Molecular imaging of bacterial infections: Overcoming the barriers to clinical translation.
Ontology highlight
ABSTRACT:
SUBMITTER: Ordonez AA
PROVIDER: S-EPMC6743081 | biostudies-literature | 2019 Sep
REPOSITORIES: biostudies-literature
Publications
Molecular imaging of bacterial infections: Overcoming the barriers to clinical translation.
Ordonez Alvaro A AA Sellmyer Mark A MA Gowrishankar Gayatri G Ruiz-Bedoya Camilo A CA Tucker Elizabeth W EW Palestro Christopher J CJ Hammoud Dima A DA Jain Sanjay K SK
Science translational medicine 20190901 508
Clinical diagnostic tools requiring direct sample testing cannot be applied to infections deep within the body, and clinically available imaging tools lack specificity. New approaches are needed for early diagnosis and monitoring of bacterial infections and rapid detection of drug-resistant organisms. Molecular imaging allows for longitudinal, noninvasive assessments and can provide key information about infectious processes deep within the body. ...[more]
Similar Datasets
Project description:Ultrasound is a widely available, cost-effective, real-time, non-invasive and safe imaging modality widely used in the clinic for anatomical and functional imaging. With the introduction of novel molecularly-targeted ultrasound contrast agents, another dimension of ultrasound has become a reality: diagnosing and monitoring pathological processes at the molecular level. Most commonly used ultrasound molecular imaging contrast agents are micron sized, gas-containing microbubbles functionalized to recognize and attach to molecules expressed on inflamed or angiogenic vascular endothelial cells. There are several potential clinical applications currently being explored including earlier detection, molecular profiling, and monitoring of cancer, as well as visualization of ischemic memory in transient myocardial ischemia, monitoring of disease activity in inflammatory bowel disease, and assessment of arteriosclerosis. Recently, a first clinical grade ultrasound contrast agent (BR55), targeted at a molecule expressed in neoangiogenesis (vascular endothelial growth factor receptor type 2; VEGFR2) has been introduced and safety and feasibility of VEGFR2-targeted ultrasound imaging is being explored in first inhuman clinical trials in various cancer types. This review describes the design of ultrasound molecular imaging contrast agents, imaging techniques, and potential future clinical applications of ultrasound molecular imaging.
| S-EPMC4545409 | biostudies-literature
Project description:BackgroundAccrual to cancer clinical trials is suboptimal. Few data exist regarding whether financial reimbursement might increase accruals.ObjectiveThe objective of this study was to assess perceptions about reimbursement to overcome barriers to trial accrual.Research designThis was a cross-sectional survey.SubjectsOncologists identified from the American Medical Association Physician Masterfile.MeasuresWe report descriptive statistics, associations of physician characteristics with perceptions of reimbursement, domains, and subthemes of free-text comments.ResultsRespondents (n=1030) were mostly medical oncologists (59.4%), ages 35-54 (67%), and male (75%). Overall, 30% reported discussing trials with >25% of patients. Barriers perceived were administrative/regulatory, physician/staff time, and eligibility criteria. National Cancer Institute cooperative group participants and practice owners were more likely to endorse higher reimbursement. Respondents indicated targeted reimbursement would help improve infrastructure, but also noted potential ethical problems with reimbursement for discussion (40.7%) and accrual (85.9%). Free-text comments addressed reimbursement sources, recipients, and concerns about the real and apparent conflict of interest.ConclusionsThough concerns about a potential conflict of interest remain paramount and must be addressed in any new system of reimbursement, oncologists believe reimbursement to enhance infrastructure could help overcome barriers to trial accrual.
| S-EPMC8026490 | biostudies-literature
Project description:Aims/questionsTo explore the barriers and facilitators to nurses accessing clinical supervision; explore the barriers and facilitators to organizations implementing clinical supervision and capture what skills nurses require to facilitate clinical supervision.DesignScoping review of peer-reviewed research and grey literature.Data sourcesCINAHL, Medline, PsychINFO and Scopus were searched for relevant papers published between 1990 and 2020. Google, Google Scholar, OpenGrey & EThOS were used to search for grey literature.Review methodsPRISMA-ScR guidelines were used during the literature review process. Eighty-seven papers were included, and data were extracted from each paper using a standardized form. Data synthesis was undertaken using Seidel's analytical framework.ResultsFive themes were identified: Definitions and Models, (Mis) Trust and the Language of Supervision, Alternative Parallel Forums and Support Mechanisms, Time and Cost and Skills required.ConclusionSince its inception in the 1990s, clinical supervision has long been regarded as a supportive platform for nurses to reflect on and develop their practice. However, this review highlights that despite an awareness of the skills required for nurses to undertake clinical supervision, and the facilitators for nurses to access and organizations to implement clinical supervision, there have been persistent barriers to implementation. This review identifies these persistent factors as 'barriers to overcoming the barriers' in the clinical supervision landscape. These require critical consideration to contribute towards moving clinical supervision forward in the spirit of its original intentions.ImpactThis review progresses the debate on clinical supervision through critically analysing the barriers to overcoming the barriers. To this end, the review is designed to stimulate critical discussions amongst nurses in different clinical spaces and key stakeholders such as policy makers and regulatory bodies for the nursing profession.
| S-EPMC9546137 | biostudies-literature
Project description:Pseudomonas aeruginosa is a bacterial pathogen of global concern and is responsible for 10-15% of nosocomial infections worldwide. This opportunistic bacterial pathogen is known to cause serious complications in immunocompromised patients and is notably the leading cause of morbidity and mortality in patients suffering from cystic fibrosis. Currently, the only line of defense against P. aeruginosa infections is antibiotic treatment. Due to the acquired and adaptive resistance mechanisms of this pathogen, the prevalence of multidrug resistant P. aeruginosa strains has increased, presenting a major problem in healthcare settings. To date, there are no approved licensed vaccines to protect against P. aeruginosa infections, prompting the urgent need alternative treatment options. An alternative to traditional vaccines is vectored immunoprophylaxis (VIP), which utilizes a safe and effective adeno-associated virus (AAV) gene therapy vector to produce sustained levels of therapeutic monoclonal antibodies (mAbs) in vivo from a single intramuscular injection. In this review, we will provide an overview of P. aeruginosa biology and key mechanisms of pathogenesis, discuss current and emerging treatment strategies for P. aeruginosa infections and highlight AAV-VIP as a promising novel therapeutic platform.
| S-EPMC9775905 | biostudies-literature
Project description:DNA sequences that form secondary structures or bind protein complexes are known barriers to replication and potential inducers of genome instability. In order to determine which helicases facilitate DNA replication across these barriers, we analyzed fork progression through them in wild-type and mutant yeast cells, using 2-dimensional gel-electrophoretic analysis of the replication intermediates. We show that the Srs2 protein facilitates replication of hairpin-forming CGG/CCG repeats and prevents chromosome fragility at the repeat, whereas it does not affect replication of G-quadruplex forming sequences or a protein-bound repeat. Srs2 helicase activity is required for hairpin unwinding and fork progression. Also, the PCNA binding domain of Srs2 is required for its in vivo role of replication through hairpins. In contrast, the absence of Sgs1 or Pif1 helicases did not inhibit replication through structural barriers, though Pif1 did facilitate replication of a telomeric protein barrier. Interestingly, replication through a protein barrier but not a DNA structure barrier was modulated by nucleotide pool levels, illuminating a different mechanism by which cells can regulate fork progression through protein-mediated stall sites. Our analyses reveal fundamental differences in the replication of DNA structural versus protein barriers, with Srs2 helicase activity exclusively required for fork progression through hairpin structures.
| S-EPMC3273818 | biostudies-other
Project description:Protein synthesis is central to life and maintaining a highly accurate and efficient mechanism is essential. What happens when a translating ribosome stalls on a messenger RNA? Many highly intricate processes have been documented in the cytosol of numerous species, but how does organellar protein synthesis resolve this stalling issue? Mammalian mitochondria synthesize just thirteen highly hydrophobic polypeptides. These proteins are all integral components of the machinery that couples oxidative phosphorylation. Consequently, it is essential that stalled mitochondrial ribosomes can be efficiently recycled. To date, there is no evidence to support any particular molecular mechanism to resolve this problem. However, here we discuss the observation that there are four predicted members of the mitochondrial translation release factor family and that only one member, mtRF1a, is necessary to terminate the translation of all thirteen open reading frames in the mitochondrion. Could the other members be involved in the process of recycling stalled mitochondrial ribosomes?
| S-EPMC4103422 | biostudies-literature
Project description:More than 13,000 children annually in the United States and Canada under the age of 20 will be diagnosed with cancer at a mortality approaching 20% 1,2. Tumor samples obtained by autopsy provide an innovative way to study tumor progression, potentially aiding in the discovery of new treatments and increased survival rates. The purpose of this study was to identify barriers to autopsies and develop guidelines for requesting autopsies for research purposes.Families of children treated for childhood cancer were referred by patient advocacy groups and surveyed about attitudes and experiences with research autopsies. From 60 interviews, barriers to autopsy and tumor banking were identified. An additional 14 interviews were conducted with medical and scientific experts.Ninety-three percent of parents of deceased children did or would have consented to a research autopsy if presented with the option; however, only half of these families were given the opportunity to donate autopsy tissue for research. The most significant barriers were the physicians' reluctance to ask a grieving family and lack of awareness about research opportunities.The value of donating tumor samples to research via an autopsy should be promoted to all groups managing pediatric cancer patients. Not only does autopsy tumor banking offer a potentially important medical and scientific impact, but the opportunity to contribute this Legacy Gift of autopsy tumor tissue also creates a positive outlet for the grieving family. Taking these findings into account, our multidisciplinary team has developed a curriculum addressing key barriers.
| S-EPMC3522778 | biostudies-literature
Project description:AIM:This paper seeks to describe best practices for conducting cross-language research with individuals who have a language barrier. DESIGN:Discussion paper. DATA SOURCES:Research methods papers addressing cross-language research issues published between 2000-2017. IMPLICATIONS FOR NURSING:Rigorous cross-language research involves the appropriate use of interpreters during the research process, systematic planning for how to address the language barrier between participant and researcher and the use of reliably and validly translated survey instruments (when applicable). Biases rooted in those who enter data into "big data" systems may influence data quality and analytic approaches in large observational studies focused on linking patient language preference to health outcomes. CONCLUSION:Cross-language research methods can help ensure that those individuals with language barriers have their voices contributing to the evidence informing healthcare practice and policies that shape health services implementation and financing. Understanding the inherent conscious and unconscious biases of those conducting research with this population and how this may emerge in research studies is also an important part of producing rigorous, reliable, and valid cross-language research. IMPACT:This study synthesized methodological recommendations for cross-language research studies with the goal to improve the quality of future research and expand the evidence-base for clinical practice. Clear methodological recommendations were generated that can improve research rigor and quality of cross-language qualitative and quantitative studies. The recommendations generated here have the potential to have an impact on the health and well-being of migrants around the world.
| S-EPMC6778489 | biostudies-literature
Project description:HLA (Human Leucocyte Antigen) sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells. In this review, we discuss currently available agents for desensitization and provide a brief analysis of data on novel biologics, which will likely improve desensitization outcomes, and have potential implications in treatment of antibody mediated rejection.
| S-EPMC5239985 | biostudies-literature
Project description:This commentary focuses on the issues of statistical power, the usefulness of hypothesis-free approaches such as in genome-wide association explorations, the necessity of expanding the research beyond common DNA variants, the advantage of combining transcriptomics with genomics, and the complexities inherent to the search for links between genotype and phenotype in exercise genomics research.
| S-EPMC3183378 | biostudies-literature