ABSTRACT
Due to the characteristics of ultra-short pulse width and ultra-high peak power, femtosecond pulse laser can effectively induce nonlinear optical effects in trapped objects. As a result, it holds great value in the fields of micro and nano manipulation, microfluidics, and cell biology. However, the nonlinear optical effects on the stiffness of femtosecond optical traps remain unclear. Calibration of trap stiffness is crucial for accurately measuring forces and manipulating small particles. In this paper, we compare the stiffness between femtosecond optical traps and continuous wave optical traps. Experimental results demonstrate that the stiffness of the femtosecond optical trap in the splitting direction is greater than that in other directions and the stiffness of the continuous wave optical trap under the same laser power condition. Additionally, as the laser power increases, the stiffnesses of both the femtosecond optical trap and the continuous wave optical trap gradually increases. In contrast to a linear increase of the continuous wave optical trap, the stiffness of the femtosecond optical trap exhibits an exponential rise with increasing laser power. This research provides guidance and reference for improving the force measurement accuracy of femtosecond optical tweezer system.
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INTRODUCTION/AIMS: Limited data exist regarding variation of electrodiagnostic (EDX) findings in amyotrophic lateral sclerosis (ALS) patients with different onset regions and specificity of thoracic paraspinal muscle (TPSP) examination for confirming a diagnosis of ALS. We aimed to demonstrate the variation of EDX features and characterize the utility of TPSP muscle examination in the electrodiagnosis of ALS. METHODS: This is a retrospective study of a large cohort of ALS patients who had a comprehensive EDX evaluation. RESULTS: The study included 448 patients; all fulfilled the Gold Coast criteria for ALS. The average age at the time of EDX study was 64 years, and 41.1% were women. The onset region was identified as follows: bulbar (N = 149), cervical (N = 127), lumbosacral (N = 162), and other (N = 10). In contrast to limb onset, bulbar-onset patients more frequently demonstrated a pattern of normal or near normal needle electromyography (EMG) (p < .0001) and less frequently had abnormalities on EMG of TPSP (p = .002). Clinical or EDX diagnosis of sensory polyneuropathy was present in 12.6% patients, more frequently in the lumbosacral onset subgroup (p < .03). EMG showed active denervation in 9.6% and chronic denervation in 59% of craniobulbar muscles examined, without observed difference among different onset regions. TPSP showed higher frequencies of active and chronic denervation in ALS than a group of patients with non-ALS neuromuscular disorders. DISCUSSION: EDX features may differ among ALS patients of different onset regions. TPSP EMG is highly useful in differentiating ALS from non-ALS neuromuscular disorders while the yield of craniobulbar muscles, especially for active denervation, is low.
Subject(s)
Amyotrophic Lateral Sclerosis , Humans , Female , Male , Amyotrophic Lateral Sclerosis/diagnosis , Retrospective Studies , Paraspinal Muscles , Electromyography , ElectrodiagnosisABSTRACT
Subretinal fibrosis can occur during neovascular age-related macular degeneration (nAMD) and consequently provokes progressing deterioration of AMD patient's vision. Intravitreal anti-vascular endothelial growth factor (VEGF) injections decrease choroidal neovascularization (CNV), however, subretinal fibrosis remains principally unaffected. So far, no successful treatment nor established animal model for subretinal fibrosis exists. In order to investigate the impact of anti-fibrotic compounds on solely fibrosis, we refined a time-dependent animal model of subretinal fibrosis without active choroidal neovascularization (CNV). To induce CNV-related fibrosis, wild-type (WT) mice underwent laser photocoagulation of the retina with rupture of Bruch's membrane. The lesions volume was assessed with optical coherence tomography (OCT). CNV (Isolectin B4) and fibrosis (type 1 collagen) were separately quantified with confocal microscopy of choroidal whole-mounts at every time point post laser induction (day 7-49). In addition, OCT, autofluorescence and fluorescence angiography were carried out at designated timepoints (day 7, 14, 21, 28, 35, 42, 49) to monitor CNV and fibrosis transformation over time. From 21 to 49 days post laser lesion leakage in the fluorescence angiography decreased. Correspondingly, Isolectin B4 decreased in lesions of choroidal flat mounts and type 1 collagen increased. Fibrosis markers, namely vimentin, fibronectin, alpha-smooth muscle actin (α-SMA) and type 1 collagen were detected at different timepoints of tissue repair in choroids and retinas post laser. These results prove that the late phase of the CNV-related fibrosis model enables screening of anti-fibrotic compounds to accelerate the therapeutic advancement for the prevention, reduction, or inhibition of subretinal fibrosis.
Subject(s)
Choroidal Neovascularization , Collagen Type I , Mice , Animals , Vascular Endothelial Growth Factor A/metabolism , Choroidal Neovascularization/diagnosis , Choroidal Neovascularization/etiology , Choroidal Neovascularization/drug therapy , Fluorescein Angiography , Disease Models, Animal , Fibrosis , Tomography, Optical CoherenceABSTRACT
INTRODUCTION/AIMS: We have encountered non-myasthenic patients being given a diagnosis of myasthenia gravis (MG). This study aims to investigate the frequency of, and factors contributing to, overdiagnosis of MG. METHODS: This is a retrospective analysis of patients referred to our tertiary neuromuscular center for evaluation due to a previously suspected/confirmed MG diagnosis during a 6-year span. RESULTS: A total of 531 patients sought a second opinion regarding their MG diagnosis, and 77 (14.5%) were found to have non-myasthenic conditions. A total of 11 patients tested positive for acetylcholine receptor (AChR) antibodies. Repeated AChR antibodies became negative in five patients while in four patients, AChR binding antibody titers were persistently low. In seven patients, striational antibody was the only positive antibody identified. In 25 patients, a prior electrodiagnostic (EDX) study was deemed positive, including 14 patients with abnormal repetitive nerve stimulation (RNS) and 12 with abnormal single fiber electromyography (SFEMG). Technical issues were noted on prior RNS studies in 8 patients, and repeat RNS was negative in 10 patients. In eight patients with previously abnormal SFEMG, results showed minimal or equivocal abnormalities. In two patients, a repeat SFEMG was normal. Further analysis revealed atypical clinical presentation, deceptively positive ice pack test, clinically insignificant antibody result and misleading EDX finding as main contributors to MG overdiagnosis. DISCUSSION: Overdiagnosis of MG is not uncommon, and occurs more frequently in seronegative patients. To make an accurate diagnosis of MG, there is a need to recognize atypical presentations, and avoid overreliance on minor or non-specific serological and electrodiagnostic findings.
Subject(s)
Myasthenia Gravis , Overdiagnosis , Humans , Retrospective Studies , Incidence , Electric Stimulation/methods , Myasthenia Gravis/diagnosis , Myasthenia Gravis/epidemiology , Electromyography/methods , Receptors, Cholinergic , AutoantibodiesABSTRACT
Myasthenic crisis (MC) is a life-threatening manifestation of myasthenia gravis (MG) defined by respiratory insufficiency that requires the use of invasive or non-invasive ventilation. This is often the result of respiratory muscle weakness but can also be due to bulbar weakness with upper airway collapse. MC occurs in approximately 15%-20% of patients with MG usually within the first 2 to 3 y of the disease course. Many crises have a specific trigger with respiratory infections being most common; however, no specific trigger is found in 30%-40% of patients. MG patients with a history of MC, severe disease, oropharyngeal weakness, muscle-specific kinase (MuSK) antibodies and thymoma appear to be at higher risk. Most episodes of MC do not occur suddenly, providing a window of opportunity for prevention. Immediate treatment is directed toward airway management and removing any identified triggers. Plasmapheresis is preferred over intravenous immune globulin as the treatments of choice for MC. The majority of patients are able to be weaned from mechanical ventilation within 1 mo and the outcomes of MC are generally favorable. The mortality rate in United States cohorts is less than 5% and mortality in MC seems to be driven by age and other medical co-morbidities. MC does not appear to affect long-term prognosis as many patients are able to eventually achieve good MG control.
Subject(s)
Myasthenia Gravis , Thymus Neoplasms , Humans , Myasthenia Gravis/diagnosis , Myasthenia Gravis/therapy , Muscle Weakness , Plasmapheresis , Respiration, Artificial , Thymus Neoplasms/therapyABSTRACT
The rapidly-developed high-power mid-infrared 2-5 µm laser technology requires a compact, flexible low-loss glass fiber for power delivery or laser generation. With the broadest bandwidth of low-loss transmission window in mid-infrared region amongst all mid-infrared glass fibers, chalcogenide glass fiber is the best candidate covering the whole 2-5 µm range. Multi-hundred-watt high-power delivery for 5.4-µm CO laser was previously demonstrated in a multimode chalcogenide fiber with a 1-mm-diameter large core, at the cost of giving up one of the most desirable fiber advantages, the flexibility. Indeed, chalcogenide glass fibers with decent flexibility have never exhibited hundred-watt-level power transmitting capability in the 2-5 µm range. In this paper, we have experimentally demonstrated 100-watt-level power transmission in multimode As2S3 chalcogenide fibers, using a customized high-power 2-µm thulium doped silica fiber laser source. With effective forced cooling, the multimode As2S3 fiber with 200 µm core diameter can resist incident laser power of 120 W and deliver transmitted power of 63 W. Nano-sized scattering center related laser damage mechanism and the cylindrical heat transfer model have been proposed to explain the high-power damage process of chalcogenide glass fibers. The calculation is in good agreement with the experiments. It is promising to further enhance the transmitted power above 100 W in flexible chalcogenide glass large-core fibers.
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Pneumocystis jirovecii (PJ) is ubiquitously present in the environment and capable of causing an interstitial pneumonia in immunocompromised subjects. It has been advocated that routine prophylaxis against PJ be given to patients with autoimmune neuromuscular conditions that require prolonged use of corticosteroid therapy and/or other immunosuppressive agents. Available data, however, suggest that the risk of PJ infection in patients with autoimmune neuromuscular diseases is extremely low and the widespread use of prophylactic therapy is likely unnecessary. Comorbidities, including intestinal lung disease, prolonged lymphopenia, low CD4 count, parenchymal organ failure, and active cancer status, appear to increase the risk for PJ infection, and it is our opinion that these risk factors should be considered to determine the risk of PJ infection and the requirement for prophylaxis.
Subject(s)
Autoimmune Diseases , Neuromuscular Diseases , Pneumocystis carinii , Pneumonia, Pneumocystis , Autoimmune Diseases/complications , Autoimmune Diseases/drug therapy , Humans , Immunocompromised Host , Neuromuscular Diseases/complications , Pneumonia, Pneumocystis/etiology , Pneumonia, Pneumocystis/prevention & controlABSTRACT
INTRODUCTION/AIMS: In this study we aimed to determine the frequency of acetylcholine receptor (AChR) binding antibody positivity via neuroautoimmunity panel testing, and describe its occurrence in a group of nonmyasthenic disorders. METHODS: This is a retrospective analysis of patients who underwent neuroautoimmunity antibody panel testing from 2010 to 2018 at the Cleveland Clinic. RESULTS: A total of 10 855 patients received neuroautoimmunity antibody panel testing, and 224 (2.1%) patients were positive for AChR binding antibody. Fifty-eight patients with a known myasthenia gravis (MG) diagnosis and 11 patients with incomplete follow-up were excluded. Among the remaining 155 patients, 30 had newly diagnosed MG and 125 were nonmyasthenic. In 35 patients, MG was within the initial differential diagnosis based on the clinical presentation. In contrast to nonmyasthenic patients, myasthenic patients were more likely to have an initial clinical presentation raising suspicion for MG (73.3% vs 10.4%, P < .001), higher mean AChR binding antibody titer (8.2 ± 15.6 vs 0.4 ± 1.6 nmol/L, P = .011), and higher frequency of abnormal AChR modulating antibody (89.3% vs 23.9%, P < .001). A combination of AChR binding antibody of >0.5 nmol/L and modulating antibody of over 20% in patients with clinical suspicion of MG is virtually diagnostic of MG. A total of 31 (24.8%) nonmyasthenic patients carried coexisting autoimmune conditions. DISCUSSION: Elevated titers of AChR binding antibody can sometimes be found in nonmyasthenic patients. Combined analysis of clinical presentation, AChR binding antibody titer, and AChR-modulating antibody results can be helpful in confirming an MG diagnosis.
Subject(s)
Myasthenia Gravis , Receptors, Cholinergic , Autoantibodies , Humans , Myasthenia Gravis/diagnosis , Retrospective StudiesABSTRACT
INTRODUCTION/AIMS: Administrative health data has been increasingly used to study the epidemiology of myasthenia gravis (MG) but a case ascertainment algorithm is lacking. We aimed to develop a valid algorithm for identifying MG patients in the older population with Medicare coverage. METHODS: Local older patients (age ≥65) who received healthcare at the Cleveland Clinic and possessed Medicare coverage in 2014 and 2015 were selected. Potential MG patients were identified by using a combination of ICD9 or ICD10 codes for MG and MG-related text-word search. Diagnosis was categorized as "definite MG", "possible MG" or "non-MG" after review of clinical summaries by 5 neuromuscular specialists. Performances of various algorithms were tested by use of the definite MG cohort as a reference standard, and calculation of sensitivity, specificity, and predictive values. RESULTS: A total of 118 988 local older patients with Medicare coverage were identified. Usage of MG ICD codes and text-word search resulted in 125 patients with definite and 67 with possible MG. A total of 45 algorithms involving ICD usage, medication prescription, and specialty visit were tested. The best performing algorithm was identified as 2 office visits using MG ICD codes separated by at least 4 weeks or 1 hospital discharge and 1 office visit each using MG ICD codes separated by at least 4 weeks within the two-year period, resulting in a sensitivity and positive predictive value of 80% for identifying definite MG patients. DISCUSSION: Algorithms using ICD codes can reliably identify patients with MG with a high degree of accuracy.
Subject(s)
Medicare , Myasthenia Gravis , Aged , Algorithms , Databases, Factual , Humans , International Classification of Diseases , Myasthenia Gravis/diagnosis , Myasthenia Gravis/epidemiology , Predictive Value of Tests , United States/epidemiologyABSTRACT
The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. The most popular bridging therapy was oral prednisone taper chosen by 38% of responders while rituximab was the most popular maintenance therapy chosen by 46%. Most responders considered maintenance immunosuppression after a second relapse in patients with neuronal surface antibodies (70%) or seronegative autoimmune encephalitis (61%) as opposed to those with onconeuronal antibodies (29%). Most responders opted to cancer screening for 4 years in patients with neuronal surface antibodies (49%) or limbic encephalitis (46%) as opposed to non-limbic seronegative autoimmune encephalitis (36%). Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.
ABSTRACT
The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. Corticosteroids alone or combined with other agents (intravenous IG or plasmapheresis) were selected as a first-line therapy by 84% of responders for patients with a general presentation, 74% for patients presenting with faciobrachial dystonic seizures, 63% for NMDAR-IgG encephalitis and 48.5% for classical paraneoplastic encephalitis. Half the responders indicated they would add a second-line agent only if there was no response to more than one first-line agent, 32% indicated adding a second-line agent if there was no response to one first-line agent, while only 15% indicated using a second-line agent in all patients. As for the preferred second-line agent, 80% of responders chose rituximab while only 10% chose cyclophosphamide in a clinical scenario with unknown antibodies. Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.
Subject(s)
Adrenal Cortex Hormones/therapeutic use , Autoimmune Diseases/diagnosis , Encephalitis/diagnosis , Immunoglobulins, Intravenous/therapeutic use , Plasmapheresis , Autoimmune Diseases/therapy , Encephalitis/therapy , Humans , Treatment OutcomeABSTRACT
Ocular myasthenia gravis (OMG) and thyroid eye disease are two autoimmune conditions that have several overlapping clinical features, and these coexist with a small but not insignificant frequency. Segregating these diagnoses is typically straightforward, but, when the two diseases co-occur in the same individual, making a diagnosis of OMG can be very challenging. In this review we address what is known about the coexistence of OMG and thyroid eye disease and we highlight the clinical features that are suggestive of overlapping conditions. We also describe the major testing approaches used in the diagnosis of these two entities, with special emphasis on the potential shortcomings of individual tests in patients with overlapping disease. In patients with thyroid eye disease, securing a diagnosis of OMG may not be possible on the basis of a single positive test. A multimodal approach using clinical, serologic, imaging, and electrodiagnostic data, is typically required.
Subject(s)
Graves Ophthalmopathy/diagnosis , Myasthenia Gravis/diagnosis , Electrodiagnosis , Graves Ophthalmopathy/complications , Graves Ophthalmopathy/physiopathology , Humans , Myasthenia Gravis/complications , Myasthenia Gravis/physiopathology , Oculomotor Muscles/physiopathologyABSTRACT
INTRODUCTION/AIMS: Ulnar nerve repetitive nerve stimulation (RNS) has been traditionally used in the electrophysiological evaluation of myasthenia gravis (MG). However, its low diagnostic sensitivity remains a limitation. Existing data may suggest that median nerve RNS outperforms that of the ulnar nerve, but a direct comparison is currently lacking. The aim of this study was to directly compare the diagnostic yields between median and ulnar nerve RNS in patients with generalized MG. METHODS: We performed a retrospective analysis of patients with MG who underwent median and ulnar nerve RNS at a single tertiary center. RESULTS: RNS studies of median nerve recording from the abductor pollicis brevis and ulnar nerve recording from the adductor digiti minimi were completed in 28 patients with generalized MG. Abnormal RNS was more frequently observed in the median compared with the ulnar nerve (60.7% vs 35.7%, P = .046). The average magnitude of decrement was higher in the median nerve compared with the ulnar nerve (17.3% vs 9.6%, P = .017). Differences between the median and ulnar nerve RNS studies were restricted to patients with mild manifestations (Myasthenia Gravis Foundation of America class II). DISCUSSION: Median nerve RNS has superior diagnostic sensitivity as compared with ulnar nerve RNS in the assessment of mild generalized MG.
Subject(s)
Electric Stimulation Therapy/standards , Median Nerve/physiology , Myasthenia Gravis/diagnosis , Myasthenia Gravis/physiopathology , Ulnar Nerve/physiology , Adolescent , Adult , Aged , Aged, 80 and over , Electric Stimulation Therapy/methods , Female , Humans , Male , Middle Aged , Retrospective Studies , Young AdultABSTRACT
INTRODUCTION/AIM: Antibody overshoot following therapeutic plasmapheresis (PLEX) is defined by subsequent increase in antibody to levels exceeding those prior to removal. It has been infrequently described in the past, and its influence on the clinical course of myasthenia gravis (MG) remains unclear. METHODS: This was a retrospective analysis of five patients with generalized MG treated with PLEX. RESULTS: All five patients possessed antibodies against acetylcholine receptor (AChR-Ab). After undergoing 3 to 12 PLEX treatment sessions, AChR-Ab titer increased to a median of 1292% of the baseline level. The median interval from the last PLEX session to peak AChR-Ab detection was 6 wk. In four patients, AChR-Ab overshoot was associated with a clinical deterioration. DISCUSSION: The AChR-Ab overshoot may occur following PLEX. In patients who deteriorate following PLEX treatment, the presence of antibody overshoot may serve as additional guidance for treatment adjustment.
Subject(s)
Autoantibodies/blood , Disease Progression , Myasthenia Gravis/blood , Myasthenia Gravis/therapy , Plasmapheresis/trends , Adult , Aged , Anti-Inflammatory Agents/therapeutic use , Female , Humans , Male , Middle Aged , Myasthenia Gravis/diagnosis , Plasmapheresis/adverse effects , Receptors, Cholinergic/blood , Retrospective StudiesABSTRACT
BACKGROUND: Occurrence of comitant ocular deviation in myasthenia gravis (MG) is not well described. METHODS: A retrospective analysis of patients with ocular or generalized MG evaluated at a neuro-ophthalmology clinic for a 6-year period. Comitant ocular deviation was defined as magnitude of deviations in all planes varying by <20% from the measurement in the primary position. RESULTS: Among the 120 patients included, 89 patients had ocular and 31 patients generalized MG. At the initial strabismus testing, comitant ocular deviation was present in 27 (22.5%) patients. Among the 16 patients who had a follow-up, ocular deviation remained comitant in 6 patients and converted to incomitant or no ocular deviation in 10 patients. An additional 7 patients demonstrated comitant ocular deviation at follow-up. Brain MRI was performed in 18 patients with comitant ocular deviation, and none showed abnormalities in the brainstem or cerebellum. CONCLUSION: Comitant ocular deviation can be an ocular manifestation of MG. Its presence does not necessarily indicate a central etiology in patients with MG neither excluding a MG diagnosis.
Subject(s)
Myasthenia Gravis , Strabismus , Humans , Myasthenia Gravis/complications , Myasthenia Gravis/diagnosis , Retrospective Studies , Strabismus/diagnosis , Strabismus/etiologyABSTRACT
BACKGROUND: We aimed to evaluate the significance of electromyographic findings in the intrinsic foot muscles (IFMs) of patients with skin biopsy proven small fiber neuropathy (SFN). METHODS: This was a single-center retrospective analysis of patients who underwent skin biopsy for intra-epidermal nerve fiber density (IENFD) measurement and electrodiagnostic (EDX) study for evaluation of polyneuropathy. RESULTS: A total of 1416 patents with normal lower extremity EDX studies proximal to the foot were included. Active denervation was seen in 16.1% of IFMs in patients with skin biopsy proven SFN and 4.1% of patients without SFN (P < .0001). Reinnervation changes without active denervation were observed in 30.4% of SFN patients and 23.8% of patients without SFN (P = .01). IENFD was lower in SFN patients with active denervation in IFMs than without (P < .0001). CONCLUSIONS: Evaluation of active denervation in the IFMs can reveal large fiber dysfunction in SFN patients with otherwise normal routine EDX findings.
Subject(s)
Foot/innervation , Muscle, Skeletal/innervation , Neural Conduction/physiology , Small Fiber Neuropathy/physiopathology , Sural Nerve/physiopathology , Action Potentials , Adolescent , Adult , Aged , Aged, 80 and over , Electrodiagnosis , Electromyography , Epidermis/pathology , Female , Foot/physiopathology , Humans , Male , Middle Aged , Muscle, Skeletal/physiopathology , Nerve Fibers/pathology , Retrospective Studies , Small Fiber Neuropathy/pathology , Thigh , Young AdultABSTRACT
Modern neuromuscular electrodiagnosis (EDX) and neuromuscular ultrasound (NMUS) require a universal language for effective communication in clinical practice and research and, in particular, for teaching young colleagues. Therefore, the AANEM and the IFCN have decided to publish a joint glossary as they feel the need for an updated terminology to support educational activities in neuromuscular EDX and NMUS in all parts of the world. In addition NMUS has been rapidly progressing over the last years and is now widely used in the diagnosis of disorders of nerve and muscle in conjunction with EDX. This glossary has been developed by experts in the field of neuromuscular EDX and NMUS on behalf of the AANEM and the IFCN and has been agreed upon by electronic communication between January and November 2019. It is based on the glossaries of the AANEM from 2015 and of the IFCN from 1999. The EDX and NMUS terms and the explanatory illustrations have been updated and supplemented where necessary. The result is a comprehensive glossary of terms covering all fields of neuromuscular EDX and NMUS. It serves as a standard reference for clinical practice, education and research worldwide. HIGHLIGHTS: Optimal terminology in neuromuscular electrodiagnosis and ultrasound has been revisited. A team of international experts have revised and expanded a standardized glossary. This list of terms serves as standard reference for clinical practice, education and research.
Subject(s)
Dictionaries as Topic , Electrodiagnosis/classification , Neuromuscular Diseases/classification , Neuromuscular Diseases/diagnostic imaging , Societies, Medical/classification , Ultrasonography/classification , Humans , United StatesABSTRACT
BACKGROUND: Limb ischemia/reperfusion (I/R) is a common clinical process that frequently induces acute lung injury (ALI). Tetrahydropalmatine (THP) is a major bioactive constituent of various traditional Chinese medicine with protective effects on inflammation and oxidation. In this study, we aimed to investigate the possible protective effect of THP on ALI induced by limb I/R. METHODS: Rats were used to establish ALI through limb I/R. After administration of three doses of THP, the lung injury was evaluated by hematoxylin-eosin staining, tissue wet/dry weight ratio and ELISA examination of myeloperoxidase (MPO), malondialdehyde (MDA) and Super Oxide Dismutase (SOD). Additionally, PI3K/AKT/mTOR pathway and autophagy markers were determined by Western blot. To confirm the role of autophagy in the effect of THP on ALI, 3-methyladenine (3-MA), THP or THP + rapamycin (RAPA) was given to the model rats, and then evaluated the parameters above mentioned. RESULTS: The pulmonary histological lesions and wet/dry were significantly induced after limb I/R. Concurrently, I/R significantly increased MPO and MDA, and decreased SOD in lung tissues. These changes were reversed after THP treatment. Additionally, THP exerted inhibitory effect on the I/R-induced decrease of phosphorylation of PI3K/AKT/mTOR and increase of autophagy activity. The effects by THP on lung injury, PI3K/AKT/mTOR signaling and autophagy were also observed after treatment with 3-MA, an autophagy inhibitor, whereas were blocked by combinational treatment with RAPA, an autophagy inducer. CONCLUSION: Our data suggested that THP had significant protection against ALI and this might be achieved by autophagy inhibition through rescuing PI3K/AKT/mTOR activity.
Subject(s)
Acute Lung Injury , Phosphatidylinositol 3-Kinases , Acute Lung Injury/drug therapy , Acute Lung Injury/etiology , Acute Lung Injury/prevention & control , Animals , Autophagy , Berberine Alkaloids , Ischemia , Proto-Oncogene Proteins c-akt , Rats , Rats, Sprague-Dawley , Reperfusion , TOR Serine-Threonine KinasesABSTRACT
Ultrasonic testing is a useful approach for quantifying the flaws in mechanical components. The height of the flaws in ultrasonic angle beam testing is closely related to the calibration value of the probe refraction angle. In order to reduce the calibration error, some ignored data during the traditional calibration process are reanalyzed and fused to determine the refraction angle. Both arithmetical measurement fusion method and weighted measurement fusion method are applied and compared. Monte Carlo simulation is used to estimate the probability distribution of the refraction angle and obtain the optimal refraction angle weights. Experiments were carried out to verify the results of Monte Carlo simulation. The applicability of data fusion on refraction angles is investigated. It was found in the study that the data fused with the refraction angle is helpful for measuring the height of flaws.
ABSTRACT
OBJECTIVE: Charcot-Marie-Tooth type 4J (CMT4J) is a rare autosomal recessive neuropathy caused by mutations in FIG4 that result in loss of FIG4 protein. This study investigates the natural history and mechanisms of segmental demyelination in CMT4J. METHODS: Over the past 9 years, we have enrolled and studied a cohort of 12 CMT4J patients, including 6 novel FIG4 mutations. We evaluated these patients and related mouse models using morphological, electrophysiological, and biochemical approaches. RESULTS: We found sensory motor demyelinating polyneuropathy consistently in all patients. This underlying myelin pathology was associated with nonuniform slowing of conduction velocities, conduction block, and temporal dispersion on nerve conduction studies, which resemble those features in acquired demyelinating peripheral nerve diseases. Segmental demyelination was also confirmed in mice without Fig4 (Fig4-/- ). The demyelination was associated with an increase of Schwann cell dedifferentiation and macrophages in spinal roots where nerve-blood barriers are weak. Schwann cell dedifferentiation was induced by the increasing intracellular Ca2+ . Suppression of Ca2+ level by a chelator reduced dedifferentiation and demyelination of Schwann cells in vitro and in vivo. Interestingly, cell-specific knockout of Fig4 in mouse Schwann cells or neurons failed to cause segmental demyelination. INTERPRETATION: Myelin change in CMT4J recapitulates the features of acquired demyelinating neuropathies. This pathology is not Schwann cell autonomous. Instead, it relates to systemic processes involving interactions of multiple cell types and abnormally elevated intracellular Ca2+ . Injection of a Ca2+ chelator into Fig4-/- mice improved segmental demyelination, thereby providing a therapeutic strategy against demyelination. Ann Neurol 2018;83:756-770.