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Article ; Online: Pathogenesis of COVID-19-induced ARDS: implications for an ageing population.

Torres Acosta, Manuel A / Singer, Benjamin D

2020 Volume 56, Issue 3

Abstract: The coronavirus disease 2019 (COVID-19) pandemic has elicited a swift response by the scientific community to elucidate the pathogenesis of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-induced lung injury and develop effective ... ...

Abstract	The coronavirus disease 2019 (COVID-19) pandemic has elicited a swift response by the scientific community to elucidate the pathogenesis of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-induced lung injury and develop effective therapeutics. Clinical data indicate that severe COVID-19 most commonly manifests as viral pneumonia-induced acute respiratory distress syndrome (ARDS), a clinical entity mechanistically understood best in the context of influenza A virus-induced pneumonia. Similar to influenza, advanced age has emerged as the leading host risk factor for developing severe COVID-19. In this review we connect the current understanding of the SARS-CoV-2 replication cycle and host response to the clinical presentation of COVID-19, borrowing concepts from influenza A virus-induced ARDS pathogenesis and discussing how these ideas inform our evolving understanding of COVID-19-induced ARDS. We also consider important differences between COVID-19 and influenza, mainly the protean clinical presentation and associated lymphopenia of COVID-19, the contrasting role of interferon-γ in mediating the host immune response to these viruses, and the tropism for vascular endothelial cells of SARS-CoV-2, commenting on the potential limitations of influenza as a model for COVID-19. Finally, we explore hallmarks of ageing that could explain the association between advanced age and susceptibility to severe COVID-19.
MeSH term(s)	Aging/physiology ; Betacoronavirus/physiology ; COVID-19 ; Coronavirus Infections/complications ; Disease Susceptibility ; Humans ; Pandemics ; Pneumonia, Viral/complications ; Respiratory Distress Syndrome/virology ; SARS-CoV-2 ; Virus Replication
Keywords	covid19
Language	English
Publishing date	2020-09-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	639359-7
ISSN	1399-3003 ; 0903-1936
ISSN (online)	1399-3003
ISSN	0903-1936
DOI	10.1183/13993003.02049-2020
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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: The impact of underrepresented minority or marginalized identity status on training outcomes of MD-PhD students.

Torres Acosta, Manuel A / Chandra, Sidhanth / Li, Sophia / Yoon, Esther / Selgrade, Daniel / Quinn, Jeanne / Ardehali, Hossein

BMC medical education

2023 Volume 23, Issue 1, Page(s) 428

Abstract: Dual-degree MD-PhD programs have historically lacked diversity of race, ethnicity, gender, sexual orientation, and other facets of identity. Like MD- and PhD-granting programs, MD-PhD program training environments are also marked by structural barriers ... ...

Abstract	Dual-degree MD-PhD programs have historically lacked diversity of race, ethnicity, gender, sexual orientation, and other facets of identity. Like MD- and PhD-granting programs, MD-PhD program training environments are also marked by structural barriers that negatively impact measurable academic outcomes of underrepresented and/or marginalized students in academic medicine (racial and ethnic minority groups considered underrepresented by the National Institute of Health, sexual and gender minorities, individuals with disabilities, and individuals of low socioeconomic status). In this article, we review the existing literature on MD-PhD program disparities affecting students from these groups and provide recommendations grounded on the reviewed evidence. Our literature review identified four generalizable barriers that can impact the training outcomes of students from these marginalized and/or underrepresented groups: 1) discrimination and bias, 2) impostor syndrome and stereotype threat, 3) lack of identity-similar mentors, and 4) suboptimal institutional policies and procedures. We propose goal-oriented interventions that may begin to ameliorate the disparities present in MD-PhD program training environments that affect students from marginalized and/or underrepresented groups in academic medicine.
MeSH term(s)	Humans ; Male ; Female ; Ethnicity ; Minority Groups ; Students ; Medicine ; Mentors ; Biomedical Research/education
Language	English
Publishing date	2023-06-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2044473-4
ISSN	1472-6920 ; 1472-6920
ISSN (online)	1472-6920
ISSN	1472-6920
DOI	10.1186/s12909-023-04399-7
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Article ; Online: The impact of underrepresented minority or marginalized identity status on training outcomes of MD-PhD students

Manuel A. Torres Acosta / Sidhanth Chandra / Sophia Li / Esther Yoon / Daniel Selgrade / Jeanne Quinn / Hossein Ardehali

BMC Medical Education, Vol 23, Iss 1, Pp 1-

2023 Volume 11

Abstract: Abstract Dual-degree MD-PhD programs have historically lacked diversity of race, ethnicity, gender, sexual orientation, and other facets of identity. Like MD- and PhD-granting programs, MD-PhD program training environments are also marked by structural ... ...

Abstract	Abstract Dual-degree MD-PhD programs have historically lacked diversity of race, ethnicity, gender, sexual orientation, and other facets of identity. Like MD- and PhD-granting programs, MD-PhD program training environments are also marked by structural barriers that negatively impact measurable academic outcomes of underrepresented and/or marginalized students in academic medicine (racial and ethnic minority groups considered underrepresented by the National Institute of Health, sexual and gender minorities, individuals with disabilities, and individuals of low socioeconomic status). In this article, we review the existing literature on MD-PhD program disparities affecting students from these groups and provide recommendations grounded on the reviewed evidence. Our literature review identified four generalizable barriers that can impact the training outcomes of students from these marginalized and/or underrepresented groups: 1) discrimination and bias, 2) impostor syndrome and stereotype threat, 3) lack of identity-similar mentors, and 4) suboptimal institutional policies and procedures. We propose goal-oriented interventions that may begin to ameliorate the disparities present in MD-PhD program training environments that affect students from marginalized and/or underrepresented groups in academic medicine.
Keywords	Dual-degree training ; MD-PhD ; Physician scientist training ; Diversity and inclusion ; Special aspects of education ; LC8-6691 ; Medicine ; R
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Peritoneal Dialysis during the COVID-19 Pandemic Is an Effective Treatment in Developing Countries: A Report from Mexico.

Villa-Torres, Alberto / Vásquez-Jiménez, Enzo / Velazquez-Silva, Ricardo Iván / Herrera-Arellano, Leticia / Acosta-García, Nayeli / Aleman-Quimbiulco, Dolores / Duarte-Pérez, Ricardo / Carmona Bautista, Carlos A / Rodríguez-Chagolla, José Manuel

Blood purification

2023 Volume 52, Issue 11-12, Page(s) 898–904

Abstract: Introduction: During the height of the coronavirus disease-19 (COVID-19) pandemic, some renal replacement therapy (RRT) modalities were insufficient, forcing medical centers to diversify the RRT modalities offered. In this study, we reported the ... ...

Abstract	Introduction: During the height of the coronavirus disease-19 (COVID-19) pandemic, some renal replacement therapy (RRT) modalities were insufficient, forcing medical centers to diversify the RRT modalities offered. In this study, we reported the outcomes of chronic peritoneal dialysis (PD) patients and acute PD in critically ill patients during COVID-19 pandemic in a tertiary care medical center in Mexico. Methods: This descriptive, longitudinal, observational, retrospective study included 47 adult patients with atypical pneumonia in a tertiary care medical center in Mexico during the first and second waves of the COVID-19 pandemic. Chronic PD patients and PD incident patients due to acute kidney injury (AKI) were included. Results: Forty-seven patients were studied (29 chronic PD patients and 18 incident PD patients due to AKI); median age was 59 (48-68) years; 63.8% were men. The ultrafiltrate volume per day was 815 (596.1-1,193.2) mL. Overall mortality was 61.7%, 55.2% in chronic PD patients, and 72.2% in PD incident patients due to AKI. A higher Sequential Organ Failure Assessment (SOFA) score, the need for mechanical ventilation at admission, and the requirement for vasopressors were predictors for mortality (p < 0.01). Conclusion: In low- and lower-middle-income countries, PD was a valid alternative for RRT during the COVID-19 pandemic. In AKI patients, PD can correct hyperkalemia, acidosis, uremia, and volume overload; however, there was higher mortality in PD incident patients due to AKI. The main risk factors for mortality were a high SOFA score at admission, the need for invasive mechanical ventilation, and the requirement for vasopressors.
MeSH term(s)	Male ; Adult ; Humans ; Middle Aged ; Female ; COVID-19/therapy ; COVID-19/complications ; Pandemics ; Retrospective Studies ; Mexico/epidemiology ; Developing Countries ; Intensive Care Units ; Peritoneal Dialysis/adverse effects ; Renal Replacement Therapy/adverse effects ; Acute Kidney Injury/etiology ; Acute Kidney Injury/therapy ; Acute Kidney Injury/epidemiology
Language	English
Publishing date	2023-10-25
Publishing country	Switzerland
Document type	Observational Study ; Journal Article
ZDB-ID	605548-5
ISSN	1421-9735 ; 0253-5068
ISSN (online)	1421-9735
ISSN	0253-5068
DOI	10.1159/000534198
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Zs.A 1872: Show issues

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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: AMP-activated protein kinase is necessary for Treg cell functional adaptation to microenvironmental stress.

Torres Acosta, Manuel A / Mambetsariev, Nurbek / Reyes Flores, Carla P / Helmin, Kathryn A / Liu, Qianli / Joudi, Anthony M / Morales-Nebreda, Luisa / Gurkan, Jonathan / Cheng, Kathleen / Abdala-Valencia, Hiam / Weinberg, Samuel E / Singer, Benjamin D

bioRxiv : the preprint server for biology

2023

Abstract: CD4+FOXP3+ regulatory T (Treg) cells maintain self-tolerance, suppress the immune response to cancer, and protect against tissue injury in the lung and other organs. Treg cells require mitochondrial metabolism to exert their function, but how Treg cells ... ...

Abstract	CD4+FOXP3+ regulatory T (Treg) cells maintain self-tolerance, suppress the immune response to cancer, and protect against tissue injury in the lung and other organs. Treg cells require mitochondrial metabolism to exert their function, but how Treg cells adapt their metabolic programs to sustain and optimize their function during an immune response occurring in a metabolically stressed microenvironment remains unclear. Here, we tested whether Treg cells require the energy homeostasis-maintaining enzyme AMP-activated protein kinase (AMPK) to adapt to metabolically aberrant microenvironments caused by malignancy or lung injury, finding that AMPK is dispensable for Treg cell immune-homeostatic function but is necessary for full Treg cell function in B16 melanoma tumors and during acute lung injury caused by influenza virus pneumonia. AMPK-deficient Treg cells had lower mitochondrial mass and exhibited an impaired ability to maximize aerobic respiration. Mechanistically, we found that AMPK regulates DNA methyltransferase 1 to promote transcriptional programs associated with mitochondrial function in the tumor microenvironment. In the lung during viral pneumonia, we found that AMPK sustains metabolic homeostasis and mitochondrial activity. Induction of DNA hypomethylation was sufficient to rescue mitochondrial mass in AMPK-deficient Treg cells, linking DNA methylation with AMPK function and mitochondrial metabolism. These results define AMPK as a determinant of Treg cell adaptation to metabolic stress and offer potential therapeutic targets in cancer and tissue injury.
Language	English
Publishing date	2023-12-01
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.11.29.568904
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Mediator complex subunit 1 architects a tumorigenic Treg cell program independent of inflammation.

Chaudhuri, Shuvam M / Weinberg, Samuel E / Wang, Dongmei / Yalom, Lenore K / Montauti, Elena / Iyer, Radhika / Tang, Amy Y / Torres Acosta, Manuel A / Shen, Jian / Mani, Nikita L / Wang, Shengnan / Liu, Kun / Lu, Weiyuan / Bui, Triet M / Manzanares, Laura D / Dehghani, Zeinab / Wai, Ching Man / Gao, Beixue / Wei, Juncheng /

Yue, Feng / Cui, Weiguo / Singer, Benjamin D / Sumagin, Ronen / Zhang, Yana / Fang, Deyu

Cell reports. Medicine

2024 Volume 5, Issue 3, Page(s) 101441

Abstract: While immunotherapy has revolutionized cancer treatment, its safety has been hampered by immunotherapy-related adverse events. Unexpectedly, we show that Mediator complex subunit 1 (MED1) is required for T regulatory ( ... ...

Abstract	While immunotherapy has revolutionized cancer treatment, its safety has been hampered by immunotherapy-related adverse events. Unexpectedly, we show that Mediator complex subunit 1 (MED1) is required for T regulatory (T
MeSH term(s)	Humans ; Animals ; Mice ; T-Lymphocytes, Regulatory ; Mediator Complex Subunit 1/metabolism ; Forkhead Transcription Factors ; Neoplasms/pathology ; Inflammation/metabolism ; Tumor Microenvironment
Chemical Substances	Mediator Complex Subunit 1 ; Forkhead Transcription Factors
Language	English
Publishing date	2024-02-29
Publishing country	United States
Document type	Journal Article
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2024.101441
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Pathogenesis of COVID-19-induced ARDS: implications for an ageing population

Torres Acosta, Manuel A / Singer, Benjamin D

Eur. respir. j

Abstract	The coronavirus disease 2019 (COVID-19) pandemic has elicited a swift response by the scientific community to elucidate the pathogenesis of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-induced lung injury and develop effective therapeutics. Clinical data indicate that severe COVID-19 most commonly manifests as viral pneumonia-induced acute respiratory distress syndrome (ARDS), a clinical entity mechanistically understood best in the context of influenza A virus-induced pneumonia. Similar to influenza, advanced age has emerged as the leading host risk factor for developing severe COVID-19. In this review we connect the current understanding of the SARS-CoV-2 replication cycle and host response to the clinical presentation of COVID-19, borrowing concepts from influenza A virus-induced ARDS pathogenesis and discussing how these ideas inform our evolving understanding of COVID-19-induced ARDS. We also consider important differences between COVID-19 and influenza, mainly the protean clinical presentation and associated lymphopenia of COVID-19, the contrasting role of interferon-Î³ in mediating the host immune response to these viruses, and the tropism for vascular endothelial cells of SARS-CoV-2, commenting on the potential limitations of influenza as a model for COVID-19. Finally, we explore hallmarks of ageing that could explain the association between advanced age and susceptibility to severe COVID-19.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #694740
Database	COVID19

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Article ; Online: Aging imparts cell-autonomous dysfunction to regulatory T cells during recovery from influenza pneumonia.

Morales-Nebreda, Luisa / Helmin, Kathryn A / Torres Acosta, Manuel A / Markov, Nikolay S / Hu, Jennifer Yuan-Shih / Joudi, Anthony M / Piseaux-Aillon, Raul / Abdala-Valencia, Hiam / Politanska, Yuliya / Singer, Benjamin D

JCI insight

2021 Volume 6, Issue 6

Abstract: Regulatory T (Treg) cells orchestrate resolution and repair of acute lung inflammation and injury after viral pneumonia. Compared with younger patients, older individuals experience impaired recovery and worse clinical outcomes after severe viral ... ...

Abstract	Regulatory T (Treg) cells orchestrate resolution and repair of acute lung inflammation and injury after viral pneumonia. Compared with younger patients, older individuals experience impaired recovery and worse clinical outcomes after severe viral infections, including influenza and SARS coronavirus 2 (SARS-CoV-2). Whether age is a key determinant of Treg cell prorepair function after lung injury remains unknown. Here, we showed that aging results in a cell-autonomous impairment of reparative Treg cell function after experimental influenza pneumonia. Transcriptional and DNA methylation profiling of sorted Treg cells provided insight into the mechanisms underlying their age-related dysfunction, with Treg cells from aged mice demonstrating both loss of reparative programs and gain of maladaptive programs. Strategies to restore youthful Treg cell functional programs could be leveraged as therapies to improve outcomes among older individuals with severe viral pneumonia.
MeSH term(s)	Age Factors ; Aging/metabolism ; Aging/physiology ; Animals ; COVID-19/complications ; COVID-19/metabolism ; COVID-19/pathology ; COVID-19/virology ; Humans ; Influenza A virus ; Influenza, Human/complications ; Influenza, Human/metabolism ; Influenza, Human/pathology ; Influenza, Human/virology ; Lung/metabolism ; Lung/pathology ; Mice, Inbred C57BL ; Pneumonia, Viral/etiology ; Pneumonia, Viral/metabolism ; Pneumonia, Viral/pathology ; Pneumonia, Viral/virology ; SARS-CoV-2 ; T-Lymphocytes, Regulatory/metabolism ; T-Lymphocytes, Regulatory/pathology ; Mice
Language	English
Publishing date	2021-03-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.141690
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Metastatic solid tumours to the penis: a clinicopathologic evaluation of 109 cases from an international collaboration.

Nova-Camacho, Luiz M / Collins, Katrina / Trpkov, Kiril / Acosta, Andres M / Sangoi, Ankur R / Akgul, Mahmut / Chou, Angela / Polonia, Antonio / Rodrigues, Ângelo / Yilmaz, Asli / Perez-Montiel, Delia / Maclean, Fiona / Queipo Gutiérrez, Francisco Javier / Contreras, Félix / Wu, Howard H / Alvarado-Cabrero, Isabel / de Torres, Inés / Ruiz, Irune / Lobo, João /

Prendeville, Susan / Manrique Celada, Manuel / Cheng, Liang / Galea, Laurence A / Hwang, Michael / Aron, Manju / García-Martos, María / Zalles, Nicole / Raspollini, Maria Rosaria / Williamson, Sean R / Ulbright, Thomas M / Panizo, Angel

Histopathology

2023 Volume 83, Issue 1, Page(s) 31–39

Abstract: Aims: To elucidate the spectrum of metastatic tumours to the penis and their clinicopathologic features.: Methods: The databases and files of 22 pathology departments from eight countries on three continents were queried to identify metastatic solid ... ...

Abstract	Aims: To elucidate the spectrum of metastatic tumours to the penis and their clinicopathologic features. Methods: The databases and files of 22 pathology departments from eight countries on three continents were queried to identify metastatic solid tumours of the penis and to characterize their clinical and pathologic features. Results: We compiled a series of 109 cases of metastatic solid tumours that secondarily involved the penis. The mean patient age at diagnosis was 71 years (range, 7-94 years). Clinical presentation commonly included a penile nodule/mass (48/95; 51%) and localised pain (14/95; 15%). A prior history of malignancy was known in 92/104 (89%) patients. Diagnosis was made mainly on biopsy (82/109; 75%), or penectomy (21/109; 19%) specimens. The most common penile locations were the glans (45/98; 46%) and corpus cavernosum (39/98; 39%). The most frequent histologic type was adenocarcinoma (56%). Most primary carcinomas originated in the genitourinary (76/108; 70%) and gastrointestinal (20/108; 18%) tracts, including prostate (38/108; 35%), urinary bladder (27/108; 25%), and colon/rectum (18/108; 17%). Concurrent or prior extrapenile metastases were identified in 50/78 (64%) patients. Clinical follow-up (mean 22 months, range 0-171 months) was available for 87/109 (80%) patients, of whom 46 (53%) died of disease. Conclusion: This is the largest study to date of metastatic solid tumours secondarily involving the penis. The most frequent primaries originated from the genitourinary and gastrointestinal tracts. Metastatic penile tumours usually presented with penile nodules/masses and pain, and they often occurred in the setting of advanced metastatic disease, portending poor clinical outcomes.
MeSH term(s)	Male ; Humans ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Penis/pathology ; Penile Neoplasms/pathology ; Adenocarcinoma/pathology ; Biopsy
Language	English
Publishing date	2023-04-18
Publishing country	England
Document type	Journal Article
ZDB-ID	131914-0
ISSN	1365-2559 ; 0309-0167
ISSN (online)	1365-2559
ISSN	0309-0167
DOI	10.1111/his.14927
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Zs.A 1328: Show issues

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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: Post-traumatic stress disorder, anxiety, and depression symptoms in healthcare workers during COVID-19 pandemic in Colombia.

European journal of trauma & dissociation = Revue europeenne du trauma et de la dissociation

2022 Volume 6, Issue 4, Page(s) 100293

Abstract: Background: Mental health outcomes in healthcare workers (HCWs) in low- and middle-income countries (LMICs) have been poorly explored during COVID-19 pandemic. Our aim was to carry out a cross-sectional study of the prevalence of mental health symptoms ... ...

Abstract	Background: Mental health outcomes in healthcare workers (HCWs) in low- and middle-income countries (LMICs) have been poorly explored during COVID-19 pandemic. Our aim was to carry out a cross-sectional study of the prevalence of mental health symptoms in HCWs in Colombia. Methods: A cross-sectional web-survey study was performed during the COVID-19 pandemic mid-2021 including HCWs in two hospitals in Colombia. The PCL-5, GAD-7, and PHQ-9 scales were used to assess the prevalence of symptoms and severity of PTSD, anxiety, and depression in Colombia. Results: From 257 surveyed respondents, 44.36% were nurses, 36.58% physicians and 19.07% other health professionals. The prevalence of PTSD, anxiety, and depressive symptoms were 18.68%, 43.19%, and 26.85%, amongst HCWs. The regression model evidence a strong risk of PTSD, anxiety, and depressive symptoms in HCWs in Colombia during the second wave of COVID-19 in the middle of 2021. Conclusions: The prevalence for several mental health symptoms in HCWs in Colombia were higher compared with the general population. HCWs are at-risk population to develop chronic symptoms and mental disorders during and after outbreaks. These results will be helpful to tailor strategies to support the physical and mental health of the HCWs in LMICs.
Language	English
Publishing date	2022-08-23
Publishing country	France
Document type	Journal Article
ISSN	2468-7499
ISSN (online)	2468-7499
DOI	10.1016/j.ejtd.2022.100293
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