Did you mean: disseminated
-
Cellular and Molecular Life Sciences :... Apr 2021Fungal infections are an increasing threat to global public health. There are more than six million fungal species worldwide, but less than 1% are known to infect... (Review)
Review
Fungal infections are an increasing threat to global public health. There are more than six million fungal species worldwide, but less than 1% are known to infect humans. Most of these fungal infections are superficial, affecting the hair, skin and nails, but some species are capable of causing life-threatening diseases. The most common of these include Cryptococcus neoformans, Aspergillus fumigatus and Candida albicans. These fungi are typically innocuous and even constitute a part of the human microbiome, but if these pathogens disseminate throughout the body, they can cause fatal infections which account for more than one million deaths worldwide each year. Thus, systemic dissemination of fungi is a critical step in the development of these deadly infections. In this review, we discuss our current understanding of how fungi disseminate from the initial infection sites to the bloodstream, how immune cells eliminate fungi from circulation and how fungi leave the blood and enter distant organs, highlighting some recent advances and offering some perspectives on future directions.
Topics: Animals; Antifungal Agents; Fungi; Host-Pathogen Interactions; Humans; Mycoses; Virulence
PubMed: 33449153
DOI: 10.1007/s00018-020-03736-z -
Journal of Biomedical Informatics Jul 2019The Research Electronic Data Capture (REDCap) data management platform was developed in 2004 to address an institutional need at Vanderbilt University, then shared with...
The Research Electronic Data Capture (REDCap) data management platform was developed in 2004 to address an institutional need at Vanderbilt University, then shared with a limited number of adopting sites beginning in 2006. Given bi-directional benefit in early sharing experiments, we created a broader consortium sharing and support model for any academic, non-profit, or government partner wishing to adopt the software. Our sharing framework and consortium-based support model have evolved over time along with the size of the consortium (currently more than 3200 REDCap partners across 128 countries). While the "REDCap Consortium" model represents only one example of how to build and disseminate a software platform, lessons learned from our approach may assist other research institutions seeking to build and disseminate innovative technologies.
Topics: Biomedical Research; Humans; Information Dissemination; Internationality; Medical Informatics; Software
PubMed: 31078660
DOI: 10.1016/j.jbi.2019.103208 -
Blood Mar 2022Disseminated intravascular coagulation (DIC) is a syndrome triggered by infectious and noninfectious pathologies characterized by excessive generation of thrombin within...
Disseminated intravascular coagulation (DIC) is a syndrome triggered by infectious and noninfectious pathologies characterized by excessive generation of thrombin within the vasculature and widespread proteolytic conversion of fibrinogen. Despite diverse clinical manifestations ranging from thrombo-occlusive damage to bleeding diathesis, DIC etiology commonly involves excessive activation of blood coagulation and overlapping dysregulation of anticoagulants and fibrinolysis. Initiation of blood coagulation follows intravascular expression of tissue factor or activation of the contact pathway in response to pathogen-associated or host-derived, damage-associated molecular patterns. The process is further amplified through inflammatory and immunothrombotic mechanisms. Consumption of anticoagulants and disruption of endothelial homeostasis lower the regulatory control and disseminate microvascular thrombosis. Clinical DIC development in patients is associated with worsening morbidities and increased mortality, regardless of the underlying pathology; therefore, timely recognition of DIC is critical for reducing the pathologic burden. Due to the diversity of triggers and pathogenic mechanisms leading to DIC, diagnosis is based on algorithms that quantify hemostatic imbalance, thrombocytopenia, and fibrinogen conversion. Because current diagnosis primarily assesses overt consumptive coagulopathies, there is a critical need for better recognition of nonovert DIC and/or pre-DIC states. Therapeutic strategies for patients with DIC involve resolution of the eliciting triggers and supportive care for the hemostatic imbalance. Despite medical care, mortality in patients with DIC remains high, and new strategies, tailored to the underlying pathologic mechanisms, are needed.
Topics: Blood Coagulation; Disseminated Intravascular Coagulation; Fibrinolysis; Hemostasis; Humans; Thrombosis
PubMed: 34428280
DOI: 10.1182/blood.2020007208 -
Cell Reports. Medicine Mar 2023Although breast cancer mortality is largely caused by metastasis, clinical decisions are based on analysis of the primary tumor and on lymph node involvement but not on...
Although breast cancer mortality is largely caused by metastasis, clinical decisions are based on analysis of the primary tumor and on lymph node involvement but not on the phenotype of disseminated cells. Here, we use multiplex imaging mass cytometry to compare single-cell phenotypes of primary breast tumors and matched lymph node metastases in 205 patients. We observe extensive phenotypic variability between primary and metastatic sites and that disseminated cell phenotypes frequently deviate from the clinical disease subtype. We identify single-cell phenotypes and spatial organizations of disseminated tumor cells that are associated with patient survival and a weaker survival association for high-risk phenotypes in the primary tumor. We show that p53 and GATA3 in lymph node metastases provide prognostic information beyond clinical classifiers and can be measured with standard methods. Molecular characterization of disseminated tumor cells is an untapped source of clinically applicable prognostic information for breast cancer.
Topics: Humans; Lymphatic Metastasis; Prognosis; Lymph Nodes
PubMed: 36921599
DOI: 10.1016/j.xcrm.2023.100977 -
Nature Communications Feb 2022Metastases are initiated by disseminated tumor cells (DTCs) that colonize distant organs. Growing evidence suggests that the microenvironment of the primary tumor primes...
Metastases are initiated by disseminated tumor cells (DTCs) that colonize distant organs. Growing evidence suggests that the microenvironment of the primary tumor primes DTCs for dormant or proliferative fates. However, the manner in which this occurs remains poorly understood. Here, using the Window for High-Resolution Intravital Imaging of the Lung (WHRIL), we study the live lung longitudinally and follow the fate of individual DTCs that spontaneously disseminate from orthotopic breast tumors. We find that spontaneously DTCs have increased levels of retention, increased speed of extravasation, and greater survival after extravasation, compared to experimentally metastasized tumor cells. Detailed analysis reveals that a subset of macrophages within the primary tumor induces a pro-dissemination and pro-dormancy DTC phenotype. Our work provides insight into how specific primary tumor microenvironments prime a subpopulation of cells for expression of proteins associated with dissemination and dormancy.
Topics: Animals; Breast Neoplasms; Cell Line, Tumor; Female; Humans; Mice; Mice, Inbred C57BL; Neoplasms, Experimental; Neoplastic Stem Cells; Phenotype; Tumor Microenvironment; Tumor-Associated Macrophages
PubMed: 35110548
DOI: 10.1038/s41467-022-28076-3 -
International Review of Cell and... 2021The actin cytoskeleton is a dynamic network that regulates cellular behavior from development to disease. By rearranging the actin cytoskeleton, cells are capable of... (Review)
Review
The actin cytoskeleton is a dynamic network that regulates cellular behavior from development to disease. By rearranging the actin cytoskeleton, cells are capable of migrating and invading during developmental processes; however, many of these cellular properties are hijacked by cancer cells to escape primary tumors and disseminate to distant organs in the body. In this review article, we highlight recent work describing how cancer cells regulate the actin cytoskeleton to achieve efficient invasion and metastatic colonization. We also review new imaging technologies that are capable of revealing the complex architecture and regulation of the actin cytoskeleton during motility and invasion of tumor cells.
Topics: Actins; Animals; Cell Cycle; Cell Movement; Epithelial-Mesenchymal Transition; Humans; Neoplasm Metastasis; Neoplasms
PubMed: 33962751
DOI: 10.1016/bs.ircmb.2020.09.004 -
BMJ Open Aug 2021Endometriosis is a debilitating chronic inflammatory condition highly burdensome to the healthcare system. The present trial will establish the efficacy of (1) yoga and... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Endometriosis is a debilitating chronic inflammatory condition highly burdensome to the healthcare system. The present trial will establish the efficacy of (1) yoga and (2) cognitive-behavioural therapy (CBT), above (3) education, on quality of life, biopsychosocial outcomes and cost-effectiveness.
METHODS AND ANALYSIS
This study is a parallel randomised controlled trial. Participants will be randomly allocated to yoga, CBT or education. Participants will be English-speaking adults, have a diagnosis of endometriosis by a qualified physician, with pain for at least 6 months, and access to internet. Participants will attend 8 weekly group CBT sessions of 120 min; or 8 weekly group yoga sessions of 60 min; or receive weekly educational handouts on endometriosis. The primary outcome measure is quality of life. The analysis will include mixed-effects analysis of variance and linear models, cost-utility analysis from a societal and health system perspective and qualitative thematic analysis.
ETHICS AND DISSEMINATION
Enrolment in the study is voluntary and participants can withdraw at any time. Participants will be given the option to discuss the study with their next of kin/treating physician. Findings will be disseminated via publications, conferences and briefs to professional organisations. The University's media team will also be used to further disseminate via lay person articles and media releases.
TRIAL REGISTRATION NUMBER
ACTRN12620000756921p; Pre-results.
Topics: Adult; Cognitive Behavioral Therapy; Cost-Benefit Analysis; Endometriosis; Female; Health Care Costs; Humans; Quality of Life; Treatment Outcome; Yoga
PubMed: 34373298
DOI: 10.1136/bmjopen-2020-046603 -
Cells Nov 2022Pancreatic cancer is a disease notorious for its high frequency of recurrence and low survival rate. Surgery is the most effective treatment for localized pancreatic... (Review)
Review
Pancreatic cancer is a disease notorious for its high frequency of recurrence and low survival rate. Surgery is the most effective treatment for localized pancreatic cancer, but most cancer recurs after surgery, and patients die within ten years of diagnosis. The question persists: what makes pancreatic cancer recur and metastasize with such a high frequency? Herein, we review evidence that subclinical dormant pancreatic cancer cells disseminate before developing metastatic or recurring cancer. We then discuss several routes by which pancreatic cancer migrates and the mechanisms by which pancreatic cancer cells adapt. Lastly, we discuss unanswered questions in pancreatic cancer cell migration and our perspectives.
Topics: Humans; Pancreatic Neoplasms; Pancreas; Cell Movement
PubMed: 36429111
DOI: 10.3390/cells11223683