Calculation and measurement of trapping stiffness in femtosecond optical tweezers.

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.

Features Suggestive of Coexisting Amyotrophic Lateral Sclerosis in Patients With Spinal Stenosis and Influence of Spinal Decompression.

BACKGROUND:  Spinal stenosis and amyotrophic lateral sclerosis (ALS) can co-occur and both manifest as signs of dysfunction of lower and/or upper motor neurons. Few studies have identified factors that alert the diagnosis of ALS in patients with spinal stenosis, and the influence of spinal decompression surgery on ALS progression remains unclear. OBJECTIVE: The objective of this study is to describe factors that are suggestive of an ALS diagnosis in patients with spinal stenosis and influence of spinal decompression surgery on the progression of ALS  Materials and methods: A retrospective review of the institutional ALS database and electronic medical records was performed to identify patients with coexisting diagnoses of ALS and moderate to severe cervical and/or lumbosacral spine stenosis. Identified patients were divided into two subgroups: those with spinal decompression surgery and those without. Comparisons of clinical features and progression of ALS were made between subgroups. RESULTS:  A total of 77 patients with ALS and coexisting moderate to severe cervical or lumbosacral spine stenosis were included. Among them, 50 patients underwent spinal decompression surgery and 27 did not. In comparison to patients with spinal decompression, patients without spinal decompression surgery were seen more frequently by neurologists (74% versus 26%), had less prominent radicular pain (19% versus 50%), demonstrated more frequent bulbar signs (30% versus 8%), experienced more likely weight loss (41% versus 4%), and disclosed more noticeable axonal loss changes on electromyography. Spinal decompression surgery did not modify the progression of ALS based on ALSFRS-R score change and analysis of survival duration. CONCLUSION: Our study identified a number of useful features that are suggestive of an ALS diagnosis when evaluating patients with spinal stenosis and may support the performance of spinal decompression surgery in a subset of selected ALS patients with symptomatic spinal stenosis.

Modulation of Extracellular Matrix Composition and Chronic Inflammation with Pirfenidone Promotes Scar Reduction in Retinal Wound Repair.

Wound repair in the retina is a complex mechanism, and a deeper understanding of it is necessary for the development of effective treatments to slow down or even prevent degenerative processes leading to photoreceptor loss. In this study, we harnessed a laser-induced retinal degeneration model (532-nm laser photocoagulation with 300 µm spot size, 60 ms duration and 60 mV pulse), enabling a profound molecular elucidation and a comprehensive, prolonged observation of the wound healing sequence in a murine laser-induced degeneration model (C57BL/6J mice, 6-12 weeks) until day 49 post-laser. Our observations included the expression of specific extracellular matrix proteins and myofibroblast activity, along with an analysis of gene expression related to extracellular matrix and adhesion molecules through RNA measurements. Furthermore, the administration of pirfenidone (10 mg/kg via drinking water), an anti-inflammatory and anti-fibrotic compound, was used to modulate scar formation after laser treatment. Our data revealed upregulated collagen expression in late regenerative phases and sustained inflammation in the damaged tissue. Notably, treatment with pirfenidone was found to mitigate scar tissue formation, effectively downregulating collagen production and diminishing the presence of inflammatory markers. However, it did not lead to the regeneration of the photoreceptor layer.

Electrodiagnostic findings in amyotrophic lateral sclerosis: Variation with region of onset and utility of thoracic paraspinal muscle examination.

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.

Protective effect of sevoflurane on lung function of elderly chronic obstructive pulmonary disease patients undergoing total hip arthroplasty.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder that affects the elderly population and increases the risk of postoperative pulmonary complications (PPCs) after major surgeries. Sevoflurane is a volatile anesthetic that has been shown to have anti-inflammatory and antioxidant properties and attenuate lung injury in animal models. AIM: To evaluate the protective effect of sevoflurane on the lung function of elderly COPD patients undergoing total hip arthroplasty (THA). METHODS: In this randomized controlled trial, we randomly assigned 120 elderly patients with COPD, who were scheduled for THA, to receive either sevoflurane (sevoflurane group) or propofol (propofol group) as the maintenance anesthetic. The primary outcome was the incidence of PPCs within seven days after surgery. The secondary outcomes were changes in the lung function parameters, inflammatory markers, oxidative stress markers, and postoperative pain scores. RESULTS: The results showed that the incidence of PPCs was significantly lower in the sevoflurane group than in the propofol group (10% vs 25%, P = 0.02). Furthermore, the decline in the forced expiratory volume in 1 s, forced vital capacity, and peak expiratory flow was significantly lesser in the sevoflurane group than in the propofol group at 24 h and 48 h after surgery (P < 0.05). The interleukin-6, tumor necrosis factor-alpha, malondialdehyde, and 8-hydroxy-2 α-deoxyguanosine levels were significantly lower in the sevoflurane group than in the propofol group at 24 h after surgery (P < 0.05). The sevoflurane group showed significantly lower postoperative pain scores than the propofol group at 6 h, 12 h, and 24 h after surgery (P < 0.05). CONCLUSION: Sevoflurane protects the lung function of elderly COPD patients undergoing THA under general anesthesia by reducing the incidence of PPCs, attenuating inflammatory and oxidative stress responses, and alleviating postoperative pain.

Clinical Reasoning: An Unusual Cause of Diplopia and Ptosis in a 67-Year-Old Woman.

Diplopia is a relatively common chief complaint encountered in an outpatient neurology clinic and carries a broad differential diagnosis. In this case, a 67-year-old woman presented with new horizontal, binocular diplopia and ptosis of 8-month duration, which persisted without significant progression. This case highlights the need for a comprehensive list of differential diagnoses for patients with acquired ophthalmoplegia and ptosis. Key learning points include an illustration of the stepwise diagnostic approach to evaluate for common etiologies, the importance of interpreting test results in the appropriate clinical setting, and the significance of recognizing specific signs and symptoms in achieving the correct diagnosis.

Autoimmunity and postural orthostatic tachycardia syndrome: Implications in diagnosis and management.

Postural orthostatic tachycardia syndrome (POTS)-sustained tachycardia upon standing without orthostatic hypotension-can be diagnosed clinically without an extensive diagnostic evaluation unless certain atypical features suggest an alternative diagnosis. A unifying pathophysiologic mechanism has not been identified, although several have been proposed. Similarities between POTS and various autoimmune disorders suggest an immune mechanism in a subset of patients. However, no causative antibody has been identified, and associated antibodies are rarely clinically relevant. Moreover, immunotherapies are not currently recommended for POTS, although clinical trials are underway to clarify their utility.

Myasthenic crisis.

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.

Oxymetazoline Hydrochloride Eye-Drops as Treatment for Myasthenia Gravis-Related Ptosis: A Description of Two Cases.

In this article, we described two patients with myasthenia gravis-related ptosis who experienced sustained improvement with the use of oxymetazoline hydrochloride ophthalmic solution 0.1%. Despite the commonly used treatments for ptosis in myasthenia gravis (MG), such as acetylcholinesterase inhibitors and corticosteroids, complete remission of ptosis is not always achieved, and these treatments are often accompanied by systemic side effects. Our case report suggests the long-term efficacy of daily use of oxymetazoline eye drops in improving ptosis, providing a potential alternative or adjunctive treatment option without significant adverse effects. Further research is necessary to confirm these observations across larger cohorts of MG patients and establish the effectiveness of oxymetazoline eye drops in MG-related ptosis.

Animal model of subretinal fibrosis without active choroidal neovascularization.

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.

Myasthenia gravis: Frequently asked questions.

Myasthenia gravis is a disorder of neuromuscular junction transmission, the result of antibodies against the post-synaptic aspect of the neuromuscular junction. Its clinical hallmark is fatigable weakness of skeletal muscles, which tends to vary in location and severity among patients. It is treated with pyridostigmine, immunotherapy, and thymectomy. Treatment is often individualized according to disease severity, antibody status, comorbidities, and other factors. This review uses a question-and-answer format to provide up-to-date, high-yield, clinically relevant information on myasthenia gravis.

Incidence and causes of overdiagnosis of myasthenia gravis.

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.

Diagnosis and Management of Myasthenia Gravis.

PURPOSE OF REVIEW: This article reviews updated diagnostic procedures and currently available treatment modalities for myasthenia gravis (MG). RECENT FINDINGS: Patients with MG can be classified based on antibody status and their clinical presentation; treatment responses may differ based on disease subtypes. Improved diagnostic methods and recognition of new antigenic targets such as lipoprotein-related protein 4 have led to improved diagnostic efficiencies. Corticosteroids remain the first-line immunotherapy, but there is a trend toward minimizing their use at high doses and for long durations. Oral immunosuppressants such as mycophenolate mofetil, azathioprine, and tacrolimus remain useful. An international, multicenter randomized trial comparing thymectomy plus prednisone with prednisone alone demonstrated that thymectomy improves clinical outcomes in selected patients with nonthymomatous MG. Eculizumab, efgartigimod, and ravulizumab have recently been approved by the US Food and Drug Administration (FDA) for adult patients with generalized MG who are acetylcholine receptor-antibody positive. These drugs take advantage of novel mechanisms of action and expand treatment options for patients with MG. Data on rituximab suggest that it can be a good option, especially for patients with MG who are positive for antibodies against muscle-specific tyrosine kinase (MuSK). The number of clinical trials and drugs in development for MG is steadily increasing. SUMMARY: The diagnosis of MG can generally be made from the patient's history, a neurologic examination, and laboratory and electrodiagnostic testing. Carefully selected treatment improves outcomes in MG. Additional treatment options for MG will likely be available in the near future.

Real-world utilization patterns of intravenous immunoglobulin in adults with generalized myasthenia gravis in the United States.

OBJECTIVE: To evaluate real-world utilization patterns of intravenous immunoglobulin (IVIg) among patients with generalized myasthenia gravis (gMG) over 3 years post-IVIg initiation. METHODS: Patients with gMG who initiated IVIg treatment were identified from a United States claims database (Symphony Health's Integrated Dataverse [IDV]®, January 1, 2014 - December 31, 2019). The frequency of subsequent IVIg treatment and associated cost during the year post-IVIg initiation were analyzed. Usage patterns of IVIg and concomitant gMG treatments during the year preceding and 3 years post-IVIg initiation were compared. RESULTS: Among 1225 patients with gMG who initiated IVIg treatment, 706 patients (57.6%) received 1 to 5 IVIg treatment courses (intermittent IVIg users), and 519 patients (42.4%) received ≥6 IVIg treatment courses (chronic IVIg users) within the subsequent year. Mean annual medical cost per patient was nearly 2.5-fold higher for chronic vs. intermittent IVIg users ($161,478 vs. $64,888, p < 0.001). The proportion of patients using corticosteroids and nonsteroidal immunosuppressive treatments (NSISTs) was not reduced over the 3-year follow-up period following IVIg initiation, even for patients who continued annual chronic IVIg for 3 consecutive years post-initiation. CONCLUSIONS: Nearly half of patients with gMG received chronic and multiple IVIg treatment courses within the first year once initiating IVIg treatment, indicating higher usage than expected. For all IVIg initiators, the proportion of patients using corticosteroids and NSISTs did not decrease over 3 years despite IVIg initiation.

Genvoya-Associated and Simvastatin-Associated Noninflammatory and Nonautoimmune Myopathy: A Case Report and Literature Review.

ABSTRACT: Patients with HIV have a higher incidence of rhabdomyolysis compared with the HIV negative population because of medication-related myotoxicity and drug-drug interactions. Statins and antiretroviral therapy have been previously reported to cause myopathy in patients with HIV when used alone or in combination. In this study, we describe a case of biopsy-proven noninflammatory and nonautoimmune myopathy associated with the use of simvastatin and Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate) and review 3 previously reported similar cases. Our patient presented with acute proximal limb weakness and significantly elevated serum creatine kinase. Muscle biopsy revealed scattered degenerating and regenerating muscle fibers without evidence for an inflammatory process. She did not respond to empiric treatment with high-dose intravenous steroids and intravenous immunoglobulin. Her creatine kinase only began to downtrend after discontinuation of both simvastatin and Genvoya, and she returned to baseline function at 2-month follow-up. Our case highlights the importance of recognizing drug-drug interactions between HIV and statin medications in causing significant noninflammatory myopathy. In these patients, both categories of medications need to be discontinued for recovery.

Flexible chalcogenide glass large-core multimode fibers for hundred-watt-level mid-infrared 2-5 µm laser transmission.

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.

Incidence and influence of hyperCKemia in Legionella infection.

INTRODUCTION: A number of case and case series descriptions established an association between Legionella infection and hyperCKemia, but the frequency and severity of hyperCKemia in Legionella infection remain unknown. This study aims to investigate the incidence, extent, and consequences of hyperCKemia in a large group of patients with Legionella infection. METHODS: This retrospective study included patients with confirmed Legionella infection during a ten-year period who received creatine kinase (CK) testing. Comparisons were performed between groups of Legionella patients with and without hyperCKemia. RESULTS: A total of 267 patients were included. HyperCKemia was present in 144 (53.9%) patients. The mean peak CK value was 9598 IU/L (range: 226 to 462,000 IU/L) while peak CK exceeded 1000 IU/L in 82 (56.9%) patients and 5000 IU/L in 33 (22.9%). When compared to patients without hyperCKemia, patients with hyperCKemia had higher incidences of neurologic symptoms (p = 0.036), acute renal failure (p = 0.028), dialysis requirement (p = 0.009), and need for ICU care (p = 0.016). HyperCKemia resolved in most Legionella patients by 7 days from CK peaking. DISCUSSION: Legionella infection requiring hospitalization appears to be associated with increased incidence of hyperCKemia and rhabdomyolysis. Greater awareness of the high incidence and the possible severity of hyperCKemia is needed when treating patients with Legionella infection.