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Contact (Thousand Oaks (Ventura County,... 2024One means by which cells reutilize neutral lipids stored in lipid droplets is to degrade them by autophagy. This process involves spartin, mutations of which cause the...
One means by which cells reutilize neutral lipids stored in lipid droplets is to degrade them by autophagy. This process involves spartin, mutations of which cause the rare inherited disorder Troyer syndrome (or spastic paraplegia-20, SPG20). A recently published paper from the team led by Karin Reinsich (Yale) suggests that the molecular function of spartin and its unique highly conserved "senescence" domain is as a lipid transfer protein. Spartin binds to and transfers all lipid species found in lipid droplets, from phospholipids to triglycerides and sterol esters. This lipid transfer activity correlates with spartin's ability to sustain lipid droplet turnover. The senescence domain poses an intriguing question around the wide range of its cargoes, but intriguingly it has yet to yield up its secrets because attempts at crystallization failed and AlphaFold's prediction is unconvincing.
PubMed: 38808280
DOI: 10.1177/25152564241255782 -
Journal of Endovascular Therapy : An... May 2024In some cases of endovascular thoracoabdominal or juxtarenal aortic aneurysm repair, a thoracic endograft in combination with a fenestrated renovisceral device may be...
PURPOSE
In some cases of endovascular thoracoabdominal or juxtarenal aortic aneurysm repair, a thoracic endograft in combination with a fenestrated renovisceral device may be needed in order to create a sufficient proximal landing zone. This study aimed to evaluate the technical aspects and postoperative morbidity of a single- or 2-stage approach.
METHODS
Eighty-seven consecutive patients undergoing thoracic endovascular aortic repair (TEVAR) in combination with elective fenestrated repair (fenestrated endovascular aortic repair [FEVAR]; fenestrated Anaconda device) from 2015 to 2022 were included in this retrospective bicentric study. Underlying pathologies, aortic morphology, technical details, and postoperative morbidity were recorded.
RESULTS
Single-staged ("1S," n=61) and 2-staged ("2S," n=26) interventions were compared. Indications were thoracoabdominal aneurysms (TAAAs) (Crawford I-IV) (n=56, 64%) and juxtarenal aneurysms (n=31, 36%). In 2S, the proportion of TAAA was higher than in 1S (2S: 77%, 1S: 59%; p=0.001). In 2S, the covered length of the descending aorta was longer (1S: 128±60 mm, 2S: 202±64 mm; p=0.003). Temporary aneurysm sack perfusion (TASP) was established in 11 (18%) of 1S and 1 (4%) of 2S patients (p=0.079), as well as cerebrospinal fluid (CSF) drainage catheter in 48 (79%) of 1S and 19 (73%) of 2S. The rate of spinal cord ischemia (SCI) and the severity of SCI were not different in both groups, with a total of 3 cases of persisting paraplegia. The rate of access complications was higher in 2S (n=6, 23%) than in 1S (n=4, 7%; p=0.027). Postoperative 30 day morbidity did not significantly differ in both groups and neither did 30 day mortality (4.6% in 1S vs 3.8% in 2S; p=0.083).
CONCLUSION
The combination of TEVAR and FEVAR using a fenestrated endograft is feasible and safe. Aortic morphology does not change significantly after endovascular repair. A single-staged strategy is feasible with excellent results, especially in Crawford IV, Crawford V, or juxtarenal aneurysms. Two-staged repair is recommended in cases with long aortic coverage and a higher American Society of Anesthesiologists (ASA) class. Follow-up data are needed to evaluate the long-term stability of the TEVAR/FEVAR interconnection.
CLINICAL IMPACT
Our study has revealed the safety and efficacy of the combination of TEVAR and FEVAR in the treatment of TAAAs and juxtarenal aneurysms with compromised supravisceral landing zones. A single-staged concept is not necessary in all cases. Staged procedures may reduce postoperative morbidity in cases with long aortic coverage and higher ASA class.
PubMed: 38804508
DOI: 10.1177/15266028241255533 -
Methods and Protocols May 2024This is a protocol for comprehensive analysis of gait and affecting factors in individuals with incomplete paraplegia due to spinal cord injury (SCI). A SCI is a...
This is a protocol for comprehensive analysis of gait and affecting factors in individuals with incomplete paraplegia due to spinal cord injury (SCI). A SCI is a devastating event affecting both sensory and motor functions. Due to better care, the SCI population is changing, with a greater proportion retaining impaired ambulatory function. Optimizing ambulatory function after SCI remains challenging. To investigate factors influencing optimal ambulation, a multi-professional research project was grounded with expertise from clinical rehabilitation, neurophysiology, and biomechanical engineering from Karolinska Institutet, the Spinalis Unit at Aleris Rehab Station (Sweden's largest center for specialized neurorehabilitation), and the Promobilia MoveAbility Lab at KTH Royal Institute of Technology. Ambulatory adults with paraplegia will be consecutively invited to participate. Muscle strength, sensitivity, and spasticity will be assessed, and energy expenditure, 3D movements, and muscle function (EMG) during gait and submaximal contractions will be analyzed. Innovative computational modeling and data-driven analyses will be performed, including the identification of clusters of similar movement patterns among the heterogeneous population and analyses that study the link between complex sensorimotor function and movement performance. These results may help optimize ambulatory function for persons with SCI and decrease the risk of secondary conditions during gait with a life-long perspective.
PubMed: 38804333
DOI: 10.3390/mps7030039 -
BMJ Neurology Open 2024Bronchial artery embolization (BAE) is the established first-line treatment for patients presenting with massive haemoptysis, a life-threatening condition that can occur...
BACKGROUND
Bronchial artery embolization (BAE) is the established first-line treatment for patients presenting with massive haemoptysis, a life-threatening condition that can occur because of numerous underlying diseases. BAE is a relatively safe procedure with control of haemorrhage achieved in 77%-90% of cases and rare occurrence of complications. Spinal cord infarction is one such rare complication, which can have severe implications in terms of morbidity.
CASE PRESENTATIONS
We present a case of a 70-year-old man who developed paraplegia with loss of pain and temperature sensation as well as sphincteric involvement following BAE for hemoptysis. MRI of the spine was suggestive of an ischaemic event involving anterolateral spinal cord segment T4-T6, so a diagnosis of anterior spinal artery syndrome post BAE was made. The patient was given corticosteroids, dual antiplatelet medications, pregabalin, supportive management and regular physiotherapy. Follow-up of the patient at 3 and 6 months failed to show any significant improvement in neurological function, although the patient did not report problem of significant hemoptysis afterward.
CONCLUSION
Spinal cord infarct is a rare and disabling complication of BAE despite it being a safe procedure with good long-term outcomes. Detailed knowledge about the anatomy of bronchial arteries and spinal arteries with detailed preprocedure investigations may lower the risk of this disabling complication.
PubMed: 38800071
DOI: 10.1136/bmjno-2024-000684 -
Scandinavian Journal of Surgery : SJS :... May 2024Blunt thoracic aortic injury (BTAI) is associated with considerable mortality and morbidity. Thoracic endovascular aortic repair (TEVAR) has essentially replaced open...
BACKGROUND
Blunt thoracic aortic injury (BTAI) is associated with considerable mortality and morbidity. Thoracic endovascular aortic repair (TEVAR) has essentially replaced open aortic repair (OAR) with superior outcome. The objective of this study was to evaluate the early and intermediate-term outcomes in patients sustaining BTAI treated with TEVAR, and to evaluate the prevalence and impact of left subclavian artery (LSA) coverage.
METHODS
This retrospective analysis includes patients undergoing TEVAR for BTAI between February 2006 and December 2022 at the Helsinki University Hospital, Finland. The primary endpoints were 30-day and 2-year mortality, technical success of stent-graft system deployment, and procedural and device-related complications. The secondary endpoints pertained to reintervention events: conversion to OAR, re-TEVAR, any endovascular/surgical reinterventions for optimal stent-graft function, or any reinterventions during follow-up.
RESULTS
A total of 38 consecutive BTAI patients treated with TEVAR were included in the analyses. Median patient age was 45.5 years (range, 15-79) and 66% were male. The median follow-up period was 39 months. Technical success was 100%, 30-day mortality was 0%, and 2-year mortality was 11% in the study cohort. Coverage of LSA without revascularization (13/18) resulted in one postoperative nondisabling stroke (1/13), no paraplegia, and one had ischemic left arm findings (1/13). Only one patient required reintervention (LSA embolization; 1/38).
CONCLUSION
In this institutional series, we provide further evidence in favor of TEVAR for BTAI treatment. We demonstrated that TEVAR is linked to highly favorable outcomes in the short and intermediate term, and coverage of LSA without revascularization was quite well tolerated.
PubMed: 38795016
DOI: 10.1177/14574969241255242 -
Microorganisms Apr 2024spp. spondylodiscitis is a rare condition for which treatment options are often limited. A further obstacle is the duration of therapy, which should be administered for...
spp. spondylodiscitis is a rare condition for which treatment options are often limited. A further obstacle is the duration of therapy, which should be administered for up to twelve months. In view of the long duration of therapy, azoles are, so far, the only oral treatment strategy that can be given as home therapy. In the case of resistance or reduced susceptibility to azoles, there are not enough comfortable treatment opportunities with adequate bone penetration and limited toxicity. We report the first case of the successful use of rezafungin for spondylodiscitis due to with reduced susceptibility to azoles. A 68-year-old patient, affected by paraplegia and short bowel syndrome, was diagnosed with spondylodiscitis, confirmed with a culture on vertebral biopsy after an 18-FDG PET/CT scan. He received 200 mg of rezafungin weekly for 26 weeks, after 10 weeks of previous antifungal treatment that was not well tolerated with voriconazole plus liposomal amphotericin B. He had a full clinical, radiologic, and biochemical response to the therapy with rezafungin, with no adverse effects. Rezafungin can be a promising therapy for Candida osteomyelitis, especially when first line therapies are ineffective, poorly tolerated, or contraindicated.
PubMed: 38792732
DOI: 10.3390/microorganisms12050903 -
Journal of Clinical Medicine May 2024People with spinal cord injuries (SCIs) often have trouble remaining active because of paralysis. In the past, exercise recommendations focused on the non-paralyzed... (Review)
Review
People with spinal cord injuries (SCIs) often have trouble remaining active because of paralysis. In the past, exercise recommendations focused on the non-paralyzed muscles in the arms, which provides limited benefits. However, recent studies show that electrical stimulation can help engage the paralyzed extremities, expanding the available muscle mass for exercise. The authors provide an evidence-based approach using expertise from diverse fields, supplemented by evidence from key studies toward the management of electrical stimulation therapies in individuals with SCIs. Literature searches were performed separately using the PubMed, Medline, and Google Scholar search engines. The keywords used for the searches included functional electrical stimulation cycling, hybrid cycling, neuromuscular electrical stimulation exercise, spinal cord injury, cardiovascular health, metabolic health, muscle strength, muscle mass, bone mass, upper limb treatment, diagnostic and prognostic use of functional electrical stimulation, tetraplegic hands, and hand deformities after SCI. The authors recently presented this information in a workshop at a major rehabilitation conference. Additional information beyond what was presented at the workshop was added for the writing of this paper. Functional electrical stimulation (FES) cycling can improve aerobic fitness and reduce the risk of cardiovascular and metabolic diseases. The evidence indicates that while both FES leg cycling and neuromuscular electrical stimulation (NMES) resistance training can increase muscle strength and mass, NMES resistance training has been shown to be more effective for producing muscle hypertrophy in individual muscle groups. The response to the electrical stimulation of muscles can also help in the diagnosis and prognosis of hand dysfunction after tetraplegia. Electrical stimulation activities are safe and effective methods for exercise and testing for motor neuron lesions in individuals with SCIs and other paralytic or paretic conditions. They should be considered part of a comprehensive rehabilitation program in diagnosing, prognosing, and treating individuals with SCIs to improve function, physical activity, and overall health.
PubMed: 38792536
DOI: 10.3390/jcm13102995 -
Journal of Neuromuscular Diseases May 2024Motor neuron diseases and peripheral neuropathies are heterogeneous groups of neurodegenerative disorders that manifest with distinct symptoms due to progressive...
Motor neuron diseases and peripheral neuropathies are heterogeneous groups of neurodegenerative disorders that manifest with distinct symptoms due to progressive dysfunction or loss of specific neuronal subpopulations during different stages of development. A few monogenic, neurodegenerative diseases associated with primary metabolic disruptions of sphingolipid biosynthesis have been recently discovered. Sphingolipids are a subclass of lipids that form critical building blocks of all cellular and subcellular organelle membranes including the membrane components of the nervous system cells. They are especially abundant within the lipid portion of myelin. In this review, we will focus on our current understanding of disease phenotypes in three monogenic, neuromuscular diseases associated with pathogenic variants in components of serine palmitoyltransferase, the first step in sphingolipid biosynthesis. These include hereditary sensory and autonomic neuropathy type 1 (HSAN1), a sensory predominant peripheral neuropathy, and two neurodegenerative disorders: juvenile amyotrophic lateral sclerosis affecting the upper and lower motor neurons with sparing of sensory neurons, and a complicated form of hereditary spastic paraplegia with selective involvement of the upper motor neurons and more broad CNS neurodegeneration. We will also review our current understanding of disease pathomechanisms, therapeutic approaches, and the unanswered questions to explore in future studies.
PubMed: 38788085
DOI: 10.3233/JND-240014 -
Frontiers in Veterinary Science 2024Fibrocartilaginous embolic myelopathy (FCEM) and acute non-compressive nucleus pulposus extrusion (ANNPE) are common causes of acute spinal cord injury in dogs. Outcome...
BACKGROUND
Fibrocartilaginous embolic myelopathy (FCEM) and acute non-compressive nucleus pulposus extrusion (ANNPE) are common causes of acute spinal cord injury in dogs. Outcome among paraplegic deep pain positive (DPP) and deep pain negative (DPN) dogs with either condition and factors influencing recovery have not been clearly established.
METHODS
Dogs with thoracolumbar FCEM or ANNPE resulting in paraplegia presenting to university hospitals between 2012 and 2022 were retrospectively included. Diagnosis of FCEM or ANNPE was based on clinical and magnetic resonance imaging findings. Outcome was defined as successful (recovery of independent ambulation) or unsuccessful (non-ambulatory ≥3 months following diagnosis or at the time of death/euthanasia). Logistic regression analysis was performed to investigate associations between clinical or imaging variables and outcome.
RESULTS
Thirty-one dogs were included. In total, 14 dogs were initially paraplegic DPP (8 FCEM, 6 ANNPE) and 17 dogs were paraplegic DPN (11 FCEM, 6 ANNPE). Outcome was available for 26 dogs (14 DPP, 12 DPN) with a median follow-up time of 182 days (range 0-2,311) including 2 dogs euthanized at the time of diagnosis; 1 of 12 DPN dogs (8.3%) regained independent ambulation, whereas 9 of 14 DPP dogs (64.3%) regained independent ambulation. DPN dogs had a significantly higher risk of not regaining independent ambulation compared with DPP dogs (OR: 47.40, 95% CI: 2.09-1073.99). No other variables were associated with outcome.
CONCLUSION
While recovery of ambulation was possible, these results confirm that the absence of pain perception is a useful negative prognostic indicator in dogs with severe thoracolumbar FCEM or ANNPE.
PubMed: 38784658
DOI: 10.3389/fvets.2024.1406843 -
Life Science Alliance Aug 2024Complexes of ERLIN1 and ERLIN2 (ER lipid raft-associated 1 and 2) form large ring-like cup-shaped structures on the endoplasmic reticulum (ER) membrane and serve as...
Complexes of ERLIN1 and ERLIN2 (ER lipid raft-associated 1 and 2) form large ring-like cup-shaped structures on the endoplasmic reticulum (ER) membrane and serve as platforms to bind cholesterol and E3 ubiquitin ligases, potentially defining functional nanodomains. Here, we show that ERLIN scaffolds mediate the interaction between the full-length isoform of TMUB1 (transmembrane and ubiquitin-like domain-containing 1) and RNF170 (RING finger protein 170). We identify a luminal N-terminal conserved region in TMUB1 and RNF170, which is required for this interaction. Three-dimensional modelling shows that this conserved motif binds the stomatin/prohibitin/flotillin/HflKC domain of two adjacent ERLIN subunits at different interfaces. Protein variants that preclude these interactions have been previously linked to hereditary spastic paraplegia. Using omics-based approaches in combination with phenotypic characterization of HeLa cells lacking both ERLINs, we demonstrate a role of ERLIN scaffolds in limiting cholesterol esterification, thereby favouring cholesterol transport from the ER to the Golgi apparatus and regulating Golgi morphology and the secretory pathway.
Topics: Humans; Membrane Proteins; Cholesterol; Ubiquitin-Protein Ligases; Endoplasmic Reticulum; HeLa Cells; Golgi Apparatus; Secretory Pathway; Protein Binding; Nerve Tissue Proteins
PubMed: 38782601
DOI: 10.26508/lsa.202402620