Project description:Cardiac rehabilitation programs across Canada have suspended in-person services as a result of large-scale physical distancing recommendations designed to flatten the COVID-19 pandemic curve. Virtual cardiac rehabilitation (VCR) offers an alternate mechanism of care delivery, capable of providing similar patient outcomes and safety profiles compared with centre-based programs. To minimize care gaps, all centres should consider developing and implementing a VCR program. The process of this rapid implementation, however, can be daunting. Centres should initially focus on the collation, utilization, and repurposing of existing resources, equipment, and technology. Once established, programs should then focus on ensuring that quality indicators are met and care processes are protocolized. This should be followed by the development of sustainable VCR solutions to account for care gaps that existed before COVID-19, and to improve cardiac rehabilitation delivery, moving forward. This article reviews the potential challenges and obstacles of this process and aims to provide pragmatic guidance to aid clinicians and administrators during this challenging time.
Project description:Plants have been developed as an alternative platform for the production of biopharmaceutical proteins, culminating recently with the FDA approval of the first plant-derived recombinant pharmaceutical enzyme for human use (ELELYSOÔ by Protalix Biotherapeutics). Among the many different plant-based technologies that have been proposed, transient expression mediated by Agrobacterium tumefaciens has proven to be particularly suitable for the rapid production of vaccines in response to emerging pandemics. However, one potential drawback of transient expression in whole plants is the large variation in recombinant protein expression levels among different leaves, which introduces a level of uncertainty in process design that can increase the regulatory burden and production costs. Transient expression is also used to test expression constructs prior to the longer and more expensive process of generating transgenic plants, and here the variation can produce misleading results leading to erroneous conclusions about the relative activity of different promoters and other regulatory elements. Such variation can be caused by loosely controlled environmental and process factors such incubation temperature, plant characteristics and the method and timing of harvesting. Here we discuss differences between transgenic plants and transient expression in intact plants, and their specific pitfalls for model building. We also highlight which aspects researchers should consider when using a DoE approach to investigate protein expression in plants, both for fundamental research and process development.
Project description:With the use of contemporary tools and techniques, it has become possible to more precisely tune the biochemical mechanisms associated with using nonviral vectors for gene delivery. Consequently, nonviral vectors can incorporate numerous vector compositions and types of genetic cargo to develop diverse genetic therapies. Despite these advantages, gene-delivery strategies using nonviral vectors have poorly translated into clinical success due to preclinical experimental design considerations that inadequately predict therapeutic efficacy. Furthermore, the manufacturing and distribution processes are critical considerations for clinical application that should be considered when developing therapeutic platforms. In this review, we evaluate potential avenues towards improving the transition of gene-delivery technologies from in vitro assessment to human clinical therapy.
Project description:Gliomas are central nervous system tumors originating from glial cells, whose incidence and mortality rise in coming years. The current treatment of gliomas is surgery combined with chemotherapy or radiotherapy. However, developing therapeutic resistance is one of the significant challenges. Recent research suggested that small interfering RNA (siRNA) has excellent potential as a therapeutic to silence genes that are significantly involved in the manipulation of gliomas' malignant phenotypes, including proliferation, invasion, metastasis, therapy resistance, and immune escape. However, it is challenging to deliver the naked siRNA to the action site in the cells of target tissues. Therefore, it is urgent to develop delivery strategies to transport siRNA to achieve the optimal silencing effect of the target gene. However, there is no systematic discussion about siRNAs' clinical potential and delivery strategies in gliomas. This review mainly discusses siRNAs' delivery strategies, especially nanotechnology-based delivery systems, as a potential glioma therapy. Moreover, we envisage the future orientation and challenges in translating these findings into clinical applications.
Project description:Managing marine nonindigenous species (mNIS) is challenging, because marine environments are highly connected, allowing the dispersal of species across large spatial scales, including geopolitical borders. Cross-border inconsistencies in biosecurity management can promote the spread of mNIS across geopolitical borders, and incursions often go unnoticed or unreported. Collaborative surveillance programs can enhance the early detection of mNIS, when response may still be possible, and can foster capacity building around a common threat. Regional or international databases curated for mNIS can inform local monitoring programs and can foster real-time information exchange on mNIS of concern. When combined, local species reference libraries, publicly available mNIS databases, and predictive modeling can facilitate the development of biosecurity programs in regions lacking baseline data. Biosecurity programs should be practical, feasible, cost-effective, mainly focused on prevention and early detection, and be built on the collaboration and coordination of government, nongovernment organizations, stakeholders, and local citizens for a rapid response.
Project description:The use of nanotechnology has the potential to revolutionize the detection and treatment of cancer. Developments in protein engineering and materials science have led to the emergence of new nanoscale targeting techniques, which offer renewed hope for cancer patients. While several nanocarriers for medicinal purposes have been approved for human trials, only a few have been authorized for clinical use in targeting cancer cells. In this review, we analyze some of the authorized formulations and discuss the challenges of translating findings from the lab to the clinic. This study highlights the various nanocarriers and compounds that can be used for selective tumor targeting and the inherent difficulties in cancer therapy. Nanotechnology provides a promising platform for improving cancer detection and treatment in the future, but further research is needed to overcome the current limitations in clinical translation.
Project description:New chemistry methods for the synthesis of radiolabeled small molecules have the potential to impact clinical positron emission tomography (PET) imaging, if they can be successfully translated. However, progression of modern reactions from the stage of synthetic chemistry development to the preparation of radiotracer doses ready for use in human PET imaging is challenging and rare. Here we describe the process of and the successful translation of a modern palladium-mediated fluorination reaction to non-human primate (NHP) baboon PET imaging-an important milestone on the path to human PET imaging. The method, which transforms [(18)F]fluoride into an electrophilic fluorination reagent, provides access to aryl-(18)F bonds that would be challenging to synthesize via conventional radiochemistry methods.
Project description:The next frontier towards a cure for B-cell non-Hodgkin lymphomas (B-NHL) is autologous cellular immunotherapy such as immune checkpoint blockade (ICB), bispecific antibodies (BsAbs) and chimeric antigen receptor (CAR) T-cells. While highly successful in various solid malignancies and in aggressive B-cell leukemia, this clinical success is often not matched in B-NHL. T-cell subset skewing, exhaustion, expansion of regulatory T-cell subsets, or other yet to be defined mechanisms may underlie the lack of efficacy of these treatment modalities. In this review, a systematic overview of results from clinical trials is given and is accompanied by reported data on T-cell dysfunction. From these results, we distill the underlying pathways that might be responsible for the observed differences in clinical responses towards autologous T-cell-based cellular immunotherapy modalities between diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL). By integration of the clinical and biological findings, we postulate strategies that might enhance the efficacy of autologous-based cellular immunotherapy for the treatment of B-NHL.
Project description:The repositioning or "repurposing" of existing therapies for alternative disease indications is an attractive approach that can save significant investments of time and money during drug development. For cancer indications, the primary goal of repurposed therapies is on efficacy, with less restriction on safety due to the immediate need to treat this patient population. This report provides a high-level overview of how drug developers pursuing repurposed assets have previously navigated funding efforts, regulatory affairs, and intellectual property laws to commercialize these "new" medicines in oncology. This article provides insight into funding programs (e.g., government grants and philanthropic organizations) that academic and corporate initiatives can leverage to repurpose drugs for cancer. In addition, we highlight previous examples where secondary uses of existing, Food and Drug Administration- or European Medicines Agency-approved therapies have been predicted in silico and successfully validated in vitro and/or in vivo (i.e., animal models and human clinical trials) for certain oncology indications. Finally, we describe the strategies that the pharmaceutical industry has previously employed to navigate regulatory considerations and successfully commercialize their drug products. These factors must be carefully considered when repurposing existing drugs for cancer to best benefit patients and drug developers alike.