Objective:
Electroconvulsive therapy (ECT) is an effective treatment for major depressive disorder; yet, its use is confined to <1% of individuals with this disorder. The authors aimed to examine ...barriers to ECT from the perspective of the provider.
Methods:
Qualitative interviews were conducted with U.S.-based ECT providers to identify potential barriers. A quantitative survey was created asking providers to rank-order barriers to starting a new ECT service or expanding existing services.
Results:
Survey responses were received from 192 physicians. Respondents were representative of all ECT providers found in the Medicare Provider Utilization and Payment Database with respect to gender and geographic distribution. Approximately one-third (N=58, 30%) of survey respondents graduated from one of 12 residency programs. Programs with dedicated hospital space were more likely to have larger services than those borrowing surgical recovery space (χ2=25.87, df=1, p<0.001). The most prominent provider-reported barriers to expanding an existing ECT service were lack of physical space, stigma on the part of patients, and transportation difficulties. The most prominent barriers to initiating a new service were lack of well-trained colleagues and ECT practitioners, lack of a champion within the institution, and lack of physical space. Wide geographic variation was found in the availability of ECT, with the highest concentration of ECT providers per 1 million individuals found in New England (6.4), and the lowest found in the West South Central (1.1).
Conclusions:
Coordinated efforts to overcome identified barriers may allow ECT to be more broadly implemented. Investments in education may increase the number of competent practitioners.
Axon degeneration is a common and often early feature of neurodegeneration that correlates with the clinical manifestations and progression of neurological disease. Nicotinamide mononucleotide ...adenylytransferase (NMNAT) is a neuroprotective factor that delays axon degeneration following injury and in models of neurodegenerative diseases suggesting a converging molecular pathway of axon self-destruction. The underlying mechanisms have been under intense investigation and recent reports suggest a central role for axonal mitochondria in both degeneration and NMNAT/WLD(S) (Wallerian degeneration slow)-mediated protection. We used dorsal root ganglia (DRG) explants and Drosophila larval motor neurons (MNs) as models to address the role of mitochondria in Wallerian degeneration (WD). We find that expression of Drosophila NMNAT delays WD in human DRG neurons demonstrating evolutionary conservation of NMNAT function. Morphological comparison of mitochondria from WLD(S)-protected axons demonstrates that mitochondria shrink post-axotomy, though analysis of complex IV activity suggests that they retain their functional capacity despite this morphological change. To determine whether mitochondria are a critical site of regulation for WD, we genetically ablated mitochondria from Drosophila MN axons via the mitochondria trafficking protein milton. Milton loss-of-function did not induce axon degeneration in Drosophila larval MNs, and when axotomized WD proceeded stereotypically in milton distal axons although with a mild, but significant delay. Remarkably, the protective effects of NMNAT/WLD(S) were also maintained in axons devoid of mitochondria. These experiments unveil an axon self-destruction cascade governing WD that is not initiated by axonal mitochondria and for the first time illuminate a mitochondria-independent mechanism(s) regulating WD and NMNAT/WLD(S)-mediated axon protection.
Axon degeneration is a common and often early feature of neurodegeneration that correlates with the clinical manifestations and progression of neurological disease. Nicotinamide mononucleotide ...adenylytransferase (NMNAT) is a neuroprotective factor that delays axon degeneration following injury and in models of neurodegenerative diseases suggesting a converging molecular pathway of axon self-destruction. The underlying mechanisms have been under intense investigation and recent reports suggest a central role for axonal mitochondria in both degeneration and NMNAT/WLD
S
(Wallerian degeneration slow)-mediated protection. We used dorsal root ganglia (DRG) explants and
Drosophila
larval motor neurons (MNs) as models to address the role of mitochondria in Wallerian degeneration (WD). We find that expression of
Drosophila
NMNAT delays WD in human DRG neurons demonstrating evolutionary conservation of NMNAT function. Morphological comparison of mitochondria from WLD
S
-protected axons demonstrates that mitochondria shrink post-axotomy, though analysis of complex IV activity suggests that they retain their functional capacity despite this morphological change. To determine whether mitochondria are a critical site of regulation for WD, we genetically ablated mitochondria from
Drosophila
MN axons via the mitochondria trafficking protein
milton. Milton
loss-of-function did not induce axon degeneration in
Drosophila
larval MNs, and when axotomized WD proceeded stereotypically in
milton
distal axons although with a mild, but significant delay. Remarkably, the protective effects of NMNAT/WLD
S
were also maintained in axons devoid of mitochondria. These experiments unveil an axon self-destruction cascade governing WD that is not initiated by axonal mitochondria and for the first time illuminate a mitochondria-independent mechanism(s) regulating WD and NMNAT/WLD
S
-mediated axon protection.
In 2020, esketamine received a supplemental indication as a therapy for major depression with suicidal ideation (MDSI), based on protocols enrolling hospitalized patients. Given the high risk of ...suicide following hospital discharge and the high relapse rates following discontinuation of esketamine, the optimal long-term treatment approach remains unclear. Cognitive behavioral therapy (CBT) is highly effective in relapse prevention and has been shown to prevent suicide attempts in high-risk populations. Here we describe the study protocol for the CBT-ENDURE trial: Cognitive Behavioral Therapy Following Esketamine for Major Depression and SUicidal Ideation for RElapse Prevention. Patients with depression (N = 100) who are admitted to hospital or are outpatients with clinically significant suicidal ideation will be enrolled in the study. All patients will receive esketamine (twice weekly for four weeks) and will be randomly assigned (1:1 ratio) to receive a 16-week course of CBT plus treatment as usual (CBT group) or treatment as usual only (TAU only group). Patients are followed for a total of 6 months. Supported under a funding announcement from NIMH to conduct safety and feasibility trials for patients at high risk for suicide, the primary outcome of the CBT-ENDURE study is feasibility (as measured by recruitment and retention), with a key secondary outcome being relapse among those who experience substantial benefit following two weeks of esketamine.
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.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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