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Purpose of review: The number of hospitalizations for gastroparesis has risen over 300% in recent decades with increased physical, psychological, and healthcare burdens. Gastric per-oral endoscopic myotomy (G-POEM) is a promising therapy for patients with refractory gastroparesis. This article reviews important considerations for G-POEM.

Recent findings: Predictive factors for clinical success after G-POEM include diabetic and idiopathic gastroparesis, shorter gastroparesis duration, symptoms predominant of nausea and emesis, and gastric emptying study showing gastric retention of > 20% at 4 h. Mucosal closure is a critical step for G-POEM; both sutures and clips have high success rates, with clips having a trend to lower success rates but with significantly shorter procedure time and cheaper cost. G-POEMs have an overall 61% pooled success rate at one year with a yearly 13% symptom recurrence rate. A careful patient selection can yield higher clinical success rates. Further studies are needed on variant G-POEM techniques for more durable outcomes.

Purpose of review: Endoscopic submucosal dissection (ESD) has been found to increase en bloc and R0 resection as well as decrease risk of recurrence. However, despite literature supporting the benefits of endoscopic submucosal dissection, adoption of ESD in the United States has been challenging, driven by factors including requirement for specialized training as well as limitations in training availability.

Recent findings: Many devices have been developed to improve ease and therefore adoption for the procedure, with advancements in stability, resection as well as closure of the mucosal defect following resection. While the Japanese model of training in ESD centers around the Master-Apprentice model, this is scarce in the United States. Most US endoscopists therefore must follow other paths to learn and become proficient at ESD. There has been a rapid expansion in literature on ESD, fellowship programs, opportunities for case observation, and significant evolution in ex vivo training models that can assist an endoscopist in receiving training in ESD. Currently, there are three main ways of learning to perform ESD in the United States: 1. Third space endoscopy fellowship; 2. Master-apprentice model; 3. Utilization of live courses and proctored procedures. ESD is the optimal method to ensure en bloc resection of large mucosal neoplasms of the gastrointestinal tract. While several barriers hinder adoption of ESD in the United States, there has been significant development both in procedural and training aspects. Further research and discussions are needed to determine criteria for credentialing and proficiency in ESD.

Purpose of review: In this review, we discuss the role of endoscopic gallbladder drainage for acute cholecystitis in non-surgical candidates, describe technical aspects, clinical outcomes, and elaborate on considerations when determining which approach to adopt for a given patient.

Recent findings: Cholecystectomy remains the criterion standard for management of acute cholecystitis in patients who can safely undergo surgery. For non-surgical candidates, percutaneous cholecystostomy (PTC-GBD) has been the traditional strategy to drain and decompress the gallbladder. Advances in endoscopy have further expanded the nonsurgical interventions and approaches to cholecystitis. Both endoscopic transpapillary gallbladder drainage (ET-GBD) and endoscopic ultrasound guided gallbladder drainage (EUS-GBD) have become acceptable alternatives to PTC-GBD, with growing literature supporting their efficacy, safety and improved patient quality of life when compared to a percutaneous approach. Choosing the appropriate endoscopic technique for gallbladder drainage should be tailored to each patient, keeping in view the specific clinical scenarios, endoscopist preference and following a multi-disciplinary approach.

Investigating the dynamic response of human tympanic membranes (TMs) exposed to blasts requires full-field-of-view and three-dimensional (3D) methodologies. Our paper introduces a system that combines high-speed 3D digital image correlation (HS 3D-DIC) and Schlieren imaging (HS-SI) with a custom-designed shock tube for generating blast waves. This integrated system allows us to measure TM surface motions under intense transient loading, capturing full-field-of-view shape deformations exceeding 100 μm with a temporal resolution of 10 μs. System characterization encompasses (i) measuring the shock tube's output levels and repeatability, (ii) assessment of the spatial and temporal resolutions of the imaging techniques, and (iii) identification of overall system limitations. Optimizing these factors is crucial for improving the reliability of our system to ensure the accurate measurement of deformations. To assess our shock tube's reliability in generating repeated blast waves, we instrumented it with high-pressure (HP) and high-frequency (HF) pressure sensors along the blast wave pathway to record overpressure waveforms and compared them with Schlieren imaging visualized blast waves. We validate our HS 3D-DIC measured deformations by comparing them with deformations measured using single-point laser Doppler vibrometry (LDV), establishing a comprehensive assessment of the TM's dynamic response and potential fracture mechanics under blast. Finally, we test our approach with 3D-printed TM-like samples and a real cadaveric human TM. This methodology lays the groundwork for further investigations of blast-related auditory damage and the invention of more effective protective and medical solutions.

The involvement of the excitatory amino acids glutamate and aspartate in cerebral ischemia and excitotoxicity is well-documented. Nevertheless, the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely understudied. The release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the penumbra. Our findings indicated that the reversible loss of field excitatory postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids (L-alanine, glycine, L-glutamine, and L-serine) at their plasma concentrations. These amino acids induce swelling in the somas of neurons and astrocytes during hypoxia, along with permanent dendritic damage mediated by N-methyl-D-aspartate receptors. Blocking N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during hypoxia. It is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels, leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor activation. Thus, previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain injury. Understanding these pathways could highlight new therapeutic targets to mitigate brain injury.

JOURNAL/nrgr/04.03/01300535-202509000-00024/figure1/v/2024-11-05T132919Z/r/image-tiff The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration. Axons and dendrites, sometimes referred to as neurites, are extensions of a neuron's cellular body that are used to start networks. Here we explored the effects of diethyl (3,4-dihydroxyphenethylamino)(quinolin-4-yl) methylphosphonate (DDQ) on neurite developmental features in HT22 neuronal cells. In this work, we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22 cells expressing mutant Tau (mTau) cDNA. To investigate DDQ characteristics, cell viability, biochemical, molecular, western blotting, and immunocytochemistry were used. Neurite outgrowth is evaluated through the segmentation and measurement of neural processes. These neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite growth. These neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal HT22. DDQ-treated mTau-HT22 cells (HT22 cells transfected with cDNA mutant Tau) were seen to display increased levels of synaptophysin, MAP-2, and β-tubulin. Additionally, we confirmed and noted reduced levels of both total and p-Tau, as well as elevated levels of microtubule-associated protein 2, β-tubulin, synaptophysin, vesicular acetylcholine transporter, and the mitochondrial biogenesis protein-peroxisome proliferator-activated receptor-gamma coactivator-1α. In mTau-expressed HT22 neurons, we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic outgrowth. Our findings conclude that mTau-HT22 (Alzheimer's disease) cells treated with DDQ have functional neurite developmental characteristics. The key finding is that, in mTau-HT22 cells, DDQ preserves neuronal structure and may even enhance nerve development function with mTau inhibition.

JOURNAL/nrgr/04.03/01300535-202509000-00022/figure1/v/2024-11-05T132919Z/r/image-tiff Poststroke cognitive impairment is a major secondary effect of ischemic stroke in many patients; however, few options are available for the early diagnosis and treatment of this condition. The aims of this study were to (1) determine the specific relationship between hypoxic and α-synuclein during the occur of poststroke cognitive impairment and (2) assess whether the serum phosphorylated α-synuclein level can be used as a biomarker for poststroke cognitive impairment. We found that the phosphorylated α-synuclein level was significantly increased and showed pathological aggregation around the cerebral infarct area in a mouse model of ischemic stroke. In addition, neuronal α-synuclein phosphorylation and aggregation were observed in the brain tissue of mice subjected to chronic hypoxia, suggesting that hypoxia is the underlying cause of α-synuclein-mediated pathology in the brains of mice with ischemic stroke. Serum phosphorylated α-synuclein levels in patients with ischemic stroke were significantly lower than those in healthy subjects, and were positively correlated with cognition levels in patients with ischemic stroke. Furthermore, a decrease in serum high-density lipoprotein levels in stroke patients was significantly correlated with a decrease in phosphorylated α-synuclein levels. Although ischemic stroke mice did not show significant cognitive impairment or disrupted lipid metabolism 14 days after injury, some of them exhibited decreased cognitive function and reduced phosphorylated α-synuclein levels. Taken together, our results suggest that serum phosphorylated α-synuclein is a potential biomarker for poststroke cognitive impairment.