Electroconvulsive Therapy:a Video-Based Educational Resource Using Standardized Patients

Objective Video-based depictions of electroconvulsive therapy (ECT) can be useful for educational purposes, but many of the readily available resources may worsen already stigmatized views of the procedure. Educators' common reliance on such material highlights the paucity of equipoised depictions of modern ECT well suited for the training of health professionals. The authors developed and tested a new educational module enhanced by videotaped depictions of a simulated patient undergoing the consent, treatment, recovery, and follow-up phases of ECT. Methods The didactic intervention interspersed 7 short video clips (totaling 14 min) into a 55-min lecture on treatment-resistant depression. The session, part of an intensive course of preclinical psychiatry, was delivered online through synchronous videoconferencing with Zoom. The primary outcome measure was change in theQuestionnaire on Attitudes and Knowledge of ECT(QuAKE). Results Fifty-three out of 63 (87%) eligible second-year medical students completed assessments at baseline and after exposure to the didactic intervention. QuAKE scores improved between baseline and endpoint: the Attitudes composite increased from 49.4 +/- 6.1 to 59.1 +/- 5.7 (pairedt10.65,p <0.001, Cohen'sd0.69), and the Knowledge composite from 13.3 +/- 1.2 to 13.9 +/- 0.8 (pairedt3.97,p <0.001, Cohen'sd0.23). Conclusions These video-based educational materials proved easy to implement in the virtual classroom, were amenable to adaptation by end-use instructors, were well received by learners, and led to measurable changes in students' knowledge of and attitudes toward ECT

Addressing Electroconvulsive Therapy Knowledge Gaps and Stigmatized Views Among Nursing Students Through a Psychiatrist-APRN Didactic Partnership

BACKGROUND:Knowledge gaps and stigmatized perceptions regarding electroconvulsive therapy (ECT) among patients and health providers contribute to the underutilization of an important therapeutic modality. The proactive education of future advanced practice registered nurses (APRNs) provides an opportunity to optimize the use of this evidence-based clinical practice.AIMS:As part of a general course in psychiatry during the first year of nursing school, we dedicated 1 hour to treatment-refractory depression, including ECT, and a second hour to a summary discussion of mood disorders. We evaluated the efficacy of this didactic offering, which was co-taught by a psychiatrist and a psychiatric APRN.METHOD:At baseline, consenting students (n= 94) provided three words they associated with ECT and then completed three validated instruments: (a) Questionnaire on Attitudes and Knowledge of ECT, (b) Opening Minds Stigma Scale for Health Care Providers, and (c) Self-Stigma of Seeking Help. Among the 67 students who repeated the assessment at endpoint, 39 attended the ECT didactic (Intervention group, 58%) and 28 did not (Control, 42%).RESULTS:After completion of the 3-month course, students showed improvement across all measures (p<.001). The only outcomes that improved differentially between the Intervention and Control groups were the Questionnaire on Attitudes and Knowledge of ECT Attitudes and Knowledge scales (p= .01). Word choice valence associated with ECT shifted favorably by endpoint (p<.001).CONCLUSIONS:An educational intervention co-led by a psychiatric-mental health APRN had a significant impact on nursing students' knowledge and perceptions of ECT. This approach can be readily implemented at other institutions. Future refinements will include the videotaped depiction of a simulated patient undergoing the consent, treatment, and recovery phases of ECT

Mechanisms of NMNAT/WLDs Mediated Axon Protection

Neurodegeneration is a hallmark of several inherited and acquired diseases of the nervous system. Though great attention in the past has been given to understanding and mitigating neuron loss in these diseases, efforts at targeting neuron cell body death pathways have yielded modest success in preventing or delaying disease onset. Often preceding neuronal death, axon degeneration is a common pathological feature of many neurodegenerative processes, and may therefore provide a therapeutic target upstream of neuronal loss. Though formerly believed to be a passive process, recent observations concerning the destruction of distal axons following transection, referred to as “Wallerian degeneration” (WD), suggest degeneration is an actively regulated process of axon self-destruction. Though the precise mechanism(s) governing axonal destruction remain elusive, insight has been gained by the discovery of a naturally occurring mutant mouse strain in which WD is delayed, the Wallerian degeneration slow (wldS) mouse. The neuroprotective properties of wldS have been mapped to a chimeric gene Ube4b/NMNAT producing a fusion, WLDS protein. Though the precise protective function of WLDS remains controversial, it is clear that NMNAT is an important neuronal maintenance factor capable of conferring axonal protection by itself. In this dissertation, I address mechanisms underlying the axon protective properties of NMNAT and WLDS in the context of WD utilizing a multidisciplinary approach that combines mammalian primary neuronal culture systems and Drosophila genetic models.</p

Dealing with Misfolded Proteins: Examining the Neuroprotective Role of Molecular Chaperones in Neurodegeneration

Human neurodegenerative diseases arise from a wide array of genetic and environmental factors. Despite the diversity in etiology, many of these diseases are considered "conformational" in nature, characterized by the accumulation of pathological, misfolded proteins. These misfolded proteins can induce cellular stress by overloading the proteolytic machinery, ultimately resulting in the accumulation and deposition of aggregated protein species that are cytotoxic. Misfolded proteins may also form aberrant, non-physiological protein-protein interactions leading to the sequestration of other normal proteins essential for cellular functions. The progression of such disease may therefore be viewed as a failure of normal protein homeostasis, a process that involves a network of molecules regulating the synthesis, folding, translocation and clearance of proteins. Molecular chaperones are highly conserved proteins involved in the folding of nascent proteins, and the repair of proteins that have lost their typical conformations. These functions have therefore made molecular chaperones an active area of investigation within the field of conformational diseases. This review will discuss the role of molecular chaperones in neurodegenerative diseases, highlighting their functional classification, regulation, and therapeutic potential for such diseases

518. Long-term lentiviral vector-mediated transgene expression in neural progenitor cells following implantation into the injured rat spinal cord

Due to their self-renewal and multi-potency, stem cells represent an attractive source for cell replacement therapy in neurological disorders. Genetic manipulation of these cells may allow controlled release of therapeutic proteins, suppress immune rejection, or produce essential neurotransmitters. Furthermore, when the expression cassette is incorporated into the host genome ex vivo, this technique also may be used as a method to trace cells following implantation into tissues of interest. We explored the possibility of transducing pluripotent fetal rat cortical neural progenitor cells using lentiviral vectors encoding either the green fluorescent protein (GFP) or neurotrophic factors (NT-3, BDNF, GDNF and CNTF) under control of the CMV promoter and the Woodchuck post-transcriptional regulatory element. Following isolation and expansion of the cells at clonal density on poly-ornithine-fibronectin-coated dishes in the presence of bFGF, cells were collected, infected and replated on the dishes. Staining of these cells for neural markers (such as nestin, GFAP, Tuj-1 and RIP) after transduction did not reveal any significant difference from non-transduced cells. However, when they were transduced with a vector encoding CNTF, cells started expressing GFAP. Cells continued to express the transgene, including when bFGF was withdrawn and when cells started to differentiate into GFAP positive cells. Following delayed (1 week) implantation into the lesion site of the moderately contused spinal cord, transduced cells survived well up to 4 weeks post-implantation (the longest time point currently examined). Migration of the cells was mainly restricted to white matter on either side of the lesion. Currently, the therapeutic and axonal growth stimulating properties of the implanted cells are being investigated in injured rats

662. The Tracking of Exogenous Cells in the Injured Central Nervous System: Viral Vector Labeling Versus an Intrinsic Genetic Marker

Transplantation of exogenous cells into the injured central nervous system and subsequent examination of how these cells survive, integrate and perform physiological functions within the host environment requires that the cells be clearly identifiable from host cells. As many of the cells used for transplantation studies are derived from cultures of cells indistinguishable from the host using immunochemical approaches, numerous dyes or genetic markers have been devised and used for this purpose. These markers used to label and track these transplanted cells need to be specific, reliable, resistant to leakage or cellular transfer, and remain chemically stable once inside the host to allow long-term tracking. In the current study we compared two labeling methods for long-term tracking of cells following transplantation into the injured rat spinal cord; lentiviral vector transduction with green fluorescent protein (GFP) and DNA in situ hybridization for the Y chromosome after male cell transplantation in female rats. Examination of labeled cells at 12 wk post-injury demonstrated that both labels did not exhibit significant fading or loss of the signal due to instability over time. The visualization procedure for the DNA in situ reaction product was significantly more labor intensive than simple identification of GFP by fluorescent microscopy. Y chromosome positive cells were, however, easier to definitely count for assessment of cell survival than GFP labeled cells, due to the presence of the label as a single point within the nucleus rather than diffuse labeling throughout the entirety of the cell. The limited presence of the signal in Y chromosome positive cells though, made examination of their ability to integrate within the injured spinal cord, migrate and associate with axons impossible without additional immunochemical methods for labeling the entire cell. The combination of immunochemistry with DNA in situ however proved to be unsuccessful with the many antibody combinations tested. In conclusion GFP delivery by lentiviral vectors was far superior to DNA in situ detection of the Y chromosome for labeling of transplanted cells due to its rapid visualization and its applicability to a wide range of assessment techniques

Lentiviral vector-mediated transduction of neural progenitor cells before implantation into injured spinal cord and brain to detect their migration, deliver neurotrophic factors and repair tissue

Stem cells represent an attractive source for cell replacement therapy in neurological disorders due to their self-renewal and multi-potency. Genetic manipulation of these cells may allow controlled release of therapeutic proteins, suppress immune rejection, or produce essential neurotransmitters. Furthermore, when the expression cassette is incorporated into the host genome ex vivo, this technique also may be used as a method to trace cells following implantation into tissues of interest. We explored the possibility of transducing pluripotent fetal rat cortical neural progenitor cells (NPCs) using lentiviral vectors encoding the green fluorescent protein (GFP) or neurotrophic factors (BDNF, CNTF, D15A, GDNF, MNT and NT-3) prior to implanting these cells into the contused spinal cord or injured brain. In vitro staining of these cells for neural markers (such as nestin, GFAP, Tuj-1 and RIP) after transduction did not reveal any significant difference from non-transduced cells. When they were transduced with a vector encoding CNTF or MNT, however, cells started expressing GFAP in vitro. Following delayed (1 week) implantation into the lesion site of the moderately contused rat spinal cord or the injured brain, transduced cells survived up to 12 weeks post-implantation (the longest time point examined) and most of the NPCs turned into an astrocytic phenotype in the spinal cord, but not in the brain. Nestin and GFP positive cells were detected in the brain, but not in the spinal cord lesion. GFP positive cells in the spinal cord migrated rostrally and caudally from the lesion/implantation site towards uninjured tissue. Novel findings in this study are the longterm expression of a foreign gene in NPCs using lentiviral vectors; this enabled tracking of the cells following implantation. This expression also allowed the observation that NPCs developed differently in the injured spinal cord and brain. Moreover, NPCs could be transduced to overexpress neurotrophic factors. In sum, NPC survival and the long-term transgene expression that allows easy tracking of migrating cells make NPCs promising candidates for implantation into the injured spinal cord or brain and a potentially powerful tool to enhance regeneration when transduced ex vivo to produce therapeutic molecules