From bench to almost bedside: the long road to a licensed Ebola virus vaccine

Introduction: The Ebola virus (EBOV) disease epidemic during 2014–16 in West Africa has accelerated the clinical development of several vaccine candidates that have demonstrated efficacy in the gold standard nonhuman primate (NHP) model, namely cynomolgus macaques.

Areas covered: This review discusses the pre-clinical research and if available, clinical evaluation of the currently available EBOV vaccine candidates, while emphasizing the translatability of pre-clinical data generated in the NHP model to clinical data in humans.

Expert opinion: Despite the existence of many successful EBOV vaccine candidates in the pre-clinical stages, only two platforms became the focus of Phase 2/3 efficacy trials in Liberia, Sierra Leone, and Guinea near the peak of the epidemic: the Vesicular stomatitis virus (VSV)-vectored vaccine and the chimpanzee adenovirus type 3 (ChAd3)-vectored vaccine. The results of three distinct clinical trials involving these candidates may soon pave the way for a licensed, safe and efficacious EBOV vaccine to help combat future epidemics.     

The long and winding road from concept to practice:

The notion of hypnotic types—of qualitative differences in the mechanisms by which people respond to hypnotic suggestions—is examined with respect to the kind of evidence that has traditionally been seen to support it. Bimodality in the distribution of hypnosis scores has been takén as evidence for two “types” of hypnotizability. It is argued that little can be said about the nature of underlying processes from the distribution of raw scores. The relationship of factor analytic results to possible underlying typologies is examined. It is concluded that the present evidence simply does not allow an evaluation of the merits of current typological formulations.     

Guest Editorial: From neuroscience to neuro-rehabilitation: transferring basic neuroscientific principles from laboratory to bedside

Several new approaches for treatment of Central Nervous System (CNS) disorders are currently under investigation, including the use of rehabilitation training strategies, which are often combined with electrical and/or pharmacological modulation of spinal locomotor circuitries. While these approaches show great promise in the laboratory setting, there still exists a large gap in knowledge on how to transfer these treatments to daily clinical use. This thematic series presents a cross section of cutting edge approaches with the goal of transferring basic neuroscience principles from the laboratory to the proverbial "bedside".     

Moving from the laboratory bench to patients' bedside: considerations for effective therapy with stem cells

Although stem cell therapy is not a new field, the field was limited to transplantation of hematopoietic stem cells. Such transplantation has provided invaluable information for the emerging field with new stem cells. Mesenchymal stem cells (MSCs) are an attractive source for therapy; reduced ethical concern, ease in expansion, as off-the-shelf stem cells. MSCs exert immune suppressive properties, providing them with the potential for immune suppressive therapy such as autoimmunity, asthma, allergic rhinitis and graft versus host disease. In addition, MSCs, as well as other stem cells, can be applied for bone and cartilage repair, cardiovascular disease, and neural repair/protection. The data thus far with MSCs are mixed. This review discusses the immune-enhancing properties of MSCs to explain the possible confounds of inflammatory microenvironment in the MSCs therapy. Although this review focuses on MSCs, the information can be extrapolated to other stem cells. The review summarizes the biology of MSCs, including multilineage differentiation potential, transdifferentiation capability, and immunological effects. We emphasize the key concepts that may predict the use of these cells in medicine, namely, the application of these cells from the bench to the bedside. Prospects on immunotherapy, neuroregeneration, and cardiovascular repair are used as examples of tissue repair.     

Postconditioning: from the bench to bedside

Infarct size is determined not only by the severity of ischemia but also by pathological processes initiated at reperfusion. Accumulating experimental evidence indicates that lethal reperfusion injury might account for up to half of the final size of the myocardial infarct. Ischemic postconditioning (brief repeated periods of ischemia-reperfusion applied at the onset of coronary reflow) has been recently described as a powerful cardioprotection mechanism that prevents lethal reperfusion injury. This is the first method proven to reduce the final infarct size by about 50% in several in vivo models and to be confirmed in recent preliminary human studies. The molecular pathways are incompletely mapped but they probably converge to a mitochondrial key target: the mitochondrial permeability transition pore (PTP) which opening during early reperfusion is an event that promotes myocardial cell death. In different animal models and experimental settings, pharmacological PTP inhibition at the onset of reperfusion reproduces all the cardioprotective effects of ischemic postconditioning. In a recent proof-of-concept trial, the administration (just before percutaneous coronary intervention) of cyclosporine A, a potent PTP inhibitor, was associated with smaller infarct size. This review will focus on the physiological preclinical data on both ischemic and pharmacological postconditioning that are relevant to their translation to clinical therapeutics.     

Treatment for chronic myelogenous leukemia: the long road to imatinib

The scientists of today have become accustomed to the extremely rapid pace of progress in the biomedical sciences spurred on by the discovery of recombinant DNA and the advent of automated DNA sequencing and PCR, with progress usually being measured in months or years at most. What is often forgotten, however, are the many prior advances that were needed to reach our present state of knowledge. Here I illustrate this by discussing the scientific discoveries made over the course of the past century and a half that ultimately led to the recent successful development of drugs, particularly imatinib mesylate, to treat chronic myelogenous leukemia.     

Making the move: from bedside to camera-side

The tele-intensive care unit (tele-ICU) uses sophisticated telemedicine technology and a remote team of critical care experts, including nurses, to provide continuous monitoring, assessment, and interventional services to a large number of patients across multiple ICUs. This new practice environment offers experienced critical care nurses an opportunity for career and knowledge expansion while reducing some of the physical and emotional risks encountered at the bedside. The role of the tele-ICU is still evolving but focuses on 4 areas of responsibility: performing virtual rounds, managing patient alerts, providing ICU support, and coaching or providing teaching moments. The transition from the bedside into the tele-ICU role can be complex as tele-ICU nurses encounter ICU acceptance barriers and a lack of or a change in professional identity. A formal orientation program focused on competency is necessary for the successful transition from bedside nurse to tele-ICU nurse.     

Epidural catheters: the long and winding road

Entrapment and knotting of epidural catheters has been described, as well as techniques for removal. Several cases of successful removal have been reported; however, significant resistance was encountered during removal. Following the techniques described previously, we successfully removed a knotted epidural catheter.