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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 -
Environmental Health : a Global Access... Dec 2022Environmental health sciences have identified and characterized a range of environmental exposures and their associated risk for disease, as well as informed the... (Review)
Review
BACKGROUND
Environmental health sciences have identified and characterized a range of environmental exposures and their associated risk for disease, as well as informed the development of interventions, including recommendations, guidelines, and policies for mitigating exposure. However, these interventions only serve to mitigate exposures and prevent disease if they are effectively disseminated, adopted, implemented, and sustained.
MAIN BODY
Numerous studies have documented the enormous time lag between research and practice, noting that dissemination and implementation are not passive processes but rely on active and intentional strategies. Implementation science seeks to build the knowledge base for understanding strategies to effectively disseminate and implement evidence and evidence-based interventions, and thus, bridge the research-to-practice gap.
CONCLUSION
Environmental health researchers are well positioned to advance health promotion and disease prevention by incorporating implementation science into their work. This article describes the rationale for and key components of implementation science and articulates opportunities to build upon existing efforts to advance environmental health supported by the National Institute of Environmental Health Sciences and National Institutes of Health broadly.
Topics: United States; Humans; Implementation Science; Environmental Health; Environmental Exposure; National Institute of Environmental Health Sciences (U.S.)
PubMed: 36564832
DOI: 10.1186/s12940-022-00933-0 -
Health Information and Libraries Journal Mar 2012While research training often takes place during every day practice, for the majority of library and information professionals, essential training will have been...
While research training often takes place during every day practice, for the majority of library and information professionals, essential training will have been received as part of the dissertation element of their degree. However, there is a danger that important dissertation study findings are not disseminated if, for example, the student has moved onto a new job. The Health Information and Libraries Journal seek to address this research/practice gap with the introduction of a new feature 'Dissertations into Practice' specifically tasked with providing a safe and structured environment for students to disseminate their dissertation project findings.
Topics: Academic Dissertations as Topic; Competency-Based Education; Cooperative Behavior; Education, Public Health Professional; Humans; Information Dissemination; Librarians; Libraries, Medical; United States
PubMed: 22335284
DOI: 10.1111/j.1471-1842.2012.00978.x -
Cancers Nov 2020Cancer immunotherapy has shifted the paradigm in cancer therapy by revitalizing immune responses against tumor cells. Specifically, in primary tumors cancer cells evolve... (Review)
Review
Cancer immunotherapy has shifted the paradigm in cancer therapy by revitalizing immune responses against tumor cells. Specifically, in primary tumors cancer cells evolve in an immunosuppressive microenvironment, which protects them from immune attack. However, during tumor progression, some cancer cells leave the protective tumor mass, disseminating and seeding secondary organs. These initial disseminated tumor cells (DTCs) should potentially be susceptible to recognition by the immune system in the new host tissues. Although Natural Killer or T cells eliminate some of these DTCs, a fraction escape anti-tumor immunity and survive, thus giving rise to metastatic colonization. How DTCs interact with immune cells and the underpinnings that regulate imperfect immune responses during tumor dissemination remain poorly understood. Uncovering such mechanisms of immune evasion may contribute to the development of immunotherapy specifically targeting DTCs. Here we review current knowledge about systemic and site-specific immune-cancer crosstalk in the early steps of metastasis formation. Moreover, we highlight how conventional cancer therapies can shape the pre-metastatic niche enabling immune escape of newly arrived DTCs.
PubMed: 33207601
DOI: 10.3390/cancers12113385 -
The British Journal of Surgery Jan 2019Effective dissemination of technology in global surgery is vital to realize universal health coverage by 2030. Challenges include a lack of human resource,... (Review)
Review
BACKGROUND
Effective dissemination of technology in global surgery is vital to realize universal health coverage by 2030. Challenges include a lack of human resource, infrastructure and finance. Understanding these challenges, and exploring opportunities and solutions to overcome them, are essential to improve global surgical care.
METHODS
This review focuses on technologies and medical devices aimed at improving surgical care and training in low- and middle-income countries. The key considerations in the development of new technologies are described, along with strategies for evaluation and wider dissemination. Notable examples of where the dissemination of a new surgical technology has achieved impact are included.
RESULTS
Employing the principles of frugal and responsible innovation, and aligning evaluation and development to high scientific standards help overcome some of the challenges in disseminating technology in global surgery. Exemplars of effective dissemination include low-cost laparoscopes, gasless laparoscopic techniques and innovative training programmes for laparoscopic surgery; low-cost and versatile external fixation devices for fractures; the LifeBox pulse oximeter project; and the use of immersive technologies in simulation, training and surgical care delivery.
CONCLUSION
Core strategies to facilitate technology dissemination in global surgery include leveraging international funding, interdisciplinary collaboration involving all key stakeholders, and frugal scientific design, development and evaluation.
Topics: Biomedical Technology; Delivery of Health Care; Developing Countries; Diffusion of Innovation; General Surgery; Global Health; Humans
PubMed: 30620068
DOI: 10.1002/bjs.11036 -
Asian Journal of Neurosurgery 2021The objective of this study was to provide an overview of acute disseminating encephalomyelitis, a potential and serious complication of COVID-19. (Review)
Review
OBJECTIVE
The objective of this study was to provide an overview of acute disseminating encephalomyelitis, a potential and serious complication of COVID-19.
METHODS
Three primary databases were used, PubMed, LitCovid, and WHO. The final review articles reported acute disseminated encephalomyelitis (ADEM) in COVID-19-positive patients and were full-text, peer-reviewed articles. Articles which did not have patient data such as studies and articles with unclear inference were excluded.
RESULTS
Out of 21 cases of ADEM, the diagnosis of severe acute respiratory syndrome-coronavirus 2 was confirmed in 18 and suspected in 3. Among the neurological symptoms, altered consciousness was most common (7/21), followed by anosmia (3), paraplegia (3/21), brain stem involvement (3/21), sphincter involvement (2/21), and quadriplegia (1/21). Raised inflammatory markers were most commonly seen in 9/17. Central nervous system imaging was abnormal in 19 cases and unavailable in 2 cases. Fifteen patients were treated with corticosteroids, 11 patients received intravenous immunoglobulin, while 3 patients received convalescent plasma. Two patients needed surgical intervention. Complications included seizures (1), acute kidney injury and septicemic shock (1), raised intracranial pressure (1), and supraventricular tachycardia secondary to hydroxychloroquine (1). One patient recovered completely and one had good recovery with mild deficits. Thirteen patients had incomplete recovery with residual neurological deficit while three patients died as the consequence of the disease.
CONCLUSION
The physicians and neurosurgeons should be diligent while treating the COVID-19 patients with neurological manifestations and include ADEM as a differential diagnosis and stress on early diagnosis and treatment to reduce mortality and achieve satisfactory clinical outcome.
PubMed: 34660355
DOI: 10.4103/ajns.AJNS_406_20 -
Cellular Microbiology Nov 2019Toxoplasma gondii (T. gondii) is a parasitic protist that can infect nearly all nucleated cell types and tissues of warm-blooded vertebrate hosts. T. gondii utilises a... (Review)
Review
Toxoplasma gondii (T. gondii) is a parasitic protist that can infect nearly all nucleated cell types and tissues of warm-blooded vertebrate hosts. T. gondii utilises a unique form of gliding motility to cross cellular barriers, enter tissues, and penetrate host cells, thus enhancing spread within an infected host. However, T. gondii also disseminates by hijacking the migratory abilities of infected leukocytes. Traditionally, this process has been viewed as a route to cross biological barriers such as the blood-brain barrier. Here, we review recent findings that challenge this view by showing that infection of monocytes downregulates the program of transendothelial migration. Instead, infection by T. gondii enhances Rho-dependent interstitial migration of monocytes and macrophages, which enhances dissemination within tissues. Collectively, the available evidence indicates that T. gondii parasites use multiple means to disseminate within the host, including enhanced motility in tissues and translocation across biological barriers.
Topics: Animals; Blood-Brain Barrier; Cell Movement; Central Nervous System Infections; Host-Pathogen Interactions; Humans; Integrins; Leukocytes; Macrophages; Monocytes; Toxoplasma; Toxoplasmosis; Transendothelial and Transepithelial Migration
PubMed: 31219666
DOI: 10.1111/cmi.13070 -
Evidence Report/technology Assessment Nov 2013This review examined how to best communicate and disseminate evidence, including uncertain evidence, to inform health care decisions. The review focused on three primary... (Review)
Review
OBJECTIVES
This review examined how to best communicate and disseminate evidence, including uncertain evidence, to inform health care decisions. The review focused on three primary objectives--comparing the effectiveness of: (1) communicating evidence in various contents and formats that increase the likelihood that target audiences will both understand and use the information (KQ 1); (2) a variety of approaches for disseminating evidence from those who develop it to those who are expected to use it (KQ 2); and (3) various ways of communicating uncertainty-associated health-related evidence to different target audiences (KQ 3). A secondary objective was to examine how the effectiveness of communication and dissemination strategies varies across target audiences, including evidence translators, health educators, patients, and clinicians.
DATA SOURCES
We searched MEDLINE®, the Cochrane Library, Cochrane Central Trials Registry, PsycINFO®, and the Web of Science. We used a variety of medical subject headings (MeSH terms) and major headings, and used free-text and title and abstract text-word searches. The search was limited to studies on humans published from 2000 to March 15, 2013, for communication and dissemination, given the prior systematic reviews, and from 1966 to March 15, 2013, for communicating uncertainty.
REVIEW METHODS
We used standard Evidence-based Practice Center methods of dual review of abstracts, full-text articles, and abstractions, and quality ratings and group consensus to resolve disagreements. We used group consensus to grade strength of evidence.
RESULTS
The search identified 4,152 articles (after removing duplicates) for all three KQs. After dual review at the title/abstract stage and full-text review stage, we retained 61 articles that directly (i.e., head to head) compared strategies to communicate and disseminate evidence. Across the KQs, many of the comparisons yielded insufficient evidence to draw firm conclusions. For KQ 1, we found that investigators frequently blend more than one communication strategy in interventions. For KQ 2, we found that, compared with single dissemination strategies, multicomponent dissemination strategies are more effective at enhancing clinician behavior, particularly for guideline adherence. Key findings for KQ 3 indicate that evidence on communicating overall strength of recommendation and precision was insufficient, but certain ways of communicating directness and net benefit may be helpful in reducing uncertainty.
CONCLUSIONS
The lack of comparative research evidence to inform communication and dissemination of evidence, including uncertain evidence, impedes timely clinician, patient, and policymaker awareness, uptake, and use of evidence to improve the quality of care. Expanding investment in communication, dissemination, and implementation research is critical to the identification of strategies to accelerate the translation of comparative effectiveness research into community and clinical practice and the direct benefit of patient care.
Topics: Communication; Delivery of Health Care; Health Educators; Humans; Information Dissemination; Patients; Physicians
PubMed: 24423078
DOI: 10.23970/ahrqepcerta213 -
Frontiers in Microbiology 2023Antibiotic resistance development and pathogen cross-dissemination are both considered essential risks to human health on a worldwide scale. Antimicrobial resistance... (Review)
Review
Antibiotic resistance development and pathogen cross-dissemination are both considered essential risks to human health on a worldwide scale. Antimicrobial resistance genes (AMRs) are acquired, expressed, disseminated, and traded mainly through integrons, the key players capable of transferring genes from bacterial chromosomes to plasmids and their integration by integrase to the target pathogenic host. Moreover, integrons play a central role in disseminating and assembling genes connected with antibiotic resistance in pathogenic and commensal bacterial species. They exhibit a large and concealed diversity in the natural environment, raising concerns about their potential for comprehensive application in bacterial adaptation. They should be viewed as a dangerous pool of resistance determinants from the "One Health approach." Among the three documented classes of integrons reported viz., class-1, 2, and 3, class 1 has been found frequently associated with AMRs in humans and is a critical genetic element to serve as a target for therapeutics to AMRs through gene silencing or combinatorial therapies. The direct method of screening gene cassettes linked to pathogenesis and resistance harbored by integrons is a novel way to assess human health. In the last decade, they have witnessed surveying the integron-associated gene cassettes associated with increased drug tolerance and rising pathogenicity of human pathogenic microbes. Consequently, we aimed to unravel the structure and functions of integrons and their integration mechanism by understanding horizontal gene transfer from one trophic group to another. Many updates for the gene cassettes harbored by integrons related to resistance and pathogenicity are extensively explored. Additionally, an updated account of the assessment of AMRs and prevailing antibiotic resistance by integrons in humans is grossly detailed-lastly, the estimation of AMR dissemination by employing integrons as potential biomarkers are also highlighted. The current review on integrons will pave the way to clinical understanding for devising a roadmap solution to AMR and pathogenicity. Graphical AbstractThe graphical abstract displays how integron-aided AMRs to humans: Transposons capture integron gene cassettes to yield high mobility integrons that target res sites of plasmids. These plasmids, in turn, promote the mobility of acquired integrons into diverse bacterial species. The acquisitions of resistant genes are transferred to humans through horizontal gene transfer.
PubMed: 37720149
DOI: 10.3389/fmicb.2023.1231938