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Journal of Thoracic Disease May 2024Anesthesia remains challenging for bronchoscopic tracheobronchial surgeries (BTS) involving surgical manipulations for central airway obstruction within shared airways....
BACKGROUND
Anesthesia remains challenging for bronchoscopic tracheobronchial surgeries (BTS) involving surgical manipulations for central airway obstruction within shared airways. To provide complete airway use through intervention with spontaneous breathing without endotracheal tubes, monitored non-intubated anesthesia has been successfully applied with electroencephalogram-derived monitored total intravenous anesthesia. This study evaluated the feasibility and the outcomes of BTS with monitored non-intubated anesthesia. The factors associated with desaturation and complications were also analyzed.
METHODS
Data from patients receiving non-intubated BTS performed between October 2019 and August 2022 were retrospectively collected. Intraoperative results and postoperative outcomes were analyzed.
RESULTS
Data of 92 patients were collected. Supraglottic airways devices and high-flow nasal oxygen were used in 68 and 24 patients respectively. Surgery was successfully completed in 87 patients (94.6%), whereas three patients required conversion to intubation because of substantial bleeding. In total, 11% of patients experienced desaturation [oxygen saturation (SpO) <90%] for an average of 9 minutes. Unexpected admission to the intensive care unit (ICU) occurred in 12.2% (5/41) of patients from outpatient department and 7.8% (4/51) of hospitalization settings because of high-grade surgical bleeding. With comparable desaturation incidence, tracheal surgery had significantly longer desaturation times (14.5±6.9 min) than bronchial surgeries (5.8±2.6 min) did.
CONCLUSIONS
Monitored non-intubated anesthesia with spontaneous breathing is feasible for BTS, with high success rate, few complications, and rapid recovery. High-grade bleeding remains the most unpredictable risk for intraoperative desaturation and postoperative ICU admission, especially in tracheal obstruction cases.
PubMed: 38883685
DOI: 10.21037/jtd-23-1935 -
Stem Cells International 2024Genetically modified intestinal organoids are being explored as potential surrogates of immortalized cell lines and gene-engineered animals. However, genetic...
Genetically modified intestinal organoids are being explored as potential surrogates of immortalized cell lines and gene-engineered animals. However, genetic manipulation of intestinal organoids is time-consuming, and the efficiency is far beyond satisfactory. To ensure the yield of the genetically modified organoids, large quantity of starting materials is required, and the procedure usually takes more than 10 days. Two major obstacles that restrict the genetic delivery efficiency are the three-dimensional culture condition and that the genetic delivery is carried out in cell suspensions. In the present study, we introduce a novel highly efficient strategy for building genetically modified intestinal organoids in which genetic delivery was performed in freshly established monolayer primary intestinal epithelial cells under two-dimensional conditions and subsequentially transformed into three-dimensional organoids. The total procedure can be finished within 10 hr while displaying much higher efficiency than the traditional methods. Furthermore, this strategy allowed for the selection of transgenic cells in monolayer conditions before establishing high-purity genetically modified intestinal organoids.
PubMed: 38882597
DOI: 10.1155/2024/2005845 -
Journal of Neuroscience Methods Jun 2024Significant research has been devoted to developing noninvasive approaches to neuromonitoring. Clinical validation of such approaches is often limited, with minimal data...
BACKGROUND
Significant research has been devoted to developing noninvasive approaches to neuromonitoring. Clinical validation of such approaches is often limited, with minimal data available in the clinically relevant elevated ICP range.
NEW METHOD
To allow ultrasound-guided placement of an intraventricular catheter and to perform simultaneous long-duration ICP and ultrasound recordings of cerebral blood flow, we developed a large unilateral craniectomy in a swine model. We also used a microprocessor-controlled actuator for intraventricular saline infusion to reliably and reversibly manipulate ICP according to pre-determined profiles.
RESULTS
The model was reproducible, resulting in over 80hours of high-fidelity, multi-parameter physiological waveform recordings in twelve animals, with ICP ranging from 2 to 78mmHg. ICP elevations were reversible and reproducible according to two predetermined profiles: a stepwise elevation up to an ICP of 30 to 35mmHg and return to normotension, and a clinically significant plateau wave. Finally, ICP was elevated to extreme levels of greater than 60mmHg, simulating extreme clinical emergency.
COMPARISON WITH EXISTING METHODS
Existing methods for ICP monitoring in large animals typically relied on burr-hole approaches for catheter placement. Accurate catheter placement can be difficult in pigs, given the thickness of their skull. Additionally, ultrasound is significantly attenuated by the skull. The open cranium model overcomes these limitations.
CONCLUSIONS
The hemicraniectomy model allowed for verified placement of the intraventricular catheter, and reversible and reliable ICP manipulation over a wide range. The large dural window additionally allowed for long-duration recording of cerebral blood flow velocity from the middle cerebral artery.
PubMed: 38880344
DOI: 10.1016/j.jneumeth.2024.110196 -
Neuroscience and Biobehavioral Reviews Jun 2024Accounts of shared representations posit that the experience of pain and pain empathy rely on similar neural mechanisms. Experimental research employing novel analytical... (Review)
Review
Accounts of shared representations posit that the experience of pain and pain empathy rely on similar neural mechanisms. Experimental research employing novel analytical and methodological approaches has made significant advances in both the identification and targeted manipulation of such shared experiences and their neural underpinnings. This revealed that painful experiences can be shared on different representational levels, from pain-specific to domain-general features, such as negative affect and its regulation. In view of direct links between such representations and social behaviors such as prosocial behavior, conditions characterized by aberrant pain processing may come along with heavy impairments in the social domain, depending on the affected representational level. This has wide potential implications in light of the high prevalence of pain-related clinical conditions, their management, and the overuse of pain medication. In this review and opinion paper, we aim to chart the path toward a better understanding of the link between shared affect and prosocial behavior.
PubMed: 38879099
DOI: 10.1016/j.neubiorev.2024.105769 -
Clinics (Sao Paulo, Brazil) Jun 2024This study aims to elucidate the role of circUSP9X (Circular RNA Ubiquitin Specific Peptidase 9 X-Linked) in the development of venous thrombosis in the lower...
OBJECTIVES
This study aims to elucidate the role of circUSP9X (Circular RNA Ubiquitin Specific Peptidase 9 X-Linked) in the development of venous thrombosis in the lower extremities.
METHODS
An animal model of Deep Vein Thrombosis (DVT) and a hypoxic model of Human Umbilical Vein Endothelial Cells (HUVECs) treated with Cobalt (II) Chloride (CoCl) were developed. The expression levels of circUSP9X, microRNA-148b-3p (miR-148b-3p), and SRC Kinase Signaling Inhibitor 1 (SRCIN1) were quantified using quantitative reverse transcription Polymerase Chain Reaction and Western blot analysis. Cell cytotoxicity, viability, apoptosis, and inflammation in HUVECs were assessed via Lactate Dehydrogenase (LDH) assay, MTT assay, flow cytometry, Enzyme-Linked Immunosorbent Assay, and Western blot, respectively. Hematoxylin and Eosin staining were employed for histopathological examination of the venous tissues in the animal model. The interaction between circUSP9X, miR-148b-3p, and SRCIN1 was further explored through dual-luciferase reporter assays and RNA Immunoprecipitation experiments.
RESULTS
The present findings reveal a significant upregulation of circUSP9X and SRCIN1 and a concurrent downregulation of miR-148b-3p in DVT cases. Knockdown of circUSP9X or overexpression of miR-148b-3p ameliorated CoCl-induced apoptosis in HUVECs, reduced LDH release, enhanced cellular viability, and mitigated inflammation. Conversely, overexpression of circUSP9X intensified CoCl's cytotoxic effects. The effects of manipulating circUSP9X expression were counteracted by the corresponding modulation of miR-148b-3p and SRCIN1 levels. Additionally, circUSP9X knockdown effectively inhibited the formation of DVT in the mouse model. A competitive binding mechanism of circUSP9X for miR-148b-3p, modulating SRCIN1 expression, was identified.
CONCLUSION
circUSP9X promotes the formation of DVT through the regulation of the miR-148b-3p/SRCIN1 axis.
PubMed: 38878321
DOI: 10.1016/j.clinsp.2024.100403 -
Cell Communication and Signaling : CCS Jun 2024Respiratory disorders are among the conditions that affect the respiratory system. The healthcare sector faces challenges due to the emergence of drug resistance to... (Review)
Review
Respiratory disorders are among the conditions that affect the respiratory system. The healthcare sector faces challenges due to the emergence of drug resistance to prescribed medications for these illnesses. However, there is a technology called CRISPR/Cas9, which uses RNA to guide DNA targeting. This technology has revolutionized our ability to manipulate and visualize the genome, leading to advancements in research and treatment development. It can effectively reverse epigenetic alterations that contribute to drug resistance. Some studies focused on health have shown that targeting genes using CRISPR/Cas9 can be challenging when it comes to reducing drug resistance in patients with respiratory disorders. Nevertheless, it is important to acknowledge the limitations of this technology, such as off-target effects, immune system reactions to Cas9, and challenges associated with delivery methods. Despite these limitations, this review aims to provide knowledge about CRISPR/Cas9 genome editing tools and explore how they can help overcome resistance in patients with respiratory disorders. Additionally, this study discusses concerns related to applications of CRISPR and provides an overview of successful clinical trial studies.
Topics: Humans; Gene Editing; CRISPR-Cas Systems; Drug Resistance; Animals; Respiration Disorders; Respiratory Tract Diseases
PubMed: 38877530
DOI: 10.1186/s12964-024-01713-8 -
Cortex; a Journal Devoted To the Study... Jun 2024The ability to inhibit movements is an essential component of a healthy executive control system. Two distinct but commonly used tasks to assess motor inhibition are the...
The ability to inhibit movements is an essential component of a healthy executive control system. Two distinct but commonly used tasks to assess motor inhibition are the stop signal task (SST) and the anticipated response inhibition (ARI) task. The SST and ARI tasks are similar in that they both require cancelation of a prepotent movement; however, the SST involves cancelation of a speeded reaction to a temporally unpredictable signal, while the ARI task involves cancelation of an anticipated response that the participant has prepared to enact at a wholly predictable time. 33 participants (mean age = 33.3 years, range = 18-55 years) completed variants of the SST and ARI task. In each task, the majority of trials required bimanual button presses, while on a subset of trials a stop signal indicated that one of the presses should be cancelled (i.e., motor selective inhibition). Additional variants of the tasks also included trials featuring signals which were to be ignored, allowing for insights into the attentional component of the inhibitory response. Electromyographic (EMG) recordings allowed detailed comparison of the characteristics of voluntary action and cancellation. The speed of the inhibitory process was not influenced by whether the enacted movement was reactive (SST) or anticipated (ARI task). However, the ongoing (non-cancelled) component of anticipated movements was more efficient than reactive movements, as a result of faster action reprogramming (i.e., faster ongoing actions following successful motor selective inhibition). Older age was associated with both slower inhibition and slower action reprogramming across all reactive and anticipated tasks.
PubMed: 38875737
DOI: 10.1016/j.cortex.2024.05.010 -
Science Advances Jun 2024Precision interferometry with quantum states has emerged as an essential tool for experimentally answering fundamental questions in physics. Optical quantum...
Precision interferometry with quantum states has emerged as an essential tool for experimentally answering fundamental questions in physics. Optical quantum interferometers are of particular interest because of mature methods for generating and manipulating quantum states of light. Their increased sensitivity promises to enable tests of quantum phenomena, such as entanglement, in regimes where tiny gravitational effects come into play. However, this requires long and decoherence-free processing of quantum entanglement, which, for large interferometric areas, remains unexplored territory. Here, we present a table-top experiment using maximally path-entangled quantum states of light in a large-scale interferometer sensitive enough to measure the rotation rate of Earth. The achieved sensitivity of 5 μrad s constitutes the highest rotation resolution ever reached with optical quantum interferometers. Further improvements to our methodology will enable measurements of general-relativistic effects on entangled photons, allowing the exploration of the interplay between quantum mechanics and general relativity, along with tests for fundamental physics.
PubMed: 38875336
DOI: 10.1126/sciadv.ado0215 -
Frontiers in Immunology 2024The five-year survival rates for pancreatic ductal adenocarcinoma (PDAC) have scarcely improved over the last half-century. It is inherently resistant to FDA-approved...
The five-year survival rates for pancreatic ductal adenocarcinoma (PDAC) have scarcely improved over the last half-century. It is inherently resistant to FDA-approved immunotherapies, which have transformed the outlook for patients with other advanced solid tumours. Accumulating evidence relates this resistance to its hallmark immunosuppressive milieu, which instils progressive dysfunction among tumour-infiltrating effector T cells. This milieu is established at the inception of neoplasia by immunosuppressive cellular populations, including regulatory T cells (T), which accumulate in parallel with the progression to malignant PDAC. Thus, the therapeutic manipulation of T has captured significant scientific and commercial attention, bolstered by the discovery that an abundance of tumour-infiltrating T correlates with a poor prognosis in PDAC patients. Herein, we propose a mechanism for the resistance of PDAC to anti-PD-1 and CTLA-4 immunotherapies and re-assess the rationale for pursuing T-targeted therapies in light of recent studies that profiled the immune landscape of patient-derived tumour samples. We evaluate strategies that are emerging to limit T-mediated immunosuppression for the treatment of PDAC, and signpost early-stage trials that provide preliminary evidence of clinical activity. In this context, we find a compelling argument for investment in the ongoing development of T-targeted immunotherapies for PDAC.
Topics: Animals; Humans; Carcinoma, Pancreatic Ductal; Immune Checkpoint Inhibitors; Immunotherapy; Lymphocytes, Tumor-Infiltrating; Pancreatic Neoplasms; T-Lymphocytes, Regulatory; Tumor Microenvironment
PubMed: 38873607
DOI: 10.3389/fimmu.2024.1406250 -
Chemosphere Jun 2024In urbanized areas, extracellular DNA (exDNA) is suspected of carrying genes with undesirable traits like virulence genes (VGs) or antibiotic resistance genes (ARGs),...
In urbanized areas, extracellular DNA (exDNA) is suspected of carrying genes with undesirable traits like virulence genes (VGs) or antibiotic resistance genes (ARGs), which can spread through horizontal gene transfer (HGT). Hence, it is crucial to develop novel approaches for the mitigation of exDNA in the environment. Our research explores the role of goethite, a common iron mineral with high adsorption capabilities, in exDNA adsorption processes. We compare well-crystalline, semi-crystalline, and nano goethites with varying particle sizes to achieve various specific surface areas (SSAs) (18.7 - 161.6 m/g) and porosities. We conducted batch adsorption experiments using DNA molecules of varying chain lengths (DNA sizes: < 11 Kb, < 6 Kb, and < 3 Kb) and assessed the impact of Ca and biomacromolecules on the adsorption efficacy and mechanisms. Results show that porosity and pore structure significantly influence DNA adsorption capacity. Goethite with well-developed meso- and macroporosity demonstrated enhanced DNA adsorption. The accumulation of DNA on the goethite interface led to substantial aggregation in the system, thus the formation of DNA-goethite conjugates, indicating the bridging between mineral particles. DNA chain length, the presence of Ca, and the biomacromolecule matrix also affected the adsorption capacity and mechanism. Interactions between DNA and positively charged biomacromolecules or Ca led to DNA compaction, allowing greater DNA accumulation in pores. However, a high concentration of biomacromolecules led to the saturation of the goethite surface, inhibiting DNA adsorption. AFM imaging of goethite particles after adsorption suggested the formation of the DNA multilayer. The study advances understanding of the environmental behavior of exDNA and its interaction with iron oxyhydroxides, offering insights into developing more effective methods for ARGs removal in wastewater treatment plants. By manipulating the textural properties of goethite, it's possible to enhance exDNA removal, potentially reducing the spread of biocontamination in urban and industrial environments.
PubMed: 38871190
DOI: 10.1016/j.chemosphere.2024.142602