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Diagnostics (Basel, Switzerland) Jul 2023Ovarian cancer is the leading cause of death among all gynecological malignancies. Most patients present with an advanced stage of the disease. The routes of spread in... (Review)
Review
INTRODUCTION
Ovarian cancer is the leading cause of death among all gynecological malignancies. Most patients present with an advanced stage of the disease. The routes of spread in ovarian cancer include peritoneal dissemination, direct invasion, and lymphatic or hematogenous spread, with peritoneal and lymphatic spread being the most common among them. The flow direction of the peritoneal fluid makes the right subphrenic space a target site for peritoneal metastases, and the most frequently affected anatomical area in advanced cases is the right upper quadrant. Complete cytoreduction with no macroscopically visible disease is the most important prognostic factor.
METHODS
We reviewed published clinical anatomy reports associated with surgery of the liver in cases of advanced ovarian cancer.
RESULTS
The disease could disseminate anatomical areas, where complex surgery is required-Morrison's pouch, the liver surface, or porta hepatis. The aim of the present article is to emphasize and delineate the gross anatomy of the liver and its surgical application for oncogynecologists. Moreover, the association between the gross and microscopic anatomy of the liver is discussed. Additionally, the vascular supply and variations of the liver are clearly described.
CONCLUSIONS
Oncogynecologists performing liver mobilization, diaphragmatic stripping, and porta hepatis dissection must have a thorough knowledge of liver anatomy, including morphology, variations, functional status, potential diagnostic imaging mistakes, and anatomical limits of dissection.
PubMed: 37510115
DOI: 10.3390/diagnostics13142371 -
PLoS Pathogens Dec 2023The upper respiratory tract (nasopharynx or NP) is the first site of influenza replication, allowing the virus to disseminate to the lower respiratory tract or promoting...
The upper respiratory tract (nasopharynx or NP) is the first site of influenza replication, allowing the virus to disseminate to the lower respiratory tract or promoting community transmission. The host response in the NP regulates an intricate balance between viral control and tissue pathology. The hyper-inflammatory responses promote epithelial injury, allowing for increased viral dissemination and susceptibility to secondary bacterial infections. However, the pathologic contributors to influenza upper respiratory tissue pathology are incompletely understood. In this study, we investigated the role of interleukin IL-17 recetor A (IL-17RA) as a modulator of influenza host response and inflammation in the upper respiratory tract. We used a combined experimental approach involving IL-17RA-/- mice and an air-liquid interface (ALI) epithelial culture model to investigate the role of IL-17 response in epithelial inflammation, barrier function, and tissue pathology. Our data show that IL-17RA-/- mice exhibited significantly reduced neutrophilia, epithelial injury, and viral load. The reduced NP inflammation and epithelial injury in IL-17RA-/- mice correlated with increased resistance against co-infection by Streptococcus pneumoniae (Spn). IL-17A treatment, while potentiating the apoptosis of IAV-infected epithelial cells, caused bystander cell death and disrupted the barrier function in ALI epithelial model, supporting the in vivo findings.
Topics: Animals; Mice; Humans; Influenza, Human; Interleukin-17; Inflammation; Streptococcus pneumoniae; Interleukins
PubMed: 38060620
DOI: 10.1371/journal.ppat.1011847 -
JMIR MHealth and UHealth Jan 2024Among the millions of mobile apps in existence, thousands fall under the category of mobile health (mHealth). Although the utility of mHealth apps has been demonstrated...
BACKGROUND
Among the millions of mobile apps in existence, thousands fall under the category of mobile health (mHealth). Although the utility of mHealth apps has been demonstrated for disease diagnosis, treatment data management, and health promotion strategies, to be effective they must reach and be used by their target audience. An appropriate marketing strategy can ensure that apps reach potential users and potentially convert them to actual users. Such a strategy requires definitions of target end users, communication channels, and advertising content, as well as a timeline for effectively reaching and motivating end users to adopt and maintain engagement with the mHealth app.
OBJECTIVE
The aim of this study was to identify strategies and elements that ensure that end users adopt and remain engaged with mHealth apps.
METHODS
A systematic search of the PubMed, PsycINFO, Scopus, and CINAHL databases was conducted for suitable studies published between January 1, 2018, and September 30, 2022. Two researchers independently screened studies for inclusion, extracted data, and assessed the risk of bias. The main outcome was dissemination strategies for mHealth apps.
RESULTS
Of the 648 papers retrieved from the selected databases, only 10 (1.5%) met the inclusion criteria. The marketing strategies used in these studies to inform potential users of the existence of mHealth apps and motivate download included both paid and unpaid strategies and used various channels, including social media, emails, printed posters, and face-to-face communication. Most of the studies reported a combination of marketing concepts used to advertise their mHealth apps. Advertising messages included instructions on where and how to download and install the apps. In most of the studies (6/10, 60%), instructions were oriented toward how to use the apps and maintain engagement with a health intervention. The most frequently used paid marketing platform was Facebook Ads Manager (2/10, 20%). Advertising performance was influenced by many factors, including but not limited to advertising content. In 1 (10%) of the 10 studies, animated graphics generated the greatest number of clicks compared with other image types. The metrics used to assess marketing strategy effectiveness were number of downloads; nonuse rate; dropout rate; adherence rate; duration of app use; and app usability over days, weeks, or months. Additional indicators such as cost per click, cost per install, and clickthrough rate were mainly used to assess the cost-effectiveness of paid marketing campaigns.
CONCLUSIONS
mHealth apps can be disseminated via paid and unpaid marketing strategies using various communication channels. The effects of these strategies are reflected in download numbers and user engagement with mHealth apps. Further research could provide guidance on a framework for disseminating mHealth apps and encouraging their routine use.
Topics: Humans; Advertising; Benchmarking; Communication; Databases, Factual; Mobile Applications; Telemedicine
PubMed: 38180796
DOI: 10.2196/50293 -
The Lancet. Digital Health Oct 2023Data sharing is central to the rapid translation of research into advances in clinical medicine and public health practice. In the context of COVID-19, there has been a... (Review)
Review
Data sharing is central to the rapid translation of research into advances in clinical medicine and public health practice. In the context of COVID-19, there has been a rush to share data marked by an explosion of population-specific and discipline-specific resources for collecting, curating, and disseminating participant-level data. We conducted a scoping review and cross-sectional survey to identify and describe COVID-19-related platforms and registries that harmonise and share participant-level clinical, omics (eg, genomic and metabolomic data), imaging data, and metadata. We assess how these initiatives map to the best practices for the ethical and equitable management of data and the findable, accessible, interoperable, and reusable (FAIR) principles for data resources. We review gaps and redundancies in COVID-19 data-sharing efforts and provide recommendations to build on existing synergies that align with frameworks for effective and equitable data reuse. We identified 44 COVID-19-related registries and 20 platforms from the scoping review. Data-sharing resources were concentrated in high-income countries and siloed by comorbidity, body system, and data type. Resources for harmonising and sharing clinical data were less likely to implement FAIR principles than those sharing omics or imaging data. Our findings are that more data sharing does not equate to better data sharing, and the semantic and technical interoperability of platforms and registries harmonising and sharing COVID-19-related participant-level data needs to improve to facilitate the global collaboration required to address the COVID-19 crisis.
Topics: Humans; COVID-19; Cross-Sectional Studies; Information Dissemination; Registries; Metadata
PubMed: 37775189
DOI: 10.1016/S2589-7500(23)00129-2 -
Journal of Experimental & Clinical... Oct 2023Disseminated tumor cells (DTCs) can enter a dormant state and cause no symptoms in cancer patients. On the other hand, the dormant DTCs can reactivate and cause...
BACKGROUND
Disseminated tumor cells (DTCs) can enter a dormant state and cause no symptoms in cancer patients. On the other hand, the dormant DTCs can reactivate and cause metastases progression and lethal relapses. In prostate cancer (PCa), relapse can happen after curative treatments such as primary tumor removal. The impact of surgical removal on PCa dissemination and dormancy remains elusive. Furthermore, as dormant DTCs are asymptomatic, dormancy-induction can be an operational cure for preventing metastases and relapse of PCa patients.
METHODS
We used a PCa subcutaneous xenograft model and species-specific PCR to survey the DTCs in various organs at different time points of tumor growth and in response to tumor removal. We developed in vitro 2D and 3D co-culture models to recapitulate the dormant DTCs in the bone microenvironment. Proliferation assays, fluorescent cell cycle reporter, qRT-PCR, and Western Blot were used to characterize the dormancy phenotype. We performed RNA sequencing to determine the dormancy signature of PCa. A drug repurposing algorithm was applied to predict dormancy-inducing drugs and a top candidate was validated for the efficacy and the mechanism of dormancy induction.
RESULTS
We found DTCs in almost all mouse organs examined, including bones, at week 2 post-tumor cell injections. Surgical removal of the primary tumor reduced the overall DTC abundance, but the DTCs were enriched only in the bones. We found that osteoblasts, but not other cells of the bones, induced PCa cell dormancy. RNA-Seq revealed the suppression of mitochondrial-related biological processes in osteoblast-induced dormant PCa cells. Importantly, the mitochondrial-related biological processes were found up-regulated in both circulating tumor cells and bone metastases from PCa patients' data. We predicted and validated the dormancy-mimicking effect of PF-562,271 (PF-271), an inhibitor of focal adhesion kinase (FAK) in vitro. Decreased FAK phosphorylation and increased nuclear translocation were found in both co-cultured and PF-271-treated C4-2B cells, suggesting that FAK plays a key role in osteoblast-induced PCa dormancy.
CONCLUSIONS
Our study provides the first insights into how primary tumor removal enriches PCa cell dissemination in the bones, defines a unique osteoblast-induced PCa dormancy signature, and identifies FAK as a PCa cell dormancy gatekeeper.
Topics: Male; Humans; Animals; Mice; Focal Adhesion Protein-Tyrosine Kinases; Neoplasm Recurrence, Local; Prostatic Neoplasms; Osteoblasts; Recurrence; Cell Line, Tumor; Tumor Microenvironment
PubMed: 37821954
DOI: 10.1186/s13046-023-02849-0 -
Emerging Microbes & Infections Dec 2023OXA-232 is one of the most common OXA-48-like carbapenemase derivatives and is widely disseminated in nosocomial settings across countries. The gene is located on a...
OXA-232 is one of the most common OXA-48-like carbapenemase derivatives and is widely disseminated in nosocomial settings across countries. The gene is located on a 6-kb non-conjugative ColKP3-type plasmid, while the dissemination of into different species and the polyclonal dissemination of OXA-232-producing revealed the horizontal transfer of . However, it's still unclear how this non-conjugative ColKP3 plasmid could facilitate the mobilization of . Here, we observed the intraspecies transfer of during a nosocomial outbreak of OXA-232-producing . We demonstrated the presence of ColKP3 OXA-232 plasmid in the outer membrane vesicles (OMVs) derived from clinical isolates, and OMVs could facilitate the horizontal transfer of among . In contrast, for the most prevalent carbapenemase genes, including and , though the presence of carbapenemase genes and plasmid backbones in the vesicular lumen was observed, OMVs couldn't promote effective transformation, probably due to the low copy number of plasmids in clinical isolates and the low number of plasmids loaded into vesicles. Conjugation assay revealed that the epidemic IncX3 NDM-1 and IncFII(pHN7A8)/IncR KPC-2 plasmids were conjugative and could be horizontally transferred via independent conjugation or with the help of a co-existent conjugative plasmid. For the large-size and low-copy number conjugative plasmids carrying carbapenemase genes, OMVs-mediated gene exchange may only serve as an alternative pathway for horizontal transfer. In conclusion, diverse mobilization strategies were employed by plasmids harboring carbapenemase genes, and plasmids display a proper choice of mobility pathway due to their individual properties.
PubMed: 38044873
DOI: 10.1080/22221751.2023.2290840 -
PLoS Pathogens Nov 2023Despite widespread immunization with Bacille-Calmette-Guérin (BCG), the only currently licensed tuberculosis (TB) vaccine, TB remains a leading cause of mortality...
Despite widespread immunization with Bacille-Calmette-Guérin (BCG), the only currently licensed tuberculosis (TB) vaccine, TB remains a leading cause of mortality globally. There are many TB vaccine candidates in the developmental pipeline, but the lack of a robust animal model to assess vaccine efficacy has hindered our ability to prioritize candidates for human clinical trials. Here we use a murine ultra-low dose (ULD) Mycobacterium tuberculosis (Mtb) challenge model to assess protection conferred by BCG vaccination. We show that BCG confers a reduction in lung bacterial burdens that is more durable than that observed after conventional dose challenge, curbs Mtb dissemination to the contralateral lung, and, in a small percentage of mice, prevents detectable infection. These findings are consistent with the ability of human BCG vaccination to mediate protection, particularly against disseminated disease, in specific human populations and clinical settings. Overall, our findings demonstrate that the ultra-low dose Mtb infection model can measure distinct parameters of immune protection that cannot be assessed in conventional dose murine infection models and could provide an improved platform for TB vaccine testing.
Topics: Animals; Mice; Humans; Mycobacterium tuberculosis; BCG Vaccine; Disease Models, Animal; Tuberculosis Vaccines; Vaccination; Mycobacterium bovis
PubMed: 38011264
DOI: 10.1371/journal.ppat.1011825 -
Microbiology Spectrum Aug 2023The global dissemination of methicillin-resistant Staphylococcus aureus (MRSA) is associated with the emergence and establishment of clones in specific geographic areas....
The global dissemination of methicillin-resistant Staphylococcus aureus (MRSA) is associated with the emergence and establishment of clones in specific geographic areas. The Chilean-Cordobes clone (ChC) (ST5-SCCI) has been the predominant MRSA clone in Chile since its first description in 1998, despite the report of other emerging MRSA clones in recent years. Here, we characterize the evolutionary history of MRSA from 2000 to 2016 in a Chilean tertiary health care center using phylogenomic analyses. We sequenced 469 MRSA isolates collected between 2000 and 2016. We evaluated the temporal trends of the circulating clones and performed a phylogenomic reconstruction to characterize the clonal dynamics. We found a significant increase in the diversity and richness of sequence types (STs; Spearman = 0.8748, < 0.0001) with a Shannon diversity index increasing from 0.221 in the year 2000 to 1.33 in 2016, and an effective diversity (Hill number; q = 2) increasing from 1.12 to 2.71. The temporal trend analysis revealed that in the period 2000 to 2003 most of the isolates (94.2%; = 98) belonged to the ChC clone. However, since then, the frequency of the ChC clone has decreased over time, accounting for 52% of the collection in the 2013 to 2016 period. This decline was accompanied by the rise of two emerging MRSA lineages, ST105-SCCII and ST72-SCCVI. In conclusion, the ChC clone remains the most frequent MRSA lineage, but this lineage is gradually being replaced by several emerging clones, the most important of which is clone ST105-SCCII. To the best of our knowledge, this is the largest study of MRSA clonal dynamics performed in South America. Methicillin-resistant Staphylococcus aureus (MRSA) is a major public health pathogen that disseminates through the emergence of successful dominant clones in specific geographic regions. Knowledge of the dissemination and molecular epidemiology of MRSA in Latin America is scarce and is largely based on small studies or more limited typing techniques that lack the resolution to represent an accurate description of the genomic landscape. We used whole-genome sequencing to study 469 MRSA isolates collected between 2000 and 2016 in Chile providing the largest and most detailed study of clonal dynamics of MRSA in South America to date. We found a significant increase in the diversity of MRSA clones circulating over the 17-year study period. Additionally, we describe the emergence of two novel clones (ST105-SCCII and ST72-SCCVI), which have been gradually increasing in frequency over time. Our results drastically improve our understanding of the dissemination and update our knowledge about MRSA in Latin America.
Topics: Humans; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Chile; Phylogeny; Tertiary Care Centers; Anti-Bacterial Agents
PubMed: 37338398
DOI: 10.1128/spectrum.05351-22 -
Microbiology Spectrum Aug 2023In this study, we screened the gene cluster among 1,541 samples obtained from patients, healthy individuals, companion animals, pigs, chicken, and pork and chicken meat...
In this study, we screened the gene cluster among 1,541 samples obtained from patients, healthy individuals, companion animals, pigs, chicken, and pork and chicken meat in Yangzhou, China. As a result, nine strains from humans, animals, and foods were positive for , which was located on plasmids or the chromosome. Seven different sequence types (STs) were identified, including ST15 ( = 2), ST580, ST1944, ST2294, ST5982, ST6262 ( = 2), and ST6265. All the positive strains were clustered into two distinct clades, and they shared a 24,087-bp core structure of , bounded by IS in the same orientation. IS could facilitate rapid and wide dissemination of in from various sources. Tigecycline has been regarded as one of the last-resort antibiotics available for the treatment of infections caused by carbapenem-resistant . The plasmid-mediated resistance-nodulation-division-type efflux pump gene cluster - is a newly identified tigecycline resistance determinant. In this study, we revealed that has disseminated among Klebsiella pneumoniae strains from poultry, food markets, and patients. It is critical to strengthen continuous monitoring, and control measures should be implemented to prevent the further dissemination of .
Topics: Humans; Animals; Swine; Tigecycline; Klebsiella pneumoniae; Klebsiella Infections; Drug Resistance, Bacterial; Anti-Bacterial Agents; Plasmids; Multigene Family; Microbial Sensitivity Tests
PubMed: 37378518
DOI: 10.1128/spectrum.05364-22 -
Antimicrobial Stewardship & Healthcare... 2023Early in the pandemic, pre-print servers sped rapid evidence sharing. A collaborative of major medical journals supported their use to ensure equitable access to...
Early in the pandemic, pre-print servers sped rapid evidence sharing. A collaborative of major medical journals supported their use to ensure equitable access to scientific advancements. In the intervening three years, we have made major advancements in the prevention and treatment of COVID-19 and learned about the benefits and limitations of pre-prints as a mechanism for sharing and disseminating scientific knowledge. Pre-prints increase attention, citations, and ultimately impact policy, often before findings are verified. Evidence suggests that pre-prints have more spin relative to peer-reviewed publications. Clinical trial findings posted on pre-print servers do not change substantially following peer-review, but other study types (e.g., modeling and observational studies) often undergo substantial revision or are never published. Nuanced policies about sharing results are needed to balance rapid implementation of true and important advancements with accuracy. Policies recommending immediate posting of COVID-19-related research should be re-evaluated, and standards for evaluation and sharing of unverified studies should be developed. These may include specifications about what information is included in pre-prints and requirements for certain data quality standards (e.g., automated review of images and tables); requirements for code release and sharing; and limiting early postings to methods, results, and limitations sections. Academic publishing needs to innovate and improve, but assessments of evidence quality remains a critical part of the scientific discovery and dissemination process.
PubMed: 37663450
DOI: 10.1017/ash.2023.410