Language	English
Publishing date	2024-04-01
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ISSN	2574-3805
ISSN (online)	2574-3805
DOI	10.1001/jamanetworkopen.2024.7604
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Article ; Online: Targeting oncogene and non-oncogene addiction to inflame the tumour microenvironment.

Petroni, Giulia / Buqué, Aitziber / Coussens, Lisa M / Galluzzi, Lorenzo

Nature reviews. Drug discovery

2022 Volume 21, Issue 6, Page(s) 440–462

Abstract: Immune checkpoint inhibitors (ICIs) have revolutionized the clinical management of multiple tumours. However, only a few patients respond to ICIs, which has generated considerable interest in the identification of resistance mechanisms. One such ... ...

Abstract	Immune checkpoint inhibitors (ICIs) have revolutionized the clinical management of multiple tumours. However, only a few patients respond to ICIs, which has generated considerable interest in the identification of resistance mechanisms. One such mechanism reflects the ability of various oncogenic pathways, as well as stress response pathways required for the survival of transformed cells (a situation commonly referred to as 'non-oncogene addiction'), to support tumour progression not only by providing malignant cells with survival and/or proliferation advantages, but also by establishing immunologically 'cold' tumour microenvironments (TMEs). Thus, both oncogene and non-oncogene addiction stand out as promising targets to robustly inflame the TME and potentially enable superior responses to ICIs.
MeSH term(s)	Humans ; Immune Checkpoint Inhibitors/pharmacology ; Immune Checkpoint Inhibitors/therapeutic use ; Immunotherapy ; Neoplasms/drug therapy ; Neoplasms/genetics ; Oncogenes/genetics ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/genetics
Chemical Substances	Immune Checkpoint Inhibitors
Language	English
Publishing date	2022-03-15
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2062954-0
ISSN	1474-1784 ; 1474-1776
ISSN (online)	1474-1784
ISSN	1474-1776
DOI	10.1038/s41573-022-00415-5
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Zs.A 5564: 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: Mind the gap - Managing tuberculosis across the disease spectrum.

Esmail, Hanif / Macpherson, Liana / Coussens, Anna K / Houben, Rein M G J

EBioMedicine

2022 Volume 78, Page(s) 103928

Abstract: We currently have a binomial approach to managing tuberculosis. Those with active disease, ideally confirmed microbiologically, are treated with a standard 6-month, multi-drug regimen and those with latent infection and no evidence of disease with ... ...

Abstract	We currently have a binomial approach to managing tuberculosis. Those with active disease, ideally confirmed microbiologically, are treated with a standard 6-month, multi-drug regimen and those with latent infection and no evidence of disease with shorter, one or two drug regimens. Clinicians frequently encounter patients that fall between these two management pathways with some but not all features of disease and this will occur more often with the increasing emphasis on chest X-ray-based systematic screening. The view of tuberculosis as a spectrum of disease states is being increasingly recognised and is leading to new diagnostic approaches for early disease. However, the 6-month regimen for treating disease was driven by the duration required to treat the most extensive forms of pulmonary TB and shorter durations appear sufficient for less extensive disease. It is time undertake clinical trials to better define the optimal treatment for tuberculosis across the disease spectrum.
MeSH term(s)	Antitubercular Agents/therapeutic use ; Humans ; Tuberculosis/diagnosis ; Tuberculosis/drug therapy ; Tuberculosis/epidemiology ; Tuberculosis, Pulmonary/diagnosis ; Tuberculosis, Pulmonary/drug therapy
Chemical Substances	Antitubercular Agents
Language	English
Publishing date	2022-03-23
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2022.103928
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Article: Metabolic abnormalities in the bone marrow cells of young offspring born to obese mothers.

Phillips, Elysse / Alharithi, Yem / Kadam, Leena / Coussens, Lisa M / Kumar, Sushil / Maloyan, Alina

bioRxiv : the preprint server for biology

2023

Abstract	Intrauterine metabolic reprogramming occurs in obese mothers during gestation, putting the offspring at high risk of developing obesity and associated metabolic disorders even before birth. We have generated a mouse model of maternal high-fat diet-induced obesity that recapitulates the metabolic changes seen in humans. Here, we profiled and compared the metabolic characteristics of bone marrow cells of newly weaned 3-week-old offspring of dams fed either a high-fat (Off-HFD) or a regular diet (Off-RD). We utilized a state-of-the-art targeted metabolomics approach coupled with a Seahorse metabolic analyzer. We revealed significant metabolic perturbation in the offspring of HFD-fed vs. RD-fed dams, including utilization of glucose primarily via oxidative phosphorylation, and reduction in levels of amino acids, a phenomenon previously linked to aging. Furthermore, in the bone marrow of three-week-old offspring of high-fat diet-fed mothers, we identified a unique B cell population expressing CD19 and CD11b, and found increased expression of Cyclooxygenase-2 (COX-2) on myeloid CD11b, and on CD11b
Language	English
Publishing date	2023-12-01
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.11.29.569274
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Article ; Online: Conservative management of hand impairment in children and adolescents with heritable disorders of connective tissue: A scoping review.

Wesley, Alison / Coussens, Marie / Chan, Cliffton / Pacey, Verity / Bray, Paula / Nicholson, Leslie L

Physical & occupational therapy in pediatrics

2023 Volume 44, Issue 1, Page(s) 19–41

Abstract: Aims: To synthesize and critically appraise available interventions in the conservative management of hand impairment for children and adolescents with heritable disorders of connective tissue (HDCT).: Methods: A search of peer-reviewed literature ... ...

Abstract	Aims: To synthesize and critically appraise available interventions in the conservative management of hand impairment for children and adolescents with heritable disorders of connective tissue (HDCT). Methods: A search of peer-reviewed literature and online platforms were included with data regarding hand impairment and function, conservative management and outcome measures extracted and appraised. Levels of evidence were applied to published literature. Results: Ten peer-reviewed papers, eleven webpages and YouTube videos met the inclusion criteria. Reported interventions included: strengthening, orthoses, assistive equipment, education and pacing. Evidence of intervention effectiveness and evidence-based guidance on dosage were absent, with no consistency of outcome measures monitoring intervention effectiveness. Online platforms posted by health professionals predominantly provided advice for families without clinical detail of interventions. Conclusions: There is a consistent suite of interventions identified in both peer-reviewed literature and online platforms used by clinicians and families to manage hand impairment for children and adolescents with HDCT. Clear dosage parameters and outcome measures are needed in future intervention studies to determine the effectiveness of interventions and guide clinicians in how best to treat hand impairment. Increasing accountability and quality of online resources posted by health professionals for families is warranted to ensure dosage details and precautions are provided.
MeSH term(s)	Adolescent ; Child ; Humans ; Conservative Treatment ; Orthotic Devices ; Outcome Assessment, Health Care ; Self-Help Devices ; Connective Tissue Diseases/genetics ; Connective Tissue Diseases/therapy
Language	English
Publishing date	2023-04-26
Publishing country	England
Document type	Systematic Review
ZDB-ID	783998-4
ISSN	1541-3144 ; 0194-2638
ISSN (online)	1541-3144
ISSN	0194-2638
DOI	10.1080/01942638.2023.2199846
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Article: Single-cell spatial architectures associated with clinical outcome in head and neck squamous cell carcinoma.

Blise, Katie E / Sivagnanam, Shamilene / Banik, Grace L / Coussens, Lisa M / Goecks, Jeremy

NPJ precision oncology

2022 Volume 6, Issue 1, Page(s) 10

Abstract: There is increasing evidence that the spatial organization of cells within the tumor-immune microenvironment (TiME) of solid tumors influences survival and response to therapy in numerous cancer types. Here, we report results and demonstrate the ... ...

Abstract	There is increasing evidence that the spatial organization of cells within the tumor-immune microenvironment (TiME) of solid tumors influences survival and response to therapy in numerous cancer types. Here, we report results and demonstrate the applicability of quantitative single-cell spatial proteomics analyses in the TiME of primary and recurrent human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) tumors. Single-cell compositions of a nine patient, primary and recurrent (n = 18), HNSCC cohort is presented, followed by deeper investigation into the spatial architecture of the TiME and its relationship with clinical variables and progression free survival (PFS). Multiple spatial algorithms were used to quantify the spatial landscapes of immune cells within TiMEs and demonstrate that neoplastic tumor-immune cell spatial compartmentalization, rather than mixing, is associated with longer PFS. Mesenchymal (αSMA
Language	English
Publishing date	2022-02-25
Publishing country	England
Document type	Journal Article
ISSN	2397-768X
ISSN	2397-768X
DOI	10.1038/s41698-022-00253-z
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Article ; Online: Inflammatory Th17 responses to infection with Mycobacterium avium subspecies paratuberculosis (MAP) in cattle and their potential role in development of Johne's disease.

DeKuiper, Justin L / Coussens, Paul M

Veterinary immunology and immunopathology

2019 Volume 218, Page(s) 109954

Abstract: Chronic intestinal inflammation typically associated with late stage Johne's disease (JD) in cattle occurs despite a lack of significant expression of the typical proinflammatory cytokines IFNγ and TNFα derived from Th1- like T cells. In contrast, these ... ...

Abstract	Chronic intestinal inflammation typically associated with late stage Johne's disease (JD) in cattle occurs despite a lack of significant expression of the typical proinflammatory cytokines IFNγ and TNFα derived from Th1- like T cells. In contrast, these cytokines appear to be relatively abundant during early infections with Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of JD in cattle. The roles of non-classical immune responses, such as those associated with Th17 cells, in response to MAP infection and development of clinical JD are less clear. In this review, we examine literature suggesting that Mycobacterial infections, including Mycobacterium tuberculosis, Mycobacterium bovis, and MAP, are all associated with expression of Th17 promoting cytokines (IL-23, IL-22, IL-17a). We discuss the possibility that Th17 associated cytokines, particularly IL-23, may act as contributing factors in development and maintenance of inflammation characteristic of clinical JD. An as yet relatively unexplored source of chronic inflammation due to over expression of IL-1α and IL-1β is also presented. We further discuss the fact that, as with the typical Th1-like cytokines IFNγ and TNFα , IL-17a is not significantly expressed in CD4+ T cells from cows with clinical JD, possibly due to T cell exhaustion. Finally, we present the notion that the Th17 driving cytokine IL-23 expressed by infected macrophages and associated epithelial cells may contribute to chronic inflammation during later stages of JD.
MeSH term(s)	Animals ; Cattle ; Cattle Diseases/immunology ; Cattle Diseases/microbiology ; Cytokines/immunology ; Female ; Inflammation ; Interleukin-17/immunology ; Interleukin-23/immunology ; Intestines/immunology ; Intestines/microbiology ; Macrophages/immunology ; Macrophages/microbiology ; Mycobacterium avium subsp. paratuberculosis ; Paratuberculosis/immunology ; Th17 Cells/immunology
Chemical Substances	Cytokines ; Interleukin-17 ; Interleukin-23
Language	English
Publishing date	2019-10-01
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	754160-0
ISSN	1873-2534 ; 0165-2427
ISSN (online)	1873-2534
ISSN	0165-2427
DOI	10.1016/j.vetimm.2019.109954
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